Wednesday, December 18, 2013

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 ChemotherapyCurrent 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.


Tuesday, December 17, 2013

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.


Monday, December 16, 2013

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.

Friday, December 13, 2013

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...

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

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....

Tuesday, December 10, 2013

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.

Monday, December 9, 2013

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.

Friday, December 6, 2013

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.