Cyclophosphamide effect on coccidioidomycosis in the rat

Coccidioidomycosis is a systemic mycosis, endemic in arid areas of the American continent. The rat was employed as an experimental host, since it had been shown to reproduce human lesions and present a chronic course of disease with granulomas mainly restricted to lungs. Given the influence of immunosuppressive therapy on the clinical course of human coccidioidomycosis, we studied the effect of cyclophosphamide (CY) in the experimental rat model. Accordingly, animals were inoculated with 400 Coccidioides immitis arthroconidia of the Acosta strain, by intracardiacal route. As single CY doses failed to alter the course of disease, three schedules were used: A) 4 daily doses of 20 mg/kg each, prior to C. immitis inoculation; B) 4 similar daily doses after infection; and C); 6 doses of 20 mg/kg each, given from day +1 to +4, then on days +8 and +9, post infection (pi), taking day 0 as the time of fungal inoculation. The first two schedules inhibited antibody formation up to day 28 pi, without modifying cellular response to coccidioidin as measured by foodpad swelling. Initially, there was greater fungal spread than in controls receiving C. immitis alone, which proved self-limiting in the latter. In contrast, schedule C led to 559r mortality, with both humoral and cellular response abrogation, accompanied by extensive C. immitis dissemination. Histology disclosed significant alterations, such as the persistence of primary infection sporangia, corresponding to the acute stage of coccidioidomycosis in the absence of granuloma development. Therefore, the observed depression in cellular immunity seems responsible for the lack of inflammatory reaction capable of restricting sporangia proliferation in tissues which, in turn, enhances pathogen spread and mortality rate.El propósito de este trabajo fue estudiar el efecto de la inmunosupresión causada por la droga ciclofosfamida (CY) sobre la infección de la rata con Coccidioides immitis por vía intracardíaca. Este huésped fue empleado como modelo experimental, ya que presenta una evolución de la enfermedad semejante a la del hombre, alcanzando una etapa crónica con granulomas principalmente restringidos a los pulmones. Se utilizaron tres esquemas de CY: A) 4 dosis de 20 mg/kg cada una, antes de la inoculación de Ci; B) 4 dosis de igual cantidad de CY, luego de la infección; y C) 6 dosis de 20 mg/kg cada una, administradas desde el día +1 hasta +4 y continuando los días + 8 y +9 post-infección (pi). Los dos primeros esquemas inhibieron la formación de anticuerpos hasta el día 28 pi, sin modificar la respuesta celular a la coccidioidina, medida como hinchazón de la almohadilla plantar. Se observó una mayor diseminación fúngica inicial, autolimi-tándose más tarde. Por el contrario, el esquema C provocó un 55% de mortalidad, disminución de la respuesta humoral y celular, acompañada de una extensa diseminación del Ci. La histología mostró alteraciones significativas, tales como persistencia de esporangios de primoinfección, correspondientes al estadio agudo de la coccidioidomicosis, con ausencia de desarrollo de granulomas. Por lo tanto, la depresión observada en la respuesta celular debido al tratamiento con CY sería la responsable de la ausencia de la reacción inflamatoria capaz de restringir la proliferación de esporangios en los tejidos, lo cual a su vez favorece la diseminación del microorganismo patógeno y el aumento de morta lidad

Demand for money in Bangladesh: a cointegration analysis

The aim of this study is to estimate the demand for real broad (M2) money in Bangladesh using the most recently developed autoregressive distributed lag approach to cointegration analyses. The empirical results show that there is a unique cointegrated and stable long-run relationship among real per capita broad money demand, real per capita income, domestic interest rates and unofficial exchange rate (UM) premiums which act as a surrogate for foreign interest rates. With money as the dependent variable, the results show that the income and interest elasticities are positive while the UM premium elasticity is negative. These results suggest that distortions in the financial and foreign exchange markets should be reduced in order to increase financial saving or monetary accumulation. Our results also reveal that the demand for money in Bangladesh is stable despite the changes in financial and exchange rate policies between 1975 and 1995.

Exchange Rate Unification Under Non-Credibility: The Haïtian Economy

E58, F31, O54,