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August 27, 2006, 7:45 AM CT

A Murine Model of Age-Related Macular Degeneration

A Murine Model of Age-Related Macular Degeneration
Rajendra S. Apte*, Jennifer Richter, John Herndon, Thomas A. Ferguson*

1 Department of Ophthalmology, Washington University School of Medicine, St. Louis, Missouri, United States of America

BackgroundAge-related macular degeneration (AMD) is the leading cause of blindness in people over 50 y of age in at least three continents. Choroidal neovascularization (CNV) is the process by which abnormal blood vessels develop underneath the retina. CNV develops in 10% of patients with AMD but accounts for up to 90% of the blindness from AMD.Although the precise etiology of CNV in AMD remains unknown, the macrophage component of the inflammatory response, which has been shown to promote tumor growth and support atherosclerotic plaque formation, is thought to stimulate aberrant angiogenesis in blinding eye diseases. The current theory is that macrophage infiltration promotes the development of neovascularization in CNV.Methods and FindingsWe examined the role of macrophages in a mouse model of CNV. IL-10−/− mice, which have increased inflammation in response to diverse stimuli, have significantly reduced CNV with increased macrophage infiltrates compared to wild type. Prevention of macrophage entry into the eye promoted neovascularization while direct injection of macrophages significantly inhibited CNV. Inhibition by macrophages was mediated by the TNF family death molecule Fas ligand (CD95-ligand).ConclusionsImmune vascular interactions can be highly complex. Normal macrophage function is critical in controlling pathologic neovascularization in the eye. IL-10 regulates macrophage activity in the eye and is an attractive therapeutic target in order to suppress or inhibit CNV in AMD that can otherwise lead to blindness. ........

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August 27, 2006, 7:16 AM CT

Topical Microbicides for Blocking HIV

Topical Microbicides for Blocking HIV
A topical microbicide can be used vaginally or rectally by a woman or a man to reduce the risk of acquiring HIV-1 infection during sexual intercourse [1–4]. An effective microbicide could make a significant contribution to reducing the global spread of HIV-1. What will it take to make one? What types of inhibitory compounds could be developed as a practical product, and what obstacles must be faced? In this article, our emphasis will be on newer technologies (Table 1, “Specific Entry Inhibitors”), rather than the earlier-generation surfactants, pH-modifiers, and polyanions (Table 1, “Non-Specific Entry Inhibitors”) that are already being tested in large-scale clinical trials [5] and have been reviewed extensively elsewhere.

We believe a successful microbicide would have to fulfill four interrelated criteria: safety, acceptability, efficacy, and affordability. We will address each issue in turn, discussing how it might affect the development of various microbicide concepts.........

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August 24, 2006, 9:14 PM CT

Mechanism Of Learning

Mechanism Of Learning
Finally confirming a fact that remained unproven for more than 30 years, scientists at MIT's Picower Institute for Learning and Memory report in the Aug. 25 issue of Science that certain key connections among neurons get stronger when we learn.

"We show what everyone has always believed: LTP (long-term potentiation) is indeed induced in the hippocampus when learning occurs," said Mark F. Bear, Picower Professor of Neuroscience. "This is a big deal for neuroresearchers because such evidence has been absent for the 30-plus years we have known about LTP".

The findings described in the Bear paper and in a second, separate paper in the same issue of Science "substantially advance the case for LTP as a neural mechanism for memory," wrote Tim Bliss of the MRC National Institute for Medical Research in the UK, Graham Collingridge of the University of Bristol, and Serge Laroche of the Universite Paris Sud in a commentary on the work.

LTP is an example of plasticity -- the amazing ability of the brain to change in response to experience. LTP builds up synapses, or the connections between neurons, while its counterpart, long-term depression, or LTD, pares unused synapses.

Since LTP was discovered in the late 1960s, thousands of papers have been published based on the assumption that the phenomenon is an important learning and memory mechanism in the hippocampus, the memory center of the brain.........

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August 24, 2006, 7:25 PM CT

Putting Gender Perspective On The Agenda

Putting Gender Perspective On The Agenda
During the past few decades, research has reported gender bias in various areas of clinical and academic medicine. To prevent such bias, a gender perspective in medicine has been requested, but difficulties and resistance have been reported from implementation attempts. Our study aimed at analysing this resistance in relation to what is considered good medical research.

Method.

We used a theoretical model, based on scientific competition, to understand the structures of scientific medicine and how they might influence the resistance to a gender perspective in medicine. The model was originally introduced to discuss how pluralism improves rationality in the social sciences.

Results.

The model provided a way to conceptualise different fields of research in medicine: basic research, applied research, medical philosophy, and 'empowering research'. It clarified how various research approaches within medicine relate to each other, and how they differ and compete. It also indicated why there might be conflicts between them: basic and applied research performed within the biomedical framework have higher status than gender research and other research approaches that are performed within divergent research paradigms.

Conclusion.

This hierarchy within medical research contributes to the resistance to a gender perspective, causing gender bias and making medical scientific rationality suboptimal. We recommend that the theoretical model can be applied in a wider medical context when different and hierarchically arranged research traditions are in conflict. In this way, the model might contribute to shape a medical community where scientific pluralism is acknowledged to enlarge, not to disturb, the scientific rationality of medicine. Key words: gender, gender bias, medical science, paradigm conflicts, pluralism, scientific rationality.........

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August 24, 2006, 7:20 PM CT

Increase In Sickness Absence With Psychiatric Diagnosis

Increase In Sickness Absence With Psychiatric Diagnosis
The aim of this study was to assess the occurence rate of sickness absence with psychiatric diagnoses from 1994-2000, and the distribution across gender, age groups, diagnostic groups and regions in a general population.

Methods.

The population at risk was defined as all individuals aged 16-66 years who were entitled to sickness benefits in 1994, 1996, 1998 and 2000 (n=2,282,761 in 2000). All individuals with a full-time disability pension were excluded. The study included approximately 77% of the Norwegian population aged 16-66 years. For each year, the study base started on 1 January and ended on 31 December. Individuals that were sick-listed for more than 14/16 consecutive days with a psychiatric diagnosis on their medical certificate were selected as cases. Included in this study were data for Norway, the capital city Oslo and five regions in the southeast of the country.

Results.

Sickness absence with psychiatric diagnoses increased in all age groups, in women and men, and in all regions. At the national level, the cumulative incidence increased in women from 1.7% in 1994 to 4.6% in 2000, and in men from 0.8% in 1994 to 2.2% in 2000. The highest cumulative incidence was found in middle-aged women and men (30-59 years). Women had a higher incidence than men in all stratification groups. The cumulative incidences in 2000 varied between 4.6% to 5.6% in women in the different regions, and for men the corresponding figures were 2.1% to 3.2%. Throughout the four years studied, women in Oslo had more than twice as high incidence levels of sickness absence with alcohol and drug diagnoses as the country as a whole. There were some differences between regions in sickness absence with specific psychiatric diagnoses, but they were small and most comparisons were non-significant.........

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August 22, 2006, 6:27 PM CT

In Pursuit Of Long Lasting Happiness

In Pursuit Of Long Lasting Happiness
Can you think of being permanently happy and cheerful? That's what a team of researchers did. A new breed of permanently 'cheerful' mouse is providing hope of a novel treatment for clinical depression. TREK-1 is a gene that can influence transmission of serotonin in the brain. Serotonin is known to have an important role in mood, sleep and sexuality. By breeding mice with an absence of TREK-1, researchers were able create a depression-resistant strain. The details of this research, which involved an international collaboration with scientists from the University of Nice, France, appear in Nature Neuroscience this week.

"Depression is a devastating illness, which affects around 10% of people at some point in their life," says Dr. Guy Debonnel an MUHC psychiatrist, professor in the Department of Psychiatry at McGill University, and principal author of the new research. "Current medications for clinical depression are ineffective for a third of patients, which is why the development of alternate treatments is so important".

Mice without the TREK-1 gene ('knock-out' mice) were created and bred together with Dr. Michel Lazdunski, co-author of the research, in his laboratory at the University of Nice, France. "These 'knock-out' mice were then tested using separate behavioral, electrophysiological and biochemical measures known to gauge 'depression' in animals," says Dr. Debonnel. "The results really surprised us; our 'knock-out' mice acted as if they had been treated with antidepressants for at least three weeks".........

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August 21, 2006, 10:17 PM CT

Reversing Friedreich's Ataxia Defect

Reversing Friedreich's Ataxia Defect
The results of the research are being published on August 20 in an advanced, online version of the journal Nature Chemical Biology.

In the new study, the scientists tested a variety of compounds that inhibited a class of enzymes known as histone deacetylases in a cell line derived from blood cells from a Fredreich's ataxia sufferer. One of these inhibitors had the effect of reactivating the frataxin gene, which is silenced in those with the disease. The scientists then went on to improve on this molecule by synthesis of novel derivatives, identifying compounds that would reactivate the frataxin gene in blood cells taken from 13 Friedreich's ataxia patients.

In fact, one of the compounds the scientists tested produced what amounted to full reactivation of the frataxin gene in 100 percent of cells tested.

"This is marvelous," said Joel Gottesfeld, Ph.D., a professor in the Scripps Research Department of Molecular Biology and leader of the project. "I've met the parents of a number of children affected with the disease and some of the patients and it would be just a dream to be able to help them."

"Dr. Gottesfeld's work holds tremendous promise of real therapeutic benefit for Friedreich's ataxia patients," said Ron Bartek, president of Friedreich's Ataxia Research Alliance (FARA). "This discovery appears to be our only near-term prospect for significantly increasing transcription of the frataxin gene. FARA is pleased to have been able to support this important work".........

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August 21, 2006, 9:07 PM CT

Bulls-eye For Antibiotic Target

Bulls-eye For Antibiotic Target
A Purdue University researcher has opened the door for possible antibiotic therapys for a variety of diseases by determining the structure of a protein that controls the starvation response of E. coli.

This research is applicable to the therapy of a number of diseases because that same protein is found in numerous harmful bacteria, including those that cause ulcers, leprosy, food poisoning, whooping cough, meningitis, sexually transmitted diseases, respiratory infections and stomach cancer, said David Sanders, an associate professor of biology. Sanders, who is part of the Markey Center for Structural Biology at Purdue, detailed his research in a paper reported in the Aug. 16 issue of the journal Structure.

"This is an important discovery for the field of antibiotics, which was greatly in need of something new," Sanders said. "The antibiotics available today face a challenge of increasing resistance and failure. This research suggests a whole new approach to combat bacterial infections. In addition, this protein is an excellent antibiotic target because it only exists in bacteria and some plants, which means the therapy will only affect the targeted bacterial cells and will be harmless to human cells".

Sanders and his collaborator, Miriam Hasson, studied the structure of exopolyphosphatase, a protein in E. coli bacteria that functions as an enzyme and catalyzes chemical reactions within the bacteria. This enzyme provides the signal for bacteria to enter starvation mode and limit.........

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August 20, 2006, 7:38 AM CT

Conjunctival FOXP3 Expression in Trachoma

Conjunctival FOXP3 Expression in Trachoma

Chlamydia trachomatis is the leading infectious cause of blindness and the most common bacterial sexually transmitted infection. In the United Kingdom, the Health Protection Agency found that in 45- to 64-y-old women, rates of chlamydial sexually transmitted infection increased by 177% between 1995 and 2003 [1]. Trachoma, which is caused by repeated ocular infection with C. trachomatis, is a progressive disease, occurring in several stages over the lifetime of the individual: active trachoma (follicular conjunctivitis due to C. trachomatis), scarring trachoma, entropion and trichiasis, and eventually blindness due to corneal opacity. The immune response elicited, although important for the control of infection and protection against trachoma [2–4], is also thought be to responsible, at least in part, for the tissue damage that ultimately leads to the scarring sequelae of the disease [5,6].

The processes that lead to the disease and its sequelae are not fully understood. Examination of the immune response as the infection unfolds is key to understanding the immunopathogenesis of ocular C. trachomatis infection (OCI). Infectious diseases are often characterised by an incubation period, in which infection is present without clinical disease; a period during which both infection and disease are present; and a period when clinical signs persist after infection has been cleared [7]. Miller et al. [8] have proposed that OCI follows such a pattern based on the clinical and microbiological observation of trachoma. Earlier work by our group supports this proposal [9]. We identified individuals with infection in the absence of clinical disease, and individuals with clinical signs in the absence of infection. Follow-up examination found that individuals who were PCR-positive but clinically negative were more likely to develop clinical signs than PCR-negative individuals. Conversely, clinical signs were twice as likely to have resolved after 1 mo in PCR-negative individuals with disease as in those who were PCR-positive. Dissection of the immune response in individuals at these times should identify key components of the immune response associated with the acquisition or resolution of infection and clinical signs of trachoma.........

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August 14, 2006, 11:44 PM CT

High-Fat Copper-Rich Diets

High-Fat Copper-Rich Diets
Among elderly adults whose diets are high in saturated and trans fats, a high intake of copper may be linked to an accelerated rate of decline in thinking, learning and memory abilities, as per a report in the recent issue of Archives of Neurology, one of the JAMA/Archives journals.

Eventhough copper, zinc and iron are essential for brain development and function, an imbalance of these metals may play a role in the development of brain plaques linked to Alzheimer's disease. Prior studies have also linked fat intake, particularly that of saturated and trans fats, to Alzheimer's disease and other forms of cognitive difficulties, as per background information in the article. One recent animal study observed that the consumption of copper in drinking water could amplify the degenerative effects of a high-fat diet on rabbit brains.

Martha Clare Morris, Sc.D., associated professor at the Institute for Healthy Aging at Rush University Medical Center, and her colleagues assessed the correlation between dietary fat and dietary copper intake in 3,718 Chicago residents age 65 years and older. Participants underwent cognitive testing at the beginning of the study, after three years and after six years. An average of one year after the study began, they filled out a questionnaire about their diets. The dietary recommended allowance of copper for adults is.9 milligrams per day. Organ meats, such as liver, and shellfish are the foods with the highest copper levels, followed by nuts, seeds, legumes, whole grains, potatoes, chocolate and some fruits. Copper pipes may also add trace amounts of the metal to drinking water.........

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