ACT Biotech's Telatinib receives orphan drug designation from FDA for treatment of gastric cancer

ACT Biotech's Telatinib receives orphan drug designation from FDA for treatment of gastric cancer..

Telatinib (see structure,  source : ChemBlink) :
(17-Demethoxy-17-allylaminogeldanamycin; Tanespimycin; 17-Allylaminogeldanamycin)

Bone drug (Zoledronic acid) suppresses wandering tumor cells in breast cancer patients

In continuation of my update on zoledronic acid, I find this info really  interesting.  Researchers from Washington University School of Medicine in St. Louis, have found that the bone-strengthening drug zoledronic acid (Zometa) can help fight metastatic breast cancer when given before surgery.

When the drug was given along with chemotherapy for three months before breast cancer surgery, it reduced the number of women who had tumor cells in their bone marrow at the time of surgery.

Tumors shed thousands of cells, which spread throughout the body and are referred to as disseminated tumor cells (DTCs). Breast cancer DTCs often lodge in bone marrow where bone growth factors help them survive.

Chemotherapy can increase bone turnover and bone growth factors, potentially exacerbating the problem of DTCs in the bone, which can resurface later to cause metastatic disease in cancer patients.

Researchers believe that zoledronic acid inhibits the release of growth factors that help support the growth of DTCs.

In this randomized phase II clinical trial, researchers split 109 women with newly diagnosed stage II or stage III breast cancer into two groups. The control group received chemotherapy alone, while the other received a combination treatment of chemotherapy and zoledronic acid. After three months of therapy, patients with DTCs in their bone marrow decreased from 43 percent to 30 percent in the combination group, compared with a decrease from 48 percent to 47 percent in the control group. This result approached statistical significance.

Zoledronic acid treatment with chemotherapy had additional benefits. Women in the combination group experienced significant gains in bone density after 12 months. This is helpful for breast cancer patients, who often develop osteoporosis as a side effect of chemotherapy and other breast cancer treatments.  

The study also suggested that zoledronic acid may help fight certain types of breast tumors directly. Aft speculates that the drug may stop the tumor from making its own blood supply, modify the immune system in a way that makes it harder for tumor cells to survive or even cause the cancer cells to commit suicide.....

Ref : http://www.ncbi.nlm.nih.gov/pubmed/20362507?dopt=Abstract

Chili peppers may cause weight loss and fight fat buildup, says study

In one of my earlier blog article, titled "Peppers may increase energy expenditure in people tying to lose weight"....have mentioned that researchers form UCLA's Center for Human Nutrition in Los Angeles, CA, lead by Dr. David Heber claimed that "peppers may increase energy expenditure in people tying to lose weight". 

Now interestingly, Steven C. Powell, has come up with new evidence that capsaicin (see below structure), the stuff that gives chili peppers their kick, may cause weight loss and fight fat buildup by triggering certain beneficial protein changes in the body. Their study, which could lead to new treatments for obesity, appears in ACS' monthly Journal of Proteome Research........details ...

Ref : Chili peppers may cause weight loss and fight fat buildup, says study  

RADIANT-3 study results show everolimus significantly extends progression-free survival in patients with advanced pancreatic neuroendocrine tumors...

We know that Everolimus (RAD-001, marketed by Novartis under the  tradenames Zortress (USA) and Certican (Europe and other countries) in transplantation medicine and Afinitor in oncology) is the 42-O-(2-hydroxyethyl) derivative of sirolimus and works similarly to sirolimus as an mTOR (mammalian target of rapamycin) inhibitor. It is currently used as an immunosuppressant to prevent rejection of organ transplants. Much research has also been conducted on everolimus and other mTOR inhibitors for use in a number of cancers.

The FDA has approved everolimus for the treatment of advanced kidney cancer on March 30, 2009 and for organ rejection prophylaxis on April 22, 2010. Now Novartis Pharmaceuticals Corporation announced that the  Phase III study of Afinitor® (everolimus, see structure) tablets plus best supportive care met its primary endpoint, showing the drug significantly extended progression-free survival, or time without tumor growth, in patients with advanced pancreatic neuroendocrine tumors (NET). The study, RADIANT-3 (RAD001 In Advanced Neuroendocrine Tumors), is part of the largest clinical trial program of its kind. 

Everolimus is approved under the trade name Afinitor® (everolimus) tablets for the treatment of patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib.  

As  per the claim by   Herve Hoppenot, President, Novartis Oncology, Everolimus was developed to inhibit the mTOR protein, which is a critical target in treating various cancers, including NET. Results from RADIANT-3 demonstrate that everolimus has the potential to become an important treatment option for patients with advanced pancreatic NET, where there is a major unmet need.

"These study results will serve as the basis of worldwide regulatory filings for everolimus and bring us one step closer to our goal of offering these patients a new therapy."...says Herve Hoppenot...

Ref : http://www.novartis.com/newsroom/media-releases/en/2010/1421290.shtml

Synthetic peptide may regenerate brain tissue in stroke victims

A synthetic version of a naturally occurring peptide promoted the   creation of new blood vessels and repaired damaged nerve cells in lab animals, according to researchers lead by Dr. Daniel Morris Sr.Staff Physician at Henry Ford Hospital in Detroit.

"Neurorestorative therapy is the next frontier in the treatment of stroke." claims Dr. Daniel Morris...

As per the claim by the researchers,  addition of  the synthetic peptide Thymosin beta 4 (structure : acetate of Thymosin beta 4 : courtesy : ChemBlink) to a group of drug treatments including statins (used for neurorestorative therapy to activate repair mechanisms) repaired and regenerated stroke-injured brain tissue.

Interestingly, this  research follows an earlier study reported by the same team in March, which found that Thymosin beta 4 improved neurological function after stroke in adult rats by increasing the formation of protective myelin around nerve fibers in brain cells.

In the latest study, adult rats were dosed with Thymosin beta 4 one day after they were subjected to a blockage in the cerebral artery, then given four more doses, once every three days. Rats treated only with saline were used as a control group. After eight weeks, the Thymosin beta 4 group showed significant overall improvement compared to the control group.

The researchers concluded that the peptide improved blood vessel density as well as promoted a certain type of immature brain cells called oligodendrocyte progenitor cells to differentiate into mature oligodendrocytes, which produces myelin to protect axons in nerve cells.

These experiments conclude that the peptide repairs and regenerates stroke-injured brain tissue. and as per the claim by the researchers,  the results of the first study also were similar to other research using the peptide to regenerate damaged heart, corneal tissue and wound repair...

Ref : http://www.henryfordhealth.org/body.cfm?id=46335&action=detail&ref=1107

Body's own proteins may lead the way in global fight against tuberculosis

Body's own proteins may lead the way in global fight against tuberculosis

Bafetinib demonstrates significant inhibition of glioblastoma multiforme cell lines (preclinical trials)..

The treatment of chronic myeloid leukemia (CML)  changed  dramatically with the emergence of the ABL tyrosine kinase inhibitor (TKI) imatinib mesilate. However, primary and secondary imatinib resistance has been frequently reported, particularly in patients with advanced-stage disease. To override imatinib resistance, three second-generation ABL TKIs, i.e., dasatinib, nilotinib and bosutinib, were developed. Bafetinib (see structure source : Chemblink :INNO-406, NS-187) is a dual ABL/Lyn inhibitor developed by the team at Kyoto University Hospital in collaboration with Nippon Shinyaku. 

Bafetinib was 25-55 times more potent than imatinib in blocking BCR/ABL autophosphorylation, while otherwise retaining specificity for ABL and Lyn. Bafetinib had antiproliferative effects against cells bearing wild-type or most mutated BCR/ABL proteins, except T315I, and also inhibited BCR/ABL-positive leukemic cell growth in the central nervous system. A phase I study on bafetinib was completed and the agent was well tolerated and demonstrated clinical activity across a range of doses. Responses occurred even in the setting of a heavily pretreated population, thus making bafetinib a viable option for CML therapy.

Recently  CytRx Corporation, announced that its drug candidate bafetinib (formerly known as INNO-406) demonstrated statistically significant inhibition of glioblastoma multiforme cell lines in a preclinical trial. The company believe that bafetinib could be efficacious in several hematological cancers and  it is  preparing to begin evaluating bafetinib in a Phase 2 proof-of-concept clinical trial in high-risk B-cell chronic lymphocytic leukemia (B-CLL) this quarter, as well as a Phase 2 clinical trial in advanced prostate cancer next quarter.... 

Ref : http://www.cytrx.com/inno_406.html

Promising treatment for aggressive lymphoma identified in new study

In continuation of my update on Lenalidomide... I found this info interesting to share with...

Promising treatment for aggressive lymphoma identified in new study

Plectasin - a new weapon against highly resistant microbes ?..

We know that Plectasin, found in Pseudoplectania nigrella (see picture), is the first defensin to  be isolated from a fungus. Plectasin has a chemical structure resembling defensins found in spiders, scorpions, dragonflies and mussels. In laboratory tests, Plectasin was especially active in inhibiting the growth of the common human pathogen Streptococcus pneumoniae, including strains resistant to conventional antibiotics. Plectasin has a low toxicity in mice, and cured them of peritonitis and pneumonia caused by S. pneumoniae as efficiently as vancomycin and penicillin, suggesting that it may have therapeutic potentia.

Now researchers lead by Prof. Dr. Hans-Georg Sahl of   Universities of Bonn, Utrecht, Aalborg and of the Danish company Novozymes AS have shed light on how the substance Plectasin,  destroy highly resistant bacteria. As per the claim by the researchers Plectasin binds to a cell-wall building block called lipid II and thus prevents it from being incorporated and thus disrupting the forming of the cell wall in bacteria so that the pathogens can no longer divide. 

In this process, plectasin behaves like a thief which steals the stones off a mason. 'It binds to a cell-wall building block called lipid II and thus prevents it from being incorporated ,' Professor Sahl explains. 'However, bacteria cannot live without a cell wall.' It comes as no surprise that the most famous antibiotic penicillin also inhibits cell-wall synthesis...

Researchers claims that, plectasin is more similar in its mode of action to another widely used drug, vancomycin. Vancomycin had been the drug of choice in combating MRSA strains since the 1980s. Meanwhile, though, there are more and more bacteria that are also resistant to vancomycin. 'However, these strains are still susceptible to plectasin,' Dr. Tanja Schneider emphasises. Nevertheless, there is no permanent solution to the resistance problem even with a new antibiotic . 'It is always just a question of time until the pathogens mutate and become insensitive ,' she says. 'It's a never ending arms race..' authors conclude that plectasin will be promising lead compound for new antibiotics...

Ref : http://www.sciencemag.org/cgi/content/abstract/328/5982/1168

Healthcare associated infection prevention....

Idiom "prevention is better than cure" is  more relevant than ever, but the awareness is lacking in the healthcare associated infection prevention. I find HAI Watch   site very informative in this aspect. 

HAI Watch is the  resource for collateral and supplies to help keep the  organization aware of the importance of healthcare associated infection prevention..... 

I really appreciate the efforts like the HAI Education Program a  part of a national infection awareness campaign for healthcare professionals called “Not on My Watch” and will provide the facility with a toolkit that contains informational flyers, patient safety tips and posters. I hope the info will definitely help the healthcare professionals in protecting the patients from preventable hospital infections....

New research finding may change direction of vaccine research for M. tuberculosis

New research finding may change direction of vaccine research for M. tuberculosis

FDA Acceptance of New Drug Application for Vilazodone for the Treatment of Major Depressive Disorder..

Vilazodone(see structure) is an antidepressant which is currently under  development by Clinical Data for the treatment of major depressive disorder, and as of 2009 has completed two phase III clinical trials with positive results. An NDA was submitted on March 23rd, 2010 in the United States and is currently pending approval by the FDA which, if approved, will likely precede vilazodone's availability on the market by the end of 2010.

Now the company claims that FDA has accepted for filing the Company's New Drug Application (NDA) for vilazodone for the treatment of major depressive disorder (MDD).

Vilazodone is a dual-acting potent and selective serotonin reuptake inhibitor and a 5-HT_1A receptor partial agonist. The NDA will be subject to a standard review. 

“The acceptance of the NDA for review by the FDA is another positive step toward our goal of bringing vilazodone to market, and if approved, vilazodone will offer a novel treatment to the millions of people suffering from depression”  says Carol R. Reed, M.D., Executive Vice President and Chief Medical Officer of Clinical Data.....

Ref : http://www.clda.com/uploads/CLDA%20NDA%20acceptance%20FINAL.pdf

Lytix Biopharma receives approval to initiate Phase I/IIa clinical trial of Lytixar for MRSA

Lytix Biopharma receives approval to initiate Phase I/IIa clinical trial of Lytixar for MRSA 

Pistachios offer multiple benefits, study suggests

Pistachios offer multiple benefits, study suggests

Nuclear magnetic resonance aids in drug design

Nuclear magnetic resonance aids in drug design

Individual's lifestyle choices can affect cholesterol, triglycerides levels: Mayo Clinic Health Letter

Sometimes, diet and lifestyle choices alone aren't enough to manage total cholesterol levels. Yet, diet and exercise are important management strategies even when cholesterol-lowering medications are indicated...

 

Individual's lifestyle choices can affect cholesterol, triglycerides levels: Mayo Clinic Health Letter

Flaxseed-fed chickens shed light on ovarian cancer.....

In continuation of my update on the benefits of  flax seeds,  I found this info interesting to share with. Researchers from College of Agricultural, Consumer and Environmental Sciences, lead by Prof. Janice Bahr, have come up with interesting info about flax seeds, i.e., hens fed a flaxseed-enriched diet for one year experienced a significant reduction in late-stage ovarian tumors.

The interesting part of the research lies in that fact that, chicken is the only animal that spontaneously develops ovarian cancer on the surface of the ovaries like humans and researchers  evaluated how a flaxseed-enriched diet affected 2-year-old laying hens (hens that have ovulated as many times as a woman entering menopause). As we know flaxseed is the richest plant source of alpha-linolenic acid, (omega-3 fatty acid). Several studies have already shown that flaxseed inhibits the formation of colon, breast, skin and lung tumors.

As per the claim by the researchers, hens fed the control diet had significantly more late-stage tumors that presented with fluid and metastases as compared to the hens fed a flaxseed diet. Though hens fed the flaxseed diet did not have a decreased incidence of ovarian cancer, they did experience fewer late-stage tumors and higher survival rates.

In addition, researchers found that hens fed the flaxseed diet had better weight control which is important because obesity increases cancer risk. Both diets had equal caloric content, however the flaxseed-fed hens weighed less at six months than the control-fed hens. But at 12 months, the flaxseed-fed hens were the same weight and the control-fed hens had loss significant weight, which was indicative of their failing health. Ultimately, the flaxseed-enriched diet helped the birds maintain a healthy weight and resulted in less sickness and death.

"Through this research, we have proven that flaxseed supplementation for one year is able to reduce the severity of ovarian cancer in hens," she said. "These findings may provide the basis for a clinical trial that evaluates the efficacy of flaxseed as a chemosuppressant of ovarian cancer in women."

Bahr believes this hypothesis is valid and is currently in the middle of a four-year study to determine if long-term dietary intervention with flaxseed will reduce the incidence of ovarian cancer development....

Ref : http://www.aces.uiuc.edu/news/stories/news5165.html

Broccoli component limits breast cancer stem cells, study finds

In continuation of my earlier blog article " Broccoli sprouts may help prevent stomach cancer !....
I found this article interesting  to sharing with...
Broccoli component limits breast cancer stem cells, study finds

Growers can boost benefits of broccoli and tomatoes

Carotenoid-enriched tomatoes produced more bioactivity in the liver than lycopene-enriched or standard tomatoes, yielding the most cancer-preventive benefits.

In their current research, researchers from College of Agricultural, Consumer and Environmental Sciences | University of Illinois,  are experimenting with ways to increase the bioactive components in these foods in order to test the efficacy of enriched broccoli and tomatoes in a new prostate cancer study....

Growers can boost benefits of broccoli and tomatoes

New details of tuberculosis protein-cleaving machinery revealed

New details of tuberculosis protein-cleaving machinery revealed

PEPCK (phosphoenolpyruvate carboxykinase) a potential target for drugs that fight tuberculosis.

 In continuation of my update on tuberculosis and drug discovery ..... A new  research conducted at Weill Cornell Medical College sheds light on a previously unrecognized aspect of fatty acid metabolism that could potentially lead to new targets for drug therapy. A team led by Dr. Sabine Ehrt, professor of microbiology and immunology at Weill Cornell Medical College, reported that Mtb relies primarily on gluconeogenic substrates for in vivo growth and persistence, and that phosphoenolpyruvate carboxykinase (PEPCK see picture) plays a pivotal role in the growth and survival of Mtb during infections in mice, making PEPCK a potential target for drugs that fight tuberculosis.

Dr. Ehrt and her colleagues found a way to silence the gene encoding PEPCK in Mtb during mouse infections to assess the importance of gluconeogenesis for Mtb's ability to maintain a chronic infection.

 "Silencing a gene when the pathogen is not or only slowly replicating, after an infection has established, is an important tool for studying diseases such as TB, which can be dormant for years only to become active again years later." says Dr.Ehrt...

 It is especially challenging as the infection can lay dormant in the body even though there are no symptoms. Researchers investigated the metabolic requirements of Mtb during acute and chronic infections and found that the gluconeogenic enzyme PEPCK is critical for both.

Interestingly, the  study used a novel mass spectrometry-based metabolic profiling tool, developed at Weill Cornell (in collaboration with Agilent Technologies) by Dr. Kyu Rhee to biochemically examine Mtb carbon metabolism. As per the claim by the researchers,  the tool has provided the first direct insights into the metabolic architecture of Mtb.

 Though the current treatments used  to treat Mtb are effective, the treatment times are too long and the regimens too complex, which  leads to treatment failures (due to poor adherence and multi drug resistance).   We need new, safer drugs that work faster to eliminate tuberculosis.  Dr. Ehrt hopes that her work will eventually lead to new drug therapies to treat tuberculosis.....

Ref : http://www.pnas.org/content/early/2010/04/26/1000715107

Eating nuts associated with improvements in cholesterol levels

In continuation of my update on cholesterol and diet......

Eating nuts associated with improvements in cholesterol levels

Yellow fever mosquito's resistance to DEET !.....

In continuation of  my update on mosquito repellents,  I found this info  interesting to share with. We know that N,N-Diethyl-meta-toluamide, DEET (see structure), is the most common active ingredient in insect repellents. It is intended to be applied to the skin or to clothing, and is primarily used to repel mosquitoes. In particular, DEET protects against tick bites, preventing several rickettsioses, tick-borne meningoencephalitis and other tick-borne diseases such as Lyme disease. It also protects against mosquito bites which can transmit dengue fever, West Nile virus, eastern equine encephalitis, and malaria. 

Now researchers from Swedish University of Agricultural Sciences (SLU) and associates in the UK, for the first time in laboratory tests have shown that yellow fever mosquito has developed a resistance to the mosquito repellent DEET.

"Through testing, we have found that yellow fever mosquitoes no long sense the smell of DEET and are thereby not repelled by it. This is because a certain type of sensory cell on the mosquito's antenna is no longer active" says Rickard Ignell, a researcher at the Division for Chemical Ecology at SLU in Alnarp....

Rickard Ignell performed the research in collaboration with Rothamstead Research in the UK. The scientists have thus seen that the sensory cell on the mosquito's antenna has stopped reacting to DEET. This have many explanations, such as the protein that binds in to DEET having mutated. The researchers are now urging restrictiveness in the use of DEET and other mosquito repellents on a large scale in a limited area, in order not to make other mosquito species resistant. The mechanism is still to be established, but in my opinion its a interesting finding....

Ref : http://www.pnas.org/content/early/2010/04/26/1001313107

Rifaximin for Irritable Bowel Syndrome.....

Rifaximin is a semisynthetic, rifamycin-based non-systemic orally  administered antibiotic drug. It is used in the treatment of traveler's diarrhea and hepatic encephalopathy, for which it received orphan drug status from the U.S. Food and Drug Administration in 1998.

Now Cedars-Sinai researchers, have come up with an interesting finding, i.e., rifaximin (see structure)  is the first drug treatment for IBS that relieves symptoms while it's being administered and continues to benefit patients after they stop taking the drug. 

Researchers lead by Dr. Mark Pimentel found that patients who took rifaximin not only experienced relief of their IBS symptoms, including specific symptoms of bloating, abdominal pain and stool consistency, while they were taking the antibiotic, but also that their relief was sustained over the 10 week follow-up period when no antibiotic was administered.

The results of the studies were presented at the Digestive Disease Week conference in New Orleans on 3rd May.

"These studies validate the role of altered gut bacteria in IBS," said  Dr. Mark Pimentel,  GI Motility Program director at Cedars-Sinai and the principal investigator of the clinical trail at Cedars. "These findings show that targeted antibiotics provide safe and long-lasting improvement for IBS patients."........

Ref : http://www.cedars-sinai.edu/About-Us/News/Past-Issue-Documents/IBSPimentelACG.pdf

Vinpocetine from the periwinkle plant, as a potent anti-inflammatory agent....

Vinpocetine (ethyl apovincaminate (see chemical structure,   is  a  semisynthetic   derivative   of  alkaloid   vincamine - an  extract  from the  periwinkle plant (see picture) Vinca minor) is a well-known natural product that was originally discovered nearly 30 years ago and is currently used as a dietary supplement for the prevention and treatment of cognitive disorders, such as stroke and memory loss, in Europe, Japan and China.

 

The therapy has no evidence of toxicity or noticeable side effects in human patients. Now scientists at the University of Rochester hope to reposition this compound as an anti-inflammatory agent for the treatment of COPD, and potentially other inflammatory conditions, such as asthma, otitis media, rheumatoid arthritis, atherosclerosis and psoriasis in the future.

As per the claim by the lead researcher Dr. Jian-Dong Li,  vinpocetine decreases inflammation by targeting the activity of a specific enzyme, known as IKK. IKK is responsible for regulating inflammation, and does so through the activation of a key protein, nuclear-factor kappaB (NF-κB). By directly inhibiting IKK, vinpocetine is able to switch off NF-κB, which normally produces pro-inflammatory molecules that cause inflammation. Halting the activity of NF-κB ultimately reduces inflammation. 

"Given vinpocetine's efficacy and solid safety profile, we believe there is great potential to bring this drug to market." claims co-author,  Dr. Bradford C. Berk...

Inflammatory diseases are a major cause of illness worldwide. For example, chronic obstructive pulmonary disease is the fourth leading cause of death in the United States. In people with COPD, airflow is blocked due to chronic bronchitis or emphysema, making it increasingly difficult to breathe. Most COPD is caused by long-term smoking, although genetics may play a role as well.....

Ref : http://www.urmc.rochester.edu/news/story/index.cfm?id=2836

Eliminating inherent drug resistance in tuberculosis....

In continuation of my update on drug resistant TB and the drug development for TB, I found this info interesting to share with.

Dr. John Blanchard of the Albert Einstein College of Medicine has come up with really  interesting  findings about how to "eliminate inherent drug resistance in tuberculosis".   

When the M. tuberculosis genome was sequenced a few years ago, the presence of  beta-lactamase enzyme was discovered. Most scientists didn't pay much attention to this discovery and beta-lactams   never have been systematically used to treat TB. However Dr. John,  thought it would be an attractive therapeutic target, considering several beta-lactamase inhibitors had been developed for other bacteria.

If we could inactivate this inactivator enzyme, it would expose TB bacteria to a whole new range of antibiotics," he says. 

While M. tuberculosis was resistant to most beta-lactamase inhibitors,  Blanchard's group found that the drug clavulanate was effective in shutting down the TB enzyme. 

The combination of clavulanate (see above right structure- its potassium salt) with the beta-lactam   meropenem (see below: left structure) could effectively sterilize laboratory cultures of TB within two weeks, including several XDR-strains (XDR strains are even more resilient than multi-drug resistant (MDR) strains).  Blanchard notes this finding was exciting since, despite such high rates of drug resistance, research into new TB drugs is not a high priority in industrialized countries (for socio-economic reasons), and thus the best short-term approach might be identifying other already FDA approved antibiotics that are effective against TB -like meropenem and clavulanate.

Blanchard is currently progressing with the next steps of the therapeutic process, which includes both detailed animal studies and setting up some small-scale trials with XDR-TB patients in developing nations...

(Source : a presentation at the American Society for Biochemistry and Molecular Biology’s annual meeting, titled “Drug resistance in tuberculosis,” by Dr. John Blanchard).

Ref : http://www.asbmb.org/News.aspx?id=7470&terms=John+Blanchard

Useful chemistry resources.....

If you are looking for interesting and informative blogs  and  other  chemistry  resources in one place,  you  can  visit  the site where in, Anna Miller (staff) has listed nearly 50 sites (chemistry blogs and chemical resources), which in my opinion are very good resources and most of the blogs I do follow on regular basis. 

Though the  website is for online degree, in my opinion its useful for each and every one who yearns for more...

The Secret of Lowering Cholesterol Through Diet...

I am really happy to share an interesting and important article  'the secret of lowering cholesterol through diet' by  Deborah Land, who has written this article exclusively for the readers of  my blog.......

The Secret of Lowering Cholesterol Through Diet

a. The Myth of Cholesterol - the Bad and the Good:

Most people think that cholesterol is always bad, but there are actually two types of cholesterol. LDL is  considered the "bad" cholesterol, and HDL is considered the "good" cholesterol. If there is too much LDL in our bloodstream, it will form plaque on our arteries. Over time, this narrows our arteries and can eventually block blood flow completely. Dietary cholesterol actually isn't the primary reason for high cholesterol in the blood; it is high amounts of saturated fat and trans fat. To keep cholesterol low, you should eat unsaturated fats, eat fibrous foods, and exercise more.

b. Number Relevance in Cholesterol :
Every adult should have their cholesterol checked at least every 5 years. When you get a cholesterol test, you'll usually get back four different results. Here are the 4 categories and the healthy range you want to be in.

Total Cholesterol - less than 200 mg/dL (5.2 mmol/L);
LDL Cholesterol - less than 100 mg/dL (2.6 mmol/L);
HDL Cholesterol - greater than 40 mg/dL (1.0 mmol/L) &
Triglycerides - less than 150 mg/dL (1.7 mmol/L).

If you are over or under the desired level on any category, it is usually indicative that a diet or exercise change is needed.

c. Heart Protection and Vitamin E:
Vitamin E, an important vitamin, is sourced in vegetable oils, nuts and leafy vegetables. Vitamin E can decrease your heart disease risk, but it will not prevent a heart attack.

d. Lowering Cholesterol with these Five Foods :
1. Oatmeal and Oat Bran: These contain a high amount of soluble fiber, which can lower LDL.
2. Fish: Fish is a great source of omega 3 fatty acids, which lowers LDL and raises HDL.
3. Nuts: Not only are nuts high in fiber, but they contain the healthy fats you need to keep LDL in check.
4. Plant Sterols: This is found in foods like margarine, salad dressing, orange juice, and functional cookies. 2  grams per day will lower your LDL by 10-15%.
5. Soy: This popular meat replacement can lower LDL by up to 3%.

e. Plant Sterols and Benefits to Health :
Foods such as VitaTops Muffin Tops, Benecol Spread, granola bars and fat free milk are rich sources of plant sterols. You can easily help your heart when you start eating foods packed with plant sterols and avoid eating foods that contain saturated fats. A saturated fat-filled diet is not canceled out by this. Exercising often as well as eating healthy food will keep your cholesterol in check.

About the Author - Deborah Land writes for Cholesterol Lowering Diet Blog  ,  her personal hobby blog focused on tips to eat healthy to prevent high cholesterol. I find the blog very informative, do visit for more details...

Hormone Spray improves male Sensitivity.....

A study by Dr. Ren- Hurlemann of Bonn University's Clinic for Psychiatry,  has revealed for the first time that emotional empathy is modulated by oxytocin (see structure), and that this applies similarly to learning processes with social multipliers.. Researchers claim that, this hormone might thus be useful as medication for diseases such as schizophrenia, which are frequently associated with reduced social approachability and social withdrawal......

Ref : http://www3.uni-bonn.de/Press-releases/hormone-spray-improves-male-sensitivity

New Data on NovaBay’s Aganocide compounds ( first-in-class anti-infectives) as presentations...

NovaBay Pharmaceuticals, Inc.  recently announced that, it is will be  presenting the latest public data on its Aganocide^® compounds (see structures : a new class of broad-spectrum antimicrobials). 

Data will be presented during three poster sessions at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in Fort Lauderdale, Florida. NovaBay's Aganocide compounds are first-in-class anti-infectives being developed for the treatment and prevention of antibiotic-resistant infections. NovaBay and Alcon, Inc., the world's leading eye care company, have a licensing and research collaboration agreement for the use of NovaBay's Aganocide compounds in the eye, ear and sinus, and for contact lens care.

The three presentations are :

1. Dichloro analog (AL-46383A) (see structure) as a Novel Topical Ophthalmic Agent, 2. In vitro evaluation of dichloro analog as an Antiviral Agent Against Adenovirus and HSV-1 and 3. topical dichloro analog,  Inhibits Adenovirus Replication in the Ocular Ad5/NZW Rabbit Replication Model.

NVC-422, or AL-46383A, is a stable compound based on the chemical structures of N-chlorotaurine (NCT) and N,N-dichlorotaurine, which are naturally occurring antimicrobial agents produced by the body's white blood cells to fight invasive pathogens.

Alcon is conducting a Phase 2 clinical trial of this compound for the treatment of viral conjunctivitis, a form of "pink eye". The randomized, placebo-controlled trial is enrolling approximately 250 patients at more than 30 medical centers in the United States and worldwide. It is designed to determine the safety and efficacy of NVC-422 or AL-46383A. 

Ref : http://www.novabaypharma.com/investors/release/apr_30_2010

Some new insights into the molecular mechanisms of pain perception....

UT Health Science Center researchers,  lead by Dr. Kenneth M. Hargreaves,  found a new family of fatty acids  produced by the body itself, that play an important role in the biology of pain.

Researchers evaluated the hypothesis that,  the heat sensitivity of TRPV1 is regulated by the generation of endogenous ligands and they found that heat-generated linoleic acid metabolites comprise a family of physiologically relevant TRPV1 agonists that contribute to the heat responsiveness of this channel. More interestingly the results also suggest, a previously unknown mechanism by which TRPV1 might mediate biological actions of oxidized linoleic acid metabolites in conditions such as inflammation and hypotension.

Encouraged by the facts that,  heat activation of TRPV1 (mechanistically distinct from capsaicin sensitivity) appears to occur in a membrane-delimited fashion (during short periods), its dependence on C terminus or voltage gating and their  own results, researchers proposed that heating leads to the generation of oxidized linoleic acid products in the plasma membrane that are important for TRPV1 responses to noxious thermal stimuli. It should be noted that in inflammatory diseases, relatively high levels of HODEs are observed even in extracellular compartments.

The data indicate that 9-HODE and 13-HODE substantially contribute to the heat responsiveness of TRPV1 in vitro and in vivo (apart from intrinsic heat sensitivity of TRPV1). Researchers claim that, heat directly activates TRPV1 with a subsequent generation of endogenous ligands that further amplifies the heat response and biological actions occur only in WT neurons and not neurons from TRPV1.

Researchers conclude by their in vitro and in vivo results that, blockade of the endogenous linoleic acid metabolites substantially decreased responses to thermal stimuli and the heat sensitivity of another member of the TRP family, TRPV4, is mediated via generation of a soluble ligand.

Previous studies have demonstrated that leukotrienes activate TRPV1, epoxyeicosatrienoic acids activate TRPV4, and 4-hydroxynonenal and 15d-PGJ₂ activate TRPA1. These results by UT researchers add HODEs as endogenous ligands for TRPV1. It is noteworthy that all these TRP ligands are lipid oxidation products and therefore encouraged the researchers to speculate that, one of the major roles of certain TRP channels in mammals is to act as sensors of membrane lipid oxidation as a surrogate for cellular damage. ..

Ref : http://www.uthscsa.edu/hscnews/singleformat2.asp?newID=3419

Combination antibiotics effective against chlamydia-induced arthritis, study finds

Combination antibiotics effective against chlamydia-induced arthritis, study finds

Peppers may increase energy expenditure in people tying to lose weight....

We know that, Capsinoids, which include capsiate, dihydrocapsiate,  and nordihydrocapsiate, are substances naturally present in chili peppers. Although they are structurally similar to capsaicin, the substance that causes pungency in hot peppers, they largely lack that characteristic. Capsinoids have an estimated “hot taste threshold” which is about 1000 times lower than of that of capsaicin. Many health effects have been ascribed to capsaicin and capsinoids, both anecdotally and through scientific study, including anticancer, anti-inflammatory, analgesic activity, and weight management.

Now researchers form UCLA's Center for Human Nutrition in Los Angeles, CA, lead by Dr. David Heber have come up with more interesting findings, i.e., "peppers may increase energy expenditure in people tying to lose weight". 


In a study designed to test the weight-loss potential of this DCT containing, non-spicy cousin of hot peppers, researchers at the UCLA Center for Human Nutrition set out to document its ability to increase heat production in human subjects consuming a weight-loss diet.

Under the direction of Dr. David Heber (Professor of Medicine and Public Health), they recruited 34 men and women who were willing to consume a very low-calorie liquid meal replacement product for 28 days. The researchers then randomized the subjects to take either placebo pills or supplements containing the non-burning DCT pepper analog. Two dosage levels of dihydrocapsiate DCT (see above structure ) were tested. At the beginning and end of the study, body weight and body fat were assessed, and the researchers determined energy expenditure (heat production) in each subject after he or she consumed one serving of the test meal.

The data provided convincing evidence that, at least for several hours after the test meal was consumed, energy expenditure was significantly increased in the group consuming the highest amount of DCT. In fact, it was almost double that of the placebo group. This suggests that eating this pepper-derived substance that doesn't burn can have the same potential benefit as hot peppers at least in part by increasing food-induced heat production. They were also able to show that DCT significantly increased fat oxidation, pushing the body to use more fat as fuel. This may help people lose weight when they consume a low-calorie diet by increasing metabolism. 


However, that a limitation to this study was that, the researchers only tested the effect of DCT on the thermic response to a single meal. Heber and colleagues also point out that that there might be a different effect in lean vs. obese subjects. But to their credit, this was the first study ever conducted to examine the potential health benefits of DCT consumed together with a very low calorie diet....

Ref : Dr. David Heber et. al., FASEB Journal 

New study confirms 98.9% specificity of the T-SPOTspan TB assay

The study highlights the very high specificity of the T-SPOT.TB assay and confirms its utility in the identification of latent TB infection....

New study confirms 98.9% specificity of the T-SPOTspan style="vertical-align:super; font-size:80%;"®/span.iTB/i assay

Rib-X Pharmaceuticals to demonstrate three presentations at Antibacterial Drug Development Conference

Rib-X Pharmaceuticals, Inc, is presenting three separate presentations at the Cambridge Healthtech Institute's 4^th Annual Antibacterial Drug Development Conference, Resistance is Futile: The Challenge of Antibacterial Drug Development, April 27 - 28, in San Diego,

The presentations include overviews on radezolid (see below structure)  

delafloxacin  (see  right  structure) and the Company's proprietary platform for unlocking the bacterial ribosome, which has allowed for the design and generation of three novel classes of antibiotics that have been tuned for both multi-drug resistant Gram-negative and Gram-positive activity and have shown efficacy in multiple animal models of infection. 

Hope these results will  lead to relief from multi-drug–resistant infections (e.g., MRSA, uSSSI  and community acquired pneumonia,CAP).


Ref : http://www.rib-x.com/news_and_events/release_2010_04_12

Chokeberry extract reduces weight gain in insulin-resistant animals.....

Chokeberries (Aronia) are a great example of those fruits that both  taste good and show a number of health benefits for the body. Chokeberries' rich antioxidant content may be beneficial as a dietary preventative for reducing the risk of diseases caused by oxidative stress. Among the models under evaluation where preliminary results show benefits of chokeberry anthocyanins are colorectal cancer, chronic inflammation, gastric mucosal disorders (peptic ulcer),eye inflammation (uveitis) and liver failure cardiovascular disease.

Now Drs. Bolin Qin and Richard Anderson from the US Department of Agriculture in Beltsville, MD, have come up with some more interesting info about chokeberries, i.e., "chokeberry extract reduces weight gain in insulin-resistant animals". 

Qin and Anderson found that at the end of the study,  the rats consuming the chokeberry-spiked water weighed less than the controls; both levels of chokeberry had the same effect in this regard. Similar beneficial effects of chokeberry consumption were found for body fat (specifically, that of the lower abdominal region). They also discovered that animals that had been drinking chokeberry extract had lower blood glucose and reduced levels of plasma triglycerides, cholesterol, and low-density lipoprotein (LDL) cholesterol when compared to the control animals. These alterations would theoretically lead to lower risk for diabetes and cardiovascular disease in humans.

To add even more evidence for a healthful impact of this super-berry, the researchers documented numerous alterations in expression of genes that would likely lead to reduced chronic inflammation and perhaps even lower cancer risk. For instance, drinking chokeberry extract lowered expression of the gene coding for interleukin-6 (IL-6), a protein that normally triggers inflammation following trauma or infection. Chronic overproduction of IL-6 has been documented in many diseases such as diabetes, arthritis, and atherosclerosis and is thought to be a partial cause of these conditions.

Researchers conclude that though human trials are essential to further substantiate their claim,  they believe their study "provides evidence that the chokeberry extract inhibits weight gain in insulin-resistant animals and that it modulates multiple genes associated with adipose tissue growth, blood glucose regulation, and inflammatory pathways."....

Ref : Bolin Qin and Richard A Anderson, :  Abstract in FASEB, 

(those interested can read other benefits and other details at the link)

MIF (Macrophage migration Inhibitory Factor) - a new molecular target for the treatment of depressant and anxiety...

Clinical depression affects 121 million people around the world,  according to the World Health Organization, but only 60% to 80% of cases are effectively treated with current medication and psychotherapy.  Now researchers from Ecole Polytechnique Fédérale de Lausann, (EPFL), have come up with an interesting target, i.e., macrophage migration inhibitory factor, MIF. 

MIF(see strucutre : wikipedia : a pro-inflammatory cytokine that is expressed in the CNS) is normally thought to play a role in tissue swelling (inflammatory mediator possibly associated with rheumatoid arthritis,  RA-severity) and even cancer development (metastatic potential in speculative models of cancer), but its precise location and function in the brain remained a mystery before Carmen Sandi's (lead researcher) study. 

 The research team, first detected a concentration of MIF protein in stem cells in the hippocampus, (a key area for memory formation and neuron generation during adulthood). New neurons are thought to be linked to the creation of new memories but they may also play an important role in curbing anxiety  (previous studies have shown that prolonged periods of stress reduce neurogenesis, and many anti-depressants actually boost the production of new neurons).

By genetically and pharmaceutically manipulating the level of MIF in the hippocampus of rats, the researchers discovered that the absence of MIF significantly reduced the production of neurons and increased anxiety They also found that the lack of MIF decreases the ability of anti-depressants to stimulate neurogenesis. 

Researchers, identified  MIF expression in neurogenic cells  (in stem cells, cells undergoing proliferation, and in newly proliferated cells undergoing maturation) in the subgranular zone of the rodent dentate gyrus. A causal function for MIF in cell proliferation was shown using genetic (MIF gene deletion) and pharmacological (treatment with the MIF antagonist Iso-1 - see (right side) chemical structure : (S,R)-3-(4-Hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid, methyl ester) approaches. 

As per the claim by the researchers,  genetic deletion of MIF resulted in increased anxiety and depression-like behaviors, as well as of impaired hippocampus-dependent memory. Researchers conclude that,   MIF as a potentially relevant molecular target for the development of treatments linked to deficits in neurogenesis, as well as to problems related to anxiety, depression, and cognition....

Ref : Carmen Sandi et. al., Molecular Psychiatry, 23 February 2010

 

HAMLET (found in breast milk) may target molecules in specific membrane regions.....

We know that HAMLET (human α-lactalbumin made lethal to tumor cells) is a molecular complex of α-lactalbumin and oleic acid (see structure courtesy : Lunds Univ). It induces apoptosis in tumor cells, but normal differentiated cells are resistant to its effect . The activity of HAMLET was discovered by serendipity, while using human milk fractions to investigate bacteria adherence to lung carcinoma cell lines. In addition to blocking adherence, one milk fraction actually killed the cells by inducing apoptosis. Cell death was accompanied by changes in morphology, nuclear condensation, cytoplasmic blebbing, and formation of apoptotic bodies, similar to cells that undergo classical apoptosis.

Further studies showed that HAMLET comprises a protein and a fatty acid that are both found naturally in breast milk. So far, however, it has not been proven that the HAMLET complex is spontaneously formed in the milk. It is speculated, however, that HAMLET can form in the acidic environment of the babies´ stomachs. Laboratory experiments have shown that HAMLET kills 40 different types of cancer, and the researchers are studying  its effect on skin cancer, tumours in the mucous membranes and brain tumours. Importantly, HAMLET kills only cancer cells and does not affect healthy cells.

Although the substance was found several years ago, it is only now that it has been possible to test it on humans. Patients with cancer of the bladder who were treated with the substance excreted dead cancer cells in their urine after each treatment, which has given rise to hopes that it can be developed into medication for cancer care in the future.

Researchers at the University of Gothenburg are focussed on how HAMLET can be taken up into tumour cells. Researchers  lead by,  Roger Karlsson attempting to gain an in-depth understanding of how the substance interacts with cell membranes. 

In their study, researchers examined the interactions of HAMLET with in vitro generated membranes of known composition, and compared HAMLET to the native or partially unfolded, fatty acid free proteins. They also examined the effect of HAMLET on plasma membrane vesicles (PMVs) obtained from tumor cells. Researchers could show that HAMLET interacts with membranes and disturbs their integrity under physiological conditions. Binding to intact tumor cell membranes showed a patchy distribution, indicating that HAMLET may target molecules in specific membrane regions.

Researchers conclude that, HAMLET engages membranes by a mechanism requiring both the protein and the fatty acid. HAMLET binding alters the morphology of the membrane and compromises its integrity, suggesting that membrane perturbation could be an initial step in inducing cell death...

Ref : Roger Karlsson et.al.,  PLoS One., February 23, 2010

PA-824 - Aerosol: New Tool Against Tuberculosis?

We know the epidemic rates of HIV/TB coinfection as well as emerging multidrug-resistant  (MDR) and extensively drug-resistant (XDR) TB strains those are contributing to increased TB-associated deaths worldwide. 

Now PA-824 (see structure), a compound capable of being formulated into a dry powder, has not only shown promising activity against MDR (multidrug-resistant tuberculosis) and XDR (extensively drug-resistant tuberculosis, or latent TB) but has also proven safe and effective in patients coinfected with HIV and TB. Previous studies showed that PA-824 was well-tolerated in tablet form, however, side effects such as headache and stomach discomfort were reported. Aerosol delivery of PA-824 directly to the primary site of infection would limit systemic exposure and ultimately eliminate potentially bothersome side effects.

About  PA-824 :

Nitroimidazoles are widely used drugs in humans for a variety of primarily anaerobic microbial infections. Metronidazole, a 5-nitroimidazole, is an important bactericidal agent for the treatment of anaerobic infections  and shows excellent selective toxicity toward anaerobic bacterial and protozoal pathogens. This class of compounds has only recently begun to be explored for Mtb, because only anaerobic activity of metronidazole against Mtb has been reported. Bicyclic 4-nitroimidazoles such as PA-824 (a nitroimidazo-oxazine) and CGI-17341 (a nitroimidazo-oxazole) have inhibitory activity against aerobically growing and nonreplicating anaerobic Mtb. Although anaerobic conditions have not been demonstrated during TB disease in humans, various authors have suggested that an anaerobic microenvironment may contribute to a nonreplicating state that may be linked with latent disease in humans. Thus, PA-824 has been developed, in part, because it may be a promising lead for therapy against latent disease that may be linked to anaerobically persisting bacilli. The Global Alliance for TB Drug Development has recently initiated phase-I clinical trials with PA-824 

Researchers from the University of North Carolina School of Pharmacy, Chapel Hill, North Carolina; and Harvard School of Engineering and Applied Sciences, Cambridge, Massachusetts, lead by  Dr. Anthony J Hickey  have achieved this interesting finding, i.e., potential use of PA-824 dry powder aerosols in the treatment of TB.

In the study guinea pigs were used to evaluate the effects of PA-824 aerosols on TB infection. One month following infection with TB some guinea pigs received high daily aerosol treatments while others received low daily treatments for 4 weeks. Lung and spleen analysis of guinea pigs receiving the high dose of aerosol PA-284 showed less inflammation, bacterial burden and tissue damage.

"The present studies indicate the potential use of PA-824 dry powder aerosols in the treatment of TB,” say the researchers".

Ref : http://aac.asm.org/cgi/content/abstract/54/4/1436.

Chitosan could repair spinal damage - first evidence....

Polyethylene glycol (PEG) was reported to seal and repair damaged spinal cord nerve cells,  by repairing the damaged membranes of nerve cells. Researchers lead by  Richard Borgens and his team claimed that, PEG can restore the spinal cord's ability to transmit signals to the brain. However, there is one possible clinical drawback: PEG's breakdown products are potentially toxic. 

So, is there a biodegradable non-toxic compound that is equally effective at targeting and repairing damaged nerve membranes? Borgens teamed up with physiologist Riyi Shi and chemist Youngnam Cho, who pointed out that some sugars are capable of targeting damaged membranes. Borgens and his team  has  now come up with an interesting finding i.e.,  chitosan (see structure; source  : Wikipedia) can repair damaged nerve cell membranes. 

Having initially tested mannose and found that it did not repair spinal cord nerve membranes, Cho decided to test a modified form of chitin, one of the most common sugars that is found in crustacean shells. Converting chitin into chitosan, Cho isolated a segment of guinea pig spinal cord, compressed a section, applied the modified chitin and then added a fluorescent dye that could only enter the cells through damaged membranes.  Viewing a section of the spinal cord under the microscope, Cho was amazed to see that the spinal cord was completely dark and none of the dye had entered the nerve cells and Cho concluded that Chitosan had repaired the damaged cell membranes.

Borgens is extremely excited by this discovery that chitosan is able to locate and repair damaged spinal cord tissue and is even more enthusiastic by the prospect that nanoparticles of chitosan could also target delivery of neuroprotective drugs directly to the site of injury.

'giving us a dual bang for our buck,' says Borgens....

 Ref :  http://jeb.biologists.org/cgi/content/full/213/9/i-a