Hepatic zonation of the induction of cytochrome P450 IVA, peroxisomal lipid beta-oxidation enzymes and peroxisome proliferation in rats treated with dehydroepiandrosterone (DHEA). Evidence of distinct zonal and sex-specific differences

Dehydroepiandrosterone (DHEA) is an intermediate product in the synthesis of male and female sex hormones in the adrenal cortex of man. In livers of rats and mice DHEA increases the levels of cytochrome P450 IVA and peroxisomal beta-oxidation enzymes associated with peroxisome proliferation. Prolonged treatment of rats with DHEA induces liver tumors that are more frequent in females arising mainly in the periportal regions of the liver lobule (Metzger et al., Toxicol. Pathol. 23, 591-605, 1995). Because of paucity of information on hepatic zonation of peroxisomal response to DHEA and controversial reports on gender-specific differences of its effects the present study was undertaken using qualitative immunohistochemical and quantitative immunoelectron microscopical techniques in addition to Western blotting. Rats were treated for 24 weeks with 0.6% DHEA supplied with diet. Immunoblot analysis revealed marked induction of peroxisomal beta- oxidation enzymes, which by quantitative analysis was equally strong in male and female animals, whilst catalase and urate-oxidase were not increased. Cytochrome P450 IVA, in contrast, was induced significantly stronger in male than in female rats. Immunohistochemistry confirmed the induction of cytochrome P450 IVA showing a marked lobular gradient in female animals with strong induction in pericentral and almost no induction in periportal regions of the liver lobule. In male animals cytochrome P450 IVA was expressed more uniformly across the liver lobule. A similar sex specific zone-dependent response was observed for peroxisomes. DHEA induced in females a significant zonal gradient with marked peroxisome proliferation and a strong induction of peroxisomal hydratase/dehydrogenase in pericentral hepatocytes and a much smaller response in periportal regions. Livers of male animals, in contrast, showed a uniform peroxisomal proliferation to DHEA with only slight zonal differences. The striking homologies of the induction patterns of cytochrome P450 IVA and the peroxisome proliferation in both sexes support the notion of a functional relationship. In view of the almost exclusive periportal localization of DHEA-induced tumors in female rats in contrast to the pericentral localization of the peroxisomal proliferation shown by this study, it seems likely that other factors in addition to peroxisome proliferation may contribute to the hepatocarcinogenic effect of DHEA.      

Radionuclide venography in the management of proximal venous occlusion. A comparison with X-ray contrast venography.

Ascending contrast venography often fails to show the proximal venous system when there is co-existing occlusion of femoral or iliac veins. Retrograde and pertrochanteric venography both have severe limitations in terms of invasiveness and reliability. Radionuclide venography (RNV) is suggested as a less invasive alternative. 100 patients were investigated by both RNV and X-ray contrast venography (XRV). There was a 72% overall correlation between two methods of investigation. The proximal definition of XRV was limited in those cases with femoral obstruction. RNV, however gave progressively better views as imaging became more proximal and this was accentuated in the presence of femoral or iliac occlusion. RNV is simple and easy to perform and less invasive than XRV. The definition at calf level is such that it cannot at this stage replace XRV as the standard diagnostic procedure. However, in patients with proximal occlusions it gives more reliable information than that obtainable by ascending contrast venography.     

Allergic disorders in the athlete

Allergic diseases are common in athletes. As such, sports medicine practitioners will be involved in the management of allergic diseases on a nearly daily basis. Appreciating the wide array of allergic manifestations in this active population is essential to their accurate and efficient treatment. Although the bulk of allergic disease in athletes is mild, some allergic manifestations are far more serious and even potentially life-threatening. Aggressive and thoughtful allergy management should ensure that all athletes can continue to compete safely and at the highest level possible.