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Younger Animals (younger + animals)
Selected Abstracts,-Amyloid immunization approaches for Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 2 2002Bruno P. Imbimbo Abstract Alzheimer's disease (AD) represents the third leading cause of death in the U.S. and the leading cause of dementia in the elderly population. Until recently, there was little hope of efficiently combating this devastating disease. The deposition of ,-amyloid (A,) is the major pathological hallmark of AD brains. Genetic, biochemical, and pharmacological evidence support the hypothesis that A, plays a key role in the development of the disease. Thus, in the last 5 years a number of pharmacological strategies have been developed to interfere with the A, cascade. The most revolutionary of these approaches was proposed in 1999 by scientists at Elan Pharmaceuticals, which immunized against A, transgenic mice with spontaneously developing A, pathology. The immunization was achieved by subcutaneous injections of a preaggregated form of the synthetic human 42-amino acid A, emulsified with Freund's adjuvant, an immune stimulant. The vaccination caused a near complete inhibition of A, plaque formation in younger animals and a marked reduction of the A, burden in older animals. The effects on A, plaques were accompanied by a reduction of A,-associated astrogliosis and neuritic dystrophy. These results were later confirmed by other groups with similar vaccination protocols, which also demonstrated that the A, immunization of transgenic animals normalize or reduce the cognitive impairment associated with A, pathology. Interestingly, effective removal of brain A, plaques was also obtained by peripherally administering A, antibodies. The mechanism with which the vaccine increases A, clearance is not fully understood. Centrally, the vaccine appears to activate A, phagocytosis by microglial monocytes. Peripherally, serum A, antibodies bind and sequester A,, thus altering its equilibrium between CNS and plasma. The dramatic results obtained in animal models of AD raised unprecedented hopes for both a preventive and a curative intervention for this devastating disorder. A vaccine preparation for human use (AN-1792) composed of preaggregated human A,42 peptide and a highly purified saponin derivative (QS-21) was developed by Elan Pharmaceuticals and Wyeth Ayerst and tested in AD patients. Unfortunately, a Phase IIa study aimed at evaluating the safety and immunological activity of AN-1792 in 360 AD patients was discontinued because 15 subjects receiving the vaccine developed serious signs of CNS inflammation. Both central activation of cytotoxic T cells and autoimmune reactions were proposed as potential mechanisms of toxicity. Other therapeutic A, vaccination strategies are being pursued, including immuno-conjugates and monoclonal antibodies. The future of these and other A, immunization approaches depend on a clear understanding of the mechanism of A, clearance and additional insight into the role of inflammation in the AD brain. Drug Dev. Res. 56:150,162, 2002. © 2002 Wiley-Liss, Inc. [source] An epidemiological study of risk factors associated with the recurrence of equine grass sickness (dysautonomia) on previously affected premisesEQUINE VETERINARY JOURNAL, Issue 2 2004J. R. Newton Summary Reasons for performing study: The reasons why equine grass sickness (EGS) recurs on premises are unknown and, consequently, practical methods for reducing the risk of recurrence are not available. Objectives: To identify risk factors associated with recurrence of EGS on premises and to gain possible insights into the pathogenesis of the disease. Methods: Data on disease history and risk factors were collected by postal questionnaire from premises with EGS cases between 1st January 1997 and 31st December 2001. Data on variation in rates of recurrence of EGS for different risk factors were analysed using Poisson regression analysis. Results: Of 509 premises contacted, 305 (60%) returned useable questionnaires and 100 of these (33%) were classified as ,recurrent' premises. An overall median incidence rate for EGS of 2.1 EGS incidents/100 horses/premises/year was recorded. There was an increased rate of recurrence with higher numbers of horses, presence of younger animals, stud farms and livery/riding establishments, loam and sand soils, rearing of domestic birds and mechanical droppings removal. The rate of recurrence decreased with chalk soil, cograzing ruminants, grass cutting on pastures and removal of droppings by hand. Several statistically significant interactions were identified. Conclusions: Many of the findings are consistent with the theory that EGS is a toxico-infectious form of botulism. Several of the significant factors identified may directly or indirectly relate to soil disturbance and consequent soil contamination of grass, thereby increasing the rate of exposure of grazing horses to Clostridium botulinum, which resides in soil. Potential relevance: Identification of potentially modifiable risk factors may, ideally following validation in appropriately designed, controlled and randomised intervention studies, lead to practical measures to reduce the incidence of EGS on previously affected premises. [source] Evaluation of an indirect serum ELISA and a bacteriological faecal culture test for diagnosis of Salmonella serotype Dublin in cattle using latent class modelsJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2004L.R. Nielsen Abstract Aims:, To evaluate a conventional bacteriological test based on faecal culture and an indirect serum ELISA for detection of S. Dublin infected cattle. To compare the predictive values of the two tests in relation to the prevalence. Methods and Results:, A total of 4531 paired samples from cattle in 29 dairy herds were analysed for presence of S. Dublin bacteria in faeces and immunoglobulins directed against S. Dublin lipopolysaccharide in an indirect serum ELISA. Sensitivity and specificity were estimated at two ELISA cut-off values using a validation method based on latent class models, which presumably provides less biased results than traditional validation methods. Stratification of data into three age groups gave significantly better estimates of test performance of the ELISA. Receiver operating characteristic (ROC) curves were constructed for comparison of overall performance of the ELISA between the three age groups. The sensitivity of the faecal culture test was low (6,14%). ELISA appeared to have a higher validity for animals aged 100,299 days of age than older or younger animals. Overall, the negative predictive value of the ELISA was 2,10 times higher than for the faecal culture test at realistic prevalence of infection in the test population. Conclusions:, The diagnostic sensitivity of the faecal culture test for detection of S. Dublin is poor, the specificity is 1. The superior sensitivity and negative predictive value of the serum ELISA makes this test preferable to faecal culture as an initial screening test and for certification of herds not infected with S. Dublin. Significance and Impact of the Study:, A quantitative estimate of the sensitivity of a faecal culture test for S. Dublin in a general population was provided. ELISA was shown to be an appropriate alternative diagnostic test. Preferably, samples from animals aged 100,299 days of age should be used as these give the best overall performance of the ELISA. Plots of ROC curves and predictive values in relation to prevalence facilitates optimisation of the ELISA cut-off value. [source] drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegansAGING CELL, Issue 4 2010Tsui-Ting Ching Summary Dietary restriction (DR) results in a robust increase in lifespan while maintaining the physiology of much younger animals in a wide range of species. Here, we examine the role of drr-2, a DR-responsive gene recently identified, in determining the longevity of Caenorhabditis elegans. Inhibition of drr-2 has been shown to increase longevity. However, the molecular mechanisms by which drr-2 influences longevity remain unknown. We report here that drr-2 encodes an ortholog of human eukaryotic translation initiation factor 4H (eIF4H), whose function is to mediate the initiation step of mRNA translation. The molecular function of DRR-2 is validated by the association of DRR-2 with polysomes and by the decreased rate of protein synthesis observed in drr-2 knockdown animals. Previous studies have also suggested that DR might trigger a regulated reduction in drr-2 expression to initiate its longevity response. By examining the effect of increasing drr-2 expression on DR animals, we find that drr-2 is essential for a large portion of the longevity response to DR. The nutrient-sensing target of rapamycin (TOR) pathway has been shown to mediate the longevity effects of DR in C. elegans. Results from our genetic analyses suggest that eIF4H/DRR-2 functions downstream of TOR, but in parallel to the S6K/PHA-4 pathway to mediate the lifespan effects of DR. Together, our findings reveal an important role for eIF4H/drr-2 in the TOR-mediated longevity responses to DR. [source] Social Stress Alters Expression of Large Conductance Calcium-Activated Potassium Channel Subunits in Mouse Adrenal Medulla and Pituitary GlandsJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2009O. Chatterjee Large conductance calcium-activated potassium (BK) channels are very prominently expressed in adrenal chromaffin and many anterior pituitary cells, where they shape intrinsic excitability complexly. Stress- and sex-steroids regulate alternative splicing of Slo-,, the pore-forming subunit of BK channels, and chronic behavioural stress has been shown to alter Slo splicing in tree shrew adrenals. In the present study, we focus on mice, measuring the effects of chronic behavioural stress on total mRNA expression of the Slo-, gene, two key BK channel , subunit genes (,2 and ,4), and the ,STREX' splice variant of Slo-,. As a chronic stressor, males of the relatively aggressive SJL strain were housed with a different unfamiliar SJL male every 24 h for 19 days. This ,social-instability' paradigm stressed all individuals, as demonstrated by reduced weight gain and elevated corticosterone levels. Five quantitative reverse transcriptase-polymerase chain assays were performed in parallel, including ,-actin, each calibrated against a dilution series of its corresponding cDNA template. Stress-related changes in BK expression were larger in mice tested at 6 weeks than 9 weeks. In younger animals, Slo-, mRNA levels were elevated 44% and 116% in the adrenal medulla and pituitary, respectively, compared to individually-housed controls. ,2 and ,4 mRNAs were elevated 162% and 194% in the pituitary, but slightly reduced in the adrenals of stressed animals. In the pituitary, dominance scores of stressed animals correlated negatively with , and , subunit expression, with more subordinate individuals exhibiting levels that were three- to four-fold higher than controls or dominant individuals. STREX variant representation was lower in the subordinate subset. Thus, the combination of subunits responding to stress differs markedly between adrenal and pituitary glands. These data suggest that early stress will differentially affect neuroendocrine cell excitability, and call for detailed analysis of functional consequences. [source] Effects of soy vs. casein protein on body weight and glycemic control in female monkeys and their offspringAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009Janice D. Wagner Abstract Nutritional interventions are important for reducing obesity and related conditions. Soy is a good source of protein and also contains isoflavones that may affect plasma lipids, body weight, and insulin action. Described here are data from a monkey breeding colony in which monkeys were initially fed a standard chow diet that is low fat with protein derived from soy. Monkeys were then randomized to a defined diet with a fat content similar to the typical American diet (TAD) containing either protein derived from soy (TAD soy) or casein,lactalbumin (TAD casein). The colony was followed for over two years to assess body weight, and carbohydrate and lipid measures in adult females (n=19) and their offspring (n=25). Serum isoflavone concentrations were higher with TAD soy than TAD casein, but not as high as when monkey chow was fed. Offspring consuming TAD soy had higher serum isoflavone concentrations than adults consuming TAD soy. Female monkeys consuming TAD soy had better glycemic control, as determined by fructosamine concentrations, but no differences in lipids or body weight compared with those consuming diets with TAD casein. Offspring born to dams consuming TAD soy had similar body weights at birth but over a two-year period weighed significantly less, had significantly lower triglyceride concentrations, and like adult females, had significantly lower fructosamine concentrations compared to TAD casein. Glucose tolerance tests in adult females were not significantly different with diet, but offspring eating TAD soy had increased glucose disappearance with overall lower glucose and insulin responses to the glucose challenge compared with TAD casein. Potential reasons for the additional benefits of TAD soy observed in offspring but not in adults may be related to higher serum isoflavone concentrations in offspring, presence of the diet differences throughout more of their lifespan (including gestation), or different tissue susceptibilities in younger animals. Am. J. Primatol. 71:802,811, 2009. © 2009 Wiley-Liss, Inc. [source] | |||||||||||||