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duminică, 5 august 2012

Researchers Develop First Potential Medicine For Patients With Most Severe Form Of Congenital Hyperinsulinism

A pilot study in adolescents and adults has found that an investigational drug shows promise as the first potential medical treatment for children with the severest type of congenital hyperinsulinism, a rare but potentially devastating disease in which gene mutations cause insulin levels to become dangerously high.

"There is currently no effective medicine for children with the most common and most severe form of hyperinsulinism," said study leader Diva D. De Leon, M.D., a pediatric endocrinologist at The Children's Hospital of Philadelphia. "Our new research shows that this investigational drug, a peptide called exendin-(9-39), controls blood sugar levels in people, a very promising result."

The study appears online ahead of print in the journal Diabetes.

In congenital hyperinsulinism (HI), mutations disrupt the insulin-secreting beta cells in the pancreas. Uncontrolled, excessive insulin levels thus sharply reduce blood glucose levels, a condition called hypoglycemia. If untreated, hypoglycemia may cause irreversible brain damage or death in children. Congenital HI occurs in an estimated one in 50,000 U.S. children, with a higher incidence among Ashkenazic Jews and certain other groups.

The standard treatment for some forms of congenital HI is diazoxide, a drug that controls insulin secretion by opening potassium channels in beta cells. However, this drug does not work in the most common types of HI, in which mutations prevent these potassium channels from forming.

When abnormal beta cells occur only in a discrete portion of the pancreas, precise surgery on the tiny organ can remove the lesion and cure HI. The Congenital Hyperinsulinism Center at The Children's Hospital of Philadelphia is a world leader in diagnosing such lesions and performing the curative surgery on newborns.

However, in roughly half of congenital HI cases, abnormal cells are diffused through the pancreas, and surgeons must remove nearly the entire pancreas. This leaves the majority of patients at high risk of developing diabetes.

The current study, which builds on previous research by De Leon and colleagues in animals, uses exendin-(9-39), which blocks the action of a hormone receptor, glucagon-like peptide-1 (GLP-1), in beta cells. The GLP-1 receptor is currently the target of drugs that treat diabetes, using the opposite effect from that investigated in this HI study.

The current pilot study included nine subjects, aged 15 to 47 years old, who had hyperinsulinism caused by mutations in potassium channels. None were being treated for HI at the time of the study, but all were at risk of hypoglycemia during periods of fasting.

In all nine subjects, the drug controlled blood glucose levels during fasting. Exendin also controlled insulin secretion in cell studies of beta cells taken from newborns with HI. The current research did not focus on the biological mechanisms that occurred, but De Leon said the results are encouraging enough to progress to a clinical study in children with HI over the next year.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our diabetes section for the latest news on this subject. Financial support for this study came from the National Institutes of Health (grant 1R03DK07835), the Lester and Liesel Baker Foundation, and the Clifford and Katherine Goldsmith Foundation. De Leon's co-authors, all from Children's Hospital, were Charles A. Stanley, M.D., Andrew C. Calabria, M.D., Changhong Li, M.D., and Paul R. Gallagher In addition to their positions at Children's Hospital, De Leon, Stanley and Li also are in the Perelman School of Medicine at the University of Pennsylvania.
"The GLP-1 Receptor Antagonist Exendin-(9-39) Elevates Blood Fasting Glucose Levels in Congenital Hyperinsulinism due to Inactivating Mutations in the ATP-sensitive Potassium Channel," Diabetes, published online Aug.1, 2012, to appear in print, October 2012. doi: 10.2337/db12-0166.
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joi, 15 decembrie 2011

Further Study Necessary To Better Utilize Nature's Medicine Cabinet

Main Category: Pharma Industry / Biotech Industry
Also Included In: Cancer / Oncology
Article Date: 15 Dec 2011 - 0:00 PST

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There are probably at least 500 medically useful chemicals awaiting discovery in plant species whose chemical constituents have not yet been evaluated for their potential to cure or treat disease, according to a new analysis by a New York Botanical Garden scientist who has more than 15 years of experience in collecting plants for natural-products discovery programs.

Currently, 135 drugs on the market are derived directly from plants; the analysis indicates that at least three times as many disease-fighting substances have yet to be found that could be developed into drugs or used as the basis for further drug research.

"Clearly, plant diversity has not been exhausted, and there is still great potential in the plant world," said James S. Miller, Ph.D., Dean and Vice President for Science at the Botanical Garden.

Dr. Miller's analysis, "The Discovery of Medicines from Plants: A Current Biological Perspective," is published in the December issue of the peer-reviewed journal Economic Botany.

To arrive at his estimate, Dr. Miller used a formula based on the ratio of the number of drugs that have been developed from plants to the number of plants that were screened to find those drugs. He then applied that ratio to the number of plant species that have not yet been screened.

Because of uncertainties in some of those numbers, the formula yields a range of potential drug discoveries. While there is no general agreement among botanists about the number of plant species that are likely to exist, Dr. Miller concluded that there are 300,000 to 350,000 species of plants. Of those, he determined that the chemistry of only 2,000 species has been thoroughly studied, and perhaps only 60,000 species have been evaluated even partially for medicinally useful chemicals.

Working with those numbers, Dr. Miller calculated that there are likely to be a minimum of 540 to 653 new drugs waiting to be discovered from plants; the actual number could be much greater.

"These calculations indicate that there is significant value in continuing to screen plants for the discovery of novel bioactive medicinally useful compounds," concludes Dr. Miller, who has run natural-products discovery programs that have collected specimens in North America, Central and Southeast Asia, and Africa for government agencies, pharmaceutical companies, and academic programs.

As part of his Economic Botany paper, Dr. Miller reviews the disappointing history of past plant-screening efforts and evaluates the potential for future programs.

Technological advances in the 1970s and 1980s gave medical researchers the capacity to evaluate large numbers of plant samples. That prompted the federal government and large pharmaceutical companies to institute aggressive plant collecting and screening programs. Those programs led to the development of several important drugs such as Taxol from Taxus brevifolia (used in cancer treatment) and Camptothecin from Camptotheca acuminata (derivatives of which are used to treat cancer). Other drugs indirectly trace their discovery to natural-products research, including the anti-viral Oseltamivir, which derives from Illicium anisatum and is marketed in the United States as Tamiflu.

The number of drug discoveries, however, was substantially less than anticipated. By the early 2000s, many of the large pharmaceutical companies had abandoned their efforts.

Dr. Miller argues that one possible explanation for the low yield is the relatively crude way in which plant extracts were tested for their pharmaceutical potential. Plants may contain as many as 500 to 800 different chemical compounds, but the screening programs of the late 20th century used extracts made from a whole plant or at best extracts that contained many hundreds of compounds.

Under those circumstances, one compound may interfere with the action of another, or the amount of one compound may be too small to register in a mix of hundreds of chemicals.

To correct this problem, new technologies now allow researchers to separate complex mixtures of natural products into a "library" of relatively pure compounds that can be tested individually. A 2002 study demonstrated that testing such libraries dramatically improves discovery rates.

Bringing these advances together with refinements in collecting strategies could lead to what Dr. Miller calls a "second renaissance" of natural-products discovery.

Miller undertook his analysis to highlight the fact that despite past collecting programs, the plant world represents a poorly explored source of potentially lifesaving drugs. That adds urgency, he said, to efforts to conserve natural habitats so that species are not driven to extinction before they can be studied.

"The natural world has a great and diverse array of interesting chemicals that have been only minimally studied and still hold considerable potential," he writes.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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15 Dec. 2011. APA

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vineri, 9 decembrie 2011

Johns Hopkins Medicine To Offer Pepsico Employees New Travel Surgery Benefit

Main Category: Heart Disease
Also Included In: Cardiovascular / Cardiology; Cosmetic Medicine / Plastic Surgery
Article Date: 09 Dec 2011 - 2:00 PST

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Johns Hopkins announced today that PepsiCo, the world's second-largest food and beverage business, will offer its employees the option to travel to Johns Hopkins Medicine in Baltimore for cardiac and complex joint replacement surgeries.

The travel surgery benefit will be extended to PepsiCo's domestic employees and their dependents almost 250,000 people making the finest in medical care available regardless of geography.

PepsiCo, which sponsors its own self-funded medical plans, will waive deductibles and coinsurance for those who elect to have their surgery at Johns Hopkins. The company will also cover the travel and lodging expenses to Baltimore for the patient and a companion. The payment methodology for these procedures is a bundled rate, an all-inclusive rate for hospital and physician charges and certain preoperative testing. This innovative reimbursement model provides payment for all the patient care over the course of a clinical episode instead of paying for each service on a fee-for-service basis.

"We're excited about the opportunity to work with an innovative company like PepsiCo that is committed to ensuring cost-effective, higher-quality care as part of its employee health benefits," says Patricia M.C. Brown, president of Johns Hopkins HealthCare LLC, the managed care arm of Johns Hopkins Medicine. "We're offering their employees some of the best health care available, which should mean fewer complications and should result in employees being able to return to work sooner. At the same time, we're offering PepsiCo predictability regarding cost."

Brown adds that Hopkins is open to similar arrangements with other large companies.

"We are pleased to work with Johns Hopkins to offer PepsiCo employees and their families access to this outstanding health care institution," says Bruce Monte, senior director, PepsiCo Health & Welfare Benefits. "This is a great example of the distinctive programs we provide on top of our already strong health care benefits. These programs are designed to help our employees and their families live healthier lives and ensure a high level of workforce support, which in turn helps PepsiCo to be a successful company."

To be eligible for the new program, the patient must be approved for surgery in advance and be healthy enough to travel. Other types of surgery may be made part of the program in the future.

Article adapted by Medical News Today from original press release. Source: Johns Hopkins Medicine
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9 Dec. 2011. APA

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