ATTENUATION OF ISCHEMIA-REPERFUSION INJURY OF THE LIVER IN DOGS BY CYCLOSPORINE A COMPARATIVE STUDY WITH ALLOPURINOL AND METHYLPREDNISOLONE
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The effects of pretreatment with cyclosporine, allopurinol, or methylprednisolone on ischemia-reperfusion injury of the liver were investigated. A total of 32 adult mongrel dogs that received one of the pretreatments were divided into four groups and were subjected to 90 min liver ischemia. Serum activities of aspartate aminotransferase (s-AST) and lactate dehydrogenase, (s-LDH) as well as animal survivals were used as indicators of liver injury. The elevation of both s-AST and s-LDH was significantly suppressed by pretreatment with cyclosporine as much as by allopurinol. However a significant improvement in animal survival was obtained only in the cyclosporine-pretreated group. Pretreatment with methylprednisolone did not affect either the activities of s-AST and s-LDH or animal survivals when compared with the control group. These data suggest that cyclosporine is a potent protector against ischemic liver injury--as effective as allopurinol or methylprednisolone. Although the precise mechanism of the effect of cyclosporine on liver ischemia still remains unknown, these observations may be of use in liver transplantation.Keywords:
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사염화탄소에 의한 간손상시 CCl₄대사에 xanthine oxidase(XO)가 관련되어지는 규명하기 위한 일환으로 allopurinol을 흰쥐 체중 Kg당 50㎎을 전처치한 다음 CCl₄를 투여한 후 처치하여 다음과 같은 결과를 얻었다. CCl₄투여로 인한 간조직의 postmitochondria 분획의 XO활성은 allopurinol을 전처치하므로서 현저히 감소되었으나 투석한 경우에는 오히려 증가되었으며 type D로부터 type O로의 전환율은 감소되었다. 또한, 투석한 간조직의 XO를 반응속도적인 측면에서 관찰해볼때 allopurinol을 전처치후 CCl₄투여군이 CCl₄단독투여군보다 Vmax가 크게 나타났다. CCl₄투여로 인한 체중당 간무게의 증가율과 혈청 alanine aminotransferase활성증가율은 allopurinol을 전처치하므로서 저하되었다. 한편 CCl₄투여로 인한 간조직중 aniline hydroxylase 및 glucose 6 phosphatase활성감소율은 allopurinol을 전처치하므로서 저하되었다. 이상의 실험결과를 종합하여볼때 실험동물에 CCl₄와 allopurinol을 병행투여시 allopurinol이 사염화탄소에 의한 간손상을 억제시키는 현상을 XO와 사염화탄소대사간에 관련성이 있음을 시사해주고 있다.
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High-dose pulsed methylprednisolone-related liver injury cases have been reported in the literature, but a prospective study in patients with multiple sclerosis (MS) has never been performed. The aim of this study was to evaluate the prevalence and severity of liver injury in patients with MS after pulsed methylprednisolone therapy.We performed a prospective observational single-center study on patients with MS treated with i.v. methylprednisolone 1,000 mg/day for 5 days. We tested the liver functionality before and 2 weeks after the treatment. In case of severe liver injury, defined according to "Hy's law," a comprehensive hepatologic workup was performed.During a 12-month observation period, we collected data on 251 cycles of i.v. steroid treatment of 175 patients with MS. After excluding eight cycles presenting a basal alteration of the biochemical liver tests, we observed a prevalence of 8.6% of liver injury in MS patients treated with pulsed methylprednisolone for clinical and neuroradiological relapses. In 2.5% of the patients, the liver injury was severe according to Hy's law; after a comprehensive hepatologic workup, three of them received a diagnosis of drug-induced liver injury and the other three of autoimmune hepatitis.Liver injury after pulsed methylprednisolone therapy in patients with MS is not infrequent, and a close monitoring of aminotransferase level before treatment and 2 weeks later seems advisable.
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[Objective] Curative effect of Qingxuetang combined with different dose of allopurinol in treating renal hyperuricemia. Try to reduce the dose of allopurinol on the basis of traditional Chinese medicine for reducing allopurinol's adverse reactions. [Methods] Ninty patients were randomly divided into three groups, with 30 cases in each group. On basis of routine treatment and Qingxuetang treatment, each group was separately given 150 mg allopurinol, 100 mg allopurinol, 50 mg allopurinol. We observe the chang of Scr、BUN、GFR、UA and symptom score at 0、2、4、8 week. [Results] The total curative effect of three groups were no statistically significant difference(P0.05). Scr, BUN, GFR and symptom score in each group was no statistically significant difference(P 0.05). In reducing UA aspect, Qingxuetang combined with allopurinol 100 mg was no statistically significant difference as allopurinol 150 mg(P 0.05). Qingxuetang combined with allopurinol 50 mg reducing UA was less than with allopurinol 150 mg(P0.05). The cases of Qingxuetang combined with allopurinol 100 mg having adverse reactions were less than with allopurinol 150 mg,and degree of adverse reaction was lighter than with allopurinol 150 mg.[Conclusion] The three groups were no statistically significant differences in improvement of renal function and clinical symptoms in renal hyperuricemia. In reducing UA aspect, Qingxuetang combined with allopurinol 100 mg can replace Qingxuetang combined with allopurinol 150 mg. Qingxuetang combined with allopurinol 100 mg was better effective and security than with allopurinol 150 mg.
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Objective To study the protective effect of methylprednisolone on intestinal isehemia?repedusion injury in rats,and to provide experimental evidence for finding its new clinical uses.Methods In male Wistar rats with or without methylprednisolone treatment,intestinal damage was induced by clamping the superior mesenteric artery for 30 min prior to reperfusion.Methylprednisolone was administered via intravenous infusion 5 min before reperfusion was achieved by removal of the clamp.60 minutes after reperfusion SOD and MDA levels were measured as indexes of mucosal injury,and histological examination of hematoxylin and eosin-stained sections was performed.Results The MDA levels in intestinal tissue and serum significantly increased 60 minutes after reperfusion(P0.01).The SOD levels,in contrast,decreased 60 minutes after reperfusion(P0.01).The results were corroborated by histological evaluation of the intestinal tissue.Administration of edaravone diminished the changes of SOD and MDA levels therapeutically.Methylprednisolone could also improve the changes of mucosa significantly.Conclusion Methylprednisolone has been demonstrated to have prophylactic-therapeutic effect on intestinal mucosal injury induced by isehemia-reperfusion in rats by scavenging free radicals in vivo.
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A patient with regional enteritis and recurrent uric acid nephrolithiasis was treated with allopurinol. While on 600 mg of allopurinol daily, she began to pass many small, soft, yellow stones. Analysis of the stones by liquid chromatographic and gas chromatograph/mass spectrometric techniques revealed that their major constituent was oxypurinol, a metabolite of allopurinol. Metabolic studies of the patient indicated that increasing doses of allopurinol were associated with increases in xanthine and oxypurinol excretion, while uric acid excretion was not reduced. This case illustrates a complication of high-dose allopurinol therapy in the treatment of uric acid nephrolithiasis.
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The present study was undertaken to examine the effects of methylprednisolone on the expression and activity of calpain in spinal cord tissue following spinal cord ischemia-reperfusion injury in rats. Adult male Sprague-Dawley rats were subjected to sham operations, ischemia-reperfusion and vehicle treated, or ischemia-reperfusion with methylprednisolone administration after injury. The expression of calpain I in the injured segments of the spinal cord as well as the degradation of the 68 kD neurofilament protein (NFP), a calpain-specific substrate, was determined at 3 h, 24 h, 72 h and 7 days after reperfusion using immunohistochemical labeling and western blot analysis, respectively. Three hours after spinal cord reperfusion, calpain I-positive cells and NFP degradation products were evident. The number of positive cells and immunoreactivity increased with time and peaked at 72 h after reperfusion. In addition, the number of calpain I-positive cells and the abundance of NFP degradation products were significantly lower in the methylprednisolone group, compared with vehicle treated animals following ischemia-reperfusion injury. The results of this study suggest that methylprednisolone can inhibit the expression and degradation activity of calpain following ischemia-reperfusion injury, providing further insight into the therapeutic benefits of methylprednisolone treatment for spinal cord injury.
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Gout is the most common inflammatory arthritis in men and is increasingly prevalent. Allopurinol is very effective at reducing plasma urate concentrations to a level sufficient to dissolve monosodium urate crystals. However, many patients fail to achieve a sufficient therapeutic response to allopurinol. Areas covered: This review covers the metabolism and pharmacokinetics of allopurinol and its active metabolite, oxypurinol and how these factors affect the plasma concentrations of urate at initiation and during long-term therapy with allopurinol. Significant aspects discussed are the importance of adherence to allopurinol therapy, allopurinol hypersensitivity reactions and insights into hyperuricemia. Expert opinion: The initial dosage of allopurinol should be low, particularly in patients with renal impairment. The dose should then be increased slowly until plasma concentrations of urate are sufficient to dissolve monosodium urate crystals (≤ 0.36 mmol/L). For this target, the maintenance dose of allopurinol can be estimated from the equation: Dose = 1413*(Up-0.36) where Up is the pre-treatment concentration of urate. Poor adherence is a major factor limiting successful therapy with allopurinol; however, its use can be improved considerably by education of patients and clinicians. Allopurinol is generally well tolerated and screening for genetic factors predictive of allopurinol hypersensitivity reactions can now be undertaken.
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