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