摘要:

This 21-day, open-label study evaluated the effects of raloxifene and tamoxifen on estrogen-induced changes in serum levels of anterior pituitary hormones (prolactin, luteinizing hormone, and follicle-stimulating hormone), sex steroids (testosterone, estradiol), and binding globulins [thyroid binding globulin (T3 resin uptake), transcortin, sex steroid binding globulin]. Seventeen healthy male volunteers completed the study after being randomized to one of three treatments: raloxifene, tamoxifen, or placebo. Six subjects received raloxifene (200 mg daily) for 10 days, 6 subjects received tamoxifen [20 mg twice a day (b.i.d.)] for 10 days, and 5 subjects received placebo for 10 days. All subjects received ethinyl estradiol (20 µg b.i.d.) for 7 days starting 3 days after initiation of study drug or placebo treatment. Results of the primary analysis of this study indicate that for six of the seven analyzable parameters of estrogen action (excluding luteinizing hormone) raloxifene blunted the estrogen response; this effect was significant only for T3 resin uptake. Tamoxifen administration significantly blunted or reversed the estrogen effect in all six of these parameters. Raloxifene, an effective antiestrogen in animal models, is also antiestrogenic in humans

ISSN:0031-7012    

DOI:10.1159/000139284

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Release of inflammatory mediators from mast cells following immunoglobulin bridging by specific allergens triggers episodes of asthma and bronchial hyperreactivity. Recent evidence has shown that neuropeptides, such as substance P (SP), may modulate the pulmonary inflammatory response in these airway diseases. This suggests that SP may affect secretory events of mast cells. To investigate these effects, resident peritoneal mast cells were collected from Sprague-Dawley male rats and stimulated with Con A (utilizes surface-bound immunoglobulin), compound 48/80 (acts in a peptide-like manner) and SP. Secretion was assessed as the release of preloaded [14C]serotonin. All secretagogues induced dose-dependent release. Pharmacologic modulation of release was then studied with two drugs employed for treatment of airway disease, hydrocortisone, a classical anti-inflammatory steroid, and disodium cromoglycate (DSCG). Following pretreatment with 5 µmol/l hydrocortisone, serotonin release induced by Con A was inhibited by 59%. No inhibition was noted with compound 48/80 or SP release. Similarly, following DSCG (300µmol/l) pretreatment, 40% inhibition of release was noted with Con A, but no inhibition occurred following compound 48/80- or SP-stimulated release. Collectively, these results suggest that mast cells possess multiple activation-secretion coupling pathways which respond differently to clinically used pharmacologic agents. Diseases involving SP modulation of mast cell mediator release may not be successfully treated with anti-inflammatory steroids or DSC

ISSN:0031-7012    

DOI:10.1159/000139285

出版商:S. Karger AG    

年代:1995

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000139286

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The purpose of the study was to test the hypothesis that the postischemic neuronal damage is accompanied by changes of the electrocorticogram (ECoG) of freely moving rats during long-term recovery after forebrain ischemia. Ten minutes forebrain ischemia was induced in male Wistar rats. ECoG was recorded 1 day before as well as 1 h, 1 day and 7 days after ischemia. The ECoG power was calculated and for characterizing postischemic ECoG development the percentage of preischemic ECoG power was evaluated. The awake state of the rats was considered for analysis only. Furthermore, the neuroprotective effect of phencyclidine (PCP, 5 mg/kg i.v., 15 min prior to ischemia) was demonstrated in the ECoG changes. One hour after ischemia the ECoG power of the theta (4.75–6.75 Hz), alpha (7.00–12.50 Hz) and beta (12.75–18.50 Hz) band was decreased compared with sham-operated controls and PCP did not influence these changes. However, 1 day after ischemia ECoG power of the saline-treated ischemic rats was completely restored and no longer different from that of the sham-operated group. PCP-treated ischemic animals showed significantly elevated ECoG power in comparison with saline-treated animals. Seven days after ischemia ECoG power of the saline-treated ischemic rats again decreased. In comparison with the ischemic controls, the ECoG activity of the PCP-treated ischemic rats was significantly higher. PCP maintained postischemic ECoG power at the non-ischemic control level. It is suggested that the decrease in the ECoG activity several days after ischemia is related to the delayed neuronal damage. PCP is known to protect neurons against this ischemic damage and, therefore, ECoG activity in PCP-treated rats is less reduced than in untreated con

ISSN:0031-7012    

DOI:10.1159/000139287

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

A long-term study to identify age-dependent alterations in vascular reactivity in obese Zucker rats, a model for non-insulin-dependent diabetes mellitus, was carried out. On aortic rings of 12-week-old obese Zucker rats, but not in older animals (36 and 52 weeks), the following different effects in comparison to the lean rat control group were observed: (i) a significantly enhanced maximal relaxation to acetylcholine and A23187, which was abolished by the nitric oxide-synthase inhibitor L-nitro-arginine methyl ester (L-NAME); relaxation of aortic rings to the endothelium-independent vasodilator nitroglycer-in was similar; (ii) more pronounced maximal 5-hydroxy-tryptamine-induced-contractions in the presence of L-NAME, and (iii) a more pronounced reduction in phenylephrine-induced contractions by verapamil. These results are suggestive of an altered calcium metabolism in the first weeks of development in the obese rat strain, which is probably responsible for the hypotension seen in this early time period.

ISSN:0031-7012    

DOI:10.1159/000139288

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The effect of protein kinase C on potassium channels in cultured endothelial cells was investigated by using whole-cell patch-clamp techniques. Activation of protein kinase C by phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDBu), but not phorbol 12-monomyristate (PMM), an inactive analogue of phorbol esters, depressed an outward calcium-dependent potassium current. The inhibitory actions of PMA and PDBu could be reversed by the kinase inhibitor H-7. Cyclopiazonic acid, an inhibitor of the sarco-plasmic reticulum calcium pump, and LP-805, a novel vasodilator which also releases endothelium-derived relaxing factors, activated the outward calcium-dependent potassium conductance. PMA and PDBu, but not PMM, reduced the outward conductance induced by cyclopiazonic acid and LP-805. These effects of PMA and PDBu on potassium currents may be mediated either by phosphorylation of ion channels, or by decreasing intracellular calcium concentration.

ISSN:0031-7012    

DOI:10.1159/000139289

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The amphiphile lysophosphatidylcholine (LPC) modulates the activity of membrane-associated enzymes such as phos-pholipase A2, adenylate and guanylate cyclases and ATPase. LPC also relaxes vascular smooth muscle through production of nitric oxide. On the basis of reports that bradykinin translocates nitric oxide synthase (NOS) from the membrane to the cytosol, we investigated whether a similar translocation occurs with LPC. It was found that LPC translocated NOS from the membrane to the cytosolic fraction. Total NOS activity remained at the control level.

ISSN:0031-7012    

DOI:10.1159/000139290

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

It has been reported that there are functional defects in the purinergic system in spontaneously hypertensive rats (SHR). The following experiments examined the gastric effects of adenosine in these animals. SHR had a significantly higher gastric mucosal blood flow (GMBF), but the secretion of acid and pepsin was not different from that of normotensive counterparts. In SHR, adenosine (s.c. 3.75 or 7.5 mg/kg) time- and dose-dependently decreased gastric acid secretion and GMBF. The nucleoside, however, did not affect the pepsin secretion. In normotensive rats, gastric acid secretion was also reduced, but not to the extent of SHR. The GMBF was increased instead. Adenosine potentiated ethanol-induced mucosal damage in SHR, which was likely caused by GMBF reduction. It is concluded that adenosine produces a greater depressive action on the stomach in SHR. These differential actions are probably due to the genetic difference between the two types of animals.

ISSN:0031-7012    

DOI:10.1159/000139291

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

In the present study, the potential anti-inflammatory activity of zinc sulfate (zinc) has been examined in rats with acute and chronic inflammation. Additionally, we studied the effect of the concurrent administration of zinc on the anti-inflammatory activity of indometacin and diclofenac and their gastric side effects. Oral or subcutaneous administration of zinc (25 and 15 mg/kg, respectively) significantly reduced carrageenan-induced paw edema. Subcutaneous co-administration of zinc (15 mg/kg) and indometacin (5 mg/kg) or diclofenac (10 mg/kg) resulted in a further reduction in paw edema which was more than either that produced by either agent alone. However, after oral co-administration of zinc and diclofenac the reduction in paw edema was not significantly different from that produced by either zinc or diclofenac alone. In rats with chronic inflammation, the administration of zinc (5 mg/kg s.c. for 7 days) proved as effective as either indometacin (3 mg/kg) or diclofenac (5 mg/kg). Co-administration of zinc with indometacin or diclofenac did not affect the level of activity of either drug. Co-administration of zinc did not affect the ulcerogenic effect of indometacin expressed as the ulcer index. In contrast to indometacin, administration of zinc markedly reduced the ulcerative action of diclofenac. In conclusion, zinc supplementation may contribute significantly to the treatment of inflammation. The combination of zinc with other anti-inflammatory drugs may provide beneficial additive effects and reduce their gastric hazards, particularly with diclofenac.

ISSN:0031-7012    

DOI:10.1159/000139292

出版商:S. Karger AG    

年代:1995

数据来源: Karger