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1.
Brain cyclooxygenases (COX), the rate-limiting enzyme in prostaglandin synthesis, is rapidly and transiently induced by convulsions in hippocampal and cortical neurons. Previous studies have explored the protective effect of naproxen (non-selective COX-inhibitor) or rofecoxib (selective COX-2 inhibitor) against chemical kindling in mice. With this background, the present study was designed to explore the possible effect of nimesulide (a preferential COX-2 inhibitor) against pentylenetetrazol (PTZ)-induced kindling epilepsy in mice. To induce kindling, PTZ was injected in a subconvulsive dose (40 mg/kg, i.p.) every other day for 15 days. Nimesulide (2.5 or 5 mg/kg, p.o.) was administered each day 45 min before either PTZ or vehicle challenge. The intensity of kindling was assessed immediately after PTZ administration according to a prevalidated scoring scale. On 16th day i.e. 24 h after the last dose of PTZ, animals were sacrificed and various biochemical parameters were assessed in the whole brain. Compared with normal control group, PTZ-kindled mice had significantly higher levels of malondialdehyde, nitrite, myeloperoxidase but had lower levels of reduced glutathione in the whole brain homogenate. Chronic treatment with nimesulide (2.5 or 5 mg/kg, p.o.) for 15 days showed significant decrease in kindling score and could play a role in controlling the accompanying biochemical alterations due to PTZ. These results suggested that nimesulide, a preferential COX-2 inhibitor offered neuroprotection against PTZ-induced kindling in mice. 相似文献
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Naveen K. Jain Chandrashekhar S. Patil R. E. Kartasasmita M. Decker J. Lehmann Shrinivas K. Kulkarni 《Drug development research》2004,61(2):66-78
Naproxen‐2‐nitrooxyethylester (S‐(+)‐2‐(6‐methoxy‐2‐naphthyl)propanoic acid‐2‐nitrooxyethylester, LE‐EK06) was synthesized from naproxen and 2‐nitrooxyethylbromide as a novel nitric oxide–releasing derivative of naproxen. Molar equivalents of LE‐EK06 (6.93–27.73 mg/kg, p.o.) to naproxen dose‐dependently exhibited greater antinociceptive activity in comparison to naproxen in a writhing assay. The compound (5.54–22.18 mg/kg, p.o.) showed greater anti‐inflammatory activity at 2 h after as comparable to its effect at 4 h after carrageenan challenge in rats. Further, LE‐EK06 (9.45 mg/kg, p.o.) was more potent in the carrageenan‐evoked hyperalgesia. LE‐EK06 (11.09 mg/kg, p.o.) and naproxen (8.0 mg/kg, p.o.) showed a comparable inhibitory effect on exudate formation and migration of polymorphonuclear leukocytes (PMNs) in a carrageenan‐induced pleurisy test. Further, the compound (11.09 mg/kg, p.o.) significantly reduced myeloperoxidase activity in carrageenan‐treated paw and demonstrated significantly less gastrotoxicity in acute and chronic (21 days) studies. The scanning electron microscopy revealed that LE‐EK06 showed only mild gastric damage (slight disruption of mucus layer) in comparison to naproxen. The present study suggested that naproxen‐2‐nitrooxyethylester (LE‐EK06) represents a novel gastric sparing NSAID. Drug Dev. Res. 61:66–78, 2004. © 2004 Wiley‐Liss, Inc. 相似文献
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Vishal S Narang Amar Lulla Geena Malhotra Shrinivas Purandare 《Pharmacological research》2004,50(5):511-516
Stavudine (d4T), a thymidine nucleoside analogue has been effectively used for treatment of patients infected with HIV. A randomized, two-way, crossover study was conducted in 24 fasting, healthy, Caucasian male volunteers to compare plasma pharmacokinetic (PK) profile and single-dose tolerability of a new d4T formulation (Stavir, Cipla Ltd, India; 40 mg capsule, test, T) with that of reference (R) formulation (Zerit), Bristol-Myers Squib, NJ, USA; capsule, 40 mg). Each volunteer received T and R formulation separated by at least 10 days of drug free wash-out period. Plasma concentrations of d4T, determined upto 24h post-dose by a validated LC-MS/MS assay were utilized to assess PK parameters such as maximum observed plasma concentration (Cmax), time to Cmax (tmax), and area under plasma concentration curve (AUC(infinity)). The primary plasma PK parameters, Cmax, and AUC(infinity), of anti-retroviral were comparable for either of the formulations. tmax was achieved within an hour suggesting rapid absorption of d4T from both formulations. Geometric mean ratios (GMR) (percentage reference) of AUC(infinity) and Cmax, and their 90% confidence intervals (CI) were 106.32 [102.52-110.26] and 102.32 [90.25-116.00], respectively. As the 90% CI of GMR were entirely within 80-125% for log-transformed parameters, two formulations were considered bioequivalent, in the extent and rate of absorption. Both formulations exhibited similar tolerability under fasting conditions. 相似文献
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目的:开展熟三七联合曲美他嗪治疗冠心病心肌缺血的临床观察。方法:将冠心病心肌缺血的患者126例随机分为对照组、曲美组和联合用药组,每组42例。对照组口服阿司匹林肠溶片和单硝酸异山梨酯缓释胶囊;曲美组在对照组的基础上,增加口服盐酸曲美他嗪片;联合用药组在对照组的基础上,增加口服盐酸曲美他嗪片和熟三七粉。结果:相较对照组和曲美组,联合用药组能有效降低冠心病患者血液中TC、TG与LDL-C的水平,升高HDL-C的水平,显著改善临床症状。其总有效率可大幅度地提高至95.24%(P<0.05),而总不良反应发生率大幅度地降低至7.14%(P<0.01)。结论:熟三七联合曲美他嗪治疗冠心病心肌缺血疗效明确,建议在临床上推广应用。 相似文献
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Rajesh Phatake Sameer Desai Manikanth Lodaya Shrinivas Deshpande Nagaraj Tankasali 《Indian Journal of Critical Care Medicine》2014,18(4):250-252
A 32-year-old male presented with a history of consuming some organophosphorous compound with suicidal intention. He was treated with atropine, pralidoxime, ventilator support. During stay patient had persistent irritability, tachycardiaand hypertension despite sedation and labetalol infusion. He developed headache, visual blurring hemiparesis and focal seizures. Magnetic resonance imaging of the brain revealed multifocal hyperintensities mainly in subcortical areas of parietal and occipital regions in T2-weighted images, with increased values of Apparent Diffusion Coefficient, suggesting posterior reversible encephalopathy syndrome (PRES). The possibilities of PRES caused by organophosphorous poisoning either due to hypertension caused by autonomic deregulation or direct neurological toxicity has been discussed. 相似文献
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