Research communications in chemical pathology and pharmacology最新文献

The effect of hydrogen peroxide on metabolism of L-arginine to L-citrulline in the biosynthesis of nitric oxide was investigated in bovine aortic endothelial cells. Addition of hydrogen peroxide (1-10 mM) to endothelial cells increased L-citrulline formation from L-arginine in a dose-dependent manner. Stimulation of L-citrulline formation was prevented by catalase (20 micrograms/ml), a hydrogen peroxide scavenger, but not by superoxide dismutase (SOD, 100 micrograms/ml), a superoxide anion scavenger. Pretreatment with NG-nitro-L-arginine (10(-5) M) and NG-methyl-L-arginine (10(-4) M), potent inhibitors of nitric oxide synthase, also inhibited L-citrulline formation induced by hydrogen peroxide. Moreover, hydrogen peroxide increased intracellular Ca2+ concentrations, and the removal of extracellular Ca2+ reduced the hydrogen peroxide-induced formation of L-citrulline. These findings show that hydrogen peroxide increases the intracellular Ca2+ concentration and stimulates the formation of L-citrulline from L-arginine coupled with nitric oxide synthesis in cultured endothelial cells.

The aim of the present study was to determine whether heat acclimation increases whole-body sensitivity to insulin. Male Wistar rats were kept at 34 degrees C for 2 weeks (HA group). Warm-acclimated rats (WA group) at 25 degrees C served as controls. The glucose infusion rate (GIR) was assessed as an index of in vivo insulin sensitivity, using a hyperinsulinemic euglycemic clamp technique. Moreover, the 125I-insulin binding capacity to purified insulin receptor preparations from m. gastrocnemius of rats after 1, 7, or 14 days of heat exposure was examined. Mean GIR values of HA group were slightly higher than those of WA group, but not significant. The great deviation of the HA group, however, appeared to exist. About half of HA rats showed markedly high GIR values (p < 0.01 vs. WA group). Mean GIR value of the remaining HA rats were significantly (p < 0.05) lower than those of the WA group. Likewise, the binding capacity to 125I-insulin was not significantly different among the periods of time of heat exposure, and the deviation went on increasing from 1 to 14 days. These results suggest that there is a wide individual difference between the changes in glucose metabolism under heat exposure. In view of such results, there appears to be a great need for further studies on the factors affecting the variation of insulin action.

The effects of ozagrel, a thromboxane A2 (TXA2) synthase inhibitor, and CV-3988, a platelet activating factor (PAF) antagonist, was investigated on the repeatedly antigenic challenge-induced airway hyperresponsiveness (AHR) in rats. Rats were actively sensitized with DNP-Ascaris antigen and received 3 inhalations of antigen (challenges) or saline (sensitized control) every 48 hr. These animals were also pretreated with ozagrel (100 mg/kg, p.o., 30 min before), CV-3988 (3 mg/kg, i.v., 5 min before) or respective vehicle (water and saline, respectively) before each inhalation of antigen or saline. The in vivo airway responsiveness to cumulatively inhaled acetylcholine (ACh; 0.001-0.03%, each for 3 min) was measured 24 hr after the last inhalation of antigen or saline under anesthesia. A marked AHR was observed after repeated antigenic challenge when compared with the sensitized control group (5.5-9.5 times in order). This AHR was significantly, but partly, attenuated by pretreatment with ozagrel although this treatment alone had no effect on the airway responsiveness to inhaled ACh in sensitized control animals. On the other hand, CV-3988 had no inhibitory effect on this AHR. These findings suggest that TXA2, but not PAF, is one of the most important mediators participating in the pathogenesis of the antigen-induced AHR in rats.

In urethane anesthetized rats the icv (lateral cerebral ventricle) administration of ketamine, at the highest utilized doses, induced bradypnea and sinus bradycardia in spontaneously breathing rats. Moreover, it partially antagonized the arrhythmogenic activities of sodium glutamate and sodium aspartate, as well as desipramine and ouabain. From these results, we conclude that ketamine had an inhibitory effect on the centrogenic arrhythmias not only acting at the level of NMDA subtype receptor, but also at beta 1 adrenergic central receptors. Moreover at high doses, ketamine can also induce centrogenic arrhythmias in spontaneously breathing rats.

To clarify the significance of intracellular degradation of newly synthesized collagen during the progression of hepatic fibrosis, we measured the intracellular degradation of newly synthesized collagen at 2, 4 and 8 weeks after the administration of CCl4, together with the measurement of collagen synthesis and serum prolyl hydroxylase concentration. Hepatic collagen synthesis and serum prolyl hydroxylase concentration did not change until 4 weeks after the CCl4 administration, but was increased significantly at 8 weeks. Intracellular degradation of newly synthesized collagen was significantly increased at 2 weeks, was unchanged at 4 weeks, and was significantly decreased at 8 weeks compared with the individual control. The percentage of the intracellular degradation relative to the total amount of collagen synthesis did not change at 2 and 4 weeks, but was significantly decreased at 8 weeks, compared with the controls. These results suggest that the intracellular degradation system may prevent an accumulation of collagen at the early stage of hepatic injury, whereas at the stage of hepatic fibrosis, the combination of an increase in collagen synthesis and a reduction of intracellular degradation may lead to a rapid accumulation of collagen.

To elucidate the relationship between active oxygen and interleukin 8 (IL-8) in patients with septic adult respiratory distress syndrome (ARDS), we determined the serum levels of alpha-tocopherol, which has an antioxidant action, and IL-8 in seven patients with this disease. Serum alpha-tocopherol and IL-8 levels determined at the time of diagnosis of septic ARDS were 0.97 +/- 0.36 mg/dl and 0.98 +/- 0.99 ng/ml, respectively. A significant correlation was found between serum alpha-tocopherol level and IL-8 level (r = -0.758, p = 0.0473). These findings suggest that IL-8 activates neutrophils, which produce active oxygen.

Elevated serum enzymes were observed due to all four cinchona alkaloids in male Sprague-Dawley rats after four day treatment. Only a slight effect on bile flow and excretion of phenolphthalein glucuronide in bile was noted. Animals treated with cinchona alkaloid for four days and then receiving CCl4 showed a partial protection against CCl4 induced hepatotoxicity. The levels of serum enzymes were lowered as compared to animals treated with CCl4 alone. Bile flow and excretion of phenolphthalein glucuronide in bile showed a trend of restoration towards control levels. All four cinchona alkaloids probably inhibit microsomal enzymes, thereby, inhibiting the bioactivation of CCl4 and hence reducing the toxicity.

The ability of the heterocyclic compound EDU (N-[2-(2-oxo-1-imidazolindinyl)-ethyl]-N'-phenylurea) to affect polymorphonuclear leukocyte (PMNL) activation was examined by measuring superoxide anion, hydrogen peroxide and hydroxyl radical release from human PMNLs stimulated by phorbol ester. Results demonstrated that EDU effectively interferes with PMNLs reactive oxygen intermediate production, making it a potentially useful compound to be used to modulate PMNL-associated oxidant damage of inflamed tissues.

We investigated the effects of vinconate, a novel indolonaphthylidine derivative, on maze performance deficits induced by an electrolytic lesion of the basal forebrain (BF) in rats. Bilateral BF lesions were produced by passing an anodal DC current (2 mA, 20 s). In the BF-lesioned groups, the latency and distance that the rat swam to escape onto the platform during training in Morris's water maze task significantly increased. Vinconate (5 and 10 mg/kg) treatment shortened the increase of escape latency to the platform in the BF-lesioned rats. The electrolytic BF lesion caused marked reductions of the contents of monoamines and their metabolites in the fronto-parietal cortex, hippocampus and striatum, while it slightly decreased choline acetyltransferase activity in the fronto-parietal cortex, but not significantly. Vinconate treatment showed a tendency to reverse the decreases of serotonin in the fronto-parietal cortex and hippocampus and dopamine in the striatum. Moreover, the reductions of their metabolites were also slightly attenuated by vinconate. These data suggest that vinconate has an anti-amnesic effect on the electrolytic BF lesion-induced amnesia by partly ameliorating the dysfunction in monoaminergic neurons.