The beneficial effects of drugs that act via nicotinic acetylcholine receptors (nAChRs) on Parkinson's disease (PD) symptomatology may explain the negative correlation between cigarette smoking and risk of this neurological condition. Varenicline, an α4β2 nAChR partial agonist approved for smoking cessation treatments, could be valuable for PD treatment. Here, we investigated varenicline effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD mouse model. From postnatal day (PN) 90 to PN119, male C57BL/6 mice were exposed daily to varenicline (2 mg/kg) by gavage. After that, MPTP was injected (30 mg/kg, ip) once a day for five days. At PN125, locomotor and anxiety-like effects were assessed with the open field test. At PN126, immobile behavior was assessed with the forced swimming test. At PN127, the frontal cerebral cortex was collected to evaluate dopamine and DOPAC levels. To verify whether varenicline was protective during the MPTP insult, a separate group of MPTP animals received varenicline from PN90 to PN124. MPTP reduced cortical dopamine content and increased dopamine turnover. Those effects were not reversed by varenicline treatment. Interestingly, varenicline reversed the MPTP-induced hyperactivity in the open field. Both maintenance of varenicline treatment during MPTP exposure or its interruption before MPTP exposure elicited similar results. No alterations were observed in anxiety-like behavior or in immobility time. Altogether, these findings suggested that varenicline treatment reduced the MPTP-induced hyperactivity, but did not protect against dopaminergic damage. Based on this partial protective effect, varenicline could exert neuroprotective effects on circuits that control motor activity in PD.

RESUMO O objetivo deste trabalho foi avaliar o tempo de permanência, o número de bocados nas estações e o deslocamento entre estações alimentares por bezerras de corte em pastagem de azevém (Lolium multiflorum Lam.) e recebendo farelo de arroz integral como suplemento em três níveis (0,0; 0,5 e 1,0% PC). O método de pastejo foi rotacionado, com número variável de animais. O período de descanso foi estabelecido pela soma térmica (ST) de 187,5ºC, equivalente à ST necessária para a emissão de 1,5 folhas de azevém. O delineamento experimental foi inteiramente ao acaso, com medidas repetidas no tempo, três níveis de suplemento e seis ciclos de pastejo. O tempo de permanência em cada estação alimentar (9,4s) foi semelhante para bezerras exclusivamente a pasto e as que receberam 1,0% PC de suplemento. As bezerras que receberam 0,5% PC de suplemento permanecem 1,1s a mais na estação alimentar quando comparadas com as bezerras nos demais níveis. O deslocamento entre estações alimentares (1,7 passos) e o número de bocados em cada estação alimentar (sete bocados) foram semelhantes independentemente do nível de farelo de arroz fornecido. As bezerras, ao receberem 0,5% PC de farelo de arroz, são mais dependentes da presença de lâminas foliares no estrato pastejável do dossel.

ABSTRACT The aim of this study was to evaluate the length of stay and number of bites in the feeding stations and displacement between feeding stations for beef heifers on ryegrass pasture (Lolium multiflorum Lam.) and receiving rice bran as a supplement in three levels (0.0; 0.5 and 1.0% BW). The grazing method was rotational with variable number of animals. The interval between grazing was set by the thermal sum (TS) of 187.5ºC equivalent to TS necessary for externalization of 1.5 leaf lamina of ryegrass. The experimental design was completely randomized with repeated measures on time, three levels of supplement and six grazing periods. The stay time at each feeding station (9.4 sec.) was similar for heifers exclusively on pasture and receiving 1.0% supplement BW. Heifers that received 0.5% supplement BW remained 1.1 sec. longer at the feeding station than heifers on other supplement levels. Displacement between feeding stations (1.7 steps) and the number of bites in each feeding station (7 bites) were similar regardless of the supplied rice bran level. Heifers receiving 0.5% rice bran BW are more dependent on the presence of leaf blades in grazeable stratum of canopy.

RESUMO O experimento foi conduzido com o objetivo de avaliar o desenvolvimento de novilhas de corte em três sistemas alimentares: exclusivamente em pastagem de azevém (Lolium multiflorum Lam.) ou em pastagem de azevém e recebendo 0,93% do peso corporal de grão de milho inteiro ou grão de aveia branca como suplemento. O delineamento experimental foi o inteiramente ao acaso, com medidas repetidas no tempo. A utilização da pastagem de azevém, com ou sem uso de grão de milho ou aveia como suplemento, possibilita desenvolvimento reprodutivo para que as bezerras sejam acasaladas aos 14 meses de idade. O peso corporal ao início da utilização da pastagem é determinante para que as bezerras atinjam adequado desenvolvimento reprodutivo no início da estação de acasalamento.

ABSTRAC The experiment was carried out to evaluate the development of beef heifers in three feeding systems: exclusively on ryegrass pasture (Lolium multiflorum Lam.) or in ryegrass pasture and receiving 0.93% of body weight of corn whole grain or oats grain as a supplement. The experimental design was completely randomized with repeated measures in time. The utilization of ryegrass pasture, with or without the use of corn or oats grain as a supplement, provides reproductive development of heifers in order for them to be mated at 14 months of age. The body weight at the beginning of pasture utilization is crucial for heifers to reach adequate reproductive development at the beginning of the mating season.

A toxicidade aguda (DL-50) da toxina da síndrome do choque tóxico (TSST-1) foi testada em linhagens de camundongos BALB/c, C57BL/6 e Suíça. Os animais (n=10) inoculados intraperitoneal com doses crescentes de toxina (0,01 - 10,0µg/animal) receberam 4h após 75µg de LPS (E. coli O111: B4). A toxicidade aguda (DL50) foi observada por um período de 72h e os dados submetidos ao teste de qui- quadrado. Os resultados e os limites de confiança foram expressos em µg de toxina/kg. A linhagem BALB/c apresentou maior sensibilidade (20µg/kg - limite de confiança a 95% entre 9,0- 92,0), seguida da C57BL/6 (38,5µg/kg - limite de confiança a 95% entre 9,11 - 401,6). A amplitude dos limites de confiança deve-se à natureza da toxina, ao mecanismo de ação, a via de inoculação e ao animal utilizado. A seleção do modelo animal e a padronização do experimento são fundamentais para o desenvolvimento de testes de soro neutralização para fins de controle de qualidade do processo de produção de vacinas.

Acute toxicity test (LD-50) using toxic shock syndrome toxin (TSST-1) was tested in BALB/c, C57BL/6 and Swiss mice. Animals (n = 10) were intraperitoneally injected with TSST-1 (0.01-10.0µg/mouse) followed 4h later by potentiating dose of lipopolysaccharide (75.0µg of LPS - E. coli O111:B4) and cumulative mortality was recorded over 72h. Control animals received either TSST-1 or LPS alone. The data were submitted to qui-Square test and acute toxicity test was calculated by probit analysis (confidence limits expressed as µg toxin/kg). BALB/c mice was the most sensitive (20.0µg/kg, 95% confidence limits: 9.0-92.0) followed by C57BL/6 (38.5µg/kg, 95% confidence limits: 9.11- 401.6). Data from Swiss mice was not conclusive, indicating only low sensitivity. Selection of the animal model and standardization of the experiment are fundamental for the development of serum neutralization tests used for final quality control of vaccine production.

A prototoxina epsílon de Clostridium perfringens tipo D foi produzida, purificada e destoxificada por estoiquiometria. Diferentes quantidades de iodo foram incorporadas à estrutura protéica da prototoxina e a toxicidade dos derivados foi analisada em estudos in vivo. Verificou-se que a toxicidade diminuiu à medida que os átomos de iodo foram incorporados à prototoxina. A análise eletroforética demonstrou a estabilidade das amostras quando armazenadas a 4ºC, -20ºC e -80ºC. A prototoxina iodada foi estocada por um período de quatro meses.

Purified epsilon prototoxin of Clostridium perfringens type D was produced, purified, and detoxified by the stoiechiometric method of non-radioactive iodine incorporation. Different degrees of iodination were perfomed and the toxicity of the derivatives were analysed by in vivo studies. Toxicity decreased inversely to the iodine incorporation. Eletrophoretic analysis showed different levels of stability of samples kept under different temperatures 4ºC, - 20ºC, and -80 ºC. The iodinated prototoxins were stocked for a period of four months.