Modulatory role of endothelial and nonendothelial nitric oxide in 5-hydroxytryptamine-induced contraction in cerebral arteries after subarachnoid hemorrhage

OBJECTIVE: Endothelial dysfunction is claimed to play a role in the pathogenesis of delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). We have examined the effect of experimental SAH on the modulatory action of endothelial and nonendothelial nitric oxide (NO) in the contractile response of goat middle cerebral artery to 5-hydroxytryptamine (5-HT). METHODS: We compared the 5-HT-induced contractile responses of cerebral arteries from control goats and from goats with SAH that had been experimentally induced 3 days earlier by delivery of autologous arterial blood into the subarachnoid space. Contractile responses were examined by recording the isometric tension in isolated cerebral arteries. To assess the influence of endothelium, this cell layer was mechanically removed in some of the arteria, segments (rubbed arteries) from both control goats and goats with SAH. RESULTS: In arteries from control goats, contractile responses to 5-HT were significantly higher in rubbed arteries than in arteries with intact endothelium; 5-HT-induced contractions were significantly enhanced by a competitive inhibitor of NO synthesis, NG-nitro-l-arginine, in arteries both with and without endothelium. In arteries from goats with SAH, 5-HT contracted cerebral arteries without showing significant differences between segments with endothelium and those that had been rubbed; in both cases, 5-HT-induced contractions were significantly higher than those obtained in arteries from control goats. NG-Nitro-l-arginine significantly enhanced the contractile response to 5-HT of cerebral arteries from goats with SAH. CONCLUSION: These results suggest that cerebral arteries after SAH exhibit hyperreactivity to 5-HT via a mechanism that involves the absence of the modulatory role of endothelial NO, that SAH does not modify the modulatory role of nonendothelial NO, and that impairment of the modulatory action of endothelial NO on vascular responses to 5-HT could contribute to the pathogenesis of cerebral vasospasm after SAH.     

Selection of task-dependent diffusion filters for the post-processing of SPECT images

Iterative reconstruction from single photon emission computed tomography (SPECT) data requires regularization to avoid noise amplification and edge artefacts in the reconstructed image. This is often accomplished by stopping the iteration process at a relatively low number of iterations or by post-filtering the reconstructed image. The aim of this paper is to develop a method to automatically select an optimal combination of stopping iteration number and filters for a particular imaging situation. To this end different error measures between the distribution of a phantom and a corresponding filtered SPECT image are minimized for different iteration numbers. As a study example, simulated data representing a brain study are used. For post-reconstruction filtering, the performance of 3D linear diffusion (Gaussian filtering) and edge preserving 3D nonlinear diffusion (Catté scheme) is investigated. For reconstruction methods which model the image formation process accurately, error measures between the phantom and the filtered reconstruction are significantly reduced by performing a high number of iterations followed by optimal filtering compared with stopping the iterative process early. Furthermore, this error reduction can be obtained over a wide range of iteration numbers. Only a negligibly small additional reduction of the errors is obtained by including spatial variance in the filter kernel. Compared with Gaussian filtering, Catté diffusion can further reduce the error in some cases. For the examples considered, using accurate image formation models during iterative reconstruction is far more important than the choice of the filter.     

A systematic antilipidemic structure-activity relationship study was carried out on a series of alcoyl- and benzoyl-phenoxy-carboxylic acids

A systematic antilipidemic structure-activity relationship study was carried out on a series of alcoyl- and benzoyl-phenoxy-carboxylic acids. The introduction of a p-chlorobenzoyl moiety into the original phenoxy-isobutyric acid enhanced antilipidemic activity significantly. Chlorine meta substitution or chlorine disubstitution abolished activity. Among the esters synthetized, the isopropylester has been selected for further studies.     

Influence of gender and the endocrine environment on the distribution of androgen receptors in the lacrimal gland

Androgens are known to regulate both the structure and function of lacrimal tissue in a variety of species. To explore the endocrine basis for this hormone action, the following study was designed to: (1) determine the cellular distribution of androgen receptors in the lacrimal gland; and (2) examine the influence of gender and the endocrine environment on the glandular content of these binding sites. Lacrimal glands were obtained from intact, castrated, hypophysectomized, diabetic or sham-operated male or female adult rats, mice or hamsters, as well as from orchiectomized rats exposed to placebo compounds or physiological levels of testosterone. The cellular location of androgen receptors was evaluated by utilizing an immunoperoxidase protocol, in which a purified rabbit polyclonal antibody to the rat androgen receptor was used as the first antibody. Our findings with lacrimal glands showed that: (1) androgen receptors are located almost exclusively in nuclei of epithelial cells; (2) the cellular distribution or intranuclear density of these binding sites is far more extensive in glands of males, as compared to females; (3) orchiectomy or hypophysectomy, but not sham-surgery or diabetes, lead to a dramatic reduction in the immunocytochemical expression of androgen receptors; and (4) testosterone administration to orchiectomized rats induces a marked increase in androgen receptor content, relative to that in placebo-exposed glands. Our results also reveal that a 10 kb androgen receptor mRNA exists in the rat lacrimal gland. Overall, these findings demonstrate that gender and the endocrine system may significantly influence the distribution of androgen binding sites in rat lacrimal tissue. Moreover, our results show that androgens up-regulate their own lacrimal gland receptors.