FDA Approves Juxtapid - New Orphan Drug for Rare Cholesterol Disorder

In continuation of my update on lomitapide..

US FDA, Juxtapid (lomitapide) to reduce low-density lipoprotein (LDL) cholesterol, total cholesterol, apolipoprotein B, and non-high-density lipoprotein (non-HDL) cholesterol in patients with homozygous familial hypercholesterolemia (HoFH). Juxtapid is intended for use in combination with a low fat diet and other lipid-lowering treatments.

FDA Approves Juxtapid - New Orphan Drug for Rare Cholesterol Disorder

FDA Approves Adasuve (loxapine) Inhalation Powder for the Acute Treatment of Agitation Associated with Schizophrenia or Bipo...

In continuation of my update on adasuve

FDA Approves Adasuve (loxapine) Inhalation Powder for the Acute Treatment of Agitation Associated with Schizophrenia or Bipo...

Discovery could increase efficacy of promising cystic fibrosis drug

We know that, Ivacaftor (trade name Kalydeco, developed as VX-770) is a potentiator approved for patients with the G551D mutation of cystic fibrosis. Ivacaftor was developed by Vertex Pharmaceuticals in conjunction with the Cystic Fibrosis Foundation.

Cystic fibrosis is caused by any one of several defects in a protein, cystic fibrosis transmembrane conductance regulator, which regulates fluid flow within cells and affects the components of sweat, digestive fluids, and mucus. The defect, which is caused by a mutation in the individual's DNA, can be in any of several locations along the protein, each of which interferes with a different function of the protein. G551D is a standard amino acid abbreviation for a mutation in which the amino acid glycine (G) in position 551 is replaced with aspartic acid (D). G551D is characterized by a dysfunctional CFTR protein on the cell surface. In the case of G551D, the protein is trafficked to the correct area, the epithelial cell surface, but once there the protein cannot transport chloride through the channel. Ivacaftor, a CFTR potentiator, improves the transport of chloride through the ion channel by binding to the channels directly to induce a non-conventional mode of gating which in turn increases the probability that the channel is open.

Accidental discovery of a mutation in CFTR, the R532 mutation, allowed MU researchers to reveal a new "non-strict coupling" relationship that occurs between the consumption of ATP, a molecule that provides energy in the body, and the opening and closing of the CFTR. They argue that the new information uncovered about this mechanism that controls the opening and closing of the CFTR and the passage of ions through it could explain how and where the new cystic fibrosis treatment Kalydeco (Vx-770) works.

"To his credit, Dr. Hwang exploited the behavior of the CFTR mutants to demonstrate that CFTR's gate is not strictly coupled to the nucleotide binding engine (NBD) that binds and splits ATP [energy] to drive conformational changes that regulate chloride flow through the CFTR protein channel," said colleague David Sheppard, PhD, an associate professor in the School of Physiology and Pharmacology at the University of Bristol in Bristol, U.K. who did not participate in the study.

In their study, MU researchers were able to observe the effects of the cystic fibrosis drug Vx-770 on the recently discovered R352 mutation. They found that Vx-770 enhances the activity of the CFTR channel by exploiting this "non-coupling" mechanism, a conclusion also supported by experimental results with the wild-type CFTR protein.

"Traditionally, researchers have defined how energy is utilized and transferred in the CFTR as a 'strict coupling' mechanism, meaning that one ATP molecule opens CFTR's gate, ions pass through and the ATP molecule is hydrolyzed and then the gate closes," Hwang said. "In this new model, we argue that the CFTR uses energy from ATP hydrolysis to carry out its function of chloride flow, but this coupling mechanism is more plastic than we thought and therefore could be subjective to manipulations by drugs such as Vx-770."

CFTR is part of a family of thousands of active transporter proteins called ABC proteins. Although CFTR may share many structural features with its ABC "cousins," as Hwang calls them, it has been unclear as to whether CFTR and its cousins may work in a similar manner.

The new idea of how the CFTR utilizes ATP to carry out its function may bear a broader implication because of the evolutionary relationship between CFTR and other ABC transporter proteins. It opens up a wide variety of therapeutic possibilities for other common diseases, such as cancer, heart disease and diabetes, Hwang said, since many other ABC proteins play critical roles in those human illnesses.

"It's taken years for scientists to solve this particular puzzle about the CFTR protein," Hwang said. "Our recent study provides evidence that these ABC transporter proteins and CFTR, a chloride channel, are two peas in a pod. Mother nature employs the same structural framework with just a little bit of modification to do two totally different things. From a basic science perspective, it's a big deal.".....

Ref : http://www.pnas.org/content/110/11/4404.abstract?sid=3e58deab-1076-4255-b20b-73ff47495950

Discovery could increase efficacy of promising cystic fibrosis drug

Pain reliever shows anti-viral activity against flu

In continuation of my update on naproxen

New influenza vaccines must be developed annually, because the surface proteins they target mutate rapidly, the way cars used to get a whole new look every year. The researchers, led by Anny Slama-Schwok of the Institut National de la Recherche Agronomique, Jouy en Josas, France, found a much more stable, reliable target for anti-influenza activity. The so-called ribonucleoprotein complexes are necessary for replication, and the researchers realized they could target the nucleoprotein, preventing assembly of the complexes. Because of its vital function, the nucleoprotein is highly conserved, making it a good potential target for antiviral drugs.

The nucleoprotein's three dimensional structure, solved in 2006, provided the basis for searching for new drugs that could interfere with its action. The researchers did a virtual screening within the Sigma-Aldrich online catalog of biochemicals. That screening identified Naproxen, better known as the over-the-counter pain reliever Aleve, and as expected, it bound to the nucleoprotein, and impeded RNA binding, says Slama-Schwok. In further testing, it reduced the viral load in cells infected with H1N1 and H3N2 influenza A virus, and in mice it demonstrated a therapeutic index against influenza A that was superior to that of any other anti-inflammatory drug.

Specifically, naproxen blocks the RNA binding groove of the nucleoprotein, preventing formation of the ribonucleoprotein complex, thus taking the vital nucleoproteins out of circulation. The researchers write that naproxen is a lead compound for drug development that could be improved by tweaking the molecule to boost its ability to bind to nucleoprotein.

As an already approved drug, naproxen could become a treatment against influenza relatively quickly, the researchers write. Its status as a non-steroidal anti-inflammatory drug (NSAID), which inhibits the COX-2 pathway, as well as an antiviral would boost its efficacy.

Ref : http://aac.asm.org/content/early/2013/02/26/AAC.02335-12.abstract?sid=e3391873-6ffe-4f2e-8737-685e5f2ca15f

Pain reliever shows anti-viral activity against flu

New chemo drug gentler on fertility, tougher on cancer

We know that, Arsenic trioxide is the inorganic compound with the formula As₂O₃. This commercially important oxide of arsenic is the main precursor to other arsenic compounds, including organoarsenic compounds. Approximately 50,000 tonnes are produced annually.Many applications are controversial given the high toxicity of arsenic compounds.

A Tiny Trojan Horse

The chemotherapy drug, arsenic trioxide, is packed into a very tiny Trojan horse called a nanobin. The nanobin consists of nano-size crystalline arsenic particles densely packed and encapsulated in a fat bubble. The fat bubble, a liposome, disguises the deadly cargo   half a million drug molecules.

"You have to wallop the tumor with a significant dose of arsenic but at the same time prevent exposure to normal tissue from the drug," said O'Halloran. The fat bubble is hundreds of times smaller than the average human cell. It is the perfect size to stealthily slip through holes in the leaky blood vessels that rapidly grow to feed tumors. The local environment of the tumor is often slightly acid; it is this acid that causes the nanobin to release its drug cargo and deliver a highly effective dose of arsenic where it is needed.

The scientists show this approach to packaging and delivering the active drug has the desired effect on the tumor cells but prevents damage to ovarian tissue, follicles or eggs.

While the drug is gentle on fertility, it is ferocious on cancer. When tested against lymphoma, it was more potent than the drug in its traditional free form.

"The drug was designed to maximize its effectiveness but reduce fertotoxicity," said O'Halloran, also the Morrison Professor of Chemistry in the Weinberg College of Arts and Sciences at Northwestern. "Many cancer drugs cause sterilization, that's why the reproductive tract is really important to focus on in the new stages of drug design. Other body systems get better when people stop taking the drug, but fertility you can't recover."

Arsenic trioxide was approved a few years ago for treating some types of blood cancers such as leukemia in humans, but O'Halloran thinks the arsenic trioxide nanobins can be used against breast cancer and other solid tumors. In his previously published preclinical research, nanobins were effective in reducing tumor growth in triple-negative breast cancer, which often doesn't respond well to traditional chemotherapy and has a poor survival rate.

Quick Test For Fertility Toxicity

Woodruff was able to show early effects of the drug on fertility by using an in vitro follicle culture and a quick, simple new test she developed. She compared the fertotoxicity of the nanobin and free drug and found the nanobin was much less toxic to female fertility than the free drug in the experimental model.

"The system can be adapted very easily for any cancer drug under development to get an early peek under the tent,"said Woodruff, also the Thomas J. Watkins Memorial Professor of Obstetrics and Gynecology at Feinberg. "As this new drug goes forward in development, we can say this is a good drug for young female cancer patients who are concerned about fertility."

The information gained from the toxicity test will help inform the treatment decisions of oncologists and their young female cancer patients to improve their chances of creating a future family.

"They may prescribe less toxic drug regimens or refer them to specialists in fertility preservation," Woodruff said...

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0058491

New chemo drug gentler on fertility, tougher on cancer

Positive results from Affinium Pharmaceuticals' Phase 2a clinical trial of AFN-1252 in ABSSSI

We know that, AFN-1252, is a selective inhibitor of Staphylococcus aureus enoyl-acyl carrier protein reductase (FabI), which is involved in fatty acid biosynthesis. 

Now, Affinium Pharmaceuticals announced today that its Phase 2a clinical trial evaluating oral AFN-1252   in acute bacterial skin & skin structure infections (ABSSSI) demonstrated excellent efficacy and safety data, marking a significant proof-of-concept milestone for Affinium's first-in-class, novel antibiotic targeted against bacterial fatty acid biosynthesis inhibition (FabI inhibitors).

A clinical study in 103 patients from 18 centers in the USA and Canada confirms excellent efficacy, safety and tolerability of 200 mg of oral AFN-1252 dosed twice daily for 5-14 days in patients with acute bacterial skin and skin structure infections (ABSSSI) due to Staphylococcus". Patients were recruited from outpatient or emergency room settings.   The enrolled patients had a variety of skin infections of ≥ 75 cm² in size, including severe abscesses (38%), cellulitis (27%), and wound infections (35%).  Investigators had the option of adding a second antibiotic to cover other potential pathogens or admitting the patient into the hospital. The vast majority of the patients were treated with oral AFN-1252 as monotherapy in the outpatient setting based on the suspicion of staphylococci from the clinical presentation and pretreatment Gram stain.  This study fully utilized recent FDA guidances for clinical trials in ABSSSI, including both entry and efficacy criteria.

Positive results from Affinium Pharmaceuticals' Phase 2a clinical trial of AFN-1252 in ABSSSI

Clinical Trials Move to the Petri Dish

In continuation of my update on azithromycinZithromax ....

The common antibiotic Zithromax received a new warning label from the U.S. Food and Drug Administration indicating it could cause dangerous arrhythmias in people with pre-existing heart conditions. Now, researchers at the Stanford University School of Medicine describe a “clinical trial in a dish” using patient-specific induced pluripotent stem, or iPS, cells to predict whether a drug will dangerously affect the heart’s function. The technique may be more accurate than the current in vitro drug-safety screening assays used by pharmaceutical companies, say the researchers, and may better protect patients from deadly side effects of common medications.

The technique allows scientists for the first time to test drugs directly on cells with mutations that cause hereditary cardiac diseases, rather than on the genetically modified human embryonic kidney cells or the Chinese hamster ovarian cells currently being used to detect cardiac toxicity.

The use of patient-specific iPS cells may help drug designers winnow heart-safe medications from those like the blockbuster anti-inflammatory drug Vioxx, which was withdrawn from the market because of unanticipated adverse cardiovascular events. It may also allow clinicians to identify sub-groups of patients, such as those with certain types of cardiac conditions, who should not be given certain drugs.

“Right now, the first time any drug sees a human heart cell is in a phase-1 clinical trial,” said Andrew Lee, a Stanford medical student and one of three lead authors of the study. “If adverse effects are seen, it can result in patient deaths, as in the case of the anti-inflammatory drug Vioxx or with cisapride, a drug previously used to treat digestive problems in people with diabetes. Right now, there are really no systematic studies to identify those people who are at risk.” Lee works in the laboratory of Joseph Wu, MD, PhD, who co-directs the Stanford Cardiovascular Institute, where the research was conducted.

The researchers anticipate that the technique, if adopted, could save millions of dollars and thousands of lives by streamlining the drug-testing process and increasing its sensitivity.

Clinical Trials Move to the Petri Dish

Soybeans can prevent cancer

Soybean meal is a bi-product following oil extraction from soybean seeds. It is rich in protein, which usually makes up around 40% of the nutritional components of the seeds and dependent on the line, and can also contain high oleic acid (a monounsaturated omega-9 fatty acid).

The study looked at the role soybeans could have in the prevention of cancer. Using a variety of soybean lines which were high in oleic acid and protein, the researchers looked to monitor bioactivity between the peptides derived from the meals of soybean and various types of human cancer cells.

The study showed that peptides derived from soybean meal significantly inhibited cell growth by 73% for colon cancer, 70% for liver cancer and 68% for lung cancer cells using human cell lines. This shows that the selected high oleic acid soybean lines could have a potential nutraceutical affect in helping to reduce the growth of several types of cancer cells.

Soybeans can prevent cancer

New class of anti-malarial compounds discovered

A group of researchers from 16 institutions around the world has identified a new class of anti-malarial compounds that target multiple stages of the malaria parasite's life cycle  These compounds could potentially be developed into drugs that treat and prevent malaria infection. Known as 4-(1H)-quinolone-3-diarylethers, the candidate anti-malarials are derived from a compound called endochin that effectively treats malaria in birds. When tested in the laboratory and in mice, the compounds demonstrated strong activity againstPlasmodium falciparum and Plasmodium vivax, the two parasites that cause most human cases of malaria. Transmitted via a mosquito bite, malaria causes cycles of chills, fever and fatigue, and is responsible for roughly 660,000 deaths per year, according to the World Health Organization. New drugs are needed because of the emergence of malaria-inducing parasites that are resistant to existing medications.

Of the 4-(1H)-quinolones, the researchers focused their efforts on the compound ELQ-300, which inhibited malaria parasites during the erythrocytic stage, when they cause symptoms in humans; as well as during the gametocyte and developmental stages in the mosquito, when the parasites are transmitted. In addition, when ELQ-300 was administered to mice infected with the Plasmodium species that cause malaria in mice, the infection was cured. The study results also suggested that the compound could be adapted into a once-daily dose in humans and would be slow to engender resistance. The researchers are currently proceeding with preclinical development of ELQ-300 (see the structure below).

Ref :1.  http://www.niaid.nih.gov/news/newsreleases/2013/Pages/ELQ300.aspx
2. http://stm.sciencemag.org/content/5/177/177ra37.short?rss=1

New class of anti-malarial compounds discovered

Drug treatment corrects autism symptoms in mouse model

The researchers tested suramin,  a well-known inhibitor of purinergic signaling used medically for the treatment of African sleeping sickness since shortly after it was synthesized in 1916 -- in mice. They found that this APT mediator corrected autism-like symptoms in the animal model, even if the treatment was started well after the onset of symptoms. The drug restored 17 types of multi-symptom abnormalities including normalizing brain synapse structure, cell-to-cell signaling, social behavior, motor coordination and normalizing mitochondrial metabolism.

"The striking effectiveness shown in this study using APT to 'reprogram' the cell danger response and reduce inflammation showcases an opportunity to develop a completely new class of anti-inflammatory drugs to treat autism and several other disorders," Naviaux said.

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0057380

 Drug treatment corrects autism symptoms in mouse model

Disinfectant mouthwashes may be effective against cancers of the mouth and throat

Patients who suffer from gingivitis are often advised to use disinfectant mouthwashes. In the future, the active ingredients in these products could be used in a completely different area. Chlorhexidin and Alexidin increase programmed cell death and may be effective against cancers of the mouth and throat.

Berg and his co-workers were successful: Chlorhexidin (below left structure), the active component in commercial oral disinfectants such as Chlorhexamed, Chlorhexal, Periogard, Corsodyl, and Chlorohex; as well as Alexidin (below right structure), the active component in Esemdent, both inhibit the binding of the apoptosis inhibitor to the apoptosis trigger. Chlorhexidin's effect is specific, while Alexidin has additional very weak effects on other proteins.

Why are apoptosis proteins interesting? Apoptosis is decreased in tumor cells, so the cells do not die off and continue to divide. One reason for this is that they produce too much of the apoptosis-inhibiting protein. In experiments with cultures of cells from various tongue and throat carcinomas, both compounds caused increased apoptosis. This effect is much stronger in the cancer cells than in healthy cells. It may be possible to use these drugs in therapeutic applications.

The researchers hope to find other protein-protein interactions that could be targeted with approved small-molecule drugs....

http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1521-3773/homepage/press/201311press.html

Disinfectant mouthwashes may be effective against cancers of the mouth and throat

Researchers identifiy elusive anti-cancer property of vitamin E

Researchers identifiy elusive anti-cancer property of vitamin E

Japanese P2 study shows potential of combined vaccine and steroid drug in castration resistant PCa

 In continuation of my update on dexamethasone

Multi-peptide vaccination therapy combined with the low-dose steroid drug dexamethasone shows promise in treating chemotherapy-naive castration resistant prostate cancer (CRPC) patients.

Japanese P2 study shows potential of combined vaccine and steroid drug in castration resistant PCa

New drugs may improve quality of life for people with Parkinson's disease

In the study, 225 people were randomized to receive either eight weeks of stable dose treatment with a placebo or the drug droxidopa, (see structure)  

 

which converts to norepinephrine. After one week of stable treatment, those who received the drug had a clinically meaningful, two-fold decrease in the symptoms of dizziness and lightheadedness, when compared to placebo. They also had fewer falls, or 0.38 falls per patient per week, compared to 1.73 for those receiving a placebo on average over the entire 10-week study duration.

The second study looked at treatment with a new drug for "wearing-off" that occurs with people who have been taking levodopa for several years. As each dose wears off, people experience longer periods of time where the motor symptoms do not respond to levodopa. For the study, 420 people who were experiencing an average of six hours of "off" time per day received a placebo or one of four dosages of the drug tozadenant in addition to their levodopa for 12 weeks. People receiving two of the dosages of the drug had slightly more than an hour less off time per day at the end of 12 weeks than they had at the start of the study. They also did not have more troublesome involuntary movements during their "on" time, called dyskinesia, that can occur. 

 
The third study looked at 321 people with early Parkinson's disease whose symptoms were not well-controlled by a dopamine agonist drug. For the 18-week study, the participants took either the drug rasagiline or a placebo in addition to their dopamine agonist. At the end of the study, those taking rasagiline had improved by 2.4 points on a Parkinson's disease rating scale. In addition, rasagiline was well tolerated with adverse events similar to placebo.

New drugs may improve quality of life for people with Parkinson's disease

Breakthrough in battle against leukemia

The research team has demonstrated that leukaemic cells can be eradicated by removing a carbohydrate modification displayed on the cell's surface.

Director of Griffith University's Institute for Glycomics, Professor Mark von Itzstein is the Australian team leader. He said the discovery is an important advance against leukemia, a cancer of malignant white blood cells that multiply uncontrollably. Acute lymphoblastic leukemia (ALL) is the most common childhood cancer.

"We have found that the leukaemic cell has an altered cell surface carbohydrate decoration compared to normal cells and this also conveys resistance to drug treatment," Professor von Itzstein said.

"We have now shown that with the removal of this carbohydrate alteration the cells die."

Professors Nora Heisterkamp and John Groffen, leaders of the US-based team, Professor von Itzstein and their colleagues have published their research findings in the latest edition of the Journal of Experimental Medicine.

Professor von Itzstein said the research could lead to new ways to fight the disease, particularly where it has become treatment resistant.

"Up until 40 years ago, only one child in five survived ALL," but advances in chemotherapy have changed that outcome and now nearly 80 percent of children with ALL will be cured," Professor von Itzstein said.

"For the remaining 20 percent, however, the disease returns necessitating additional rounds of intensive chemotherapy. Unfortunately, most relapsed patients die within one year because their cancer cells are resistant to chemotherapy.

Breakthrough in battle against leukemia

Drug may improve outcomes after heart attack

 We know that, Eplerenone (INN)  is an aldosterone antagonist used as an adjunct in the management of chronic heart failure. It is similar to the diuretic spironolactone, though it is much more selective for the mineralocorticoid receptor in comparison (i.e., does not possess any antiandrogen, progestogen, or estrogenic effects), and is specifically marketed for reducing cardiovascular risk in patients following myocardial infarction. It is marketed by Pfizer under the trade name Inspra. Eplerenone is a potassium-sparing diuretic, meaning that it helps the body get rid of water but still keep potassium....

Now,

The REMINDER (Reduction of heart failure morbidity in patients with acute ST-elevation myocardial infarction) trial was a randomized, double-blind trial of 1,012 patients who had a heart attack caused by a complete blockage of one of the heart's arteries. Patients had no signs or history of heart failure. They were given either eplerenone or placebo in addition to standard therapy. Overall, patients taking eplerenone were 38 percent less likely to have poor outcomes than those given a placebo.

Eplerenone counteracts a hormone called aldosterone, which can increase blood pressure. The drug is currently approved to treat hypertension and as a treatment for patients who have heart failure several days after a heart attack.

"This is the first randomized trial to test a mineralocorticoid receptor agonist during the acute phase of heart attack, and the results suggest a clinical benefit," said Gilles Montalescot, MD, PhD, lead investigator of the study and professor of cardiology and head of the Cardiac Care Unit at Pitié-Salpétrière Hospital, Paris.

About 5.8 million Americans have heart failure, a condition in which the heart cannot pump enough blood to meet the body's oxygen and energy needs. Improvements in heart attack treatment have increased chances of survival, but damage after heart attack is one risk factor for heart failure. Clinical trials and registries show that in the 30 days after a first heart attack, between 8.6 percent and 40 percent of patients will be diagnosed with heart failure.

Drug may improve outcomes after heart attack

Clot-busting drug as effective as angioplasty, study suggests

 A clot-busting therapy may benefit some heart attack patients who cannot have immediate angioplasty, according to research presented today at the American College of Cardiology's 62nd Annual Scientific Session.

Clot-busting drug as effective as angioplasty, study suggests

Promising new drug treats and protects against radiotherapy-associated oral mucositis

Mouse model studies show that administered genetically or topically, protein Smad7 protects against or heals mouth sores commonly associated with cancer treatment.

Ref : http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3118.html

Promising new drug treats and protects against radiotherapy-associated oral mucositis

Bitter melon juice prevents pancreatic cancer in mouse models

"Three years ago researchers showed the effect of bitter melon extract on breast cancer cells only in a Petri dish. This study goes much, much farther. We used the juice  people especially in Asian countries are already consuming it in quantity. We show that it affects the glucose metabolism pathway to restrict energy and kill pancreatic cancer cells," says Rajesh Agarwal, PhD, co-program leader of Cancer Prevention and Control at the CU Cancer Center and professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences.

Agarwal's interest came from connecting the dots of existing research in a novel way. Diabetes tends to presage pancreatic cancer and bitter melon has been shown to effect type-II diabetes, and has been used for centuries against diabetes in the folk medicines of China and India. Following this line of thinking, Agarwal and colleagues wondered what would happen if they closed out the middle man of diabetes and directly explored the link between bitter melon and pancreatic cancer.

The result, Agarwal says, is, "Alteration in metabolic events in pancreatic cancer cells and an activation of the AMP-activated protein kinase, an enzyme that indicates low energy levels in the cells."

Perhaps not coincidentally, bitter melon also regulates insulin secretion by pancreatic beta cells. After studies in cell cultures, the group showed that mouse models of pancreatic cancer that were fed bitter melon juice were 60 percent less likely to develop the disease than controls.

"It's a very exciting finding," Agarwal says. "Many researchers are engineering new drugs to target cancer cells' ability to supply themselves with energy, and here we have a naturally-occurring compound that may do just that."

The Agarwal Lab is now applying for grants that will allow them to move the study of bitter melon into further chemoprevention trials in mouse models of pancreatic cancer.

Ref : dx.doi.org/10.1093/carcin/bgt081

 

Bitter melon juice prevents pancreatic cancer in mouse models

New Drugs May Offer Hope to Parkinson's Patients - Drugs.com MedNews

"Progress is being made to expand our use of medications, develop new medications and to treat symptoms that either we haven't been able to treat effectively or we didn't realize were problems for patients," said Dr. Robert Hauser, professor of neurology and director of the University of South Florida Parkinson's Disease and Movement Disorders Center in Tampa.

Parkinson's disease, a degenerative brain disorder, affects more than 1 million Americans. It destroys nerve cells in the brain that make dopamine, which helps control muscle movement. Patients experience shaking or tremors, slowness of movement, balance problems and a stiffness or rigidity in arms and legs.

In one study, Hauser evaluated the drug droxidopa (see the structure right),  which is not yet approved for use in the United States, to help patients who experience a rapid fall in blood pressure when they stand up, which causes light-headedness and dizziness. About one-fifth of Parkinson's patients have this problem, which is due to a failure of the autonomic nervous system to release enough of the hormone norepinephrine when posture changes.

Hauser studied 225 people with this blood-pressure problem, assigning half to a placebo group and half to take droxidopa for 10 weeks. The drug changes into norepinephrine in the body.

Those on the medicine had a two-fold decline in dizziness and lightheadedness compared to the placebo group. They had fewer falls, too, although it was not a statistically significant decline.

In a second study, Hauser assessed 420 patients who experienced a daily "wearing off" of the Parkinson's medicine levodopa (see structure left), during which their symptoms didn't respond to the drug. He compared those who took different doses of a new drug called tozadenant, which is not yet approved, with those who took a placebo. All still took the levodopa.

At the start of the study, the patients had an average of six hours of "off time" a day when symptoms reappeared. After 12 weeks, those on a 120-milligram or 180-milligram dose of tozadenant (see structure below) had about an hour less of "off time" each day than they had at the start of the study.

Tozadenant, which works on brain receptors thought to regulate motor function, merits further study in future trials, Hauser said.

In another study, Hauser looked at 321 patients with early stage Parkinson's whose symptoms weren't handled well by a medicine called a dopamine agonist, typically the first drug prescribed for Parkinson's patients. During the 18-week study, Hauser assigned them to take either their usual medicine plus an add-on drug called rasagiline (brand name Azilect see below structure) or their usual medicine and a placebo.

Azilect is approved for use in patients with early stage disease as a single therapy or as an add-on to levodopa, Hauser said, but not yet as an add-on to dopamine agonists.

Those taking the Azilect   but not those taking the placebo   improved by 2.4 points on a standard Parkinson's disease rating scale.

Costs of the still unapproved drugs are not known. Azilect costs about $200 monthly at the 1-milligram daily dose used in the study.

Each of the studies was funded by the pharmaceutical company making the particular drug: Chelsea Therapeutics paid for the blood-pressure study; Biotie Therapies Inc., supported the "wearing-off" study; and Teva Pharmaceutical Industries sponsored the Azilect study. Hauser is a consultant for all three companies.

New Drugs May Offer Hope to Parkinson's Patients - Drugs.com MedNews

Can Green Tea, Coffee Reduce Stroke Risk? - Drugs.com MedNews

In continuation of my update on green tea...

This study of about 83,000 people suggests that drinking green tea or coffee daily might lower stroke risk by about 20 percent, with even more protection against a specific type of stroke.

"The regular action of daily drinking [of] green tea and coffee is a benefit in preventing stroke," said lead researcher Dr. Yoshihiro Kokubo, chief doctor in the department of preventive cardiology at the National Cerebral and Cardiovascular Center, in Osaka.

"If you cannot readily improve your lifestyle, try to prevent stroke by drinking green tea every day," he said.

Although it isn't certain why coffee and tea may have this effect, Kokubo thinks it might be due to certain properties in these drinks that keep blood from clotting.

In addition, green tea contains catechins, which have an antioxidant, anti-inflammatory effect. Some chemicals in coffee, such as chlorogenic acid, may cut the risk of stroke by lowering the chances of developing type 2 diabetes, he explained.

Coffee also contains caffeine, which may have an impact on cholesterol levels and blood pressure, and may cause changes in insulin sensitivity, which affects blood sugar, he added.

One expert, Dr. Ralph Sacco, past president of the American Heart Association, cautioned that this type of study cannot say for sure that the lower risk of stroke is really the result of drinking coffee or tea.

"Such association studies are still limited in [the] ability to tell whether it is some ingredients in the coffee or tea or some other behavior common to coffee and tea drinkers that is driving the protective effects," said Sacco, chairman of neurology at the University of Miami Miller School of Medicine.

Can Green Tea, Coffee Reduce Stroke Risk? - Drugs.com MedNews

Novel drug seems to increase effectiveness of usual chemotherapy against IBC

Novel drug seems to increase effectiveness of usual chemotherapy against IBC

Grape seed and skin extract: A weapon in the fight against kidney disease caused by high-fat diets

Researchers examined the effect of GSSE processed from a grape cultivar ('Carignan') of Vitis vinifera from northern Tunisia on rats. Rats were fed a high-fat diet that induced a low-grade reno-lipotoxicity, that is, kidney damage associated with lipids. This was characterized by elevations in plasma urea and protein in the urine. The researchers found increased deposits of triglycerides (TG) (especially saturated fatty acids), increased signs of oxidative stress and depleted copper levels in the kidneys. There was also histological evidence of disturbance in the kidney structure. When the animals received GSSE at 500 mg/kg bw (which corresponds to 35g/day for a 70 kg human adult) along with the high-fat diet there was a partial reversal of the TG deposition as well as the histological damage. The authors suggest polyphenols including resveratrol are likely the components in GSSE responsible for the positive effects. Furthermore the GSSE prevented the oxidative stress and copper depletion.

"In our research, obesity-induced leaky kidney and proteinuria are shown to be prevented by GSSE, which suggests the use of GSSE as a preventive nutriceutical for high-risk patients," said co-author Kamel Charradi, a researcher with the Laboratory of Bioactive Substance at the Center of Biotechnology of Borj-Cedria (CBBC) in Tunisia. This research group has previously published work showing the benefits of GSSE in combating obesity, heart dysfunction, brain lipotoxicity and kidney cancer.....

Ref : http://www.nrcresearchpress.com/doi/story/10.4141/news.2013.02.27.116#.UTM-5KJTCYk

Grape seed and skin extract: A weapon in the fight against kidney disease caused by high-fat diets

New chemical probe provides tool to investigate role of malignant brain tumor domains in chromatin structure and regulation

Researchers lead by assistant professor in the lab of Stephen Frye, Fred Eshelman Distinguished Professor in the UNC School of Pharmacy and member of the UNC Lineberger Comprehensive Cancer Center, announced the discovery of a chemical probe that can be used to investigate the L3MBTL3 methyl-lysine reader domain. The probe, named UNC1215, will provide researchers with a powerful tool to investigate the function of malignant brain tumor (MBT) domain proteins in biology and disease.....

New chemical probe provides tool to investigate role of malignant brain tumor domains in chromatin structure and regulation

High-Fiber Diet Helps Heart Too, Expert Says - Drugs.com MedNews

Eating a high-fiber diet does more than promote digestive well-being; it's also good for your heart, an expert says.

 

Dietary fiber from fruits, vegetables, whole grains and beans "has been shown in research to help lower cholesterol," Jody Gilchrist, a nurse practitioner at the Heart and Vascular Clinic at the University of Alabama, Birmingham.

"Most nutrition experts say that a person needs at least 25 grams of fiber a day as part of a balanced diet," Gilchrist said. "The American Heart Association recommends that a good rule of thumb is 14 grams of fiber for every 1,000 calories consumed, and at least 10 grams should come from soluble fiber."

Soluble fiber makes you feel full quickly, which helps control how much you eat. Research has shown that soluble fiber also helps lower "bad" LDL cholesterol by interfering with how the body absorbs cholesterol from foods.

High-Fiber Diet Helps Heart Too, Expert Says - Drugs.com MedNews

Pernix Therapeutics Receives FDA Approval for Vituz

Pernix Therapeutics Receives FDA Approval for Vituz

FDA Approves Stivarga for Advanced Gastrointestinal Stromal Tumors

In continuation of my update on  Regorafenib (BAY 73-4506)

FDA Approves Stivarga for Advanced Gastrointestinal Stromal Tumors