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Wisniewski T.,New York University | Goi F.,New York University | Goi F.,University of Uruguay
Expert Review of Anti-Infective Therapy | Year: 2012

All prion diseases are currently without effective treatment and are universally fatal. The underlying pathogenesis of prion diseases (prionoses) is related to an autocatalytic conformational conversion of PrP C (C for cellular) to a pathological and infectious conformer known as PrP Sc (Sc for scrapie) or PrP Res (Res for proteinase K resistant). The past experience with variant Creutzfeldt-Jakob disease, which originated from bovine spongiform encephalopathy, as well as the ongoing epidemic of chronic wasting disease has highlighted the necessity for effective prophylactic and/or therapeutic approaches. Human prionoses are most commonly sporadic, and hence therapy is primarily directed to stop progression; however, in animals the majority of prionoses are infectious and, as a result, the emphasis is on prevention of transmission. These infectious prionoses are most commonly acquired via the alimentary tract as a major portal of infectious agent entry, making mucosal immunization a potentially attractive method to produce a local immune response that can partially or completely prevent prion entry across the gut barrier, while at the same time producing a modulated systemic immunity that is unlikely to be associated with toxicity. A critical factor in any immunomodulatory methodology that targets a self-antigen is the need to delicately balance an effective humoral immune response with potential autoimmune inflammatory toxicity. The ongoing epidemic of chronic wasting disease affecting the USA and Korea, with the potential to spread to human populations, highlights the need for such immunomodulatory approaches. © 2012 Expert Reviews Ltd. Source


Wisniewski T.,New York University | Goni F.,New York University | Goni F.,University of Uruguay
Expert Review of Vaccines | Year: 2010

Prion diseases are a unique category of illness, affecting both animals and humans, where the underlying pathogenesis is related to a conformational change of a normal self protein called cellular prion protein to a pathological and infectious conformer known as scrapie prion protein (PrP Sc). Currently, all prion diseases lack effective treatment and are universally fatal. Past experiences with bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease mainly in Europe, as well as the current epidemic of chronic wasting disease in North America, have highlighted the need to develop prophylactic and/or therapeutic approaches. In Alzheimers disease that, like prion disease, is a conformational neurodegenerative disorder, both passive and active immunization has been shown to be highly effective in model animals at preventing disease and cognitive deficits, with emerging data from human trials suggesting that this approach is able to reduce amyloid-related pathology. However, any immunomodulatory approach aimed at a self-antigen has to finely balance an effective humoral immune response with potential autoimmune toxicity. The prion diseases most commonly acquired by infection typically have the alimentary tract as a portal of infectious agent entry. This makes mucosal immunization a potentially attractive method to produce a local immune response that partially or completely prevents prion entry across the gut barrier, while at the same time producing modulated systemic immunity that is unlikely to be associated with toxicity. Our results using an attenuated Salmonella vaccine strain expressing the prion protein showed that mucosal vaccination can protect against prion infection from a peripheral source, suggesting the feasibility of this approach. It is also possible to develop active and/or passive immunomodulatory approaches that more specifically target PrP Sc or target the shared pathological conformer found in numerous conformational disorders. Such approaches could have a significant impact on many of the common age-associated dementias. © 2010 Expert Reviews Ltd. Source


Riganti A.A.,University of Uruguay | Cafferata M.L.,University of Uruguay | Althabe F.,Institute for Clinical Effectiveness and Health Policy | Gibbons L.,Institute for Clinical Effectiveness and Health Policy | And 3 more authors.
International Journal of Gynecology and Obstetrics | Year: 2010

Objective: To determine the prevalence of the use of prenatal corticosteroids in women who delivered prematurely in 3 Latin American counties and to evaluate the maternal characteristics associated with use. Methods: A multicenter, prospective, descriptive study was conducted in 4 hospitals in Ecuador, 5 in Uruguay, and 3 in El Salvador between 2004 and 2008. Women who had delivered between 24 and 34 weeks of pregnancy responded to a questionnaire assessing sociodemographic characteristics, obstetric history, prenatal care, women's attitudes to health services and knowledge of preterm risk factors, prenatal corticosteroid administration, and characteristics of the delivery and neonate. The association between the prenatal corticosteroid use and the study variables was evaluated through a logistic regression analysis based on a hierarchical model. Results: A total of 1062 women who had a preterm birth were included in the study. Prenatal corticosteroid use was 34.8% (95% CI, 29.9%-39.9%) in Ecuador, 54.6% (95% CI, 49.6%-59.6%) in El Salvador, and 71.0% (95% CI, 65.3%-76.2%) in Uruguay. Hospital admission-to-delivery time was associated with the use of prenatal corticosteroids in all 3 countries. Conclusion: The study revealed a varied pattern of use of prenatal corticosteroids across the 3 countries, and a diversity of influencing factors. © 2009 International Federation of Gynecology and Obstetrics. Source


Beretta V.,University of Uruguay | Simeone A.,University of Uruguay | Elizalde J.C.,University of Uruguay | Franco J.,University of Uruguay | And 5 more authors.
Animal Production Science | Year: 2010

An experiment was conducted to evaluate the effect of fibre source (FS) in high-grain feedlot diets on liveweight gain (LWG) of steers and calves and carcass traits of steers at slaughter. Eighteen steers (330 ± 27.3 kg) and 18 calves (153 ± 11.9 kg) were randomly allotted within animal category to one of three high-grain diets varying in the FS, including either grass hay (H, 66% neutral detergent fibre (NDF)), rice hulls (RH, 85% NDF) or wood chips (W, 90% NDF), and a total mixed ration formulated for equal levels of digestible DM, crude protein and NDF, within category. Animals were individually fed (3 kg DM/100 kg LW, distributed in four meals) during 56 days. The LW increased linearly with time in all treatments (P < 0.01). FS did not affect calves' LWG (P > 0.05), but it resulted in differences in steers LWG (H: 1.77b; RH: 1.51c; W: 2.02a kg/day, P < 0.05). However, no differences were observed in hot carcass weight (P < 0.05), which resulted in higher carcass yield (P < 0.05) for steers fed RH (55.0%) compared with H (53.5%) and W (53.3%). There was a significant interaction (P < 0.05) for feed:gain ratio, with an improvement of this value observed only for steers fed the W diet. Although varying the FS affected rumination of calves and steers (P < 0.01) and the time spent eating of steers (P < 0.05), it did not represent any constraint for animal production. This study suggests by-products high in fibre content, such as RH and W, could be used in substitution to H in high-grain feedlot diets when fed at equal NDF concentration in the ration, both for calves and steers. Because calves are sometimes grown on a high-concentrate diet during winter before spring grazing, further research is needed to quantify potential residual effects on LWG after they return to pasture. © 2010 CSIRO. Source

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