Study may help develop novel ways to combat lipotoxic cardiomyopathy, related heart disease

A team led by Rolf Bodmer, Ph.D. at Sanford-Burnham Medical Research Institute recently unraveled an alternative pathway to lipotoxic cardiomyopathy in fruit flies – a genetic mechanism that occurs independently of a diet high in fat.

Since overactive SREBP seems to be the cause of heart disease in this system, can it be targeted to reduce heart disease? The researchers addressed this question by inhibiting SREBP or its fat-synthesizing target genes through genetic manipulation. In doing so, they were able to restore fat balance and rescue PE-deficient flies from heart malfunction. These beneficial effects were also achieved by reducing SREBP in just the heart, rather than the whole fly. As a result, the flies were still obese, but their hearts functioned normally. These findings further underscore the importance of SREBP in excess fat-related heart diseases, like lipotoxic cardiomyopathy.

"Here we identified a new metabolic pathway that exhibits striking similarities to obesity- and diabetes-related heart failure in humans," explained Dr. Bodmer, professor and director of the development and aging program at Sanford-Burnham and senior author of the study. "This information might now allow us to interfere with the toxic effects of high fat in the heart by directly manipulating these genes in the heart muscle."

Source: Sanford-Burnham Medical Research Institute

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Magnetic maneuverable capsule safe and well-tolerated in the stomach

A study from researchers in Germany showed that magnetic maneuvering of a modified capsule endoscope in the stomach of healthy volunteers under clinical conditions is safe, well-tolerated, and technically feasible. Maneuverability of the capsule within the stomach was excellent and visualization of the gastric mucosa, the inner lining of the stomach, was satisfactory in the majority of subjects.

The study participants swallowed the MMC and sherbet powder to distend the stomach, which flattens the folds of the stomach. The external magnetic paddle was used to manipulate the MMC within the stomach. MMC responsiveness was evaluated on a screen showing the MMC film in real time. The main outcome measurements were safety and tolerability, time the MMC remained in the stomach, its responsiveness to the magnetic paddle, and the area of the stomach lining visualized.

Results

The MMC was always clearly attracted by the magnetic paddle and responded to its movements. In seven participants, maneuverability was graded as excellent because the MMC followed the rotating and tilting movements of the magnetic paddle smoothly. It remained in the stomach for approximately 39 minutes (plus or minus 24 minutes). In seven subjects, both the cardia (part of the stomach immediately adjacent to the esophagus) and the pylorus (part of the stomach through which contents are emptied into the small intestine) were inspected and 75 percent or more of the gastric mucosa was visualized (greater than or equal to 50 percent in all of the remaining subjects). The researchers noted that a learning curve was clearly recognizable (identification of MMC localization, intended movements). Some limitations of the study included small amounts of fluid that blocked the view of an area of the stomach called the fundus and gastric distention was not sufficient to flatten all gastric folds. There were no adverse events.

Study participants completed a questionnaire after the procedure, asking about difficulties swallowing, pain or other complaints. Nine participants reported no complaints and one reported mild complaints of feeling pressure. The researchers concluded that remote control of the MMC in the stomach of healthy volunteers using a handheld magnet is safe and feasible. Responsiveness of the MMC was excellent, and visualization of the stomach lining was good, although not complete, in the majority of subjects. The system appeared to be clinically valuable and should be developed further.

Source: American Society for Gastrointestinal Endoscopy

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Antioxidants may cause fertility problems in females

Antioxidants are sold over the counter everywhere. They’re added to food, drink and face cream. But according to Prof. Nava Dekel of the Biological Regulation Department, we still don’t have a complete understanding of how they act in our bodies. New research by Dekel and her team, recently published in the Proceedings of the National Academy of Sciences USA (PNAS), has revealed a possible unexpected side effect of antioxidants: They might cause fertility problems in females.

Among other things, these results help fill in a picture that has begun to emerge in recent years of fertility and conception, in which it appears that these processes share a number of common mechanisms with inflammation. It makes sense, says Dekel, that substances which prevent inflammation in other parts of the body might also get in the way of normal ovulation, and so more caution should be taken when administering such substances.

Much of Dekel’s research has focused on fertility — her previous results are already helping some women become pregnant. Ironically, the new study has implications for those seeking the opposite effect. Dekel: ‘On the one hand, these findings could prove useful to women who are having trouble getting pregnant. On the other, further studies might show that certain antioxidants might be effective means of birth control that could be safer than today’s hormone-based prevention.’

Dekel and her team are now planning further studies to investigate the exact mechanics of this step in ovulation and to examine its effect on mice when administered in either food or drink. In addition, they plan to collect data on the possible link between females being administered antioxidant supplements and the difficulty to conceive.

Source: Weizmann Institute of Science

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Positive results from PLX4032 Phase 3 Trial in patients with metastatic melanoma

Plexxikon today announced positive data from an interim analysis of the BRIM3 trial, a large multi-center Phase 3 clinical study of PLX4032 in patients with previously untreated metastatic melanoma with the BRAF mutation. Patients treated with PLX4032 had an improved overall survival compared to patients treated with dacarbazine, the current standard of care.

Recently, Plexxikon announced its agreement to co-promote PLX4032 in the U.S. with Genentech, and is planning to begin building its commercial organization and sales force this year. PLX4032 is being co-developed with Roche, and now Genentech, a member of the Roche Group, under a 2006 license and collaboration agreement between Plexxikon and Roche. The companies plan to file for marketing approval with the health authorities in the U.S. and in Europe for PLX4032, and for its companion diagnostic, in 2011.

Combination trials with PLX4032, as well as trials in other BRAF-mutated cancers, are also planned.

In other recent news, the U.S. Patent and Trademark Office issued Plexxikon’s U.S. Patent No. 7,863,288, covering composition-of-matter claims for PLX4032 and providing a patent term until 2029. The accelerated development of a personalized medicine such as PLX4032 not only provides patient access to new medicines more quickly, but also maximizes patent life, thereby contributing substantive value to the program. The new U.S. patent further broadens Plexxikon’s intellectual property portfolio.

Source: Plexxikon Inc

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Higher fruit and vegetable intake lowers risk of dying from ischaemic heart disease

A European study investigating the links between diet and disease has found that people who consume more fruit and vegetables have a lower risk of dying from ischaemic heart disease – the most common form of heart disease and one of the leading causes of death in Europe.

Dr Crowe said: "The main message from this analysis is that, in this study, people who consume more fruits and vegetables have lower risk of dying from IHD. However, we need to be cautious in our interpretation of the results because we are unsure whether the association between fruit and vegetable intake and risk of IHD is due to some other component of diet or lifestyle.

"If we could understand, by means of well-designed intervention studies, the biological mechanisms that could underlie the association between fruits and vegetables and IHD, this might help to determine whether or not the relation between fruit and vegetables with IHD risk is causal."

In an accompanying editorial, Professor Sir Michael Marmot, director of the University College London (UCL) International Institute for Society and Health, head of the UCL Department of Epidemiology and Public Health, and chairman of the Commission on Social Determinants of Health, writes that it is difficult to reach firm conclusions about causation from results that show a 22% lower risk of dying from IHD (an odds ration of 0.78) in people who eat eight portions of fruit and vegetables a day.

He continues: "Such an odds ratio is, however, of huge practical importance. Cardiovascular disease is the most common cause of death. A reduction of 22% is huge. But… this reduction in mortality comes with consumption of eight portions a day, or 640g. Such a high consumption was found in only 18% of the men and women in these eight cohorts. There would need to be big shift in dietary patterns to achieve this healthy consumption of eight portions a day. It is worth trying to move in that direction. Reductions in cancers of several sites, in blood pressure and stroke, would add to this reduction in fatal CHD. Moving to a diet that emphasises fruit and vegetables is of great importance to public health."

SOURCE European Heart Journal

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Cancer cells brought back under normal control

Scientists at The University of Nottingham have brought cancer cells back under normal control ??” by reactivating their cancer suppressor genes. The discovery could form a powerful new technology platform for the treatment of cancer of the breast and other cancers.

And, in a breakthrough, they showed it is important to use oocytes from the ovary, because if the oocytes are ovulated these activities are lost. We thought that by treating cancer cells with extracts made from axolotl oocytes we could reverse the epigenetic marks on tumour suppressor genes, causing these genes to reactivate, and thereby stopping the cancerous cell growth."

The identification of the proteins responsible for this tumour reversing activity in axolotl oocytes is a major goal of future research which could form a powerful new technology platform for the treatment of cancers from the breast, and other tissues.

The University of Nottingham has a broad research portfolio but has also identified and badged 13 research priority groups, in which a concentration of expertise, collaboration and resources create significant critical mass. Key research areas at Nottingham include energy, drug discovery, global food security, biomedical imaging, advanced manufacturing, integrating global society, operations in a digital world, and science, technology & society.

Through these groups, Nottingham researchers will continue to make a major impact on global challenges.

nottingham.ac/news/pressreleases/2011/january/cancercellsundercontrol.aspx

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Positive preliminary results from Soligenix's SGX202 in GARS model

Soligenix, Inc., a late-stage biopharmaceutical company, announced today promising preliminary results from a preclinical study of SGX202 in a canine gastrointestinal acute radiation syndrome model.

"These preliminary results suggest that SGX202 may significantly improve survival from GARS," stated Dr. Georges. "SGX202 may potentially inhibit the cellular and innate immune mechanisms within the gut mucosa that exaggerate mucosal damage, and improve GI recovery after radiation. In the challenging area of radiation injury, the study met its primary objective in protecting dogs from GARS and extending their survival. We are completing our analysis of the data so that we may extend our investigations of SGX202 in GI recovery after radiation exposure and build upon these promising results."

"The current dog model of GARS used by Dr. Georges appears to be a robust model for studying the supportive care needs after TBI and for evaluating countermeasures for improving survival after TBI," stated Robert N. Brey, PhD, Chief Scientific Officer of Soligenix. "These results are encouraging and suggest that SGX202 may be an effective post exposure therapy for acute radiation syndrome.  Further, these findings support the active pharmacology of oral BDP and may have positive implications for the ongoing NCI-supported Phase 1/2 clinical study in radiation enteritis. We believe that these promising results merit further investigation and potential government funding of radiation injury in the Defense sector."

SOURCE Soligenix, Inc.

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