Drug may guard against periodontitis, related chronic diseases

A drug currently used to treat intestinal worms could protect people from periodontitis, an advanced gum disease, which untreated can erode the structures   including bone   that hold the teeth in the jaw. The research was published ahead of print in Antimicrobial Agents and Chemotherapy. Current treatment for periodontitis involves scraping dental plaque, which is a polymicrobial biofilm, off of the root of the tooth. Despite this unpleasant and costly ordeal, the biofilm frequently grows back. But the investigators showed in an animal model of periodontitis that the drug Oxantel inhibits this growth by interfering with an enzyme that bacteria require for biofilm formation, says corresponding author Eric Reynolds, of the University of Melbourne, Australia. It does so in a dose-dependent manner, indicating efficacy.

The researchers began their search for a therapy for periodontitis by studying the symbioses of the periodontal pathogens, using genomics, proteomics, and metabolomics, in animal models of periodontitis. They soon found that the periodontal biofilm depended for growth on the availability of iron and heme (an iron-containing molecule related to hemoglobin), and that restricting these reduced levels of the enzyme, fumarate reductase. Since Oxantel (see structure)  was known to inhibit fumarate reductase in some bacteria, they then successfully tested its ability to inhibit fumarate reductase activity in Porphyromonas gingivalis, one of the major bacterial components of periodontitis biofilms. Fumarate reductase is absent from humans, making it an ideal drug target.

They also showed that Oxantel disrupted the growth of polymicrobial biofilms containing P. gingivalis, Tannerella forsythia, and Treponema denticola, a typical composition of periodontal biofilms, despite the fact that the latter alone is unaffected by Oxantel.

The researchers found that treatment with Oxantel downregulated six P. gingivalis gene products, and upregulated 22 gene products, all of which are part of a regulon (a genetic unit) that controls availability of heme.

Periodontitis affects an estimated 30-47 percent of the adult population with severe forms affecting 5-10 percent. It also increases the risks of diabetes, heart disease, stroke, arthritis, and dementia, says Reynolds. These risks arise due to the pathogenic bacteria that enter the blood stream from periodontitis, as well as from the chronic inflammation caused by this disease, he says. Additionally, periodontitis correlates with increased risk of cancers of the head and neck, the esophagus, the tongue, and the pancreas, the investigators report.

http://aac.asm.org/content/early/2013/10/22/AAC.01375-13

Drug may guard against periodontitis, related chronic diseases

Peptide derived from cow's milk kills human stomach cancer cells in culture

New research from a team of researchers in Taiwan indicates that a peptide fragment derived from cow's milk, known as lactoferricin B25 (LFcinB25), exhibited potent anticancer capability against human stomach cancer cell cultures. The findings, published in the Journal of Dairy Science^®, provide support for future use of LFcinB25 as a potential therapeutic agent for gastric cancer.

"Gastric cancer is one of the most common causes of cancer-related mortality worldwide, especially in Asian countries," says Wei-Jung Chen, PhD, of the Department of Biotechnology and Animal Science of National Ilan University, Taiwan Republic of China. "In general, the main curative therapies for gastric cancer are surgery and chemotherapy, which are generally only successful if the cancer is diagnosed at an early stage. Novel treatment strategies to improve prognosis are urgently needed."

Investigators evaluated the effects of three peptide fragments derived from lactoferricin B, a peptide in milk that has antimicrobial properties. Only one of the fragments, LFcinB25 reduced the survival of human AGS (Gastric Adenocarcinoma) cells in a dose-dependent and time-dependent manner.

Under a microscope the investigators could see that after an hour of exposure to the gastric cancer cells, LFcinB25 migrated to the cell membrane of the AGS cells, and within 24 hours the cancer cells had shrunken in size and lost their ability to adhere to surfaces. In the early stages of exposure, LFcinB25 reduced cell viability through both apoptosis (programmed cell death) and autophagy (degradation and recycling of obsolete or damaged cell parts). At later stages, apoptosis appeared to dominate, possibly through caspase-dependent mechanisms, and autophagy waned.

"This is the first report describing interplay between apoptosis and autophagy in LFcinB-induced cell death of cancer cells," says Dr. Chen.

Ref : http://www.journalofdairyscience.org/article/S0022-0302(13)00722-4/abstract

Peptide derived from cow's milk kills human stomach cancer cells in culture

New antifungal composition effectively inhibits wide variety of fungi

In order to overcome resistance to antifungal variety of pathogenic fungi and yeast, researchers from the University of Alicante have developed a novel and efficient antifungal composition with pharmacological applications in agriculture and food industry, among others. 

The composition, developed and patented by the UA Research Group in Plant Pathology, is based on the combined use of chitosan, or chitosan oligosaccharides (right structure, COS), antifungal agents and additives that synergistically affect the growth of a variety of pathogenic fungi.

"Chitosan is a non-toxic biopolymer, biocompatible and naturally degradable, with antibacterial, antiviral and antifungal properties obtained from chitin, the main constituent of hard body parts of invertebrates, such as the shells of shrimp, lobsters, crabs, and other marine crustaceans, and is part of the fungal cell wall," as explained by lecturer Luis Vicente López Llorca, Director of the UA Research Group in Plant Pathology and head of the research work.

"Because many fungal pathogens develop resistance to prolonged treatment with antifungal drugs, it is desirable to find alternatives for their control in medical, agricultural and those applications in which the fungi cause damage. In clinics, pathogenic fungi resistant to antifungal drugs are a major cause of mortality in patients. Chitosan and the antifungal additives, some based on the identification of molecular targets of chitosan, contribute to produce a novel alternative to control fungal diseases and in particular antifungal resistant strains" López Llorca said.

The various experiments carried out by the research group are proof of the significant synergistic effect of the combination of chitosan (or COS) and other antifungals and ARL1 gene inhibitor, in inhibiting the growth of mold and yeast . "Chitosan is nontoxic to mammals, making it suitable for use as an antifungal in various applications," Luís Vicente López adds.

New antifungal composition effectively inhibits wide variety of fungi

First in-human trial of endoxifen shows promise as breast cancer treatment

Estrogen receptor α (ERα) ligand; potent antiestrogen. Metabolite of tamoxifen (Cat. No. 0999). Primary metabolite responsible for the effectiveness of tamoxifen in ER-positive breast cancer...

First in-human trial of endoxifen shows promise as breast cancer treatment

Compound in grapes, red wine could help treat multiple types of cancer

In continuation of my update on resveratrol

A recent study by a University of Missouri researcher shows that resveratrol, a compound found in grape skins and red wine, can make certain tumor cells more susceptible to radiation treatment. This research, which studied melanoma cells, follows a previous MU study that found similar results in the treatment of prostate cancer. The next step is for researchers to develop a successful method to deliver the compound to tumor sites and potentially treat many types of cancers.

"Our study investigated how resveratrol and radiotherapy inhibit the survival of melanoma cells," said Michael Nicholl, MD, assistant professor of surgery at the MU School of Medicine and surgical oncologist at Ellis Fischel Cancer Center in Columbia, Mo. "This work expands upon our previous success with resveratrol and radiation in prostate cancer. Because of difficulties involved in delivery of adequate amounts of resveratrol to melanoma tumors, the compound is probably not an effective treatment for advanced melanoma at this time."

The study found that melanoma cells become more susceptible to radiation if they were treated first with resveratrol. The MU researcher found that when the cancer was treated with resveratrol alone, 44 percent of the tumor cells were killed. When the cancer cells were treated with a combination of both resveratrol and radiation, 65 percent of the tumor cells died.

Nicholl said his findings could lead to more research into the cancer-fighting benefits of the naturally occurring compound.

"We've seen glimmers of possibilities, and it seems that resveratrol could potentially be very important in treating a variety of cancers," Nicholl said. "It comes down to how to administer the resveratrol. If we can develop a successful way to deliver the compound to tumor sites, resveratrol could potentially be used to treat many types of cancers. Melanoma is very tricky due to the nature of how the cancer cells travel throughout the body, but we envision resveratrol could be combined with radiation to treat symptomatic metastatic tumors, which can develop in the brain or bone."

Ref : http://dx.doi.org/10.1016/j.jss.2013.02.037

Compound in grapes, red wine could help treat multiple types of cancer

Broccoli compound protects rats from lethal radiation....

In continuation of my update on 3,3′-Diindolylmethane...

We know that, 3,3′-Diindolylmethane or DIM is a compound derived from the digestion of indole-3-carbinol, found in cruciferous vegetables such as broccoli, Brussels sprouts, cabbage and kale. The reputation of Brassica vegetables as healthy foods rests in part on the activities of diindolylmethane. Also DIM has the biological properties listed in the chart below....

Now researchers, have found that, DIM compound protected rodents from lethal doses of radiation in recent experiments....

Broccoli compound protects rats from lethal radiation | Science News

Toxicity limits benefits of bevacizumab–erlotinib NSCLC maintenance therapy

In continuation of my update on bevacizumab and erlotinib 

Two targeted anticancer drugs used together after first-line chemotherapy for advanced stage non-small-cell lung cancer (NSCLC) improve progression-free survival (PFS), the results of a large, prospective study show.

Median PFS was 4.8 months for patients treated with bevacizumab plus erlotinib versus 3.7 months for those treated with bevacizumab plus placebo (hazard ratio [HR] = 0.71). There was no overall survival (OS) advantage, however, and the two-drug combination was associated with more adverse events than bevacizumab alone, say the study investigators.

Toxicity limits benefits of bevacizumab–erlotinib NSCLC maintenance therapy

A potential new class of fast-acting antidepressant

Scientists from the University of Chicago have discovered that selectively blocking a serotonin receptor subtype induces fast-acting antidepressant effects in mice, indicating a potential new class of therapeutics for depression. The work was published Oct. 29 in Molecular Psychiatry.

Of the subtypes, serotonin 2C receptors stood out. Selectively blocking these receptors in mice significantly reduced depression-like behaviors in only five days, compared to a minimum of two weeks for a control antidepressant medication.

"We observed fast-acting therapeutic effects in multiple behavioral tasks after we administered compounds that selectively block serotonin 2C receptors," said Mark Opal, a graduate student at the University of Chicago and lead author of the paper. "We began our measurements at five days, but we think there's a possibility it could be effective even sooner than that."

Serotonin 2C receptors normally inhibit the release of dopamine, another neurotransmitter commonly associated with mood, from certain neurons. When 2C is blocked, the researchers believe, more dopamine is released into regions of the brain such as the prefrontal cortex. The team also observed the induction of biomarkers that indicate antidepressant action.

This is the first new biological mechanism that has shown the ability to rapidly alleviate symptoms of depression since ketamine and scopolamine, and it potentially represents a much safer alternative. Some current antidepressants on the market already affect serotonin 2C receptors, although not selectively, and Dulawa believes the safety profile is favorable for human use. The team is now investigating compounds suitable for clinical trials.

"One of the primary advantages to our discovery is that this is much more of an innocuous target than others that have been identified," Dulawa said.

A potential new class of fast-acting antidepressant

Olysio (simeprevir) Approved By FDA To Treat Hepatitis C Virus | MediMoon

We know that, Simeprevir (see structure below, formerly TMC435; trade name Olysio) is a drug for the treatment and cure of hepatitis C. It was developed by Medivir and Johnson & Johnson's pharmaceutical division Janssen Pharmaceutica. In the United States, simeprevir is approved by the Food and Drug Administration for use in combination withpeginterferon-alfa and ribavirin. Simeprevir has been approved in Japan for the treatment of chronic hepatitis C infection, genotype 1

Olysio (simeprevir) Approved By FDA To Treat Hepatitis C Virus | MediMoon

Health Benefits of Ragi | Medindia

Finger millet (Eleusine coracana L.) also known as Ragi in India is one of the important cereals which occupies the highest area under cultivation among the small millets. The state of Karnataka is the largest producer of ragi in India. Ragi is a crop which can withstand severe drought conditions and can be easily grown throughout the year. Nutritionally, when ragi is used as a whole grain, it is higher in protein and minerals in comparison to all other cereals and millets. It is a remarkable source of protein, making it perfect for vegetarian diets.....

 

Finger millet contains important amino acids viz., isoleucine, leucine, methionine and phenyl alanine which are not present in other starchy meals. It has the highest amount of calcium (344 mg %) and potassium (408 mg %). Ragi is a great source of iron making it beneficial for individuals with low hemoglobin levels.        

Millets also contains B vitamins, especially niacin, B6 and folic acid. Some of the health benefits of ragi are attributed to its polyphenol and dietary fiber contents. Due to its high content of polyphenols and dietary fiber ragi exhibits anti-diabetic and antioxidant and antimicrobial properties; it protects against tumors and atherosclerosis (narrowing and hardening of blood vessels). Being low in fat and gluten free, ragi is easy to digest. It is therefore, given as first foods to babies in the form of ragi porridge.

Malted ragi grains are ground and consumed, mixed with milk, boiled water or yogurt. In southern parts of India, it is a recommended food, by doctors, for infants of six months and above because of its high nutritional content. Homemade ragi malt is one of the most popular infant foods till date.  Malting characteristics of finger millet are superior to other millets. On malting the vitamin-C is elaborated, phosphorus availability is increased, digestion is easier and amino acids are synthesized. In south India, the malted ragi flour is extensively used in preparation of weaning foods, instant mixes and beverages.

Despite finger millet's rich nutrient profile, low cost and easy availability recent studies indicate its lower consumption in general by urban Indians. Obesity has become a matter of health concern in India. Unhealthy foods have increasingly become a part of the food choices made by youth. Large populations of children in the country are malnourished and are deficient in calcium and protein. The millet ragi then could be the answer to all the above problems relating to nutrient deficiencies. Ragi is truly a wonder cereal grain and should be consciously incorporated in the diets in one way or the other.

 

Health Benefits of Ragi | Medindia

New Drug Shows Early Promise in Treating Parkinson's Psychosis

We know that, Pimavanserin (ACP-103) is a drug developed by Acadia Pharmaceuticals which acts as an inverse agonist on the serotonin receptorsubtype 5-HT_2A, with 40x selectivity over 5-HT_2C, and no significant affinity or activity at 5-HT_2B or dopamine receptors. As of September 3 2009, pimavanserin has not met expectations for Phase III clinical trials for the treatment of Parkinson's disease psychosis, and is in Phase II trials for adjunctive treatment of schizophrenia alongside an antipsychotic medication. It is expected to improve the effectiveness and side effect profile of antipsychotics...

Now  a study published in the Nov. 1 online issue of The Lancet and funded by Acadia Pharmaceuticals, the makers of pimavanserin.

"There are no first-line approved treatments for psychosis in people with Parkinson's disease," said lead researcher Dr. Clive Ballard, a professor of age-related diseases at King's College, London.

"Existing antipsychotics are either ineffective or not tolerated. Pimavanserin is not yet licensed, but could potentially offer a change in the treatment of these distressing and impactful symptoms," he said.

An expert not involved with the study talked about the need for a medication alternative.

"The Parkinson's disease community has been waiting for a potentially new approach for the treatment of psychosis and hallucinations," said Dr. Michael Okun, national medical director of the National Parkinson Foundation.

New Drug Shows Early Promise in Treating Parkinson's Psychosis - Drugs.com MedNews

Researchers identify potential way to combat TB

Researchers have identified a potential way to manipulate the immune system to improve its ability to fight off tuberculosis (TB).

TB is a major problem for both humans and cattle and the new findings could help scientists to create better drugs to combat the disease in both.

The disease is caused by the bacterium Mycobacterium tuberculosis, which infects the lungs. The mycobacteria are able to establish persistent TB infections by taking up residence in macrophages - cells of the immune system that would normally destroy invading microorganisms.

Now, in early stage research published in the Journal of Biological Chemistry, researchers from Imperial College London and Stanford University have revealed precisely how unusual sugars on the surface of the mycobacteria that cause TB are able to latch onto the macrophages and disarm them. They now hope that scientists at Imperial and elsewhere can use this knowledge to develop small molecule drugs that latch tightly onto the same site.

These drugs could potentially fight tuberculosis in a number of ways, say the researchers. They could create a barrier to prevent the mycobacteria from attaching to the macrophages; they could transport drugs to kill the mycobacteria; or they could change how the macrophages behave, so that they destroy the mycobacteria rather than harbouring them.

Professor Kurt Drickamer, a lead author of the research from the Department of Life Sciences at Imperial College London, said: "TB is hard to fight effectively because it can hide inside the cells of the immune system that should be able to destroy it. We were surprised to find that there is an extensive interaction between the macrophage and one particular type of molecule on the surface of the mycobacteria. The nature of the interaction gives us hope that we can make simple molecules that block the ability of the mycobacteria to subvert the macrophages.

Ref : http://www.jbc.org/content/288/40/28457.abstract?sid=eeb4801e-b429-4bbf-b0cd-446229088668

"Researchers identify potential way to combat TB

New drug cuts risk of deadly transplant side effect in half

The study, the first to test this treatment in people, combined the drug vorinostat (see structure) with standard medications given after transplant, resulting in 22 percent of patients developing graft-vs.-host disease compared to 42 percent of patients who typically develop this condition with standard medications alone. Results of the study appear in The Lancet Oncology.

"Graft-vs.-host disease is the most serious complication from transplant that limits our ability to offer it more broadly. Current prevention strategies have remained mostly unchanged over the past 20 years. This study has us cautiously excited that there may be a potential new way to prevent this condition," says lead study author Sung Choi, M.D., assistant professor of pediatrics at the U-M Medical School.

Vorinostat is currently approved by the U.S. Food and Drug Administration to treat certain types of cancer. But U-M researchers, led by senior study author Pavan Reddy, M.D., found in laboratory studies that the drug had anti-inflammatory effects as well -- which they hypothesized could be useful in preventing graft-vs.-host disease, or GVHD, a condition in which the new donor cells begin attacking other cells in the patient's body.

The study enrolled 61 older adults from the University of Michigan and Washington University in St. Louis who were undergoing a reduced-intensity bone marrow transplant with cells donated from a relative. Patients received standard medication used after a transplant to prevent GVHD. They also received vorinostat, which is given as a pill taken orally. Fifty of the 61 participants completed the full 21-day course of vorinostat.

New drug cuts risk of deadly transplant side effect in half

Plant Sterols prove to be better cholesterol in Alzheimer`s disease

"Plant sterols are present in various combinations in nuts, seeds and plant oils. As plant sterols are the equivalents of animal cholesterol, they can in principal influence metabolic processes, where cholesterol is involved," explained Marcus Grimm, Head of the Experimental Neurology Laboratory at Saarland University. "Because they also lower cholesterol levels, they are extensively used in the food industry and as dietary supplements."

High cholesterol levels have long been discussed to increase the risk of developing Alzheimer's disease. "Studies have already shown that cholesterol promotes the formation of so-called senile plaques," said Grimm. These plaques, which are composed of proteins, particularly beta-amyloid proteins, deposit at nerve cells within the brain and are regarded as one of the main causes of Alzheimer's disease.

The research team based at Saarland University's medical campus in Homburg collaborated with scientists from Bonn, Finland and the Netherlands to examine how the sterols that we ingest influence the formation of these plaque proteins. It was found that one sterol in particular, stigmasterol, actually inhibited protein formation. "Stigmasterol has an effect on a variety of molecular processes: it lowers enzyme activity, it inhibits the formation of proteins implicated in the development of Alzheimer's disease, and it alters the structure of the cell membrane," explained Dr Grimm. "Together, these effects synergistically reduce the production of beta-amyloid proteins." The research team has been able to confirm the positive effect of stigmasterol in tests on animals.

Overall, the researchers were able to demonstrate that the various plant sterols influence different cellular mechanisms and therefore have to be assessed individually. "Particularly in the case of Alzheimer's disease, it seems expedient to focus on the dietary intake of specific plant sterols rather than a mixture of sterols," explained Dr Grimm. In future studies, the research team wants to determine which other cellular processes in the brain are affected by phytosterols.

Ref : http://www.jneurosci.org/content/33/41/16072.full

        http://www.uni-saarland.de/nc/aktuelles/artikel/nr/9230.html

Plant Sterols prove to be better cholesterol in Alzheimer`s disease

Research brings hope of new treatment for asthma patients resistant to corticosteroids

New research from Japan brings hope of a new treatment for asthma patients resistant to corticosteroids. In a study published today in the journal Nature Communications, researchers from the RIKEN Center for Integrative Medical Sciences and Keio University in Japan report that a type of lymphocytes called natural helper (NH) cells plays a critical role in corticosteroid resistance and demonstrate that the anti-psychotic drug Pimozide can be used to overcome resistance to steroids in severe asthma patients.

Research brings hope of new treatment for asthma patients resistant to corticosteroids