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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of mergocriptine (2-methyl-a-ergocryptine; CBM36-733; CAS 81968-16-3) on ischemia-induced brain damages were studied using both a global and a focal ischemia model. First, immediately after 5 min of forebrain ischemia induced by ligation of the bilateral carotid arteries of Mongolian gerbils, the animals were intraperitoneally injected with 3 mg/kg or 10 mg/kg CBM36-733. Seven days after ischemia, perfusion-fixed brains were processed by conventional histology. The number of neurons per mm in the CA 1 pyramidal cell layer was calculated and they were labelled neuronal density. In the control group, the neuronal density was 69.7 +/- 7.2 (mean +/- SEM/mm), in the vehicle group and 3 mg/kg of CBM36-733 treated group, they were 12.2 +/- 4.4 and 11.6 +/- 5.1, respectively. The neuronal density in the 10 mg/kg of CBM36-733 treated group was 42.2 +/- 8.4. These data indicate that 10 mg/kg of CBM36-733 protects on the CA 1 neurons against ischemia induced delayed neuronal death. Second, the effect of long-term administration of 3 mg/kg CBM36-733 on focal brain ischemia of the rats was studied by measuring regional cerebral blood flow and glucose metabolism by autoradiograms. After 90 min of middle cerebral artery occlusion, the rats were intraperitoneally injected with 3 mg/kg of CBM36-733 every day for 2 weeks. There were no significant differences in cerebral blood flow and glucose metabolism between the treated group and the vehicle group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of mergocriptine on postischemic brain damages. 181 Feb 56

Eosinophils generate and release leukotrienes C4 and B4 (LTC4, LTB4) and platelet activating factor (PAF), all of which have the capacity to cause inflammation and tissue injury in the airways. This study has examined the effects of a new 5-lipoxygenase inhibitor, 6-hydroxy-2-(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiazo le hydrochloride (CAS 120164-49-0, E6080) on the release of LTC4, LTB4 and PAF by human eosinophils, Eosinophils stimulated by 1 mumol/l calcium ionophore A23187 for 15 min released 37.5 +/- 2.2 ng, 2.3 +/- 0.3 ng and 4.0 +/- 0.3 pmol per 10(6) cells of immunoreactive LTC4, LTB4 and PAF, respectively (mean +/- SEM, n = 4). LTC4 and LTB4 releases were inhibited dose-dependently by the addition of E6080 to the cell suspension. The IC50 values were 0.26 mumol/l for LTC4 and 0.23 mumol/l for LTB4. PAF release was not inhibited. These results suggest that E6080 is a potent inhibitor of LTC4 and LTB4 release from eosinophils and may provide a protective effect against bronchoconstriction during late-phase asthmatic responses.
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PMID:Inhibition of leukotriene C4 and B4 release by human eosinophils with the new 5-lipoxygenase inhibitor 6-hydroxy-2(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiazo le hydrochloride. 748 99

In this randomized single-blind cross-over study the gastroduodenal damaging effect of indometacin 75 mg bid alone and in combination with roxatidine acetate (CAS 78628-28-1, Roxit) 75 mg nocte or 75 mg bid was evaluated in 12 healthy male volunteers. Prior to the start of the three therapeutic periods subjects underwent endoscopic examination to exclude gastroduodenal mucosa lesions. On days 7 and 14 of therapy 2 h after the application of the last indometacin dose subjects underwent endoscopy again. The 7- and 14-days administration of indometacin 75 mg bid, indometacin 75 mg bid plus roxatidine 75 mg nocte and indometacin 75 mg bid plus roxatidine 75 mg bid led to gastroduodenal mucosa lesion scores of 1.67 +/- 0.40 and 2.00 +/- 0.35, 1.33 +/- 0.28 and 1.50 +/- 0.29, 0.42 +/- 0.23 and 1.00 +/- 0.33 (mean +/- SEM), respectively. These differences were statistically significant when comparing indometacin 75 mg bid versus indometacin 75 mg bid plus roxatidine 75 mg bid (p < 0.004 and < 0.008, respectively). This study shows that roxatidine acetate represents an effective alternative in the prophylaxis of NSAID-induced gastroduodenal mucosa lesions.
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PMID:[Effective prevention of indomethacin-induced gastroduodenal mucosal lesions with roxatidine acetate]. 757 52

For prophylaxis of gastroduodenal lesions induced by non-steroidal antirheumatic drugs (NSAID) acid-lowering as well as mucosa protective substances are used. Direct comparison of both therapeutic regimens are lacking. In randomized parallel studies the gastroduodenal tolerability of 100 mg diclofenac daily in slow-release form was evaluated in the presence and absence of 150 mg roxatidine (CAS 78273-80-0) daily as well as in the presence of 75 mg bid roxatidine or 200 micrograms bid misoprostol (CAS 59122-46-2). The drugs were taken over a period of 14 days. Endoscopic controls were performed at entry, as well as after 14 days of treatment. A quantitative damaging score was used. Study A: Both treatment groups (n = 20) had at entry comparable mucosal damages: placebo/diclofenac: 0.9 +/- 0.1 (+/- SEM), roxatidine/diclofenac: 0.9 +/- 0.1; after 14 days of treatment the score increased in the diclofenac/placebo group to 7.6 +/- 1.9 and, in the corresponding diclofenac/roxatidine group, only to 2.1 +/- 0.9. The difference between the two treatment groups after 14 days was significant (p < 0.05). Study B: Both treatment groups (n = 24) had comparable mucosal damages at entry: diclofenac/roxatidine: 0.9 +/- 0.1, diclofenac/misoprostol: 0.8 +/- 0.1. Following 14 days treatment with 100 mg diclofenac daily the damaging score in both group rose to comparable levels: roxatidine group 2.1 +/- 0.7 and misoprostol group 2.0 +/- 0.4 (n.s.). The data suggest that for prophylaxis of NSAID-induced gastroduodenal lesions substances with different mechanism of action can be used. The findings underline the complex way by which NSAID can damage the mucosa of the upper gastrointestinal tract.
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PMID:[Comparison of the protective effects of roxatidine and misoprostol on diclofenac gastroduodenal pathology. An endoscopic, controlled study of volunteers]. 781 85

The oral non-ergot D2-dopamine agonist quinagolide (CV 205-502, CAS 87056-78-8) has proven to be highly effective in suppressing elevated prolactin (PRL) levels. It was the aim of this study to search for possible interference of the drug with other endocrine systems which are partly under dopaminergic control, and to compare such effects to those of previously investigated prolactin inhibitors. Twelve patients suffering from macroprolactinoma were treated for at least 6 months with daily doses ranging from 50 up to 300 micrograms. During the first two months, individual doses were gradually increased either until serum PRL levels reached the normal range (n = 7) or until side effects made a further dose increase intolerable (n = 5). Mean basal PRL level fell from 255 +/- 65 (SEM) ng/ml before treatment to 19 +/- 8 ng/ml, after the definite dose was reached (p < 0.01). Luteinizing hormone (LH) rose from 0.6 +/- 0.8 (SD) to 1.7 +/- 1.6 mU/ml (p < 0.05). While basal levels of aldosterone, renin, follicle-stimulating hormone (FSH), triiodothyronine (T3), testosterone, and estradiol in females were not affected by the treatment, we found a significant rise in thyroxine (T4) and a decrease of estradiol in males. Blood pressure and renal clearances of creatinine, sodium, potassium, and chloride failed to show any significant change. Following stimulation with metoclopramide, aldosterone and renin rose sharply before treatment was initiated. When the test was repeated during treatment, the increase of plasma renin was slightly dampened, whereas the rise of aldosterone remained unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of macroprolactinoma with the new potent non-ergot D2-dopamine agonist quinagolide and effects on prolactin levels, pituitary function, an the renin-aldosterone system. Results of a clinical long-term study. 809 4

The inhibiting effect of the calcium channel blocker nisoldipine (CAS 63675-72-9, Baymycard, Syscor) on potassium-induced contraction on bovine mesenteric veins and arteries and human peripheral veins was investigated. Nisoldipine inhibited the contraction on bovine mesenteric veins at a significantly lower concentration (1 x 10(-10) mol/l) than nifedipine and glyceryl trinitrate (GTN) (1 x 10(-7) mol/l). When the preparations were preincubated with the drugs, nisoldipine reduced the contraction, measured as area under the curve (AUC), with 47 +/- 8% (mean +/- SEM) and nifedipine with 29 +/- 13% in veins. It was necessary to use an inconsiderably higher concentration of nisoldipine to relax bovine mesenteric arteries contracted by potassium. Preincubation of these arteries with nisoldipine (1 x 10(-7) mol/l) reduced contraction measured as AUC by 46 +/- 10% and preincubation with nifedipine (1 x 10(-7) mol/l) by 77 +/- 3%. Nisoldipine also caused a marked relaxation in human saphenous veins. The introduction of nisoldipine (1 x 10(-8) mol/l) after potassium-induced contraction caused 54 +/- 8% relaxation.
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PMID:Inhibition of nisoldipine on bovine mesenteric arteries and veins and on human peripheral veins. 857 21

Endothelium-dependent responses are depressed in coronary and peripheral blood vessels after the onset of pacing-induced heart failure in dogs and heart failure of various etiologies in humans. The present study was designed to examine whether these responses were due to decreases in the expression of endothelial cell NO synthase (ecNOS) and cyclooxygenase-1 (COX-1). After 1 month of left ventricular pacing, 8 mongrel dogs were monitored for heart failure as defined by clinical signs and left ventricular end diastolic pressures > 25 mm Hg. Total RNA and protein were isolated from endothelial cells scraped from the thoracic aorta and analyzed by Northern and Western blotting, respectively. Blots probed with 32P-labeled cDNAs for ecNOS and COX-1 were quantified densitometrically, and results were normalized against GAPDH or von Willebrand factor (vWF). In arbitrary units, the ratios of ecNOS to GAPDH were 2.66 +/- 0.77 (mean +/- SEM, n = 17) and 1.12 +/- 0.37 (n = 6 and the ratios of COX-1 to GAPDH were 1.52 +/- 0.52 and 0.56 +/- 0.15 before and after heart failure, respectively. These represent 56% to 64% (P < .05) reductions in ecNOS and COX-1 gene expression. There was no change in the ratios of either COX-1 or ecNOS to vWF. There was also a marked reduction in ecNOS protein after heart failure, estimated at 70%. A marked reduction in nitrite production, a measure of enzyme activity, from thoracic aortas in response to stimulation by either acetylcholine or bradykinin also occurred. To determine whether ecNOS and COX-1 could be independently regulated, an orally active NO-releasing agent, CAS 936, was given to 7 normal dogs for 7 days, and aortic ecNOS and COX-1 mRNAs were analyzed. The ratio of ecNOS to GAPDH was depressed by 52% (P < .05) in aortas from these dogs, whereas the ratio of COX-1 to GAPDH was unchanged. Similar results were found when data were normalized to vWF. These results suggest that at least two endothelial vasodilator gene products are reduced in heart failure, as opposed to a selective defect in NO synthase gene expression.
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PMID:Reduced gene expression of vascular endothelial NO synthase and cyclooxygenase-1 in heart failure. 860 6

In a randomized double-blind parallel study the gastroduodenal tolerability of 300 mg acetylsalicylic acid (ASA) daily has been evaluated in the presence of placebo, 15 mg lansoprazole (CAS 103577-45-3, Agopton) and 300 mg ranitidine daily (8 a.m.) in 30 healthy volunteers using upper gastrointestinal tract endoscopy. The treatment periods lasted 14 days. Endoscopic controls were performed at entry and repeated at day 14. At entry, the mean endoscopic score averaged 1.0 +/- 0.0 (+/- SEM) in the ASA/placebo (n = 10), in the ASA/ lansoprazole 15 mg (n = 10) and the ASA/300 mg ranitidine group. In the placebo experiments 300 mg ASA daily induced marked gastroduodenal lesions at day 14 (lesion score of 10.1 +/- 1.4) (+/- SEM). Concomitant administration of 15 mg lansoprazole daily offered significant protection against 300 mg ASA daily on day 14 (3.6 +/- 1.2) (p < 0.05), 300 mg ASA plus 300 mg ranitidine daily reduced the damaging score to 5.8 +/- 1.3 (p n.s. vs ASA/placebo). Our data suggest that co-administration of 15 mg lansoprazole daily reduces significantly gastroduodenal lesions evoked by 300 mg ASA.
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PMID:[Studies on the protective effect of lansoprazole on human gastric mucosa against low-dose acetylsalicylic acid. An endoscopic controlled double-blind study]. 928 2

Deltamethrin (CAS registry No. 52918-63-5), a synthetic dibromo-pyrethroid insecticide is highly effective against a broad spectrum of insects, and is widely used on crops and in public health programs. Data on the genotoxicity and carcinogenicity of deltamethrin are rather controversial, depending on the genetic system or the assay used. The aim of the present study was to analyze previously demonstrated metabolic changes using aspecific noninvasive methods in rats which are potentially applicable for monitoring occupational exposure. Since human exposure to pesticides occurs not only to active principles but to all chemicals present in a commercial formulation, we tested both the pure compound and a deltamethrin-based commercial formulation. Groups of rats were treated, i.p., consecutively for 7 days. The daily doses tested were 5 and 10 mg/kg body weight for pure deltamethrin, corresponding to volumes of 178.57 and 377.14 microliter/kg body weight for the commercial formulation (containing 2.8% deltamethrin). Urine was analyzed for mutagenic metabolites, thioethers, and D-glucaric acid content. Faeces extracts were tested for mutagenicity. Results show that DGA urinary excretion values did not mirror the phase I enzyme induction capability of the insecticide. Results obtained for urinary thioethers do not agree completely with those obtained on the influence of deltamethrin on glutathione S-transferase activity in rat liver. In fact, after administration of the deltamethrin commercial formulation, highest thioether excretion values were obtained during the treatment time for treated animals, as compared to controls. The mean values (+/-SEM) of thioether excretion were 0. 033 +/- 0.002 micromole -SH/24 h for control animals, 0.122 +/- 0. 004 and 0.185 +/- 0.025 for the two treatment groups. Thence, thioether determination in urine samples seems to be a suitable aspecific noninvasive method for assessing exposure to deltamethrin-based formulations, particularly those containing xylene and mesitylene as solvents, as in the tested formulation. Negative or toxic results obtained in the urinary and faecal mutagenicity test seem to exclude the formation and excretion of mutagenic metabolites following treatment with deltamethrin.
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PMID:Applicability of aspecific noninvasive methods for biomonitoring of occupational exposure to deltamethrin: preliminary study using an animal model. 935 11

In a randomised double-blind parallel study the gastroduodenal tolerability of 300 mg acetylsalicilic acid daily (ASA, CAS 50-78-2) has been evaluated in the presence of placebo (n = 8), 40 mg pantoprazole (CAS 102625-70-7) daily (8 a.m.) (n = 16) and 300 mg ranitidine (CAS 66357-35-5) daily (8 a.m.) (n = 16) in healthy volunteers using upper GI-endoscopy. The treatment period lasted 14 days, endoscopic controls were performed at entry and repeated at day 14. At entry, the mean endoscopic score averaged 1.0 +/- 0.0 (+/- SEM) in the ASA/placebo, in the ASA/pantoprazole and the ASA/ranitidine group. In the placebo experiments 300 mg ASA daily induced marked gastroduodenal lesions at day 14 (lesion score of 6.8 +/- 1.4 (+/- SEM). Concomitant administration of 40 mg pantoprazole daily offered significant protection against 300 mg ASS daily on day 14 (2.1 +/- 0.6) (+/- SEM) (p < 0.05) vs ASA/placebo. 300 mg ASA plus 300 mg ranitidine daily reduced the damaging score to 4.9 +/- 1.2 (+/- SEM) (n.s. vs ASA/ placebo). Our data suggest that coadministration of 40 mg pantoprazole daily reduces significantly gastroduodenal lesions evoked by 300 mg ASA daily.
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PMID:[The action of the proton pump inhibitor pantoprazol against acetylsalicylic acid-induced gastroduodenopathy in comparison to ranitidine. An endoscopic controlled, double blind comparison]. 963 15


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