ProstaCaid (33-ingredient comprehensive polyherbal preparation) against prostate cancer......

We have seen  many benefits of natural products rich in  Quercetin,   Epigallocatechin gallate (EGCG) and many other polyphenol antioxidant from natural products like green tea, broccoli peaches and plums. Interestingly, now researchers from  Columbia University have come up with an interesting finding, i.e., ProstaCaid is a 33-ingredient comprehensive polyherbal preparation with supplements of vitamin C, vitamin D3, zinc, selenium, quercitin, 3,3′-diinodolymethane (DIM), and lycopene was able to stop abnormal cell growth and induce apoptosis (programmed cell death) in both hormone sensitive and hormone resistant prostate cancer cell lines at unusually low concentrations, which makes the findings more significant...

Herbal extracts include the extracts from turmeric root, saw palmetto berry, grape skin, pomegranate, pumpkin seed, pygeum bark, sarsaparilla root, green tea, and Japanese knotweed. Hence, it is rich in natural polyphenols, including quercetin, resveratrol, epigallocatechin gallate (EGCG), and ellagic acid, which have previously demonstrated anticancer potential. The unique formula contains 3 medicinal mushrooms grown on an herbal-enhanced medium. The mushrooms included are Phellinus linteus, Ganoderma lucidum, and Coriolus versicolor, each with known anticancer properties.

Researchers claim that, ProstaCaid was designed based on constituents that exhibit antiprolifetaive, antioxidant, and apoptotic activities; however, its efficacy and the mechanisms of action are yet to be examined. Researchers looked at the effectiveness of the preparation in suppressing several types of prostate cancer cell lines in culture and attempt to delineate the mechanism of action for justification in pursuing animal to determine efficicacy invivo.

Researchers conclude that, the anticancer activity of ProstaCaid may be ascribed to its polyphenolic flavonoids and curcuminoids derived from various herbs as well as other supplements, such as DIM. The preparation contains supplements such as quercetin (15%), Curcuma longa root extract complex with enhanced bioavailability (BCM-95; 20%), DIM (3%), and resveratrol (0.2%). Some of these components have shown a strong doseand time-dependent growth inhibition and apoptotic death in prostate cancer cells; 25 mM of quercetin inhibited about 50% PC3 cell growth for 72 hours. At 24 hours, 50 mM and 100 mM quercetin induced G2/M arrest and apoptosis, manifested by the decrease in G2/M-related protiens.

Researchers summarise  that,    ProstaCaid has anti-cancer activities in both AD and AI prostate cancer cells at very low concentrations (25 mg/mL). It also suggests that ProstaCaid inhibits cell growth and survival, at least through the inhibition of AKT and MAPK signaling. The effect on AI cell lines is especially of importance as there is presently no curative therapy for hormone refractory prostate cancer.

Researchers postulate that ProstaCaid may affect activity of Cdc2/cyclin B1 kinase by reducing this complex formation. Cdc2 could be dephosphorylated by Cdc25C and become inactive or be phosphorylated by protein kinase, such as Wee1, and then converted into an inactive form. They also suggest that more studies are needed in the future to test it and to define its upstream events in PC3 cells.

Ref : Jun Yan and Aaron E. Katz, Integr Cancer Ther 2010 9: 186

Carfilzomib could become new option for patients with relapsed myeloma, IMF says

 In continuation of my update on Carfilzomib
 

The International Myeloma Foundation (IMF), the oldest and largest foundation dedicated to improving the life and care of myeloma patients, today said promising data suggest that the new drug "carfilzomib" could become an important new option for patients whose myeloma stops responding to other therapies. Carfilzomib, from Onyx Pharmaceuticals, is a next-generation proteasome inhibitor that disrupts the life cycle of a cancer cell, and carfilzomib has shown favorable tolerability. Based on this Phase II clinical trial, Onyx could seek accelerated drug approval from the FDA by the end of 2010.

More....

Ref : http://myeloma.org/ArticlePage.action?tabId=0&menuId=0&articleId=3082&aTab=-1

Impressive Results of Velcade(R) (bortezomib) Based Therapy in Multiple Myeloma...

 In continuation of my update on Bortezomib [1, 2]

The Takeda Oncology Company today reported new correlative science data from the pivotal PINNACLE trial of VELCADE^® (bortezomib) in patients with relapsed/refractory mantle cell lymphoma (MCL). The data, derived from an analysis of archived tumor samples, tested pre-specified biomarkers for their association with time to progression and response to treatment with VELCADE in patients with relapsed MCL. The results add to the body of data supporting the potential usefulness of biomarkers in predicting outcome of MCL and predicting responsiveness to single agent VELCADE.

"This analysis of the PINNACLE study opens the door for additional research into targeted approaches to VELCADE treatment."..

The PINNACLE trial was a Phase II, open-label, single-arm, multicenter study of 155 patients with relapsed/refractory MCL and was the basis of the 2006 approval of VELCADE for the treatment of patients with relapsed/refractory MCL who had received one prior therapy. The overall response rate in the trial was 31 percent, with a median duration of response of 9.3 months; the CR rate was 8 percent, with a median duration of response of 15.4 months.

The Goy analysis used archived tumor samples from 73 patients who participated in the PINNACLE trial. The biopsies were examined for biomarkers associated with poor prognosis in MCL or those regulated by the proteasome. The biomarker levels were then compared to the effect of VELCADE on patients, according to response rates including overall survival and time to progression...

Ref : http://investor.millennium.com/phoenix.zhtml?c=80159&p=irol-newsArticle&ID=1434934&highlight=

New Class of Drugs for Treating Epileptic Seizures....

A chemical compound called Galanin,  that boosts the action of a molecule normally produced in the brain may provide the starting point for a new line of therapies for the treatment of epileptic seizures, according to a new study by scientists at "The Scripps Researcher Institute".

"This compound really provides a new angle for developing drugs to treat seizures," says Scripps Research Assistant Professor Xiaoying Lu..

Galanin is a peptide, a fragment of a protein, produced in the brain to regulate a variety of functions, such as pain, memory, addition, mood, and appetite. In the late 1990s, researchers discovered that galanin is also a potent anticonvulsant.

Recent research suggests that when seizures occur the brain steps up production of galanin, possibly as a way to protect itself against the seizures. As a result, mice engineered to lack galanin are more susceptible to developing seizures.

Because galanin seems to play a role in reducing seizures, several groups of researchers, including those at Scripps Research, have been working to develop drugs that target the galanin system. The first category of such compounds consists of synthetic molecules that mimic galanin's functions (called agonists) and include Galnon, developed by Bartfai's group. Galnon and other galanin agonists have been shown to act as anticonvulsants when given to animals that were rendered prone to developing seizures. But these agonists have several drawbacks as potential therapeutic agents. For one thing, because Galnon acts relativly broadly, it may have unwanted side effects.

Interestingly, now Lu, Roberts, Bartfai, and colleagues at Scripps Research have now designed a compound that targets the galanin system but, unlike the previous agonists, is more selective in its action. The compound, dubbed CYM2503, binds to one of the three receptors for galanin on nerve cells, the galanin receptor type 2 (GalR2). On its own, CYM2503 has no effect on GalR2, but when galanin also binds to the receptor, CYM2503 boosts galanin's function.

The researchers tested the effects of CYM2503 on mice and rats that had received a chemical causing them to have seizures. The animals that received CYM2503 took longer to get the seizures and, when they did, the seizures lasted for a shorter time. Most importantly, when the researchers looked at the animals after 24 hours, the rats that had been treated with CYM2503 had a dramatically higher survival rate than those that had not.

This mechanism of action, modifying a receptor's function, is common to many successful drugs that have been developed for the treatment of a number of conditions, including epilepsy, hyperparathyroidism, and AIDS, but not yet for drug candidates targeting galanin system.

Because CYM2503 only works when galanin, a natural molecule, is also present, the researchers predict it will have fewer side effects than drugs that work on their own. This study provides the first evidence that modulating the GalR2 receptor is an effective strategy for treating seizures, thus opening the door for the development of drugs that target this mechanism.

"It is a double breakthrough" . "The compound is a first new mode-of-action anticonvulsant and it represents a new mechanism of molecular action." Also based on the known functions of the GalR2 receptors, it may also work in treating depression and in protecting the brain from damage," says Lu...

Ref : http://www.scripps.edu/news/press/20100728.html

Scientists develop obesity drug without neurological side effects....

We know the side effects of Rimonabant, (see structure) the first selective CB1 receptor blocker to be approved for use anywhere in the world. In Europe, it was indicated for use in conjunction with diet and exercise for patients with a body mass index greater than 30 kg/m², or patients with a BMI greater than 27 kg/m² with associated risk factors, such as type 2 diabetes or dyslipidaemia. In the UK, it was available beginning in July 2006. As of 2008, the drug was available in 56 countries. On October 23, 2008, the European Medicines Agency (EMEA) issued a press release stating that its Committee for Medical Products for Human Use (CHMP) had concluded that the benefits of Acomplia no longer outweighed its risks and subsequently recommended that the product be suspended from the UK market. Sanofi-Aventis later released a press statement stating that the drug had been suspended. Approval of the drug was officially withdrawn by the EMEA on January 16, 2009. But never approved for use in the US because of serious neurological side effects including depression and anxiety.

Now researchers from National Institutes of Health, Bethesda, and Alexandros Makriyannis, at Northeastern University, Boston lead by Dr. George Kunos, have developed a drug (see structure AM6545)  that has the same positive effects in mice on levels of glucose and fats in the blood as rimonabant but none of the neurological side effects.

As per researchers claim AM6545 is a non-brain-penetrant neutral CB1R antagonist. First-generationCB1R antagonists, such as rimonabant, are highly lipid soluble and readily penetrate the blood-brain barrier. In order to reduce brain penetrance, we introduced several modifications into the structure of rimonabant. AM6545 is less lipid soluble than rimonabant (estimated partition coefficient [log P], 3.3 vs. 6.4 for rimonabant) but retains high affinity and selectivity for CB1R. In radioligand displacement assays, AM6545 has a KI of 3.3 nM for CB1R, which is similar to that of rimonabant and greater than 100-fold CB1/CB2 selectivity. Unlike rimonabant, AM6545 does not reduce GTPγS binding in mouse brain membranes and is therefore a neutral antagonist.

As per the claim by the researchers, this drug did not cause weight loss or neurological side effects, which rimonabant does, but did have effects on levels of glucose and fats in the blood that should reduce the risk of the serious health consequences of obesity.

The authors therefore hope that this approach of targeting only peripheral CB1R can be translated into the clinic to reduce health risks in obese patients..

Ref : http://www.jci.org/articles/view/42551/pdf

The Engineering of an Orally Active Conotoxin (Snail Spit) for the Treatment of Neuropathic Pain...

The mollusks use a deadly dose of conotoxins (peptide toxins, e.g., α/ω-conotoxin peptides) that disrupt myriad biological functions. The mollusks  inject into passing prey with hypodermic-needle-like teeth that shoot from their mouths like harpoons.

Within the conotoxin brew are several peptides that relieve tough-to-treat neuropathic pain just as well as morphine does but without its addictive properties. Although scientists have tried to turn such compounds into pain relievers, they've been hamstrung with problems administering such drugs. The pain reliever Prialt (see structure,  Ziconotide),  a synthetic version of ω-conotoxin MVIIA, but it must be injected directly into the spinal cord with a surgically implanted pump.

Now interestingly, scientists in Australia lead  by Prof. David Craik (Institute for Molecular Bioscience at the University of Queensland), have managed to engineer a conotoxin that can be taken orally. Researchers found that,  by linking the N-terminus of α-conotoxin Vc1.1—a compound derived from Conus victoriae—to its C-terminus, they could make the 16-residue peptide orally active.  In the cyclized peptide, which is known as α-conotoxin cVc1.1, the protein's head and tail are tethered by a string of six amino acids—two alanines flanked on each side by two glycines. Prof. Craik says he chose the linker because it was inexpensive, wouldn't add any functionality to the molecule, and would be easy to characterize with nuclear magnetic resonance. In tests with rats, the cyclized peptide proved to be as potent a painkiller as gabapentin, the most popular drug for neuropathic pain, even though the conotoxin-based peptide was administered at a dose that is less than 1% of the dose typically given for gabapentin (other orally prescribed peptide is Ciclosporin a immunosuppressant).

Craik's group has shown that cyclizing larger peptides can make them orally available. His team's analysis of the protein database shows that up to 25% of all proteins have their ends within 10 Å of one another a distance that could easily be spanned with linkers of six to 10 amino acids.

"All you need is for the ends to be roughly close to one another," Prof. Clark says.

Craik says the cyclization also enhances hydrogen bonding across the entire molecule, making it resistant to the endopeptidases that attack a protein's interior amino acids. He says it's sort of like a zipper: "A zipper can be regarded as a series of hydrogen bonds all interlocking together, and when you zip it all up, you've got a beautiful set of coordinated hydrogen bonds. But you've still got two ends, and when you pull apart those two ends of the zipper, then the first hydrogen bond goes, then the next, and then the next. Craik has discovered several other examples of cyclic peptides, which he calls cyclotides (C&EN, April 19, 2004, page 40). He's hoping to use their structural features to guide the engineering of other peptides, as he did with α-conotoxin cVc1.1 At the moment, Craik is trying to raise funds so enough preliminary experiments can be done to file an Investigational New Drug Application. "The most challenging aspect has been just raising the money to get it commercialized," he says. "Pharmaceutical companies are always a little nervous about peptides. We need more success stories so that they'll see peptides not only as fantastic leads but also as potential drugs."...

Ref : http://www3.interscience.wiley.com/journal/123500852/abstract

Phenolic compounds (chlorogenic & neo-chlorogenic acids) in peaches, plums kill breast cancer cells..

We know that Peaches and plums are both high in Potassium, Phosphorus, Magnesium, Calcium, and Vitamins A, C, Niacin, and Folate and antioxidant rich. A recent study performed at Texas A&M University revealed that peaches and plums may present an even sweeter, juicier treat in their ability to fight breast cancer. According to research scientists Dr. Luis Cisneros-Zevallos and Dr. David Byrne from AgriLife Research at Texas A&M, extracts found in commercial varieties of peaches and plums have been to kill breast cancer cells while not harming normal cells.

The AgriLife research scientists identified two phenolic compounds (slightly acidic and may be associated with traits such as aroma, taste or color)  within the Rich Lady peach and Black Splendor (commercial varieties) plum that are responsible for killing the cancer cells. Phenols are organic compounds that occur in fruits and may affect traits such as aroma, taste or color. Stone fruits such as peaches and plums have especially high levels of phenols.

Byrne and Dr. Luis Cisneros-Zevallos originally studied the antioxidants and phytonutrients in plums and found them to match or exceed the blueberry which had been considered superior to other fruits in those categories.

"These extracts killed the cancer cells but not the normal cells," Cisneros-Zevallos said...

As per the claim by the researchers,  two specific phenolic acid components - chlorogenic and neochlorogenic ( structures, source :ChemBlink) - were responsible for killing the cancer cells while not affecting the normal cells. Researchers add that the two compounds are very common in fruits, the researchers said, but the stone fruits such as plums and peaches have especially high levels. The team said laboratory tests also confirmed that the compounds prevented cancer from growing in animals given the compounds.

"So this is very, very attractive from the point of view of being an alternative to typical chemotherapy which kills normal cells along with cancerous ones," Byrne claims..

Researchers conclude that,  phenolic acids present (chlorogenic- left above structure and neo-chlorogenic acids-right below structure)  have potential as chemopreventive dietary compounds because of the relatively high growth inhibition exerted on the estrogen-independent MDA-MB-435 breast cancer cell line and low toxicity exerted in the normal MCF-10A cells.

Dr. Byrne plans to examine more fully the lines of the varieties that were tested to see how these compounds might be incorporated into his research of breeding plums and peaches. Dr.  Cisneros-Zevallos will continue testing these extracts and compounds in different types of cancer and conduct further studies of the molecular mechanisms involved. Hope they come up with substantial results to support their claim....

Ref : Dr.Luis Cisneros-Zevallos et. al., J. Agric. Food Chem., 2009, 57 (12), pp 5219–5226...

Scientists identify new catalytic process to create pharmaceuticals with less chemical waste

Scientists identify new catalytic process to create pharmaceuticals with less chemical waste

I have read about co-operative catalysis (heterogeneous catalysts), but this is something interesting to me..

"Cooperative catalysis by carbens and Lewis acids in a highly stereoselective route to γ-lactams."

Ref : http://www.nature.com/nchem/journal/vaop/ncurrent/full/nchem.727.html

Valproic Acid Shown to Halt Vision Loss in Patients With Retinitis Pigmentosa...

Researchers at the University of Massachusetts Medical School (UMMS) believe, they may have found a new treatment for retinitis pigmentosa (RP), a severe neurodegenerative disease of the retina that ultimately results in blindness. One of the more common retinal degenerative diseases, RP is caused by the death of photoreceptor cells. RP typically manifests in young adulthood as night blindness or a loss of peripheral vision and in many cases progresses to legal blindness by age 40. Dr. Shalesh Kaushal,  chair of ophthalmology and associate professor of ophthalmology and cell biology at UMMS, and his team, describe a potential new therapeutic link between valproic acid and RP, which could have tremendous benefits for patients suffering from the disease. In a retrospective study, valproic acid -  approved by the FDA to reduce seizures, treat migraines and manage bipolar disorder -- appeared to have an effect in halting vision loss in patients with RP and in many cases resulted in an improved field of vision. Results from this study, in conjunction with prior in vitro data, suggest valproic acid may be an effective treatment for photoreceptor loss associated with RP.

UMass Medical School will be the coordinating site for a $2.1 million, three-year clinical trial funded by the Foundation Fighting Blindness/National Neurovision Research Institute quantifying the potential of valproic acid as a treatment for RP. The clinical trials will build upon Kaushal's work in the retrospective study in which patients were treated off-label with doses of valproic acid ranging from 500mg to 750mg per day over the course of two to six months. Treated at a time when patients normally experience rapid vision loss as a result of RP, five of the seven patients in the study experienced improvement in their field of vision.

"Inflammation and cell death are key components of RP," said Kaushal. "It appears the valproic acid protects photoreceptor cells from this. If our observations can be further substantiated by randomized clinical trials then low dose valproic acid could have tremendous potential to help the thousands of people suffering from RP."

Dr. Kaushal and colleagues, having previously demonstrated the use of the small molecule, retinoid, as a pharmacological agent capable of increasing the yield of properly folded RP rhodopsins, began screening other small molecules for similar attributes. Because of its already known qualities as a potent inhibitor of the inflammatory response pathway and cell death, valproic acid was believed to have a unique profile making it a potential candidate as a retinal disease treatment...

Ref : http://www.umassmed.edu/VALPROIC_ACID_SHOWN_TO_HALT_VISION_LOSS_IN_PATIENTS.aspx

New tablet for type 2 diabetes sufferers.....

We know that, Vildagliptin (previously identified as LAF237, trade name Galvus) is a new oral anti-hyperglycemic agent (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vildagliptin inhibits the inactivation of GLP-1 and GIP by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucagon release by the alpha cells of the islets of Langerhans in the pancreas. Vildagliptin has been shown to reduce hyperglycemia in type 2 diabetes mellitus.

Novartis has since withdrawn its intent to submit vildagliptin to the FDA, as of July 2008.  The FDA  had demanded additional clinical data before it could approve vildagliptin including extra evidence that skin lesions and kidney impairment seen during an early study on animals have not occurred in human trials.While the drug is still not approved for use in the US, it was approved in Feb 2008 by European Medicines Agency for use within the EU.

Now as per the claim by Prof Greg Fulcher of Director of diabetes services at Sydney's Royal North Shore Hospital, Galvus, will lower blood sugar effectively without increasing body weight and conclude that this medicine will "significantly increase" the likelihood of diabetes 2 patients reaching blood glucose targets of less than seven per cent (together, the clinical effectiveness and good tolerability of Galvus) and there by reinforce its potential for helping patients with type 2 diabetes and their doctors to better manage this chronic disease. These tablets would be taken once or twice in a day. The details of the treatment are to appear on the Pharmaceutical Benefits Scheme from August 1., in Australia.

Ref : http://www.perthnow.com.au/news/national/new-tablet-for-type-2-diabetes-sufferers/story-e6frg15u-1225897294390

Cytrx’s tamibarotene achieves molecular complete remission in advanced acute promyelocytic leukemia..

CytRx Corporation, announced that a 44-year-old female patient with advanced acute promyelocytic leukemia (APL) achieved molecular complete remission with no evidence of disease in the blood cells and/or bone marrow following treatment with CytRx's oncology drug candidate tamibarotene (see structure, an orally active, synthetic retinoid, developed to overcome all-trans retinoic acid (ATRA) resistance, with potential antineoplastic activity. As a specific retinoic acid receptor (RAR) alpha/beta agonist, tamibarotene is approximately ten times more potent than ATRA in inducing cell differentiation and apoptosis in HL-60 -human promyelocytic leukemia cell lines in vitro.). 

"This event represents a very significant milestone for CytRx and our drug candidate tamibarotene. Tamibarotene has saved a life and nothing can compare with that," said CytRx President and CEO Steven A. Kriegsman. "These important results indicate that tamibarotene warrants further evaluation as a third-line treatment and in combination as a first-line treatment for APL. We are also considering developing tamibarotene for other cancers as well.

Previously published reports indicate that tamibarotene is 10-times more potent and may be better tolerated than all trans retinoic acid (ATRA). Researchers believe that the combination of tamibarotene and arsenic trioxide (ATO) could produce a complete response rate similar to the ATRA and ATO combination with fewer toxicities such as APL differentiation syndrome.  The company is currently conducting a dose escalation trial combining tamibarotene with ATO as an important step in their ultimate goal of evaluating tamibarotene as a first-line treatment for APL. The company claims that, In addition to maintaining a complete remission six months following the last dose, tamibarotene was also well tolerated. In the CytRx's STAR-1 registration trial, patient was treated with tamibarotene for 56 days at the Department of Biopathology at the University of Rome 'Tor Vergata'. A molecular complete remission in the bone marrow was documented at the end of the treatment period and again six months following the last treatment with tamibarotene...

Ref ; http://www.cytrx.com/tamibarotene.html

New evidence that chili pepper ingredient fights fat..

In continuation of my update on Capsaicin may cause weight loss....

In an effort to find out, the scientists lead by Jong Won Yun of of Daegu University, Kyungsan, Korea,  fed high-fat diets with or without capsaicin to lab rats used to study obesity. The capsaicin-treated rats lost 8 percent of their body weight and showed changes in levels of at least 20 key proteins found in fat. The altered proteins work to break down fats.

"These changes provide valuable new molecular insights into the mechanism of the antiobesity effects of capsaicin the scientists say"...

Through secretion of adipokines into the blood, adipose tissue plays a central role in development of these syndromes. In particular, white adipose tissue (WAT) functions as an energy storage organ through formation of triacylglycerol and release of fatty acids into the bloodstream during a shortage of energy. In association with overnutrition, excess WAT play a major role in obesity and obesity-related disorders through dysregulation of adipokine secretion from WAT. Therefore, inhibition of excess WAT can be an efficient strategy for prevention of obesity and metabolic disorders.

Researchers concludes that, thermogenesis and lipid metabolism related proteins were markedly altered upon capsaicin treatment in WAT, suggesting that capsaicin may be a useful phytochemical for attenuation of obesity....

Ref:http://pubs.acs.org/stoken/presspac/presspac/full/10.1021/pr901175w

Phase 3 study: Tapentadol ER lowers incidence of gastrointestinal adverse events..

Tapentadol (see structure) is a new molecular entity that is structurally similar to tramadol (Ultram). It is a centrally-acting analgesic with a dual mode of action as an agonist at the μ-opioid receptor and as a norepinephrine reuptake inhibitor. While its action reflects aspects of tramadol and morphine its ability to kill pain is more on the order of hydrocodone and oxycodone. Interestingly it  has opioid and nonopioid acitivity in a single compound.  Tapentadol is FDA approved for the treatment of moderate to severe acute pain. Due to the dual mechanism of action as an opioid agonist and norepinephrine reuptake inhibitor is potential for off use in chronic pain.

Tapentadol was developed by Grünenthal in conjunction with Johnson & Johnson Pharmaceutical Research and Development. It is being marketed as immediate release oral tablets of 50 mg, 75 mg, and 100 mg under the brabd name Nucynta.

A Phase 3 open-label study (by Johnson & Johnson Pharmaceutical Research & Development, L.L.C), recently published online by Pain Practice, has compared tapentadol extended release (ER) tablets, an investigational pain medication, to an existing prescription pain medication, oxycodone controlled release (CR) tablets.

The study found tapentadol ER was associated with a lower overall incidence of gastrointestinal adverse events than oxycodone CR (tapentadol ER, 52.0 percent; oxycodone CR, 64.1 percent) in patients with chronic knee or hip osteoarthritis pain or chronic low back pain, including: Constipation (tapentadol ER, 22.6 percent; oxycodone CR, 38.6 percent); Nausea (tapentadol ER, 18.1 percent; oxycodone CR, 33.2 percent); and Vomiting (tapentadol ER, 7.0 percent; oxycodone CR, 13.5 percent).

The median duration of treatment was substantially longer with tapentadol ER (268 days) than with oxycodone CR (59 days), and the incidence of overall gastrointestinal treatment-emergent adverse events (TEAEs) leading to study discontinuation was approximately 2.5 times greater in the oxycodone CR group than in the tapentadol ER group (oxycodone CR, 21.5 percent; tapentadol ER, 8.6 percent). In addition, the incidence of constipation leading to study discontinuation was 4.5 times greater in the oxycodone CR group than in the tapentadol ER group (oxycodone CR, 7.2 percent; tapentadol ER, 1.6 percent).

The study also found tapentadol ER provided sustainable relief of moderate to severe chronic knee or hip osteoarthritis pain or chronic low back pain for up to one year. At baseline, mean pain intensity scores in the tapentadol ER and oxycodone CR groups, respectively, were 7.6 and 7.6; at endpoint, they had decreased to 4.4 and 4.

"We are encouraged by these study results as they illustrate the tolerability of tapentadol ER compared with oxycodone CR, a standard chronic pain treatment," said Dr. Bruce Moskovitz, Therapeutic Area Leader for Pain, Ortho-McNeil Janssen Scientific Affairs, LLC. "We are pleased about the possibility of bringing this important investigational compound forward to patients in the future."

This study of tapentadol ER examined its long-term safety and tolerability compared to oxycodone CR and the primary objective of this study was to evaluate the safety of twice-daily doses of tapentadol ER (100 to 250 mg) over one year. Patients were randomized in a 4:1 ratio to receive controlled, adjustable, oral, twice-daily doses of tapentadol ER (100-250 mg) or oxycodone HCl CR (20-50 mg) in open-label treatment for up to one year. There were 1,117 patients in the study that received at least one dose of study medication (tapentadol).

Ref : http://www.jnjpharmarnd.com/jnjpharmarnd/news_release_02042010.html

Toward a new generation of superplastics

Toward a new generation of superplastics

No Firm Conclusions About HDL Cholesterol Can Be Drawn from JUPITER Sub-Analysis

The European Society of Cardiology (ESC) is concerned that interpretations of a paper about cholesterol, published in the Lancet , could act to deter ongoing research efforts into developing new therapeutic strategies to increase high density lipoprotein (HDL) cholesterol. Caution, the ESC experts advise, should be displayed in the interpretation of the results.....

In the Lancet study, Paul Ridker and colleagues, from Brigham and Women's Hospital (Boston, MA, USA), undertook a retrospective post-hoc analysis of the JUPITER trial. The results show that if a normal, healthy individual has level of low density lipoprotein (LDL), known as "bad cholesterol", substantially lowered with a potent statin, then the level of HDL "good cholesterol" in that person no longer bears any relation to the remaining cardiovascular risk. More.....

Ref : http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2960713-1/fulltext