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

"Dawn phenomenon"

Q. My blood sugar levels are very high when I first wake up in the
morning (dawn phenomenon). Should I skip breakfast to bring my blood
sugar down?

A.The answer in short is Absolutely NOT. First the reason that your
blood sugar levels are so high first thing in the morning is
because as morning approaches your body starts releasing
energizing hormones to rev you up for the day. These antagonize the
action of insulin and stimulate the liver to produce more glucose,
even if the glucose level in the blood is already abnormally high.
Will eating make it rise even higher? The answer is probably, but
because breakfast is the most important meal of the day for weight
loss and nutritional benefits we must find alternative measures to
fight against this phenomenon known as the dawn phenomenon.

Here are a few tips you can try

1. If you are currently taking Melabic, you can try taking one more
tablet before you go to bed. To find out more about how Melabic
can help you stabilize your blood sugar visit Melabic.com

2. Start checking you blood sugar levels earlier in the morning 6:30
-7:00am.

3. Trying controlling the morning spikes by being proactive and
trying different things the night before. Try eating a little less
food in the evening or maybe even try a little exercise before you
go to bed.

[Article written by Julia Hanf author of the book "How to Play the
Diabetes Diet Game and Win"]