HUB OF BIOSCIENCES

Colles Fracture - Late Complications

2009-10-07T07:49:00.000-07:00

- extensor pollicis longus rupture:
- RSD
- often RSD following colles fractures will result from over distraction of an external fixator;
- in the presentation by D Stoffelen and PL Broos (15 th Annual Meeting of the Orthopaedic Trauma Association 1999), the authors found
use of calcitonin to be helpful in treating this disorder;
- vitamin C: Can Vitamin C Prevent Complex Regional Pain Syndrome in Patients with Wrist Fractures?
- loss of reduction and secondary deformity;
- median nerve compression;
- Predictors of Acute Carpal Tunnel Syndrome Associated With Fracture of the Distal Radius
- malunion:
- distal radioulnar joint injury;
- extension of Colles frx into the RU joint has a worse prognosis;
- in stable extra-articular fractures, there will often be frx extension into the DRUJ, which is the most likely source of symptoms;
- patients may note:
- weak grip;
- localized pain;
- loss of supination;

Colles Fracture - Radiographic Findings

2009-10-07T07:44:00.000-07:00

- x-ray appearance is that of a dorsally angulated fracture of distal radial metaphysis (2-3 cm proximal to wrist joint),
w/ or w/o associated frx of ulnar styloid;
- initial frx line is almost always on volar side & is single line;

Colles Fracture - Associated Injuries

2009-10-07T07:40:00.000-07:00

- ulnar styloid frx
- TFCC tear
- according to the report by Richards et al 1997 et, TFCC tears occurred in 53% of extra-articular distal radius fractures vs 35% of intra-articular fractures;
- scapholunate dissociation:
- Intercarpal Ligament Injuries Associated with Fractures of the Distal Part of the Radius

Colles Fracture- Frykman Classification

2009-10-07T07:38:00.000-07:00

Fracture Distal Ulnar Fracture:
Absent Present
Extra articular I II
Intra articular involving radiocarpal joint III IV
Intra articular involving distal RU joint V VI
Intra articular involving both radiocarpal & VI VIII
distal radioulnar joints

- Discussion:
- Frykman classification considers involvement of radiocarpal & RU joint,
in addition to presnce or absence of frx of ulnar styloid process;
- classification does not include extent or direction of initial displacement,
dorsal comminution, or shortening of the distal fragment;
- hence, it is less useful in evaluating outcome of treatment

Incidence of Colles' fracture in a North American community.( A generalised example )

2009-10-07T07:35:00.000-07:00

In a 30-year period, 1,137 adult residents of Rochester, Minnesota experienced 1235 Colles' fractures. Fracture incidence among women increased over sixfold between ages 35-39 and 60-64 and then leveled off. Male rates were lower in every age group and did not rise as dramatically. Fractures associated with moderate trauma were responsible for the increased incidence with age and the excess among women. Overall, Rochester rates were 30 per cent or more greater than those reported from communities in other countries

Colles Fracture (Dinner fork deformity)

2009-10-07T07:31:00.000-07:00

This frx was described by Abraham Colles in 1814, originally described as low energy extra articular frx of distal radius occuring in elderly individuals;
- frx is typically dorsally displaced and angulated;
- mechanism:
- fracture is also caused by a forced dorsiflexion of the wrist;
- occurs in pts > 50 years of age who fall on out stretched hand;
- dorsal surface undergoes compression while volar surface undergoes tension;

Japan's swine flu cases top 2,000: health ministry

2009-07-09T04:49:00.000-07:00

TOKYO (AFP) — Japan's tally of swine flu cases topped 2,000 on Wednesday but no deaths or serious conditions have been reported among them, the health ministry said.

The number of A(H1N1) virus infections in Japan reached 2,033 by midday but most of them have already been cured, the ministry added.

The total has increased daily by around 100 cases in the past few days, the ministry said, adding that the infections have been reported in all but one of the country's 47 prefectures.

Japan's first cases, in a Japanese teacher and two students who had returned from a study trip to North America, were reported on May 9. The number had reached 1,000 by June 25.

Zanamivir ( Relenza ) An Anti-Flu Drug

2009-07-09T04:40:00.000-07:00

Zanamivir (INN) (pronounced /zəˈnæmɨvɪr/) is a neuraminidase inhibitor used in the treatment of and prophylaxis of both Influenzavirus A and Influenzavirus B. Zanamivir was the first neuraminidase inhibitor commercially developed. It is currently marketed by GlaxoSmithKline under the trade name Relenza.

Oseltamivir ( Tamiflu ) drug for Swine Flu

2009-07-07T07:54:00.000-07:00

Oseltamivir (INN) (pronounced /ɒsəlˈtæmɨvɪr/) is a drug that blocks the influenza virus from spreading between cells in the body. Thus it is an antiviral drug that is used in the treatment and prophylaxis of both Influenzavirus A and Influenzavirus B infection. Like zanamivir, oseltamivir is a neuraminidase inhibitor. It acts as a transition-state analogue inhibitor of influenza neuraminidase, preventing progeny virions from detaching from infected cells.

Oseltamivir was the first orally active neuraminidase inhibitor commercially developed. It is a prodrug, which is hydrolysed hepatically to the active metabolite, the free carboxylate of oseltamivir (GS4071). It was developed by US-based Gilead Sciences and is currently marketed by Hoffmann–La Roche (Roche) under the trade name Tamiflu. In Japan, it is marketed by Chugai Pharmaceutical Co., which is more than 50% owned by Roche. Oseltamivir is generally available by prescription only.^[1]

Hoffmann–La Roche estimates that 50 million people have been treated with oseltamivir.^[2] The majority of these have been in Japan, where an estimated 35 million have been treated.^[3]

Flu Vaccine (Influenza Immunization) FAQ's Answered

2009-07-07T07:43:00.000-07:00

What is flu?

The flu (or common flu) is a viral infection that is spread from person to person in secretions of the nose and lungs, for example when sneezing. Medically it is referred to as influenza. Flu is a respiratory infection, that is, an infection that develops primarily in the lungs. Respiratory infections caused by other viruses often are called flu, but this is incorrect. Influenza usually causes higher fever, more malaise, and severe body aches. Although other viruses may cause these symptoms, they do so less commonly.

The flu is a common illness. Every year in the United States, on average:

5% to 20% of the population gets the flu,
more than 200,000 people are hospitalized from flu complications, and

about 36,000 people die from the flu.

Why vaccinate for the flu?

The flu is highly infectious and is a serious viral respiratory infection. Whereas with other viral respiratory infections the symptoms usually are mild and most people can continue working or going to school while ill, with the flu, the symptoms are severe and prolonged and cause individuals to miss days of work or school. The infection stresses the body. In addition, superinfections may occur. Superinfections are bacterial infections that occur on top of a respiratory infection. Bacterial respiratory infections also are a serious type of infection, and the simultaneous viral and bacterial infection can overwhelm the function of the lungs and the body. Among the elderly and the very young, it can cause death. Because of its infectiousness, morbidity (severity of symptoms and time lost from work or school), and the potential for death, it is important to prevent the flu by vaccination. Although there are medications to treat the flu, they are expensive, not as effective as vaccination, and need to be started within 24-48 hours of the start of symptoms.

What is the flu vaccine?

Flu vaccine is an inactivated vaccine, meaning that it contains killed influenza virus. The killed influenza virus is injected into muscles and stimulates the immune system to produce an immune response (antibodies) to the influenza virus. When the virus enters a person who has been vaccinated, the antibodies attack and kill the virus and prevent infection.

Each year, the influenza virus can change slightly, making the vaccine used in previous years ineffective. Each year, a new vaccine must be prepared that will be effective against the expected type of influenza virus. The trick is to be able to predict which influenza viruses are going to cause infection and to prepare a vaccine against those viruses. Usually scientists can predict accurately which types of influenza virus will cause infections and prepare an appropriate vaccine. The viruses that are used to prepare flu vaccine are grown in eggs.

The vaccine is generally effective against the influenza virus within two weeks of the injection. The vaccine is only effective against the strains of the virus that match the vaccine. These strains vary from flu season to flu season each year. This is the reason that revaccination is required annually with the vaccine that matches the strains of influenza that are currently prevalent.

Flu season can begin in October and last as late as May. October and November are considered the best times to receive the vaccination, but it is still effective when administered later.

Flu vaccination does not protect against infection caused by microbes other than the influenza virus.

Who should receive the flu vaccine?

While anyone who wishes to reduce their risk of getting the flu can be vaccinated, the U.S. Centers for Disease Control and Prevention (CDC) recommends that certain groups of people (who are at risk for serious complications from the flu) be vaccinated each year. When vaccine supplies are limited or delayed, the CDC makes recommendations for priority groups of people who should receive the vaccination. The CDC recommends vaccination for the following groups:

1. People at high risk for complications from the flu, including:

people ages 65 and older,

people who live in nursing homes and other long-term care facilities that house those with long-term illnesses,

adults and children 6 months and older with chronic heart or lung conditions, including asthma,

adults and children 6 months and older who needed regular medical care or were in a hospital during the previous year because of a metabolic disease (like diabetes), chronic kidney disease, or weakened immune system (including immune system problems caused by medicines or by infection with human immunodeficiency virus [HIV/AIDS]),

children 6 months to 18 years of age who are on long-term aspirin therapy (children given aspirin while they have influenza are at risk of Reye syndrome),

women who will be pregnant during the influenza season,

all children 6 to 23 months of age, and

people with any condition that can compromise respiratory function or the handling of respiratory secretions (that is, a condition that makes it hard to breathe or swallow, such as brain injury or disease, spinal cord injuries, seizure disorders, or other nerve or muscle disorders).

2. People 50 to 64 years of age. Almost one-third of people in this age group in the U.S. have one or more medical conditions that place them at increased risk for serious flu complications.

3. People who can transmit flu to others at high risk for complications .This means that all health-care workers, caregivers of children 6 to 23 months of age, close contacts of people 65 years and older, or any person in close contact with someone in a high-risk group (see above) should be vaccinated so that they do not spread the infection to a high-risk population.

How is the flu vaccine administered?

The inactivated flu vaccine is administered as a single dose of 0.5 mL of liquid injected through the skin into muscle (intramuscular or IM). Typically the injection is into the deltoid muscle at the side of the arm, using alcohol rubbed over the skin for sterilization. The vaccine is given annually, each fall.

What side effects can occur with flu vaccination?

Side effects of the inactivated flu vaccine are not common. Side effects include soreness at the site of the injection, muscle aching, fever, and feeling unwell. Very rarely, serious allergic reactions have been reported.

Guillain-Barre syndrome (GBS) is an illness characterized by fever, nerve damage, and muscle weakness. In 1976, vaccination with the swine flu vaccine was associated with development of GBS. Studies have been done to evaluate if other flu vaccines were associated with GBS, with only one of the studies showing an association. That single study suggested that one person out of 1 million vaccinated persons may be at risk of GBS associated with the vaccine.

Who should not receive the flu vaccine?

Those who should avoid the flu vaccine include:

people with a history of allergic reactions to eggs,

those with a history of hypersensitivity to the vaccine,

those with recent febrile (having fever) illness (although you can be vaccinated if you have a cold or other mild illness without fever), and

subsequent vaccination should be avoided for people known to have developed the rare nerve disease Guillain-Barré syndrome (GBS, see above) within six weeks of a previous vaccination.

How effective is the flu vaccine?

The effectiveness of the flu vaccine is dependent upon the extent of the match between the virus strains used to prepare the vaccine and those viruses in actual circulation. The age and health status of the individual also play a role in determining the effectiveness of the vaccine. Research has shown that when there is a good match between the virus strains chosen for the vaccine and those in circulation, the vaccine prevents influenza illness in approximately 70%-90% of healthy adults under 65 years of age.

A study of children from 1 to 15 years of age showed that inactivated influenza vaccine was 77%-91% effective in preventing influenza respiratory illness. The effectiveness of the vaccine in preventing respiratory illness in people over 65 is somewhat lower. Among older people who reside in nursing homes, influenza vaccine is most effective in preventing severe illness, secondary complications, and deaths. The vaccine can be 50%-60% effective in preventing influenza-related hospitalization or pneumonia and 80% effective in preventing influenza-related death, although the effectiveness in preventing influenza respiratory illness can be as low as from 30%-40%.

What is the nasal spray flu vaccine?

A newer vaccine is available that is administered via a nasal spray. The nasal-spray flu vaccine (sometimes called LAIV for Live Attenuated Influenza Vaccine, brand name FluMist) was first licensed in 2003. It is directed against the same strains of virus as the flu shot but differs in that it contains weakened live influenza viruses instead of killed viruses and is administered by nasal spray instead of injection. The vaccine is termed an attenuated vaccine because the viruses are weakened so that they do not cause severe flu symptoms. The nasal spray flu vaccine (LAIV) has been approved by the U.S. Food and Drug Administration (FDA) for use in nonpregnant healthy people between the ages of 5 and 49 years. In September 2007, the FDA also approved use of the nasal flu vaccine for healthy children 2-4 years old (24-59 months old) without a history of recurrent wheezing.

People at risk for serious complications from the flu (as described above) should not receive the nasal spray flu vaccine. In particular, certain groups are advised to receive the inactivated flu vaccine rather than the nasal spray vaccine, including:

children younger than 5 years of age who have recurrent wheezing,

people with chronic health problems, including heart and lung disease,

pregnant women,

people with suppressed immune function and those who care for or come into contact with those with a suppressed immune system,

adults over age 50 or children 6 months to 2 years of age, and

children or adolescents receiving aspirin therapy.

The live viruses in the nasal spray vaccine are weakened so that they do not cause severe symptoms. However, mild symptoms can occur as a side effect of the vaccination. Side effects of the nasal spray flu vaccine can include runny nose, headache, sore throat, and cough. Children who receive the vaccine may also develop mild fever and muscle aches.

How swine flu virus hopscotched the globe

2009-07-07T07:29:00.000-07:00

CHICAGO - A 5-year-old Mexican boy takes ill in his dusty village. He coughs, he sneezes, he gasps for breath.

Hundreds of Edgar Hernandez's neighbors in La Gloria — villagers who live among smelly pig-breeding farms that attract swarms of flies — already have flu-like symptoms. After they complain repeatedly, government workers arrive to conduct medical tests.

Edgar recovers, but his illness remains a mystery to his family — at least for a while.

A 9-year-old boy arrives at a medical clinic in Elyria, Ohio, an industrial city 20 miles southwest of Cleveland. He has a sore throat, body aches, fever and dizziness.

His mother consults a pediatric nurse practitioner, Sally Fenik; she thinks it's strep throat or an allergy. She also mentions to the nurse they've just returned from visiting relatives in Mexico but doesn't think it's swine flu because no one else in the family is sick.

But on her way to work, Fenik has heard a radio news report about swine flu turning up in states bordering Mexico. She's far away, in the industrial Midwest, but remembers thinking, "Boy, I hope that doesn't start spreading and getting worse."

After a rapid strep test on the boy comes back negative, Fenik does a nasal swab.

A half-hour later, the lab calls. It's the type of influenza linked to swine flu virus.

This past Sunday, the Centers for Disease Control and Prevention confirmed the third-grader from Ohio had swine flu. And then on Monday, the Veracruz governor swooped in by helicopter to La Gloria to tell Edgar's mother what medical experts already know — the kindergartner was Mexico's first confirmed case of swine flu.

Two boys, two pieces of the puzzle
Two boys in communities 1,700 miles apart — two pieces of a vast epidemiological puzzle.

In this age of global trade and travel, the swine flu outbreak has proven itself a global illness — a strange new virus that respects no border as it hopscotches from the dirt roads of Mexican villages to the concrete canyons of big-city America to a glittering Hong Kong hotel.

The list of the nationalities of some of its victims, in the last week alone, reads like the index of an atlas: Austria, Britain, Canada, Germany, Israel, Mexico, the Netherlands, Spain, Switzerland, the United States.

U.S. swine flu deaths hit double digits

Britain criticized for efforts to halt spread

Could H1N1 become resistant to drugs?

MSN's swine flu coverage

Discuss: How concerned are you?

Swine flu has been confirmed in 16 deaths, all from Mexico (one Mexican toddler died in Houston). It has sickened nearly 350 people in Mexico, and about 250 others from New York to New Zealand, including children, teens, adults, students and tourists. It has rattled the world's financial markets, pushed oil prices down, caused a run on surgical masks and hand sanitizers, closed schools and churches, postponed sporting events, prompted travel bans, rerouted cruise ships.

It even stopped a superhero in his hairy tracks: Hugh Jackman canceled an appearance in Mexico City to promote "X-Men Origins: Wolverine."

No one knows precisely where the swine flu virus will pop up next.

All they know is that it will.

"Influenzas are hard to predict," Dr. Gregory Gray, director at the Center for Emerging Infectious Diseases at the University of Iowa College of Public Health, said at midweek. "I don't think this will go away in a few days. The way it's moving and the way air transportation goes ... I think this thing is going to spread to every continent in the next week."

'No idea where it came from'
Where and how it all began is a medical mystery.

But one of the first hints of trouble surfaced toward the end of winter, just when the flu season should be wrapping up. It came from the Mexican state of Veracruz — a region that includes a high plain that supplies Mexico with much of its cured pork products and has many villages that are surrounded by pig-breeding farms.

Edgar Hernandez lives in one of them, La Gloria, a hillside hamlet (population 3,000) where people started complaining of bad colds at the end of February. On March 23, Veracruz health officials arrived to take saliva samples.

About a third of some 1,300 townspeople who sought medical attention — 450 or so — were diagnosed with acute respiratory infections and given surgical masks and antibiotics.

Edgar fell ill a bit later; the energetic 5-year-old retreated to his bed with a high fever. Other kids in his school already were sick.

People in his town have long complained that some of the pits that hold pig waste are not properly lined; they fear their groundwater is contaminated. They're frustrated and angry, too, about the stench and the swarms of flies that invade their village.

Granjas Carroll de Mexico, half-owned by U.S.-based Smithfield Foods Inc., operates dozens of farms around La Gloria. Smithfield said in a statement this week that it has found no signs or symptoms of swine influenza in its herd or its workers.

Whether La Gloria is ground zero in this outbreak is not yet known.

Mexican health officials downplayed the possibility, pointing out Edgar had the only positive saliva sample among just 35 people tested for the new virus. It wasn't until last week that authorities confirmed the little boy was infected with a new H1N1 strain — a strange hybrid of pig, bird and human flu virus.

Two children from La Gloria died before being tested; their parents refused to let them be exhumed.

Mexico's chief epidemiologist, Dr. Miguel Angel Lezana, says officials haven't ruled out Mexico, the United States, Asia or Europe as the origin of the swine flu virus.

The CDC has no firm answers either.

"We have no idea where it came from," says Michael Shaw, the CDC's associate director for laboratory science. "Everybody's calling it swine flu, but the better term is swine-like. It's like viruses we have seen in pigs — it's not something we know was in pigs. It doesn't really have any close relative."

By early April, the Veracruz government notified Mexican authorities of a possible flu outbreak in La Gloria. This alert happened to come around Holy Week, a time when lots of people in this largely Catholic country travel to visit family.

On April 12, Mexican health authorities notified the CDC and the Pan American Health Organization of the unexplained cases of severe respiratory illness.

One day later, people started dying.

Swine flu hits young, healthy adults hard

2009-07-07T07:25:00.000-07:00

The young and healthy who feel invincible from the H1N1 "swine flu" influenza pandemic may not be as bulletproof as they think, warn public health experts.

Nearly two-thirds of Canadians hospitalized due to swine flu, and half of those who have died, had no underlying health conditions.

Experts do not yet understand why the new strain affects some healthy people so severely, ravaging their lungs with an aggressive pneumonia and forcing them to spend weeks in hospital, attached to breathing machines.

"They are ending up on ventilators and it can last from weeks to months," said Michael Gardam, director of infectious diseases at the Ontario Agency for Health Protection and Promotion. "I would like people to be concerned about H1N1, without panicking. More concerned than they are about seasonal flu."

A new study tracking the epidemic in Mexico also found the flu strain hits those between the ages of 20 and 50 the hardest, with a higher death rate than other age groups.

In recent weeks, as swine flu has faded from the world's radar, infectious disease specialists worry that people have become complacent about the pandemic, which is expected to infect one third of the population, or about 10 million Canadians. (In contrast, seasonal flu affects about one in 10 people.)

"You should not be worried that your child will suddenly die of H1N1," Dr. Gardam said. "But you should be prepared that a family member will get sick."

The World Health Organization has confirmed 77,201 cases of H1N1 as of July 1, with 332 deaths.

As of June 29, 2009, a total of 7,983 laboratory-confirmed cases of H1N1 flu virus have been reported in all provinces and territories in Canada. To date, 538 people have been admitted to hospital and there have been 25 laboratory-confirmed deaths - including Rubjit "Ruby" Thindal.

The Grade 1 student from Brampton, Ont. died in her father's arms June 15 en route to the hospital, a day after first complaining of achy arms and legs, and a slight fever. Doctors await autopsy results to find out whether she had an underlying health condition that contributed to her death.

According to the Public Health Agency of Canada, two-thirds of 94 hospitalized cases where information was available showed the patients were perfectly healthy before being admitted.

Of the 25 Canadians who died with H1N1, 13 had other health problems. These can range from obesity, diabetes and mild asthma to chronic lung or heart disease. Also at risk are smokers, those who are immune-compromised, and pregnant women, who have a greater chance of developing complications.

"By the time you add up all these underlying health conditions, you end up with a large chunk of the population," Dr. Gardam observes.

Epidemiologists are studying cases of healthy people who have become severely ill after contracting the virus, to gain insight into why they are vulnerable.

"[We are] trying to understand from a medical standpoint why they would be affected this way by the virus, and whether this is a signal that the virus is changing and becoming more virulent," David Butler-Jones, Canada's chief public health officer, said in a statement. "It is because of these severe cases, although a minority, that we must remain vigilant, both at the government level by continuing to investigate these cases, and at the individual level, by taking personal action to prevent infection."

The other troubling characteristic of the swine pandemic is that, unlike other flus, it is not tapering off in the summer months.

Instead, Canada is experiencing five times the rate of flu activity it normally does at this time of year, all of it H1N1. "The other flu bugs have vanished. But not H1N1," Dr. Gardam says.

The other key difference is the age of those infected: most are aged 20 to 50. With seasonal flu, one quarter of those infected are over the age of 65, Dr. Butler-Jones says.

In Mexico, 87 per cent of the deaths, and 71 per cent of the cases of severe pneumonia due to H1N1 occurred in people between the ages of 5 and 59. With seasonal flu, usually one third of those affected are in this age group.

Doctors speculate that this could be because the H1N1 virus resembles a strain of flu that circulated before 1957, to which older people have been exposed, says Colin Lee, associate medical officer of health in Ontario's Simcoe-Muskoka region.

The first detailed study of the swine flu outbreak in Mexico, H1N1's original epicentre, was published last week in the New England Journal of Medicine.

"The features of the H1N1 epidemic are somewhat similar to past influenza pandemics in that circulation of a new influenza virus is associated with an unseasonal wave of disease affecting a younger population," wrote authors Gerardo Chowell-Puente, an epidemiologist at Arizona State University, and Stefano Bertozzi of the National Institute of Public Health in Mexico.

Dr. Butler-Jones reiterated his message that prevention is key in stopping the spread of all flu viruses, and urged people to wash their hands, cough into their sleeves, and avoid others when they're ill. People with a fever and cough who develop shortness of breath or difficulty breathing should get medical attention right away, he added.

H1N1 Flu (Swine Flu) Pandemic

2009-07-07T07:23:00.000-07:00

A Pandemic Is Declared

On June 11, 2009, the World Health Organization (WHO) raised the worldwide pandemic alert level to Phase 6 in response to the ongoing global spread of the novel influenza A (H1N1) virus. A Phase 6 designation indicates that a global pandemic is underway.

More than 70 countries are now reporting cases of human infection with novel H1N1 flu. This number has been increasing over the past few weeks, but many of the cases reportedly had links to travel or were localized outbreaks without community spread. The WHO designation of a pandemic alert Phase 6 reflects the fact that there are now ongoing community level outbreaks in multiple parts of world.

WHO’s decision to raise the pandemic alert level to Phase 6 is a reflection of the spread of the virus, not the severity of illness caused by the virus.

Swine Flu Is More Severe Than Seasonal Flu, Ferret Study Finds

2009-07-07T07:18:00.000-07:00

Swine flu caused more-severe illness in ferrets than seasonal flu, according to two studies in the journal Science that help explain why the H1N1 virus causes symptoms not seen in regular flu such as nausea and vomiting.

The H1N1 swine flu virus went further into the ferrets’ lungs, and also penetrated the gastrointestinal tract while seasonal flu stayed in the nasal cavity, researchers from the U.S. and the Netherlands found. Ferrets are affected by flu viruses much as humans are, the researchers said.

Swine flu has struck at least 77,201 people in 113 nations worldwide, killing 332, according to laboratory-confirmed reports compiled by the World Health Organization, which has declared the first flu pandemic since 1968. While the virus causes little more than a fever and cough in most people, a previous study showed that about 40 percent of those infected have developed symptoms such as diarrhea, vomiting and nausea.

“These data suggest that the 2009 A(H1N1) influenza virus has the ability to persist in the human population, potentially with more severe clinical consequences,” wrote the Dutch study authors, led by Ron Fouchier at the Erasmus Medical Center in Rotterdam.

The two studies were published online today. Both groups found that ferrets infected with swine flu lost more weight than those exposed to seasonal flu, and that the swine flu virus was more widespread in the animals’ bodies.

When they examined the transmissibility of the virus, the two groups found conflicting evidence. Fouchier and colleagues, who used a strain of swine flu taken from the first person infected in the Netherlands, said ferrets passed it to each other through the air as easily as seasonal flu.

Efficiency Finding

The U.S. researchers, led by Terrence Tumpey at the Atlanta-based Centers for Disease Control and Prevention, said the ferrets in their study didn’t transmit the swine flu strains they used, taken from patients in California, Texas and Mexico, as efficiently as seasonal flu strains.

Swine flu doesn’t latch on to healthy cells in the human respiratory tract as easily as seasonal flu because of a genetic mutation, the CDC researchers said.

Inefficient transmission suggests the virus would need to mutate to become as transmissible as seasonal flu or the 1918 pandemic virus, they said.

Swine Flu Symptoms

2009-07-07T07:13:00.000-07:00

Although the name 'swine flu' brings up a lot of extra fear and worry, it is important to note that swine flu is just an influenza A H1N1 virus.

That means that it is just another type of flu virus, just like that causes our typical seasonal flu symptoms. The big difference is that the current swine influenza A (H1N1) virus has components of pig and bird influenza viruses in it, so that humans don't have any immunity to it. That makes it more likely to become a pandemic virus (have the ability to cause a global outbreak) if it can easily spread from person-to-person.

So far, even as you see swine flu cases increase on this swine flu map, experts don't know if this swine influenza A (H1N1) virus will become a pandemic strain of flu. It could or we just continue to see sporadic cases for a few weeks or months until it stops.

We do know that swine flu symptoms are just like seasonal flu symptoms.

Swine Flu Symptoms

According to the CDC, like seasonal flu, symptoms of swine flu infections can include:

fever, which is usually high, but unlike seasonal flu, is sometimes absent
cough
runny nose or stuffy nose
sore throat
body aches
headache
chills
fatigue or tiredness, which can be extreme
diarrhea and vomiting, sometimes, but more commonly seen than with seasonal flu

Signs of a more serious swine flu infection might include pneumonia and respiratory failure.

If your child has symptoms of swine flu, you should avoid other people and call your pediatrician who might do a rapid flu test to see if he has an influenza A infection. Further testing can then be done to see if it is a swine flu infection. (Samples are being sent to local and state health departments and the CDC for confirmation of swine flu.)

Serious Swine Flu Symptoms

More serious symptoms that would indicate that a child with swine flu would need urgent medical attention include:

Fast breathing or trouble breathing
Bluish or gray skin color
Not drinking enough fluids
Severe or persistent vomiting
Not waking up or not interacting
Being so irritable that the child does not want to be held
Flu-like symptoms improve but then return with fever and worse cough

Swine Flu Symptoms vs. a Cold or Sinus Infection

It is important to keep in mind most children with a runny nose or cough will not have swine flu and will not have to see their pediatrician for swine flu testing.

This time of year, many other childhood conditions are common, including:

spring allergies - runny nose, congestion, and cough
common cold - runny nose, cough, and low grade fever
sinus infections - lingering runny nose, cough, and fever
strep throat - sore throat, fever, and a positive strep test

What You Need To Know

Swine flu likely spreads by direct contact with respiratory secretions of someone that is sick with swine flu, like if they were coughing and sneezing close to you.
People with swine flu are likely contagious for one day before and up to seven days after they began to get sick with swine flu symptoms.
Droplets from a cough or sneeze can also contaminate surfaces, such as a doorknob, drinking glass, or kitchen counter, although these germs likely don't survive for more than a few hours.
Anti-flu medications, including Tamiflu (oseltamivir) and Relenza (zanamivir), are available to prevent and treat swine flu.
The latest swine flu news from the CDC includes advice that students should stay home if they have swine flu symptoms, but schools do not need to close unless they have large clusters of cases that are affecting school functioning. Schools that closed based on previous recommendations, such as if they had a single confirmed case or probable case, can now likely reopen.

The 1918 Swine Flu Outbreak

2009-07-07T07:05:00.000-07:00

The 1918 Swine Flu outbreak was exceptionally severe, and affected approximately one-third of the world's population, which amounted to about five-hundred million people at the time. The rate of death associated with this outbreak of SIV was estimated to be between fifty-million and one-hundred million people.

Map of Latest 2009 H1N1 Swine Flu Outbreak Cases and Death Statistics

The SIV outbreak of the years 1918-1919 had an impact that was not limited to the years during which it occurred. Every influenza pandemic that has occurred since that time, in fact – nearly all cases of SIV worldwide, have been caused by the descendants of the 1918 virus; to include the H1N1, H2N2, and H3N2 viruses. The latter viruses are composed of key genes from the 1918 virus which subsequently incorporated avian flu genes, making the 1918 virus the, 'mother of all pandemics.'

Even though there were both clinical and epidemiological similarities to the influenza pandemics of 1889, 1847, and earlier pandemics, many people questioned where this explosively fatal disease of 1918 could even be influenza at all. The question did not even begin to reach some form of resolution until the 1930's when closely related flu viruses were isolated. Studies known as, 'Seroepidemiologic,' studies linked viruses to the 1918 pandemic, and subsequent studies indicate that descendants of the 1918 virus still persist in pigs. These viruses most likely still circulate in human beings as well, undergoing gradual antigenic shifts which cause annual epidemics. H1N1 viruses, descended from the 1918 strain, along with H3N2 viruses, have been co-circulating around the world for decades, showing little evidence of imminent extinction.

Both before and after 1918, the majority of flu pandemics developed in Asia and spread from there to the rest of the world. The pandemic of 1918 spread in three distinct waves over a more-or-less twelve month period of time in Asia, Europe, and North America. Neither the historical or epidemiological data provide adequate information to identify the exact geographical origin of the virus that caused this pandemic. The next outbreak of swine flu occurred in 1976

FLU PANDEMIC 2009

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The 2009 flu pandemic is an A(H1N1) pandemic and a global outbreak of a new strain of influenza A virus subtype H1N1, identified in April 2009, commonly referred to as "swine flu", which is transmitted between humans. It is thought to be a mutation—more specifically, a reassortment—of four known strains of influenza A virus subtype H1N1: one endemic in humans, one endemic in birds, and two endemic in pigs (swine). Experts now assume that the virus "most likely" emerged from pigs in Asia, and the virus was carried to North America by infected people. There is further evidence that the new strain has been circulating among pigs, possibly among multiple continents, for many years prior to its transmission to humans. Virtually all transmission is from human to human; cooked pork products are safe for humans and the virus cannot be transmitted from foods..

The outbreak began in Mexico, and there is evidence that Mexico was already in the midst of an epidemic for months before the outbreak was recognized. Soon after, their government closed down most of Mexico City's public and private offices and facilities to help contain the spread. In early June, as the virus spread globally, the World Health Organisation (WHO) declared the outbreak to be a pandemic, while also noting that the virus has so far been of "moderate severity." WHO anticipates a bleaker picture, however, as the virus spreads to less developed countries with poorer health care systems. As of July, the virus was continuing to spread worldwide, especially in Southern Hemisphere countries, where the winter flu season has started.

The virus typically spreads from coughs and sneezes or by touching contaminated surfaces and then touching the nose or mouth. Symptoms are similar to those of seasonal flu, and may include fever, sneezes, sore throat, coughs, headache, and muscle or joint pains. The CDC notes that most hospitalizations have been of people that also had underlying conditions such as asthma, diabetes, obesity, heart disease, or a weakened immune system. In an attempt to slow the spread of the illness, a number of countries, especially in Asia, have enforced strict quarantines on travelers showing any symptoms, along with travelers seated nearby any infected persons. Some have even requested pre-screening passengers before they travel.

WHO anticipates having some vaccines ready by September 2009, and by mid October for the U.S., but even then they expect that the supply will be limited. Two or three vaccine injections will be required for maximum immunity from both the swine flu and seasonal flu. There is also concern that the virus could mutate later in the year and become more virulent and less susceptible to any new vaccine. This concern is partly due to the memory of the 1918 flu pandemic, which is thought to have killed between 40 million and 100 million people, and was preceded by a wave of milder cases in the spring.

Diabetic Medications

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When diet, exercise and ideal body weight aren’t enough to maintain normal blood sugar level, you may need to start medication. Medications used to treat diabetes include insulin too. Usually, people with Type 1 diabetes don't use oral medications. Diabetes Medications work best in people with Type 2 diabetes who are having high blood sugar for less than ten years with normal weight or obesity. Some people who begin treatment with oral medications eventually need to take insulin. Unfortunately, insulin cannot be taken in pills form because enzymes in your stomach alter it, which makes it ineffective. Hence, insulin is taken with insulin syringe or insulin pump.

Insulin and oral diabetes medications deliberately work to lower your blood sugar. In certain cases medications taken for other conditions may affect glucose levels. Blood sugar levels may rise due to corticosteroids. Thiazides medications are used to control high blood pressure and niacin is used to lower high cholesterol. Your doctor has to change your diabetes treatment, if you need to take certain high blood pressure medications.

Number of drug options exists in market for treating type 2 diabetes, including

SULFONYLUREAS

Since 1994, sulfonylureas is the only drug used for diabetes in United States. It stimulates the pancreas for the production of more insulin to lower down the blood sugar. It can be effective when the pancreas can release some insulin by its own. Sulfonylureas such as glipizide (Glucotrol, Glucotrol XL), glyburide (DiaBeta, Glynase PresTab, Micronase) and glimepiride (Amaryl) are prescribed more often. If your body is sensitive to sulfa drug then you must avoid sulfonylureas.

Side Effects:

BIGUANIDES

Metformin (Glucophage, Glucophage XR) is the generic name of this drug. It works by inhibiting the production and release of glucose from your liver. It also lowers down the insulin secretion. One good thing about biguanides drug is that it tends to low down weight gain than do others. It can also improve blood cholesterol level, which is generally high if you are type 2 diabetic.

Side Effects:

If you already have a kidney problem, metformin may build up in your body. Inform your doctor when you are placed on this medication regarding your kidney problem.
If you are vomiting, have diarrhea, and can't drink enough fluids, you may need to stop taking this diabetes medication for a few days.
You may feel metallic taste.
If you are going for medical test using dye, or planning to opt for any surgery, then inform your doctor about your metformin intake. He will instruct you to stop taking metformin for some specific period.

Alpha-glucosidase Inhibitors

Alpha-glucosidase inhibitors are of two types, acarbose and miglitol. They block the enzymes of digestive system which are responsible for the break down of the starches you eat. The sugar produced is absorbed slowly and helps prevent the rise of blood sugar level throughout the day, but usually right after meals. Drugs under this class are Acarbose (Precose) and Miglitol (Glyset).

Side Effects:

Stomach problems such as gas, bloating and diarrhea etc.- temporary effects.
High dosages may cause permanent changes in liver.

Treatment for Gestational Diabetes

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Women with gestational diabetes have healthy pregnancies and healthy babies if, they follow a treatment plan from their health care provider. It is required to keep your blood glucose levels in a target range. Each woman should have a specific plan designed just for her needs, so one can follow these general tips to stay healthy with gestational diabetes:

Know your blood sugar and keep it under control
Eat a healthy diet
Get regular, moderate physical activity
Keep a healthy weight

Women with gestational diabetes should note down their blood sugar level, physical activity and everything she eats and drinks, in a daily record book. This can help track how well the treatment is working and what is to be done further to maintain the normal blood sugar level. Some women with gestational diabetes will also need to take insulin, to help manage their diabetes if blood sugar is shooting up, in spite of all this. The extra insulin can help them lower their blood sugar level.

Symptoms of Gestational Diabetes

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Often women with gestational diabetes exhibit no symptoms. Screening glucose challenge test is a preliminary screening test performed between 26-28 weeks. However, symptoms of gestational diabetes are similar as Type II diabetes. It includes increased thirst, increased urination, fatigue, nausea and vomiting, bladder and yeast infection, and blurred vision.

Gestational Diabetes – Risk of diabetes in Future:

Gestational diabetes is only a temporary phase, it disappears after pregnancy. But once you are diagnosed with gestational diabetes, your chances are 2 in 3 that it will return in future. It is hard to tell whether the particular woman has diabetes due to gestational diabetes or type 2 diabetes. There seems to be a link between the tendency to get gestational diabetes and type 2 diabetes. Gestational diabetes and type 2 diabetes both involve insulin resistance.

Risk factors for gestational diabetes include:

Strong family history of type 2 diabetes
Mother’s age - a woman is at higher risk if she is aged at the time of pregnancy
Obesity
Fallen prey to gestational diabetes in previous pregnancy
A previous pregnancy that resulted in a child with a birth weight of 9 pounds or more
If you are diagnosed with prediabetes, impaired glucose tolerance, or impaired fasting glucose

Gestational Diabetes Test

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Depending on risk factors, the doctor will decide when you need to be checked for diabetes. If you are at higher risk, the blood glucose level may be checked at your first prenatal visit. If your test results are normal, you will be checked again sometime between weeks 24 and 28 of your pregnancy.

Depending on the risk and your test results, you may have one or more of the following tests:

Fasting blood glucose or random blood glucose test: When plasma glucose level is >126 mg/dl or when random plasma glucose >200 mg/dl is confirmed on a subsequent day then the woman is at risk to develop GDM. Hence, you will be suggested by your doctor to go for some confirmatory tests.

Screening glucose challenge test: It is a preliminary screening test, which is performed between 26-28 weeks. This test will diagnose whether diabetes exists or not by indicating whether or not the body is using glucose. The Glucose Challenge Screening is now considered to be a standard test performed during the second trimester of pregnancy.

Oral glucose tolerance test (OGTT): Women who are considered at risk for gestational diabetes are being asked to go for this test. The glucose challenge is performed by giving 1.76 oz of glucose drink and then drawing a blood sample an hour later and measuring the level of blood glucose present. Women with a blood sugar level greater than 140 mg/dl may have gestational diabetes, and require a follow up test called a 3-hour oral glucose tolerance test (OGTT).

According to ADA following values are considered to be abnormal for the OGTT:

Fasting Blood Glucose Level≥95 mg/dl
1 Hour Blood Glucose Level≥180 mg/dl
2 Hour Blood Glucose Level≥155 mg/dl
3 Hour Blood Glucose Level≥140 mg/dl

Types of Gestational Diabetes

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There are 2 types of gestational diabetes:

Type A1: Only diet modification is sufficient to maintain normal glucose levels.
Type A2: Insulin or other medications along with diet are required to maintain normal range of blood glucose.

Gestational diabetes is also classified into different forms of diabetes which existed prior to pregnancy:

Type B: onset at age 20 or older or with duration of less than 10 years.
Type C: onset at age 10-19 or duration of 1-19 years.
Type D: onset before age 10 or duration greater than 20 years.
Type F: diabetic nephropathy.
Type R: diabetic retinopathy.
Type H: diabetes with ischemic heart disease.
Type T: diabetes requiring kidney transplant.

Gestational Diabetes

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Gestational diabetes is a form of diabetes which affects pregnant women. It is believed that the hormones produced during pregnancy reduce a woman's receptivity to insulin, leading to high blood sugar levels. Gestational diabetes affects about 4% of all pregnant women. It is estimated that about 135,000 cases of gestational diabetes arise in the United States each year.

Hormones involved in development of placenta, which helps the baby to develop also blocks, the action of the mother's insulin in her body. This problem is called insulin resistance. During pregnancy a mother may need up to three times more insulin for glucose to leave the blood and transform to energy. When body is not able to use insulin due to insulin resistance it develops into Gestational Diabetes. Glucose builds up in the blood to high level, it is called hyperglycemia.

Gestational diabetes affects the mother in late pregnancy and the baby too. Insulin does not cross the placenta, as glucose and other nutrients do. Extra blood glucose passes through the placenta that gives the baby a high blood glucose level. It results the baby's pancreas to make extra insulin to get rid of the blood glucose. Since the baby is getting more energy than it needs to develop and grow, the extra energy is stored as fat. It can lead to Macrosomia i.e. “Fat” baby. At birth this fat baby develops problem in breathing or may develop hypoglycemia due to over production of insulin.

Why there is a need to take care of gestational diabetes

Gestational diabetes can harm you and your baby, so you need to consider about it seriously and start caring at once. The main aim of gestational diabetes treatment is to keep blood glucose levels equal to those of normal pregnant women. It needs a planned meal and scheduled physical activity, even blood glucose testing and insulin injections if required. If gestational diabetes is taken care off properly, reduces the risk of a cesarean section birth that high weight babies may require.

Diabetes Diet

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Diet plays a significant role in controlling the diabetes. The diabetic diet may be used alone or else in combination with insulin doses or with oral hypoglycemic drugs. Main objective of diabetic diet is to maintain ideal body weight, by providing adequate nutrition along with normal blood sugar levels in blood. The diet plan for a diabetic is based on height, weight, age, sex, physical activity and nature of diabetes. While planning diet, the dietician has to consider complications such as high blood pressure, high cholesterol levels.

With respect to the above factors, a dietician will assess calories to be given, like scheming the carbohydrates, proteins, fats, type of carbohydrate, amount of fiber and so on.

Exchange meal plan is a diet program which balances the amount of carbohydrate that we intake per day. Glucose is a sugar released from carbohydrate so, if we want to control blood sugar we have to limit the consumption of simple carbohydrate. Carbohydrate foods are given as value per portion, known as the exchange. This plan helps us to decide on the type of food to be taken, the amount of food and also the time to eat. You can plan for more flexible meals as you get more knowledge about the diet for a diabetic, may be like the counting carbohydrate meal plan or constant carbohydrate. But there is no common diet that works for everyone. Nor is there any particular diet that works perfectly for any diabetic over a long period. While planning diabetes Diet we should adhere to certain important factors, they are as follows:

Fiber should be at least 1.4 oz / day
Instead of 3 heavy meals, we should go for 4-5 small mid intervals
Replace bakery products and fast foods by simple whole cooked cereals, and don't eat carbohydrates 2 hours before bedtime
Consume fresh fruit and vegetables at least 5 exchange/ day

Diabetics always need to take care of their diet and also about the food they eat. Care has to be taken because all foods contain not only carbohydrate, but also some energy value. Protein and fat available in the food are converted to glucose in the body. This glucose has some effect on the blood sugar level, which has to be taken care of. Furthermore, you needn’t have to eat only the bland boring diet. Instead, you can eat more fruits, vegetables and whole grains. All it means is that you need to select foods that are high in nutrition and low in calories.

Diabetes Mellitus Outlook Treatment Care

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Diabetes mellitus is a disorder in which blood sugar (glucose) levels are abnormally high because the body does not produce enough insulin to meet its needs.

Urination and thirst are increased, and people lose weight when they are not trying to.
Diabetes damages the nerves and causes problems with sensation.
Diabetes damages blood vessels and increases the risk of heart attack, stroke, and kidney failure.
Doctors diagnose diabetes by measuring blood sugar levels.
People with diabetes need to follow a low-sugar, low-fat diet, exercise, and usually take drugs.

Insulin, a hormone released from the pancreas, controls the amount of sugar in the blood. When people eat or drink, food is broken down into materials, including the simple sugar glucose, that the body needs to function. Sugar is absorbed into the bloodstream and stimulates the pancreas to produce insulin. Insulin allows sugar to move from the blood into the cells. Once inside the cells, it is converted to energy, which is either used immediately or stored as fat or glycogen until it is needed.

The levels of sugar in the blood vary normally throughout the day. They rise after a meal and return to normal within about 2 hours after eating. Once the levels of sugar in the blood return to normal, insulin production decreases. The variation in blood sugar levels is usually within a narrow range, about 70 to 110 milligrams per deciliter (mg/dL) of blood. If people eat a large amount of carbohydrates, the levels may increase more. People older than 65 years tend to have slightly higher levels, especially after eating.

If the body does not produce enough insulin to move the sugar into the cells, the resulting high levels of sugar in the blood and the inadequate amount of sugar in the cells together produce the symptoms and complications of diabetes.

Doctors often use the full name diabetes mellitus, rather than diabetes alone, to distinguish this disorder from diabetes insipidus, a relatively rare disorder that does not affect blood sugar levels (see Pituitary Gland Disorders: Central Diabetes Insipidus).

Types

Prediabetes: Prediabetes is a condition in which blood sugar levels are too high to be considered normal but not high enough to be labeled diabetes. People have prediabetes if their fasting blood sugar level is between 101 mg/dL and 126 mg/dL or if their blood sugar level 2 hours after a glucose tolerance test is between 140 mg/dL and 200 mg/dL. Identifying people with prediabetes is important because the condition carries a higher risk for future diabetes as well as heart disease. Decreasing body weight by 5 to 10 % through diet and exercise can significantly reduce the risk of developing future diabetes.

Type 1: In type 1 diabetes (formerly called insulin-dependent diabetes or juvenile-onset diabetes), more than 90% of the insulin-producing cells of the pancreas are permanently destroyed. The pancreas, therefore, produces little or no insulin. Only about 10% of all people with diabetes have type 1 disease. Most people who have type 1 diabetes develop the disease before age 30.

Scientists believe that an environmental factor—possibly a viral infection or a nutritional factor in childhood or early adulthood—causes the immune system to destroy the insulin-producing cells of the pancreas. A genetic predisposition may make some people more susceptible to the environmental factor.

Type 2: In type 2 diabetes (formerly called non-insulin-dependent diabetes or adult-onset diabetes), the pancreas continues to produce insulin, sometimes even at higher-than-normal levels. However, the body develops resistance to the effects of insulin, so there is not enough insulin to meet the body's needs.

Type 2 diabetes was once rare in children and adolescents but has recently become more common. However, it usually begins in people older than 30 and becomes progressively more common with age. About 15% of people older than 70 have type 2 diabetes. People of certain racial and ethnic backgrounds are at increased risk of developing type 2 diabetes: blacks, Native Americans, and Hispanics who live in the United States have a twofold to threefold increased risk. Type 2 diabetes also tends to run in families.

Obesity is the chief risk factor for developing type 2 diabetes, and 80 to 90% of people with this disorder are overweight or obese. Because obesity causes insulin resistance, obese people need very large amounts of insulin to maintain normal blood sugar levels.

Certain disorders and drugs can affect the way the body uses insulin and can lead to type 2 diabetes. High levels of corticosteroids (from Cushing's disease or from taking corticosteroid drugs) and pregnancy (gestational diabetes—see Pregnancy Complicated by Disease: Gestational Diabetes) are the most common causes of altered insulin use. Diabetes also may occur in people with excess production of growth hormone (acromegaly) and in people with certain hormone-secreting tumors. Severe or recurring pancreatitis and other disorders that directly damage the pancreas can lead to diabetes.

Symptoms

The two types of diabetes have very similar symptoms. The first symptoms are related to the direct effects of high blood sugar levels. When the blood sugar level rises above 160 to 180 mg/dL, sugar spills into the urine. When the level of sugar in the urine rises even higher, the kidneys excrete additional water to dilute the large amount of sugar. Because the kidneys produce excessive urine, people with diabetes urinate large volumes frequently (polyuria). The excessive urination creates abnormal thirst (polydipsia). Because excessive calories are lost in the urine, people lose weight. To compensate, people often feel excessively hungry. Other symptoms include blurred vision, drowsiness, nausea, and decreased endurance during exercise.

Type 1: In people with type 1 diabetes, the symptoms often begin abruptly and dramatically. A condition called diabetic ketoacidosis may quickly develop. Without insulin, most cells cannot use the sugar that is in the blood. Cells still need energy to survive, and they switch to a back-up mechanism to obtain energy. Fat cells begin to break down, producing compounds called ketones. Ketones provide some energy to cells but also make the blood too acidic (ketoacidosis). The initial symptoms of diabetic ketoacidosis include excessive thirst and urination, weight loss, nausea, vomiting, fatigue, and—particularly in children—abdominal pain. Breathing tends to become deep and rapid as the body attempts to correct the blood's acidity (see Acid-Base Balance: Acidosis). The breath smells like nail polish remover, the smell of the ketones escaping into the breath. Without treatment, diabetic ketoacidosis can progress to coma and death, sometimes within a few hours.

Type 2: People with type 2 diabetes may not have any symptoms for years or decades before they are diagnosed. Symptoms may be subtle. Increased urination and thirst are mild at first and gradually worsen over weeks or months. Eventually, people feel extremely fatigued, are likely to develop blurred vision, and may become dehydrated.

Sometimes during the early stages of diabetes, the blood sugar level is abnormally low, a condition called hypoglycemia (see Hypoglycemia).

Because people with type 2 diabetes produce some insulin, ketoacidosis does not usually develop. However, the blood sugar levels can become extremely high (often exceeding 1,000 mg/dL). Such high levels often happen as the result of some superimposed stress, such as an infection or drug use. When the blood sugar levels get very high, people may develop severe dehydration, which may lead to mental confusion, drowsiness, and seizures, a condition called nonketotic hyperglycemic-hyperosmolar coma.

Complications

People with diabetes may experience many serious, long-term complications. Some of these complications begin within months of the onset of diabetes, although most tend to develop after a few years. Most of the complications are progressive. The more strictly people with diabetes are able to control the levels of sugar in the blood, the less likely it is that these complications will develop or become worse.

Most complications are the result of problems with blood vessels. High sugar levels over a long time cause narrowing of both the small and large blood vessels. The narrowing reduces blood flow to many parts of the body, leading to problems. There are several causes of blood vessel narrowing. Complex sugar-based substances build up in the walls of small blood vessels, causing them to thicken and leak. Poor control of blood sugar levels also tends to cause the levels of fatty substances in the blood to rise, resulting in atherosclerosis (see Atherosclerosis) and decreased blood flow in the larger blood vessels. Atherosclerosis is between 2 and 6 times more common in people with diabetes than in people who do not have diabetes and tends to occur at younger ages.

Over time, elevated levels of sugar in the blood and poor circulation can harm the heart, brain, legs, eyes, kidneys, nerves, and skin, resulting in angina, heart failure, strokes, leg cramps on walking (claudication), poor vision, kidney failure, damage to nerves (neuropathy), and skin breakdown. Heart attacks and strokes are more common among people with diabetes.

Poor circulation to the skin can lead to ulcers and infections and causes wounds to heal slowly. People with diabetes are particularly likely to have ulcers and infections of the feet and legs. Too often, these wounds heal slowly or not at all, and amputation of the foot or part of the leg may be needed.

People with diabetes often develop bacterial and fungal infections, typically of the skin. When the levels of sugar in the blood are high, white blood cells cannot effectively fight infections. Any infection that develops tends to be more severe.

Did You Know...

People who can strictly control their blood sugar levels may be able to minimize or delay diabetes complications.

Damage to the blood vessels of the eye can cause loss of vision (diabetic retinopathy—see Retinal Disorders: Diabetic Retinopathy). Laser surgery can seal the leaking blood vessels of the eye and prevent permanent damage to the retina. Therefore, people with diabetes should have yearly eye examinations to check for damage.

The kidneys can malfunction, resulting in kidney failure that may require dialysis or kidney transplantation. Doctors usually check the urine of people with diabetes for abnormally high levels of protein (albumin), which is an early sign of kidney damage. At the earliest sign of kidney complications, people are often given angiotensin-converting enzyme (ACE) inhibitors, drugs that slow the progression of kidney damage.

Damage to nerves can manifest in several ways. If a single nerve malfunctions, an arm or leg may suddenly become weak. If the nerves to the hands, legs, and feet become damaged (diabetic polyneuropathy), sensation may become abnormal, and tingling or burning pain and weakness in the arms and legs may develop (see Peripheral Nerve Disorders: Causes). Damage to the nerves of the skin makes repeated injuries more likely because people cannot sense changes in pressure or temperature.

Long-Term Complications of Diabetes
Tissue or Organ Affected	What Happens	Complications
Blood vessels	Fatty material (atherosclerotic plaque) builds up and blocks large or medium-sized arteries in the heart, brain, legs, and penis. The walls of small blood vessels are damaged so that the vessels do not transfer oxygen to tissues normally, and the vessels may leak.	Poor circulation causes wounds to heal poorly and can lead to heart disorders, strokes, gangrene of the feet and hands, erectile dysfunction (impotence), and infections.
Eyes	The small blood vessels of the retina are damaged.	Decreased vision and, ultimately, blindness occur.
Kidney	Blood vessels in the kidney thicken. Protein leaks into urine. Blood is not filtered normally.	The kidneys malfunction, and ultimately, kidney failure occurs.
Nerves	Nerves are damaged because glucose is not metabolized normally and because the blood supply is inadequate.	Legs suddenly or gradually weaken. People have reduced sensation, tingling, and pain in their hands and feet.
Autonomic nervous system	The nerves that control blood pressure and digestive processes are damaged.	Swings in blood pressure occur. Swallowing becomes difficult. Digestive function is altered, and sometimes bouts of diarrhea occur. Erectile dysfunction develops.
Skin	Blood flow to the skin is reduced, and sensation is decreased, resulting in repeated injury.	Sores and deep infections (diabetic ulcers) develop. Healing is poor.
Blood	White blood cell function is impaired.	People become more susceptible to infections, especially of the urinary tract and skin.
Connective tissue	Glucose is not metabolized normally, causing tissues to thicken or contract.	Carpal tunnel syndrome and Dupuytren's contracture develop.

The Foot in Diabetes

Diabetes causes many changes in the body. The following changes in the feet are common and difficult to treat.

Damage to the nerves (neuropathy) affects sensation to the feet, so that pain is not felt. Irritation and other forms of injury may go unnoticed. An injury may wear through the skin before any pain is felt.
Changes in sensation alter the way people with diabetes carry weight on their feet, concentrating weight in certain areas so that calluses form. Calluses (and dry skin) increase the risk of skin breakdown.
Diabetes can cause poor circulation in the feet, making ulcers more likely to form when the skin is damaged and making the ulcers slower to heal.

Because diabetes can affect the body's ability to fight infections, a foot ulcer, once it forms, easily becomes infected. Because of neuropathy, people may not feel discomfort from the infection until it becomes serious and difficult to treat, leading to gangrene. People with diabetes are more than 30 times more likely to require amputation of a foot or leg than are people without diabetes.

Foot care is critical (see Caring for the Feet). The feet should be protected from injury, and the skin should be kept moist with a good moisturizer. Shoes should fit properly and not cause areas of irritation. Shoes should have appropriate cushioning to spread out the pressure caused by standing. Going barefoot is ill advised. Regular care from a podiatrist, such as having toenails cut and calluses removed, may also be helpful. Also, sensation and blood flow to the feet should be regularly evaluated by doctors.

Diagnosis

The diagnosis of diabetes is made when people have abnormally high levels of sugar in the blood. Blood sugar levels are often checked during a routine physical examination. Checking the levels of sugar in the blood annually is particularly important in older people, because diabetes is so common in later life. People may have diabetes, particularly type 2 diabetes, and not know it. Doctors may also check blood sugar levels in people who have symptoms of diabetes such as increased thirst, urination, or hunger. Doctors may also check blood sugar levels in people who have disorders that can be complications of diabetes, such as frequent infections, foot ulcers, and yeast infections.

To measure the blood sugar levels, a blood sample is usually taken after people have fasted overnight. However, it is possible to take blood samples after people have eaten. Some elevation of blood sugar levels after eating is normal, but even after a meal the levels should not be very high. Fasting blood sugar levels should never be higher than 126 mg/dL. Even after eating, blood sugar levels should not be higher than 200 mg/dL.

Doctors can also measure the level of a protein in the blood, hemoglobin A_1C (also called glycosylated or glycolated or hemoglobin). Glycosylated hemoglobin forms when the blood has been exposed to high blood sugar levels over a period of time. Doctors do not usually use this test to diagnose diabetes, but the test can help confirm the diagnosis when blood sugar levels are not extremely high. The test demonstrates long-term trends in blood sugar levels.

Another kind of blood test, an oral glucose tolerance test, may be done in certain situations, such as in routine screening of pregnant women for gestational diabetes (see Pregnancy Complicated by Disease: Gestational Diabetes) or in older people who have symptoms of diabetes but normal glucose levels when fasting. However, it is not routinely used for testing for diabetes, including in pregnant women at very low risk. In this test, people fast, have a blood sample taken to determine the fasting blood sugar level, and then drink a special solution containing a large, standard amount of glucose. More blood samples are then taken over the next 2 to 3 hours and are tested to determine whether the level of sugar in the blood rises abnormally high.

Did You Know...

Many people have type 2 diabetes and are not aware of it.

Treatment

Treatment of diabetes involves diet, exercise, education, and, for most people, drugs. If people with diabetes strictly control blood sugar levels, complications are less likely to develop. The goal of diabetes treatment, therefore, is to keep blood sugar levels within the normal range as much as possible. Treatment of high blood pressure and cholesterol levels can prevent some of the complications of diabetes as well. A low dose of aspirin Some Trade Names
ECOTRIN
ASPERGUM
taken daily is also helpful.

People with diabetes benefit greatly from learning about the disorder, understanding how diet and exercise affect their blood sugar levels, and knowing how to avoid complications. A nurse trained in diabetes education can provide information about managing diet, exercising, monitoring blood sugar levels, and taking drugs.

People with diabetes should always carry or wear medical identification (such as a bracelet or tag) to alert health care practitioners to the presence of diabetes. This information allows health care practitioners to start life-saving treatment quickly, especially in the case of injury or altered mental status.

Diet management is very important in people with both types of diabetes. Doctors recommend a healthy, balanced diet and efforts to maintain a healthy weight. Some people benefit from meeting with a dietitian to develop an optimal eating plan.

People with type 1 diabetes who are able to maintain a healthy weight may be able to avoid the need for large doses of insulin Some Trade Names
HUMULIN
NOVOLIN
. People with type 2 diabetes may be able to avoid the need for all drugs by achieving and maintaining a healthy weight. Some people who have been unsuccessful in losing weight through diet and exercise may take drugs to help them lose weight or may even undergo stomach reduction surgery.

In general, people with diabetes should not eat much sweet food. They should also try to eat meals on a regular schedule. Long periods between eating should be avoided. People with diabetes also tend to have high levels of cholesterol in the blood, so limiting the amount of saturated fat in the diet is important. Drugs may also be needed to help control the level of cholesterol in the blood.

Appropriate amounts of exercise can also help people control their weight and maintain blood sugar levels within the normal range. Because blood sugar levels go down during exercise, people must be alert for symptoms of low blood sugar. Some people need to eat a small amount of food with sugar during prolonged exercise, decrease their insulin dose, or both. People with diabetes should stop smoking and consume only moderate amounts of alcohol (up to one drink per day for women and two for men).

Diabetic ketoacidosis is a medical emergency, because it can cause coma and death. Hospitalization, usually in an intensive care unit, is necessary. Large amounts of fluids are given intravenously along with electrolytes, such as sodium, potassium, chloride, and phosphate, to replace those fluids and electrolytes lost through excessive urination. Insulin Some Trade Names
HUMULIN
NOVOLIN
is generally given intravenously so that it works quickly and the dose can be adjusted frequently. Blood levels of sugar, ketones, and electrolytes are measured every few hours. Doctors also measure the blood's acid level. Sometimes, additional treatments are needed to correct a high acid level. However, controlling the levels of sugar in the blood and replacing electrolytes usually allow the body to restore the normal acid-base balance.

Nonketotic hyperglycemic-hyperosmolar coma is treated much like diabetic ketoacidosis. Fluids and electrolytes must be replaced. The levels of sugar in the blood must be restored to normal levels gradually to avoid sudden shifts of fluid into the brain. The blood sugar levels tend to be more easily controlled than in diabetic ketoacidosis, and blood acidity problems are not severe.

Insulin Replacement Therapy

People with type 1 diabetes almost always require insulin Some Trade Names
HUMULIN
NOVOLIN
therapy, and many people with type 2 diabetes require it as well. Insulin Some Trade Names
HUMULIN
NOVOLIN
is injected. It currently cannot be taken by mouth because insulin Some Trade Names
HUMULIN
NOVOLIN
is destroyed in the stomach. A nasal spray form of insulin Some Trade Names
HUMULIN
NOVOLIN
was available but has been discontinued. New forms of insulin Some Trade Names
HUMULIN
NOVOLIN
, such as forms that can be taken by mouth or applied to the skin, are being tested.

Insulin

Insulin Some Trade Names
HUMULIN
NOVOLIN
is injected under the skin into the fat layer, usually in the arm, thigh, or abdominal wall. Small syringes with very thin needles make the injections nearly painless. An air pump device that blows the insulin Some Trade Names
HUMULIN
NOVOLIN
under the skin can be used for people who cannot tolerate needles. An insulin Some Trade Names
HUMULIN
NOVOLIN
pen, which contains a cartridge that holds the insulin Some Trade Names
HUMULIN
NOVOLIN
, is a convenient way for many people to carry insulin Some Trade Names
HUMULIN
NOVOLIN
, especially for people who take several injections a day outside the home. Another device is an insulin Some Trade Names
HUMULIN
NOVOLIN
pump, which pumps insulin Some Trade Names
HUMULIN
NOVOLIN
continuously from a reservoir through a small needle left in the skin. Additional doses of insulin Some Trade Names
HUMULIN
NOVOLIN
can be released at programmed times, or release can be triggered as needed. The pump more closely mimics the way the body normally produces insulin Some Trade Names
HUMULIN
NOVOLIN
. For some people, the pump offers an added degree of control, whereas others find wearing the pump annoying or develop sores at the needle site.

Insulin Some Trade Names
HUMULIN
NOVOLIN
is available in three basic forms, divided by speed of onset and duration of action:

Rapid-acting insulin, such as regular insulin Some Trade Names
HUMULIN
NOVOLIN
, is fast and short acting. Regular insulin Some Trade Names
HUMULIN
NOVOLIN
reaches its maximum activity in 2 to 4 hours and works for 6 to 8 hours. Lispro, aspart, and glulisine insulins, special types of regular insulin Some Trade Names
HUMULIN
NOVOLIN
, are the fastest of all, reaching maximum activity in about 1 hour and working for 3 to 5 hours. Rapid-acting insulin Some Trade Names
HUMULIN
NOVOLIN
is often used by people who take several daily injections and is injected 15 to 20 minutes before meals or just after eating.
Intermediate-acting insulin (such as insulin Some Trade Names
HUMULIN
NOVOLIN
zinc suspension, lente, or isophane insulin Some Trade Names
HUMULIN
NOVOLIN
suspension) starts to work in 1 to 3 hours, reaches its maximum activity in 6 to 10 hours, and works for 18 to 26 hours. This type of insulin Some Trade Names
HUMULIN
NOVOLIN
may be used in the morning to provide coverage for the first part of the day or in the evening to provide coverage during the night.
Long-acting insulin (such as extended insulin Some Trade Names
HUMULIN
NOVOLIN
zinc suspension, ultra-lente, or glargine) has very little effect in the first few hours but provides coverage for 20 to 36 hours depending on which of these types is used.

Insulin Some Trade Names
HUMULIN
NOVOLIN
preparations are stable at room temperature for months, allowing them to be carried, brought to work, or taken on a trip. Insulin Some Trade Names
HUMULIN
NOVOLIN
should not, however, be exposed to extreme temperatures.

The choice of insulin Some Trade Names
HUMULIN
NOVOLIN
is complex. The following factors are considered before deciding which insulin Some Trade Names
HUMULIN
NOVOLIN
is best:

How willing and able people are to monitor their blood sugar levels and adjust the insulin Some Trade Names
HUMULIN
NOVOLIN
dosage
How varied daily activity is
How adept people are at learning about and understanding the disorder
How stable blood sugar levels are during the day and from day to day

The easiest regimen to follow is a single daily injection of an intermediate-acting insulin Some Trade Names
HUMULIN
NOVOLIN
. However, such a regimen provides the least control over blood sugar levels and is, therefore, rarely the best approach. Stricter control may be achieved by combining two insulins—a rapid-acting and an intermediate-acting insulin Some Trade Names
HUMULIN
NOVOLIN
—in one morning dose. This combination requires more skill, but it offers people greater opportunity to adjust the blood sugar levels. A second injection of one insulin Some Trade Names
HUMULIN
NOVOLIN
or both may be taken at dinner or at bedtime. Strictest control is usually achieved by injecting a rapid-acting and an intermediate-acting insulin Some Trade Names
HUMULIN
NOVOLIN
in the morning and evening along with several additional injections of rapid-acting insulin Some Trade Names
HUMULIN
NOVOLIN
during the day. Adjustments can be made as insulin Some Trade Names
HUMULIN
NOVOLIN
needs change. Measuring blood sugar levels at various times during the day helps determine the adjustment. Although this regimen requires the most knowledge of the disorder and attention to the details of treatment, it is considered the best option for most people who are treated with insulin Some Trade Names
HUMULIN
NOVOLIN
, especially people with type 1 diabetes.

Some people, especially older people, take the same amount of insulin Some Trade Names
HUMULIN
NOVOLIN
every day. Other people adjust the insulin Some Trade Names
HUMULIN
NOVOLIN
dose daily depending on their diet, exercise, and blood sugar patterns. In addition, insulin Some Trade Names
HUMULIN
NOVOLIN
needs may change if people gain or lose weight or experience emotional stress or illness, especially infection.

Over time, some people develop resistance to insulin Some Trade Names
HUMULIN
NOVOLIN
. Because the injected insulin Some Trade Names
HUMULIN
NOVOLIN
is not exactly like the insulin Some Trade Names
HUMULIN
NOVOLIN
the body manufactures, the body can produce antibodies to the insulin Some Trade Names
HUMULIN
NOVOLIN
. Although this is less common with newer insulin Some Trade Names
HUMULIN
NOVOLIN
preparations, these antibodies may interfere with the insulin Some Trade Names
HUMULIN
NOVOLIN
's activity, requiring very large doses.

Insulin Some Trade Names
HUMULIN
NOVOLIN
injections can affect the skin and underlying tissues. An allergic reaction, which occurs rarely, produces pain and burning, followed by redness, itchiness, and swelling around the injection site for several hours. More commonly, the injections either cause fat deposits, making the skin look lumpy, or destroy fat, causing indentation of the skin. Many people rotate the injection sites, for example, using the thigh one day, the stomach another, and an arm the next, to avoid these problems.

Insulin Replacement Therapy

Oral Antihyperglycemic Drugs

Oral antihyperglycemic drugs can often lower blood sugar levels adequately in people with type 2 diabetes. However, they are not effective in type 1 diabetes. There are several types. Sulfonylureas (for example, glyburide Some Trade Names
DIABETA
MICRONASE
) and meglitinides (for example, repaglinide Some Trade Names
PRANDIN
) stimulate the pancreas to produce more insulin Some Trade Names
HUMULIN
NOVOLIN
( insulin Some Trade Names
HUMULIN
NOVOLIN
secretagogues). Biguanides (for example, metformin Some Trade Names
GLUCOPHAGE
) and thiazolidinediones (for example, rosiglitazone Some Trade Names
AVANDIA
) do not affect the release of insulin Some Trade Names
HUMULIN
NOVOLIN
but increase the body's response to it ( insulin Some Trade Names
HUMULIN
NOVOLIN
sensitizers). Doctors may prescribe one of these drugs alone or with a sulfonylurea drug. Another class of drug is the glucosidase inhibitors, such as acarbose Some Trade Names
PRECOSE
, which work by delaying absorption of glucose in the intestine.

Oral antihyperglycemic drugs are usually prescribed for people with type 2 diabetes if diet and exercise fail to lower the levels of sugar in the blood adequately. The drugs are sometimes taken only once a day, in the morning, although some people need two or three doses. More than one type of oral drug may be used if one is not adequate. If oral antihyperglycemic drugs cannot control blood sugar levels well enough, insulin Some Trade Names
HUMULIN
NOVOLIN
injections alone or in combination with the oral drugs may be needed.

Oral Antihyperglycemic Drugs

Drug

Number of Daily Doses

Selected Side Effects

Biguanides

Metformin Some Trade Names
GLUCOPHAGE

2 to 3

Diarrhea

Increased acidity of body fluids (rare)

Liver failure (rare)

Extended-release metformin Some Trade Names
GLUCOPHAGE

1 to 2

Sulfonylureas

Acetohexamide Some Trade Names
DYMELOR

1 to 2

Weight gain

Low sodium in blood (hyponatremia) with chlorpropamide Some Trade Names
DIABINESE

Chlorpropamide Some Trade Names
DIABINESE

Glimepiride Some Trade Names
AMARYL

Glipizide Some Trade Names
GLUCOTROL

1 to 2

Glyburide Some Trade Names
DIABETA
MICRONASE

1 to 2

Micronized glyburide Some Trade Names
DIABETA
MICRONASE

1 to 2

Tolazamide Some Trade Names
TOLINASE

1 to 2

Tolbutamide Some Trade Names
ORINASE

1 to 2

Meglitinides

Nateglinide Some Trade Names
STARLIX

Minimal weight gain

Repaglinide Some Trade Names
PRANDIN

Thiazolidinediones

Pioglitazone Some Trade Names
ACTOS

Weight gain

Fluid retention (edema)

Rosiglitazone Some Trade Names
AVANDIA

1 to 2

Weight gain

Fluid retention (edema)

Possible increase in heart attacks

Alpha-glucosidase inhibitors

Acarbose Some Trade Names
PRECOSE

Diarrhea

Abdominal pain

Bloating

Miglitol Some Trade Names
BLYSERT

Dipeptidyl peptidase-4 inhibitor

Sitagliptin

Headache

Diarrhea

Lung infections

Glucagon-like peptide agonists

Exenatide

Nausea

Vomiting

Amylin analog

Pramlintide

Nausea

Low blood sugar levels

Monitoring Treatment

Monitoring blood sugar levels is an essential part of diabetes care. People with diabetes must adjust their diet, exercise, and take drugs to control blood sugar levels. Monitoring blood sugar levels provides the information needed to make those adjustments. Waiting until symptoms of low or high blood sugar levels develop is a recipe for disaster.

Many things cause blood sugar levels to change:

Diet
Exercise
Stress
Illness
Drug
Time of day

The blood sugar levels may jump after people eat foods they did not realize were high in carbohydrates. Exercise may cause the levels of sugar in the blood to fall low, requiring that additional sugar be eaten. Emotional stress, an infection, and many drugs tend to increase blood sugar levels. Blood sugar levels increase in many people in the early morning hours because of the normal release of hormones (growth hormone and corticosteroids), a reaction called the dawn phenomenon. And blood sugar may shoot too high if the body releases sugar in response to low blood sugar levels (Somogyi effect).

Blood sugar levels can be measured easily at home or anywhere. Most blood sugar monitoring devices use a drop of blood obtained by pricking the tip of the finger with a small lancet. The lancet holds a tiny needle that can be jabbed into the finger or placed in a spring-loaded device that easily and quickly pierces the skin. Most people find the pricking nearly painless. Then, a drop of blood is placed on a reagent strip. In response to sugar, the reagent strip undergoes some chemical changes. A machine reads the changes in the test strip and reports the result on a digital display. Most of these machines time the reaction and read the result automatically. Some devices allow the blood sample to be obtained from other sites, such as the palm, forearm, upper arm, thigh, or calf. The machines are smaller than a deck of cards.

A newer device reads blood sugar through the skin without needing a sample of blood. The device is worn like a wristwatch and can measure the level of sugar in the blood every 15 minutes. Alarms on the device can be set to sound when blood sugar levels drop too low or climb too high. Disadvantages of this device are that it must be calibrated periodically with a blood test, it may irritate the skin, and it is somewhat large. Other devices can monitor glucose continuously. However, these devices are not routinely used, as they are expensive and have not been shown to be better than glucose meters. In certain circumstances, these devices are less reliable, such as in severe hypoglycemia.

Most people with diabetes should keep a record of their blood sugar levels and report them to their doctors or nurses for advice in adjusting the dose of insulin Some Trade Names
HUMULIN
NOVOLIN
or the oral antihyperglycemic drug. Many people can learn to adjust the insulin Some Trade Names
HUMULIN
NOVOLIN
dose on their own as necessary.

Spotlight on Aging

Older people need to follow the same general principles of diabetes management—education, diet, exercise, and drugs—as younger people. However, risking hypoglycemia by strictly controlling blood sugar levels may not be beneficial for people with a short life expectancy, such as those with advanced cancer. Also, managing diabetes can be more difficult for older people. Poor eyesight may make it hard for them to read glucose meters and dose scales on insulin Some Trade Names
HUMULIN
NOVOLIN
syringes. They may have problems manipulating the syringe because they have arthritis or Parkinson's disease or have had a stroke. When older people have hypoglycemia, their symptoms may be less obvious. If they have hypoglycemia but have difficulty communicating, dementia or both, they may not be able to let anyone know they are having symptoms.

Education: In addition to learning about diabetes itself, older people may have to learn how to fit management of diabetes in with their management of other disorders. Learning about how to avoid complications, such as dehydration, skin breakdown, and circulation problems, and to manage factors that can contribute to diabetes, such as high blood pressure and high cholesterol levels, is especially important. Such problems become more common as people age, whether they have diabetes or not.

Diet: Many older people have difficulty following a healthy, balanced diet that can control blood sugar levels and weight. Changing long-held food preferences and dietary habits may be hard. Some older people have other disorders that can be affected by diet and may not understand how to integrate the dietary recommendations for their various disorders.

Some older people cannot control what they eat because someone else is cooking for them―at home or in a nursing home or other institution. When people with diabetes do not do their own cooking, the people who shop and prepare meals for them must also understand the diet that is needed. Older people and their caregivers usually benefit from meeting with a dietitian to develop a healthy, feasible eating plan.

Exercise: Older people may have a difficult time adding exercise to their daily life, particularly if they have not been active or if they have a disorder that limits their movement, such as arthritis. However, they may be able to add exercise to their usual routine. For example, they can walk instead of drive or climb the stairs instead of take the elevator. Also, many community organizations offer exercise programs designed for older people.

Drugs: Taking the drugs used to treat diabetes, particularly insulin Some Trade Names
HUMULIN
NOVOLIN
, may be difficult for some older people. For those with vision problems or other problems that make accurately filling a syringe difficult, a caregiver can prepare the syringes ahead of time and store them in the refrigerator. People whose insulin Some Trade Names
HUMULIN
NOVOLIN
dose is stable may purchase pre-filled syringes. Prefilled insulin Some Trade Names
HUMULIN
NOVOLIN
pen devices may be easier for people with physical limitations to use. Some of these devices have large numbers and easy-to-turn dials.

Monitoring blood sugar levels: Poor vision, limited manual dexterity due to arthritis, tremor, or stroke, or other physical limitations may make monitoring blood sugar levels more difficult for older people. However, special monitors are available. Some have large numerical displays that are easier to read. Some provide audible instructions and results. Some monitors read blood sugar levels through the skin and do not require a blood sample. People can consult a diabetes educator to determine which meter is most appropriate.

Complications of treatment: The most common complication of treating high blood sugar levels is low blood sugar levels. The risk is greatest for older people who are frail, who are sick enough to require frequent hospital admissions, or who are taking several drugs. Of all available drugs to treat diabetes, long-acting sulfonylurea drugs are most likely to cause low blood sugar levels in older people. When they take these drugs, they are also more likely to have serious symptoms, such as fainting and falling, and to have diffculty thinking or using parts of the body due to low blood sugar levels.

Although urine can also be tested for the presence of sugar, checking urine is not a good way to monitor treatment or adjust therapy. Urine testing can be misleading because the amount of sugar in the urine may not reflect the current level of sugar in the blood. Blood sugar levels can get very low or reasonably high without any change in the sugar levels in the urine.

Doctors can monitor treatment using a blood test called hemoglobin A_1C. When the blood sugar levels are high, changes occur in hemoglobin, the protein that carries oxygen in the blood. These changes are in direct proportion to the blood sugar levels over an extended period. Thus, unlike the blood sugar measurement, which reveals the level at a particular moment, the hemoglobin A_1C measurement demonstrates whether the blood sugar levels have been controlled over the previous few months. People with diabetes aim for a hemoglobin A_1C level of less than 7%. Achieving this level is difficult, but the lower the hemoglobin A_1C level, the less likely people are to have complications. Levels above 9% show poor control, and levels above 12% show very poor control. Most doctors who specialize in diabetes care recommend that hemoglobin A_1C be measured every 3 to 6 months. Fructosamine, an amino acid that has bonded with glucose, is also useful for measuring blood sugar control over a period of a few weeks.

Monitoring and Preventing Complications

At the time of diagnosis and then at least yearly, people are monitored for the presence of diabetes complications, such as kidney, eye, and nerve damage. Worsening of complications can be prevented or delayed by strict blood sugar control or by early drug treatment. Risk factors for heart problems, such as increased blood pressure and high cholesterol levels, are evaluated at each doctor visit and are treated with drugs if necessary. Another common problem in people with diabetes is gum disease (gingivitis), and regular visits to the dentist for cleaning and preventive care are important.

Hypoglycemia: Keeping blood sugar levels from getting too high is difficult. The main difficulty with trying to strictly control the levels of sugar in the blood is that low blood sugar levels (hypoglycemia) may occur (see Hypoglycemia). Recognizing the presence of low blood sugar is important because treatment of hypoglycemia is an emergency. Symptoms may include hunger pangs, racing heart beat, shakiness, sweating, and inability to think clearly. Sugar must get into the body within minutes to prevent permanent harm and relieve symptoms. Most of the time, people can eat sugar. Almost any form of sugar will do, although glucose works more quickly than table sugar (typical table sugar is sucrose). Many people with diabetes carry glucose tablets or foil packets of a glucose-containing liquid. Other options are to drink a glass of milk (which contains lactose, a type of sugar), sugar water, or fruit juice or to eat a piece of cake, some fruit, or another sweet food. In more serious situations, it may be necessary for emergency medical practitioners to inject glucose into a vein.

Another treatment for hypoglycemia involves the use of glucagon. Glucagon can be injected into the muscle and causes the liver to release large amounts of glucose within minutes. Small transportable kits containing a syringe filled with glucagon are available for people with diabetes to use in emergency situations.

Experimental Treatments

Experimental treatments are also showing promise for the treatment of type 1 diabetes. In one such treatment, insulin-producing cells are transplanted into body organs. This procedure is not yet routinely done, however, because immunosuppressant drugs must be given to prevent the body from rejecting the transplanted cells. Newer techniques may make suppression of the immune system unnecessary

Blood and Lymph Diseases

2009-06-14T09:24:00.000-07:00

s most of the cells in the human body are not in direct contact with the external environment, the circulatory system acts as a transport system for these cells. Two distinct fluids move through the circulatory system: blood and lymph. Blood carries oxygen and nutrients to the body's cells, and carries waste materials away. Blood also carries hormones, which control body processes, and antibodies, to fight invading germs. The heart is the pump that keeps this transport system moving. Together, the blood, heart, and blood vessels form the circulatory system.

The lymphatic system (lymph, lymph nodes and lymph vessels) supports the circulatory system by draining excess fluids and proteins from tissues back into the bloodstream, thereby preventing tissue swelling. It also serves as a defense system for the body, filtering out organisms that cause disease, producing white blood cells, and generating antibodies.

The biochemical make up of lymph — the fluid found in the lymphatic vessels — varies with the site of origin. For example, lymph from bone marrow, spleen, and thymus have high concentrations of white blood cells for fighting infection, while lymph from intestines is high in fat that has been absorbed during digestion. Damage to the lymphatic and circulatory systems leaves the body more susceptible to sickness and infection, as well as to serious conditions such as cancer.

Gaucher disease

2009-06-14T09:20:00.003-07:00

Gaucher (pronounced "go-SHAY") disease is an inherited illness caused by a gene mutation. Normally, this gene is responsible for an enzyme called glucocerebrosidase that the body needs to break down a particular kind of fat called glucocerebroside. In people with Gaucher disease, the body is not able to properly produce this enzyme, and the fat can not be broken down. It then accumulates, mostly in the liver, spleen, and bone marrow. Gaucher disease can result in pain, fatigue, jaundice, bone damage, anemia, and even death.

Gaucher disease is considerably more common in the descendants of Jewish people from Eastern Europe (Ashkenazi), although individuals from any ethnic group may be affected. Among the Ashkenazi Jewish population, Gaucher disease is the most common genetic disorder, with an incidence of approximately 1 in 450 persons. In the general public, Gaucher disease affects approximately 1 in 100,000 persons. According to the National Gaucher Foundation, 2500 Americans suffer from Gaucher disease.

In 1991, enzyme replacement therapy became available as the first effective treatment for Gaucher disease. The treatment consists of a modified form of the glucocerebrosidase enzyme given intravenously. Performed on an outpatient basis, the treatment takes about 1–2 h and is given every 2 weeks. Enzyme replacement therapy can stop and often reverse the symptoms of Gaucher disease, allowing patients to enjoy a better quality of life.

Clusters of Orthologous Groups

2009-06-14T09:20:00.002-07:00

	COGs Phylogenetic classification of proteins encoded in complete genomes

Clusters of Orthologous Groups of proteins (COGs) were delineated by comparing protein sequences encoded in complete genomes, representing major phylogenetic lineages. Each COG consists of individual proteins or groups of paralogs from at least 3 lineages and thus corresponds to an ancient conserved domain.

66 genomes
38 orders
28 classes
14 phyla

Unicellular clusters FTP

Initial

version

Science 1997 Oct 24;278(5338):631-7,
BMC Bioinformatics 2003 Sep 11;4(1):41.

Euryarchaeota
Methanobacteriales		Mth
Methanococcales		Mja
Halobacteriales		Hbs
Thermoplasmatales		Tac Tvo
Thermococcales		Pho Pab
Archaeoglobales		Afu
Methanopyrales		Mka
Methanosarcinales		Mac

Crenarchaeota
Thermoproteales		Pya
Sulfolobales		Sso
Desulfurococcales		Ape

Ascomycota
Saccharomycetales		Sce
Schizosaccharomycetales		Spo

Microsporidia
Apansporoblastina		Ecu

Aquificae
Aquificales		Aae

Thermotogae
Thermotogales		Tma

Cyanobacteria
Nostocales		Nos
Chroococcales		Syn

Deinococcus-Thermus
Deinococcales		Dra

Fusobacteria
Fusobacterales		Fnu

Spirochaetes
Spirochaetales		Tpa Bbu

Chlamydiae
Chlamydiales		Ctr Cpn

Actinobacteria
Actinomycetales		Cgl Mtu MtC Mle

Firmicutes
Clostridiales		Cac
Bacillales		Sau Lin Bsu Bha
Lactobacillales		Lla Spy Spn
Mycoplasmatales		Uur Mpu Mpn Mge

Proteobacteria
Pseudomonadales		Pae
Enterobacteriales		Eco EcZ Ecs Ype Sty Buc
Xanthomonadales		Xfa
Vibrionales		Vch
Pasteurellales		Hin Pmu
Burkholderiales		Rso
Neisseriales		Nme NmA
Campylobacterales		Hpy jHp Cje
Caulobacterales		Ccr
Rhizobiales		Atu Sme Bme Mlo
Rickettsiales		Rpr Rco

Upcoming microbial genomes

genomes	genera	orders	classes	phyla
261	126	63	33	17

[N] Nano

[A] Euryarchaeota (8)

* *Methanobacteria*		* *Methanococci*
* *Methanomicrobia*		* *Halobacteria*
* *Thermoplasmata*		* *Thermococci*
* *Archaeoglobi*		* *Methanopyri*

[R] Creno (3)

[D] Deinococcus (2)

[T] Actinobacteria (3)

[P]	Proteobacteria (26)

	α (6)	β (5)	γ (10)	δ (4)	ε (1)

[O] Other (9)

*																							Bacteroidetes
*																							Chlorobi
*																							Fusobacteria
*																							Aquificae
*																							Chloroflexi
*																							Thermotogae
*																							Planctomycetes
*																							Spirochaetes
*																							Chlamydiae

[F] Firmicutes (7)

*Mollicutes* (3)
*Bacilli* (2)
*Clostridia* (2)

[C] Cyanobacteria (4)

* *Gloeobacteria*
* *Nostocali*
* *Prochlorali*
* *Chroococcali*

Eukaryotic Clusters FTP
Code	Name	Abbreviation
A	Arabidopsis thaliana (thale cress)	ath
C	Caenorhabditis elegans (worm)	cel
D	Drosophila melanogaster (fruit fly)	dme
H	Homo sapiens (human)	hsa
Y	Saccharomyces cerevisiae (baker yeast)	sce
P	Schizosaccharomyces pombe (fission yeast)	spo
E	Encephalitozoon cuniculi (Microsporidia)	ecu

Upcoming eukaryotic genomes
O	Oryza sativa (rice)	osa
Q	Anopheles gambiae (mosquito)	aga
Z	Pan troglodytes (chimpanzee)	ptr
W	Canis familiaris (dog)	cfa
M	Mus musculus (mouse)	mmu
R	Rattus norvegicus (rat)	rno
Ascomycota genomes including
L	Magnaporthe grisea	mgr
N	Neurospora crassa	ncr

Using GPS Phones to Track Virtual Infections - and Real Epidemics

2009-06-14T09:16:00.000-07:00

Japanese wireless carrier Softbank has planned tests that track the progression of a virtual disease using GPS-enabled cellphones belonging to schoolchildren as they go through a routine day of classes. The experiment in virtual epidemic monitoring is meant to find new ways to use Japan's well-appointed wireless data networking systems to inform the public and prevent the spread of real diseases.

A few months from now, a highly contagious disease will spread through a Japanese elementary school. The epidemic will start with several unwitting children, who will infect others as they attend classes and wander the halls.

If nothing is done, it will quickly gain momentum and rip through the student body, then jump to parents and others in the community. However, officials will attempt to stymie the disease and save the school -- using mobile phones.

The sickness will be a virtual one, in an experiment funded by the Japanese government. A subsidiary of Softbank, a major Japanese Internet and cellular provider, has proposed a system that uses phones to limit pandemics.

Fast-Acting Epidemic

The exact details have yet to be fixed, but Softbank hopes to pick an elementary school with about 1,000 students and give them phones equipped with GPS. The locations of the children will be recorded every minute of the day and stored on a central server.

A few students will be chosen to be considered "infected," and their movements over the previous few days will be compared with those of everyone else. The stored GPS data can then be used to determine which children have crossed paths with the infected students and are at risk of having contracted the disease.

The families of exposed students will be notified by messages to their mobile phones, instructing them to get checked out by doctors. In a real outbreak, that could limit the rate of new infections.

"The number of people infected by such a disease quickly doubles, triples and quadruples as it spreads. If this rate is decreased by even a small amount, it has a big effect in keeping the overall outbreak in check," said Masato Takahashi, who works on infrastructure strategy at Softbank.

He demonstrates with a calculation: If an infected person makes about three more people sick per day, and each newly infected person then makes another three people sick, on the 10th day about 60,000 people would catch the disease. If each sick person instead infected two people a day, on the 10th day about 1,500 people would get sick.

GPS Tracking

The experiment was conceived before the current outbreak of swine flu, but has drawn fresh attention now that Japan has the highest number of confirmed cases outside of North America.

It is one of 24 trials the government recently approved as part of a program to promote new uses for Japan's Internet and cellular infrastructure. The country boasts some of the most advanced mobile phone technology in the world. It is blanketed in high-speed cellular networks, and phones come standard with features like GPS, TV and touchless train passes.

The mobile phone market is largely saturated, however, and fees are being driven down by an ongoing price war. For Softbank, a government-backed health-monitoring service could be boon to business.

GPS has its shortcomings, including hazy readings indoors. However, Softbank believes it could keep readings accurate to several yards, at least for an experiment in a limited area.

Until now, technologies like GPS have mainly been used to help people figure out where they are and what is nearby. As networked devices like the iPhone become more popular, new applications let people track their children or friends, and could give companies and governments access to their location.

Aoyama Gakuin University, a prestigious school in Tokyo, is giving Apple's (Nasdaq: AAPL) iPhone 3G to students, partially as a way to check attendance via GPS readings from an application running on the phone.

That kind of project raises privacy concerns, and one of the goals of the Japanese experiment is to judge how participants feel about having their location constantly recorded.

Incoming Text: You're Infected

If a disease-tracking system were launched for real, no one would be required to sign up, said Takuo Imagawa, an official at the Ministry of Internal Affairs and Communications.

Another concern for the experiment is how to inform people that they may be infected, even if it's just a virtual disease.

"If we don't think carefully about the nature of the warning, people that get such a message could panic," said Katsuya Uchida, a professor at the Institute of Information Security in Yokohama. Uchida serves on a board that evaluates such proposals for the government.

Softbank Telecom, the subsidiary that made the original proposal, might not be chosen by the ministry to run the experiment in the fall. However, Takahashi says that whichever company is chosen, he hopes the potential benefits of a monitoring system are enough to persuade people to sign up and reveal their whereabouts.

"I think it would have a bigger impact than Tamiflu," he said.

Emerging Biotechnology Cluster

2009-06-07T23:34:00.000-07:00

Boston, San Francisco, San Diego, and Cambridge are on everyone’s list of the top biotech clusters. Medicon Valley, straddling the border of Sweden and Denmark, Switzerland’s BioValley, Seattle, and Paris may be on that list, too, and no wonder. These are areas where biotech thrives. Biotech is so successful at attracting brainpower, related industries, and money to regions that today almost everybody is trying to get into the act.

Obviously, some regions will fare better than others. Many of these clusters have formed because of local political interest. “Consequently, many of the clusters don’t reach critical mass,” notes Willy DeGreef, secretary general, EuropaBio.

There are many great research universities throughout the world, and most regions with a nascent biotech industry have at least one. Good ideas and the scientific capital to bring them to fruition, therefore, are plentiful. It’s the business aspects of growing a biotech cluster that are often most difficult, and that can make the difference between success and mediocrity or even failure. As Glen Giovannetti, global biotech leader at Ernst & Young, points out, “The secret sauce for biotech success is experienced venture capital, experienced management, and a serial entrepreneurial culture.”

GEN talked with a number of biotech industry thought leaders to identify some of the most promising emerging biotech clusters. One point they all made is that it’s nearly impossible to choose the best, and that even the term biotech is hard to define. The term “emerging” had some challenges, too. Nonetheless, here are some of the regions that are capturing their attention.

Belo Horizonte, São Paulo, and Rio de Janeiro are the three leading biotech clusters. Generic manufacturers are currently predominant, but they realize the need for innovative new compounds, according to Sarah Frew, Ph.D., research associate at McLaughlin-Rotman Centre for Global Health at the University Health Network and the University of Toronto.

The biotech sector is dominated by small to medium-sized companies that are focused on agriculture, although some small innovative drug firms exist. Collaborations tend to be with Brazilian universities and with foreign companies, but not with other Brazilian companies, and usually are for services like marketing or for access to information. Private financing remains challenging, and public funds are limited.

Belo Horizonte, in the northern part of the country, is the capital of Minas Gerais, and was Brazil’s first planned city. It has three universities, including the University of Minas Gerais, which is known for its science and technology. The Biominas Foundation also is located in Belo Horizonte. The Foundation has helped 33 biotech companies generate business opportunities since its inception in 1990, and its Incubator of Companies program has introduced 21 start-ups to the market since 1997. Biominas is an active lobbyist for the biotech industry, and its officers have close ties to the government and to the venture capital community.

São Paulo is home to the Butantan Institute, which is one of two vaccine suppliers to the Brazilian Program for National Immunization (PNI), universities, and to Intrials, which claims to be the largest full-service clinical trials research organization in Brazil.

Rio de Janerio has the Oswaldo Cruz Foundation, which plays a major role in developing healthcare products. The Immunobiologicals Technology Institute, known as Biomanguinhos, is the other vaccine supplier to the PNI and is located in Rio.

Canada

Both Toronto and Vancouver have good, small companies, but they’re struggling for capital. They have the benefit of government support and strong universities, particularly the University of Toronto, the University of Guelph, and the University of British Columbia. Entrepreneurship skills need to be honed, however.

In the heart of Toronto, the MaRS Center incubates a host of companies within about a mile of five teaching hospitals, the University of Toronto, the provincial parliament, and the financial district. The local government takes a close interest in the Center’s success, and several promising research projects are moving toward commercialization.

Vancouver, on Canada’s west coast, consistently ranks as a fast-growing cluster, attracting more than 90 companies, some with late-stage trials. The University of British Columbia has an active tech-transfer department that has spun out several companies.

China

The People’s Republic of China has declared the development of a vibrant biotech industry to be one of its top priorities, and several biotech parks have emerged. Shanghai and Beijing are home to the largest groupings of biotech companies, according to Dr. Frew. Both cities boast good universities.

“Shanghai is the new center of business and commerce in China, rivaling Hong Kong,” according to Zhu Shen, Ph.D., CEO of BioForesight. The Shanghai Zhangjiang Hi-tech Park, located in the Pudong New Area, is home to more than 3,600 companies focused on life sciences, software, and information technology. Of those, more than 250 are life sciences companies, employing a total of 20,000 life sciences professionals. About half the Park revenues are from life sciences, Dr. Shen adds.

The Zhangjiang Drug Valley, as that park is nicknamed, has developed 17 square kilometers of the 25 square kilometers within the park. Companies include 7 of the top 10 big pharma companies and more than 110 indigenous CRO or outsourcing firms, novel drug discovery firms, contract manufacturers, and others. Nearby organizations include the Shanghai Institute for Biological Sciences, and Shanghai University of Traditional Chinese Medicine.

About 80 kilometers west, “Suzhou BioBay is hungrier and more aggressive, and focuses on early-stage and innovative companies,” Dr. Shen says. “Government officials at Suzhou BioBay and at Suzhou Industrial Park tend to be younger, energetic, and well-versed in English and Western-style business operations.” The parks are known for consistent policies, pro-business mentalities, and large private funding networks.

Beijing is home to numerous government agencies and savvy entrepreneurs who know how to work with government. The Beijing Zhong-guan-cum Life Science Park is one of China’s older biotech parks, Genzyme and Bayer Schering both have announced plans to develop R&D centers there. The Institute of Biotechnology, Beijing Normal University, Peking University, Beijing University, and other universities are located here.

Although China in general has some cost advantages, thought leaders say they still hear concerns about intellectual property “which is getting better,” Giovanneti points out. As yet the companies and universities are doing discovery research, and clinical trials, but the industry hasn’t yet moved into late-stage research.

India

“There’s been a lot of activity here in public/private partnerships for biotech parks,” Giovannetti says. Overall, the region is still strong in generics, but some innovative companies are coming out of Genome Valley, about 20 miles from Hyderabad, and also from Bangalore. Within the next two to three years, India expects to have about 27 biotech parks, according to Ernst & Young.

ICICI Knowledge Park was founded in 2000 on 200 acres of land. It currently is 100% occupied, with 80,000 square feet of wet labs and about 1,400 employees onsite, according to the just-released Ernst & Young study, “Biotechnology Clusters in India”. Genome Valley also includes the Shapoorji Pallonji Biotech Park with modular wet labs, pilot plants, a business incubation center, and business support facilities. Its 140-acre phase I site is operational, and the phase II site is expected to be completed by 2015.

Hyderabad is dominated by the generics industry but has some biotech companies that are working on innovative drugs. CROs, including GVK Biosciences, are growing, spanning the gap between discovery and development. Strengths include the University of Hyderabad, which has a strong private partnership culture.

Biocon anchors the biotech industry in Bangalore. Spin-offs Syngene and Clinigene also are there, as well as the Indian Institute of Science and the Institute for Bioinformatics and Biotech. In addition, “the Biocon CEO has been a driving force for biotechnology in India,” Dr. Frew says.

“India released a biotech strategic plan last year,” Dr. Frew adds. The plan aims to streamline a confusing and bureaucratic regulatory process and, she says, “signals a willingness to work together.” The downsides to India, as well as any other developing country, Dr. Frew says, are that “tech transfer is a huge barrier,” and capital is in short supply.

France

Lille capitalizes on ties to Lille University, where Louis Pasteur developed the purification process now known as pasteurization. The Pas de Calais area around Lille has some 800 healthcare and biotech companies. The Eurasante Bio-business Park, based in Lille, currently has about 30 biotech firms employing some 3,700 people. It is growing quickly because of its proximity to major universities, seven hospitals, the Pasteur Institute, and other international institutions. The region has a well-developed infrastructure to support life science research and development.

Japan

Tokyo’s biotech cluster is patterned after the bionetworks in Chiba, Yokohama, and Tsukuba. Tokyo has a large concentration of companies focused on monoclonal research and also on stem cell research.

Universities in the city include the University of Tokyo and the Tokyo Institute of Technology, which both have graduate-level biotechnology programs. Tokyo University of Science and a long list of other schools also contribute to the scientific acumen of the city, as does its strong IT industry. The three cities comprising the Tokyo Bay Biotech cluster are close by.

Israel

In 2006, Silico Research Limited ranked Rehovot as number eight in its list of the top non-U.S. biotech clusters, citing its work in monoclonals. About 20 kilometers from Tel Aviv, Rehovot is home to the 250-acre Tamar Science Park, the Weizmann Institute of Science, as well as Hebrew University’s Faculty of Agriculture. Rehovot, which is known as Israel’s science city, has a higher than average population of university-educated citizens.

Israel has more than 900 life sciences companies. Of those, 55% are devoted to medical devices, and about 21% are focused on biotechnology. Pharmaceuticals constitute another 12% of the market, according to ILSI. Most of the pharmaceutical companies are engaged in generics, but 25% are developing new chemical entities. The country is entrepreneurial, and companies are spinning off from the universities in Tel Aviv and Jerusalem. About 14% are at clinical stage.

Singapore

The Biopolis at the One-North corporate park has attracted some of the world’s leading researchers and also persuaded many R&D and manufacturing companies to locate facilities there. The hope is that those activities will spur local entrepreneurs. Like many emerging regions, it still needs a vibrant venture capital community. Biopolis is near the National University of Singapore and the National University Hospital.

Phase one includes seven buildings—two for the private sector and five for public institutions. Phase two, completed in 2006, brought total research space to 222,000 square meters (about 2.4 million square feet).

Biopolis is home to the Agency of Science, Technology, and Research (A*STAR), which leads the country’s scientific research and development efforts for the Ministry of Trade and Industry.

What is a gene?

2009-06-07T23:32:00.001-07:00

he One-Gene/One-Polypeptide Hypothesis
• Beadle and Tatum concluded that genes produce their effects by specifying the structure of enzymes, and that each gene encodes the structure of one enzyme. Today, this is commonly referred to as the one-gene/one-polypeptide relationship.

How DNA Encodes Protein Structure
• Over 50 years of research has yielded clear evidence that DNA is the molecule responsible for the inheritance of traits from one generation to the next, and that DNA is divided into functional subunits, or genes, located on chromosomes.

How does DNA replicate?

2009-06-07T23:31:00.000-07:00

The Meselson-Stahl Experiment: DNA Replication Is Semiconservative
• Meselson and Stahl demonstrated that DNA replication is semiconservative because each strand of the original duplex becomes one of the two strands in each new duplex. (p. 288)

The Replication Process
• Replication of E. coli begins at a specific origin, proceeds bidirectionally, and ends at a specific terminus.
• Many enzymes function in DNA replication, including DNA primase, which creates a short RNA primer complementary to a DNA template; DNA helicase, which unwinds the helix in front of DNA polymerase, which then synthesizes new DNA by adding nucleotides to the growing strands; and DNA ligase, which creates phosphodiester bonds between adjacent Okazaki fragments.
• Replication can be divided into three stages: initiation, elongation, and termination.

Eukaryotic DNA Replication
• The major difference between prokaryotic and eukaryotic replication is that eukaryotic chromosomes have multiple replication origins, whereas prokaryotic chromosomes have a single point of origin.

What is the structure of DNA?

2009-06-07T23:30:00.000-07:00

The Chemical Nature of Nucleic Acids
• Both DNA and RNA are formed of nucleotides joined together in series. Each nucleotide is composed of a five-carbon sugar, a phosphate group, and a nitrogen-containing base.
• Chargaff's Rule states that in reference to the nitrogen-containing bases, adenine always pairs with thymine, and guanine always pairs with cytosine. Thus, there are always equal proportions of purines and pyrimidines.

The Three-Dimensional Structure of DNA
• Franklin was able to obtain the first glimpse of DNA using X-ray diffraction in 1953, while Watson and Crick theorized that DNA exists in a double-helical, antiparallel configuration.
• Using a spiral staircase analogy, the handrails of the staircase represent the sugar-phosphate backbone of the DNA double helix, and the steps represent the hydrogen-bonded base pairs.

DNA : The Genetic material

2009-06-07T23:25:00.000-07:00

1) What is the genetic material?

The Hammerling Experiment: Cells Store Hereditary Information in the Nucleus
• Hammerling conducted a series of experiments and discovered that hereditary information in Acetabularia resided in the foot, which is also the location of the nucleus.

Transplantation Experiments: Each Cell Contains a Full Set of Genetic Instructions
• Later experiments in the mid-1950s showed that the nucleus of eukaryotic cells includes a full set of genetic information.

The Griffith Experiment: Hereditary Information Can Pass Between Organisms
• Griffith found that transformation occurs when genetic material is transferred from one cell to another, and that live cells can be transformed by dead cells.

The Avery and Hershey-Chase Experiments: The Active Principle Is DNA
• Avery provided conclusive evidence that DNA is the heredity material for the bacterial specimens under investigation.
• Hershey and Chase provided further evidence that heredity material in bacteriophages was found in DNA, not in proteins.

The Molecular Analysis of a Human Mutation

2009-06-06T21:51:00.000-07:00

Labels: Tools of Human Molecular Genetics
How does one proceed when one has a patient with a genetic disorder known or suspected to be due to a mutation in a particular gene? For example, consider a patient with a diagnosis of β-thalassemia, an autosomal recessive defect in the β-globin gene. The initial diagnosis is generally made on the basis of clinical and hematological findings alone. However, it is important to examine the gene itself, first to confirm the clinical diagnosis and second, to determine the specific mutation in the β-globin locus both for future use in carrier testing and possible prenatal diagnosis in the patient's family, and for increasing the understanding of the relationship between specific mutations in the gene and the resulting patho-psychology.Several tests can be used initially to examine the gross integrity of the β-globin gene itself and its mRNA. Is the gene present in the patient in both normal amount (i.e., two copies) and structure? Or is one or both copies of the gene deleted or structurally rearranged, as has been described in some cases of β-thalassemia? If the gene is present, is it transcribed? The Southern blotting technique is now a standard method for using a cloned gene probe (in this case, for the β-globin gene) to examine the integrity of a DNA sample. Southern blotting can address the question of whether it is grossly normal in structure. By this method one can detect large molecular defects that are well below the level of sensitivity of chromosome analysis. However, as currently used in diagnostic laboratories, it cannot reveal the presence of single mutations, such as base-pair changes or very small deletions of only a few base pairs. In order to examine whether mRNA is present, a technique called Northern blotting is used. This approach also enables one to detect major changes in mRNA levels or structure for a specific gene, but not to detect minor alterations.Having asked whether there are gross changes in the gene or in its mRNA, one can proceed to a number of methods developed to examine gene structure and expressions at increasingly finer levels of analysis. In β-thalassemia, as in many other genetic disorders, particular mutations responsible for the disease in other patients. To determine whether one of these already known mutations is responsible for a particular case of β-thalassemia, one can apply particular direct molecular tests. Some of these entail the approach of allele-specific oligonucleotides (ASOs) that enable one to detect specific single base-pair mutations. In addition, it may be desirable to actually clone the mutant β-globin genes (or cDNAs) from the patient for comparison with a normal β-globin gene. Cloning of individual mutant genes (or portions of genes) from a patient's material is facilitated by use of polymerase chain reaction (PCR) to specifically generate many million of copies of a particular gene fragment. Once the mutant gene is isolated, one can then analyze it at the finest level possible by determining the DNA sequence of base pairs in the mutant gene for comparison with the normal gene. In this way, the specific mutation responsible for the genetic disorder in the patient can be determined and used to develop direct screening tests for that mutation in the patient's family.

The language of Molecular Cloning

2009-06-06T21:50:00.000-07:00

Labels: Tools of Human Molecular Genetics
cDNA (Complementary DNA):
A synthetic DNA copied from messenger RNA (mRNA) by the enzyme reverse transcriptase. Used to refer to either a single-stranded copy or its double-stranded derivative. Usage: "a cDNA clone", "a cDNA library" or "to isolate a cDNA".
Clone:
A recombinant DNA molecule containing a gene or other DNA sequence of interest. Also, the act of generating such a molecule. Usage: "to isolate a clone" or "to clone a gene"
Host:
The organism used to isolate and propagate a recombinant DNA molecule. Usually a strain of the bacterium Escherichia coli or the yeast Saccharomyces cerevisiae. Usage: "What host did they use?"
Hybridization:
The act of two complementary single-stranded nucleic acid molecules forming bonds and becoming a double-stranded molecule. Usage: "The probe hybridized to a gene".
Insert:
A fragment of human DNA cloned into a particular vector. Usage:"They purified the insert"
Library:
A collection of recombinant clones from a source known to contain the gene, cDNA, or other DNA sequences of interest. In principle, a library may contain all the DNA sequences represented in the original cell, tissue, or chromosome. Usage: "a muscle cDNA library" or "a human genomic library"
Ligation:
The act of forming phosphodiester bonds to join two double-stranded DNA molecules with the enzyme DNA ligase. Ligation is the essential step in creating recombinant DNA molecules. Usage: "The fragments were ligated together"
Probe:
A cloned DNA or RNA molecule, labeled with radioactivity or another detectable tracer, used to identify its complementary sequences by molecular hybridization; also, the act of using such a molecule. Usage: "the beta-globin probe" or "to probe a patient's DNA"
Restriction endonucleases (restriction enzymes):
Enzymes that recognize specific double-stranded DNA sequences and cleve the DNA at or near the recognition site. Usage: "a restriction enzyme digest" (or just "a restriction digest") or "the restriction enzyme EcoRI".
Southern Blot:
A filter to which DNA has been transferred, usually after restriction enzyme digestion and gel electrophoresis to separate DNA molecules by size (named after the developer of the technique, Ed Southern); also, the act of generating such a filter and hybridizing it to a specific probe. Usage: "to probe a Southern blot" or "they did a Southern".
Vector:
the DNA molecule into which the gene or other DNA fragment of interest is cloned, capable of replicating in a particular host. Examples include plasmids, bacteriophage lambda, cosmids, and yeast artificial chromosomes. Usage: "a cloning vector" or "the cosmid vector".

A new record in sorting large amounts of data by Researchers at the Karlsruhe Institute of Technology

2009-06-05T21:51:00.001-07:00

Researchers at the Karlsruhe Institute of Technology (KIT) has developed a new robust method for sorting large quantities of data. They beat the previous record held by the Massachusetts Institute of Technology (MIT) and, more importantly, less consumption of resources.Networked computers on the Internet produce quantities of increasingly large data. In order to treat, it is necessary, first, the following order of criteria. Efficient sorting of data is of growing importance to search engines or databases and a central research topic both in theory and in practice.For years, the Sort Benchmark, a table for free on the Internet, identifies the current record data sorting. Queen in the discipline, it is sort of the earliest at least 100 billion Byte. Prof. around. Peter Sanders, a team of researchers from the Institute for theoretical KIT imposed in two categories of Sort Benchmark. They managed to sort 100 Terabyte in less than three hours, which equates to an average of 564 GB per minute. To achieve such a feat, they used a combination of computers including 200 nodes. A team of giant Yahoo has exceeded the value of 564 GB per minute, but had to use to this end, 17 times more nodes.In addition, researchers of KIT increased the record number of records that can be sorted in one minute. This value amounted to 950 GB. This is three times more than the previous record held by MIT and two times more than the record for Yahoo in this category. KIT researchers have also improved the record for Google to sort the fastest one Terabyte down the record from 68 to 64 seconds, again with a lower consumption of resources.

World Environment Day: "Your planet needs you"

2009-06-05T21:50:00.000-07:00

World - It now stands as the World Day of Environment. An event that was created in 1972 by the United Nations and the 2009 edition which is of course under the banner of the fight against global warming."Your planet needs you - united against climate change", here the theme of World Environment Day during which many events are held around the world.While the Copenhagen summit is close upon us, it is now for the UN to raise awareness about the urgent and necessary fight against climate change, so that it agrees also in the way sustainable development.The United Nations intend to "promote an understanding that communities are essential in changing attitudes" and "defend the partnership which will ensure all nations and peoples enjoy a safer future and more prosperous."For the 2009 edition of this day is the Mexico that is showcased. The country was chosen by the United Nations Environment Program (UNEP) in particular for its commitment to the "1 Billion Trees". "Mexico, with the support of its president and its people, has invested heavily in this commitment and has planted 25 percent of the trees in this campaign," says the UN. Since its launch in 2006, 3 billion trees were planted, and the end of 2009, this figure expected to reach 7 billion.Animations, conferences, cleaning operations or planting, concert events will take place all day and throughout the world in the fight against global warming.

Spacebel recently delivered ground software for the mini observatory sun "Picard"

2009-06-05T21:42:00.000-07:00

The engineering company Liège Spacebel, developed the center's scientific mission Picard, the 150 kg microsatellite whose mission will be to study solar activity. Two versions of the mission center were carried out successively to adapt to the integration of the satellite. Spacebel has just completed a successful delivery and installation of the final version to the observatory at Uccle plateau Uccle where the scientific data recorded by satellite will be treated. While waiting for the launching of Picard from Russia, on November 30, the mission center is used to test the whole system (satellite control center and center of mission).The center of scientific expedition Picard fulfills various essential functions. It will provide the programming of the payload, ie scientific instruments aboard the satellite, and at the same time check the health of them. In addition, it will centralize all requests for acquisition of images, receive, process and archive the data collected by the instruments and make them available in science laboratories."Picard" concerns a scientific observation of the Sun which is in the pipeline Myriade Center National d'Etudes Spatiales (CNES), the French space agency. Its purpose is twofold: firstly, knowledge of the operation and the physical structure of the star and, on the other hand, better understand the influence of solar activity on Earth's climate. Named in honor of the french astronomer Jean Picard (1620-1682), who made the first precision measurements of the solar diameter in the seventeenth century, Picard will have a lifetime in orbit of 3 years. A team of 3 engineers worked for 2 years on this project, which represents a turnover of around 1.1 million. Based in Liege Science Park Angleur the company was founded in 1988 in the context of economic and political integration of Europe and the role of Belgium in space research.By contributing to the success of many programs initiated by the European Space Agency, Spacebel has built a name in the space field. Its systems to measure and fit high performance platforms and instruments on board satellites, ground facilities for receiving, processing and dissemination of data recorded aboard the satellite, test benches and related products (simulators and emulators ) networks and satellite communications.With the resumption of the Da Vinci in 1998, Spacebel has extended its activities to the enhancement of images taken by satellites to Earth observation. It develops and markets systems to support decision making for land management, environment, natural disasters.

Genetic survey finds healthy human skin is crawling with bacteria

2009-05-30T21:30:00.000-07:00

Think a good antibacterial hand soap is keeping your skin relatively microbe and bacteria free? You might want to think again. Scientists and germophobes alike have long known that human skin—from head to toe—is literally crawling with bacteria and microbes. And a new study, published today in Science shows that skin is host to many, many more of the tiny organisms than previously thought. Researchers at the National Institutes of Health's (NIH) new Human Microbiome Project sequenced genes from skin samples from volunteers and found bacteria that hailed from 19 different phyla, 205 genera and possessed more than 112,000 individual gene sequences. (Previous studies of skin cultures supposed that just one type of bacteria, Staphylococcus—a virulent strain of which is responsible for staph infections—was the main resident of human skin.) But no need to overdo it on the antibacterials; most of the tiny organisms aren't doing any harm. All of these samples were collected from 20 different disease-prone spots on the bodies of 10 healthy volunteers—from forehead to heel, with stops such as the buttock and inner elbow along the way.After completing this initial survey, researchers aim to establish a bacterial baseline so as to better treat skin diseases, such as acne or eczema, where bacterial populations might be out of whack. "The skin is…an ecosystem, harboring microbial communities that live in a range of physiologically and topographically distinct niches," the study authors write. "For example, hairy, moist underarms lie a short distance from smooth, dry forearms, but these two niches are as ecologically dissimilar as rainforests are to deserts." Can you guess the location with the most types of bacteria? No, it's not the "rainforest" or below the belt. Try the forearm, which boasts an average of 44 different species.

Largest Ever Autism Study Identifies Two Genetic Culprits

2009-05-30T21:29:00.000-07:00

The largest genome scan ever conducted to get to the bottom of autism has pinpointed two locations in the human genetic makeup that may trigger the mysterious mental condition. The Autism Genome Project, a collaboration of 120 scientists representing 19 countries and 50 institutions, compared the genomes of 1,168 families that each had at least two autism sufferers in them to try to track down the regions. The consortium reports its findings in this week's issue of Nature Genetics.
Autism is a mental disorder characterized by behavioral problems that may include a lack of social and communications skills, such as failure to respond to one's own name, intense tantrums and general detachment. In the last decade the diagnosis of autism has increased 10-fold. It is now believed to affect one in 166 children born in the U.S. and four boys for every girl.
"Although we know autism is highly inheritable, complex gene interactions and submicroscopic anomalies create a din of statistical noise that drowns out detection of signals from linked sites in the genome," says study co-author Bernie Devlin, a human geneticist at the University of Pittsburgh. "To amplify these signals, we brought to bear gene chip technology with a huge sample, and also screened for these fine-level anomalies, factoring them into the analysis."
Using a DNA microarray, or gene chip, the team was able to scan large stretches of sequence for tiny deletions common within the study families. They also sought out copy number variations and large-scale insertions or deletions of genetic material. In the two-fold analysis, the researchers implicated the gene neurexin 1, located on chromosome 2, as well as a swath of sequence on chromosome 11.
Neurexin 1 is part of a three-member family of genes coding for proteins involved in communication between neurons. It is associated with glutamate, the neurotransmitter known to elevate neuronal activity and play a role in wiring the brain during early development. Glutamate functioning has been implicated in other syndromes involving mental retardation of which autism is often a symptom, such as fragile X syndrome and tuberous sclerosis. Neurexin 1 is specifically believed to be involved in building glutamate synapses, the links through which glutamate neurons send and receive electrical signals.
"Often you don't have any idea of what a gene does, but in this case we know neurexin 1 is involved at sites where the neurotransmitter glutamate is released," says study coauthor Gerard Schellenberg, a medical researcher at the University of Washington. "As for the chromosome 11 location, we think there is another susceptibility gene there and we are actively pursuing it. We are in the neighborhood and have a plan to find it. The section of chromosome 11 identified in the study has been linked to proteins that ferry glutamate across synapses.
Genetic anomalies, from tiny deletions or substitutions of single bases to large stretches of missing code or even multiple copies of the same code, often crop up in the human genome and, occasionally, can create a disposition to a particular type of disorder. Among the variations found in the Autism Genome Project subjects was the deletion of the neurexin 1 gene. Much of the autism research community believes there may be roughly six major genes involved in autism, and maybe 30 others that may confer some risk. A combination of mutations in any of these genes could contribute to the likelihood of being born with autism. Because a number of different genetic factors may contribute to this disease, identifying these markers is made very difficult and large sample sizes are needed to get significant results.
"These findings are a piece of the puzzle," says Geraldine Dawson, director of the University of Washington's Autism Center. "As we identify these genes we will be able to screen young children for autism at an early age and begin interventions earlier, which can have a dramatic effect for some children."
These results are the culmination of phase 1 of the Autism Genome Project, which began in 2002 with the sharing of samples and data from labs around the world. Phase 2 will follow up on the leads discovered in the first phase. The $14.5 million project will receive funding from various institutions such as the National Institutes of Health and Autism Speaks, an organization dedicated to increasing the awareness of and finding a cure for autism spectrum disorders.
"Autism is a very difficult condition for families—communication is taken for granted by parents of healthy children but is so greatly missed by those with autistic children," says study co-author, Jonathan Green, a child psychiatrist at the University of Manchester in England. "We hope that these exciting results may represent a step on the way to further new treatments in the future."

A study on a large scale identify the genes implicated in mental retardation

2009-05-30T21:16:00.000-07:00

X-linked mental retardation (XLMR) is a common cause of moderate to severe intellectual disability in males. XLMR is very heterogeneous, and about two-thirds of patients have clinically indistinguishable non-syndromic (NS-XLMR) forms, which has greatly hampered their molecular elucidation. A few years ago, international consortia overcame this impasse by collecting DNA and cell lines from large cohorts of XLMR families, thereby paving the way for the systematic study of the molecular causes of XLMR. Mutations in known genes might already account for 50% of the families with NS-XLMR, and various genes have been pinpointed that seem to be of particular diagnostic importance. Eventually, even therapy of XLMR might become possible, as suggested by the unexpected plasticity of the neuronal wiring in the brain, and the recent successful drug treatment of a fly model for fragile X syndrome.

NEW 'OME' IN TOWN

2009-05-27T03:55:00.001-07:00

We're living in an "omic" world. Some of these "omes," such as the genome and the proteome, are familiar; others, less so. Now the metabonome, one of the newest omes in name if not in reality, has joined the pantheon of global biological measurements.
METHOD OF CHOICE NMR is the most popular method for metabonomics experiments. The NMR facility at Imperial College is shown here.COURTESY OF JEREMY NICHOLSON The "omics" suffix has come to signify the measurement of the entire complement of a given level of biological molecules and information. Therefore, genomics measures the entire genetic makeup of an organism, while proteomics measures all the proteins expressed under given conditions. Metabonomics is no different. As the name might imply, metabonomics is defined as measurement of the complete metabolic response of an organism to an environmental stimulus or genetic modification. Some people use the term metabolomics to refer to metabonomics at the level of a single cell type, rather than a larger system.
The omics can provide information for basic biological research and for pharmaceutical and clinical applications. One of the challenges is integrating the information from the various omics, something that really is only beginning. The goal of a meeting held last month in San Francisco by the California Separation Science Society was just such an integration. In the process, the organizers coined yet another word--systeomics--which was defined as the integration of genomics, proteomics, and metabonomics.
Despite the goal of integration, scientists appear to be sticking with their favorite ome. Most speakers concentrated on one of the areas without addressing how to fit the three together.
Metabonomics may be the most recently named of the omics, but it's one of the oldest. In fact, metabonomics harkens back to old-fashioned biochemistry, with its emphasis on metabolism, the sum of the processes to acquire and use energy in an organism, to biosynthesize cellular components, and to catabolize wastes.
"We've been doing toxicological and disease diagnostics based on metabolic profiling for more than 20 years. That's before genomics or proteomics raised their ugly heads," Jeremy Nicholson, professor of biological chemistry at Imperial College of Science, Technology & Medicine in London, told C&EN.
Nicholson believes that metabonomics is "more closely related to things in the clinical world" than either genomics or proteomics, owing to the fact that metabonomic signatures reflect both genetic information and environmental influences.
John Lindon, another professor of biological chemistry at Imperial College, agrees. "Genomics and proteomics are in 'omics world.' They're not in the real world," Lindon said. "What you're trying to do is relate changes in gene expression or changes in protein level with some real-world endpoints that relate to a disease or toxic episode."
Adelbert Roscher, professor of biochemical genetics on the medical faculty at the University of Munich, said that metabolite profiling "measures the real outcome of potential changes suggested by genomics and proteomics."
Image is available in( Adobe PDF format only)

BIG PICTURE Metabonomics offers the opportunity to find patterns and changes in the entire metabolism, represented here by the metabolic pathways chart designed by Donald E. Nicholson, retired from the University of Leeds.©INTERNATIONAL UNION OF BIOCHEMISTRY & MOLECULAR BIOLOGYTHE VALUE OF genomic and proteomic measurements, Nicholson believes, is "considerably more limited than most people think." For example, changes in gene and protein expression needn't result in an "endpoint change." That is, the change in one gene or protein could be compensated elsewhere, resulting in no net change. "That's always the big problem with genes and proteins," Nicholson said. "Their up or down regulation can be part of the overall homeostatic or corrective process of the cell, not necessarily part of the pathology."
Nicholson suspects that most diseases have a metabolic signature at some level. The challenge is finding that signature. Finding the right matrix is important, whether it be urine, blood, cerebrospinal fluid, or solid tissue.
"Urine carries information on almost everything, because [the kidney is] your ultimate excretory organ, where homeostasis is maintained," Nicholson said. "There's a tremendous amount of information that can be obtained from urine, if you can analyze all the thousands of metabolites that are in there."
Metabonomics experiments are carried out by analyzing biological fluids or tissue extracts with techniques--such as nuclear magnetic resonance spectroscopy, mass spectrometry, or infrared spectroscopy--that provide many data points simultaneously. Even intact tissue samples taken during biopsies can be analyzed, using the NMR technique known as magic angle spinning.
The metabonomic profile is dominated by molecules smaller than 1,000 daltons. That molecular weight range "incorporates pretty much all energy pathways, all catabolic pathways, and many biosynthetic pathways," Nicholson told C&EN.
Nicholson and his colleagues focus on NMR measurements. The subtle differences in NMR spectra are practically impossible to identify just by visual inspection. Data mining and statistical techniques must be used to pull out what Nicholson calls "latent diagnostic information."

Metabolomics: Is it just another Omics?

2009-05-27T03:54:00.000-07:00

The omics
One would not be mistaken for thinking that a new omics word enters our scientific vocabulary every week, from behaviouromics and cytomics to transgenomics and vaccinomics [ref www.genomicglossaries.com/content/omes.asp]. By far the most important and widely established omics terms include genomics - the high throughput analyses of multiple genes including gene sequencing and function; transcriptomics – the study of mRNAs transcribed from a cell’s genome; and proteomics – the determination of the structures and functions of all proteins in a cell or organism. The complete characterisation of cellular processes, whether associated with normal homoeostasis or as a result of disease, toxic insult or genetic manipulation, also requires information on the metabolic status of the cell or organism. Indeed it can be argued that the cellular metabolic status is the most functional measure of the cell’s phenotype (Figure 1). The twenty first century has witnessed the rapid explosion of a new omics science associated with the measurement of metabolites.
What’s in a name?
So what name do we give to the high throughput and comprehensive analysis of metabolites within a cell or organism under a defined physiological state? Metabolomics has emerged as the obvious terminology, although many other variants exist such as metabolic profiling, metabolic fingerprinting and metabonomics. The latter originated from Professor Jeremy Nicholson’s laboratory at Imperial College London, a pioneer of the field, who defines metabonomics as ‘the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification’ (Nicholson, et al. 1999 #3). As with any new research field the definitions continue to evolve, and a formal nomenclature will soon be decided by the new Metabolomics Society.
Applications in the biological and clinical sciences
To date, relatively few metabolomics studies have been published that provide significant new insight into biological processes. Noteworthy papers include the application of metabolomics to the study of drug toxicity (Nicholson, et al. 2002 #2), identification of the phenotype of silent gene mutations (Raamsdonk, et al. 2001 #4), and clinical applications such as the diagnosis of coronary heart disease (Brindle, et al. 2002 #1). Metabolomics has simply had insufficient time to prove itself compared with the more mature omics approaches of genomics and transcriptomics. Indeed, considerable work still remains in developing the bioanalytical and bioinformatic technologies that underpin this science, without which its full potential will never be realised. One of the two primary goals of my research group is exactly that, to develop and optimise metabolomics methodologies at Birmingham, which can then be applied to a range of applications (Figure 2) (Viant, 2003 #5). My group’s other focus is to apply these methods to study the effects of environmental stressors on fish and aquatic invertebrates. To that end I was fortunate to be awarded an NERC Advanced Fellowship, which started in November 2003.
Metabolomics technologies
Birmingham attracted me for several reasons, not least because of it’s new £7.7m nuclear magnetic resonance (NMR) facility named the Henry Wellcome Building for Biomolecular NMR Spectroscopy (HWB•NMR), under the Executive Directorship of Professor Michael Overduin in the School of Medicine. This national facility, which opened officially in November 2004, houses state-of-the-art NMR equipment including the world’s most powerful 900 MHz spectrometer. NMR spectroscopy is currently the most widely used bioanalytical technique for metabolomics, and following recent NERC and BBSRC awards the HWB•NMR is now purchasing additional equipment dedicated to Birmingham’s emerging metabolomics program (Figure 3). Mass spectrometry is an equally important toolset for metabolomics and also proteomics, and the School of Biosciences is currently purchasing an ultra-high mass precision FT ICR mass spectrometer for ‘omics’ research, under the direction of Professor John Heath, Head of School, and Dr Helen Cooper, a newly appointed Wellcome Trust University Technology Fellow. Collectively these instruments and associated expertise have the potential to position Birmingham as an international centre of excellence for metabolomics. In addition, we are well placed to develop the necessary spectral processing tools and bioinformatics for metabolomics studies that are needed to extract the metabolic information from the NMR and mass spectra. This draws upon extensive expertise from across campus and includes Drs. Ulrich Günther and Christian Ludwig (HWB•NMR), Drs. Francesco Falciani and Dov Stekel (School of Biosciences) and Dr. Theo Arvanitis (School of Engineering).
Environmental metabolomics
Metabolomics is ideal for studying the impact of stressors such as pollution and climate change on environmental species, not least because no species-specific DNA sequence information is required. Lactate is lactate whether you are studying a fish, earthworm or human! Current environmental projects at Birmingham, funded by the NERC, include developing a predictive biomarker model for the marine and estuarine environments, based upon metabolomic and bioinformatic methods that use the European flounder and common mussel as sentinel species (Figure 4). This project complements research by Professor Kevin Chipman’s group who are using transcriptomics to characterise the responses of flounder to several classes of toxicants. Recently we have secured a £1.6m NERC Consortium grant, coordinated by Birmingham and in collaboration with a number of UK universities, to identify and define the bases of individual and population susceptibility and adaptation to environmental pollutants in fish using an integrated ‘omic’ approach. Disease processes are also amenable to study. On-going projects include an investigation of withering syndrome in the red abalone, a marine shellfish, in collaboration with the University of California, Davis (Figure 5) (Viant, et al. 2003), and a collaboration with the Centre for Environment, Fisheries and Aquaculture Science at Weymouth in which we are characterising the metabolic consequences of tumour formation in the liver of dab, a marine flatfish.
Birmingham’s Metabolomics Initiative
The application of metabolomics to cancer extends far beyond environmental studies, and not surprisingly this involves the Institute for Cancer Studies in the School of Medicine at Birmingham. In particular, a newly-funded EU project with Dr. Ulrich Günther, Dr. Chris Bunce (School of Biosciences) and me, aims to develop advanced NMR technologies for metabolomics and to use these to investigate the role of specific enzymes in cancer. Other projects include Dr Andrew Peet’s metabolomics studies in paediatric neuro-oncology at the Birmingham Children’s Hospital. Aside from medical studies, metabolomics projects are now starting in several Schools across the campus, including an investigation of acid stress in E. coli by Dr. Pete Lund in Biosciences, and projects by Professor Anton Wagenmakers in Sport and Exercise Sciences and Professor Mohamed Al-Rubeai in Chemical Engineering. In summary, Birmingham is now entering an extremely exciting and productive period of metabolomics research that includes three important components – state of the art equipment and infrastructure, experts in bioanalytical and bioinformatic method development, and world class biological and clinical scientists – and crucial to our success is the highly collaborative environment on which The University of Birmingham thrives.

Environmental Metabolomics: The Study of Disease and Toxicity in Wildlife

2009-05-27T03:53:00.002-07:00

With the completion of the Human Genome Project, we have now truly entered the exciting era of post-genomics biology. Several new scientific disciplines have emerged of which metabolomics holds significant promise for the understanding and diagnosis of diseases both in humans and wildlife. This introduction to the new field of metabolomics will describe several applications of this approach for monitoring the health of organisms in the environment.

The inside of a Californian red abalone shell, Haliotis rufescens (compare size to the coin in photo). The shellfish is susceptible to a disease called withering syndrome. Source: Wikimedia Commons.
Introduction to metabolomics
It’s the study of small naturally occurring molecules.
Metabolomics is the study of all the naturally occurring small molecules, called metabolites, in biological samples such as cells, biofluids, or tissues. These small molecules are the products of metabolism and include, for example, sugars (or carbohydrates), fats (or lipids), and amino acids. The collection of all the metabolites within a cell is called the metabolome. Scientists have started to characterize the metabolome in a quest to better understand and diagnose disease.
It requires input from various disciplines, such as chemistry.
Metabolomics incorporates the use of bioinformatics, the application of computer and statistical techniques to the understanding and management of biological information, to search for unique patterns of metabolites that are indicative of a particular disease.
Metabolomics is a multidisciplinary approach involving biologists, computer scientists, and analytical chemists. The tools used to measure the metabolites are more commonly associated with chemistry laboratories and include nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry.
It measures the interactions of genes with the environment.
The advantage of metabolomics for disease diagnosis, whether in humans or wildlife, stems from the fact that this approach measures the phenotype of an organism, the biological characteristics of an organism that result from the interaction of its genetic make-up with the environment. When an organism becomes diseased or stressed, thus triggering specific molecular changes, the phenotype becomes altered. This change can then, in principle, be measured using metabolomics.
Current applications in human disease diagnosis
A person’s health can be assessed quickly and comprehensively.
For many years doctors have been measuring specific metabolites in a patient’s blood or urine to diagnose particular diseases. Perhaps the most familiar is the measurement of glucose to diagnose diabetes. Metabolomics is opening up new horizons as hundreds of metabolites can be measured rapidly and simultaneously, providing a much more comprehensive assessment of a patient’s health status. Recently, notable applications of metabolomics in the study of human diseases have begun to emerge:
It helps diagnose heart disease and some neurological conditions.
Detection of the presence and severity of coronary heart disease using NMR-based metabolomics.1 This noninvasive approach identified the disease from human serum samples and in the future could reduce the use of angiography, which is highly invasive.
Prediction of the clinical outcome of a sudden hemorrhage of a blood vessel over the surface of the brain (termed subarachnoid hemorrhage), by means of metabolomics analysis of cerebral spinal fluid.2
Classification of patients with progressive neurological diseases (e.g., amyotrophic lateral sclerosis, in which loss of nerve cells produces muscle paralysis) into clinically relevant groups on the basis of metabolite profiles in serum samples.3
Metabolomics in the environmental sciences
Researchers have been developing and applying these methods to study the effects of both diseases and chemicals on wildlife species, or “environmental organisms.” This is a particularly important area of science for several reasons, ranging from concern over the health of the environment to maximizing profits for the aquaculture industry. Environmental metabolomics may prove of major benefit in a variety of ways:
Certain species are used to monitor environmental health.
Environmental monitoring using so-called “sentinel species” of vertebrate and invertebrate animals. Many organizations, typically government related, monitor the prevalence of diseases in certain species of wildlife as indicators of the health of the environment. For example, within the United Kingdom the National Marine Monitoring Program collects several fish species to assess the effects of disease, pollutants, and other stressors such as climate change on fish stocks and biodiversity in the aquatic environment.
Chemical risk assessment of pharmaceuticals, pesticides, and other household and industrial chemicals. Prior to the use of any new chemicals in society, the company that has developed and manufactured the chemical must assess the risk posed to wildlife and the environment. Only if a new chemical poses minimal harm can it be licensed and sold.
Metabolomics can ensure healthy animal stocks.
Maintenance of healthy stocks of animals in the aquaculture industry, including fish and invertebrates. As with any type of intensive farming, rearing large numbers of animals in close proximity can drastically increase the occurrence and spread of diseases. Maintaining healthy animals is important for both animal welfare and productivity.
Identification of cancer in marine flatfish
Studies identified liver cancer in fish.
Metabolomics and proteomics, the study of thousands of proteins simultaneously, have been used to study liver cancer in a marine flatfish species called dab (Limanda limanda).4 Scientists had noted high levels of tumours in up to 14 percent of the fish collected from the open sea and estuaries around the United Kingdom. It was hypothesised that metabolomics and proteomics could identify differences between healthy and diseased dab livers, and that these differences, or biomarkers, could be used to rapidly diagnose liver cancer in the future.
Initial studies using mass spectrometry did indeed find molecular differences between healthy and diseased livers, although the exact metabolites remain unidentified. The goal of the investigation is to identify the specific causes within the environment that may be responsible for the disease. Potential causes include chemical pollutants that are ingested by the bottom-feeding dab or biological factors such as bacteria or viruses.
Chemical risk assessment in fish, mammals, and earthworms
Many chemicals in the environment can be monitored simultaneously.
A number of research groups have been developing and using metabolomics to study the effects of chemicals on organisms in the environment. In addition to the work on aquatic organisms, several studies on terrestrial invertebrates have been conducted, and a limited number of studies on terrestrial mammals have been reported. The advantage of metabolomics over traditional approaches for assessing the effects of chemical toxicity is that earlier methods tend to measure only a small number of responses. With metabolomics, hundreds of metabolites can be monitored simultaneously, providing a much more comprehensive snapshot of the effects that a particular chemical has on a living organism.
It gives a snapshot of what a particular chemical does to an organism.
Studies were conducted using Japanese medaka (Oryzias latipes), a species that is widely used in toxicity testing, to investigate the effects of trichloroethylene, an environmental pollutant, and the pesticide dinoseb on the development of fish embryos.5,6
Other metabolomics studies have identified biomarker patterns in earthworms (Eisenia veneta) following exposure to pollutants such as a nitrophenol7 and fluorinated anilines.8
The effects of arsenic, a common environmental contaminant, on kidney metabolism in the bank vole (Clethrionomys glareolus) have also been investigated using NMR-based metabolomics.9
A bacterial infection has been decimating abalone populations.
Monitoring withering syndrome in California red abalone
Red abalone (Haliotis rufescens), an important shellfish species that lives along the Pacific Coast of the United States, is susceptible to a disease called withering syndrome. This fatal disease is caused by a bacterial infection and is known to have decimated more than 90 percent of the related black abalone (Haliotis cracherodii) population in southern California.
Abalone aquaculture is economically important in the US.
The potential impact of withering disease on the aquaculture industry prompted the use of metabolomics to identify and measure multiple biomarkers associated with the disease. Using NMR-based metabolomics, characteristic fingerprints of metabolites were detected in the foot muscle, digestive gland, and hemolymph (blood) in diseased abalone that were different from those in healthy animals.10
Metabolomics provides a biomarker indicating the health of abalone.
Building upon this research, scientists have since investigated the influence of food availability, temperature, and bacterial infection on the health status of the red abalone.11 They have shown that withering syndrome depends on bacterial infection, and that metabolomics correlate well with the more painstaking inspection of the tissue under a microscope.
Furthermore, scientists confirmed that a particular ratio of two metabolites, glucose and homarine, in foot muscle serves as a biomarker for distinguishing diseased animals from both healthy and starved abalone.
Metabolomics have also been used to determine whether treatment with an antibiotic, oxytetracycline, can reverse the effects of withering syndrome. The results from this study are still pending (for further information, check the websites listed at the end of this article).
Future developments in environmental metabolomics
The goal is to diagnose health and identify factors that cause disease.
Although much progress has been made in environmental metabolomics in the past few years, researchers have only scratched the surface in terms of potential applications. This is partly because this approach is still technically complicated, limiting its widespread introduction into environmental laboratories. Indeed, considerable work still remains in developing the chemical and computational technologies that underpin this science. As the technology advances, we will better realize and exploit the advantages of metabolomics for studying disease and toxicity in wildlife. The point is to be able to diagnose the health of organisms using metabolomics analyses of minute blood samples, and then to relate these measurements on individuals to the overall health of the environment, particularly the impacts of pollution, climate change, and other manmade stressors.

Transgenic Animals: Their Benefits To Human Welfare

2009-05-27T03:53:00.001-07:00

Nowadays, breakthroughs in molecular biology are happening at an unprecedented rate. One of them is the ability to engineer transgenic animals, i.e., animals that carry genes from other species. The technology has already produced transgenic animals such as mice, rats, rabbits, pigs, sheep, and cows. Although there are many ethical issues surrounding transgenesis, this article focuses on the basics of the technology and its applications in agriculture, medicine, and industry.
What is a transgenic animal?
There are various definitions for the term transgenic animal. The Federation of European Laboratory Animal Associations defines the term as an animal in which there has been a deliberate modification of its genome, the genetic makeup of an organism responsible for inherited characteristics.5
A transgenic animal is one whose genome has been changed to carry genes from other species.
The nucleus of all cells in every living organism contains genes made up of DNA. These genes store information that regulates how our bodies form and function. Genes can be altered artificially, so that some characteristics of an animal are changed. For example, an embryo can have an extra, functioning gene from another source artificially introduced into it, or a gene introduced which can knock out the functioning of another particular gene in the embryo. Animals that have their DNA manipulated in this way are knows as transgenic animals.20
The majority of transgenic animals produced so far are mice, the animal that pioneered the technology. The first successful transgenic animal was a mouse.6 A few years later, it was followed by rabbits, pigs, sheep, and cattle.8,14,15,16
Why are these animals being produced? The two most common reasons are:
Transgenic animals are useful as disease models and producers of substances for human welfare.
Some transgenic animals are produced for specific economic traits. For example, transgenic cattle were created to produce milk containing particular human proteins, which may help in the treatment of human emphysema.
Other transgenic animals are produced as disease models (animals genetically manipulated to exhibit disease symptoms so that effective treatment can be studied). For example, Harvard scientists made a major scientific breakthrough when they received a U.S. patent (the company DuPont holds exclusive rights to its use) for a genetically engineered mouse, called OncoMouse® or the Harvard mouse, carrying a gene that promotes the development of various human cancers.22
How are transgenic animals produced?
Since the discovery of the molecular structure of DNA by Watson and Crick in 1953, molecular biology research has gained momentum. Molecular biology technology combines techniques and expertise from biochemistry, genetics, cell biology, developmental biology, and microbiology.2
Scientists can now produce transgenic animals because, since Watson and Crick’s discovery, there have been breakthroughs in:
The insertion of a foreign gene (transgene) into an animal is successful only if the gene is inherited by offspring.
The success rate for transgenesis is very low and successful transgenic animals need to be cloned or mated.
recombinant DNA (artificially-produced DNA)
genetic cloning
analysis of gene expression (the process by which a gene gives rise to a protein)
genomic mapping
The underlying principle in the production of transgenic animals is the introduction of a foreign gene or genes into an animal (the inserted genes are called transgenes). The foreign genes “must be transmitted through the germ line, so that every cell, including germ cells, of the animal contain the same modified genetic material.”26 (Germ cells are cells whose function is to transmit genes to an organism’s offspring.)
To date, there are three basic methods of producing transgenic animals:
DNA microinjection
Retrovirus-mediated gene transfer
Embryonic stem cell-mediated gene transfer
Gene transfer by microinjection is the predominant method used to produce transgenic farm animals. Since the insertion of DNA results in a random process, transgenic animals are mated to ensure that their offspring acquire the desired transgene. However, the success rate of producing transgenic animals individually by these methods is very low and it may be more efficient to use cloning techniques to increase their numbers. For example, gene transfer studies revealed that only 0.6% of transgenic pigs were born with a desired gene after 7,000 eggs were injected with a specific transgene.27
DNA microinjection is the predominant transgenesis method.
1. DNA Microinjection
The mouse was the first animal to undergo successful gene transfer using DNA microinjection.6 This method involves:
transfer of a desired gene construct (of a single gene or a combination of genes that are recombined and then cloned) from another member of the same species or from a different species into the pronucleus of a reproductive cell19
the manipulated cell, which first must be cultured in vitro (in a lab, not in a live animal) to develop to a specific embryonic phase, is then transferred to the recipient female
2. Retrovirus-Mediated Gene Transfer
The second method produces chimeras, altered animals with mixed DNA.
A retrovirus is a virus that carries its genetic material in the form of RNA rather than DNA. This method involves:26
retroviruses used as vectors to transfer genetic material into the host cell, resulting in a chimera, an organism consisting of tissues or parts of diverse genetic constitution
chimeras are inbred for as many as 20 generations until homozygous (carrying the desired transgene in every cell) transgenic offspring are born
The method was successfully used in 1974 when a simian virus was inserted into mice embryos, resulting in mice carrying this DNA.10
3. Embryonic Stem Cell-Mediated Gene Transfer
The presence of transgenes can be tested at the embryonic state in this third method.
This method involves:7,19,26
isolation of totipotent stem cells (stem cells that can develop into any type of specialized cell) from embryos
the desired gene is inserted into these cells
cells containing the desired DNA are incorporated into the host’s embryo, resulting in a chimeric animal
Unlike the other two methods, which require live transgenic offspring to test for the presence of the desired transgene, this method allows testing for transgenes at the cell stage.
How do transgenic animals contribute to human welfare?
The benefits of these animals to human welfare can be grouped into areas:
Agriculture
Medicine
Industry
The examples below are not intended to be complete but only to provide a sampling of the benefits.
1. Agricultural Applications
Transgenesis will allow larger herds with specific traits.
a) breeding Farmers have always used selective breeding to produce animals that exhibit desired traits (e.g., increased milk production, high growth rate).11,15,17 Traditional breeding is a time-consuming, difficult task. When technology using molecular biology was developed, it became possible to develop traits in animals in a shorter time and with more precision. In addition, it offers the farmer an easy way to increase yields.
Scientists can improve the size of livestock genetically.
b) quality Transgenic cows exist that produce more milk or milk with less lactose or cholesterol12, pigs and cattle that have more meat on them8,17, and sheep that grow more wool18. In the past, farmers used growth hormones to spur the development of animals but this technique was problematic, especially since residue of the hormones remained in the animal product.
Disease-resistant livestock is not a reality just yet.
c) disease resistance Scientists are attempting to produce disease-resistant animals, such as influenza-resistant pigs, but a very limited number of genes are currently known to be responsible for resistance to diseases in farm animals.19
2. Medical Applications
Transplant organs may soon come from transgenic animals.
a) xenotransplantation Patients die every year for lack of a replacement heart, liver, or kidney. For example, about 5,000 organs are needed each year in the United Kingdom alone.25 Transgenic pigs may provide the transplant organs needed to alleviate the shortfall.9 Currently, xenotransplantation is hampered by a pig protein that can cause donor rejection but research is underway to remove the pig protein and replace it with a human protein.25
Milk-producing transgenic animals are especially useful for medicines.
b) nutritional supplements and pharmaceuticals Products such as insulin, growth hormone, and blood anti-clotting factors may soon be or have already been obtained from the milk of transgenic cows, sheep, or goats.3,12,23 Research is also underway to manufacture milk through transgenesis for treatment of debilitating diseases such as phenylketonuria (PKU), hereditary emphysema, and cystic fibrosis.3,13,23,25
In 1997, the first transgenic cow, Rosie, produced human protein-enriched milk at 2.4 grams per litre. This transgenic milk is a more nutritionally balanced product than natural bovine milk and could be given to babies or the elderly with special nutritional or digestive needs.4,21,23 Rosie’s milk contains the human gene alpha-lactalbumin.
A transgenic cow exists that produces a substance to help human red cells grow.
c) human gene therapy Human gene therapy involves adding a normal copy of a gene (transgene) to the genome of a person carrying defective copies of the gene. The potential for treatments for the 5,000 named genetic diseases is huge and transgenic animals could play a role. For example, the A. I. Virtanen Institute in Finland produced a calf with a gene that makes the substance that promotes the growth of red cells in humans.24
Uses in industry include material fabrication and safety tests of chemicals.
3. Industrial Applications
In 2001, two scientists at Nexia Biotechnologies in Canada spliced spider genes into the cells of lactating goats. The goats began to manufacture silk along with their milk and secrete tiny silk strands from their body by the bucketful. By extracting polymer strands from the milk and weaving them into thread, the scientists can create a light, tough, flexible material that could be used in such applications as military uniforms, medical microsutures, and tennis racket strings.1
Toxicity-sensitive transgenic animals have been produced for chemical safety testing. Microorganisms have been engineered to produce a wide variety of proteins, which in turn can produce enzymes that can speed up industrial chemical reactions.20
What are the ethical concerns surrounding transgenesis?
This article focuses on the benefits of the technology; however, thoughtful ethical decision-making cannot be ignored by the biotechnology industry, scientists, policy-makers, and the public. These ethical issues, better served in their own article, include questions such as:
Ethical concerns must be addressed as the technology grows, including the issue of lab animal welfare.
Should there be universal protocols for transgenesis?
Should such protocols demand that only the most promising research be permitted?
Is human welfare the only consideration? What about the welfare of other life forms?
Should scientists focus on in vitro (cultured in a lab) transgenic methods rather than, or before, using live animals to alleviate animal suffering?
Will transgenic animals radically change the direction of evolution, which may result in drastic consequences for nature and humans alike?
Should patents be allowed on transgenic animals, which may hamper the free exchange of scientific research?
Conclusion: Transgenic technology holds great potential in agriculture, medicine, and industry.
Conclusion
Interestingly, the creation of transgenic animals has resulted in a shift in the use of laboratory animals — from the use of higher-order species such as dogs to lower-order species such as mice — and has decreased the number of animals used in such experimentation,26 especially in the development of disease models. This is certainly a good turn of events since transgenic technology holds great potential in many fields, including agriculture, medicine, and industry.
Acknowledgements: The updated information in this article is based on the author’s graduate student paper written for the course, Introduction to Science Philosophy (PPS 702), in 2001. The author is deeply grateful to professors Rudy C. Tarumingkeng, Ph.D. and Zahrial Coto, Ph.D. for their help.

Primer on Ethics and Crossing Species Boundaries

2009-05-27T03:51:00.000-07:00

Ancient Greek mythology is replete with references to part-human animals. There is the monstrous half-human, half-bull Minotaur; the Gorgon sisters (one of whom is Medusa) with hair of writhing snakes; the Sirens who are sweet singing sea nymphs each with the head of a woman and the body of a bird; and, not to be forgotten, there is the infamous Sphinx with the head and breasts of a woman, the body of a lion, and the wings of a bird. Part-human creatures are also a staple of modern science fiction, as in H. G. Wells’ The Island of Dr Moreau,1 where animals are vivisected into part-human creatures, or George Langelaan’s The Fly, in which a scientist emerges from his disintegrator-reintegrator machine with the head and arms of a fly.2
But part-human animals are not only science fiction—they are also science fact. While not as monstrous as the creatures of lore, part-human laboratory animals raise some important ethical and societal issues.
What does it mean to cross species boundaries?
First, from a biological perspective, it is surprisingly difficult to answer the question What does it mean to cross species boundaries? This is true not only because of the number of species concepts (according to some, as many as 22),3 but also because species boundaries are not fixed.
How do we define a species?
Is the boundary between species real or artificial?
Species concepts: One classic definition of species is the biological species concept. This definition emphasizes the importance of reproductive isolation or lack of genetic exchange that separates species.4 By this account, crossing species boundaries would involve the transfer of genetic materials between populations of organisms that do not interbreed. In cases where such interbreeding can be achieved artificially, as in the laboratory, the raison d’etre of the biological species concept is undermined. Other accounts of species may be brought to bear in place of the biological species concept, but the consensus among biologists is that no single species concept will be sufficient for all situations.
Species boundaries: One of the consequences of our evolutionary past is that genes, gene regulatory networks, epigenetic developmental processes, and features of the biophysical environment are widely shared by different kinds of creatures. The idea of fixed or rigid breaks between species plays no role whatsoever in contemporary biology. Indeed, the fluidity of species boundaries has been revealed through the techniques of comparative genomics, warning against the interpretation of species as unique types.
Crossing the boundary implies combining genetic or cellular material from two organisms.
Given the difficulty in defining species once and for all, and also the flexibility of species boundaries,5 what does it mean to cross species boundaries?
When we refer to species and the crossing of species boundaries,5 we do so based on the following simple idea: Every individual human contains a human genome. In all likelihood, this genome will not be representative of other human genomes and will contain a lot of DNA that is contained in many other kinds of organisms, thanks to our evolution from a common ancestor. The same will be true with nonhuman organisms, such as a rose or a rat or a Rhesus macaque. As such, when we refer to crossing species boundaries, we refer to the combination of genetic or cellular material from two organisms that would generally be understood, in lay terms, as belonging to different species: a human as understood by most lay people, a Rhesus macaque as understood by most lay people, and so on.6
Parents of hybrids are different species.
Genetically modified food is a transgenic product.
Chimeras have cells from two genetically distinct organisms.
Hybrids, transgenics, and chimeras

A geep: a sheep-goat chimera produced by combining the embryos of a goat and a sheep. Not to be confused with a sheep-goat hybrid, which can result when a goat mates with a sheep. Photo: Dr. Gary B. Anderson of Univ. of California, Davis.
There are many types of interspecies organisms including hybrids, transgenics, and chimeras, each of which is created through different sorts of processes. Hybrids are created through breeding. Transgenics are produced through genetic manipulation and modification. Chimeras are the result of cell or tissue transplants.
Hybrids are created by breeding across species. Hybrids are generally the result of combining an egg from one species with sperm from another to form a single embryo. Hybrids contain recombined genetic material throughout their genome and throughout all the tissues in their body.
Transgenics are the result of gene transfer. Typically, transgenics contain transferred or manipulated genes in addition to the host nuclear and mitochondrial DNA. One exception may be a transgenic embryo comprised of the entire complement of nuclear DNA from one organism fused with an enucleated egg cell from another.
Chimeras comprise a mixture of cells from two or more genetically distinct organisms of the same or different species. They are mosaics at the cellular level; individual cells are derived from either the host or the donor but not both.7
Note that chimeras and transgenics need not cross species boundaries, whereas hybrids are always interspecific.
Multiple applications
Crossing species boundaries happens all the time in nature and in agricultural settings, and it has a long history in developmental biology and immunology laboratories. Consider just a few examples:
Nature and breeding programs cross boundaries.
lateral gene transfer between bacteria, whereby genetic material is transmitted horizontally from one organism to another8
the crossing of strains of wheat; the insertion of genes from a plant (or an animal) into a plant to improve crop yield and robustness9
the mating of a horse with a donkey to create a mule; the fusion of sheep and goat cells to create a “geep”10
the transplantation of cells and tissues from one species of frog to another, and of neural tissue from quails to chickens, to study the complex processes of development11-13
Gene transfer from animals to humans and vice versa is common.
Crossing species boundaries between human and nonhuman animals is also commonplace:
Animal tissues, cells, and their derivatives are often transferred to humans, whether by using insulin produced from pig or cow pancreases, injecting flu vaccines cultured in fertilized chicken eggs, or transplanting heart valves from pigs into humans.
Human genes and cells are often transferred to animal hosts to create humanized animal models (such as OncoMouse, which develops human cancers14), to grow humanized tissues that can be transplanted back into humans (such as sheep with human livers15), or to test the developmental potential of transplants.16
Stem cell research
Stem cell research and cloning ignited debate.
In the first few years of human stem cell research, most of the ethics discussions centered on the use of human embryos as sources of stem cells. Research to derive human embryonic stem (hES) cells involves removing cells from the inner cell mass of a human blastocyst, which destroys the developing embryo. While this debate continued, further debate on the ethics of cloning to produce children, and cloning for biomedical research, emerged. This debate arose in response to claims about the anticipated benefit of future stem cell therapies using cells from cloned embryos, which would allow patients to receive transplants of cells containing their own DNA.17
The debate has encompassed part-human animals.
While these issues remain ethically contentious, a new debate has recently emerged concerning the ethics of crossing species boundaries to make part-human chimeras. Stem cell scientists and others insist that this cross-species work is important to basic science and a necessary step on the path to regenerative medicine. They maintain that it would be unethical to involve humans in stem cell transplantation research without first having studied the safety and efficacy of the human cells in nonhuman animals.
Ethical controversy
Issues of health and safety, especially given the possibility of zoonosis, or the transfer of a disease from nonhuman animals to humans, have long been front and center in the ethics debate about cross-species work.18 In the last decade or so, with the increase in science options for the crossing of species boundaries, other ethical issues have come to the fore.
Attempts to patent a humanzee failed but caused a stir.
In 1997, Stuart Newman, a developmental biologist sponsored by biotechnology activist Jeremy Rifkin, sought to preclude the creation of a humanzee—a part-human, part-chimpanzee chimera. Together, Newman and Rifkin tried to patent the relevant technology so that they would be able to restrict its use and to promote a vigorous social dialogue about the desirability of such part-human beings.19 They were unsuccessful in obtaining the patent, leaving open the possibility that humanzees may soon walk among us, with or without patent protection. Examples of recent research involving the transplantation of cells and tissues into prenatal nonhuman animals (embryos and fetuses), the transplantation of cells and tissues into nonhuman animal brains, and the transplantation of cells and tissues into the brains of nonhuman primates, serve to make this point:
Part-human animals already exist.
Scientists want to test human cells in other primates.
Scientists at Harvard University have published their research involving the transfer of human neural stem cells into the developing fetal brain of bonnet monkeys.20
Scientists in Israel have reported that human embryonic stem cells transplanted into chick embryos differentiated into neurons.21
Scientists in Nevada have reported on inserting human neural stem cells into fetal sheep to assess their developmental potential.22
Scientists in California have reported on the development of functional neurons in mouse brains, where the neurons were derived from human embryonic stem cells.23
While this research is ongoing, a debate has erupted about the ethics of creating part-human beings in response to proposals from some stem cell scientists to use nonhuman primates as an assay system for testing the developmental potential of human stem cells. The fact that biologists are especially interested in transplanting human neural stem cells into the brains of nonhuman primates24 intensifies the controversy about humanzee-like chimeras.
The ethics of creating part-human beings
Is it natural and moral to develop part-human animals?
The ethical debate has been multivocal, with moral considerations raised from many perspectives, both religious and secular. The central moral concerns with creating part-human beings include worries about the following:
the unnaturalness and intuitive repugnance of certain kinds of creatures, such as part-human combinations25
the threat of intensified moral confusion regarding the creation of novel part-human beings who violate the pragmatically clear moral demarcation line between species upon which current institutions, structures, and social practices are based5
the potential for transferring moral status to nonhuman animals by conferring on them characteristically human cognitive capacities, which may or may not threaten human dignity24,26
the possibility that enhanced animals would deserve to be treated as if they were human subjects but would continue being treated as if they were unenhanced nonhuman animals27
the moral status of nonhuman animals, especially primates, as experimental animals28
Some see the medical benefits of the research.
Others see it as a way to improve humans.
Scientists and others who advocate cross-species work argue that the part-human animals will be useful as disease models, assay systems, or organ sources.16,29 They dismiss the worries about repugnance, deny the potential for moral confusion, and endeavor to sidestep concerns about moral status and potential threats to human dignity. They also rely heavily on current norms for research involving humans to legitimate preclinical cross-species research in nonhuman animals.
Additionally, advocates of transhumanism, the movement to enhance humans using biotechnology, argue that the creation of hybrids, transgenics, and chimeras may be useful in the quest to radically alter humans.30 They see an opportunity to improve upon human nature and to enhance cognitive and physical performance—an idea that is itself morally controversial.31
More debate is needed about the value and ethics of such research.
Toward a constructive public debate
Unfortunately, much of the public debate on the ethics of crossing species boundaries is characterized by sensationalism and political posturing. While some commentators have attempted to explore the moral dimensions of interspecies research in careful and respectful terms, many of the media reports have exaggerated the conflict, providing more heat than light. Even so, attempts at public education and public engagement have tended to reveal the persistence of the moral controversy. This suggests the need for scientists, ethicists, and others to take seriously the ethical concerns that have been raised. The voluntary guidelines for human embryonic stem cell research recently published by the National Academy of Sciences arguably are an attempt to do just this.32 As we have argued elsewhere, however, considerably more debate and discussion is needed about the fundamental underlying values.33,34

DEAFNESS GENE

2009-05-27T03:26:00.000-07:00

MicroRNA mir-96 mutation leads to loss of hearing if it is present in a single copy and deafness if it is present in two copies.

The results of a search conducted under the projects "Sirocco" and "Eurohear" which was funded by the European Union was posted in nature genetics journal.The association between a new type of gene and progressive loss of hearing is concerned in this discovery.The mir-96 gene is a small piece of RNA that affect the process of generation of other molecules in sensory hair cells of the inner ear .

The results came from the collaboration of two research groups, one Spanish and one English.

Karen Steel who was one of the coordinators of the team of British Sanger Institute, said "We were able to demonstrate relatively quickly if the mice that were carriers of one copy of the variant of this gene suffer from progressive loss of hearing, and if they were carrying both genes, they were suffering from severe hearing loss. The main principal questions to be answered concerning the possibility to determine which variant was involved and how influences on hearing ".

Chromosome 7 which was identified recently is the possible location of the gene altered the two groups of researchers have sequenced the gene in each "homologous genomic regions in man and mouse that are associated with hearing loss" and it has showed the presence of a mutation in the gene mir - 96.

Miguel Angel Moreno-Pelayois is the author of the study and researcher at the Hospital Ramon y Cajal in Spain.He said "We know a number of genes associated with deafness in humans and mice, but we discovered with surprise that this belongs to a new class of MicroRNA genes defined. No one had observed a mutation that can cause disease in a couple of MicroRNA sequence. This is the first MicroRNA gene associated with hearing loss and e 'is significant that the first to be associated with a hereditary condition. "

Experts recognized that the MicroRNA may bind to the active messengers in the generation of cell protein, effectively stopping the process and now have discovered that it is possible to analyze the role of mutation in mice. It also seems that the sensory hair cells in the mutant mice are affected by mir-96 gene, while mice carrying two copies of the gene mutant hair cells are deformed from birth and cells subjected to a degeneration in the early stages of life.

Morag Lewis of the Sanger Institute who discovered the mutation had commented that "The mutation, or variation of a single letter of genetic code from A to T in this tiny extension, is sufficient to cause a serious loss in mice".

This mechanism may also occur in human beings.But, according to analysis of the two families used as a sample, the mutation does not happen ever in the same regions where the mouse, although affect neighboring regions, and always very important for the proper functioning of mir-96 .