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.

 

Bristol-Myers Squibb Receives US FDA sNDA Approval for Use of SUSTIVA® (efavirenz) in HIV-1 Infected Pediatric Patients | BMS Newsroom

FDA Approves Tafinlar (dabrafenib) for Advanced Melanoma

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.

FDA Approves Tafinlar (dabrafenib) for Advanced Melanoma

FDA Approves Mekinist (trametinib) for Advanced Melanoma

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.

FDA Approves Mekinist (trametinib) for Advanced Melanoma

Cancer Fighting Foods.............

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.

Orange Juice:

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.

Milk:

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.

Beans:

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.

Salad :

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!

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)

Arbor Pharmaceuticals Announces FDA Approval of Nymalize

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).

Arbor Pharmaceuticals Announces FDA Approval of Nymalize

First drug to significantly improve heart failure mortality in over a decade

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."

First drug to significantly improve heart failure mortality in over a decade

Research aims for insecticide that targets malaria mosquitoes

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....

 Ref : http://www.sciencedirect.com/science/article/pii/S0048357513000655#f0025

Research aims for insecticide that targets malaria mosquitoes

Fish Oil Pills Might Cut Diabetes Risk....

Supplements, also known as omega-3 fatty acids, increase levels of a hormone called adiponectin that's linked to insulin sensitivity, Harvard researchers found. Higher levels of this hormone in the bloodstream have also been linked to a lower risk for heart disease.

"While prior animal studies found fish oil increased circulating adiponectin, whether similar effects apply in humans is not established," the study's lead author, Jason Wu, from the Harvard School of Public Health, said in a news release from the Endocrine Society.

For their study, the researchers conducted a "meta-analysis" of 14 clinical trials. A meta-analysis reviews existing research and attempts to find a consistent pattern. In this case, the studies that were reviewed were all randomized, placebo-controlled trials, which is considered the gold standard in research.

"By reviewing evidence from existing randomized clinical trials, we found that fish oil supplementation caused modest increases in adiponectin in the blood of humans," Wu explained.

Overall, the new study looked at 682 people who took fish oil supplements, and 641 who were given placebos such as sunflower or olive oil.

Among the people treated with fish oil, adiponectin levels increased by 0.37 micrograms per milliliter of blood. This hormone plays a beneficial role in processes that affect metabolism, such as blood sugar regulation and inflammation.

Because the effects of fish oil varied significantly in the studies analyzed, the researchers suggested that omega-3 fatty acids could have a stronger effect in certain groups of people. The investigators concluded that more research is needed to determine which people would benefit most from fish oil supplements.

"Although higher levels of adiponectin in the bloodstream have been linked to lower risk of diabetes and coronary heart disease, whether fish oil influences glucose [blood sugar] metabolism and development of type 2 diabetes remains unclear," Wu said.

More - Read at

Fish Oil Pills Might Cut Diabetes Risk, Researchers Say - Drugs.com MedNews

Mycobacterium tuberculosis is extraordinarily sensitive to killing by a vitamin C-induced Fenton reaction : Nature Communications : Nature Publishing Group

In a striking, unexpected discovery, researchers at Albert Einstein College of Medicine of Yeshiva University have determined that vitamin C kills drug-resistant tuberculosis (TB) bacteria in laboratory culture. The finding suggests that vitamin C added to existing TB drugs could shorten TB therapy, and it highlights a new area for drug design.

Dr. Jacobs and his colleagues observed that isoniazid-resistant TB bacteria were deficient in a molecule called mycothiol. "We hypothesized that TB bacteria that can't make mycothiol might contain more cysteine, an amino acid," said Dr. Jacobs. 

"So, we predicted that if we added isoniazid and cysteine to isoniazid-sensitive M. tuberculosis in culture, the bacteria would develop resistance. Instead, we ended up killing off the culture  something totally unexpected."

The Einstein team suspected that cysteine was helping to kill TB bacteria by acting as a "reducing agent" that triggers the production of reactive oxygen species (sometimes called free radicals), which can damage DNA.

"To test this hypothesis, we repeated the experiment using isoniazid and a different reducing agent vitamin C," said Dr. Jacobs. "The combination of isoniazid and vitamin C sterilized the M. tuberculosis culture. We were then amazed to discover that vitamin C by itself not only sterilized the drug-susceptible TB, but also sterilized MDR-TB and XDR-TB strains."

To justify testing vitamin C in a clinical trial, Dr. Jacobs needed to find the molecular mechanism by which vitamin C exerted its lethal effect. More research produced the answer: Vitamin C induced what is known as a Fenton reaction, causing iron to react with other molecules to create reactive oxygen species that kill the TB bacteria.

"We don't know whether vitamin C will work in humans, but we now have a rational basis for doing a clinical trial," said Dr. Jacobs. "It also helps that we know vitamin C is inexpensive, widely available and very safe to use. At the very least, this work shows us a new mechanism that we can exploit to attack TB.".....

Ref : http://www.einstein.yu.edu/news/releases/907/study-finds-vitamin-c-can-kill-drug-resistant-tb/


Mycobacterium tuberculosis is extraordinarily sensitive to killing by a vitamin C-induced Fenton reaction : Nature Communications : Nature Publishing Group

New tumor-killer shows great promise in suppressing cancers

A molecule  based on a natural protein present in human breast milk, which has been found to have strong and wide-ranging tumour killing properties when bound to certain lipids. Lipids are organic molecules like amino acids and carbohydrates, made up of carbon and hydrogen, and help to store energy and to form biological membranes.

The protein-lipid molecule complex, is known as HAMLET, which stands for Human Alpha-lactabumin Made Lethal to Tumour cells. It has been proven to be safe and effective as it only targets tumour cells, leaving healthy human cells intact.

HAMLET has most recently been shown to successfully suppress colon cancer in laboratory mice.

The scientists have also successfully identified and isolated specific components of HAMLET called peptide-oleate bound forms, which have the tumour-killing effect. Peptides are short chain amino acids commonly found in the human body.

These latest breakthroughs are led by Professor Catharina Svanborg and Dr Manoj Puthia from Lund University, Sweden, and Professor Gerhard Grüber from NTU's School of Biological Sciences. The HAMLET complex was first discovered by Professor Svanborg's research group.

The findings were published recently in Gut and in PLoS ONE. The researchers found that laboratory mice genetically modified to develop colon cancer, were protected to a large extent when fed with HAMLET- laced water. This suggested that HAMLET was killing emerging tumour cells faster than these cells could grow and proliferate.

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0053051

New tumor-killer shows great promise in suppressing cancers

Most Commonly Used Glaucoma Drug Can Cause Droopy Eyelids | Massachusetts Eye and Ear Infirmary

Prostaglandin analogues (PGAs), drugs which lower intraocular pressure, are often the first line of treatment for people with glaucoma, but their use is not without risks. PGAs have long been associated with blurred vision, dryness, changes in eye color and other side effects. Now a new study has found that these drugs also cause upper and lower eyelid drooping and other issues that can interfere with vision.

"We identified important side effects of PGAs, namely the loss of periorbital fat in the upper and lower lid and the presence of ptosis," said senior author Louis R. Pasquale, M.D., F.A.R.V.O., director of the Glaucoma Service at Mass. Eye and Ear and associate professor of ophthalmology at Harvard Medical School. "The loss of periorbital fat was previously described by us in a small series of unilateral PGA users. In fact, those observations did ultimately lead to a change in drug labeling. These new findings could change labeling for the PGAs, as the upper lid ptosis could aggravate pre-existing visual field loss."

Researchers performed this study to confirm whether prostaglandin-associated periorbitopathy (PAP) is clearly associated with PGA application among bilateral users using a validated grading scheme applied by masked observers and confirmed by clinical examination. They performed multivariable analyses to assess whether PAP was independently associated with PGA use or if it was the result of confounding features such as age, ethnicity, BMI or use of other classes of glaucoma medications. They studied 343 patients (186 females and 157 males) over the course of seven months in 2011.

The study showed associations between current bilateral PGA use and deepened upper eyelid sulci, hollowing of the inferior periorbital fat pads, upper eyelid ptosis with levator muscle dysfunction, and lower lid retraction. Their work demonstrated that PAP is fairly common and consists of findings that extend beyond deepening of the upper eyelid sulcus.

Most Commonly Used Glaucoma Drug Can Cause Droopy Eyelids | Massachusetts Eye and Ear Infirmary

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0061638

Scientists Uncover How Grapefruits Provide a Secret Weapon in Medical Drug Delivery...

Lipids (right panel first three tubes) derived from grapefruit. GNVs can efficiently deliver a variety of therapeutic agents, including DNA, RNA (DIR-GNVs), proteins and anti-cancer drugs (GNVs-Drugs) as demonstrated in this study. University of Louisville researchers have uncovered how to create nanoparticles using natural lipids derived from grapefruit, and have discovered how to use them as drug delivery vehicles.

"These nanoparticles, which we've named grapefruit-derived nanovectors (GNVs), are derived from an edible plant, and we believe they are less toxic for patients, result in less biohazardous waste for the environment, and are much cheaper to produce at large scale than nanoparticles made from synthetic materials," Zhang said.

The researchers demonstrated that GNVs can transport various therapeutic agents, including anti-cancer drugs, DNA/RNA and proteins such as antibodies. Treatment of animals with GNVs seemed to cause less adverse effects than treatment with drugs encapsulated in synthetic lipids.

"Our GNVs can be modified to target specific cells -- we can use them like missiles to carry a variety of therapeutic agents for the purpose of destroying diseased cells," he said. "Furthermore, we can do this at an affordable price."

The therapeutic potential of grapefruit derived nanoparticles was further validated through a Phase 1 clinical trial for treatment of colon cancer patients. So far, researchers have observed no toxicity in the patients who orally took the anti-inflammatory agent curcumin encapsulated in grapefruit nanoparticles.

Ref : http://www.nature.com/ncomms/journal/v4/n5/full/ncomms2886.html

Experimental drug beneficial in trial to treat a rare sarcoma

We know that, Cediranib (tentative trade name Recentin), also known as AZD2171, is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases. It is being developed by AstraZeneca as a possible anti-cancer chemotherapeutic agent for oral administration. Beginning in 2007, it is undergoing Phase I clinical trials for the treatment of non-small cell lung cancer, kidney cancer, and colorectal cancer in adults, as well as tumors of the central nervous system in children. Phase I trials of interactions with other drugs used in cancer treatment are also underway.\

On February 27, 2008, AstraZeneca announced that the use of Recentin in non-small cell lung cancer will not progress into phase III after failing to meet its main goal. On 8th March 2010, AstraZeneca issued a press-release stating that Recentin had failed Phase III clinical trials for use in first-line metastatic colorectal cancer when it was compared clinically with the market-leader bevacizumab. 

As of November 2012, it is currently in double-blind studies for the treatment of methylated Glioblastoma Multiforme at the University of Washington Medical Center at a 20mg daily dose.

Now...

Patients with advanced alveolar soft part sarcoma (ASPS), a rare cancer, achieved some control of their disease using an experimental anti-cancer drug called cediranib. The results from this largest clinical trial on ASPS to date were published online ahead of print on April 29, 2013, in the Journal of Clinical Oncology.

Ref : http://jco.ascopubs.org/content/early/2013/04/29/JCO.2012.47.4288

Experimental drug beneficial in trial to treat a rare sarcoma

Nearly five million asthmatics worldwide could benefit from antifungal therapy

Clinical studies have shown that oral antifungal drugs significantly improve symptoms and asthma control in asthmatics with ABPA, treatment endorsed by the Cochrane Collaboration. This is the first time that a global estimate of ABPA numbers has been made.

In national league tables of asthma rates in adults, only Australia and Sweden have a higher prevalence than the UK. In global league tables of ABPA occurrence, New Zealand tops the list with a 3.5% rate in new patients attending chest clinics at hospitals. The rates were 2.6% in Cape Town, 2.3% in Saudi Arabia, 2.5% in China and 0.7% in an older study from Ireland. No population-based studies have been done.

Itraconazole

Posaconazole

Voriconazole

In addition to standard asthma therapy, the antifungal therapy used is itraconazole  now a generic, inexpensive antifungal  with a response rate of 60%. The researchers also found that antifungal therapy also benefits patients with severe asthma sensitized to fungi, called SAFS.

Alternatives include voriconazole and posaconazole, which have 75-80% response rates. In a recent assessment of voriconazole and posaconazole for both ABPA and SAFS, 75% of patients were able to stop taking oral corticosteroids, a major benefit, and 38% of patients had their asthma severity downgraded on antifungal therapy.

Professor David Denning, professor of medicine and medical mycology at the University of Manchester and Director of the University Hospital of South Manchester's National Aspergillosis Centre, led the study into the total number of asthmatics worldwide. He said the study results implied that asthma admissions and deaths could be avoided with more extensive use of antifungal therapy.

"We were surprised by the number of patients with ABPA, and by the lack of community based studies done," he said. "Our National Aspergillosis Centre treats hundreds of these patients each year, generally with major improvement, and so a conscious program to seek out ABPA from all asthmatics is required."

Professor Donald Cole of the Dalla Lana School of Public Health at the University of Toronto was the senior author of the study and contributed his expert epidemiological knowledge to the development of the model and provided a 'reality' check of the model's estimates.

Nearly five million asthmatics worldwide could benefit from antifungal therapy