PakMed Info Forum

Caffeine as cancer-cell killer generates buzz among researchers

Caffeine as cancer-cell killer generates buzz among researchers

Washington: University of Alberta researchers are abuzz after using fruit flies to find new ways of taking advantage of caffeine’s lethal effects on cancer cells-results that could one day be used to advance cancer therapies for people.

Previous research has established that caffeine interferes with processes in cancer cells that control DNA repair, a finding that has generated interest in using the stimulant as a chemotherapy treatment.

But given the toxic nature of caffeine at high doses, researchers from the faculties of medicine and dentistry and science instead opted to use it to identify genes and pathways responsible for DNA repair.

“The problem in using caffeine directly is that the levels you would need to completely inhibit the pathway involved in this DNA repair process would kill you,” said Shelagh Campbell, co-principal investigator.

“We’ve come at it from a different angle to find ways to take advantage of this caffeine sensitivity,” the researcher noted.

Lead authors Ran Zhuo and Xiao Li, both PhD candidates, found that fruit flies with a mutant gene called melanoma antigen gene, or MAGE, appeared normal when fed a regular diet but died when fed food supplemented with caffeine.

On closer inspection, the researchers found that the mutant flies’ cells were super-sensitive to caffeine, with the drug triggering “cell suicide” called apoptosis. Flies fed the caffeine-laden diet developed grossly disfigured eyes.

Through this work, the research team identified three genes responsible for a multi-protein complex, called SMC5/SMC6/MAGE, which regulates DNA repair and the control of cell division. Neither process works properly in cancer cells.

Co-principal investigator Rachel Wevrick explained that this finding is significant because it means that scientists one day could be able to take advantage of cancer-cell sensitivity to caffeine by developing targeted treatments for cancers with specific genetic changes.

“Unless you actually know what it is those proteins are doing in the first place to make a cell a cancer cell instead of a normal cell, it’s hard to know what to do with that information,” she said.

“You need to know which genes and proteins are the really bad actors, how these proteins work and which of them work in a pathway you know something about where you can actually tailor a treatment around that information,” she added.

Their results were published in the March issue of the peer-reviewed journal PLOS One.

Why Mediterranean diet is good for older adults

Why Mediterranean diet is good for older adults

Washington: A baseline adherence to a Mediterranean diet (MeDiet) was found to be associated with a lower risk of hyperuricemia, defined as a serum uric acid (SUA) concentration higher than 7mg/dl in men and higher than 6mg/dl in women, according to a study.

Hyperuricemia has been associated with metabolic syndrome, hypertension, type 2 diabetes, mellitus, chronic kidney disease, gout, and cardiovascular morbidity and mortality.

The MeDiet is characterized by a high consumption of fruits, vegetables, legumes, olive oil, nuts, and whole grain; a moderate consumption of wine, dairy products, and poultry, and a low consumption of red meat, sweet beverages, creams, and pastries.

Due to its antioxidant and anti-inflammatory properties, the MeDiet might play a role in decreasing SUA concentrations.

Conducted by Marta Guasch-Ferre and 11 others, this study is the first to analyze the relationship between adherence to a MeDiet in older adults and the risk of hyperuricemia.

The five-year study looks at 7,447 participants assigned to one of three intervention diets (two MeDiets enriched with extra virgin olive oil or mixed nuts, or a control low-fat diet). Participants were men aged 55 to 80 years and women aged 60 to 80 years who were free of cardiovascular disease but who had either type 2 diabetes mellitus or were at risk of coronary heart disease.

The findings below demonstrate the positive health effects of a MeDiet in older adults:

Rates of reversion were higher among hyperuricemic participants at baseline who had greater adherence to the MeDiet.

Consuming less than one serving a day of red meat compared with higher intake is associated with 23 percent reduced risk of hyperuricemia.

Consuming fish and seafood increased the prevalence of hyperuricemia.

Drinking more than seven glasses of wine per week increased the prevalence of hyperuricemia.

Consuming legumes and sofrito sauce reduced the prevalence of hyperuricemia.

Reversion of hyperuricemia was achieved by adherence to the MeDiet alone, without weight loss or changes to physical activity.

The study was published in the Journals of Gerontology Series A: Biological Sciences and Medical Sciences.

Hookah ‘not safe alternative to cigarette smoking’

Hookah ‘not safe alternative to cigarette smoking’

Washington: Many people believe that smoking tobacco through a hookah is less harmful than smoking cigarettes.

But in a new study at UC San Francisco, researchers measuring chemicals in the blood and urine have concluded that hookah smoke contains a different – but still harmful – mix of toxins.

UCSF research chemist Peyton Jacob III, PhD, and UCSF tobacco researcher Neal Benowitz, MD, both based at San Francisco General Hospital and Trauma Center, said hookah use exposes smokers to higher levels of carbon monoxide, especially hazardous to those with heart or respiratory conditions, and to higher levels of benzene, long associated with leukemia risk.

“People want to know if it is a lesser health risk if they switch from cigarettes to smoking a water pipe on a daily basis. We found that water-pipe smoking is not a safe alternative to cigarette smoking, nor is it likely to be an effective harm-reduction strategy,” Jacob said.

And compared to non-smokers, Benowitz said, “If you are smoking from a hookah daily, you are likely to be at increased risk for cancer.”

Jacob said, “In addition to delivering toxic substances from the charcoal and tobacco, the heat causes chemical reactions in the mixture which produce toxic volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). Some PAHs are highly carcinogenic and can cause lung cancer.”

Intake of nicotine, the addictive component of tobacco, was less with water pipe use.

The findings are published in Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research.

Running or jumping may worsen cartilage damage in arthritis patients

Running or jumping may worsen cartilage damage in arthritis patients

Washington: In the earliest stages of arthritis, high-impact exercises such as running or jumping may worsen cartilage damage, according to MIT engineers.

Osteoarthritis leads to deterioration of cartilage, the rubbery tissue that prevents bones from rubbing together.

By studying the molecular properties of cartilage, MIT engineers have now discovered how the earliest stages of arthritis make the tissue more susceptible to damage from physical activities such as running or jumping.

The findings could help researchers develop tests to diagnose arthritis earlier in patients at high risk for the disease and also guide engineers in designing replacement cartilage.

The results also suggested that athletes who suffer traumatic knee injuries, such as a torn anterior cruciate ligament (ACL) – which gives them a greater chance of developing arthritis later in life – should be cautious when returning to their sport following surgery.

Cartilage is packed with protein-sugar complexes known as aggrecans, each made of about 100 highly charged molecules called glycosaminoglycans (GAGs). Those molecules protect joints by absorbing water and causing the tissue to stiffen as pressure is applied.

“The cartilage is a stiff sponge, filled with fluid, and as we compress it, fluid has to percolate through these closely spaced GAG chains,” said Alan Grodzinsky, an MIT professor of biological, electrical and mechanical engineering and senior author of the study.

“The GAG chains provide resistance to flow, so the water can’t get out of our cartilage instantly when we compress it. That pressurization at the nanoscale increases the stiffness of our cartilage to high-loading-rate activities,” he added.

The MIT team set out to investigate how the molecular structure of GAG generates this stiffening over such a wide range of activity – from sitting and doing nothing to running or jumping at high speed. To do this, they developed a new, highly sensitive type of atomic force microscopy (AFM), allowing them to measure how aggrecan reacts at the nanoscale to very high loading rates (the speeds at which forces are applied).

Using this system, the researchers compared normal cartilage and cartilage treated with an enzyme that destroys GAG chains, mimicking the initial stages of osteoarthritis. In this early phase, collagen, which gives cartilage its structure, is usually still intact.

The researchers found that when exposed to very high loading rates – similar to what would be seen during running or jumping – normal cartilage was able to absorb fluid and stiffen normally. However, in the GAG-depleted tissue, fluid leaked out rapidly.

“That’s what puts the collagen in trouble, because now this becomes a very floppy sponge, and if you load it at higher rates the collagen network can be damaged. At that point you begin an irreversible series of activities that can result in damage to the collagen and eventually osteoarthritis,” Grodzinsky said.

Researchers in Grodzinsky’s lab are now working to identify possible drugs that might halt the loss of aggrecan, as well as designing tissue scaffolds that could be implanted into patients who need cartilage-replacement surgery.

The findings appeared in a recent issue of the Biophysical Journal.

Needle-Nose Parasite Inspires New Surgical Bandage

Doctors perform surgery at St. Vincent Infirmary Medical Center, Little Rock, Ark

A fish parasite with a needle-like nose that pierces the intestines of its host has inspired a revolutionary medical invention that could replace surgical staples now used to hold skin grafts in place and close serious wounds.

Researchers at Brigham and Women’s Hospital in Boston, Massachusetts, led by biomedical engineer Jeffrey Karp, say they saw a need for an improved medical adhesive and looked to nature for ideas.

“When we started looking into the parasite literature, we quickly stumbled upon worms and, in particular, this spiny-headed worm that has a needle-like proboscis [nose] that inserts in the intestine of fish … and only the needles swell, so it kind of mechanically locks into place,” said Karp, describing a freshwater-fish parasite called Pomphorhynchus laevis, whose swelling and locking needle-nose design gave his team a model for the new and improved surgical bandage with unique adhesive properties.

Karp’s prototype, a microneedle-lined bandage that plumps up when exposed to water, locks painlessly into the patient’s subdermal tissue and adheres 3-and-a-half times more strongly than any clinical bandage now in use.

The elongated microneedle tips, made with a rigid plastic core, attach to stiff plastic inner and outer layers of highly absorbent material that is similar to the inside of a disposable diaper. When wet, the needles form a mechanical bond with the tissue.

The microneedle patch is also designed to eliminate two specific problems with surgery involving skin-grafts.

According to Karp, who consulted with Dr. Bo Pomahac, head of face transplant surgery at Brigham and Women’s, when conventional staples hold skin grafts in place, they can produce holes 2-to-3 times larger than the width of the staple itself, allowing for potentially harmful bacterial infections. The grafts, Karp says, are also susceptible to filling with accumulated fluids, which can prevent healing.

“Instead of using staples,” Karp said, “we would apply a microneedle patch directly on top of the skin graft that will push down to the underlying tissue and essentially lock that graft in place.”

Karp also envisions impregnating microneedle patches with antibiotics and other drugs that would infuse slowly into wounds, helping to keep them clean and quick-healing. Researchers are attempting to develop a microneedle patch that can be used to help seal, and heal, internal organs following surgery.

When it comes to removing the bandage, Karp doesn’t think it would hurt more than pulling out surgical staples, which penetrate skin more deeply than the microneedles on the new bandage patch.

The work by Karp and colleagues was funded in part by the National Institutes of Health. An article describing a new micro-needle surgical bandage is published in Nature Communications.

WHO: Immunizations Save 2-3 Million Lives Each Year

A mother holds her baby as he receives a pneumococcal vaccination during a national vaccination campaign in Managua,

GENEVA — The World Health Organization estimates immunization saves the lives of two- to three million children every year.  In advance of World Immunization Week, which starts April 20, the U.N. agency is calling on nations to help immunize more children against preventable diseases so more lives can be saved.

The World Health Organization estimates nearly 80 percent of infants worldwide are receiving the full course of vaccinations against killer diseases, such as diphtheria, measles and whooping cough.  But 20 percent, or 22 million children, are not protected from dangerous diseases with basic vaccines.

WHO Director of Immunization, Vaccination and Biologicals, Jean-Marie Okwo-Bele, says the lack of universal coverage is the reason why global efforts to eradicate polio and to eliminate measles are behind schedule.

In addition, he notes cost is putting some of the newer vaccines out of the reach of children in poor countries.

“The newer vaccines that are available against the two top killers of children-pneumonia and diarrhea-that these vaccines are not accessible to the majority of children in the world,” said Okwo-Bele. “And, we know that child deaths will be reduced by an additional one to one-and-one- half million deaths with increased access to all vaccines.”

The World Health Organization reports most of the 22 million unvaccinated children live in Africa and Southeast Asia.  It says 10 countries account for 80 percent of those who lack immunization against preventable diseases.  These countries include Nigeria, the Democratic Republic of Congo, India, Indonesia and Pakistan.

Dr. Okwo-Bele says inefficient health and delivery systems threaten the ability of poorer nations to receive good quality vaccines.  For example, he notes many countries have problems receiving a good supply of vaccines because they are unable to keep them at the correct temperature.

He says many vaccines are being packaged and designed to meet the needs of developing countries.

“In Benin last year, for the first time we used the vaccine, the new vaccine that has been produced for combating Meningitis A epidemics in Benin and West Africa,” Okwo-Bele explained. “So, we used that vaccine outside the cold chain for up to four days in district and health facility levels.  And, this is a big step to help with vaccination campaigns especially in these areas where we do not have a ready cold chain.”

The World Health Organization says vaccination is the best way to protect children against preventable diseases that could kill them.  It says health officials and governments must do a better job of communicating the benefits provided by vaccines.

It says it is important to shatter myths that claim vaccines do not work or have damaging and long-term side effects and can even be fatal.

The World Health Organization rejects assertions that measles vaccines can cause Autism.  It says this is false.

China: Human Transmission of Bird Flu is Possible

Nurses collect patients’ blood samples at a specialized fever clinic inside the Ditan Hospital, where a Chinese girl is being treated for the H7N9 strain of bird flu, in Beijing

A top health official in China says it is possible that a deadly, new strain of bird flu could spread among humans, but cautioned there is no reason to fear a widespread pandemic.

Feng Zijian, a director at the Chinese Center for Disease Control and Prevention, says human-to-human transmission of the H7N9 strain of bird flu is possible in theory, though highly sporadic.

China has reported 17 deaths since the virus was reported in humans for the first time last month. In total, 82 people have been infected, most were near Shanghai.

Until now, the virus was believed to have only been transmitted from birds to humans, greatly limiting its ability to spread. But officials say 40 percent of those infected appear to have had no contact with poultry.

The World Health Organization confirmed the finding, but warned there is no evidence of “sustained human-to-human transmission.”

John Oxford, a professor of virology at Queen Mary University of London, tells VOA he is not overly concerned the situation will spiral out of control. He says many of those infected may not have realized they came into contact with birds.

“It could be their friend who is working with chickens, whose got his fingers and hands covered in chicken down,” he said. “So it’s not necessarily a real person to person transmission, you’re both getting it from the same source.”

Of particular interest is a case involving an 87-year-old Chinese man who suffered China’s first human death from H7N9. One of his sons was confirmed to have contracted the virus, and recovered. Another son later died, though the cause of his death is unclear.

Chinese authorities are investigating whether cases like this mean long-term and unprotected exposure to the infected person might result in a person-to-person transmission.

But Oxford says even if this is the case, that does not mean that the virus will easily spread quickly outside the family.

“The family is a very unique structure – people share things, share towels, even toothbrushes, and live very closely together, and the hygiene can be quite low. So you can’t base a whole philosophy of what’s going to happen [with a virus] based on a family transmission,” he said.

China has been working on developing vaccines and other treatment for the virus, as part of a wider plan to combat any potential outbreak. It has also slaughtered thousands of birds and closed many poultry markets in an attempt to slow the spread of the disease.

This is believed to be the first time humans have contracted the H7N9 bird flu virus. It previously existed only in birds. The more common strain of avian flu, H5N1, has killed more than 360 people worldwide in the last decade.

China is considered one of the countries at greater risk for bird flu because it has the world’s biggest poultry population and many chickens in rural areas are kept close to humans.

Exclusive, Extended Breastfeeding Lowers Mother-to-Infant HIV Risk

World Breastfeeding Week, which occurs August 1-7, has a simple goal: to increase the number of mothers who breastfeed.

A new study has found that HIV-infected mothers are less likely to transmit the virus to their newborns if they breastfeed their child exclusively for more than four months.  The findings have important implications in sub-Saharan Africa, where infants are at greater risk of contracting and dying from diarrheal diseases or pneumonia.

Breastfeeding is widely regarded as the best form of nutrition for newborns because human milk transfers not only  essential nutrients but also important immune-system factors from mother to child, protecting the baby against potentially life-threatening infections.

But Louise Kuhn of Columbia University’s Mailman School of Public Health in New York says there has always been some controversy about breastfeeding by HIV-infected mothers, since the virus that causes AIDS canalso be transmitted through breast milk.

Public health experts estimate that HIV-infected mothers have a 10 to 15 percent chance of passing the virus to their newborns through their breast milk. Kuhn and her colleagues wanted to find out if changes in breastfeeding routines would affect the levels of HIV in the breast milk.

They studied just over 950 HIV-infected women in Lusaka, Zambia in 2006 – before antiretroviral drugs were given to nursing mothers – and encouraged all of them to exclusively breastfeed their babies from birth for at least four months.   Throughout the study, the newborns were regularly tested for HIV.

At the four-month mark, half of the mothers were asked to stop nursing, while the other half continued to breastfeed exclusively. At four-and-a-half months, Kuhn says samples of breast milk were collected from all of the study participants and analyzed.

“We found that stopping breastfeeding early was a really bad idea for several different reasons,” said Kuhn.

Kuhn says investigators discovered the highest concentrations of HIV in the breast milk of women who had stopped breast feeding at four months.  More than three-quarters of them had evidence of the virus in their milk, compared to just under 40 percent of the women who were still breastfeeding. The two groups of women showed no differences in HIV levels two weeks earlier, when they were both tested at the four-month mark.

Women in a control group who nursed an average of 16 months and supplemented breastfeeding with other nutrition also had higher HIV concentrations in their milk compared to those who breastfed exclusively beyond four months.

Investigators believe changes in breast tissue that occur during sudden weaning could account for higher concentrations of HIV in women who stopped nursing at four months.

Kuhn says the results show that even subtle decreases in breastfeeding frequency during a child’s infancy can increase concentrations of HIV in an infected mother’s breast milk.  That suggests that it is in the interest both of the mother and child for women to practice exclusive and extended breastfeeding.

Kuhn notes that breastfeeding is actually a very inefficient way to transmit the AIDS virus.  She says the risk is minimal among mothers who nurse and take antiretroviral drugs at the same time.

“If antiretroviral drugs are given and an HIV-positive woman is fully adherent with the treatment throughout the duration of breastfeeding, the actual risk of transmitting HIV through breast milk is exceedingly low.  It’s probably in the one to two percent [range] if not lower with complete adherence with antiretroviral therapy,” she said.

An article on reducing the risk of mother-to-child HIV transmission through breast milk is published in the journal Science Translational Medicine.