URINE TEST FOR DIABETES

Home Urine Test Measures Insulin Production in Diabetes

February 24th, 2011

A simple home urine test has been developed which can measure if patients with Type 1 and Type 2 diabetes are producing their own insulin. The urine test, from Professor Andrew Hattersley's Exeter-based team at the Peninsula Medical School, replaces multiple blood tests in hospital and can be sent by post as it is stable for up to three days at room temperature. Avoiding blood tests will be a particular advantage for children. The urine test measures if patients are still making their own insulin even if they take insulin injections. Researchers have shown that the test can be used to differentiate Type 1 diabetes from Type 2 diabetes and rare genetic forms of diabetes. Making the correct diagnosis can result in important changes in treatment and the discontinuation of insulin in some cases. Jillian, 35 has recently benefitted from the home urine test. She was diagnosed with diabetes aged 19 and put on insulin injections. The urine test identified that she is still making her own insulin 14 years after being diagnosed and a DNA test confirmed that she has a genetic type of diabetes. After 14 years of insulin treatment, Jillian is now off her insulin injections. "Being told I don't have to take insulin injections any more has changed my life", she said. The key studies, led by Dr Rachel Besser and Dr Angus Jones and were funded by Diabetes UK and the National Institute of Health Research, are published in leading diabetes journals, Diabetes Care and Diabetic Medicine. Dr Rachel Besser, who has led the studies on over 300 patients, commented: "The urine test offers a practical alternative to blood testing. As the urine test can be done in the patients own home we hope that it will be taken up more readily, and more patients can be correctly diagnosed and be offered the correct treatment". Dr. Iain Frame, Director of Research at leading health charity Diabetes UK, said: "Dr. Besser's research is an excellent example of Diabetes UK's commitment to fund scientists at the beginning of their careers in diabetes research. With growing numbers of people with diabetes, it's more important than ever to ensure that medically trained graduates are encouraged to enter the field of diabetes research to help improve the lives of people with the condition. Many aspects of diabetes, from diagnosis to treatment, are invasive. Therefore, we welcome Dr. Besser's research and look forward to further developments." Source: Peninsula College of Medicine & Dentistry

AFFECT OF CELL PHONE ON THE BRAIN

Cell phones show effect on brain activity most pronounced near the antenna

February 24th, 2011

In a study of the effects of cell phone usage on brain cell activity, NIH scientists and their colleagues at the U.S. Department of Energy's Brookhaven National Laboratory found that 50 minutes of cell phone usage (with the phone muted to avoid confounding effects from auditory stimulation) elevated brain glucose metabolism significantly in the parts of the brain closest to the phone's antenna. Elevations in glucose metabolism, a measure of brain cell activity, were correlated with the estimated strength of the electromagnetic field emitted by the phone in those regions. The findings are published in the in the February 22, 2011, issue of JAMA. Arrow in the left image shows the location in the orbitofrontal cortex in one subject where glucose metabolism was increased during cell phone use. Red and orange areas shows higher brain metabolic activity. On the right is a baseline image with the cell phone turned off, showing lower activity. "Although we cannot determine the clinical significance, our results give evidence that the human brain is sensitive to the effects of radiofrequency-electromagnetic fields from acute cell phone exposures," said Nora Volkow, the study's lead author. Discrepancies among studies on the effects of RF-electromagnetic fields (RF-EMF) from cell phones on the human brain highlight the need for additional research. Prior studies of the acute effects of cell phone use on human brain function, including measurements of cerebral blood flow monitored by positron emission tomography (PET), have yielded inconsistent results, which might have reflected, in part, the small sample sizes of such studies (the largest studies had 14 subjects). Arrow in the left image shows the location in the orbitofrontal cortex in one subject where glucose metabolism was increased during cell phone use. Red and orange areas shows higher brain metabolic activity. On the right is a baseline image with the cell phone turned off, showing lower activity. The current study, also using PET, provides a more direct measure of brain activity than cerebral blood flow. It uses a radioactively "tagged" form of glucose known as [18F]fluoro-deoxyglucose, or FDG, to measure glucose metabolism in specific regions of the brain. "FDG is a direct substitute for glucose, the brain's fuel. Measuring its concentration in the brain gives a highly specific measure of brain cell metabolism, which is a more direct measure of brain activity than measures of blood flow," Volkow said. Also, because brain glucose metabolic measures obtained with FDG reflect the averaged brain activity occurring over a 30-minute period, this method can assess the cumulative effects of cell phone exposure on resting brain metabolism, unlike blood flow measures, which isolate a more restricted point in time. Scientists conducted the study in 47 healthy individuals. All participants had two scans done on separate days. On both days, prior to the scans, two cell phones, one placed on the left and one on the right ear, were used so subjects wouldn't know which cell phone was active. For one of the days both cell phones were off. For the other day the right cell phone was on but muted while receiving a call from a recorded text. The order of conditions was randomly assigned, and participants did not know when an active phone was being tested. With the cell phones secured to their heads, the subjects sat in a quiet room, not speaking, with eyes open for 20 minutes prior to being injected with the FDG tracer, and then for 30 more minutes, for a total cell phone exposure time of 50 minutes . RF-EMF emissions were recorded once before the call (background) and every five minutes during the "on" phase to ensure that the call was not terminated. Using computational and photographic methods, the scientists were also able to calculate the relative amplitude of the cell phone's electric field at every position in the brain. After the exposure period, the phones were removed and the subjects were placed in the PET scanner for measurements of brain activity. There were no differences in overall brain metabolism between the on and off conditions, but during the on condition, the specific regions of the brain closest to the phone's antenna showed significant increases in brain glucose metabolism. The regions expected to have the greater absorption of RF-EMF from the cell phone exposure were the ones that showed the largest increases in glucose metabolism. "The linear association between cell phone-related increases in metabolism and electric field strength suggests that the metabolic increases are secondary to the absorption of RF-EMF from cell phone exposures," Volkow said. "Further studies are needed to assess if the effects we observed could have potential long-term consequences." This research was funded by the Intramural Research Program of the National Institutes of Health (NIH) using infrastructure supported at Brookhaven Lab by DOE's Office of Science. Source: Brookhaven National Lab

New insight on diabetes

Missing sugar molecule raises diabetes risk in humans

February 24th, 2011

Researchers at the University of California, San Diego School of Medicine and Rady Children's Hospital-San Diego say an evolutionary gene mutation that occurred in human millions of years ago and our subsequent inability to produce a specific kind of sugar molecule appears to make people more vulnerable to developing type 2 diabetes, especially if they're overweight. The findings are published in the Feb. 24 online edition of The FASEB Journal, a publication of the Federation of American Societies of Experimental Biology. Corresponding study author, Jane J. Kim is an assistant professor in the UCSD Department of Pediatrics and a member of the Pediatric Diabetes Research Center and Rady Children's Hospital-San Diego, a research and teaching affiliate of the UCSD School of Medicine. Kim said the findings represent the first documented evidence linking the sugar production to insulin and glucose metabolism problems associated with diabetes. "It opens up a new perspective in understanding the causes of diabetes," said Kim. "Given the global epidemic of obesity and diabetes, we think that these findings suggest that evolutionary changes may have influenced our metabolism and perhaps increased our risk of the disease." Type 2 diabetes is caused by both genetic and environmental factors, such as a fatty diet and lack of exercise, that result in progressively dysfunctional pancreatic beta cells, elevated blood sugar levels due to insulin resistance and eventual health complications, sometimes fatally so. Diabetes is an expanding problem, nationally and globally. In the United States, more than 25 million adults and children � almost nine percent of the population - have diabetes, according to the American Diabetes Association. Another 79 million Americans are estimated to be prediabetic. Worldwide, roughly 285 million people are believed to have the disease. Sialic acids are sugar molecules found on the surfaces of all animal cells, where they act as vital contact points for interaction with other cells and with their surrounding environment. Virtually all mammals produce two types: N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). Humans are the exception. For reasons lost in the mists of evolution, a mutation in a gene called CMAH occurred 2 to 3 million years ago, inactivating an enzyme in humans that catalyzes production of Neu5Gc by adding a single oxygen atom to Neu5Ac. Researchers compared two groups of mice: one with a functional CMAH gene, the other with an altered CMAH gene similar to the human mutation. Both groups of mice were fed a high-fat diet. Mice in both groups became obese and developed insulin resistance. However, only mice with the CMAH gene mutation experienced pancreatic beta cell failure � the cells that make and release insulin, a hormone that controls blood sugar levels. Kim said the findings help refine understanding of why obese humans appear to be particularly vulnerable to type 2 diabetes, and also suggest that current animal models used to study diabetes may not accurately mirror the human condition. In clinical terms, she said further research to determine how sialic acid composition affects pancreatic beta cell function may reveal new strategies to preserve the cells, improve insulin production and prevent diabetes. Co-authors of the study are Sarah Kavaler and Alice Jih, UCSD Department of Pediatrics and Rady Children's Hospital-San Diego; Hidetaka Morinaga and WuQuiang Fan, UCSD Department of Medicine; Maria Hedlund and Ajit Varki, UCSD departments of Medicine, Cellular and Molecular Medicine and UCSD Glycobiology Research and Training Center. Funding support was provided by the National Institutes of Health Source: UC San Diego Credit: Eurekalert

BONES AND MALE FERTILITY

Skeleton regulates male fertility

February 17, 2011

Researchers at Columbia University Medical Center have discovered that the skeleton acts as a regulator of fertility in male mice through a hormone released by bone, known as osteocalcin.

The research, led by Gerard Karsenty, M.D., Ph.D., chair of the Department of Genetics and Development at Columbia University Medical Center, is slated to appear online on February 17 in Cell, ahead of the journal's print edition, scheduled for March 4.
Until now, interactions between bone and the reproductive system have focused only on the influence of gonads on the build-up of bone mass.
"Since communication between two organs in the body is rarely one-way, the fact that the gonads regulate bone really begs the question: Does bone regulate the gonads?" said Dr. Karsenty.
Dr. Karsenty and his team found their first clue to an answer in thereproductive success of their lab mice. Previously, the researchers had observed that males whose skeletons did not secrete a hormone called osteocalcin were poor breeders.
The investigators then did several experiments that show that osteocalcin enhances the production of testosterone, a sex steroid hormone controlling male fertility. As they added osteocalcin to cells that, when in our body produce testosterone, its synthesis increased. Similarly, when they injected osteocalcin into male mice, circulating levels of testosterone also went up.
Conversely, when osteocalcin is not present, testosterone levels drop, which causes a decline in sperm count, the researchers found. When osteocalcin-deficient male mice were bred with normal female mice, the pairs only produced half the number of litters as did pairs with normal males, along with a decrease in the number of pups per litter.
Though the findings have not yet been confirmed in humans, Dr. Karsenty expects to find similar characteristics in humans, based on other similarities between mouse and human hormones.
If osteocalcin also promotes testosterone production in men, low osteocalcin levels may be the reason why some infertile men have unexplained low levels of testosterone.
Skeleton Regulates Male Fertility, But Not Female
Remarkably, although the new findings stemmed from an observation about estrogen and bone mass, the researchers could not find any evidence that theskeleton influences female reproduction.
Estrogen is considered one of the most powerful hormones that control bone; when ovaries stop producing estrogen in women after menopause, bone mass rapidly declines and can lead to osteoporosis.
Sex hormones, namely estrogen in women and testosterone in men, have been known to affect skeletal growth, but until now, studies of the interaction between bone and the reproductive system have focused only on how sex hormones affect the skeleton.
"We do not know why the skeleton regulates male fertility, and not female. However, if you want to propagate the species, it's probably easier to do this by facilitating the reproductive ability of males," said Dr. Karsenty. "This is the only rationale I can think of to explain why osteocalcin regulates reproduction in male and not in female mice."
Other Novel Functions of Osteocalcin Reported Earlier
The unexpected connection between the skeleton and male fertility is one of a string of surprising findings in the past few years regarding the skeleton. In previous papers, Dr. Karsenty has found that osteocalcin helps control insulin secretion, glucose metabolism and body weight.
"What this work shows is that we know so little physiology, that by asking apparently naïve questions, we can make important discoveries," Dr. Karsenty says. "It also shows that bone exerts an important array of functions all affected during the aging process. As such, these findings suggest that bone is not just a victim of the aging process, but that it may be an active determinant of aging as well."
Next Steps and Potential Drug Development
Next, the researchers plan to determine the signaling pathways used by osteocalcin to enhance testosterone production.
And as for potential drug development, since the researchers have also identified a receptor of osteocalcin, more flexibility in designing a drug that mimics the effect of osteocalcin is expected.
Whether it's for glucose metabolism or fertility, says Dr. Karsenty, knowing the receptor will make it easier for chemists to develop a compound that will bind to it.
"This study expands the physiological repertoire of osteocalcin, and provides the first evidence that the skeleton is a regulator of reproduction," said Dr. Karsenty.

Provided by Columbia University Medical Center

anti TB drug

2 in 1: Multi-tasking protein provides new approaches for anti-tuberculosis drugs

February 15, 2011

In a paper published today in PNAS, scientists from the European Molecular Biology Laboratory (EMBL) in Hamburg, Germany, reveal new insights into the workings of enzymes from a group of bacteria including Mycobacterium tuberculosis, the bacterium that causes tuberculosis. The new findings present possible new opportunities for developing organism-specific drugs, which target the pathogen but leave other microorganisms, which are beneficial to us, untouched.

Tuberculosis remains one of the largest threats to human health worldwide, and one of the most frequent causes of death in HIV patients. With the increasing emergence of strains of Mycobacterium tuberculosis that are hyper-resistant to drugs, it becomes ever more urgent that novel treatments be developed, and the search for novel strategies for drug development is an important step in this process.
In the current study, Matthias Wilmanns and his group at EMBL identified a multi-tasking enzyme from Mycobacterium tuberculosis that catalyses reactions on two different molecules, or substrates. In most organisms, cells need two specific enzymes, known as HisA and TrpF, in order to produce two essential amino acids – histidine and tryptophan. However, in Mycobacterium tuberculosis, the encoding gene for TrpF is missing, and the two reactions are instead catalysed by a single enzyme, which is able to recognize and bind to two different substrates. This enzyme is known as PriA.
Using the Mycobacterium tuberculosis version of the PriA enzyme as a model, the researchers were able to unravel the hitherto unknown mechanism of bi-substrate specific binding observed in this group of bacteria.
"When we solved the three-dimensional structure of PriA, we found that it has the unique ability to form two different substrate-specific active sites," Wilmanns says: "it can form a reaction-specific active site, or undergo what we call 'substrate-induced metamorphosis' to form a different active site."
To further verify these observations, Wilmanns and colleagues screened 20,000 small molecule compounds, and identified a handful which inhibited both PriA-catalysed reactions but had no effect on TrpF activity.
"We believe that this ability for bi-substrate catalysis in Mycobacterium tuberculosis could be a new opportunity for future drug development," Wilmanns concludes: "This organism-specific reaction process could be exploited, since only the pathogen but none of the other bacteria living in or on humans, many of which are important for our well being, would be targeted."

Provided by European Molecular Biology Laboratory

Losing hair at 20

Losing hair at 20 is linked to increased risk of prostate cancer in later life

February 15, 2011

Men who start to lose hair at the age of 20 are more likely to develop prostate cancer in later life and might benefit from screening for the disease, according to a new study published online in the cancer journal, Annals of Oncology today.

The French study compared 388 men being treated for prostate cancer with a control group of 281 healthy men and found that those with the disease were twice as likely as the healthy men to have started going bald when they were 20. However, if the men only started to lose their hair when they were 30 or 40, there was no difference in their risk of developing prostate cancer compared to the control group. The study found no association between early hair loss and an earlier diagnosis of prostate cancer, and nor was there any link between the pattern of hair loss and the development of cancer.
Until now there has been conflicting evidence about the link between balding and prostate cancer; this is the first study to suggest a link between going bald at the young age of 20 and the development of prostate cancer in later life.
Professor Philippe Giraud (M.D., PhD), Professor of Radiation Oncology at the Paris Descartes University (Paris, France) and at the European Georges Pompidou Hospital (Paris, France), who led the research, said: "At present there is no hard evidence to show any benefit from screening the general population for prostate cancer. We need a way of identifying those men who are at high risk of developing the disease and who could be targeted for screening and also considered for chemo-prevention using anti-androgenic drugs such as finasteride. Balding at the age of 20 may be one of these easily identifiable risk factors and more work needs to be done now to confirm this."
Androgenic alopecia, sometimes known as male pattern baldness, is common in men, affecting 50% throughout their lifetime. A link has been established between baldness and androgenic hormones, and androgens also play a role in the development and growth of prostate cancer. Finasteride blocks the conversion of testosterone to an androgen called dihydrotestosterone, which is thought to cause hair loss, and the drug is used to treat the condition. It has also been shown to decrease the incidence of prostate cancer.
From September 2004 Prof Giraud and his colleagues asked the men in their study to answer a questionnaire about their personal history of prostate cancer (if any) and to indicate on four pictures any balding patterns that they had at ages 20, 30 and 40. The pictures showed four stages of hair loss: no balding (stage I), frontal hair loss (receding hairline around the temples), vertex hair loss (a round bald patch at the top of the head), or a combination of both types of hair loss (stage IV). The men's doctors were also asked to provide a medical history of their patients, including any diagnosis of prostate cancer, age at diagnosis, stage of the disease and treatment. The study ran for 28 months. The men with prostate cancer were diagnosed with the disease between the ages of 46 and 84.
Dr Michael Yassa (M.D.), currently Assistant Professor at the University of Montreal (Montreal, Canada) and a radiation oncologist at the Maisonneuve-Rosemont Hospital in Montreal, but who previously worked as a radiation oncology Fellow at the European Georges Pompidou Hospital, said: "There were only three men with stage III and none with stage IV hair loss at the age of 20, but the data revealed that any balding at stages II-IV (37 cases and 14 controls) was associated with double the risk of prostate cancer later in life. This trend was lost at ages 30 and 40.
"We were unable to find an association between the type or pattern of hair loss and the development of cancer. This might be due to the very low prevalence of stage III and IV hair loss at the ages of 20 and 30 in our study."
The researchers say the link between baldness and the development of prostate cancer is still unclear. "Further work should be done, both at the molecular level and with larger groups of men, to find the missing link between androgens, early balding and prostate cancer," said Dr Yassa.

More information: "Male pattern baldness and the risk of prostate cancer".Annals of Oncology. doi:10.1093/annonc/mdq695

Provided by European Society for Medical Oncology