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

Proteasome inhibitor bortezomib inhibits T cell-dependent inflammatory responses - a new hope for autoimmune and inflammatory diseases?

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

Japanese scientists lead by Dr. Koichi Yanaba, of Department of Dermatology at Nagasaki University Graduate School of Biomedical Sciences used mice to show that bortezomib, currently used to treat cancers that affect white blood cells, induces cell death only in harmful (active and proliferating) T cells, leaving the rest unharmed. If the results prove true in humans, it offers hope that this drugs or others similar to it might be used to treat inflammatory diseases without the side effects of current drugs that affect all T cells equally.

To make this discovery, scientists used two groups of mice the first treated with bortezomib and the second with saline. Researchers induced contact hypersensitivity reaction with oxazolone, a chemical allergen used for immunological experiments and found that bortezomib significantly inhibited the contact hypersensitivity responses. Results strongly suggest that bortezomib treatment enhanced T cell death by inhibiting NF-kappa B activation, which plays a key role in regulating the immune response to infection. This in turn led to the suppression of inflammatory responses in immune cells by reducing interferon-gamma production.

"We believe that this new-type remedy for autoimmune and inflammatory disease could successfully treat them in the near future", claims Dr. Koichi Yanaba...

As per the claim by the researchers, bortezomib potently inhibited CHS responses. The attenuation of CHS responses was associated with decreased inflammatory cell infiltration in the challenged skin. Specifically, bortezomib-treated mice showed significantly decreased numbers of CD4⁺ and CD8⁺ T cells in the challenged skin and draining lymph nodes. Cytoplasmic IFN- production by CD4⁺ and CD8⁺ T cells in the draining lymph nodes was decreased substantially by bortezomib treatment. Notably, bortezomib enhanced T cell apoptosis by inhibiting NF-B activation during CHS responses. Thus, bortezomib treatment is likely to induce T cell death, thereby suppressing CHS responses by reducing IFN- production. These findings suggest that bortezomib treatment could be a promising strategy for treating autoimmune and inflammatory disease.

Ref :http://www.jleukbio.org/cgi/content/abstract/88/1/117

How honey kills bacteria..........

We know that, honey has antibiotic activity and has been used specially in burn injuries. Now researchers lead by Dr.Sebastian A.J. Zaat, of Department of Medical Microbiology at the Academic Medical Center in Amsterdam, have come up with an explanation for this antibiotic activity of honey. This first explanation to explain how honey kills bacteria. Specifically, the research shows that bees make a protein that they add to the honey, called defensin-1, which could one day be used to treat burns and skin infections and to develop new drugs that could combat antibiotic-resistant infections.

"We have completely elucidated the molecular basis of the antibacterial activity of a single medical-grade honey, which contributes to the applicability of honey in medicine," said Dr. Sebastian A.J. Zaat...

To make the discovery, Dr. Zaat and colleagues investigated the antibacterial activity of medical-grade honey in test tubes against a panel of antibiotic-resistant, disease-causing bacteria. They developed a method to selectively neutralize the known antibacterial factors in honey and determine their individual antibacterial contributions. Ultimately, researchers isolated the defensin-1 protein, which is part of the honey bee immune system and is added by bees to honey. All bacteria tested, including Bacillus subtilis, methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase producing Escherichia coli, ciprofloxacin-resistant Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus faecium, were killed by 10–20% (v/v) honey, whereas 40% (v/v) of a honey-equivalent sugar solution was required for similar activity.

After analysis, the scientists concluded that the vast majority of honey's antibacterial properties come from that protein. This information also sheds light on the inner workings of honey bee immune systems, which may one day help breeders create healthier and heartier honey bees.

http://www.fasebj.org/cgi/content/abstract/24/7/2576