Researchers hypothesized that NSAIDs modulate clonal evolution by reducing SGA acquisition rate. Researchers evaluated thirteen individuals with BE. Eleven had not used NSAIDs for 6.2±3.5 (mean±standard deviation) years and then began using NSAIDs for 5.6±2.7 years, whereas two had used NSAIDs for 3.3±1.4 years and then discontinued use for 7.9±0.7 years. 161 BE biopsies, collected at 5–8 time points over 6.4–19 years, were analyzed using 1Million-SNP arrays to detect SGAs. Even in the earliest biopsies there were many SGAs (284±246 in 10/13 and 1442±560 in 3/13 individuals) and in most individuals the number of SGAs changed little over time, with both increases and decreases in SGAs detected. The estimated SGA rate was 7.8 per genome per year (95% support interval [SI], 7.1–8.6) off-NSAIDs and 0.6 (95% SI 0.3–1.5) on-NSAIDs. Twelve individuals did not progress to EA. In ten we detected 279±86 SGAs affecting 53±30 Mb of the genome per biopsy per time point and in two researchers detected 1,463±375 SGAs affecting 180±100 Mb. In one individual who progressed to EA we detected a clone having 2,291±78 SGAs affecting 588±18 Mb of the genome at three time points in the last three of 11.4 years of follow-up. NSAIDs were associated with reduced rate of acquisition of SGAs in eleven of thirteen individuals. Barrett's cells maintained relative equilibrium level of SGAs over time with occasional punctuations by expansion of clones having massive amount of SGAs. More...
Wednesday, June 26, 2013
We know that, Telavancin (trade name Vibativ) is a bactericidal lipoglycopeptide for use in MRSA or other Gram-positive infections. Telavancin is a semi-synthetic derivative of vancomycin. The FDA approved the drug in September 2009 for complicated skin and skin structure infections (cSSSI)...
Now U.S. Food and Drug Administration today expanded the approved use of the antibiotic Vibativ (telavancin) to treat patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by Staphylococcus aureus. Vibativ should be used for the treatment of HABP/VABP only when alternative treatments are not suitable...
Wednesday, June 19, 2013
Despite success with BRAFV600E inhibitors, therapeutic responses in patients with metastatic melanoma are short-lived because of the acquisition of drug resistance. Researchers identified a mechanism of intrinsic multidrug resistance based on the survival of a tumor cell subpopulation. Treatment with various drugs, including cisplatin and vemurafenib, uniformly leads to enrichment of slow-cycling, long-term tumor-maintaining melanoma cells expressing the H3K4-demethylase JARID1B/KDM5B/PLU-1. Proteome-profiling revealed an upregulation in enzymes of mitochondrial oxidative-ATP-synthesis (oxidative phosphorylation) in this subpopulation. Inhibition of mitochondrial respiration blocked the emergence of the JARID1Bhigh subpopulation and sensitized melanoma cells to therapy, independent of their genotype. Our findings support a two-tiered approach combining anticancer agents that eliminate rapidly proliferating melanoma cells with inhibitors of the drug-resistant slow-cycling subpopulation.
Tuesday, June 18, 2013
In continuation of my update on Pioglitazone
We know that, Pioglitazone is a prescription drug of the class thiazolidinedione (TZD) with hypoglycemic (antihyperglycemic, antidiabetic) action to treat diabetes. It is used to improve glucose control in adults over the age of 18 with type 2 diabetes. Pioglitazone is marketed as trademarks Actos in the USA, Canada, the UK and Germany, Glustin in Europe, Glizone and Pioz in India by Zydus Cadila and USV Limited, respectively and Zactos in Mexico by Takeda Pharmaceuticals....
Now Researchers in Spain have found that a drug used to control Type II diabetes can help repair the spinal cords of mice suffering from the inherited disease adrenoleukodystrophy which, untreated, leads eventually to a paralysis, a vegetative state and death. They believe that their findings may be relevant to other neurodegenerative diseases. A Phase II trial will be starting shortly. ...
More : http://brain.oxfordjournals.org/content/136/3/891.abstract?sid=08e53c88-b470-4a40-844f-4a1e57b570d9
Monday, June 17, 2013
Flamel Technologies today announced that the U.S. Food and Drug Administration (FDA) has approved the company's New Drug Application (NDA) for Bloxiverz (neostigmine (see structure below) methylsulfate), a drug used intravenously in the operating room for the reversal of the effects of non-depolarizing neuromuscular blocking agents after surgery. Flamel expects to launch Bloxiverz in July 2013 in 0.5 and 1.0 mg/mL strengths.
"We are extremely excited and pleased to receive this FDA approval for Bloxiverz, the first product from the portfolio of Éclat products acquired in March 2012," said Mike Anderson, Chief Executive Officer of Flamel.
Bloxiverz is the first FDA-approved version of neostigmine, even though other versions of neostigmine have been on the market as unapproved, grandfathered products under the Food, Drug and Cosmetic Act of 1938. Today, neostigmine is the most common agent used for the reversal of the effects of other agents used for neuromuscular blocks.
Posted by dr.umesh l at 6:34 AM
Labels: Bloxiverz (neostigmine methylsulfate), FDA approval, non-depolarizing neuromuscular blocking agents after surgery
Friday, June 14, 2013
Androgen receptors are found inside cells and have complex surfaces with multiple "docking points" where various proteins can bind to the receptor. Each docking point has a unique shape, so only a correctly shaped molecule will fit.
Androgen hormones, such as testosterone, are the primary molecules that bind to androgen receptors. Such binding sets off a chain of events that activates several different processes in the human body, including stimulating the development and maintenance of male characteristics.
Looking for a new approach to battle prostate cancer, Ahn and his colleagues keyed in on blocking a critical docking point on the androgen receptor.
"When a tumor is trying to grow, activation of this location provides what the tumor needs," Ahn said. "There are other surfaces on the androgen receptor that are free to continue working with their respective proteins and to continue functioning. We sought to block only one set of interactions that contribute to prostate cancer growth. That's why we thought our approach might lead to potent efficacy with fewer side effects."
Using computer-assisted molecular modeling, Ahn designed a helix-mimicking small molecule (see structure)
that fits precisely into a pocket on the androgen receptor that is associated with prostate cancer. Collaborating with senior study author Dr. Ganesh Raj, associate professor of urology at UT Southwestern and a specialist in treating urologic cancers, the researchers tested the compound in animal and isolated human tissue. Without exhibiting noticeable toxicity, the compound prevented the androgen receptor from recruiting its protein partners and it blocked the growth of prostate cancer cells.
According to the researchers, D2 (Methyl 4-(3-isobutoxy-4-nitrobenzamido)-3-isobutoxybenzoate, above structure) is stable, non-toxic and efficiently taken up by prostate cancer cells. Importantly, D2 blocks androgen-induced nuclear uptake and genomic activity of the androgen receptor. Furthermore, D2 abrogates androgen-induced proliferation of prostate cancer cells in vitro with an IC50 of 40 nM, and inhibits tumour growth in a mouse xenograft model. D2 also disrupts androgen receptor–coregulator interactions in ex vivo cultures of primary human prostate tumours. These findings provide evidence that targeting androgen receptor–coregulator interactions using peptidomimetics may be a viable therapeutic approach for patients with advanced prostate cancer.
"We have shown that our molecule binds very tightly, targeting the androgen receptor with very high affinity," Ahn said. "We also have confirmed that it inhibits androgen function in these cells, which is a promising finding for drug development. We showed that it does work through these mechanisms, and it is as effective in inhibiting the proliferation of prostate cancer cells as other compounds currently in clinical trials."
Ref : http://www.nature.com/ncomms/journal/v4/n5/full/ncomms2912.html
Ref : http://www.nature.com/ncomms/journal/v4/n5/full/ncomms2912.html
Posted by dr.umesh l at 6:57 AM
Labels: Androgen hormones, Androgen receptors, Methyl 4-(3-isobutoxy-4-nitrobenzamido)-3-isobutoxybenzoate
Thursday, June 13, 2013
FDA Approves Revlimid (lenalidomide) for the Treatment of Patients with Relapsed or Refractory Mantle Cell Lymphoma
In continuation of my update on Lenalidomide
We know that, Lenalidomide (Revlimid) is a derivative of thalidomide introduced in 2004. It was initially intended as a treatment for multiple myeloma, for which thalidomide is an accepted therapeutic treatment. Lenalidomide has also shown efficacy in the class of hematological disorders known as myelodysplastic syndromes (MDS). Lenalidomide has significantly improved overall survival in myeloma (which generally carries a poor prognosis), although toxicity remains an issue for users.
Wednesday, June 12, 2013
We know that, Tobramycin is an aminoglycoside antibiotic derived from Streptomyces tenebrarius and used to treat various types of bacteria infections, particularly Gram-negative infections. It is especially effective against species of Pseudomonas.
The U.S. Food and Drug Administration today approved TOBI Podhaler (tobramycin inhalation powder) for the management of cystic fibrosis patients with Pseudomonas aeruginosa, a bacterium that causes lung infections.
Tuesday, June 11, 2013
Bristol-Myers Squibb Receives US FDA sNDA Approval for Use of SUSTIVA® (efavirenz) in HIV-1 Infected Pediatric Patients | BMS Newsroom
We know that, Efavirenz (EFV, brand names Sustiva, Stocrin, Efavir etc.) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and is used as part of highly active antiretroviral therapy (HAART) for the treatment of a human immunodeficiency virus (HIV) type 1.
For HIV infection that has not previously been treated, the United States Department of Health and Human Services Panel on Antiretroviral Guidelines currently recommends the use of efavirenz in combination with tenofovir/emtricitabine (Truvada) as one of the preferred NNRTI-based regimens in adults and adolescents .
Efavirenz is also used in combination with other antiretroviral agents as part of an expanded postexposure prophylaxis regimen to reduce the risk of HIV infection in people exposed to a significant risk (e.g. needlestick injuries, certain types of unprotected sex etc.).
The usual adult dose is 600 mg once a day. It is usually taken on an empty stomach at bedtime to reduce neurological and psychiatric adverse effects.
Efavirenz was combined with the popular HIV medication Truvada, which consists of tenofovir and emtricitabine, all of which are reverse transcriptase inhibitors. This combination of three medications approved by the U.S. Food and Drug Administration (FDA) in July 2006 under the brand name Atripla, provides HAART in a single tablet taken once a day. It results in a simplified drug regimen for many patients.
Monday, June 10, 2013
In conyinaution of my update on Dabrafenib
GlaxoSmithKline plc announced today that the U.S. Food and Drug Administration (FDA) has approved Tafinlar (dabrafenib). Tafinlar is indicated as a single-agent oral treatment for unresectable melanoma (melanoma that cannot be removed by surgery) or metastatic melanoma (melanoma which has spread to other parts of the body) in adult patients with BRAF V600E mutation. Tafinlar is not indicated for the treatment of patients with wild-type BRAF melanoma. The mutation must be detected by an FDA-approved test, such as the companion diagnostic assay from bioMérieux S.A., THxID™-BRAF.
Friday, June 7, 2013
In continuation of my update on Trametinib
GlaxoSmithKline plc announced today that the U.S. Food and Drug Administration (FDA) has approved Mekinist (trametinib) as a single-agent oral treatment for unresectable or metastatic melanoma in adult patients with BRAF V600E or V600K mutations. Mekinist is not indicated for the treatment of patients who have received a prior BRAF inhibitor therapy. The mutation must be detected by an FDA-approved test, such as the companion diagnostic assay from bioMérieux S.A., THxID™-BRAF.
Thursday, June 6, 2013
Cancer Fighting Foods:
How can food fight cancer, you ask? In many, many ways! Certain healthy foods can lower your risk for cancer by repairing damaged cells and protect sensitive skin. Incorporating more plant-based foods into your diet is a relatively small lifestyle change that can really reduce your cancer risk.
Oranges are high in folate, and recent research suggests that people with low levels of folate are more likely have mutations occur in their DNA, which can lead to mutated cancer cells. Leafy greens, like spinach and Brussels sprouts, are also high in folate. In recent research, men who consumed their daily suggested intake of folate were able to decrease their risk for pancreatic cancer by 50-percent.
We’ve all heard that calcium is important for healthy bones, but milk is also high in vitamin D, another nutrient that is linked to combating cancer—researchers suggest that vitamin D helps stop the growth of cancerous cells. In fact, it has been shown to significantly decrease the risk of breast cancer.
The more you eat, the more you—well, the more you decrease your risk for cancer. Beans, in addition to being high in protein and fiber (great for vegetarian diet), are also high in antioxidants that are key in the fight against cancer. Antioxidants protect your cells against free radicals—free radicals, which can come from activities like smoking, cause damage to cells, leading to cancer and other complications.
Other foods that are high in antioxidants: Berries, cruciferous vegetables (think broccoli and cabbage), potatoes and nuts. A good general rule of thumb is to eat fruits and veggies that have a lot of color to them, as they usually contain the highest amount antioxidants.
Your mom was right—you really should eat up all of your leafy greens . Leafy greens (like spinach and kale) contain a substance called chlorophyllin, which can help fight cancer—it works by blocking toxins. People who consume more leafy greens show lower rates of stomach cancer.
And A Glass of Wine!
Grapes and wine contain resveratrol, which is another substance that slows the growth of cancerous cells. It does so by limiting growth and acts as a catalyst for apoptosis (a cancer cell death). In addition to it’s anti-carcinogenic properties, it also helps prevent Alzheimer’s and diabetes. More importantly (ha-ha), it’s also been linked to anti-aging properties: it helps stimulate the production of SIRT1, a serum that helps slow the aging process.
So, there you have it; your first steps to prevent cancer (along with SPF and quitting smoking) are right here. A healthier diet with more fruits and veggies will do more than lower your risk of cancer; it will change your quality of life. And, if eating healthy is not your thing, start with small changes, and build from there!
Virginia Cunningham is a freelance writer from Los Angeles whose writing covers a range of health topics, including holistic alternatives, healthy cooking and personal fitness. She not only includes these cancer-fighting foods into her diet, but she enjoys them as well!
Posted by dr.umesh l at 2:01 PM
Tuesday, June 4, 2013
Raptor Pharmaceutical's PROCYSBI™ Receives FDA Approval for the Treatment of Nephropathic Cystinosis
Cysteamine bitartrate, is a cystine depleting agent which lowers the cystine content of cells in patients with cystinosis, an inherited defect of lysosomal transport. It is an aminothiol, beta-mercaptoethylamine. Cysteamine bitartrate is a highly water soluble white powder with a molecular weight of 227 and the molecular formula C2H7NS • C4H6O6. It has the following chemical structure:
Now, U.S. Food and Drug Administration today approved Procysbi (cysteamine bitartrate) for the management of nephropathic cystinosis in children and adults. Procysbi was granted orphan product designation because it is intended to treat a rare disease or condition....
Multimedia Now Available: Raptor Pharmaceutical's PROCYSBI™ Receives FDA Approval for the Treatment of Nephropathic Cystinosis (NASDAQ:RPTP)
Monday, June 3, 2013
We know that, Nimodipine (marketed by Bayer as Nimotop) is a dihydropyridine calcium channel blocker originally developed for the treatment of high blood pressure. It is not frequently used for this indication, but has shown good results in preventing a major complication of subarachnoid hemorrhage (a form of cerebral hemorrhage) termed vasospasm; this is now the main use of nimodipine.
Now FDA, has approved its New Drug Application (NDA) for Nymalize (nimodipine) oral solution. Nymalize was previously granted Orphan designation which provides seven years of market exclusivity. Nymalize is the first and only nimodipine oral solution indicated for the improvement of neurological outcome in adult patients with subarachnoid hemorrhage (SAH).
Sunday, June 2, 2013
We know that, Coenzyme Q10, also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ10, CoQ, or Q10 is a 1,4-benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the number of isoprenyl chemical subunits in its tail.
This oil-soluble, vitamin-like substance is present in most eukaryotic cells, primarily in the mitochondria. It is a component of the electron transport chain and participates in aerobic cellular respiration, generating energy in the form of ATP. Ninety-five percent of the human body’s energy is generated this way. Therefore, those organs with the highest energy requirements—such as the heart, liver and kidney—have the highest CoQ10 concentrations.There are three redox states of CoQ10: fully oxidized (ubiquinone), semiquinone (ubisemiquinone), and fully reduced (ubiquinol). The capacity of this molecule to exist in a completely oxidized form and a completely reduced form enables it to perform its functions in the electron transport chain and as an antioxidant respectively.
Now double blind controlled trials have shown that CoQ10 improves symptoms, functional capacity and quality of life in patients with heart failure with no side effects. But until now, no trials have been statistically powered to address effects on survival.
The Q-SYMBIO study (2) randomised 420 patients with severe heart failure (New York Heart Association (NYHA) Class III or IV) to CoQ10 or placebo and followed them for 2 years. The primary endpoint was time to first major adverse cardiovascular event (MACE) which included unplanned hospitalisation due to worsening of heart failure, cardiovascular death, urgent cardiac transplantation and mechanical circulatory support. Participating centres were in Denmark, Sweden, Austria, Slovakia, Poland, Hungary, India, Malaysia and Australia.
CoQ10 halved the risk of MACE, with 29 (14%) patients in the CoQ10 group reaching the primary endpoint compared to 55 (25%) patients in the placebo group (hazard ratio=2; p=0.003). CoQ10 also halved the risk of dying from all causes, which occurred in 18 (9%) patients in the CoQ10 group compared to 36 (17%) patients in the placebo group (hazard ratio=2.1; p=0.01).
CoQ10 treated patients had significantly lower cardiovascular mortality (p=0,02) and lower occurrence of hospitalisations for heart failure (p=0.05). There were fewer adverse events in the CoQ10 group compared to the placebo group (p=0.073).
Professor Mortensen said: "CoQ10 is the first medication to improve survival in chronic heart failure since ACE inhibitors and beta blockers more than a decade ago and should be added to standard heart failure therapy."
Saturday, June 1, 2013
Acetylcholinesterase helps regulate nervous system activity by stopping electrical signaling in nerve cells. If the enzyme can't do its job, the mosquito begins convulsing and dies. The research team's goal is to develop compounds perfectly matched to the acetylcholinesterase molecules in malaria-transmitting mosquitoes, he said.
"A simple analogy would be that we're trying to make a key that fits perfectly into a lock," Bloomquist said. "We want to shut down the enzyme, but only in target species."
Bloomquist and colleagues at Virginia Tech, where the project is based, are trying to perfect mosquito-specific compounds that can be manufactured on a large scale and applied to mosquito netting and surfaces where the pests might land.
It will take at least four to five years before the team has developed and tested a compound enough that it's ready to be submitted for federal approval, Bloomquist said.
As per the claims by the researchers, conventional insecticides targeting acetylcholinesterase (AChE) typically show high mammalian toxicities and because there is resistance to these compounds in many insect species, alternatives to established AChE inhibitors used for pest control are needed. Here researchers used a fluorescence method to monitor interactions between various AChE inhibitors and the AChE peripheral anionic site, which is a novel target for new insecticides acting on this enzyme. The assay uses thioflavin-T as a probe, which binds to the peripheral anionic site of AChE and yields an increase in fluorescent signal. Three types of AChE inhibitors were studied: catalytic site inhibitors (carbamate insecticides, edrophonium, and benzylpiperidine), peripheral site inhibitors (tubocurarine, ethidium bromide, and propidium iodide), and bivalent inhibitors (donepezil, BW284C51, and a series of bis(n)-tacrines). All were screened on murine AChE to compare and contrast changes of peripheral site conformation in the TFT assay with catalytic inhibition. All the inhibitors reduced thioflavin-T fluorescence in a concentration-dependent manner with potencies (IC50) ranging from 8 nM for bis(6)-tacrine to 159 μM for benzylpiperidine. Potencies in the fluorescence assay were correlated well with their potencies for enzyme inhibition (R2 = 0.884). Efficacies for reducing thioflavin-T fluorescence ranged from 23–36% for catalytic site inhibitors and tubocurarine to near 100% for ethidium bromide and propidium iodide. Maximal efficacies could be reconciled with known mechanisms of interaction of the inhibitors with AChE. When extended to pest species, we anticipate these findings will assist in the discovery and development of novel, selective bivalent insecticides acting on AChE....
Research aims for insecticide that targets malaria mosquitoes