Differential effect of culture epimastigotes and blood-form Trypamastigotes on normal mouse splenocyte responsiveness to mitogens

Blood form trypomastigotes of the Y strain of T. cruzi, produced a strong inhibition of the blastogenic response to T and B cell mitogens, of the C3H/He, C57BLand BALB/cJ strains of mice, while culture epimastigotes of the Y strain kept in a medium that allows parasite growth at 26°. 30° and 37°C produced a strong stimulatory effect that was even higher than the effect of the mitogens alone. Both the inhibitory or the stimulatory effects were dose-dependent. The stimulatory effect of epimastigotes was also temperature-dependent producing increasedstimulation indexes as the temperature of parasite cultures was raised. Metabolically active,living parasites seemed to be necessary for an improved lymphocyte stimulation suggesting a potential role of secreted metabolites as polyclonal activators of mouse lymphocytes.

Effect of salbutamol on pulmonary responsiveness in chronic pulmonary allergic inflammation in guinea pigs

Beta-2-agonists have been widely used by asthmatic subjects to relieve their obstructive symptoms. However, there are reports that continuous use could lead to loss of bronchial protection and exacerbation of asthma symptoms. We evaluated the effect of two regimens of salbutamol administration (twice and five times a week) in a model of chronic airway inflammation in male Hartley guinea pigs (protocol starting weight: 286 ± 30 g) induced by repeated exposures to aerosols of ovalbumin (OVA). After sensitization, guinea pigs were exposed to aerosols of 0.1 mg/ml salbutamol solution twice a week (OVA + S2x, N = 7) or five times a week (OVA + S5x, N = 8). We studied allergen-specific (OVA inhalation time) and -nonspecific (response to methacholine) respiratory system responsiveness. Seventy-two hours after the last OVA challenge, guinea pigs were anesthetized and tracheostomized, respiratory system resistance and elastance were measured and a dose-response curve to inhaled methacholine chloride was obtained. Specific IgG1 was also quantified by the passive cutaneous anaphylactic technique. OVA-sensitized guinea pigs (N = 8) showed reduction of the time of OVA exposure before the onset of respiratory distress, at the 5th, 6th and 7th exposures (P < 0.001). The OVA + S2x group (but not the OVA + S5x group) showed a significant increase in OVA inhalation time. There were no significant differences in pulmonary responsiveness to methacholine among the experimental groups. OVA + S2x (but not OVA + S5x) animals showed a decrease in the levels of IgG1-specific anaphylactic antibodies compared to the OVA group (P < 0.05). Our results suggest that, in this experimental model, frequent administration of ß2-agonists results in a loss of some of their protective effects against the allergen.

Dose inseminante utilizada na fertilização artificial de ovócito de piracanjuba (Brycon orbignyanus)

A piracanjuba (Brycon orbignyanus Valenciennes, 1849) é uma espécie de peixe migratória, ameaçada de extinção. O objetivo do presente estudo foi determinar a dose inseminante na fertilização artificial de ovócitos de piracanjuba. Para isso, utilizou-se delineamento em blocos casualizados, com quatro tratamentos e três repetições. Três casais de piracanjuba, selecionados dos tanques de reprodutores da Estação Ambiental de Itutinga (EAI - CEMIG), no período de piracema 2006/2007, receberam aplicação de hormônio extrato bruto de hipófise de carpa (EBHC) para obtenção dos gametas. Adotaram-se quatro tratamentos diferentes para a fertilização de 0,1 grama de ovócitos: 10µL, 20µL, 30µL e 40µL de sêmen. As amostras foram ativadas com 5 mL de água do próprio tanque e, em seguida, levadas para incubadoras, dotadas de renovação constante de água, à temperatura de 28ºC. Após 8 e 16 horas, analisaram-se as taxas de fertilização (ovos viáveis) e de eclosão dos ovos, respectivamente. Os resultados obtidos foram comparados pelo teste de Tukey a 5%. As relações sêmen-ovócitos testadas não alteraram as taxas de fertilização e eclosão (P>0,05). O número de espermatozoides-ovócitos, variando de 10,4 x10(5) a 41,6 x10(5), foi eficiente para obtenção de boas taxas de fertilidade.

Ampicilina K em dose única, por via oral, no tratamento da gonorréia

Foram tratados 70 pacientes do sexo masculino portadores de uretrite gonocócica aguda com 3,0 g de Ampicilina K por via oral, em dose única. Em 87,1% dos casos houve desaparecimento da secreção uretral; na grande maioria dos casos entre 24 e 72 horas. Considerados mais 3 casos em que houve persistência da secreção pós tratamento, mas com ausência de gonococos aos exames bacteriológicos (cura bacteriológica) o sucesso terapêutico pode ser elevado para 91,4%.

Hetacilina em dose única no tratamento da gonorréia

Foram tratados 155 pacientes do sexo masculino, portadores de uretrite gonocócica aguda, com 3,0 g de Hetacilina K por via oral (70 casos) ou 1,0 g do mesmo medicamento por via intramuscular (85 casos). Em 88,6% dos casos tratados pela via oral, e em 93% dos casos tratados com uma injeção intramuscular, o corrimento desapareceu em um tempo médio de 48 horas. Não foram observadas reações de intolerância ao medicamento.

Cicatrização de lesões cutâneas de leishmaniose americana com dose única de pamoato de cicloguanil

Relata-se a completa cicatrização de lesões de leishmaniose tegumentar americana, com Pamoato de Cicloguanil (Comolar Parke-Davis) em 33 pacientes, dos quais 28 receberam dose única e 5 dose dupla desse quimioterápico. O diagnóstico foi comprovado pela presença de leishmanias ao exame direto de laboratório. A idade das lesões variou de 8 dias até 12 meses, com 82% dos casos entre 8 e 30 dias. O tempo médio de cicatrização foi de 104 dias variando entre 60 e 170 dias, para os doentes que receberam apenas uma dose do medicamento. Os doentes que receberam duas doses tiveram a completa cicatrização com tempo médio de 163 dias, após a primeira dose e 85 dias após a segunda. Após a cicatrização, os doentes foram controlados por um período médio de 8,4 meses variando entre 3 e 19 meses. A observação mostrou que a cura das lesões é de forma mais retardada, podendo em muitos casos haver uma recrudescência das lesões e, em alguns casos, uma segunda dose acelera a cura.

Quantificação de anticorpos diftéricos em cobaias: I - persistência do título de anticorpos séricos em animais inoculados com uma dose de toxóide diftérico

Foi estudado o comportamento da cinética de anticorpogénese em cobaias inoculadas com uma dose de toxóide diftérico precipitado pelo alúmen. Paralelamente, foi estudada a dinâmica da imunidade passiva naturalmente transmitida aos filhotes. Em cobaias vacinadas com uma dose de antígeno, foi verificado que a síntese de antitoxina diftérica persiste, em títulos detectáveis, até 36 meses após. Os anticorpos transferidos, passivamente, da mãe vacinada para os filhotes atingiram, nestes, concentrações plasmáticas superiores, sendo que a imunidade perdurou em títulos detectáveis até cerca de três meses de idade dos mesmos.

Studies in search of a suitable experimental insect model for xenodiagnosis of hosts with Chagas' disease: 4 - The reflection of parasite stock in the responsiveness of different vector species to chronic infection with different Trypanosoma cruzi stocks

Previous studies (1982,1987) have emphasized the superiority of sylvatic vector species over domestic species as xenodiagnostic agents in testing hosts with acute or chronic infections by T. cruzi "Y" stock. The present study, which is unique in that it contains data on both infectivity rates produced by the same stock in 11 different vector species and also the reaction of the same vector species to seven different parasite stocks, establishes the general validity of linking efficiency of xenodiagnosis to the biotope of its agent. For example, infectivity rates produced by "São Felipe" stock varied from 82.5% to 98.3% in sylvatic vectors but decreased to 42.5% to 71.3% in domestic species. "Colombiana" stock produced in the same sylvatic vectors infectivity rates ranging from 12.5% to 45%. These shrank to 5%-22.5% in domestic bugs. The functional role of the biotope in the vector-parasite interaction has not been eluddated. But since this phenomenon has been observed to be stable and easy to reproduce, it leads us to believe that the results obtained are valid. Data presented also provide increasing evidence that the infectivity rates exhibited by bugs from xenodiagnosis in chronic hosts, are parasite stock specific. For example, infectivity rates produced by "Berenice", "Y", "FL" and "CL" varied in R. neglectus from 26.3% to 75%; in P. megistus from 56.3% to 83.8%; in T. sordida from 28.8% to 58.8% in T. pseudomaculata from 41.3% to 66.3% and in T. rubrovaria from 48.8% to 85%. Data from xenodiagnosis in the same hosts, carrying acute infections by the same parasite stocks, gave the five sylvatic vectors a positive rating of approximately 100%, thus suggesting that the heavy loads of parasites circulating in the acute hosts obscured the characteristic interspecific differences for the parasite stock. Nonetheless these latter were revealed in the same hosts with chronic infections stimulated by very low numbers of the same parasite stocks. Certain observations here described lead us to speculate as to the possibility of further results from other parasite stocks, allowing the association of the infectivity rates produced in bugs by different parasite stocks with the isoenzymic patterns revealed by these stocks.

Efeito dose-resposta de fatores de risco para a doença isquêmica do coração

Resultados de diversos estudos têm apontado a relevância da hipertensão arterial, do hábito de fumar e da hipercolesterolemia como fatores de risco para a doença isquêmica do coração (DIC). Poucos autores têm investigado a existência de gradiente linear relacionando a quantidade destas exposições com os eventos coronarianos. Com o objetivo de avaliar o efeito de diferentes graus de exposição a estas variáveis sobre a DIC, procedendo-se ao ajustamento para possíveis variáveis de confusão, foi feito estudo planejado sob a forma de desenho tipo caso-controle, tendo a coleta de dados se estendido de março de 1993 a fevereiro de 1994. Foram estudados 833 indivíduos de ambos os sexos, na faixa etária compreendida entre 30 e 69 anos completos, sendo todos residentes no Município de São Paulo, SP (Brasil). Foram comparados 280 casos com 553 controles (285 controles de vizinhança e 268 controles hospitalares). A técnica estatística utilizada para a análise dos dados foi a regressão logística multivariada. Os resultados permitiram identificar gradiente linear para as variáveis duração da hipertensão arterial e para número de cigarros consumidos/dia. As variáveis duração do hábito de fumar e duração da hipercolesterolemia, embora tendo apresentado "odds ratios" significantes para as respectivas categorias de exposição, não apresentaram gradiente linear. Foram discutidos aspectos metodológicos que poderiam exercer influência sobre a tendência dos "odds ratios" nas categorias de exposição das variáveis duração do hábito de fumar e duração da hipercolesterolemia. Conclui-se que os efeitos dose-resposta observados para as variáveis duração da hipertensão arterial e número de cigarros consumidos/dia foram independentes da presença nos modelos de potentes fatores de risco para a doença isquêmica do coração.

Suppression of humoral immunity and lymphocyte responsiveness during experimental trypanosoma cruzi infections

C3H/He and C57B1/6 mice were inoculated with 500 Trypanosoma cruzi trypomastigotes (Strain Y). During the acute phase infected mice presented parasitemia and enlargement of lymph nodes and spleens and intracellular parasites were observed in the heart. Examinations of cells derived from spleen and lymph nodes showed increased numbers of IgM and IgG-bearing cells. During the peak of splenomegaly, about day 17 post-infections, splenic lymphocytes showed a marked decrease in responsiveness to T and B-cell mitogens, parasite antigens and plaque forming cells (PFC) to sheep red blood cells (SRBC). Unfractionated or plastic adherent splenic cells from mice, obtained during the acute phase were able to suppress the response to mitogens by lymphocytes from uninfected mice. During the chronic phase. Disappearance of parasitemia and intracellular parasites in the hearts as well as a decrease in spleen size, was observed. These changes preceded the complete recovery of responsiveness to mitogens and T. cruzi antigens by C57B1/6 splenic lymphocytes. However, this recovery was only partial in the C3H/He mice, known to be more sensitive to T. cruzi infection. Partial recovery of humoral immune response also occurred in both strains of mice during the chronic phase.

Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique

A clinical trial involving 80 patients of both sexes, from ages 15 to 55, with chronic intestinal or hepatointestinal schistosomiasis mansoni, was carried out to evaluate the therapeutical efficacy of different dose regimens of praziquantel. The patients were randomly allocated into four groups with an equal number of cases and were then treated with one of the following dosages: 60 mg/kg for 1 day; 60 mg/kg daily for 2 days; 60 mg/kg daily for 3 days; and 30 mg/kg daily for 6 days. The assessment of parasitological cure was based on the quantitative oogram technique through rectal mucosa biopsies which were undertaken prior to, as well as, 1,2,4 and 6 months post-treatment. Concurrently, stool examinations according to the qualitative Hoffman, Pons & Janer (HPJ) and the quantitative Kato-Katz (K-K) methods were also performed. The best tolerability was observed with 30 mg/kg daily for 6 days whereas the highest incidence of side-effects (mainly dizziness and nausea) was found with 60 mg/kg daily for 3 days. No serious adverse drug reaction has occurred. The achieved cure rates were: 25% with 60 mg/kg for 1 day; 60% with 60 mg/kg daily for 2 days; 89.5% with 60 mg/kg daily for 3 days; and 90% with 30 mg/kg daily for 6 days. At the same time there has been a downfall of 64%, 73%, 87% and 84% respectively, in the median number of viable S. mansoni ova per gram of tissue. Thus, a very clear direct correlation between dose and effect could be seen. The corresponding cure rates according to stool examinations by HPJ were 39%, 80%, 100% and 95%; by K-K 89%, 100%, 100% and 100%. This discrepancy in results amongst the three parasitological methods is certainly due to their unequal accuracy. In fact, when the number of viable eggs per gram of tissue fell below 5,000 the difference in the percentage of false negative findings between HPJ (28%) and K-K (80%) became significative. When this number dropped to less than 2,000 the percentage of false negative results obtained with HPJ (49%) turned significant in relation to the oogram as well. In conclusion, it has been proven that praziquantel is a highly efficacious agent against S. mansoni infections. If administered at a total dose of 180 mg/kg divided into either 3 or 6 days, it yields a 90% cure rate. Possibly, one could reach 100% by increasing the total dose to 240 mg/kg. Furthermore, it was confirmed that the quantitative oogram technique is the most reliable parasitological method when evaluating the efficacy of new drugs in schistosomiasis mansoni.

A randomized clinical trial with high dose of chloroquine for treatment of Plasmodium falciparum malaria in Brazil

This clinical trial compared parasitological efficacy, levels of in vivo resistance and side effects of oral chloroquine 25 mg/Kg and 50 mg/Kg in 3 days treatment in Plasmodium falciparum malaria with an extended followed-up of 30 days. The study enroled 58 patients in the 25 mg/Kg group and 66 in the 50 mg/Kg group. All eligible subjects were over 14 years of age and came from Amazon Basin and Central Brazil during the period of August 1989 to April 1991. The cure rate in the 50 mg/Kg group was 89.4% on day 7 and 71.2% on day 14 compared to 44.8% and 24.1% in the 25 mg/Kg group. 74.1% of the patients in the 25 mg/Kg group and 48.4% of the patients in the 50 mg/Kg group had detectable parasitaemia at the day 30. However, there was a decrease of the geometric mean parasite density in both groups specially in the 50 mg/Kg group. There was 24.1% of RIII and 13.8% of RH in the 25 mg/Kg group. Side effects were found to be minimum in both groups. The present data support that there was a high level resistance to chloroquine in both groups, and the high dose regimen only delayed the development of resistance and its administration should not be recommended as first choice in malaria P. falciparum therapy in Brazil.

Caracterização da dose letal mínima por irradiação gama para Penicillium citrinum

O uso das radiações ionizantes na destruição de microrganismos responsáveis pela deterioração de alimentos ou causadores de infecções ou toxinfecções alimentares, constituiu-se aplicação da energia nuclear, para fins verdadeiramente pacíficos. Penicillium citrinum é um fungo produtor de micotoxinas, responsáveis por intoxicações em humanos e animais que se utilizam de alimentos contaminados. Há escassez de informações sobre a resistência do P. citrinum à irradiação gama; assim esta pesquisa objetivou determinar a dose letal por irradiação gama para esse microrganismo. Foram irradiadas 76 suspensões, contendo aproximadamente 100.000 esporos por mililitro, com doses entre 0,2 e 2,2 KGy (KiloGray), sendo os sobreviventes re-irradiados com doses até 3,0 KGy. O fungo foi totalmente destruído com dose de 2,2 KGy. P. citrinum descendentes dos sobreviventes de 2,0 KGy, quando re-irradiados também foram totalmente destruídos com dose de 2,2 KGy. Observou-se um aumento da resistência às doses mais baixas em relação ao fungo não irradiado