摘要:

In a meta-analysis often studies in elderly patients, paroxetine (n = 387) was as effective an antidepressant as active controls (amitriptyline n= 110; clomipramine n= 109; doxepin n = 102; mianserin n = 28). The change over 5-6 weeks of therapy, on the Hamilton Depression Rating Scale, was significantly better with paroxetine compared with active controls. A similar advantage was seen when the responder rate was considered. Adverse events were less frequent and less severe with paroxetine treatment, especially anticholinergic adverse events. Paroxetine was effective in treating anxiety symptoms associated with depression, yet caused significantly less sedation compared with active controls. There was little difference in the overall safety profiles seen between the paroxetine and active control groups. However, data are available indicating reduced cardiotoxicity for paroxetine and a beneficial effect on suicidal thoughts. Overall, the results indicate paroxetine is an alternative first-line therapy to these older antidepressants and should be considered when treating elderly patients.

ISSN:0031-7012    

DOI:10.1159/000139327

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Taxol, an inhibitor of microtubule disaggregation, is used in the therapy of breast, ovarian, and other human malignancies. The toxicity of taxol administration is due in part to the polyoxyethylated castor oil (Cremaphor®) vehicle in which it is administered; taxol embryotoxicity appears also to be partially attributable to vehicle toxicity. Liposome encapsulation is a novel vehicle for drug administration. The administration of taxol encapsulated in liposomes was evaluated in the chick embryo. Albumen injections of taxol doses up to 30 µg/egg were used to characterize dose-response curves for free and liposome-encapsulated taxol, compared to liposome-only and saline-injected control eggs. Sixty percent embryotoxicity (death or malformation) occurred with taxol doses of 1.5 µg/ egg. A 20-fold higher dose was necessary to produce the same degree of toxicity with liposome-encapsulated taxol. Curve-fitting equations were used to estimate median effective doses (ED50S) and slope functions of the dose response curves. The ED50 for taxol was more than an order of magnitude lower than that for liposome-encapsulated taxol. Estimated slope functions for the two dosage forms of taxol were the same, suggesting similar mechanisms of toxicity. The toxicity of liposomes alone was l

ISSN:0031-7012    

DOI:10.1159/000139328

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The effects of a 1- or 24-hour pretreatment regimen with monophosphoryl lipid A (MLA, 35 µg/kg i.v.) on myocardial stunning produced by repetitive coronary occlusions were studied in barbital-anesthetized dogs. Regional segment function (%SS) and myocardial blood flow were measured by sonomicrometry and the radioactive microsphere technique, respectively. In controls, six 5-min periods of coronary occlusion interpersed with 10-min periods of reperfusion and ultimately followed by 2 h of reperfusion produced regional segment dysfunction. Pretreatment with MLA for 1 h prior to the first occlusion period had no effect on %SS, however, pretreatment with MLA 24 h prior to the first occlusion period resulted in a significant (p < 0.05) improvement in the recovery of %SS at all reperfusion periods as compared to the control group. In addition, segment dysfunction during each occlusion period was significantly less severe in animals receiving a 24-hour pretreatment with MLA as compared to the controls. These results are the first to demonstrate that MLA, a lipid A derivative of endotoxin, preserves contractile function of ischemic myocardium in an in vivo canine model and that its cardio-protection is time dependent.arret

ISSN:0031-7012    

DOI:10.1159/000139329

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Male albino rats were fed a high lipid diet for 5 consecutive weeks. We studied the development of paw inflammation after an injection with Freund’s complete adjuvant. Increasing the lipid content of the diet significantly increased the rate of paw inflammation. Also the effect on this process of oral administration of a xanthine oxidase inhibitor (allopurinol, 50 mg/kg) for 15 consecutive days was studied. Results indicated that inflammation was significantly inhibited by allopurino

ISSN:0031-7012    

DOI:10.1159/000139330

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We tested the ability of carvedilol, an antihypertensive β-adrenoreceptor antagonist with antioxidant properties, to protect rat aorta rings from free-radical-induced endothelial cell (EC) dysfunction. Rings were exposed to the superoxide generator pyrogallol. Vascular function of intact rings was assessed by observing acetylcholine (ACh)-induced vasorelaxation following submaximal contraction by U-46619. Function of rings denuded of ECs was assessed by observing S-nitroso-N-acetylpenicillamine (SNAP)-induced vasorelaxation following submaximal contraction by U-46619. Carvedilol exerted a significant protective effect against pyrogallol-induced vasoconstriction (17.1 ± 4.8 vs. 31.9 ± 5.4% for vehicle, p < 0.05). Carvedilol also demonstrated significant protection against pyrogallol-induced endothelium dysfunction, enhancing vasorelaxation to 1,000 nmol/l ACh (73 ± 3.9 vs. 48 ± 3.0% vehicle, p < 0.01). These protective effects were not seen with propanolol, a pure β-receptor antagonist. Carvedilol mixed with pyrogallol and SNAP preserved SNAP-induced vasorelaxation in rings denuded of ECs (80.4 ± 5.3 vs. 63.7 ± 4.8% control, p < 0.05). Carvedilol appears to protect vascular function by scavenging free radicals and enhancing the effect

ISSN:0031-7012    

DOI:10.1159/000139331

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

It has been reported that 3-({[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl}methyl)amino-N-methylbenzamide (DQ-2511: ecabapide) effectively increases gastric mucosal blood flow in rats, suggesting that this property may contribute to the antiulcer activity. To clarify the mechanisms underlying the increase in gastric mucosal blood flow, we investigated the dilator response of rat isolated thoracic aorta, mesenteric artery and celiac artery smooth muscle preparations to DQ-2511. This compound prevented noradrenaline-induced contraction in both the presence and absence of endothelium in the arterial specimen, and it (0.01–1 mM) inhibited these contractions induced by noradrenaline in all tissues in a concentration-dependent manner. This inhibitory effect of DQ-2511 was most evident in the celiac artery. The dilator response to DQ-2511 (0.1 mM) was abolished after pretreatment with methylene blue (3 µM), a guanylate cyclase inhibitor. Under the same conditions, methylene blue inhibited the dilator response to acetylcholine (1 µAf), but not that to papaverine (10 µM). Furthermore, when DQ-2511 (0.01–1 mM) was incubated with the arterial preparations, this compound increased cyclic GMP content in segments in a concentration-dependent manner. These findings demonstrate that the vasodilation induced by DQ-2511 is independent of the endothelium and is related to the augmentation of intracellular cyclic GMP content, which may consequently contribute to the increased gastric mucosal bloo

ISSN:0031-7012    

DOI:10.1159/000139332

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The present study investigated the effects of extracellular calcium on washed platelets of guinea pigs, rabbits, rats and humans. CaC l2 without agonists induced platelet aggregation in guinea pigs and rabbits, but not in rats or humans. CaCl2 increased platelet [Ca2+]i in Fura-2-loaded guinea pig platelets. Calcium-induced platelet aggregation was inhibited by W-7 (a calmodulin antagonist), aspirin, indomethacin, TMB-8 (an inhibitor of intracellular Ca2+ release) and also nicardipine (a calcium antagonist). These data suggest that CaCl2-induced platelet aggregation is mediated by calmodulin, cyclooxygenase and other, as yet unknown, mechanisms.

ISSN:0031-7012    

DOI:10.1159/000139333

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Magnesium (Mg2+) is one of the most abundant ions in the body. In the human body, Mg2+ plays important roles including cofactors in many crucial enzyme systems, especially those involving energy transfer, storage and utilization. Alteration of the concentration of Mg2+ may cause neuromuscular hyperactivity, psychiatric disturbances, calcium/potassium abnormalities, and overactivity of cardiac muscle. Most information on the effect of Mg2+ on muscle contraction has been obtained from studies on cardiac, skeletal, and vascular muscle; much less is known about the effect of Mg2+ in other smooth muscle systems. In the current study, we investigated the effect of Mg2+ on the contraction and intracellular free calcium of rabbit urinary bladder detrusor muscle in response to carbachol and transmural field stimulation (FS). The results can be summarized as follows: (1) Reduction of the concentration of magnesium [Mg2+] from normal Ty-rode’s solution enhanced the spontaneous basal activity, whereas addition of Mg2+ gradually abolished this spontaneous activity. (2) Muscle contraction induced by FS or carbachol was enhanced in Mg2+-free Tyrode’s solution. Addition of Mg2+ inhibited the response to both forms of stimulation in a dose-dependent manner. (3) Inhibitory effects of Mg2+ were potentiated when the Ca2+ concentration in the Tyrode’s solution was reduced to 0.6 mM, whereas increasing the extracellular concentration of Ca2+ (5.4 mM) reduced the inhibitory effects of Mg2+. (4) Using FURA-2 to monitor intracellular free calcium simultaneous with contractile tension, we demonstrated that the alterations in the contractile responses observed at different concentrations of extracellular Mg2+ correlated with similar changes in intracellular free calcium. We conclude from this study that Mg2+ can significantly alter the contractile responses to FS and muscarinic stimulation by alteration of calcium influx during contra

ISSN:0031-7012    

DOI:10.1159/000139334

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Wood creosote, principally a mixture of non-, alkyl- and/or alkoxy-substituted phenolic compounds, was orally administered to adult male volunteers to determine its metabolites and pharmacokinetic parameters. After a 133-mg single dose, its major constituents (i.e. phenol 15 mg, guaiacol 32 mg, p-cresol 18 mg and creosol 24 mg) were found in peripheral venous blood and urine, mostly as glucuronic acid and, except for creosol, as sulfate conjugates. Low concentrations of un-conjugated phenols were also detected. The metabolites in the serum started to increase 15 min after the dose, and they reached their maximum concentrations 30 min after administration. The maximum concentrations of glucuronides were 0.18 ± 0.07,0.91 ± 0.38,0.33 ± 0.18 and 0.47 ± 0.23 mg/l; those of sulfates were 0.16 ± 0.06,0.22 ± 0.09,0.17 ± 0.07 and < 0.04 mg/l for phenol, guaiacol, p-cresol and creosol, respectively. The 24-hour urinary recoveries of the sum of each compound and its metabolites were 75 ± 35, 45 ± 36, 103 ± 51 and 74 ± 36%, in the above order. The presence of guaiacol glucuronide in blood and urine was directly verified by its isolation and structur

ISSN:0031-7012    

DOI:10.1159/000139335

出版商:S. Karger AG    

年代:1995

数据来源: Karger