摘要:

The observations that people infected with HIV suffer not only from an inflammatory stress but also from depleted glutathione levels have led to a general hypothesis that these two are causally related, and that treatment of AIDS should include thiol-replenishment therapy. In particular, inflammatory stimulations are dependent on intracellular thiol levels, as they are potentiated at low glutathione levels (oxidative stress) and inhibited at high glutathione levels. Inflammatory stress may itself lead to decreased levels of glutathione. HIV has taken advantage of inflammatory signals to regulate its own replication; thus, the HIV infection is exacerbated by low levels of glutathione. We have shown that N-acetylcysteine can inhibit inflammatory stimulations, including that of HIV replication. Since N-acetylcysteine can replenish depleted glutathione levels in vivo, we suggest that it be used as an adjunct in the treatment of AIDS.

ISSN:0031-7012    

DOI:10.1159/000139037

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The effect of hypothyroidism on isolated rat cardiac sarcoplasmic reticulum (SR) calcium transport activity was determined. Cardiac SR was studied 2, 4 and 6 weeks following surgical removal of the thyroid gland. Thyroidectomized rats had reduced body weight and left ventricular weight 4 and 6 weeks after thyroidectomy. The rate of SR calcium transport activity was not affected 2 weeks after thyroidectomy, but was reduced 4 and 6 weeks after thyroidectomy. To elucidate the mechanism responsible for altered calcium transport activity, the roles of endogenous SR acylcarnitine and SR calcium pump protein were determined. Thyroidectomy did not affect the level of endogenous acylcarnitine associated with the SR membranes isolated at the time points studied. The level of acylphosphoprotein, putatively the SR calcium pump protein, was not affected 2 weeks following thyroidectomy, but was significantly reduced in SR 4 weeks postthyroidectomy. These studies suggest that the quantity of SR calcium pump sites is reduced in hypothyroidism and that this reduction may explain the altered SR calcium transport activity observed.

ISSN:0031-7012    

DOI:10.1159/000139038

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The effect of the phosphodiesterase inhibitors (tibenelast, theophylline) and placebo on isoproterenol-induced changes in heart rate, cAMP and norepinephrine levels in normal male volunteers was studied. Heart rates in response to isoproterenol dosing were fitted by linear regression, and horizontal shifts in the regression lines were examined between the three treatments. The shift of the regression line after placebo compared to the preplacebo line was to the right by 2.6 ± 2.2 ng ISO/kg/min, theophylline pretreatment shifted this line to the left by 2.4 ± 1.8 ng/kg/min (p < 0.05) and tibenelast by 3.7 ± 1.9 ng/kg/min (p < 0.02). Both tibenelast and theophylline increased the heart rate response to isoproterenol infusion, whereas norepinephrine and cAMP levels were not different in any treatme

ISSN:0031-7012    

DOI:10.1159/000139039

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Cilazapril (C), an angiotensin-converting enzyme inhibitor with effective antihypertensive efficacy, was examined for its ability to alter exercise tolerance testing (ETT) and respiratory oxygen uptake in 33 patients with congestive heart failure (CHF). C was administered in capsules daily to patients with New York Heart Association Class II or Class III CHF for 12 weeks, in parallel double-blind treatment groups of 0 mg (n = 8), 0.5 mg (n = 8), 1.0 mg (n = 9), and 2.5 mg (n = 8). The blood pressure (BP) was reduced by 2.5 mg C: systolic BP (SBP) from 126 to 114 mm Hg; diastolic BP from 76 to 69 mm Hg. The maximum heart rate (MHR) during ETT was increased by 2.5 mg C from 137 to 143 bpm, as was the double product (MHR × maximum SBP × 0.01) from 237 to 251. There was an insignificant change in duration of exercise (548–610 s), anaerobic threshold (AT), and maximum oxygen uptake (14.1–15.7 ml/kg/min). The results suggest a positive effect of 2.5 mg C on energy utilization in CHF pat

ISSN:0031-7012    

DOI:10.1159/000139040

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

In previous investigations we have shown a striking relationship between the activity of glycogenolytic glucose producing acid hydrolases in pancreatic islet tissue and certain insulin-releasing processes. In the present investigation we have studied the relation between islet lysosomal enzyme activities and glucose-induced insulin secretion in vitro in the presence of various insulin secretory inhibitors. It was observed that the nonmetabolizable glucose analogue, mannoheptulose (5 mmol/l) did induce a 2-fold increase in insulin release at low (1 mmol/l) glucose, and a total suppression of insulin release at high (16.7 mmol/l) glucose. These changes in the insulin-secretory pattern were accompanied by similar changes in the activity of islet acid α-glucosidase. The activities of neutral α-glucosidase (endoplasmic reticulum) or acid phosphatase and N-acetyl-β-D-glucosaminidase (lysosomes) were not affected by mannoheptulose. 2-Deoxyglucose (5 mmol/l), another glucose analogue, did not increase insulin secretion or acid α-glucosidase activity at low glucose. At high glucose, however, a partial inhibition of both insulin release (approximately 50%) and acid α-glucosidase activity was seen. 2-Deoxyglucose slightly suppressed acid phosphatase activity but did not influence the activities of neutral α-glucosidase or N-acetyl-β-D-glucosaminidase. Direct addition of glucose to islet homogenates showed a suppressive effect on α-glucosidase activity at pH 4.0 and 5.0. The glucose analogues displayed only marginal (–10 %) inhibition of α-glucosidase activity at pH 5.0. No effect of the analogues was seen at pH 4.0. Mannoheptulose, but not 2-deoxyglucose, interacted with low glucose levels to induce an increased (60%) inhibition of enzyme activity at pH 5.0; (expected inhibition was 30 %). Neither glucose nor the glucose analogues affected islet acid phosphatase activity on direct addition to homogenates. 2-Deoxyglucose inhibited N-acetyl-β-D-glucosaminidase activity by 15–20%. In incubated islets the α2-adrenoceptor agonist clonidine, a ‘general’ inhibitor of insulin secretion, markedly decreased glucose-induced insulin secretion without affecting the islet lysosomal enzyme activities or the neutral α-glucosidase. Clonidine also completely suppressed the mannoheptulose-induced insulin release at low glucose. The data lend further support to our hypothesis that acid glycogenolytic hydrolases are somehow involved in glucose-induced insulin secretion. The results also conform with previous suggestions that clonidine exerts an important inhibitory action on distal events in the stimulus

ISSN:0031-7012    

DOI:10.1159/000139041

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The laboratory rat has been used as an animal model to investigate the effects of cocaine on body temperature and to determine if abuse of the drug is a risk factor in the pathogenesis of exercise-induced heat stroke. Animals were trained to run on a treadmill which was enclosed so that the ambient temperature could be regulated. Exercise at ambient temperatures of 20 and 30 °C led to a similar rise in core temperature of ≈1 °C, although the starting core temperature was higher in the rats at 30°C(38.5 ± 0.10 °C compared to 37.9 ± 0.06 °C). Cocaine (20 mg/kg) led to a transient fall in core temperature in the 20 °C group; the temperature then rapidly recovered, so that after 60 min exercise there was no significant difference between these and the control animals. At the higher ambient temperature cocaine augmented the rise in core temperature during running, although the animals had regained thermal balance by 30 min and core temperature was maintained at 40.2 ± 0.13 °C until the end of the exercise period. The dopamine D1 receptor antagonist SCH 23390 (0.1, 0.3 or 1.0 mg/kg) led to suppression of spontaneous motor activity so that the rats could be persuaded to exercise for only 30–45 min after treatment. Pretreatment with the antagonist did not affect the rise in core temperature induced by cocaine at 30 °C which again stabilized by 30 min at 40.0 ± 0.12 °C. It is concluded that toxic doses of cocaine can precipitate exercise-induced heat stroke at elevated ambient temperatures. Dopamine D1 antagonists would not seem to offer a useful therapeutic adjunct to the management of patients who develop hyperthermia after ingestion of cocaine; the first line of treatment should be directed at lowering body temperature by

ISSN:0031-7012    

DOI:10.1159/000139042

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Wood creosote administered to rats prevented castor-oil-induced diarrhea with an ED50 of 53 mg/kg p.o. This antidiarrheal effect was apparently produced by acceleration of net fluid absorption from the intestine, as shown by a 52% decrease (p < 0.001) of residual fluid volume in an intestinal loop, and partly by suppression of intestinal motility. Wood creosote also inhibited spontaneous longitudinal contractions of isolated ileal segments in rats (IC50 = 28 mg/l) and guinea pigs (IC50 = 17 mg/l). Contractions of the guinea pig ileum induced by electrical stimulation, bradykinin and acetylcholine were also inhibited dose-dependently. We conclude that wood creosote has an antidiarrheal activity and that this effect is exerted by inhibition of intestinal motility and by augmentation of net fluid absorption from the intestine.

ISSN:0031-7012    

DOI:10.1159/000139043

出版商:S. Karger AG    

年代:1993

数据来源: Karger