Coffee and Tea May Contribute to a Healthy Liver

 — Surprise! Your morning cup of tea or coffee may be doing more than just perking you up before work.

An international team of researchers led by Duke-NUS Graduate Medical School (Duke-NUS) and the Duke University School of Medicine suggest that increased caffeine intake may reduce fatty liver in people with non-alcoholic fatty liver disease (NAFLD).

Worldwide, 70 percent of people diagnosed with diabetes and obesity have NAFLD, the major cause of fatty liver not due to excessive alcohol consumption. It is estimated that 30 percent of adults in the United States have this condition, and its prevalence is rising in Singapore. There are no effective treatments for NAFLD except diet and exercise.

Using cell culture and mouse models, the study authors -- led by Paul Yen, M.D., associate professor and research fellow, and Rohit Sinha, Ph.D of the Duke-NUS Graduate Medical School's Cardiovascular and Metabolic Disorders Program in Singapore -- observed that caffeine stimulates the metabolization of lipids stored in liver cells and decreased the fatty liver of mice that were fed a high-fat diet. These findings suggest that consuming the equivalent caffeine intake of four cups of coffee or tea a day may be beneficial in preventing and protecting against the progression of NAFLD in humans.

The findings will be published in the September issue of the journal Hepatology.

"This is the first detailed study of the mechanism for caffeine action on lipids in liver and the results are very interesting," Yen said. "Coffee and tea are so commonly consumed and the notion that they may be therapeutic, especially since they have a reputation for being "bad" for health, is especially enlightening."

The team said this research could lead to the development of caffeine-like drugs that do not have the usual side effects related to caffeine, but retain its therapeutic effects on the liver. It could serve as a starting point for studies on the full benefits of caffeine and related therapeutics in humans.

In addition to Yen and Sinha, collaborators included Christopher Newgard, PhD, director of the Sarah W. Stedman Nutrition and Metabolism Center at Duke University School of Medicine, where the metabolomics analysis of the data was conducted.

The study was supported by funding from Singapore's Agency for Science, Technology, and Research; the Ministry of Health; and the Ministry of Education.

How to Stop Bleeding in the ER Caused by Warfarin

 — Prothrombin complex concentrates (PCCs) are faster and more effective than fresh frozen plasma at reversing hemorrhage caused by the anti-coagulant warfarin, despite plasma being the most commonly used therapy. A literature review published last month in Annals of Emergency Medicinesuggests that physicians in the United States should join those around the world in following recommendations of multiple specialty organizations to use PCCs as the first line of defense in this common and life-threatening emergency ("Rapid Reversal of Warfarin-Associated Hemorrhage in the Emergency Department by Prothrombin Complex Concentrates").

"The typical remedies for hemorrhage caused by warfarin are slow and unpredictable," said author Kenneth Frumkin, PhD, MD of the Naval Medical Center in Portsmouth, Va. "By contrast, prothrombin complex concentrates reverse warfarin anticoagulation in minutes rather than hours. Its relative underuse in the U.S. compared to other countries seems to derive from lack of familiarity and infrequent availability."

PCCs (products made from pooled human plasma) were initially developed to treat hemophilia. They can be infused rapidly and generally reverse anticoagulation three to five times faster than fresh frozen plasma, which must be thawed. Recombinant Activated Factor VII (Factor rVIIa), while approved in the United States only for surgery or bleeding in hemophiliacs, has been used to reverse warfarin-associated bleeding. Factor rVIIa works faster than fresh frozen plasma, but carries more risk and costs much more.

"The April 2013 approval by the Food and Drug Administration of a form of PCC specifically intended for warfarin reversal should expand the use of these life-saving products," said Dr. Frumkin.

The views expressed by Dr. Frumkin are his own, and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government.

                             courtesy:science daily

Ileus: causes 
MD SPUGERS:
Mesenteric ischemia
Drugs (see below)
Surgical (post-op)
Peritonitis/ Pancreatitis (sentinnel loop)
Unresolved mechanical obstruction (eg mass, intussusception, blockage)
Gram negative sepsis
Electrolyte imbalance (eg hypokalemia)
Retroperitoneal bleed or hematoma
Spinal or pelvic fracture
Drugs are Aluminum hydroxide, Ba++, Ca carbonate, opiates, TCA, verapamil

MNEMONIC FOR ABDOMINAL PAIN:MEDICAL CAUSES
"ABDOMENAL PANE" [abdominal pain]:
Acute rheumatic fever
Blood [purpura, a/c hemolytic crisis]
DKA
cOllagen vascular disease
Migraine [abdominal migraine]
Epilepsy [abdominal epilepsy]
Nephron [uremia]
Abdominal angina
Lead
Porphyria
Arsenic
NSAID's
Enteric fever

Calcium Linked to Increased Risk of Heart Disease and Death in Patients With Kidney Disease

 — Kidney patients who take calcium supplements to lower their phosphorus levels may be at a 22 per cent higher risk of death than those who take other non-calcium based treatments, according to a new study by Women's College Hospital's Dr. Sophie Jamal.

---

The study, published today in theLancet, calls into question the long-time practice of prescribing calcium to lower phosphate levels in patients with chronic kidney disease. The researchers suggest some of the calcium is absorbed into the blood stream and may expedite hardening of the arteries, leading to a higher risk of heart disease and even death. Cardiovascular disease is a leading cause of death for people with chronic kidney disease.

"Doctors commonly prescribe calcium supplements to prevent elevated phosphate levels, which can damage the body, but a growing number of studies have shown calcium supplements may actually increase the risk of heart disease," explains Dr. Sophie Jamal, a physician at Women's College Hospital and an associate professor of medicine at the University of Toronto. "Our study validates these claims and, for the first time, shows the long-term consequences of taking calcium supplements can be dangerous for patients with kidney disease."

As part of their analysis, researchers reviewed 11 randomized, controlled studies that included more than 4,600 patients. The researchers assessed the risk of heart disease, including heart attack, stroke, and hardening of the arteries, along with death among individuals prescribed the medication containing calcium and those prescribed the medication without calcium. They found:

• A 22% reduction in death among patients who took non-calcium based treatments sevelamer and lanthanum.
• Less artery calcification (hardening) in patients who did not take calcium supplements.

"Some researchers and physicians have been saying for years that kidney disease patients need to get off calcium, now we think our review shows there is much more solid evidence to argue for that change to clinical practice," the study's senior author Ross Tsuyuki from the University of Alberta's faculty of medicine and dentistry.

In the meantime, given the study's findings, the researchers suggest non-calcium containing treatments be used as a first line of treatment to lower phosphate for patients with chronic kidney disease.

"The findings of our study provides the best evidence as to what doctors should be prescribing their patients, but further research is necessary to help us understand how exactly calcium increases the risk of death, if non calcium-based treatments reduce the risk of death, and whether certain types of treatments may be more effective and beneficial than others," says Dr. Jamal.

                                      courtesy:science daily

THE SOUNDS OF SUCCESS..............

Successful Restoration of Hearing and Balance

 — The sounds of success are ringing at Kansas State University through a research project that has potential to treat human deafness and loss of balance

Philine Wangemann, university distinguished professor of anatomy and physiology in the College of Veterinary Medicine, and her international team have published the results of their study in the July issue of the journal PLOS Genetics.

"When the SLC26A4 gene is mutated, it leads to a loss of pendrin expression, which causes swelling of the inner ear and loss of hearing and balance," Wangemann said. "In my research, I have been interested in how the inner ear functions. We worked on the idea that if you keep one domino in the chain standing, then the others would continue to stand and function normally. In other words, if we could restore the proper expression of pendrin in the endolymphatic sac and thereby prevent swelling of the sac, this may prevent swelling of other parts of the inner ear and rescue hearing and balance."

More than 28 million people in the United States suffer some form of hearing loss. Wangemann said mutation of SLC26A4is one of the most common forms of hereditary hearing loss in children, not only in the U.S. and Europe, but also in China, Japan and Korea, which makes this research very significant on a global scale.

The foundation of Wangemann's study is that this human disease is largely recapitulated in a mutant mouse model. SLC26A4 is normally found in the cochlea and vestibular organs of the inner ear as well as in the endolymphatic sac, which is a non-sensory part of the inner ear. When the mutant mice lack SLC26A4 expression, their inner ears swell during embryonic development. This leads to failure of the cochlea and the vestibular organs, resulting in deafness and loss of balance. The multitude of sites where SLC26A4 is located made the goal to restore function look futile, unless some sites were more important than others.

"We generated a new mutant mouse that expresses SLC26A4 in the endolymphatic sac, but not in the cochlea or the vestibular organs of the inner ear," Wangemann said. "Fantastically, this mouse did not develop the detrimental swelling of the inner ear and even more exciting, the mouse developed normal hearing and balance."

That restoration of hearing and balance lasted for the duration of the testing period, which suggests that the restoration is permanent.

"Our study provides the proof-of-concept that a therapy aimed at repairing the endolymphatic sac during embryonic development is sufficient to restore a lifetime of normal hearing and balance," Wangemann said.

While these findings are made in a mouse model, Wangemann said that eventually the idea is to develop a pharmacological treatment for human patients, but much more research will be necessary, such as to understand how fluid secretion and absorption is supported and how the balance of secretion and absorption is maintained to prevent the detrimental swelling.

Wangemann's study was supported by the College of Veterinary Medicine at Kansas State University and by grants from the National Institutes of Health, the National Institutes on Deafness and Other Communication Disorders, the Kansas IDeA Network of Biomedical Research Excellence and other sources.

Her team includes researchers from Kansas State University, the National Institutes on Deafness and Other Communication Disorders, Georges-Pompidou European Hospital and Sorbonne University Paris Cite in France, and the University of Utah.

                                  courtesy:science daily

NEW PLAN OF ATTACK AGAINST CANCER..........

New Plan of Attack in Cancer Fight: Two-Drug Combination, Under Certain Circumstances, Can Eliminate Disease

— New research conducted by Harvard scientists is laying out a road map to one of the holy grails of modern medicine: a cure for cancer.

As described in a paper recently published in eLife, Martin Nowak, a professor of mathematics and of biology and director of the Program for Evolutionary Dynamics, and co-author Ivana Bozic, a postdoctoral fellow in mathematics, show that, under certain conditions, using two drugs in a "targeted therapy" -- a treatment approach designed to interrupt cancer's ability to grow and spread -- could effectively cure nearly all cancers.

Though the research is not a cure for cancer, Nowak said it does offer hope to researchers and patients alike.

"In some sense this is like the mathematics that allows us to calculate how to send a rocket to the moon, but it doesn't tell you how to build a rocket that goes to the moon," Nowak said. "What we found is that if you have a single point mutation in the genome that can give rise to resistance to both drugs at the same time, the game is over. We need to have combinations such that there is zero overlap between the drugs."

Importantly, Nowak said, for the two-drug combination to work, both drugs must be given together -- an idea that runs counter to the way many clinicians treat cancer today.

"We actually have to work against the status quo somewhat," he said. "But we can show in our model that if you don't give the drugs simultaneously, it guarantees treatment failure."

In earlier studies, Nowak and colleagues showed the importance of using multiple drugs. Though temporarily effective, single-drug targeted therapy will fail, the researchers revealed, because the disease eventually develops resistance to the treatment.

To determine if a two-drug combination would work, Nowak and Bozic turned to an expansive data set supplied by clinicians at New York's Memorial Sloan-Kettering Cancer Center that showed how patients respond to single-drug therapy. With data in hand, they were able to create computer models of how multidrug treatments would work. Using that model, they then treated a series of "virtual patients" to determine how the disease would react to the multidrug therapy.

"For a single-drug therapy, we know there are between 10 and 100 places in the genome that, if mutated, can give rise to resistance," Nowak explained. "So the first parameter we use when we make our calculations is that the first drug can be defeated by those possible mutations. The second drug can also be defeated by 10 to 100 mutations.

"If any of those mutations are the same, then it's a disaster," he continued. "If there's even a single mutation that can defeat both drugs, that is usually good enough for the cancer -- it will become resistant, and treatment will fail. What this means is we have to develop drugs such that the cancer needs to make two independent steps -- if we can do that, we have a good chance to contain it."

How good a chance?

"You would expect to cure most patients with a two-drug combination," Bozic said. "In patients with a particularly large disease burden you might want to use a three-drug combination, but you would cure most with two drugs."

The trick now, Nowak and Bozic said, is to develop those drugs.

To avoid developing drugs that are not vulnerable to the same mutation, Bozic said, pharmaceutical companies have explored a number of strategies, including using different drugs to target different pathways in cancer's development.

"There are pharmaceutical companies here in Cambridge that are working to develop these drugs," Nowak said. "There may soon be as many as 100 therapies, which means there will be as many as 10,000 possible combinations, so we should have a good repertoire to choose from.

"I think we can be confident that, within 50 years, many cancer deaths will be prevented," Nowak added. "One hundred years ago, many people died from bacterial infections, and now they would be cured. Today, many people die from cancer, and we can't help them, but I think once we have these targeted therapies, we will be able to help many people -- maybe not everyone -- but many people."
                                                courtesy:science daily