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Prostate cancer patients who receive brachytherapy and remain free of disease for five years or greater are unlikely to have a recurrence at 10 years, according to a study in the July 1 issue of the International Journal of Radiation Oncology Biology Physics, the official journal of the American Society for Radiation Oncology (ASTRO).

Brachytherapy is the placement of radioactive sources in or just next to a tumor either permanently or temporarily, depending upon the cancer.

In the study, researchers at The Mount Sinai Medical Center Departments of Radiation Oncology and Urology in New York followed 742 prostate cancer patients who were treated with brachytherapy alone, brachytherapy and hormonal therapy, or combined brachytherapy and external beam radiotherapy (EBRT) between 1991 and 2002. None of these patients had recurred during their first five years posttreatment. They found that the PSA level taken at five years was an indicator of how well a patient would do in the future and the overall chance of being cancer free at 10 years was 97 percent. Also, none of the study participants developed metastatic disease or died from prostate cancer.

“Our data have indicated that improvements in treatment are continuing and that these will continue to have an effect on prostate brachytherapy data for years to come,” Richard Stock, M.D., lead author of the study and chairman of radiation oncology at The Mount Sinai Medical Center, said. “Late failure rates will continue to decrease, making prostate brachytherapy alone and combined with hormonal therapy and/or EBRT an increasingly attractive treatment option.”

ASTRO is the largest radiation oncology society in the world, with more than 10,000 members who specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, biology and physics, the Society is dedicated to improving patient care through education, clinical practice, advancement of science and advocacy.

Like astronomers counting stars in the familiar universe of outer space, chemists in Switzerland are reporting the latest results of a survey of chemical space the socalled chemical universe where tomorrows miracle drugs may reside. The scientists conclude, based on this phase of the ongoing count, that there are 970 million chemicals suitable for study as new drugs. Scheduled for the July 1 issue of the Journal of the American Chemical Society, the study represents the largest publicly available database of virtual molecules ever reported, the researchers say.

JeanLouis Reymond and Lorenz Blum point out that the rules of chemical bonding allow simple elements such as carbon, hydrogen, oxygen, nitrogen and fluorine to potentially form millions of different molecules. This socalled “chemical universe” or “chemical space” has an enormous potential for drug discovery, particularly for identifying socalled “small molecules” made of 10 to 50 atoms. Most of todays medicines consist of these small molecules. Until now, however, scientists had not attempted a comprehensive analysis of the molecules that populate chemical space.

In the report, Reymond and Blum describe development of a new searchable database, GDB13, that scientists can use in the quest for new drugs. It consists of all molecules containing up to 13 atoms of carbon, nitrogen, oxygen, sulfur, and chlorine under rules that define chemical stability and synthetic feasibility. The researchers identified more than 970 million possible structures, the vast majority of which have never been produced in the lab. Some of these molecules could lead to the design and production of new drugs for fighting disease, they say.

“970 Million Druglike Small Molecules for Virtual Screening in the Chemical Universe Database GDB13″

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Transferring just one embryo at a time to a womans womb after embryos have undergone preimplantation genetic diagnosis (PGD) and freezing at the blastocyst stage has become a real option after researchers achieved pregnancy rates that were as good as those for blastocysts that had not had a cell removed for PGD before freezing. Their results mean that it will be possible to reduce the number of multiple pregnancies after PGD and the consequent complications associated with these pregnancies.

The research was presented at the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam and published online in Europes leading reproductive medicine journal, Human Reproduction, simultaneously.

Dr Yacoub Khalaf, director of the assisted conception unit at Guys and St Thomas Hospital, London (UK), told the conference “To the best of our knowledge, our study is the first to provide reassurance that a strategy of elective single embryo transfer in good prognosis patients seeking PGD, backed by an efficient PGD cryopreservation service, can result in pregnancy rates that are comparable to those for nonbiopsied embryos that are frozen as part of conventional fertility treatment. These results should empower fertility centres to include PGD cycles for inherited genetic disorders in their efforts to reduce the multiple pregnancy rates after various forms of assisted conception treatment. Given the increasing number of PGD cycles performed each year, the advantage of widespread application of this policy would be considerable.”

Until now, fertility specialists have not applied a single embryo transfer policy to PGD for inherited genetic disorders because of concerns about how well biopsied embryos survive after freezing and thawing. “It was thought that the effect of the biopsy might reduce the embryos tolerance to freezing. This concern was not based on any scientific evidence, only on observations of low survival rates of biopsied frozen embryos,” said Dr Khalaf.

From January 2006 to July 2008 Dr Khalaf and his colleagues offered single embryo transfer together with freezing of surplus blastocysts to couples seeking PGD for single inherited genetic disorders such as cystic fibrosis. All the embryos were biopsied for the purposes of PGD on the third day after fertilisation, which is the time that they start to divide. Healthy embryos were cultured in the laboratory for a further two to three days to check that they were capable of reaching the next appropriate stage of development the blastocyst stage. At this point, 32 couples who had two or more embryos that had successfully reached the blastocyst stage were offered the option of having one transferred to the womb and the rest frozen.

The researchers compared the pregnancy outcomes from a subsequent 32 frozenthawed PGD cycles in these couples with the pregnancy outcomes from a control group of couples where 191 cycles of conventional IVF/ICSI were carried out using embryos that were frozen and thawed before implantation, but not biopsied at any stage.

They found that the blastocyst survival rate after thawing was similar between the PGD and IVF/ICSI groups (87% versus 88% respectively). There was no significant difference in the implantation and clinical pregnancy rates (35% versus 29% and 34% versus 36% respectively). The overall ongoing pregnancy rate for all frozen cycles (PGD and IVF/ICSI) was 34%, which compares favourably with the UK national average for frozen cycles (currently 18% live birth rate per thaw).

When the same period was compared with the period before the single embryo transfer policy was introduced for PGD couples, the multiple pregnancy rate in the cycles of fresh PGD dropped from 36% to 10% with no reduction in pregnancy rates.

Dr Khalaf said “This research suggests that responsible clinical decisions do not have to come at the expense of reducing effectiveness of treatment. You can be responsible and maintain the chances of success for your patients by good clinical judgment and using the appropriate techniques.

“For patients, this provides reassurance that a couples chance of having a healthy child is not reduced by replacing only one blastocyst and freezing the surplus ones. Those frozen blastocysts do have a very good chance of leading to a healthy pregnancy too, and, therefore, patients will not feel pressurised to have more than one embryo replaced (with the increased risk of multiple pregnancies) in order to make use of their biopsied, unaffected embryos for which, otherwise, they might have little use. Now, these frozen blastocysts offer them the chance of an additional healthy pregnancy without having to go through the whole treatment cycle again.”

The first author of the paper in Human Reproduction, Dr Tarek ElToukhy, a consultant in reproductive medicine and PGD at the assisted conception unit at Guys and St Thomas Hospital, said “This study represents a continuation of our efforts to advance IVF and PGD safety through single blastocyst transfer and embryo freezing.”

Source
Mary Rice

The UK spends around £2.5 billion each year on dental materials to replace or strengthen teeth*. The Chewing Robot is a new biologically inspired way to test dental materials and it will be shown to the public for the first time at this years Royal Society Summer Science Exhibition [30 June to 4 July].

Researchers at the University of Bristols Department of Mechanical Engineering in collaboration with the Department of Oral and Dental Science have developed the Chewing Robot to study dental wear formation on human teeth.

Dental elements, such as crowns and bridges, are made from wellknown metals, polymers and ceramics but their dental wear properties are often poorly understood. Clinical trials examining the wear of human teeth are expensive and timeconsuming. By the time a new material has been tested, it is often obsolete.

The movements and forces involved in natural chewing action have been replicated using the new chewing simulator the Chewing Robot. The robot is based on a threedimensional mechanism with six linear actuators that reproduce the motion and forces sustained by teeth within a human mouth.

A human jaw is a powerful and complex piece of natural machinery, allowing a person to chew in many different ways. The lower jaw and the teeth move with six degrees of freedom, translating and rotating along each of the Cartesian axes.

Dr Kazem Alemzadeh, Senior Lecturer in the Department of Mechanical Engineering recognised that the StewartGough platforms have been used to provide and control the same six degrees of freedom in aircraft simulators, and so he proposed the Chewing Robot concept based on just such a platform. The design and development of the Chewing Robot was carried out by Daniel Raabe, a PhD student in the Department of Mechanical Engineering.

The robot has the potential to dramatically improve the process of developing and testing new dental materials.

Daniel Raabe said “By reproducing natural bite forces and movements, the Chewing Robot can help improve and accelerate the process of developing new dental restorative materials that may someday be found in a persons mouth.”

Notes

The Royal Society Summer Science Exhibition is the premier annual showcase for scientific excellence in the UK, and runs from Tuesday 30 June to Saturday 4 July at the Royal Society in London.

The exhibit, The Chewing Robot a new biologicallyinspired way to test dental materials , sponsored by the Engineering and Physical Sciences Research Council (EPSRC), the Wellcome Trust, the Bristol Robotics Laboratory (BRL), Holford and Partners and the Department of Oral and Dental Science, is located in the City of London Room, ground floor.

Visitors to the stand will have the opportunity to find out more about biologically inspired design. Two interactive units will complement the Chewing Robot exhibit. The first being a teeth counting activity. The second interactive activity will enable people of all ages to make a mould of an upper or lower set of teeth using modelling LabPutty. The Chewing Robot replicates the human jaw, allowing it to generate wear formation on single dental elements.

The exhibit has been developed with the support of the Universitys Centre for Public Engagement, which encourages academics to engage with the public.

For more information on the Chewing Robot visit bristol.ac.uk/mecheng/news/2009/004

Source
Joanne Fryer

The challenge to the Prime Minister by Mark Harper MP, Shadow Minister for Disabled People, to remove Section 141 of the Mental Health Act which strips an MP of their seat in Parliament if detained under the Act for more than six months, and his tabling of an amendment to the Equality Bill on this issue, are both very welcome and long overdue.

This unacceptable discrimination against people with mental health conditions by placing them in the same category as criminals, who also lose their seat in the House (as opposed to people off sick for more than six months with physical health conditions, who do not), has never been acted upon, but the very existence of this measure helps to create a climate of stigma and fear for people with mental health conditions.

RADAR welcomes and thoroughly supports Mr. Harpers efforts to consign this measure, which recalls the days of Bedlam and tickets to see the “lunatics”, to history, where it belongs.

David Stocks, RADAR Empowerment Project Manager, said

“I welcome Mark Harper MPs statement regarding the removing the legislation that allows the removal of an MP from office if they have been sectioned under the Mental Health Act. It is legislation that belongs to the Dark Ages and not to the 21st century. The existence of such legislation is symbolic and by its removal a clear message will be sent out that diversity is embraced in all levels of leadership.”

“With a bipolar mental health condition myself I have long campaigned for such changes. I now have the chance to help others attain leadership positions through RADARs Empowerment Programme a programme that celebrates human diversity, providing people with the confidence and skills required for leadership. The abolition of this act will go a long way towards bringing this diversity into positions of leadership in Parliament.”

Notes

1. RADAR, founded in 1977, is the UKs largest disability campaigning network with over 1000 individual and organisational members. RADAR stands for the Royal Association of Disability and Rehabilitation.

White House officials said Thursday that biotech drugs (also known as biologics) should only be protected from generics competition for seven years, Reuters reports.

“The amount of protection for brandname companies is a sticking point among lawmakers working to set up a legal pathway for approval of generic forms of biotech drugs. The brandname versions can cost tens of thousands of dollars per year. Industry groups representing brandname makers are lobbying for 12 to 14 years, saying it is crucial for encouraging companies to invest in development of new medicines.”

The White House, “in a letter to Rep. Henry Waxman, DCalif., said seven years strikes the appropriate balance between innovation and competition by providing for seven years of exclusivity.”

The biologic drugs are manmade versions of human proteins and treat conditions like anemia, rheumatoid arthritis and cancer, Reuters reports. The drug industry is worried that such a move will make researching and developing new drugs less attractive to drug makers (Richwine, 6/25).

Bloomberg “Unlike conventional pills, biologics cant be copied even after patents expire. Patient groups, payers and generic drugmakers have battled biotechnology companies for more than two years over how to allow competition. … Amgen, of Thousand Oaks, California, and Genentech, a unit of Swiss drugmaker Roche, are the largest U.S. makers of biologics. They say their medicines cant be replicated like conventional pills produced through chemical synthesis because of complex manufacturing and finished products that have slight variances … Generic biologics may be sold at a 10 percent to 30 percent discount, allowing for substantial consumer savings without eroding market share for brandname drug companies, the Federal Trade Commission said in a June 10 report” (Larkin, 6/25).

This information was reprinted from kaiserhealthnews.org with kind permission from the Henry J. Kaiser Family Foundation. You can view the entire Kaiser Daily Health Policy Report, search the archives and sign up for email delivery at kaiserhealthnews.org.

© Henry J. Kaiser Family Foundation. All rights reserved.

A revolutionary new protein stabilisation technique has been developed by scientists funded by the Biotechnology and Biological Sciences Research Council (BBSRC) which could lead to 30 per cent more proteins being available as potential targets for drug development opening up exciting possibilities in drug discovery.

Understanding the structure of proteins is a vital first step in developing new drugs, but to date, drug development has been slowed because due to their instability, proteins are difficult to work with in lab conditions. However, using nanoparticles, scientists from the Universities of Birmingham and Warwick have found a way to preserve membrane proteins intact, enabling detailed analysis of their structure and molecular functions.

These new findings, which have just been published online in the Journal of the American Chemical Society, will give scientists access to previously ignored proteins deemed too unstable to work with.

Professor Michael Overduin, from the University of Birmingham, who led the study, explained “We have shown how a polymer can wrap around and preserve membrane proteins intact in stable nanoparticles. Membrane proteins are the most valuable but technically challenging targets for drug discovery. Finding a gentle solution that preserves their structure and activity, yet is robust enough for experimental interrogation, has eluded scientists for decades, but is now available.”

Using a polymer styrene maleic acid lipid particles (SMALPs), the researchers solubilised a pair of membrane proteins. They found that not only did the proteins maintain their folded structure, binding and enzyme activities in the SMALPs, but also that using the nanoparticles allowed them to be simply and rapidly used for virtually any laboratory analysis.

Advantages of SMALPs over traditional ways to solubilise proteins such as detergents include enhanced stability, activity and spectral quality of the protein membranes.

Dr Tim Dafforn who jointly ran the study, said “In the past, studies have concentrated largely on soluble proteins as membrane proteins are so difficult to make. However, the discovery of the SAMLPs removes this barrier and opens up access to membrane proteins this has exciting clinical implications as it may enable drug discovery on receptors that are currently too difficult to produce or study by current methods.”

Commenting on the findings, BBSRC Chief Executive Professor Doug Kell, said “The attrition rate in developing new drugs is phenomenal. Only a tiny fraction make it into the clinic to benefit patients. Research such as this that can help to increase the number of potential targets will mean a larger pipeline for scientists to develop new drugs from and, ultimately more, better drugs for patients. Fundamental bioscience working in coordination with medical research is vital to deliver new, effective drugs.”

Source Biotechnology and Biological Sciences Research Council

It may have been the biggest curveball of Seattle Mariners pitcher Brandon Morrows life type 1 diabetes. Diabetes Forecast, the consumer magazine of the American Diabetes Association, features an interview with the bazookaarmed athlete in the July 2009 issue. Morrow shares insights on being a professional athlete while managing a chronic disease, his decision to stay in the bullpen, his supportive teammates and his unique and unexpected opportunity to mentor fellow Mariners reliever Mark Lowe, who also has diabetes.

Morrow was diagnosed with type 1 diabetes during his senior year of high school, around the same time scouts were zeroing in on his talent. After experiencing some of the common symptoms of diabetes such as frequent urination, excessive thirst, and unexplained weight loss Morrow went to see a doctor and was immediately hospitalized and diagnosed with type 1 diabetes. For Morrow, this was a challenge he would meet head on, and in the years since, he has developed a routine that consistently brings out his best performance. He wears an insulin pump (although he prefers to take it off when pitching), checks his blood glucose (sugar) at regular intervals, and incorporates his diabetes management routine into his bullpen routine. “It takes time to learn your body and know what you need to do and how your body will adjust,” he says. “Its a long process.”

Now Morrow is able to offer guidance and support to fellow pitcher Mark Lowe, who was diagnosed with diabetes just last year. “I think its good for both of us to have each other there to compare blood sugars and keep each other in good range and not slack off with eating habits or schedules,” Morrow says of Lowe. “We were close to begin with… And, you know, this can only bring you closer, to have [diabetes] in common and be able to talk about it and talk about routines and foods.”

This friendship, along with the teams support, has provided Morrow with a positive outlook. “You dont really hear about any athletes having diabetes or anything like that,” he says. “It was a scare at first. You dont know what to expect. But once you get on track, you realize nothing is really different.” Morrow goes on to tell the magazine about his advice for athletes with diabetes, thoughts about staying in the bullpen and his predictions for this season.

The July 2009 issue also brings you answers to crucial questions you may have had about exercising with diabetes How much aerobic activity should I get? How does exercise affect my blood glucose? When is the best time to work out? Do oral diabetes medications put me at risk for exerciseinduced hypoglycemia? What about insulin? How can I motivate myself?

This issue of Diabetes Forecast also brings you information about

A Teen on a Mission The American Diabetes Associations National Youth Advocate speaks to the Centers for Disease Control and Prevention Convention and lobbies on Capitol Hill.
A Healthier Way to Lose Weight ADAfunded researcher looks at weight loss and cardiac complications.
Not Too Sweet to Eat Experts share a few tricks to making delicious sugarfree foods.

Diabetes Forecast has been Americas leading diabetes magazine for more than 60 years, offering the latest news on diabetes research and treatment to provide information, inspiration, and support to people with diabetes.

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Experts have long suspected that part of the process of turning fleeting shortterm memories into lasting longterm memories occurs during sleep. Now, researchers at the RIKENMIT Center for Neural Circuit Genetics of MITs Picower Institute for Learning and Memory have shown that mice prevented from “replaying” their waking experiences while asleep do not remember them as well as mice who are able to perform this function.

The work, which has a profound implication in the centuryold search for the purpose of sleep, will be reported in the June 25 issue of Neuron.

It is widely believed that memories of events and spaces are stored briefly in the hippocampus before they are consolidated in the neocortex for permanent storage. The seahorseshaped hippocampus is thought to play a key role in learning and memory, but the precise circuits and mechanisms involved are not well understood.

“Our work demonstrates the molecular link between postexperience sleep and the establishment of longterm memory of that experience,” said Susumu Tonegawa, the Picower Professor of Biology and Neuroscience at MIT and lead author of the study. “Ours is the first study to demonstrate this link between memory replay and memory consolidation. The sleeping brain must replay experiences like video clips before they are transformed from shortterm into longterm memories.”

The researchers looked at a circuit within the hippocampus known as the trisynaptic pathway, in which neuronal information passes through the hippocampus three main substructures before moving on. “We demonstrated that this pathway is crucial for the transformation of a recent memory, formed within a day, to a remote memory that still exists at least six weeks later,” Tonegawa said.

Creating a strain of engineered mice in which a change of diet shuts down trisynaptic circuits, the researchers implanted electrodes that monitored the activities of the animals hippocampal cells as the animals ran a maze and then slept.

Notsoinstant replay

While they were still awake and running, the mice formed within their brains a pattern of place cells, or neurons that were firing in recognition of the maze the mice had learned to negotiate. During their postrun sleep, particularly during a deep sleep phase called slowwave, the specific sequence of place cells that fired during the run was “replayed” in a similar sequence.

In human studies testing the role of slowwave sleep in memory consolidation, the group that napped after memorizing word pairs such as “fruitbanana” and “toolpliers,” was able to recall a greater number of word pairs than those who did not nap.

This replay during sleep had been speculated, but has never been demonstrated, to be important for converting the recent memory stored in the hippocampus to a more permanent memory stored in the neocortex. “We have demonstrated that in the mutant mice in which the trisynaptic pathway is blocked, this replay process during the slowwave sleep is impaired,” Tonegawa said. The animals were able to form longterm memories of the maze only when their trisynaptic pathways were functioning after the formation of the shortterm memory.

“Our conclusion is that the trisynaptic pathwaymediated replay of the hippocampal memory sequence during sleep plays a crucial role in the formation of a longterm memory,” he said.

In addition to Tonegawa, authors are Picower Institute research scientist Toshiaki Nakashiba, Picower Institute postdoctoral associate Derek L. Buhl and Picower Institute research scientist Thomas J. McHugh.

This work was supported by the National Institutes of Health and Otsuka Pharmaceutical Development & Commercialization Inc. based in Tokyo.

Written by Deborah Halber, Picower Institute

MorphoSys AG (FSE MOR; Prime Standard Segment, TecDAX) today announced that the Company has submitted an application for the authorization of a phase 1b/2a clinical study in patients with active rheumatoid arthritis (RA) for its lead drug MOR103, a fully human HuCALderived monoclonal antibody directed against Granulocyte MacrophageColony Stimulating Factor. The trial, which will be conducted in multiple centers in several European countries, is expected to enroll 135 patients in total beginning in the second half of 2009. Additionally, the Company today reported positive results from the phase 1 clinical study for MOR103 in healthy volunteers. The results of this study indicate that MOR103 is generally safe and well tolerated at all doses administered.

“We are pleased to advance the clinical development of this promising compound into a phase 1b/2a clinical trial to further evaluate safety and tolerability as well as clinical activity in RA patients,” commented Dr. Arndt Schottelius, Chief Development Officer of MorphoSys. “In combination with the attractive preclinical profile the results we have seen in the phase 1 trial support our plans to develop MOR103 as a safe and efficacious drug for the treatment of inflammatory disorders. In addition to the excellent characteristics the antibody has shown so far with regard to affinity, specificity and stability, we have been able to demonstrate a robust serum halflife in humans.”

The completed phase 1 trial was designed as a randomized, doubleblind, placebo controlled single ascending dose study to assess the safety, tolerability and pharmacokinetic parameters of MOR103 in healthy volunteers. In total, 63 volunteers received ascending doses of MOR103 up to a concentration of 3 mg/kg or placebo in seven dose cohorts via intravenous infusion. No maximum tolerated dose (MTD) was reached in the study. Analysis of the pharmacokinetic properties of MOR103 showed a serum halflife typical of a fully human antibody which could translate into a competitive dosing regimen. The overall safety, tolerability and pharmacokinetic properties of MOR103 provide a solid foundation for the Companys development plans, including the forthcoming Phase 1b/2a study in patients.