Opposite effects of angiotensin-II and corticotropin on bovine adrenocortical cell steroidogenic responsiveness.

The long-term effects of angiotensin-II (A-II) and corticotropin (ACTH) on bovine adrenal fasciculata cells (BAC) were studied. Cells were pretreated for 3 days with either A-II or ACTH followed by an examination of the acute steroidogenic response to both hormones as well as the ability to convert several steroid precursors to cortisol and corticosterone. ACTH pretreatment caused a marked increase in cortisol output associated with a decrease in corticosterone secretion in response to both hormones leading to a 50-fold decrease in the corticosterone/cortisol ratio compared to control cells. After incubation with saturating concentrations (5 X 10(-5) M) of 22 R-hydroxycholesterol, pregnenolone or progesterone, ACTH-pretreated cells produced more cortisol than corticosterone whereas the contrary was observed in control cells. However, the conversion of 17 alpha-hydroxyprogesterone and 11-deoxycortisol to cortisol by ACTH-pretreated cells was lower than by control cells. Thus, the main effects of ACTH were a marked increase of 17 alpha-hydroxylase and a small but significant decrease of 21-hydroxylase and 11 beta-hydroxylase activities. A-II pretreatment produced, in a concentration-dependent manner, a down-regulation of its own receptors and homologous and heterologous steroidogenic desensitization. At maximal concentrations (10(-6) M) A-II reduced by 70% its own receptors while the steroidogenic response to A-II and ACTH was reduced by 95% and 75%, respectively. However, the coupling of A-II receptors to phosphoinositide pathway and to Ca2+ influx, as well as its potentiation effect on ACTH-induced cAMP production were similar in control and A-II pretreated cells. Moreover, the conversion of several steroid precursors to corticosterone was similar in control cells and A-II-pretreated cells, whereas the conversion to cortisol was reduced by approximately 30% due mainly to a decrease of 17 alpha-hydroxylase activity. Thus, the marked steroidogenic desensitization induced by A-II is most likely related to some alteration located beyond the activation of the two branches of the phosphoinositide pathway and before the first steps of steroidogenesis.     

The QT interval: standardization, limits and interpretation

Despite clinical importance of ventricular repolarisation, it remains difficult to analyse. Conventionally, quantification of the electrocardiographic ventricular repolarization is usually performed with reference to axis of the T wave and QT interval duration. A variety of factors can prolong the QT interval, such as drug effects, electrolyte imbalances, and myocardial ischemia. The biggest risk with prolongation of the QT interval is the development of torsades de pointes. Commonly accepted reference ranges for the electrocardiogram (ECG) have been in use, with little change, for many years. Populations throughout the world present several differences: age, ethnic compositions, and are exposed to different environmental factors. Recent studies have reported reference data for QT interval in healthy population and have evaluated the influence of age, gender, QRS duration and heart rate on this interval. In this review, we address several issues relative to the measurement, and interpretation of QT interval and its adjustment for rate, age, gender and QRS duration.     

Polysialic acid is required for active phases of morphological plasticity of neurosecretory axons and their glia

The morphology of axons and astrocytes in the neurohypophysis changes considerably during physiological stimulation, increasing neurovascular contact and facilitating neurosecretion. We here assessed the contribution of alpha2, 8-linked polysialic acid (PSA), which intervenes in axonal changes during development and covers all neurohypophysial axon and glial surfaces. Using an in vitro model, we first analyzed neurohypophysial ultrastructure under different conditions of plasticity. After 2 h incubation in hyperosmotic medium or with the beta-adrenergic agonist, isoprenaline, neurovascular contact significantly increased, due essentially to an enhanced number of terminals, and gliovascular contact decreased correspondingly. This morphology was maintained during 22 h exposure to isoprenaline and reversed 2 h after agonist washout. Removal of PSA from cell surfaces with endoneurominidase prevented stimulation-related induction and reversal of axon and glial changes but had no effect once remodeling had occurred. PSA, therefore, by promoting dynamic cell interactions, is necessary for plasticity of axons and their associated glia.     

Bladder involvement in scleroderma: report of 3 cases

Lower urinary tract involvement is the common manifestation of systemic sclerosis. It may represent a troublesome disturbance affecting the quality of life in systemic sclerosis patients. We report three patients with progressive systemic sclerosis who manifested pathologic abnormalities in the urinary bladder. The first patient manifested a recurrent macroscopic hematuria requiring transfusions. Both other patients developed functional and urodynamic abnormalities. With a review of the literature on this involvement of the bladder in systemic sclerosis we try to more understand urinary symptoms and urodynamics features of vesical involvement in systemic sclerosis patients.     

Synthesis of piperazino and morpholino derivatives of aryloxypropane with potential analgesic and possible antimigraine activities

Abstract  

Modeling studies demonstrate that aryl piperazines (I), aryloxyalkylamines (II), phenylalkykamines (III) and indolylalkylamines (VI) may interact at 5-HT receptors in a similar manner. Examination of these structures (I–VI) reveals that all possess an aromatic moiety and terminal amine binding sites (Glennon et al., J Med Chem 32(8):1921–1926, 1989). In the present investigation a new series of aryloxyalkylamines (4, 5, 8, and 9) was designed and synthesized, in which the aromatic moiety is a phenyl group substituted at the 2,3-, 2,4-, 2,5-, or 2,6-positions by halogens and the terminal amine is N-methylpiperazine, or morpholine. In addition, the alkyl side chain is ethyl, or substituted ethyl at the α- or β-carbon by a methyl group. The length of the alkyl chain that separates the terminal amine from the ether oxygen atom of the aryloxy group is of major importance, and two-carbon chain appears optimal. The structures of the new compounds were assessed by microanalyses, IR, and NMR. The analgesic activity of selected compounds was performed on experimental animals and proved to be in the range of 85–100% relative to aspirin.