MSRA can be stopped before it becomes dangerous ....

In continuation of my update on MRSA (methicillin-resistant Staphylococcus aureus), I found the following info interesting.

C. Jeffrey Brinker research group has determined that the very first stage of staph infection, when bacteria switch from a harmless to a virulent form, occurs in a single cell and that this individual process can be stopped by the application of a simple protein (as against the belief that, staph infections are caused by many bacterial cells that signal each other to emit toxins. The signaling process is called quorum sensing). The most significant results from the researchers are :

1. isolation of Staphylococcus aureus bacteria in individual (isolation of an individual bacterium
previously had been achieved only computationally);

2. demonstration of release of signaling peptides from a single cell, not a quorum &

3. introduction of an inexpensive, very low-density lipoprotein (VLDL) to bind to the
messenger peptide, they stopped the single cell from reprogramming itself.

One aspect of experimental rigor was the team's ability to organize living cells into a nanostructured matrix. The researchers has already done it with yeast, and just extended the process to bacteria. Researchers are optimistic about finding a mechanism to locate bacteria reprogramming in the body so that the antidote can be delivered in time. If they achieve what they are optimistic, so there will selectivity of targeting the bacteria (human gastro-intestinal system contains many useful bacteria) which in my opinion will be a remarkable feat....

Ref : http://www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.264.html

Anticancer & Antiinflammatory properties of Lunasin (Soy Peptide) established ?...

We know that many researchers have tried to establish the anticancer activity of the peptide lunasin (which has been already accepted as neutraceutical agent). Now researchers from University of Illinois have come up with more interesting facts, Soy peptide often discarded in the waste streams of soy-processing plants, may have important health benefits that include fighting leukemia and blocking the inflammation that accompanies such chronic health conditions as diabetes, heart disease, and stroke.

The researchers confirmed lunasin's bioavailability in the human body by doing a third study in which men consumed 50 grams of soy protein--one soy milk shake and a serving of soy chili daily-for five days. Significant levels of the peptide in the participants' blood give us confidence that lunasin-rich soy foods can be important in providing these health benefits.

In the cancer study, de Mejia's group identified a key sequence of amino acids- arginine, glycine, and aspartic acid, (the RGD motif)--that triggered the death of leukemia cells by activating a protein called caspase-3. The scientists also verified lunasin's ability to inhibit topoisomerase 2, an enzyme that marks the development of cancer, and they were able to quantify the number of leukemia cells that were killed after treatment with lunasin in laboratory experiments.

More interesting out come of their study is lunasin's potential anti-inflammatory activity, (first time) they showed that lunasin blocked or reduced the activation of an important marker called NF-kappa-B, a link in the chain of biochemical events that cause inflammation. They also found statistically significant reductions in interleukin-1 and interleukin-6, both important players in the inflammatory process (the reduction in interleukin-6 was particularly strong). As per the claim by the group, although the high cost of obtaining lunasin from soy waste limits its use for nutritional interventions, soy flour does contain high concentrations of the peptide (depending on some genotype soy).

Its good see the diverse activities associated with Soy......

Source : http://pubs.acs.org/doi/abs/10.1021/jf803303k?prevSearch=Elvira%2Bde%2BMejia&searchHistoryKey=

Discovery Of Novel New Class of Antimicrobial Agents... ......

We know that most of the bacteria are getting resistant to the present drugs and there is an urgent need to find a solution for resistant bacteria. Inn this global fight against resistant bacteria many companies are trying different ways and now Chaperone Technologies, Inc has come up with something innovative and interesting way, i.e., the company is trying to develop antimicrobial compounds that work by inhibiting bacterial hsp70 proteins (an entirely new mechanism of action).

Chaperone’s antimicrobial program focuses on development of peptide as well as small molecule hsp70 inhibitor drugs that block the effect of this important class of molecular “chaperones” whose role is to help mediate or respond to toxic misfolded proteins within bacteria. Inhibition of this critical bacterial protein has been proven to kill bacterial pathogens. Besides antimicrobials, the inhibition of hsp70 molecular chaperone proteins present in other cell-types has a range of therapeutic applications that are being investigated by the company.

Using sophisticated computerized molecular modeling techniques, proprietary high-throughput screening tools developed by Chaperone and other approaches, the company has significantly expanded its library of novel hsp70 inhibitor compounds including CHP-267 and CHP-281, just two of the many promising drug candidates from this highly promising family of small molecule inhibitors discovered by the Company. Chaperone is looking at hsp70 inhibitors as stand alone antimicrobial agents as well as in combination with other antimicrobials (e.g., Finafloxacin.HCl : see the structure -which is under phase II clinical trials). The company recently received a US Patent covering a method of significantly amplifying the effectiveness of other antimicrobials by combining their use with that of an hsp70 inhibitor. Combining a bacterial hsp70 inhibitor with another antimicrobial yields increased bacterial killing of clinically important pathogens and the potential for combination therapy.

Chaperone’s drug candidates have been proven effective against dangerous bacteria such as MRSA, acinetobacter, and vancomycin resistant enterococci. When combined with other antibiotics, Chaperone’s compounds stimulate powerful antibiotic synergy, providing superior efficacy even while using significantly lower doses of the combined agents.

Source : http://www.biospace.com/news_story.aspx?NewsEntityId=118501

Combination of EGCG & DAPH-12 - a treatment for brain disorders ?

Amyloid plaques are tightly packed sheets of proteins that infiltrate the brain. These plaques, which are stable and seemingly impenetrable, fill nerve cells or wrap around brain tissues and eventually (as in the case of Alzheimer's) suffocate vital neurons or brain cells, causing loss of memory, language, motor function and eventually premature death.

To date, researchers have had no success in destroying plaques in the human brain and only minimal success in the laboratory. One reason for these difficulties in finding compounds that can dissolve amyloids is their immense stability and their complex composition.

Yet, Dr. Duennwald ( Boston Biomedical Research Institute , BBRI) and co workers from Pennsylvania School of Medicine, experienced success in previous studies when he exposed amyloids in living yeast cells to EGCG (see the above structure). Furthermore, he and his collaborators also found before that DAPH-12, (see below structure) too, inhibits amyloid production in yeast.

About EGCG :

Epigallocatechin gallate, also known as Epigallocatechin 3-gallate, is the ester of epigallocatechin and gallic acid and a type of catechin. EGCG is the most abundant catechin in most notably tea, among other plants, and is also a potent antioxidant and that may have therapeutic properties for many disorders including cancer. It is found in green tea, but not black tea, as EGCG is converted into thearubigins in black teas. EGCG can be found in many supplements.

These findings are significant because it is the first time a combination of specific chemicals (EGCG & DAPH-12) has successfully destroyed diverse forms of amyloids at the same time.

Though the detailed mechanism is still to be established, its a good achievement and hope this combinatorial therapy will help those sufferings from Alzheimer's and other degenerative diseases (Huntington's, and Parkinson's) in the days to come.....

Ref : http://www.nature.com/nchembio/journal/v5/n12/pdf/nchembio.246.pdf

Nizatidine as an Oral Solution.....

About Nizatidine :

Nizatidine is a histamine H₂-receptor antagonist that inhibits stomach acid production, and commonly used in the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD). It was developed by Eli Lilly and is marketed under the trade names Tazac and Axid.


Recently FDA approved the Nizatidine Oral Solution in the 15 mg/mL strength. Nizatidine Oral Solution is the first available generic in oral solution form and marks Amneal’s fourth liquid approval. It represents the company’s first exclusive generic – Amneal has 180-day exclusivity to market the product beginning from the date of first shipment......

Source : http://www.amneal.com/headlines/archive/Nizatidine_Oral_Solution_12-04-09.pdf

Statins may protect against GVHD complications

Statins may protect against GVHD complications

First live targeting of tumors with RNA-based technology

Researchers at Duke University Medical Center have devised a way they might deliver the right therapy directly to tumors using special molecules, called aptamers, (Aptamers are oligonucleotides or peptide molecules that bind to a specific target molecule) which specifically bind to living tumor tissue.......

More....First live targeting of tumors with RNA-based technology

CASD-NMR a boon to structure validation....

CASD-NMR(Critical Assessment of Automated Structure Determination) of Proteins is a rolling community-wide experiment involving developers of software tools / protocols for the automated calculation of protein structures from NMR data. The goal of CASD-NMR is to help advance the relevant methodology in order to reach the level of quality and reliability required for direct structure deposition in the PDB. CASD-NMR will also produce extensive data sets that will be useful to develop better methods for NMR structure validation. The more significance of this project is : In the future, automation in NMR will allow 'unsupervised' results to be accepted by the community as being correct and viable, ready for inclusion in the Protein Data Bank (PDB) straight away. The PDB is a database that stores macromolecular structural data that is freely and publicly available for further research.

Ref : http://www.e-nmr.eu/CASD-NMR

New target for diabtes type 2 treatment ?

Mitochondria provide energy for cellular activity. Mitochondrial damage causes people with type 2 diabetes to lose insulin-producing cells, a finding that could lead to new treatments, researchers say.

The researchers (Dr. E. Dale Abel, chief of the endocrinology and metabolism division at the University of Utah School of Medicine in Salt Lake City) found that when insulin-producing beta cells in the pancreas can't respond to circulating insulin, it triggers a "molecular cascade" that damages the normal action of a certain molecular receptor on the surface of the mitochondria. The damaged mitochondria then begin to destroy adenosine triphosphate, the prime fuel for cellular activity. As a result, the beta cells die.

The study provides novel insights into the role of insulin signaling in the regulation of the BAD/GK complex, glycolytic enzyme activity and mitochondrial metabolism in pancreatic β-cells. Ser112-BAD_S and its upstream kinases may be potential targets for the maintenance of the BAD/GK complex that is necessary for normal mitochondrial function and the regulation of β-cell survival....

Source : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007983

CCII capsules offer safe and effective treatment for rheumatoid arthritis

Chicken collagen can provide relief from rheumatoid arthritis (RA) symptoms. A randomised, controlled trial, published in BioMed Central's open access journal Arthritis Research & Therapy, has found that Chicken type II collagen (CCII), a protein extracted from the cartilage of chicken breast, is a safe and effective treatment for RA.

More....CCII capsules offer safe and effective treatment for rheumatoid arthritis

Positive data from rose bengal disodium for psoriasis & atopic dermatitis....

Acid Red 94, (Rose Bengal sodium salt), 3,4,5,6-tetrachloro-2-(2,4,5,7-tetraiodo-6-oxido-3-oxoxanthen-9-yl)benzoate :

Provectus Pharmaceuticals, Inc announced preliminary data for the company’s PH-10 Phase 2 clinical trial for Psoriasis as well as for its Phase 2 clinical trial for Atopic Dermatitis. As per the claim by the company, in its Phase 2 trial of PH-10 (0.001% Rose Bengal) for psoriasis, preliminary data shows that 79% of 29 subjects in the clinical trial demonstrated improvement in the Psoriasis Scoring Index (PSI) during four weeks of daily treatment with PH-10. In addition, 83% of the subjects reported no or only mild pruritus (itching) by week four of the trial, with no significant safety issues noted. The 30^th and final subject will complete final evaluation in early December.

In its Phase 2 trial of PH-10 for atopic dermatitis (“eczema”), preliminary data from the first 18 subjects indicated that 94% of subjects had improvement in the Eczema Area Severity Index (EASI) during four weeks of treatment. Subjects applied PH-10 daily for up to four weeks to skin areas affected by atopic dermatitis, with response observed weekly throughout this treatment phase and for one month after the end of this period. As in the psoriasis study, the treatments were generally well tolerated with no significant safety issues identified. Hope a sigh of relief for those suffering from psoriasis and atopic dermatitis....

Ref : http://www.pvct.com/pressrelease.html?article=20091201

Positive Results from Chronic Study of Rivaroxaban (anticoagulant drug)...

Rivaroxaban, is an oral anticoagulant invented and manufactured by Bayer; in a number of countries it is marketed as Xarelto. If approved by the United States FDA, it will be marketed by Ortho-McNeil Pharmaceutical. It is the first available orally active direct inhibitor of coagulation Factor Xa. Rivaroxaban is well absorbed from the gut and maximum inhibition of factor Xa occurs three hours after a dose. The effects lasts 8–12 hours, but factor Xa activity does not return to normal within 24 hours so once-daily dosing is possible.

Rivaroxaban is undergoing review by the FDA, On March 19, 2009, an advisory panel recommended FDA approval of rivaroxaban 10 mg once daily for use in patients undergoing hip or knee replacement surgery. The advisory panel concluded that the record trials demonstrate that rivaroxaban is non-inferior and possibly superior to subcutaneous enoxaparin 40 mg once daily. However, they also found an increased risk of bleeding with rivaroxaban and did not address the question of long-term (i.e. > 35 days) use. The advisory panel noted that 1 participant out of 6183 randomized to rivaroxaban died of liver toxicity.....

Source :http://abstracts.hematologylibrary.org/cgi/content/abstract/112/11/436?maxtoshow=&HITS=50&hits=50&RESULTFORMAT=&searchid=1&FIRSTINDEX=0&displaysectionid=Oral+Session&fdate=1/1/2008&tdate=12/31/2008&resourcetype=HWCIT

S-methylmethionine (Vitamin U) as antiulcer agent .......

About S-methylthionine :

S-Methylmethionine, or S-methyl-L-methionine, is a derivative of methionine In plants, it is produced from methionine by the enzyme methionine S-methyltransferase. S-Methyl- methionine is sometimes called vitamin U in naturopathic medicine, but it is not recognized as a vitamin by mainstream nutrition science. Methionine in itself has not been demonstrated as effective for treating peptic and duodenal ulcers. Its proponents claim that sources of methionine are limited, or claim it can be found only in raw cabbage; however, these claims are incorrect. Methionine is a common amino acid found in a wide variety of fruits, vegetables, and legumes.

More interesting results by the researchers from the Stanford University, have further substantiated the claim that it can be used to treat peptic and duodenal ulcers.

Acetaminophen is a pain reliever present in many over-the-counter cold and flu medicines. It is broken down, or metabolized, in the body into byproducts , one of which can be very toxic to the liver. At normal, therapeutic levels, this byproduct is easily deactivated when it binds to a naturally occurring, protective molecule called glutathione. But the body's glutathione stores are finite, and are quickly depleted when the recommended doses of acetaminophen are exceeded. Acetaminophen overdose is the most common cause of liver transplantation and the only effective antidote is an unpalatable compound called NAC that can induce nausea and vomiting, and must be administered as soon as possible after the overdose.

As per the claim by the authors, an enzyme called Bhmt2 helped to generate more glutathione. Bhmt2 works by converting the diet-derived molecule S-methylmethionine, or SMM, into methionine, which is subsequently converted in a series of steps into glutathione. The researchers confirmed the importance of the pathway by showing that SMM conferred protection against acetaminophen-induced liver toxicity only in strains of mice in which the Bhmt2 pathway was functional.

By administering SMM, which is found in every flowering plant and vegetable, we were able to prevent a lot of the drug’s toxic effect,” said Peltz. He and his colleagues are now working to set up clinical trials at Stanford to see whether it will have a similar effect in humans. In the meantime, though, he cautions against assuming that dosing oneself with SMM will protect against acetaminophen overdose....

Source : http://med.stanford.edu/ism/2009/november/peltz.html

Top 10 Amazing Chemistry Videos

Top 10 Amazing Chemistry Videos

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Mode of action of tetrathiomolybdate (a drug for Wilson's disaese) established ?

We know that Ammonium tetrathiomolybdate ([NH₄]₂MoS_4), was first used therapeutically in the treatment of copper toxicosis in animals. It was then introduced as a treatment in Wilson's disease, a hereditary copper metabolism disorder, in humans; it acts both by competing with copper absorption in the bowel and by increasing excretion. It has also been found to have an inhibitory effect on angiogenesis, potentially via the inhibition of Cu ion dependent membrane translocation process invovling a non-classical secretion pathway. This makes it an interesting investigatory treatment for cancer, age-related macular degeneration, and other diseases featuring excessive blood vessel deposition. Though the activity was established mode of action was to be established. Now researchers from Northwestern University , have achieved something which was eluding so for. As per the claim by the researchers, the three-dimensional structure of TM bound to copper-loaded metallochaperones. The drug sequesters the chaperone and its bound copper, preventing both from carrying out their normal functions in the cell. For patients with Wilson disease and certain cancers whose initial growth is helped by copper-dependent angiogenesis, this is very promising. O'Halloran and his research team studied the copper chaperone protein Atx1, which provides a good model of copper metabolism in animal cells.

The drug brings three copper chaperones into close quarters, weaving them together through an intricate metal-sulfur cluster in a manner that essentially shuts down the copper ferrying system.

The nest-shaped structure of the metal-sulfur cluster discovered by the researchers was completely unanticipated. The sulfur atoms in the tetrathiomolybdate bound to the copper atoms to form an open cluster that bridged the chaperone proteins. In this manner, three copper proteins were jammed onto one thiomolybdate. More interestingly the structure of the complex has been concluded by X-ray studies. Based on the structure and additional experiments, the scientists propose that the drug inhibits the traffic of copper within the cell because of its ability to sequester copper chaperones and their cargo in clusters, rendering the copper inactive.

Copper also is an important cofactor for tumor angiogenesis, the process of growing new blood vessels to feed the tumor. Researchers believe this is why tetrathiomolybdate has shown promise as an anti-cancer drug. Hope the clinical trials (phase II) of tetrathiomolybdate (as anticancer drug) a success and wide applications of this drug (as amyotrophic lateral sclerosis (ALS), Parkinson's disease, multiple sclerosis and Alzheimer's disease, primary pulmonary hypertension and left ventricular hypertrophy) will help patients to breathe a sigh of relief...

Ref : http://www.northwestern.edu/newscenter/stories/2009/11/crystal.html