Structure of Key Molecule in Immune System Provides Clues for Designing Drugs, According to Penn Study
|
|
PHILADELPHIA - A team from the University of Pennsylvania School of Medicine and Utrecht University has deciphered a key step in an evolutionarily old branch of the immune response. This system, called complement, comprises a network of proteins that “complement” the work of antibodies in destroying foreign invaders. It serves as a rapid defense mechanism in most species from primitive sponges to humans.
In a study published in the December 24 issue of Science, the groups of John Lambris, PhD, the Dr. Ralph and Sally Weaver Professor of Research Medicine at Penn, and Piet Gros at Utrecht, detail the atomic structure of two key transient enzyme complexes in the human complement system.
Complement proteins mark both bacterial and dying host cells for elimination by the body’s cellular cleanup services and have been implicated in at least 30 diseases, including stroke, myocardial infarction, and age-related macular degeneration. The findings, Lambris says, provide a molecular scaffold for designing novel drug therapeutics.
Study on effects of resveratrol and quercetin on inflammation and insulin resistance
|
|
A study was carried out to examine the extent to which quercetin and trans-resveratrol (RSV) prevented inflammation or insulin resistance in primary cultures of human adipocytes treated with tumor necrosis factor-a (TNF-a)—an inflammatory cytokine elevated in the plasma and adipose tissue of obese, diabetic individuals. Cultures of human adipocytes were pretreated with quercetin and trans-RSV followed by treatment with TNF-a. Subsequently, gene and protein markers of inflammation and insulin resistance were measured. The authors report that quercetin, and to a lesser extent trans-RSV, attenuated the TNF-a–induced expression of inflammatory genes such as interleukin (IL)-6, IL-1b, IL-8, and monocyte chemoattractant protein-1 (MCP-1) and the secretion of IL-6, IL-8, and MCP-1.
Forum members were concerned about certain aspects of the study, especially the extrapolation of in vitro results to in vivo situations. The in vitro conditions the authors describe are minimally representative of an in vivo condition. In vivo, after consumption of quercetin or resveratrol, these compounds undergo extensive metabolism, leading to glucuronidated, sulphated or methylated compounds. In a previous study, quercetin 3-glucoside was transformed to 3,4-dihydroxyphenylacetic acid, acetate and butyrate in cells from human gut; only 3’-methylquercetin has been detected in human plasma, present at a concentration of 0.1 to 0.2 µM after 3 h. The authors of the current paper are using concentrations up to 60 µM, concentrations which have not been found in vivo.
There were also concerns with the work on cell uptake of quercetin and resveratrol. Primary adipocytes were incubated with the polyphenols, but it is not clear whether or not the concentrations used were subtoxic. Our current knowledge is limited about local concentration of the molecules we are studying in subcellular compartments, their interaction with alternative targets, and eventually their transformation into products that could be more or less active on a given specific pathway.
Rituximab Maintenance Significantly Improves Progression-Free Survival In Patients With Follicular Lymphoma
|
|
Patients with follicular lymphoma, a slow-growing common type of non-Hodgkin’s lymphoma, who are given 2 years of rituximab-maintenance therapy after immunochemotherapy, have significantly better progression-free survival (PFS) and higher response rates compared with patients who do not receive this intervention. These findings from the largest randomised trial of follicular lymphoma to date, published Online First in The Lancet, support rituximab-maintenance therapy as a first-line treatment option for these patients.
Most patients with follicular lymphoma, a cancer of the lymphatic system, respond well to initial treatment, but relapse is common. Over the past decade, the monoclonal antibody rituximab has shown considerable benefit in patients with the disease. Rituximab plus chemotherapy induction regimens have improved overall survival and have become the standard first-line treatment for follicular lymphoma. But the potential benefit of continuing rituximab treatment after completion of chemotherapy is not known.
The PRIMA study was designed to assess the effect of 2 years of rituximab-maintenance therapy on the outcome of patients with follicular lymphoma. 1217 patients with previously untreated follicular lymphoma were enrolled from 223 centres across 25 countries and given an induction regimen of rituximab plus chemotherapy. After induction, 1019 eligible patients who achieved a complete or partial response were then randomly assigned to 2 years of rituximab maintenance (505 patients) or no treatment (513).
Factors linked to speech/swallowing problems after treatment for head and neck cancers
|
|
Most patients with locally advanced head and neck cancers who successfully complete treatment with chemotherapy and radiation manage to do so without losing the ability to speak clearly and swallow comfortably, according to researchers at the Duke Cancer Institute.
“This is good news,” said Joseph K. Salama, MD, an assistant professor of radiation oncology at Duke and the corresponding author of the study. “I hope it brings some comfort to newly-diagnosed patients who are understandably worried about what long-term effects treatment might involve.”
The study findings appear in the Dec. 20 issue of the Archives of Otolaryngology & Head and Neck Surgery.
Features of the metabolic syndrome common in persons with psoriasis
|
|
Individuals with psoriasis have a high prevalence of the metabolic syndrome, according to a report posted online today that will appear in the April 2011 print issue of Archives of Dermatology, one of the JAMA/Archives journals.
According to background information in the article, individual features of the metabolic syndrome include obesity, high blood pressure, diabetes and high total cholesterol and triglycerides. Additional background information notes that while past studies have suggested a link between psoriasis and individual components of the metabolic syndrome, there is little data available regarding the association between psoriasis and the metabolic syndrome as a whole.
Using data from the National Health and Nutrition Examination Survey, Thorvardur Jon Love, M.D., of Landspitali University Hospital, Reykjavik, Iceland, and colleagues, examined the association between psoriasis and the metabolic syndrome. The study included 6,549 individuals, and the mean (average) age of participants was 39, half were men and the mean body mass index (BMI) was 28.
Acid suppressive medication may increase risk of pneumonia
|
|
Using acid suppressive medications, such as proton pump inhibitors and histamine2 receptor antagonists, may increase the risk of developing pneumonia, states an article in CMAJ (Canadian Medical Association Journal).
Acid suppressive drugs are the second leading medication worldwide, totaling over US$26 billion in sales in 2005. Recently, medical literature has looked at unrecognized side effects in popular medications and their impact on public health.
This systematic review, which incorporated all relevant studies on the association of acid suppressive medications and pneumonia that could be identified to August 2009, showed that out of every 200 inpatients being treated with acid suppressive medication one will develop pneumonia.
A possible cause – and cure – for genital cancer in horses?
|
|
The problem of cervical cancer in humans has been considerably reduced by the development of an efficient and cheap vaccine. Horses also suffer from genital cancer but surprisingly we are only now taking the first steps towards learning what causes the disease. Work by Sabine Brandt and colleagues at the University of Veterinary Medicine, Vienna – together with the British pathologist Tim Scase and with Alastair Foote and his group from Rossdale’s Equine Hospital and Diagnostic Centre in Newmarket – provides strong evidence that a novel papillomavirus is involved and may thus pave the way for the development of a cure. The initial results are published in the current issue of the Equine Veterinary Journal.
Horses are prone to develop genital cancer, especially as they grow older. Male horses are more commonly affected than mares but both sexes suffer from the condition, which is extremely difficult to treat and may result in the animals’ death. Because of the similarity of the disease to human genital cancer it seemed possible that a similar agent might be responsible. Several human genital cancers, including cervical tumours, are known to be caused by a papillomavirus infection, so Brandt and her coworkers used genetic techniques to look for papillomavirus DNA in tissue samples from horses bearing genital squamous cell carcinomas (SCC).
Johns Hopkins faculty highly value involvement of nearby urban community for improving research
|
|
A survey conducted by Johns Hopkins faculty found strong support among their peers for working more closely with the minority, inner-city community that surrounds the institution. Overall, 91 percent of faculty responders said closer ties make research more relevant to those it ultimately serves, and 87 percent said it improves the quality of research.
“This is a huge, stunning finding,” says Nancy Kass, Sc.D., deputy director for public health at the Johns Hopkins Berman Institute of Bioethics. “Faculty are giving a ringing endorsement of how important working with the community can be when conducting research.”
Beyond these sentiments, the survey also found that Hopkins health researchers who conducted studies in the surrounding community were more likely to hire and collaborate with local residents.
Most Medicare stroke patients rehospitalized or dead within year
|
|
Nearly two-thirds of Medicare beneficiaries discharged from hospitals after ischemic stroke die or are readmitted within one year, researchers report in Stroke: Journal of the American Heart Association.
Stroke is the second leading cause of hospital admissions among older adults in the United States, according to American Heart Association/American Stroke Association statistics. Ischemic stroke, which occurs as a result of an obstruction within a blood vessel supplying blood to the brain, accounts for 87 percent of all strokes.
Only a few contemporary studies have examined the full burden of hospital readmission and death after ischemic stroke, said Gregg C. Fonarow, M.D., study lead author and professor of cardiovascular medicine at the University of California-Los Angeles.
Mount Sinai researchers develop mouse model to help find how a gene mutation leads to autism
|
|
Researchers from Mount Sinai School of Medicine have found that when one copy of the SHANK3 gene in mice is missing, nerve cells do not effectively communicate and do not show cellular properties associated with normal learning. This discovery may explain how mutations affecting SHANK3 may lead to autism spectrum disorders (ASDs). The research is currently published in Molecular Autism.
“We know that SHANK3 mutation plays a central, causative role in some forms of autism spectrum disorders, but wanted to learn more about how it does this,” said Joseph Buxbaum, PhD, Director of the Seaver Autism Center and Professor of Psychiatry, Neuroscience and Genetics and Genomic Sciences at Mount Sinai School of Medicine. “These data provide critical insight into the mechanism behind the development of the cognitive and social changes associated with autism.”
Previous research has shown that gene mutation in SHANK3 is associated with delayed language abilities, learning disability, and ASDs.
Novel drug offers hope for early intervention in cystic fibrosis patients
|
|
Cystic fibrosis (CF) patients with normal to mildly impaired lung function may benefit from a new investigational drug designed to help prevent formation of the sticky mucus that is a hallmark of the disease, according to researchers involved in a phase 3 clinical trial of the drug. Called denufosol, the investigational medication can be given early in the CF disease process, and may help delay the progression of lung disease in these patients, the researchers found.
The findings were published online ahead of the print edition of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.
“Although the lungs of children with CF are thought to be normal at birth, studies have demonstrated significant lung damage that occurs early in life in children suffering from cystic fibrosis,” said lead investigator Frank Accurso, MD, professor of pediatrics, University of Colorado School of Medicine, Denver. “Many patients continue to suffer progressive loss of lung function despite treatment of complications. Because denufosol can be used early in life, it offers hope for delaying or preventing the progressive changes that lead to irreversible airflow obstruction in CF patients.”
New Research Finds Delaying Surgical Procedures Increases Infection Risk and Health Care Cost
|
|
Delaying elective surgical procedures after a patient has been admitted to the hospital significantly increases the risk of infectious complications and raises hospital costs, according to the results of a new study in the December issue of the Journal of the American College of Surgeons.
The occurrence of infection following surgical procedures continues to be a major source of morbidity and expense despite extensive prevention efforts that have been implemented through educational programs, clinical guidelines, and hospital-based policies. The authors of the study queried a nationwide sample of 163,006 patients, 40 years of age and older, from 2003 to 2007. They evaluated patients who developed postoperative complications following one of three high-volume elective surgical procedures: 87,318 coronary artery bypass graft (CABG) procedures, 46,728 colon resections, and 28,960 lung resections.
The infectious complications evaluated included pneumonia, urinary tract infections, postoperative sepsis and surgical site infections.
Vioxx harmful even after patients stopped taking it
|
|
Merck’s withdrawn painkiller Vioxx may have continued to cause blood clots and perhaps deaths even after patients dropped it, U.S. researchers said Monday.
The drug was recalled by Merck in 2004 after a colon-polyp prevention study showed it increased the risk of heart disease and death in users. But over the five years it was on the market, researchers estimate it caused nearly 40,000 deaths.
The new findings, published in the Archives of Internal Medicine, are based on data made available by Merck during multibillion-dollar litigation against the company.
Vaccine boosts your immune system
|
|
Researchers at BRIC, the University of Copenhagen, have discovered that the human body can create its own vaccine, which boosts the immune system and helps prevent chronic inflammatory diseases. The researchers’ results have just been published in the prestigious Journal of Clinical Investigation and may have significant consequences in developing new medicine.
Researchers at the Biotech Research and Innovation Centre (BRIC) at the University of Copenhagen have discovered a protein normally found in the body that can act to prevent chronic tissue inflammation. When administered in the form of a therapeutic vaccine it is able to effectively prevent and treat a number of different inflammatory disease models for multiple sclerosis (MS), rheumatoid arthritis (RA), skin hypersensitivity and allergic asthma (AA).
The results of this study have just been published by the prestigious Journal of Clinical Investigation in the article entitled “Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates multiple tissue-specific inflammation in mice”.
Widespread vitamin D deficiency a concern in Asia
|
|
Strategies to improve vitamin D status are essential, say experts; global vitamin D maps in development
Bone health experts attending the 1st Asia-Pacific Osteoporosis Meeting in Singapore this week have flagged vitamin D deficiency as a major concern in the region, particularly in South Asia where the problem is especially severe and widespread across the entire population.
Dr. Nikhil Tandon, Professor of Endocrinology and Metabolism at the All India Institute of Medical Sciences of New Delhi, India highlighted the results of various studies which show severe deficiency across India and Pakistan in all age groups, as well as insufficiency in populations of South-East and East Asia. “A lack of exposure to sunshine, genetic traits and dietary habits are all factors which influence vitamin D levels. In certain regions, vitamin D deficiency can also be attributed to skin pigmentation and traditional clothing, as well as air pollution and limited outdoor activity in urban populations,” he stated.
