Dietary sodium restriction impairs insulin sensitivity in noninsulin-dependent diabetes mellitus

Dietary sodium restriction has a variety of effects on metabolism, including activation of the renin-angiotensin system. Angiotensin II has complex metabolic and cardiovascular effects, and these may be relevant to the effects of both nonpharmacological and pharmacological interventions in noninsulin-dependent diabetes mellitus (NIDDM). We have assessed the effect of dietary sodium restriction on insulin sensitivity and endogenous glucose production in eight normotensive patients with diet-controlled NIDDM who underwent hyperinsulinemic clamp studies in a randomized, double-blind, placebo-controlled cross-over protocol after two 4-day periods on sodium replete (160 mmol/day) and sodium deplete (40 mmol/day) diets. Mean +/- SD 24-h urinary sodium was 197 +/- 76.0 mmol (replete) and 67 +/- 19.5 mmol (deplete), P = 0.03. Insulin sensitivity was 42.0 +/- 11.3 mumol/kg.min (replete) and 37.0 +/- 11.6 mumol/kg.min (deplete), P = 0.04 (a reduction of 12%). Blood pressure was 130 +/- 21/78 +/- 11 mmHg (replete) and 128 +/- 12/73 +/- 10 mmHg (deplete). Dietary sodium restriction may result in a decrease in peripheral insulin sensitivity in normotensive patients with NIDDM, possibly via an elevation in prevailing angiotensin II concentrations.     

Pharmacologic adjuncts to mechanical ventilation in acute respiratory distress syndrome

This article reviews pharmacologic approaches to treating acute respiratory distress syndrome (ARDS). The authors discuss the therapeutic effects of ketoconazole, antioxidants, corticosteroids, surfactant, ketanserin, pentoxifylline, bronchodilators, and almitrine in ARDS. Current animal data and proposed mechanics which may foster future pharmacologic therapies are also examined.     

Amphetamine-induced behavior, dopamine release, and c-fos mRNA expression: modulation by environmental novelty

We have shown recently that the psychomotor activating effects of amphetamine in the rat are much greater when this drug is administered in association with environmental novelty than when it is given in a home environment. The main purpose of the present study was to explore the neural basis of this phenomenon. We found, using in situ hybridization of c-fos mRNA, that the pattern of neuronal activation in the cortex, in the caudate, in the shell and core of the nucleus accumbens, and in other subcortical structures was markedly different when amphetamine (2.0 mg/kg, i.p.) was given in association with exposure to environmental novelty relative to when it was given at home. In most brain regions the magnitude of c-fos expression was over two times greater in rats given amphetamine plus novelty than in rats given amphetamine alone. In contrast, an in vivo microdialysis study indicated that environmental novelty did not affect amphetamine-induced dopamine release in either caudate or nucleus accumbens. Furthermore, a unilateral 6-hydroxydopamine lesion of the mesostriatal dopamine system reduced amphetamine- but not novelty-induced c-fos expression. Finally, we found no differences in the amount of corticosterone secreted after exposure to novelty, amphetamine, or both, suggesting that corticosterone does not play a critical role in the ability of novelty to modulate amphetamine-induced psychomotor activation. In conclusion, it seems that environmental novelty alters the neurobiological effects of amphetamine independently of the primary neuropharmacological actions of this drug in the striatum.     

Enzymatic and molecular diagnosis of Gaucher disease

Advances in the knowledge of the molecular genetics of Gaucher disease has made diagnosis more certain. Carrier detection in kindreds in which the responsible mutation has been defined is completely reliable now. Coupled with enzymatic assays, the diagnostic capabilities are greater than before. Use of these methods provides important information to individuals at risk and allows them to make critical decisions. The new, simplified methods reviewed in this article permit the molecular diagnosis of the disease and carrier stage of large numbers of samples within 1 week.     

Heparin-induced thrombocytopenia: IgG-mediated platelet activation, platelet microparticle generation, and altered procoagulant/anticoagulant balance in the pathogenesis of thrombosis and venous limb gangrene complicating heparin-induced thrombocytopenia

Until recently, the confusing clinical profile of HIT and the widespread unavailability of reliable diagnostic assays have conspired to produce under-recognition-if not frank skepticism-of the clinical importance of HIT. However, during the 1990s, HIT has emerged as one of the major-if not the most important-immunohematologic problems in clinical medicine. The clinical and laboratory investigations summarized here have contributed to a greater understanding of the frequency, clinical spectrum, pathogenesis, laboratory diagnosis, and-potentially-the prevention of this important drug allergy. Further, the demonstration of increased platelet procoagulant activity and, thrombin generation in HIT, together with insights into the pathogenesis of a new clinicopathologic syndrome (venous limb gangrene), help explain how a disorder characterized by IgG-mediated platelet activation can lead to such diverse clinical sequelae as venous thrombosis, pulmonary embolism, disseminated intravascular coagulation, and venous limb gangrene. These studies should lead to improved treatment of HIT (new emphasis on suppression of thrombin generation, eg, hirudin and its analogs), future avoidance of HIT (preparation of low-molecular-weight heparins and heparinoids that are less immunogenic), and a greater understanding of the interaction between platelet activation and procoagulant/anticoagulant processes.