Investigation of the role of hyperbaric oxygen therapy in cisplatin-induced nephrotoxicity in rats

Cisplatin (CP) is an effective chemotherapeutic agent used in the treatment of a variety of solid tumours. The most frequently observed side-effect of the use of CP is nephrotoxicity. Recently, evidence has been demonstrated that reactive oxygen species forming in the tubular epithelium play an important role in CP-linked nephrotoxicity. The aim of the study was to observe the effect of hyperbaric oxygen (HBO) therapy on CP nephrotoxicity, a subject which has not been studied previously. Wistar rats were treated with CP (a single intraperitoneal (IP) dose of 0.6 mg/100 g) alone and in combination with HBO (60 min every day for seven days at 2.5×atmospheric pressure). Effects of the treatment on renal function and histology were determined. In analyses at the end of the study it was observed that serum urea, creatinine, and daily urinary protein excretion levels of the CP group were higher than at the start of the study, and that the creatinine clearance level had fallen (P<0.05). There was no significant difference between the CP+HBO group and HBO group serum urea, creatinine, creatinine clearance, and daily urinary protein excretion levels at the beginning and end of the study (P>0.05). Histopathological examination showed that the necrosis score in the proximal tubule epithelial cells and average apoptitic cell numbers in the CP group were higher than those in the CP+HBO and HBO groups (P<0.05). There was no statistical difference between the CP+HBO group and the HBO group in terms of necrosis score in the proximal tubule epithelial cells and the percentage of distal tubules containing hyaline casts in the lumen. In conclusion, in this study it was observed that in experimental study of CP nephrotoxicity the synchronous application of HBO therapy with CP prevents kidney damage.     

Lycopene, a carotenoid, attenuates cyclosporine-induced renal dysfunction and oxidative stress in rats

The aim of this study was to investigate the possible protective role of antioxidant treatment with lycopene on cyclosporine A-induced nephrotoxicity using biochemical and histopatological approaches. Adult male Sprague-Dawley rats were randomly divided into four groups. The control group received physiological saline; animals in the lycopene group received only lycopene (10 mg/kg); animals in the cyclosporine A group received only cyclosporine A (15 mg/kg) and animals in cyclosporine plus lycopene group received cyclosporine and lycopene for 21 days. The effects of lycopene on cyclosporine A-induced nephrotoxicity were evaluated by plasma creatinine, urea, sodium and calcium concentrations; kidney tissue thiobarbituric acid reactive species, reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and catalase activities and histopatological examinations. Administration of cyclosporine A to rats induced a marked renal failure, characterized with a significant increase in plasma creatinine and urea concentrations. Cyclosporine A also induced oxidative stress as indicated by increased kidney tissue concentrations of thiobarbituric acid reactive species and GSH, and reduced activities of GSH-Px and catalase. Moreover, the kidneys of cyclosporine A-treated rats showed tubular necrosis, degeneration, dilatation, thickened basement membranes, luminal cast formation and inter-tubular fibrosis. Lycopene markedly reduced elevated plasma creatinine, urea levels and counteracted the deleterious effects of cyclosporine A on oxidative stress markers. In addition, lycopene ameliorated cyclosporine A-induced pathological changes including tubular necrosis, degeneration, thickened basement membranes and inter-tubular fibrosis when compared to the alone cyclosporine A group. These data indicate that the natural antioxidant lycopene might have protective effect against cyclosporine-induced nephrotoxicity and oxidative stress in rat.     

Alpha-tocopherol and alpha-lipoic acid enhance the erythrocyte antioxidant defence in cyclosporine A-treated rats

The aim of this study was to determine the effects of dietary antioxidant supplementation with alpha-tocopherol and alpha-lipoic acid on cyclosporine A (cyclosporine)-induced alterations to erythrocyte and plasma redox balance. Rats were randomly assigned to either control, antioxidant (alpha-tocopherol 1000 IU/kg diet and alpha-lipoic acid 1.6 g/kg diet), cyclosporine (25 mg/kg/day), or cyclosporine + antioxidant treatments. Cyclosporine was administered for 7 days after an 8 week feeding period. Plasma was analysed for alpha-tocopherol, total antioxidant capacity, malondialdehyde, and creatinine. Erythrocytes were analysed for glutathione, methaemoglobin, superoxide dismutase, catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, alpha-tocopherol and malondialdehye. Cyclosporine administration caused a significant decrease in superoxide dismutase activity (P<0.05 control versus cyclosporine) and this was improved by antioxidant supplementation (P<0.05 cyclosporine versus cyclosporine + antioxidant; P<0.05 control versus cyclosporine + antioxidant). Animals receiving cyclosporine and antioxidants showed significantly increased (P<0.05) catalase activity compared to both groups not receiving cyclosporine. Cyclosporine administration induced significant increases in plasma malondialdehyde and creatinine concentration (P<0.05 control versus cyclosporine). Antioxidant supplementation prevented the cyclosporine induced increase in plasma creatinine (P<0.05 cyclosporine versus cyclosporine + antioxidant; P>0.05 control versus cyclosporine + antioxidant), however, supplementation did not alter the cyclosporine induced increase in plasma malondialdehyde concentration (P>0.05 cyclosporine versus cyclosporine + antioxidant). Antioxidant supplementation resulted in significant increases (P<0.05) in plasma and erythrocyte alpha-tocopherol in both of the supplemented groups compared to non-supplemented groups. In conclusion, dietary supplementation with alpha-tocopherol and alpha-lipoic acid enhanced the erythrocyte antioxidant defence and reduced nephrotoxicity in cyclosporine treated animals.     

Therapeutic efficacy of DL-alpha-lipoic acid on cyclosporine A induced renal alterations

The present study was designed to evaluate the possible beneficial effect of lipoic acid in preventing the renal damage induced by cyclosporine A in rats. Male albino rats of Wistar strain were divided into four groups and treated as follows. Two groups received cyclosporine A by oral gavage (25 mg/kg/body weight) for 21 days to induce nephrotoxicity, one of which simultaneously received lipoic acid treatment (20 mg/kg body weight) for 21 days. A vehicle (olive oil) and a lipoic acid drug control were also included. Cyclosporine A induced renal damage was evident from the decreased activities of tissue marker enzymes (alkaline phosphatase, acid phosphatase, lactate dehydrogenase, aspartate transaminase and alanine transaminase) and decreased activities of ATPases (Na+, K+-ATPase, Ca2+-ATPase and Mg2+ ATPase). An apparent increase in the levels of serum constituents (urea, uric acid and creatinine) and urinary marker enzymes (N-acetyl-beta-D-glucosaminidase, beta-glucosidase, beta-galactosidase, cathepsin-D and gamma-glutamyl transpeptidase) along with significant decline in creatinine clearance were seen in the cyclosporine treated rats, which was reversed upon treatment with lipoic acid. Ultrastructural observations were also in agreement with the above abnormal changes. Lipoic acid effectively reverted these abnormal biochemical changes and minimized the morphological lesions in renal tissue. Hence, this study clearly exemplifies that lipoic acid might be an ideal choice against cyclosporine A induced cellular abnormalities.     

Beneficial effects of nilotinib,tyrosine kinase inhibitor on cyclosporine-A induced renal damage in rats

Nilotinib is a known tyrosine kinase inhibitor that has been approved for treatment of leukemia. The possible protective effect of nilotinib on cyclosporine A-induced nephropathy was investigated in this study and the possible underlying mechanism was explored. Nilotinib (25 mg/kg, orally) and cyclosporine A (15 mg/kg/day, subcutaneous) were given to male SD rats for 28 days. Cyclosporine A alone was found to significantly increase serum creatinine, blood urea nitrogen, lactate dehydrogenase, urinary micrototal protein, renal thiobarbituric acid reactive substance, Bax, cytosol cytochrome c release and nuclear factor kappa B activation. Moreover, cyclosporine A significantly reduced serum albumin, creatinine clearance, urinary total antioxidant, superoxide dismutase, glutathione and Bcl2 protein levels. Pathological results showed that in the model group; there was an obvious shrinkage and congestion of the glomeruli and widening of urinary spaces of renal corpuscles, in addition to marked renal tubular injury and fibrosis, while in the group pretreated with nilotinib all measured serum, renal and pathological changes were significantly reduced. This protective effect of nilotinib is linked to the enhanced antioxidant status and reduced inflammation and apoptosis induced by cyclosporine A.     

依达拉奉联合高压氧辅助治疗急性脑梗死42例

目的 观察依达拉奉联合高压氧辅助治疗急性脑梗死的临床疗效。方法 选择发病24 h内的急性脑梗死患者82例,随机分为联合治疗组42例和对照组40例。联合治疗组应用依达拉奉静脉给药,剂量为30 mg,bid,共14 d,48 h内开始联合高压氧治疗,每次60 min,qd,共12次,压力为2.5个绝对大气压（ATA）。其余治疗与对照组相同。治疗前,治疗后7,14及21 d对患者进行欧洲卒中量表（ESS）评估。结果 两组治疗后7,14及21 d与治疗前比较神经功能评分ESS均有明显改善。联合治疗组神经功能评分ESS在治疗后7 d与对照组比较差异无显著性（P>0.05）,在治疗后14 d优于对照组,差异有显著性（P<0.05）,在治疗后21 d优于对照组,差异有极显著性（P<0.01）。结论 依达拉奉联合高压氧辅助治疗急性脑梗死,对脑组织有显著保护作用.     

Taurine attenuates hypertension and renal dysfunction induced by cyclosporine A in rats

Cyclosporine A (CsA) is the first-line immunosuppressant used for the management of solid organ transplantation and autoimmune diseases. Nephrotoxicity is the major limitation of CsA use. Recent evidence suggests that reactive oxygen species (ROS) play an important role in mediating CsA-induced hypertension and nephrotoxicity. Taurine, the major intracellular free beta-amino acid, is known to be an endogenous anti-oxidant and membrane-stabilizing agent. The present study was designed to investigate the effects of taurine on CsA-induced oxidative stress, hypertension and renal dysfunction. 2. Animals were assigned into four groups of seven rats each as follows: (i) control group, receiving vehicle (olive oil; 1 mL/kg, s.c.); (ii) CsA group, given CsA (25 mg/kg per day, s.c.) for 21 days; (iii) taurine group, supplemented with taurine (1% in the drinking water); and (iv) taurine + CsA group, treated with taurine 3 days before and concurrently during CsA injections for 21 days. 3. Cyclosporine A administration elevated blood pressure, reduced serum nitric oxide (NO) levels and deteriorated renal function, as assessed by increased serum creatinine levels and proteinuria and reduced urine flow rate and creatinine clearance compared with vehicle-treated rats. Cyclosporine A induced oxidative stress, as indicated by increased renal tissue concentrations of thiobarbituric acid-reactive substances and reduced concentrations of renal glutathione, glutathione peroxidase and superoxide dismutase. Conversely, no change was noted in renal catalase activity. Moreover, the kidneys of CsA-treated rats showed interstitial inflammation and renal tubular atrophy. 4. Taurine markedly reduced elevated blood pressure, attenuated renal dysfunction and the reduction in serum NO levels and counteracted the deleterious effects of CsA on oxidative stress markers. Furthermore, taurine ameliorated CsA-induced morphological changes. 5. These data clearly indicate the protective potential of taurine against CsA-induced hypertension and nephrotoxicity and suggest a significant contribution of its anti-oxidant property to this beneficial effect.     

Amelioration of cyclosporine A-induced renal, hepatic and cardiac damages by ellagic acid in rats

Treatment with cyclosporine A has significantly improved long-term survival after organ transplantations. Cyclosporine A also causes a dose-related decrease in body functions in experimental animals and human beings. The generation of reactive oxygen species has been implicated in cyclosporine A-induced dysfunctions. The aim of this study was to determine the effects of ellagic acid on cyclosporine A-induced alterations in the kidney, liver and heart oxidant/antioxidant system. The control group was treated with placebo and subcutaneous injection of 0.5 ml isotonic saline + 0.5 ml slightly alkaline solution for 21 days. The cyclosporine A group received a subcutaneous injection of cyclosporine A (15 mg/kg) + 0.5 ml slightly alkaline solution for 21 days. The ellagic acid group was treated with a subcutaneous injection of 0.5 ml isotonic saline + ellagic acid (10 mg/kg) for 21 days. The cyclosporine A plus ellagic acid group received a subcutaneous injection of cyclosporine A + ellagic acid for 21 days. Ellagic acid and slightly alkaline solution were administered by gavage. The rats were killed at the end of the treatment period. Malondialdehyde (MDA) and reduced glutathione (GSH) levels, glutathione peroxidase (GSH-Px) and catalase (CAT) activities were determined in kidney, liver and heart tissues. While administration of cyclosporine A increased the MDA levels in kidney, liver and heart tissues, it decreased the GSH, GSH-Px and CAT in these samples when compared to the control group. However, the simultaneously administration of ellagic acid markedly normalized the cyclosporine A-induced liver and heart MDA levels, liver CAT activities and GSH-Px activities of all samples. Cyclosporine A caused marked damages in the histopathological status of kidney, liver and heart tissues, which were partially ameliorated by ellagic acid administration. In conclusion, ellagic acid may be used in combination with cyclosporine A in transplantation treatment to improve the cyclosporine A-induced oxidative stress parameters and other adverse effects.     

高压氧对大鼠急性胰腺炎T细胞亚群及电镜超微结构变化的影响

目的 研究急性胰腺炎（AP）时是否存在CD4＋、CD8＋细胞亚群的改变及高压氧治疗对其影响,并同时观察治疗7 d后的电镜超微结构变化.方法 56只大鼠随机分为急性胰腺炎高压氧治疗组（治疗组24只）,急性胰腺炎空白对照组（对照组24只）和急性胰腺炎假手术组（假手术组8只）,其中对照组和治疗组均采用胰管结扎的方法制备胰腺炎模型,造模后每组再随机分为三个亚组：每个亚组8只,分别在造模后1 d,3 d,7 d处死,且治疗组进行高压氧干预,假手术组仅进行开腹关腹手术.两组均留取胰腺组织标本及血液样本.使用流式细胞仪进行T细胞亚群分析.了解高压氧对急性胰腺炎T细胞亚群的影响.同时进行胰腺细胞电镜检查进行细胞核,线粒体,粗面和滑面内质网评分,了解超微结构变化.结果 对照组CD4＋细胞的减少和CD4＋/CD8＋细胞比值的明显降低.高压氧治疗7 d后,治疗组的CD4＋细胞及CD4＋/CD8＋细胞比值明显升高,且电镜下胰腺组织在细胞核,线粒体,粗面和滑面内质网等评分均较对照组明显改善,胰腺内分泌部的酶原颗粒也较未进行高压氧治疗的对照组明显增多.结论 高压氧治疗能改善急性胰腺炎组织的氧供,调节T细胞免疫功能.     

Hyperbaric oxygen improves survival in heatstroke rats by reducing multiorgan dysfunction and brain oxidative stress

Hyperbaric oxygen has been found to be beneficial in treating heatstroke animals. We attempted to further assess the possible mechanism of therapeutic protection offered by hyperbaric oxygen in experimental heatstroke. Anesthetized rats, immediately after the onset of heatstroke, were randomized into the following groups and given: a) hyperbaric oxygen (100% O(2) at 253 kPa for 1 h); or b) normal air. They were exposed to 43 degrees C temperature to induce heatstroke. When the untreated rats underwent heat stress, their survival time values were found to be 20-24 min. Resuscitation with hyperbaric oxygen increased the survival time to new values of 152-176 min. All untreated heatstroke rats displayed cerebrovascular dysfunction (evidenced by hypotension, intracranial hypertension, and cerebral hypoperfusion, hypoxia, and ischemia), hypercoagulable state (evidenced by increased levels of activated partial thromboplastin time, prothrombin time, and D-dimer, but decreased values of platelet count and protein C in plasma), and tissue ischemia/injury (evidenced by increased levels of creatinine, serum urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in plasma, and dihydrobenzoic acid, lipid peroxidation, and oxidized-form glutathione/reduced-form of glutathione ratio in hypothalamus). The cerebrovascular dysfunctions, hypercoagulable state, tissue ischemia/injury, and brain oxidative stress that occurred during heatstroke were all suppressed by hyperbaric oxygen therapy. The current results indicate that hyperbaric oxygen therapy may resuscitate rats that had a heatstroke by decreasing multiple organ dysfunction and brain oxidative stress.     

Effect of molsidomine and L-arginine in cyclosporine nephrotoxicity: role of nitric oxide

Cyclosporine A (CsA) is a potent and effective immunosuppressive agent, but its action is frequently accompanied by severe renal toxicity. To determine if the renal alterations are mediated directly by cyclosporine or by secondary homodynamic alterations induced by cyclosporine, we evaluated if L-arginine and a nitric oxide donor, molsidomine could prevent these alterations. Eight groups of rats were employed in this study, group 1 served as control, group 2 rats were treated with CsA (20 mg/kg, s.c. for 21 days), group 3 received CsA along with L-arginine (125 mg/kg in drinking water concurrently with CsA), groups 4 and 5 received CsA along with molsidomine (5 and 10 mg/kg, p.o. 24 h before and 21 days concurrently with CsA), group 6 received CsA along with L-arginine (125 mg/l in drinking water concurrently with CsA) and L-NAME (10 mg/kg), groups 7 and 8 received L-NAME (10 mg/kg) along with CsA and molsidomine (5 and 10 mg/kg), respectively. Renal function was assessed by measuring serum creatinine, blood urea nitrogen, creatinine and urea clearance. Tissue and urine nitrite and nitrate levels were measured to estimate the total nitric oxide levels. The renal oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels and by enzymatic activity of catalase and superoxide dismutase. Renal morphological alterations were assessed by histopathological examination. CsA administration for 21 days resulted in a marked renal oxidative stress, significantly deranged the renal functions as well as renal morphology. Treatment with L-arginine as well as with molsidomine significantly improved the renal dysfunction; tissue and urine total nitric oxide levels, renal oxidative stress and prevented the alterations in renal morphology. This protection against CsA nephrotoxicity was attenuated by treatment with L-NAME, clearly indicating that NO plays a pivotal role in renoprotective effect of L-arginine and molsidomine against cyclosporine nephrotoxicity.     

血必净对免疫抑制脓毒症模型的保护作用

目的 观察血必净对免疫抑制脓毒症小鼠的影响。方法 使用随机数字表法将152只小鼠分为对照组（Control）、免疫抑制组（IM）、免疫抑制脓毒症模型组（ISM）、血必净治疗组（XT）,每组38只小鼠。IM组沿下腹正中线旁边腹腔注射环孢素A免疫抑制,25 mg/kg,隔日1次,共3次。ISM组免疫抑制后沿下腹正中线旁边腹腔注射300 μL浓度为1×109 CFU /mL的大肠杆菌44102;XT组免疫抑制脓毒症造模后30 min,沿下腹正中线旁边腹腔注射血必净4mL/kg,30 min后按相同剂量重复注射1次;Control组注射等体积的生理盐水。（1）造模8 h,各组取4只小鼠,进行血细菌培养。（2）造模12 h,各组取10只小鼠,使用流式细胞法检测外周血CD3+CD4+和CD3+CD8+。（3）造模12 h,各组取10 只小鼠,采用酶联免疫吸附试验（ELISA）检测外周血肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6。（4）造模12 h,各组取4只小鼠,采用蛋白免疫印迹法测定高迁移率蛋白（HMGB1）。（5）造模12 h,各组取10只小鼠,使用全自动分析仪检测外周血丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、尿素氮（BUN）、血肌酐（CR）。结果 与ISM组相比,XT组的CD3+CD4+/CD3+CD8+的比值明显升高,血细菌培养数量明显降低;肝肾功能指标ALT、AST、CR、BUN和炎症指标TNF-α、IL-6、HMGB1均明显下降。结论 血必净能够明显调节免疫抑制脓毒症小鼠的免疫系统,对抗细菌,抑制炎症反应,并对重要器官有保护作用。     

The role of vitamin C, vitamin E, and selenium on cadmium-induced renal toxicity of rats

The aim of this study was to determine whether vitamin C, vitamin E, and selenium have protective effects against cadmium-induced renal toxicity of rats. Vitamin C (250 mg/kg/day), vitamin E (250 mg/kg/day), and sodium selenate (0.25 mg/kg/day) were given to rats orally for 8 days. Cadmium (2 mg/kg/day CdCl2) was given to rats intraperitoneally. Vitamin C, vitamin E, and selenium (in the same dose and time) were given 1 h prior to the administration of cadmium every day. The tissue and blood samples were taken from the rats for histological evaluation and biochemical analyses on the Day 9. Lipid peroxidation (LPO) and glutathione (GSH) determination were made in kidney tissue. In addition, urea and creatinine levels were determined in serum. The damage to the kidney tissue was moderate in the rats given cadmium. In this group, the distinctive changes in the proximal tubules were observed. Degenerative changes in kidney tissue were also observed in rats given vitamin C, vitamin E, selenium, and cadmium. LPO levels significantly increased and GSH levels decreased in kidney tissues following cadmium administration. Serum urea and creatinine levels were also increased in rats given cadmium. The administration of vitamin C, vitamin E, and selenium caused a significant decrease in LPO levels and an increase in GSH levels in the kidney of rats given cadmium. Serum urea and creatinine levels were decreased in rats given both the antioxidant and cadmium. It is concluded that vitamin C, vitamin E, and selenium showed some protective effect on the rat kidney.     

The Role of Vitamin C,Vitamin E,and Selenium on Cadmium-Induced Renal Toxicity of Rats

The aim of this study was to determine whether vitamin C, vitamin E, and selenium have protective effects against cadmium-induced renal toxicity of rats. Vitamin C (250 mg/kg/day), vitamin E (250 mg/kg/day), and sodium selenate (0.25 mg/kg/day) were given to rats orally for 8 days. Cadmium (2 mg/kg/day CdCl₂) was given to rats intraperitoneally. Vitamin C, vitamin E, and selenium (in the same dose and time) were given 1 h prior to the administration of cadmium every day. The tissue and blood samples were taken from the rats for histological evaluation and biochemical analyses on the Day 9. Lipid peroxidation (LPO) and glutathione (GSH) determination were made in kidney tissue. In addition, urea and creatinine levels were determined in serum. The damage to the kidney tissue was moderate in the rats given cadmium. In this group, the distinctive changes in the proximal tubules were observed. Degenerative changes in kidney tissue were also observed in rats given vitamin C, vitamin E, selenium, and cadmium. LPO levels significantly increased and GSH levels decreased in kidney tissues following cadmium administration. Serum urea and creatinine levels were also increased in rats given cadmium. The administration of vitamin C, vitamin E, and selenium caused a significant decrease in LPO levels and an increase in GSH levels in the kidney of rats given cadmium. Serum urea and creatinine levels were decreased in rats given both the antioxidant and cadmium. It is concluded that vitamin C, vitamin E, and selenium showed some protective effect on the rat kidney.     

Cyclosporine A-induced changes to erythrocyte redox balance is time course-dependent

Cyclosporine A-treated transplant recipients develop pronounced cardiovascular disease and have increased oxidative stress and altered antioxidant capacity in erythrocytes and plasma. These experiments investigated the time-course of cyclosporine A-induced changes to redox balance in plasma and erythrocytes. Rats were randomly assigned to either a control or cyclosporine A-treated group. Treatment animals received 25 mg/kg of cyclosporine A via intraperitoneal injection for either 7 days or a single dose. Control rats were injected with the same volume of the vehicle. Three hours after the final injections, plasma was analysed for total antioxidant status, alpha-tocopherol, malondialdehyde, and creatinine. Erythrocytes were analysed for reduced glutathione (GSH), alpha-tocopherol, methaemoglobin, malondialdehyde, and the activities of superoxide dismutase, catalase, GSH peroxidase, and glucose-6-phosphate dehydrogenase (G6PD). Cyclosporine A administration for 7 days resulted in a significant increase (P<0.05) in plasma malondialdehyde, methaemoglobin, and superoxide dismutase and catalase activities. There was a significant decrease (P<0.05) in erythrocyte GSH concentration and G6PD activity in cyclosporine A animals. There were no significant differences (P>0.05) between groups following a single dose of cyclosporine A in any of the measures. In summary, cyclosporine A alters erythrocyte redox balance after 7 days administration, but not after a single dose.     

Disseminated granuloma annulare: efficacy of cyclosporine therapy

Granuloma annulare is an anatomo-clinical entity that is frequently encountered in everyday dermatological practice. We report our experience regarding 4 patients with disseminated granuloma annulare. Each patient was treated with a cycle of cyclosporine therapy for six weeks. A cycle of systemic cyclosporine therapy was started at a dose of 4 mg/kg/day for four weeks, subsequently reduced by 0.5 mg/kg/day every two weeks. The clinical picture more or less completely resolved within three weeks in all of the patients, and there were no relapses during the dose-tapering period or the following 12 months. Cyclosporine was optimally tolerated by all four patients, none of whom experienced any therapy-related side effects. Cyclosporine is a valid therapeutic option for the treatment of disseminated granuloma annulare, although we recommend its use in a protected hospital environment that facilitates patient monitoring.     

Therapeutic drug monitoring of cyclosporine-lipoprotein levels

Cyclosporine therapy is complicated by nephrotoxicity that is not predicted by drug levels. In this study serial trough blood samples were obtained from 11 allogeneic marrow transplant recipients after initiation of intravenous cyclosporine 2 mg/kg every 12 hours for a period extending 4 weeks after transplantation. Renal dysfunction, assessed by an increase in serum creatinine levels to twice baseline values or when greater than 175 mumol/L, was found in four patients. No associations between renal dysfunction and cyclosporine levels in whole blood, total plasma, or lipoprotein fractions were found. The ratios of maximum and mean high-density low-density lipoprotein cyclosporine concentrations were greatest in patients with renal dysfunction (p less than 0.001). The data suggest therapeutic drug monitoring of cyclosporine in various biologic fluids does not predict onset of drug-associated renal dysfunction. However, the relative role of high-density to low-density lipoprotein transport of cyclosporine may provide an index of renal functional changes associated with the agent.     

3种 头孢菌素对肾功能及环孢素血浓度的影响

５１例肾移植术后患者中随机分组，考查３种新头孢菌素分别与环孢素合并使用时对肾功能及环孢素全血药浓浓度的影响，在合并用头孢菌素前，合并用药７ｄ，停药后７ｄ测定患者的血清肌酐、尿素氮和环孢素全血药物浓度。     

高压氧联合治疗突发性耳聋临床疗效分析

目的：探讨高压氧治疗突发性耳聋的疗效及治疗时机。方法：对照组采用药物治疗,高压氧治疗组在药物治疗的基础上,分超早期（发病第1～2天）和早期（发病第5～7天）高压氧治疗。结果：高压氧治疗组总有效率为69.8%,对照组有效率为28.6%,两组差异有统计学意义（P〈0.01）,超早期高压氧治疗组的有效率为82.2%,疗效明显优于早期高压氧治疗组（有效率为58.82%;P〈0.05）。结论：超早期高压氧辅助药物治疗突发性耳聋疗效明显。     

Cyclosporine reduces hepatic antioxidant capacity: protective roles of antioxidants

The immunosuppressive agent cyclosporine A (CsA) has been reported to exert measurable hepatotoxic effects. One of the causes leading to hepatotoxicity is thought to be reactive oxygen radical formation. Therefore, this study was designed to elucidate possible relation between cyclosporine A treatment and antioxidant capacity (AOC) of hepatic tissue and, to determine if antioxidant supplementation is beneficial. Cyclosporine A was given to 20 rabbits orally for 10 days. Vitamins E and C combination were given intramuscularly. Vitamin therapy was started 3 days before cyclosporine A treatment and continued for 10 days. In each group (control, cyclosporine A, cyclosporine A+vitamin, and vitamin only) there were five animals. After the animals were sacrificed, their livers were removed to be used in the AOC measurement. AOC was found to be lower in cyclosporine A group compared to control and vitamin groups. Results suggest that reduced antioxidant capacity may play part in the cyclosporine A-induced hepatotoxicity and use of some antioxidants may give beneficial results.