Toxicological Evaluation of Anti-Scrapie Trimethoxychalcones and Oxadiazoles

An altered form of the cellular prion protein, the PrPScor PrPRes, is implicated in the occurrence of the still untreatable transmissible spongiform encephalopathies. We have previously synthesized and characterized aromatic compounds that inhibit protease-resistant prion protein (PrPRes) accumulation in scrapie-infected cells. These compounds belong to different chemical classes, including acylhydrazones, chalcones and oxadiazoles. Some of the active compounds were non-toxic to neuroblastoma cells in culture and seem to possess drugable properties, since they are in agreement with the Lipinski´s rule of 5 and present desirable pharmacokinetic profiles as predicted in silico. Before the evaluation of the in vivo efficacy of the aromatic compounds in scrapie-infected mice, safety assessment in healthy mice is needed. Here we used Swiss mice to evaluate the acute toxicity profile of the six most promising anti-prionic compounds, the 2,4,5-trimethoxychalcones (J1, J8, J20 and J35) and the 1,3,4-oxadiazoles (Y13 and Y17). One single oral administration (300 mg/kg) of J1, J8, J20, J35, Y13 and Y17 or repeated intraperitoneal administration (10 mg/kg, 3 times a week, for 4 weeks) of J1, J8 and J35, did not elicit toxicity in mice. We strongly believe that the investigated trimethoxychalcones and oxadiazoles are interesting compounds to be further analyzed in vivo against prion diseases

Contagem de células somáticas e produção de leite em vacas holandesas confinadas Somatic cells count and milk yield in confined holstein cows

A relação entre contagem de células somáticas do leite (CCS) e produção de leite é objeto de estudo de inúmeras pesquisas em diversos países, porém, no Brasil a literatura a esse respeito é escassa. Desse modo, o objetivo do presente trabalho é verificar se as perdas na produção de leite devidas ao aumento da CCS são proporcionais à produção, ou absolutas, independendo desta, e a partir de que valor de CCS elas começam a ser evidentes. Para o estudo foram utilizadas 13.725 observações, colhidas mensalmente de seis rebanhos, no período de janeiro de 2001 a junho de 2002. O modelo de análise, para curva de lactação, foi baseado na função gama incompleta, considerando os efeitos de ordem de lactação, rebanho e época do parto. A CCS foi incluída nesse modelo de duas formas: como fator multiplicativo (representando perdas relativas) e como fator aditivo (representando perdas absolutas). A escolha do melhor modelo foi baseada no critério de informação de Schwarz (BIC). Concluiu-se que as perdas são absolutas, evidentes a partir de 17.000 células/mL e, para cada aumento de uma unidade na escala do logaritmo natural a partir desse valor, estimam-se perdas de 238 e 868 mL/dia para primíparas e multíparas, respectivamente.<br>The relationship between milk somatic cells count (SCC) and milk yield has been the aim of countless researches in several countries; however, in Brazil, the literature related to this subject is scarce. Therefore, the objective of this study is to verify if the losses in milk yield due to SCC increase are proportional to the yield, or absolute (independent of it) and starting from which SCC, the losses become evident. For this study, 13.725 observations were used, collected monthly from 6 different herds, from January/2001 up to June/2002. The analysis model, for lactation curve, was based upon the incomplete gama function, considering the effects of lactation order, herd and calving season. The SCC entered in that model in two ways: as multiplicative factor (representing relative losses) and as addictive factor (representing absolute losses). The best model was chosen based on the information criteria of Schwarz (BIC). It is concluded that the losses are absolute, becoming evident from 17.000 cells/mL, and they are 238 and 868 mL/day for each increase of one unit in the natural logarithm scale, starting from that SCC, respectively, for primiparous and multiparous