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The fungus Paracoccidioides brasiliensis has been isolated from nine-banded armadillos ( Dasypus novemcinctus ) in different regions where paracoccidiodomycosis (PCM) is endemic. The link between PCM and these animals has provided the first valuable clue in the effort to elucidate the ecological niche of P . brasiliensis . The present study was aimed at correlating P . brasiliensis infection in armadillos with local ecological features and, if possible, the presence of the fungus in the soil in the Botucatu hyperendemic area of PCM. In this region the mean temperature ranges from 14.8 to 25.8°C and the annual average precipitation is 1520 mm. The sites where 10 infected animals (positive group) were collected were studied and compared with the sites where five uninfected animals were found. The occurrence of the fungus in soil samples collected from the positive armadillos' burrows and foraging sites was investigated by the indirect method of animal inoculation. Environmental data from the sites of animal capture, such as temperature, rainfall, altitude, vegetation, soil composition, presence of water and proximity of urban areas, were recorded. All 37 soil samples collected from the sites had negative fungal cultures. Positive animals were found much more frequently in sites with disturbed vegetation, such as riparian forests and artificial Eucalyptus or Pinus forests, in altitudes below 800 m, near water sources. The soil type of the sites of positive animals was mainly sandy, with medium to low concentrations of organic matter. The pH was mainly acidic at all the sites, although the concentrations of aluminum cations (H+Al) were lower at the sites where positive animals were found. Positive armadillos were also captured in sites very close to urban areas. Our data and previous studies indicate that P . brasiliensis occurs preferentially in humid and shady disturbed forests in a strong association with armadillos. [ABSTRACT FROM AUTHOR]

Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis (PCM), the most important systemic mycosis in Latin America. The armadillo, Dasypus novemcinctus , has been confirmed as the primary natural reservoir of this fungus. Its geographic distribution is similar to that of human PCM. In this study, virulence profiles of 10 P. brasiliensis isolates from different armadillos and of two clinical isolates were tested in an experimental hamster model. Pathogenicity was evaluated by counting cfu and performing histopathological analysis in the testis, liver, spleen and lung. Circulating specific antibodies were measured using enzyme-linked immunosorbent assay (ELISA). All isolates from armadillos were virulent in the model, with dissemination to many organs. The clinical isolates, which had long been stored in cultured collections, were less virulent. The isolates were classified into four virulence categories according to number of cfu per gram of tissue: very high, high, intermediate and low. This study confirms that armadillos harbor pathogenic genotypes of P. brasiliensis , probably the same ones that infect humans. [ABSTRACT FROM AUTHOR]

Abstract: Although it is long known that the tricyclic antidepressants amitriptyline, nortriptyline and imipramine inhibit the noradrenaline transporter and α1-adrenoceptors with similar affinities, which may lead to self-cancelling actions, the selectivity of these drugs for α1-adrenoceptor subtypes is unknown. The present study investigates the selectivity of amitriptyline, nortriptyline and imipramine for human recombinant and rat native α1-adrenoceptor subtypes. The selectivity of amitriptyline, nortriptyline and imipramine was investigated in HEK-293 cells expressing each of the human α1-subtypes and in rat native receptors from the vas deferens (α1A), spleen (α1B) and aorta (α1D) through [3H]prazosin binding, and noradrenaline-induced intracellular Ca2+ increases and contraction assays. Amitriptyline, nortriptyline and imipramine showed considerably higher affinities for α1A- (∼25- to 80-fold) and α1D-adrenoceptors (∼10- to 25-fold) than for α1B-adrenoceptors in both contraction and [3H]prazosin binding assays with rat native and human receptors, respectively. In addition, amitriptyline, nortriptyline and imipramine were substantially more potent in the inhibition of noradrenaline-induced intracellular Ca2+ increases in HEK-293 cells expressing α1A- or a truncated version of α1D-adrenoceptors which traffics more efficiently towards the cell membrane than in cells expressing α1B-adrenoceptors. Amitriptyline, nortriptyline and imipramine are much weaker antagonists of rat and human α1B-adrenoceptors than of α1A- and α1D-adrenoceptors. The differential affinities for these receptors indicate that the α1-adrenoceptor subtype which activation is most increased by the augmented noradrenaline availability resultant from the blockade of neuronal reuptake is the α1B-adrenoceptor. This may be important for the behavioural effects of these drugs. [Copyright &y& Elsevier]