Four-and-a-half LIM domains 1 (FHL1) is a cytoskeletal protein that plays a critical role in sensing the biomechanical stress response that triggers cardiac hypertrophy, according to research published Nov. 3 in the Journal of Clinical Investigation.
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Abstract: Background: This work sought to determine the effects of hypothalamic proline-rich peptide (PRP)-1 in a rat model of Alzheimer’s disease.Methods: Complex histochemical, electrophysiologic, and behavioral analyses were performed on intact or diseased Wistar rats (n = 28). Pathologic conditions were induced by bilateral intracerebroventricular injection of amyloid peptide A?25–35. The diseased rats received systemic administration of PRP-1 or placebo control.Results: A?25–35 caused cellular neurodegeneration with marked glial reaction in the hippocampal complex and almost full destruction of the dentate fascia, which was not observed in conditions of PRP-1 administration after A?25–35 injection. Hippocampal neurons of intact animals responded to high-frequency (tetanic) stimulation of entorhinal cortex of ipsilateral cerebral hemisphere by tetanic and posttetanic potentiation of a different intensity and duration, which was accompanied by posttetanic depression. A?25–35 led to significant changes in the level and pattern of hippocampal neuronal activity, indicating the absence of both tetanic and posttetanic activity. Poststimulus activity manifestations rarely occurred and rapidly decreased after repeated trials. This indicated the focal character of lesion. Regular administration of PRP-1 for 4 weeks resulted in optimal restoration of electrophysiologic parameters. PRP-1 maintained the initial learning level achieved in a behavioral study in a Morris water maze.Conclusions: Systemic administration of PRP-1 possesses neuroprotective effects and can prevent the neurodegeneration in hippocampus induced by A?25–35. This suggests that PRP-1 could be a potential therapeutic agent for specific neurodegenerative diseases.
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A study appearing November 5 in the journal Cell Metabolism demonstrates that a synthetic new chemical entity protects against diet-induced obesity, improves glucose tolerance and insulin sensitivity and enhances exercise endurance by enhancing fat utilization in certain target tissues. The new chemical entity was developed by Sirtris, a a GSK company, and the research study was led by EPFL professor Johan Auwerx, MD.
Background:Chlamydia trachomatis, an obligate intracellular human pathogen, is the most prevalent bacterial sexually transmitted infection worldwide and a leading cause of preventable blindness. HtrA is a virulence and stress response periplasmic serine protease and molecular chaperone found in many bacteria. Recombinant purified C. trachomatis HtrA has been previously shown to have both activities. This investigation examined the physiological role of C. trachomatis HtrA.Results:The C. trachomatis htrA gene complemented the lethal high temperature phenotype of Escherichia coli htrA- (>42degreesC). HtrA levels were detected to increase by western blot and immunofluorescence during Chlamydia heat shock experiments. Confocal laser scanning microscopy revealed a likely periplasmic localisation of HtrA. During penicillin induced persistence of C. trachomatis, HtrA levels (as a ratio of LPS) were initially less than control acute cultures (20 h post infection) but increased to more than acute cultures at 44 h post infection. This was unlike IFN- persistence where lower levels of HtrA were observed, suggesting C. trachomatis IFN-gamma persistence does not involve a broad stress response. Conclusion:The heterologous heat shock protection for E. coli, and increased HtrA during cell wall disruption via penicillin and heat shock, indicates an important role for HtrA during high protein stress conditions for C. trachomatis.
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The goal in treating patients with gout is to reduce acute attacks by lowering serum urate levels, which are usually high in this disease. At the same time, high serum urate levels have been shown to lower the risk of developing Parkinson’s disease (PD). A new study compared the safety and efficacy of febuxostat, a new drug being developed for gout that was recently approved for use in Europe, and a commonly used drug that has been around for years.
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Reuters - Once elderly patients are diagnosed with Alzheimer’s disease, the presence of other illnesses and the patients’ ethnic background appear to affect their length of survival, investigators report in the medical journal Neurology.
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Once elderly patients are diagnosed with Alzheimer’s disease, thepresence of other illnesses and the patients’ ethnic backgroundappear to affect their length of survival, investigators report inthe medical journal Neurology.
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Background:The mammary gland undergoes a sophisticated program of developmental changes during pregnancy and lactation, however little is known about processes involving initiation of apoptosis at involution following weaning. We used fur seals as models to study the molecular process of involution as these animals display a unique mammary gland phenotype. Fur seals have long lactation periods whereby mothers cycle between secreting copious quantities of milk for 2-3 days suckling pups on land, with trips to sea alone to forage for up to 23 days during which time mammary glands remain active without initiating apoptosis or involution. Results:We show the molecular basis by which alpha-lactalbumin (LALBA), a secreted milk protein, is absent in Cape fur seals and demonstrate an apoptotic function for LALBA when exposed to mammary cells. Conclusion:We propose that apoptosis does not occur in fur seal mammary glands due to lack of LALBA in fur seal milk, allowing evasion of involution during a foraging trip. Our work identifies LALBA as a milk factor which feeds back on the mammary gland to regulate involution.
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Background:Childhood immunization is a cost effective public health strategy. Expanded Programme on Immunisation (EPI) services have been provided in a rural Nigerian community (Sabongidda-Ora, Edo State) at no cost to the community since 1998 through a privately financed vaccination project (private public partnership). The objective of this survey was to assess vaccination coverage and its determinants in this rural community in NigeriaMethods:A cross-sectional survey was conducted in September 2006, which included the use of interviewer-administered questionnaire to assess knowledge of mothers of children aged 12-23 months and vaccination coverage. Survey participants were selected following the World Health Organization’s (WHO) immunization coverage cluster survey design. Vaccination coverage was assessed by vaccination card and maternal history. A child was said to be fully immunized if he or she had received all of the following vaccines: a dose of Bacille Calmette Guerin (BCG), three doses of oral polio (OPV), three doses of diphtheria, pertussis and tetanus (DPT), three doses of hepatitis B (HB) and one dose of measles by the time he or she was enrolled in the survey, i.e. between the ages of 12-23 months. Knowledge of the mothers was graded as satisfactory if mothers had at least a score of 3 out of a maximum of 5 points. Logistic regression was performed to identify determinants of full immunization status.Results:Three hundred and thirty-nine mothers and 339 children (each mother had one eligible child) were included in the survey. Most of the mothers (99.1%) had very positive attitudes to immunization and >55% were generally knowledgeable about symptoms of vaccine preventable diseases except for difficulty in breathing (as symptom of diphtheria). Two hundred and ninety-five mothers (87.0%) had a satisfactory level of knowledge. Vaccination coverage against all the seven childhood vaccine preventable diseases was 61.9% although it was significantly higher (p=0.002) amongst those who had a vaccination card (131/188, 69.7%) than in those assessed by maternal history (79/151, 52.3%). Multiple logistic regression showed that mothers’ knowledge of immunization (p=0.006) and vaccination at a privately funded health facility (p <0.001) were significantly correlated with the rate of full immunization. Conclusion:Eight years after initiation of this privately financed vaccination project (private-public partnership), vaccination coverage in this rural community is at a level that provides high protection (81%) against DPT/OPV. Completeness of vaccination was significantly correlated with knowledge of mothers on immunization and adequate attention should be given to this if high coverage levels are to be sustained.
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Neglect or abuse can be minimised by high quality care services, according to a new CSCI report released today. Safeguarding: A study of the effectiveness of arrangements to safeguard adults from abuse found that councils with higher overall quality ratings are more likely to have better safeguarding practices in place. This resulted in less abuse and more support to those who experienced abuse.