Discovery opens door to new drug options for serious diseases

Researchers have discovered how oxidative stress can turn to the dark side a cellular protein that's usually benign, and make it become a powerful, unwanted accomplice in neuronal death.
This finding, reported today in Proceedings of the National Academy of Sciences, could ultimately lead to new therapeutic approaches to many of the world's debilitating or fatal diseases.
The research explains how one form of oxidative stress called tyrosine nitration can lead to cell death. Through the common link of inflammation, this may relate to health problems ranging from heart disease to chronic pain, spinal injury, cancer, aging, and amyotrophic lateral sclerosis, or Lou Gehrig's disease.
As part of the work, the scientists also identified a specific "chaperone" protein damaged by oxidants, which is getting activated in this spiral of cellular decline and death. This insight will provide a new approach to design therapeutic drugs.
The findings were published by scientists from the Linus Pauling Institute at Oregon State University; Maria Clara Franco and Alvaro Estevez, now at the University of Central Florida; and researchers from several other institutions. They culminate a decade of work.
"These are very exciting results and could begin a major shift in medicine," said Joseph Beckman.
Beckman is an LPI principal investigator, distinguished professor of biochemistry, and director of the OSU Environmental Health Sciences Center. He also last year received the Discovery Award from the Medical Research Foundation of Oregon, given to the leading medical scientist in the state.
"Preventing this process of tyrosine nitration may protect against a wide range of degenerative diseases," Beckman said. "The study shows that drugs could effectively target oxidatively-damaged proteins."
Scientists have known for decades about the general concept of oxidative damage to cells, resulting in neurodegeneration, inflammation and aging. But the latest findings prove that some molecules in a cell are thousands of times more sensitive to attack.
In this case, heat shock protein 90, or HSP90, helps monitor and chaperone as many as 200 necessary cell functions. But it can acquire a toxic function after nitration of a single tyrosine residue.
"It was difficult to believe that adding one nitro group to one protein will make it toxic enough to kill a motor neuron," Beckman said. "But nitration of HSP90 was shown to activate a pro-inflammatory receptor called P2X7. This begins a dangerous spiral that eventually leads to the death of motor neurons."
The very specificity of this attack, however, is part of what makes the new findings important. Drugs that could prevent or reduce oxidative attack on these most vulnerable sites in a cell might have value against a wide range of diseases.
"Most people think of things like heart disease, cancer, aging, liver disease, even the damage from spinal injury as completely different medical issues," Beckman said. "To the extent they can often be traced back to inflammatory processes that are caused by oxidative attack and cellular damage, they can be more similar than different. It could be possible to develop therapies with value against many seemingly different health problems."
Beckman has spent much of his career studying the causes of amyotrophic lateral sclerosis, and this study suggested the processes outlined in this study might be relevant both to that disease and spinal cord injury.
Key to this research were new methods that allowed researchers to genetically engineer nitrotyrosine into HSP90. This allowed scientists to pin down the exact areas of damage, which may be important in the identification of drugs that could affect this process, the researchers said.
Source:Proceedings of the National Academy of Sciences

Green Tea May Reduce Breast Cancer Risk in Post-Menopausal Women

Phytochemicals present in green tea change the metabolism of estrogen and can reduce the risk of breast cancer especially in post-menopausal women, according to a study from NIH's National Cancer Institute.The incidence of breast cancer is 3 to 4 times higher in the U.S. compared to Japan. Again, green tea, commonly consumed in Japan, is an important source of dietary phytochemicals that fight cancers. Since there are limited studies of green tea intake and risk of breast cancer and most studies of green tea have not considered pre- and postmenopausal women separately, Barbara Fuhrman at Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, USA and her colleagues set out to examine the associations of green tea intake and caffeine intake with urinary estrogens and estrogen metabolites among cancer-free pre-menopausal and postmenopausal Japanese American women. 
Estrogen (estradiol, estriol, and estrone) are hormones produced by the ovaries to regulate fertility and help in development of the female reproductive system. The estrogen levels reduce during menopause and may cause hot flashes and mood swings but high levels of estrogen may increase the risk of breast cancer, especially in post menopausal women. 
'Because green tea catechins have been observed to reduce catalytic activity of certain cytochrome p450 (CYP) enzymes, we hypothesized that green tea may influence breast cancer risk, in part, by modifying the production or metabolism of estrogens, known carcinogens of the breast. Caffeine, present in teas and other foods, is also known to modify expression and/or activity of some metabolic enzymes, but has not been found to have a consistent effect on breast cancer risk', said the researchers. 
The study, published in the Nutrition Journal, included 191 Japanese-American women without breast cancer (119 pre-menopausal women and 72 postmenopausal women) who were asked to provide 12-hour overnight urine samples. During in-person interviews, the participants were queried about frequency of intake of green tea, black tea, coffee, decaffeinated coffee and caffeinated soda. 

Results showed that - 
• Daily intake of green tea was more prevalent in postmenopausal than in pre-   menopausal women. 

• Intake of green tea was significantly associated with older age and Asian birthplace. 

• Among pre-menopausal women, consumption of green tea was associated with  significantly lower urinary concentrations of total estrogens and estrogen metabolites. 

• In postmenopausal women, urinary estrone and estradiol were approximately 20 percent lower and 40 percent lower, respectively, in women drinking green tea daily compared to those drinking less than once a week, irrespective of their BMI, Asian origin, age at menarche and consumption of soy. 

• Green tea intake was inversely associated with 16-hydroxylated estrogen metabolites, which are prone to behave like 'super-estrogen' and can result in mutations, abnormal growth and increased risk of breast cancer. Interestingly, a study published in the February issue of Cancer Research pointed out that urinary 17-epiestriol, rather than 16-hydroxylated estrogen metabolites, were associated with increased risk of breast cancer. Urinary 17-epiestriol, too, showed a significant, inverse trend with green tea intake in the present study. 
The researchers also found that the geometric mean urinary concentrations of total estrogens and estrogen metabolites of the postmenopausal Japanese-American group was about half of the levels that were found in Caucasian postmenopausal women from New York. However, this difference was not noted in pre-menopausal women, whether Japanese American or Caucasian American. The researchers are not sure if these differences are due to ethnicity, diet, cultural practices, or technical factors. 
What they are sure of is the finding that green tea may reduce postmenopausal breast cancer risk. In their words - 'Our finding that green tea intake is associated with reduced urinary estrone and estradiol in our sample of postmenopausal Japanese-American women, does support the hypothesis that green tea intake may reduce postmenopausal breast cancer risk by modifying exposures to endogenous estrogens (estrogens produced by the body)'. 

Reference: Fuhrman BJ, Pfeiffer RM, Wu AH, Xu X, Keefer LK, Veenstra TD, Ziegler RG. Green tea intake is associated with urinary estrogen profiles in Japanese-American women. Nutr J. 2013 Feb 15;12(1):25. doi: 10.1186/1475-2891-12-25.  

 
 

Women Have Smaller but More Efficient Brain: New Study

Women can have the last laugh now! A new research from UCLA and Universidad Autónoma de Madrid, Spain, indicated that although the brain in women is smaller than in men, women use their brain more efficiently.

The study, published in the journal Intelligence, carried out a series of intelligence tests by applying a method for automated segmentation of the hippocampus in 3D high-resolution structural brain MRI scans. 
Hippocampus is a part of the limbic system in the brain responsible for storing, processing and retrieving memories, and also experiencing emotions such as fear and anger. 
For the study, Roberto Colom from the University of Madrid and his colleagues, selected 104 healthy young adults (59 women and 45 men in the age range from 18 to 27 years) who were asked to complete 21 tasks measuring abstract, verbal, and spatial intelligence, along with working memory, executive control, attention, and processing speed. 
They found that hippocampal structural differences were related to spatial intelligence, working memory, and executive control, but were not related to verbal intelligence, attention, and processing speed. 
Larger the hippocampus and more the neurons, means higher the intelligence, but only in men. On the other hand, in women, a larger hippocampus, although smaller than men's, did not indicate greater intelligence. Rather, the researchers reasoned, smaller the hippocampus, the better. 
They confirmed the earlier studies that women are better at inductive reasoning (a kind of reasoning that evaluates general propositions that are derived from specific examples) and also found that women are better at tracking a changing situation. The men, in contrast, have better performance in intelligence tests. 
The study concluded: 'At this structural level, females might show greater efficiency requiring less neural material for achieving behavioral results on a par with males'. That is, women's brains are able to complete complicated tasks with less energy and fewer neurons as compared with men's brain. 
Trevor Robbins, professor of neuroscience at the University of Cambridge while commending the study suggested further examination. The better efficiency of the female brain could be because of 'more intense mobilization of neurons or more active signals between them' and that they operate more efficiently in females due to the small structure, he said. 
He continued, 'the research indicates that a smaller hippocampus size in women means better performance and the structure size of the brain does not necessarily indicate the presence of any relationship with the efficiency of performance'. 

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Expert Says Painkillers Damaging Kidneys in Youngsters

In youngsters, painkillers and stress-reducing drugs are the primary reason for kidney ailments, says a leading urologist.
"Young people use painkillers rampantly these days. Besides, they take stress-reducing medicines to deal with pressure. This wreaks havoc on their kidneys," Shivaji Basu, urologist at the Fortis Hospitals here, told IANS. 
"For any kind of pain, they (youngsters) take painkillers and this has become a trend. They do not realise that frequent use of such drugs is bad for their kidneys," Basu said. 
According to Basu, owing to fast paced lifestyle, youngsters are prone to pop a pill to combat any kind of problem. And since they are constantly travelling, they do not consume the required amount of water. 
Basu also dubbed diabetes and blood pressure as "silent killers of the kidney". 
"Earlier, aged people were affected by blood pressure and diabetes. Now the young generation is also affected by them." 
"Those who have problems of blood pressure should get their check-up done at least once a year for signs of kidney disorders," said Basu. 
The National Kidney Foundation of India estimates that about 100 people in a million suffer from kidney ailments in the country and around 90,000 kidney transplants are required annually in India.
Source-IANS