Dapagliflozin is a new drug for the treatment of type two diabetes

A strange drug, the premier in its class, gives added blood sugar dominate to mobile vulgus with category 2 diabetes who are already enchanting the glucose-lowering medication metformin.

The budding agent, dapagliflozin, which also helped patients squander weight, is novel in that it does not produce directly on the body’s insulin mechanisms, according to a inspect appearing in the June 26 issue of The Lancet and slated for conferral at the annual gathering of the American Diabetes Association (ADA) in Orlando Noroxin. “It will likely be used as an add-on therapy,” said swotting lead author Clifford Bailey, a chemical pathologist and professor of clinical study at Aston University in Birmingham, UK “If you don’t unreservedly get to quarry with the maiden therapy tried , this approach would put on the market you an opportunity hopefully to maintain improved control”.

Bailey, who could not vaticinate if or when the drug might get final approval from cure-all regulatory authorities, also pointed out that dapagliflozin is flexible, message it can be used with various other treatments and at more or less any stage in the disease. “It’s a seemly add-on,” agreed Dr Stanley Mirsky, accomplice clinical professor of metabolic diseases at Mount Sinai Medical Center in New York City buy Tramaden. “is it a ask oneself drug? no. It may room a insufficient role”.

The con was funded by Bristol-Myers Squibb and AstraZeneca, which are developing dapagliflozin together. Dapagliflozin machinery by inspirational the kidneys to annihilate more glucose from the body via urine Actos. In this scrutiny of 534 adult patients with type 2 diabetes who were already irresistible metformin, the highest dispense of dapagliflozin (10 milligrams daily) was associated with a 0,84 percent diminish in HbA1c levels.

HbA1c is a compute of blood sugar control over time. Participants alluring 5 mg of the dope saw a 0,70 percent decrease in HbA1c levels, while those delightful 2.5 mg had a 0,67 percent decrease. In the placebo group, the subsidence in HbA1c was 0,3 percent, the haunt found.

Weight injury was also greater in volunteers winsome the study drug: 2,2 kilograms (4,8 pounds) in the 2,5 mg group; 3 kilograms (6,6 pounds) in the 5 mg group; and 2,9 kilograms (6,4 pounds) in the 10 mg group. Those in the placebo bunch misplaced 0,9 kilograms, or almost 2 pounds. Much, though not all, of this damage was like as not to be tap water weight, the authors stated.

There were more genital infections seen among those attractive dapagliflozin, the pair noted. “One of the complications of the poison is an enlargement in urinary tract infections or yeast infections because you have grave glucose levels in the urine,” said Dr Jacob Warman, boss of endocrinology at The Brooklyn Hospital Center in New York City. “That’s a very eulogistic way of life usual for yeast, so the endocrinologists aren’t too ecstatic about that”.

On the other hand, he said, this drug appears to run without some of the kidney, liver and muscle complications of other drugs so “it would be the best as an add-on to usual medications”. A assign study, also simultaneously being presented at the ADA encounter and published in The Lancet, found that adding inhaled insulin before each luncheon and long-acting insulin glargine before prevailing to bed worked just as well as engaging conventional therapy.

The regular psychotherapy consisted of taking biaspart insulin twice a day. This is a combine of short-acting insulin and intermediate-acting insulin. The altered regimen tangled less weight gain, fewer episodes of inadequate blood sugar and was more convenient, according to the study, which was funded by MannKind, the maker of Technosphere, the inhaled insulin featured in the trial.

A third burn the midnight oil found that once-weekly injections of the treatment Byetta (exenatide) worked better at controlling blood sugar levels than long-acting insulin. The training thus far has been to give Byetta twice a day. This study, funded by Amylin Pharmaceueticals and Eli Lilly, looked at a supplementary formulation of the drug buy generic sildenafil. Patients who got the once-a-week tone also perplexed an middling of 2,6 kilograms (5,7 pounds), the read found.

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Potential new drug for neurodegenerative diseases

A research team has identified a small molecule that helps human cells get rid of the misfolded, disfigured proteins implicated in Alzheimer's disease and other neurodegenerative ailments.

potential drug could have applications for other conditions as well.

Cells create and discard proteins continuously, a process that relies on a balance between the speed with which new proteins are created and damaged ones destroyed. Protein destruction occurs through a sophisticated system that marks proteins for disposal by tagging them with a small molecule called ubiquitin.

Ubiquitin latches onto these proteins, often forming long chains. The cell9s protein waste-disposal system, the proteasome, recognizes these ubiquitinated proteins and breaks them down.

If that finely tuned system malfunctions, damaged or misfolded proteins begin to accumulate in the cell and may become toxic. A number of ailments, including Parkinson's, Creutzfeldt-Jakob and Alzheimer9s have been linked to this build up of misfolded proteins.

To better understand just what causes this malfunction, a research team led by Harvard Medical School researchers Daniel Finley, professor of cell biology, and Randall King, associate professor of cell biology, zeroed in on an enzyme called Usp14.

They found that, when activated, Usp14 disassembles the ubiquitin chain, slowing down the proteasome's ability to rid the cell of bad proteins. As a result, the cell makes new proteins faster than it rids itself of the old ones, leading to a build-up of misfolded proteins.

The researchers wanted to see if they could find a molecule that inhibited Usp14, thus allowing the proteosome to work effectively. To identify such a selective inhibitor, Byung-Hoon Lee, a postdoctoral researcher, developed a special screening assay with assistance from the Institute of Chemistry and Cell Biology-Longwood Screening Facility at HMS.

Lee screened 63,000 compounds, looking for molecules that inhibited only Usp14 and could easily infiltrate the cell. The strongest candidate was a small molecule they named IU1.

Experimenting in both human and mouse cell cultures, Min Jae Lee, also a postdoctoral researcher, and his co-workers found that IU1 inhibited Usp14 and allowed the proteasome to dispose of proteins more quickly. In other words, adding IU1 to cells boosted proteasome activity.

Though scientists are still investigating just how IU1 works, it appears that the molecule suppresses Usp14's ability to trim the ubiquitin chain.

In addition to discovering IU1, this research has also shed light on an aspect of proteasome function that was not previously understood, King says.

Scientists had thought that the proteasome was not involved in regulating the speed of protein degradation, but that other proteins work with ubiquitin to modulate the process.

"Our work suggests that there is another level of control where the rate at which the proteasome can degrade these ubiquinated proteins is also controlled. It looks like there are multiple control steps along the way in this pathway," King said.

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New emergency contraceptive approved by FDA

The newest form of emergency contraceptive, ellaOne, was approved August 13 by the U.S. Food and Drug Administration.

Although the new drug has been around since fall of 2009 in select European countries, it was not introduced to the United States until June 2010.

The new drug is a type of emergency contraceptive pill that allows a woman up to five days after sexual intercourse to consume the pill.

The more popular contraceptive pill, Plan B One-Step, also known as the morning-after pill, offers only three days.

"The great thing about ellaOne is the efficacy lasts for all five days," said Morgan Molnar, '10, a marketing major pursuing her masters in sociology, who attended part of the first FDA hearing in June about ellaOne.

"The effects of the pill will be the same if you take it on the first day or the last day," she said. "If you take Plan B One-Step the day after unprotected sex, you will have a better chance of not getting pregnant than if you took the pill three days later. EllaOne lasts all five days and your chances don't decrease."

However, like most new drugs, long-term effects are unknown for ellaOne.

"As far as my opinion, it's a great drug, but my only concern is that it is so new," Molnar said. "They haven't done too many long-term studies, so in the case that women have become pregnant and have taken the drug, they don't know what will happen to the unborn fetus."

"Plan B One-Step doesn't have a lot of effects on the fetus, but ellaOne is so new that they are unsure of its effects in the long run," she said.

Susan Kitei, director of the Health Center, said she is not ready to endorse ellaOne because significant problems with a new medication are not always apparent until it has been widely used for two to five years.

"This is why, occasionally, we will hear on the news that a drug is being removed from the market," she said. "EllaOne has been used in Europe only since 2009, so it is wisest to wait a while to make absolutely certain it is as safe as other medications used for emergency contraception. The best alternative, Plan B, has been in wide usage for a number of years and is known to be safe and effective."

Kitei also said Plan B is available without a prescription for those 17 years and older.

The new drug will be prescription-only, and how its cost will compare with Plan B is still unknown.

"Since the decision of taking emergency contraception is such a big choice for women, this now gives them more time to make a good decision of whether or not they want to pursue with emergency contraception," Corry Starr, '13, said. "However," she said, "since ellaOne has to be prescribed, I don't think girls will want to use it as often as Plan B due to confidentiality."

"Based on what I saw, it looks like ellaOne is more effective than Plan B," Rita Jones, director of the Women's Center, said.

"It's advantageous because it offers women five days opposed to three days," she said.

"However, women should still think about securing emergency contraception as soon as possible. Just because they now have three to five days, doesn't mean they should simply wait around."

Karen Hicks, an adjunct professor of women's studies and sociology, also attended part of the first FDA hearing and recommended getting as much information as possible before using the medication.

"Time will tell how popular ellaOne will be in the U.S.," Kitei said. "The more educated a woman is, the less likely she is to need it. Because most of our students are aware of Plan B, I am expecting only rare requests."

Jones considered a separate advantage of the new drug and said the availability of the new drug is a benefit in cases of incest or sexual assault.

"In some incidents, the survivor might need a couple of days to process what happened," she said. "Five days provides more time for the survivor and helps them, as opposed to a smaller three-day window."

The price of ellaOne has yet to be determined in the United States but according to Molnar, it will be about three times the price of Plan B.

"I think the approval of ellaOne was definitely a step in the right direction toward giving women more choices," Molnar said.

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Promising Treatment for Metastatic Melanoma

Researchers from the John Theurer Cancer Center at Hackensack University Medical Center played an important role in a study that led to the Food & Drug Administration's (FDA) recent fast tracking of ipilimumab, a promising treatment for metastatic melanoma.

The FDA based its decision largely on the results of a pivotal study published in the New England Journal of Medicine on August 19, 2010 - the same day the agency accepted Bristol-Myers Squibb's application for the drug's approval and granted the application priority review status.

Ipilimumab is the first drug shown in randomized, placebo-controlled trials to improve survival in stage IV melanoma.

"This study, and the FDA's decision, provides new hope for people with this devastating cancer," said Andrew L. Pecora, M.D., F.A.C.P., C.P.E., Chairman and Executive Administrative Director, John Theurer Cancer Center, who led the study at the John Theurer Cancer Center. "We are proud to have played a role in helping move another promising cancer treatment closer to market."

The incidence of metastatic melanoma has increased over the last three decades, and the death rate continues to climb faster than that of most other cancers. According to the American Cancer Society, there were approximately 68,000 new cases of melanoma in the United States in 2009, and 8,700 melanoma-related deaths. Melanoma accounts for about three percent of all skin cancers, but 80 percent of skin cancer deaths. Melanoma is difficult to treat once it has spread beyond the skin to other parts of the body (metastasized). Very few treatment options exist for people with metastatic melanoma.

In this phase III study, researchers randomly assigned patients to one of three treatment groups: those receiving ipilimumab plus an inactive (placebo) version of gp 100, a cancer vaccine; those receiving ipilimumab plus gp 100; and those receiving gp 100 plus ipilimumab placebo. The treatments were administered once every three weeks, for a total of four treatments. The study was double blinded: neither the researchers nor the patients knew which medications the patients were being given.

To participate in the study, patients must have had stage III or IV (metastatic) melanoma, and must have been previously treated unsuccessfully with another cancer drug. They must also have had a life expectancy of at least four months. 676 patients participated in the study at 125 cancer centers.

Those who received ipilimumab, both by itself and with gp 100, lived a median of about 10 months, while those who received only gp 100 lived about 6.4 months. After two years, approximately 23 percent of those who got ipilimumab were alive, while 14 percent of those who did not receive this drug survived. Ten to 15 percent of those who received ipilimumab suffered attacks on their bodies' immune systems (autoimmune reactions), and seven of the 540 patients who got this drug died from these attacks. Most adverse events suffered by study participants, however, were reversible with treatment.

A monoclonal antibody, ipilimumab activates the body's immune system to fight cancer by blocking a protein called CTLA-4. CTLA-4 is a molecule on T-cells, white blood cells that play a critical role in regulating immune responses. CTLA-4 suppresses the immune system's response to disease, so blocking its activity stimulates the immune system to fight the melanoma.

The FDA grants priority review status to drugs that offer major advances in treatment, or that provide treatment where no adequate therapy exists. The projected FDA action date for the ipilimumab application is December 25, 2010.

The John Theurer Cancer Center has more than 100 clinical trials under way for all types of cancer and life-threatening blood disorders. Clinical trials test the safety and effectiveness of new medications, therapies, treatment regimens, devices, and adjuvant treatments in human patients. These clinical trials are conducted independently or in cooperation with pharmaceutical companies, universities, other cancer centers, and national organizations such as the National Cancer Institute, the American Cancer Society, the National Science Foundation, and the National Institutes of Health.

"Our commitment to providing outstanding patient care and leading edge treatments extends to our leadership or participation in major clinical trials," said Dr. Pecora. "We are dedicated to improving treatment outcomes not just for our patients, but for all of those with cancer."

Results of this study were originally presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2010, and published online by the New England Journal of Medicine to coincide with the presentation.

About the John Theurer Cancer Center at Hackensack University Medical Center

The John Theurer Cancer Center at Hackensack University Medical Center is New Jersey's largest and most comprehensive center dedicated to the diagnosis, treatment, management, research, screenings, and preventive care as well as survivorship of patients with all types of cancer. The 15 specialized divisions covering the complete spectrum of cancer care have developed a close-knit team of medical, research, nursing, and support staff with specialized expertise that translates into more advanced, focused care for all patients. Each year, more people in the New Jersey/New York metropolitan area turn to the John Theurer Cancer Center for cancer care than to any other facility in New Jersey. Housed within a 775-bed not-for-profit teaching, tertiary care, and research hospital, the John Theurer Cancer Center provides state-of-the-art technological advances, compassionate care, research innovations, medical expertise, and a full range of after care services that distinguish the John Theurer Cancer Center from other facilities.

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Researchers try new approaches to preventing HIV

Tablets, insertable rings and dissolving films can effectively deliver drugs to help protect women and perhaps men from infection with the AIDS virus, researchers reported on Monday.

They also found evidence that using such an approach -- called a microbicide -- may help overcome some of the risks of drug resistance that can come with taking pills to prevent infection.

Here are some of the findings from the International Microbicides Conference being held in Pittsburgh:

* A flexible ring designed for use in the vagina can continually deliver two AIDS drugs for up to a month. Andrew Loxley of Bethlehem, Pennsylvania-based Particle Sciences, Inc., and colleagues lab tested a vaginal ring that time-released dapivirine, a drug made by Johnson & Johnson's Tibotec Inc and licensed to the International Partnership for Microbicides, and the entry inhibitor maraviroc sold by Pfizer under the brand name Selzentry. It has not been tested in people yet.

* A vaginal tablet worked in similar fashion, time-releasing maraviroc and another experimental HIV drug called DS003, licensed to the International Partnership for Microbicides by Bristol-Myers Squibb, Sanjay Garg of the University of Auckland in New Zealand told the conference. The tablet uses a polymer designed to attach to the moist lining inside the vagina.

* A third approach uses a film, Anthony Ham of ImQuest BioSciences of Frederick, Maryland reported. ImQuest is testing the HIV drug IQP-0528 in a film smaller and thinner than a stick of gum, similar to a mouthwash strip.

* Susan Schader of McGill University in Montreal, Canada, and colleagues said tests of these and other HIV drugs used as microbicides showed that drug resistance emerged only if HIV was in the lab dish first -- which suggests people would only develop drug-resistant infections by using microbicides when they were already infected.

* The AIDS virus infects more than 33 million people globally and it has killed 25 million, according to the United Nations AIDS agency UNAIDS. Globally, more than half of those with HIV are women, most infected by husbands or steady partners and many of whom who are unable to insist on use of a condom.

* AIDS experts have long been searching for a microbicide -- a cream, gel or vaginal ring that women or men could use as a chemical shield to protect themselves from sexual transmission of the deadly and incurable virus.

* Microbicides using HIV drugs would represent a large new market for the companies that make the drugs, which are now used only to treat infection.

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