Safety Concerns May Prevent FDA Approval Of Ligand's Drug Aprela

By October 3, 2013, the U.S. Food and Drug Administration (FDA) will decide whether to approve Ligand Pharmaceutical's (LGND) drug Aprela for the treatment of menopausal symptoms and the prevention of postmenopausal osteoporosis in non-hysterectomized women. This drug is being developed by Ligand in partnership with Pfizer (PFE). After reviewing Aprela's clinical trial results and relevant scientific literature, we believe Aprela will fail to receive FDA approval and, consequently, Ligand's stock will underperform in the near term.

Background

Ligand Pharmaceutical is a small biotechnology company with a focus on acquiring and developing drugs that will generate royalty revenue. Aprela, its current lead product, has been developed for the treatment of menopause.

Menopause is the cessation of menstruation. It is a biological process that occurs naturally among women but can also arise from surgical interventions that affect ovary function. The main menopausal symptoms include hot flashes, night sweats, sleep disturbances, vaginal dryness, and vulvar and vaginal atrophy. Hot flashes are the most common type of symptom associated with menopause. In addition, menopause is also a major risk factor for osteoporosis.

Hormone therapy (HT) is the only FDA-approved treatment for menopause. However, the FDA recently approved a non-hormonal therapy named Brisdelle for menopausal hot flashes. HT was considered the gold standard among treatment options until 2002 when a study published by the Women's Health Initiative suggested that HT might increase the risk of breast cancer, venous thromboembolism, and stroke. As a result, the number of women taking HT precipitously dropped.

Aprela combines conjugated estrogens (CE) with bazedoxifene (BZA), a selective estrogen receptor modulator. Estrogens have established efficacy in relieving menopausal symptoms and postmenopausal osteoporosis, while BZA has demonstrated protective effects on the uterus and breast. BZA has been approved in Europe and Japan for the treatment of postmenopausal osteoporosis.

BZA/CE improves menopausal symptoms, but less effectively than standard HT

The efficacy and safety of BZA/CE have been evaluated in multicenter, randomized, double-blind, placebo- and active-controlled, phase III studies referred to as the SMART trials. In total, there are five SMART trials. SMART-1 evaluated the endometrial safety of six BZA/CE doses. Two doses (BZA at 20mg and CE at 0.45 or 0.625 mg) were selected for subsequent trials.

The efficacy of BZA/CE for vasomotor symptoms was evaluated in the SMART-2 trial in 332 symptomatic women. At week 12, treatment with BZA/CE at both doses significantly reduced the number of hot flashes by 74% (10.3 hot flashes at baseline vs. 2.8 at week 12) and 80% (10.4 vs. 2.4), respectively, versus 51% (10.5 vs. 5.4) with placebo. The mean daily hot flush severity was also significantly reduced for both BZA/CE doses compared with placebo at week 12. However, based on results from the Women's Hope study, HT reduced the number of hot flashes from baseline by over 90% and the improvement with mean daily hot flush severity was also greater compared with the two BZA/CE doses.

The efficacy of BZA/CE for vulvar/vaginal atrophy was evaluated using four measures in the SMART-3 trial in 664 postmenopausal women. BZA/CE was shown to be effective at treating these vaginal symptoms compared with placebo or BZA alone.

The efficacy of BZA/CE for osteoporosis prevention was evaluated using bone mineral density (BMD) measures in SMART-4 and SMART-5, and two sub-studies within the SMART-1 trial. In the SMART-1 trial, BZA/CE at both doses significantly increased lumbar spine and total hip BMD compared with placebo at 2 years. Similar phenomenon was observed in the SMART-4 and -5 trials. In SMART-4, however, the increases of BZA/CE on spine BMD (~0.80% increase from baseline) were significantly lower than those observed for HT (~2.22% increase from baseline). In SMART-5, the increases of BZA/CE on spine BMD were also lower than those observed for HT. Although both BZA/CE and HT could effectively increase BMD compared to placebo, HT consistently shows a better efficacy profile with regard to BMD.

BZA/CE trials could not determine long-term safety

The safety of BZA/CE was evaluated against HT or placebo in the SMART-1, -4 and -5 trials. SMART-1, -4, and -5 evaluated endometrial safety as indicated by the incidence of endometrial hyperplasia. Endometrial hyperplasia is excessive growth of cells lining the endometrium or uterus and poses a risk factor for the development of endometrial cancer. At year one, the incidence of endometrial hyperplasia with BZA/CE was similar to that in the placebo group in the SMART-1 and SMART-5 trials. At year one of SMART-4 trial, no cases of endometrial hyperplasia were identified in the BZA 20-mg/CE 0.45-mg group, the CE group, or the placebo group. However, three cases (1.1%) were confirmed for the BZA 20-mg/CE 0.625-mg group. One explanation for this is the difference in the administered BZA/CE formulations. The bioavailability of BZA in the formulation was 18% lower than the formulation used previously, resulting in insufficient level of BZA to maintain endometrial safety. Such formulation and stability issues could serve as a hurdle in the FDA approval process.

High breast density is a risk factor for developing breast cancer. In the SMART-1 trial, BZA/CE demonstrated non-inferiority versus placebo while HT showed a significant increase in mean percent breast density at one year, suggesting a potential advantage of BZA/CE over HT. There was a higher incidence of AEs leading to study discontinuation in the HT group due to metorrhagia, uterine hemorrhage, and vaginal hemorrhage.

For a one-year period, BZA/CE did seem to have a favorable safety/tolerability profile. The overall incidence of adverse events was similar among treatment groups. However, these studies could not properly evaluate longer-term safety effects of BZA/CE. Specifically, the studies did not evaluate AEs such as cancers that occur relatively infrequently. Notably, this cancer risk is a primary concern with HT. Thus, despite having compromised efficacy, BZA/CE may not have better long-term safety than standard HT.

The FDA has set a high safety bar for alternative therapy to treat menopause

Previously, the FDA delayed approval of BZA for the treatment of postmenopausal osteoporosis because of concerns about the incidence of stroke and blood clotting. In particular, the agency required additional analysis of the incidence of stroke and venous thrombotic events, raising doubt about the BZA/CE combination therapy quickly gaining approval.

Recently, the FDA approved the first non-hormonal therapy, Brisdelle, for the treatment of hot flashes. The approval was considered somewhat surprising given the poor efficacy of Brisdelle compared to HT. Overall, this suggests that the FDA prioritizes safety over efficacy in menopausal therapeutics, which further decreases the likelihood of Aprela being approved. In addition, Pfizer previously sought an extended label for its drug Pristiq to cover hot flashes, but received a complete response letter requesting additional studies on the safety of the drug. Generally, the FDA has set a high bar for safety of alternative menopausal therapy and, in our opinion, Aprela does not clear this bar.

A solid business model and extensive pipeline may overcome any short-term setbacks

In early August, many analysts downgraded Ligand's stock. This was likely due to a combination of a run-up in price and a halt in the development of two drug candidates being developed in partnership with The Medicines Company (MDCO) and Merck (MRK). This news came on the heels of the company's second quarter earnings report, which shows revenue up by 67% and royalty payments up by 63% over the previous quarter. The company has also doubled it shareholder's equity from one year ago and is currently generating a positive cash flow. With 85 drugs in its pipeline and the potential to double its royalty-generating assets over the next few years, Ligand can tolerate a few setbacks. Thus, we see Ligand stock as a promising long-term investment, but one to avoid through the beginning of October.

Summary

Ligand's Aprela improves menopausal symptoms and postmenopausal osteoporosis simultaneously, although its efficacy seems to be not as good as that for HT. Regarding safety, currently available data do not provide sufficient evidence that Aprela has a better long-term safety profile than HT. We believe that the FDA will likely continue applying stringent safety criteria to potential menopause drugs, leading us to conclude that Aprela is unlikely to obtain FDA approval. Nevertheless, the company's business model and extensive drug pipeline has gained considerable positive attention from investors, which we believe is well deserved.

Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. (More...)

Business relationship disclosure: Beacon VP Investments is a team of analysts. This article was written by Dr. Hyun Ji Noh and Sophie Wang, two of our team members. We are not receiving compensation for the article (other than from Seeking Alpha). We have no business relationship with any company whose stock is mentioned in this article.

View the original article here

Electronic medical records calculate health risk score, to prevent unplanned readmissions

Main Category: Public Health
Also Included In: IT / Internet / E-mail
Article Date: 19 Aug 2013 - 0:00 PDT Current ratings for:
Electronic medical records calculate health risk score, to prevent unplanned readmissions

A health risk score calculated automatically using routine data from hospital electronic medical records (EMR) systems can identify patients at high risk of unplanned hospital readmission, reports a study in the September issue of Medical Care, published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

The score, called the Rothman Index, may provide a useful tool for lowering the rate of avoidable repeat hospitalizations, according to the report by Elizabeth Bradley, PhD, of Yale School of Public Health and colleagues. They write, "Clinicians can use the Rothman index to target hospital programs and supports to patients at highest risk of readmission."

Routine Data Identify Patients at High Risk of Readmission

The researchers evaluated the Rothman Index as a "practical tool" for assessing readmission risk. The Rothman Index software uses information from the hospital EMR system to provide a continuously updated score indicating the likelihood of death or readmission within 30 days.

The score is calculated automatically using routine data on each patient's vital signs, routine nursing assessments, skin condition, heart rhythms, and laboratory tests. Lower Rothman Index scores (from a maximum of 100) indicate a higher risk of readmission.

Dr Bradley and colleagues evaluated the ability of the Rothman Index to predict hospital readmission, based on data from more than 2,700 patients hospitalized during 2011. (During this time, doctors and nurses did not have access to the Rothman Index scores.) Sixteen percent of the patients had an unplanned readmission within 30 days after hospital discharge.

The Rothman Index was strongly associated with the risk of unplanned readmission. For patients in the highest-risk category - Rothman Index less than 70 - readmission risk was more than 1 in 5. By comparison, for those in the lowest-risk category - Rothman Index 80 or higher - the risk was about 1 in 10.

After adjustment for other factors, patients in the highest versus lowest risk category were more than two and a half times as likely to be readmitted within 30 days of discharge. The Rothman Index predicted readmission across diagnoses and medical specialties.

Rothman Index Could Help Efforts to Lower Repeat Hospitalizations

Unplanned hospital admissions are a major quality and cost issue in the US healthcare system. About 20 percent of Medicare patients are readmitted to the hospital within 30 days, at an estimated cost of $17 billion per year. Hospitals are looking for more effective ways of reducing readmissions - especially now that Medicare has begun reducing payments to hospitals with high readmission rates.

The Rothman index is especially valuable because it is calculated automatically from routine data, requiring no manual input from busy healthcare professionals. It was developed by brothers Michael and Steven Rothman in memory of their mother, who died unexpectedly four days after hospital discharge following heart surgery.

During their mother's illness, the Rothman brothers were surprised to learn that the hospital's EMR system did not generate summary patient health measures that might have alerted doctors to unrecognized complications that were present at discharge. While neither of the brothers had medical training, both were computer scientists with experience in applying complex analytical tools to massive electronic databases.

The new study suggests that the Rothman Index could help reduce rates of unplanned readmission, identifying a group of patients two to three times more likely to be readmitted. Implemented into daily care, the Rothman Index could provide "a practical way for clinicians to identify patients who might be at higher risk for unplanned readmission and intervene specifically for these patients to try to avert unplanned readmission," Dr Bradley and coauthors write.

"We know the Rothman Index is associated with readmissions, but we do not know if it can be used to improve decision making at the bedside in terms of when patients are discharged," commented Dr Bradley, who is professor of public health at the Yale School of Public Health and faculty director at the Yale Global Health Leadership Institute.

"We also don't know if physicians would benefit from using it as part of determining what kinds of added supports at home and in the community might be arranged at discharge," Dr Bradley added. "Answering these questions will determine if the Rothman Index can be used prospectively by clinicians to reduce readmissions and adverse events post-hospitalization."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our public health section for the latest news on this subject.

Dr Bradley's coauthors were Olga Yakusheva, PhD, Leora I. Horwitz, MD, Heather Sipsma, PhD, and Jason Fletcher, PhD.

Wolters Kluwer Health

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Health, Wolters Kluwer. "Electronic medical records calculate health risk score, to prevent unplanned readmissions." Medical News Today. MediLexicon, Intl., 19 Aug. 2013. Web.
19 Aug. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Electronic medical records calculate health risk score, to prevent unplanned readmissions'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

What are blisters? How to prevent blisters

Editor's Choice
Main Category: Dermatology
Article Date: 16 Aug 2013 - 14:00 PDT Current ratings for:
What are blisters? How to prevent blisters

Blisters are small pockets of liquid that form on the outer layer of the skin after the skin becomes damaged (usually caused by forceful rubbing or burning).

Blisters prevent the area from becoming further damaged by protecting the skin underneath and giving it adequate time to heal.

Blisters are filled with serum, which is essentially blood plasma without fibrinogens (the red blood cells and clotting agents are removed). However, some blisters may be filled with blood (blood blisters) - if they become infected or inflamed they can also be filled with pus.

A blister can form on any part of the body, but the most common parts are the feet and hands.

Friction blisters are more likely to develop in skin areas with a thick horny layer held tightly to the underlying structures, such as the soles of the feet or the palms of the hands.

There are a number of different reasons why blisters develop. After the skin has become damaged fluid builds up between the the upper layer of the skin and the layers below. Some of the most common causes of blisters are listed below:

Blisters on feet caused by running without shoes.Friction or rubbing on the skin - intense friction or rubbing on the skin can result in the formation of a blister if it continues for long enough.

This typically occurs after a long walk or by wearing improper shoes - they more easily develop if the skin is wet or moist. These blisters can eventually lead to more serious complications such as infection.

Exposure to chemicals - when the skin comes in contact with chemicals found in detergents and solvents blisters can develop. This is also called contact dermatitis. Exposure to certain blister agents, such as mustard gas, can lead to severe and large blisters.
High temperatures - extreme temperatures can cause first and second degree burns. Blisters that arise from second degree burns typically manifest themselves almost immediately after the skin becomes damaged, whereas those that develop because of first degree burns tend to appear a couple of days after the skin damage.
Medical conditions - the most common are herpes, impetigo, dyshidrosis, and chickenpox.

Other conditions include: bullous pemphigoid, pemphigus, dermatitis herpetiformis, chronic bullous dermatosis, cutaneous radiation syndrome, and epidermolysis bullosa.

There are many ways to prevent blisters from developing in the first place.

Wearing comfortable shoes and using socks that can manage moisture can prevent blisters from developing on the feet, particularly among those who sweat a lot - sport socks help keep the feet dry.

Using a protective layer of padding and using a friction management patch applied to shoes also help prevent blisters.

Talcum powder can be applied on the skin to reduce the friction from gloves and shoes.

You can protect yourself from blisters caused by chemicals by wearing gloves.

Blisters caused by sunburn can be prevented if you apply a good sunscreen, wear protective clothing (including a hat), and limit your exposure.

Researchers from the US Army Research Laboratory, Maryland, reported in the journal Sports Medicine1 that:

Antiperspirants with emollients and drying powders applied to the feet do not reduce the risk of developing friction blisters.
Closed cell neoprene insoles may reduce the incidence of foot blisters in runners.
Runners who wear foot socks made of acrylic tend to have fewer blisters.
"A thin polyester sock, combined with a thick wool or polypropylene sock that maintains its bulk when exposed to sweat and compression reduces blister incidence in Marine recruits."
After sun lotion can ease discomfort of burns

If the pain is not unbearable, leave the blister alone, do not try to burst it. A layer of padding filled with liquid over damaged skin allows it to repair itself.

The blister cushions the affected skin and protects it from infection.

Although most blisters will heal naturally over time, there are ways to alleviate the symptoms of the pain:

Cover the blisters with a plaster, gauze pad or dressingHydrocolloid dressings can prevent discomfortApply an ice pack to the affected area right after the injury in order to relieve the pain. Do not apply ice directly onto the skinIn the case of burns use moisturizing and after-sun or calamine lotions to ease the discomfort.

According to the National Health Service2, UK, you should not peel off the dead skin on top of the blister if it bursts.

Let the fluid inside the blister drain. Then cover it with a dry, sterile dressing. Hydrocolloid dressings, which can be bought OTC (over the counter) in pharmacies, help protect the burst blister from infection.

If the top layer of dead skin has already rubbed off the burst blister, do not try and peel any of the remaining skin.

Written by Joseph Nordqvist

Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today Visit our dermatology section for the latest news on this subject. Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Nordqvist, Joseph. "What are blisters? How to prevent blisters." Medical News Today. MediLexicon, Intl., 16 Aug. 2013. Web.
16 Aug. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'What are blisters? How to prevent blisters'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Simple ultrasound could prevent post-op kidney damage

Featured Article
Academic Journal
Main Category: Urology / Nephrology
Also Included In: Preventive Medicine
Article Date: 05 Aug 2013 - 0:00 PDT Current ratings for:
Simple ultrasound could prevent post-op kidney damage

Acute kidney injury, in which the kidneys suddenly stop working properly, is a potentially severe condition that often follows major surgery and causes serious complications for patients. Now for the first time, researchers show that treatment with ultrasound beforehand can help prevent the problem in mice.

The protection from acute kidney injury (AKI) comes from the anti-inflammatory effects of this simple, drug-free, non-invasive treatment, the scientists believe.

Mark Okusa and Joseph Gigliotti of the University of Virginia and colleagues report their findings in the Journal of the American Society of Nephrology.

Dr. Mark Okusa told the press:

"Our studies using non-invasive ultrasound now provide us with an active treatment that appears to be simple, effective, and nontoxic for the prevention of acute kidney injury.

"To our knowledge this has never been described for the prevention of tissue or organ injury."

Acute kidney injury is becoming an increasingly common complication in patients who have major surgery. It occurs because sometimes during major surgery the normal blood flow to the kidneys is disrupted. Once AKI sets in, it is very difficult to treat.

Acute kidney injury not only affects quality of life for patients, but also increases healthcare costs, and raises the risk of death following major surgery, note the authors.

A study published in 2008, showed that risk of death persists in heart patients with AKI even after discharge from hospital.

For their study, the researchers exposed anesthetized mice to ultrasound 24 hours before disrupting the blood supply to their kidneys.

They used the same kind of device that clinicians use to take regular ultrasound images.

Once blood flow was restored, they found that the health of the animals' kidneys had been preserved.

Another group of mice that received a sham treatment did not show preserved kidney health: their kidneys showed significant injury.

On further analysis, the researchers found that the ultrasound seemed to have stimulated the spleen to produce an anti-inflammatory response that protected the kidneys.

The researchers believe that the mechanisms that cause the acute kidney injury may also be responsible for similar damage to lung, heart and liver and that this type of treatment could prevent injury in other organs too.

Experts suggest the study offers numerous and promising possibilities because there are many procedures that carry a high risk of AKI.

In an editorial in the same issue of the journal, Alain Le Moine of Erasme Hospital in Belgium, and colleagues, note that:

"In searching for novel approaches to prevent and even cure AKI, we believe that splenic ultrasound stimulation has a bright future ahead."

Progress is also being made in predicting which post-operative patients are at higher risk for acute kidney injury. Current methods - such as measuring serum creatinine and urine output - may not show changes for several days, allowing time for serious kidney damage to have happened already.

But in an international study published earlier this year, researchers found two biomarkers that spot AKI risk sooner.

Written by Catharine Paddock PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today Visit our urology / nephrology section for the latest news on this subject. "Ultrasound prevents renal ischemia-reperfusion injury by stimulating the splenic cholinergic anti-inflammatory pathway," Gigliotti JC, Huang L, Ye H et al, JASN, published online ahead of print, 1 August 2013; DOI: 10.1681/ASN.2013010084; Abstract/summary. Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Paddock, Catharine. "Simple ultrasound could prevent post-op kidney damage." Medical News Today. MediLexicon, Intl., 5 Aug. 2013. Web.
5 Aug. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Simple ultrasound could prevent post-op kidney damage'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Mathematical biologists study how to best prevent bullet deaths

Main Category: Public Health
Article Date: 30 Jul 2013 - 1:00 PDT Current ratings for:
Mathematical biologists study how to best prevent bullet deaths

Aiming to quell heated national debate about gun control with factual answers, two UC Irvine mathematicians have designed parameters to measure how to best prevent both one-on-one killings and mass shootings in the United States. Their paper appears in the journal PLOS ONE.

"It's time to bring a scientific framework to this problem," said lead author Dominik Wodarz, a mathematical biologist who works on disease and evolutionary dynamics. His co-author and wife, Natalia Komarova, a mathematician who studies biomedical and social trends, added: "Can we design a rational way to argue about guns?"

Both were appalled not just by the December shooting deaths of 20 youngsters and eight adults in Newtown, Conn., but also by the bitterly emotional dispute over weapons that erupted anew. They decided to put their professional expertise to work.

"This debate cannot be settled satisfactorily by verbal arguments alone, since these are often driven by opinion and lack a solid scientific backing," the authors write. "What is under debate is essentially an epidemiological problem: How do different gun control strategies affect the rate at which people become killed by attackers, and how can this rate be minimized?"

The duo reviewed available data stretching as far back as World War I, then drew up equations to compute whether policies ranging from a total firearm ban to "arm everyone" increase or decrease homicides. After running the numbers, they found that in more common domestic and one-on-one crimes, reduced legal gun availability - if properly enforced - is likelier to lower deaths. But in rare mass shootings, armed citizens might save lives if sufficiently trained to avoid accidentally shooting fleeing bystanders.

They note that data is missing that could strengthen their results. For instance, homeowners who used a weapon to stop a robbery might not make a report to police. "Stand your ground" laws being widely discussed in the wake of Trayvon Martin's killing could influence the parameters too. "Whether such laws better protect the public or increase deaths needs to be determined statistically," Wodarz said. "Do you have a greater chance of dying if you run or if you face your attacker with a weapon?"

The authors say key parts of their equations should be studied more closely: the fraction of offenders who illegally possess a gun, the statistical degree of protection provided by legal gun ownership, and the number of people who are legally carrying a gun when attacked. Comprehensive data in those areas, they say, could further aid the development and implementation of effective policies.

Federal funding for gun control research was essentially nonexistent for nearly two decades, but President Barack Obama in January labeled firearm deaths a public health crisis and ended the longstanding freeze. About 11,000 Americans die each year from gunshot homicides.

A large number of peer reviews - 11 in total - were solicited by journal editors; two or three are the norm. A wide array of opinions were expressed, ranging from enthusiastically positive and constructive to a critic who stated that scientific methods would never be useful in this area.

The authors were warned to be prepared for heated responses to their paper but believe it's critical to bring the best tools of research to the issue.

"If the current discussion could be steered toward science, rather than having a heated debate without much of a logical foundation, a big step forward toward saving lives would be achieved," they said.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our public health section for the latest news on this subject. Please use one of the following formats to cite this article in your essay, paper or report:

MLA

University of California - Irvine. "Mathematical biologists study how to best prevent bullet deaths." Medical News Today. MediLexicon, Intl., 30 Jul. 2013. Web.
30 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Mathematical biologists study how to best prevent bullet deaths'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Discovery of gene function may help prevent kidney stones

Main Category: Genetics
Also Included In: Urology / Nephrology
Article Date: 26 Jul 2013 - 2:00 PDT Current ratings for:
Discovery of gene function may help prevent kidney stones

The discovery of a gene's function in E. coli and other bacteria might lead to a probiotic to prevent the most common type of kidney stone, according to a Purdue University study.

Human cells can't metabolize oxalate, an acidic chemical found in nearly all plants we eat, so any oxalate we absorb from food must be excreted from the body. Calcium-oxalate urinary stones can form when oxalate reaches a high concentration in the kidneys. About 80 percent of kidney stones are composed of insoluble calcium oxalate.

T. Joseph Kappock, assistant professor of biochemistry, and his research team made the discovery during a study of genes in Acetobacter aceti, a harmless bacterium that is typically used to convert wine to vinegar. Acetobacter aceti, which normally lives on plant tissue, thrives in acidic conditions that easily kill most other bacteria, Kappock said.

The researchers were searching for other acids in addition to acetic acid, the acid present in vinegar, that the bacterium can metabolize.

"We were very excited when we realized E. coli has the same genetic setup as Acetobacter aceti," said Kappock, whose findings were published in the journal PLOS ONE.

Kappock and doctoral students Elwood A. Mullins and Kelly L. Sullivan found that Acetobacter aceti and E. coli each contain an enzyme with a previously unknown function, called YfdE in E. coli.

DNA sequencing had identified related genes in each bacterium, but provided little insight about its function.

"When we look at a bacterial genome by DNA sequencing, we can't tell what many of the proteins in the organism do," Kappock said. "I compare it to knowing that a vehicle has an internal combustion engine. You don't know if it's in an Indy car or a diesel truck. DNA sequencing tells us we have an internal combustion engine in this organism, but we don't know what it's for or what it can do."

Many other bacteria have the same genes but don't seem to be capable of using them.

"A few bacteria in the gastrointestinal tract eat oxalate, and we think we know how those work," Kappock said. "But we don't know why so many others are killed by oxalate, even though they have genes that would seem to be able to protect them. Oxalate is a very hard nut to crack. It's a very stable molecule that is difficult to decompose. The enzymes that process it are pretty specialized and don't seem to connect to normal bacterial metabolic pathways in an obvious way."

The researchers determined which chemicals are processed by the YfdE enzyme, following a hunch that it would use oxalate. Their results connected oxalate degradation to the core of bacterial metabolism.

Assigning a function to YfdE may help identify beneficial bacteria that could serve as probiotic agents in the human gastrointestinal tract to reduce the risk of kidney stone formation. Kidney stones, which affect more than 5 percent of the U.S. population, can cause painful blockages of the urinary tract.

"If we understand what bacteria need to degrade oxalate, then we might have a better idea how to identify strains that can do that, and thereby suppress the uptake of dietary oxalate" he said. "There are probably bacteria out there that have engineered themselves to do this for us."

Genome-sequencing information will increase the speed of the search, Kappock said.

"Because we've figured out what the gene product does, we will be able to find it in any organism and can zero in on those that might be beneficial," he said.

The researchers used X-ray crystallography to pinpoint the most important regions of the YfdE enzyme.

Kappock said the information has other applications, as well. Scientists and engineers who are interested in mapping and reprogramming microbial metabolism now know what one more gene product does.

"Our one piece of the puzzle will help others understand other metabolic networks," he said.

Agricultural Research at Purdue, the National Science Foundation and the U.S. Department of Energy funded the research.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our genetics section for the latest news on this subject.

Abstract:

Acetyl-CoA:Oxalate CoA-transferase 1 Function and X-ray Crystal Structure of Escherichia coli YfdE

Elwood A. Mullins 1, 2; Kelly L. Sullivan 1; T. Joseph Kappock 1;

1 Dept. of Biochemistry, Purdue University, West Lafayette, Indiana, USA

2 Dept. of Chemistry, Washington University, St. Louis, Missouri, USA

Many food plants accumulate oxalate, which humans absorb but do not metabolize, leading to the formation of urinary stones. The commensal bacterium Oxalobacter formigenes consumes oxalate by converting it to oxalyl-CoA, which is decarboxylated by oxalyl-CoA decarboxylase (OXC). OXC and the class III CoA-transferase formyl-CoA:oxalate CoA-transferase (FCOCT) are widespread among bacteria, including many that have no apparent ability to degrade or to resist external oxalate. The EvgA acid response regulator activates transcription of the Escherichia coli yfdXWUVE operon encoding YfdW (FCOCT), YfdU (OXC), and YfdE, a class III CoA-transferase that is ~30% identical to YfdW. YfdW and YfdU are necessary and sufficient for oxalate-induced protection against a subsequent acid challenge; neither of the other genes has a known function. We report the purification, in vitro characterization, 2.1- A crystal structure, and functional assignment of YfdE. YfdE and UctC, an orthologue from the obligate aerobe Acetobacter aceti, perform the reversible conversion of acetyl-CoA and oxalate to oxalyl-CoA and acetate. The annotation of YfdE as acetyl-CoA:oxalate CoA-transferase (ACOCT) expands the scope of metabolic pathways linked to oxalate catabolism and the oxalate-induced acid tolerance response. FCOCT and ACOCT active sites contain distinctive, conserved active site loops (the glycine-rich loop and the GNxH loop, respectively) that appear to encode substrate specificity.

Purdue University

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

University, Purdue. "Discovery of gene function may help prevent kidney stones." Medical News Today. MediLexicon, Intl., 26 Jul. 2013. Web.
29 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Discovery of gene function may help prevent kidney stones'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

New stem cell gene therapy gives hope to prevent Sanfilippo - an inherited neurological disease

Main Category: Neurology / Neuroscience
Also Included In: Stem Cell Research;  Genetics
Article Date: 25 Jul 2013 - 1:00 PDT Current ratings for:
New stem cell gene therapy gives hope to prevent Sanfilippo - an inherited neurological disease

Scientists from The University of Manchester have used stem cell gene therapy to treat a fatal genetic brain disease in mice for the first time.

The method was used to treat Sanfilippo - a fatal inherited condition which causes progressive dementia in children - but could also benefit several neurological, genetic diseases.

Researchers behind the study, published in the journal Molecular Therapy this month, are now hoping to bring a treatment to trial in patients within two years.

Sanfilippo, a currently untreatable mucopolysaccharide (MPS) disease, affects one in 89,000 children in the United Kingdom, with sufferers usually dying in their mid-twenties. It is caused by the lack of SGSH enzyme in the body which helps to breakdown and recycle long chain sugars, such as heparan sulphate (HS). Children with the condition build up and store excess HS throughout their body from birth which affects their brain and results in progressive dementia and hyperactivity, followed by losing the ability to walk and swallow.

Dr Brian Bigger, from the University of Manchester's Institute of Human Development who led the research, said bone marrow transplants had been used to correct similar HS storage diseases, such as Hurler syndrome, by transplanting normal cells with the missing enzyme but the technique did not work with Sanfilippo disease. This is because monocytes, a type of white blood cell, from the bone marrow, did not produce enough enzyme to correct the levels in the brain.

Dr Bigger said: "To increase SGSH enzyme from bone marrow transplants, and to target it to the cells that traffic into the brain, we have developed a stem cell gene therapy which overproduces the SGSH enzyme specifically in bone marrow white blood cells.

"We have shown that mice treated by this method produce five times the normal SGSH enzyme levels in the bone marrow and 11 per cent more compared to normal levels in the brain.

"The enzyme is taken up by affected brain cells and is enough to correct brain HS storage and neuro inflammation to near normal levels and completely corrects the hyperactive behaviour in mice with Sanfilippo.

"This is extremely exciting and could have huge implications for treatments. We now hope to work to a clinical trial in Manchester in 2015."

The University of Manchester team is now manufacturing a vector - a tool commonly used by molecular biologists to deliver genetic material into cells - for use in humans and hope to use this in a clinical trial with patients at Central Manchester University Hospital NHS Foundation Trust by 2015.

The stem cell gene therapy approach was recently shown by Italian scientists to improve conditions in patients with a similar genetic disease affecting the brain called metachromatic leukodystrophy, with results published in the journal Science earlier this month.

Manchester scientists refined the vector used by the Italian scientists. "This approach has the potential to treat several neurological genetic diseases," Dr Bigger added.

The research was funded by the UK MPS Society and the Sanfilippo Children's Research Foundation based in Canada.

Christine Lavery MBE, Chief Executive of the UK MPS Society, said: "Since 1970 over 130 children and young adults have lost their lives to Sanfilippo disease (MPS III) in the UK alone.

"Whilst new therapies for other MPS diseases are changing children's lives, parents of children with Sanfilippo disease can do no more than give the best possible care and live in hope that a treatment is around the corner. The positive results of Dr Brian Bigger's gene therapy programme in mice provides optimism for future generations of Sanfilippo children."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our neurology / neuroscience section for the latest news on this subject.

The research is published in the journal Molecular Therapy this month.

The University of Manchester

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

The University of Manchester. "New stem cell gene therapy gives hope to prevent Sanfilippo - an inherited neurological disease." Medical News Today. MediLexicon, Intl., 25 Jul. 2013. Web.
26 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'New stem cell gene therapy gives hope to prevent Sanfilippo - an inherited neurological disease'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Beagle Food To Prevent Health Problems

A Beagle can effectively consume large amounts of food, the main problem may be the dog has a tendency to put on pounds. You do not need to determine a body fat, ugly Beagle with illness. Beagles can consume food rapidly and don't particularly have preferences for several kinds of food. A powerful olfaction sometimes takes the Beagle to undesirable places searching for food. Dog proprietors therefore have been in an issue regarding just how much they have to feed their pets to be able to prevent them from engaging in harmful situations.

Feed A Little A Lot More Than Needed

You might need a while to gauge the quantity of food your Beagle can eat. It is a safe wager to give your pet a little a lot more than the conventional recommendation. For instance, just one cup or a couple of high-quality meals are all that's needed. A Beagle is small , weighs in at roughly twenty to thirty pounds. So it doesn't require more. Feed your dog two whole cups initially to see if it gains weight. Exercise the Beagle a little more until it's tired and sleepy.

The sooner you begin, the faster you understand just how much meals are needed. Ideally, you house train your Beagle like a puppy after which follow standard instructions to give your dog. Compensate with a lot more treats included in the behavior training training course. Quite simply, the greater positive your pet works out to become, the greater treats it will get. Care should automatically get to avoid addiction or reliance on food products outdoors normal foods.

Precisely What In The Event You Feed a Beagle Puppy

Before the puppy is eight days old, it takes mother's milk for healthy nutrition. Solid food ought to be introduced once the dog is about five days old. It's the proper time to obtain your Beagle utilized to home-made food. Non-vegetarians don't have much to complete, except feed their dogs soft meat combined with cooked grain and veggies. Sharp chicken bones should be prevented. Commercial Beagle food consists of chemical preservatives not necessarily required for your dog.

People frequently add milk substitutes to normalcy food to produce a wet broth. The Beagle puppy adjusts better and it is generally pleased with the meal. Milk substitutes could be gradually replaced with similar volume of solid food. Sufficient body fat should be incorporated within the food, or you can get health issues including lethargy and weight problems.

Helpful Information On Adult Pet Food

Housebreaking is a vital facet of training your dog to reside quietly in your house. The Beagle must understand that eating food belongs to a normal routine and should therefore be given sufficient quantity to help keep it satisfied during the day. Commercial food does contain some undesirable chemicals. Effectively, this means you need to feed your dog a lot more than needed.

Beagles are hounds and typically resided on meat for 100s of years. Altering fundamental qualities including food habits is unwarranted. You could regulate the kind of meat your pet consumes based on availability. Since Beagles require moderate but healthy food choices, a routine is definitely established with minimum effort. Begin feeding your pet quite early, and you'll never regret your time and efforts to maintain your beloved dog happy and healthy.

View the original article here