The synthetic prostaglandin E1 analogue rioprostil reduces the nephrotoxic potential of cyclosporine A

Acute CyA nephrotoxicity involves alteration in the proximal tubule and leads to glomerular lesions. Administration of a vasodilatator agent such as the prostaglandin E1 analogue Rioprostil (Bayer AG, BAY 06893) might prevent preglomerular vasoconstriction and hence reduce cyclosporin nephrotoxicity. As an increased excretion of urinary enzymes as a consequence of CyA-nephrotoxicity is well known we investigated in 40 male Wistar rats the excretion of three urinary enzymes: the brush border enzyme gamma-glutamyltransferase (GGT), the leucine aminopeptidase (LAP), and the lysosomal enzyme N-acetyl-beta-glucosaminidase (NAG). Additionally we determined s-creatinine and CyA plasma level. The kidneys were studied histologically at the end of the study. Wistar rats receiving 20 or 50 mg CyA/kg/d showed a marked deterioration in renal function and an increase of all urinary enzymes determined. In the rats receiving 20 mg CyA/kg/d and Rioprostil (150 micrograms/d) renal function and the enzymes determined remained in the normal range. There was no change in the enzyme excretion and only a minor improvement of renal function in rats receiving 50 mg CyA/kg/d and Rioprostil. Histological findings showed prevention of CyA nephrotoxicity in the 20 mg/kg/d group and diminished renal damage in the 50 mg/kg/d group.     

Single- vs Multiple-Dose Pharmacokinetics of Clozapine in Psychiatric Patients

Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t1/2 m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P less than 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402-405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis-Menten kinetics.     

Tissue distribution, disposition, and metabolism of cyclosporine in rats

Tissue distribution, disposition, and metabolism of 3H-cyclosporine were studied in rats after single and repeated oral doses of 10 and 30 mg/kg and after an iv dose of 3 mg/kg. The oral doses of 10 and 30 mg/kg were dissolved in polyethylene glycol 200/ethanol or in olive oil/Labrafil/ethanol. Absorption from both formulations was slow and incomplete, with peak 3H blood levels at 3-4 hr. Approximately 30% of the radioactive dose was absorbed, which is consistent with oral bioavailability data for cyclosporine. More than 70% of the radioactivity was excreted in feces and up to 15% in urine. Elimination via the bile accounted for 10 and 60% of the oral and iv doses, respectively. Since unchanged cyclosporine predominated in both blood and tissues at early time points, the half-lives of the distribution phases (t 1/2 alpha) of parent drug and of total radioactivity were similar. In blood, kidney, liver, and lymph nodes, t 1/2 alpha of cyclosporine ranged from 6-10 hr. Elimination of radioactivity from the systemic circulation was multiphasic, with a terminal half-life of 20-30 hr. 3H-Cyclosporine was extensively distributed throughout the body, with highest concentrations in liver, kidney, endocrine glands, and adipose tissue. The concentrations of both total radioactivity and parent drug were greater in tissues than in blood, which is consistent with the high lipid solubility of cyclosporine and some of its metabolites. Skin and adipose tissue were the main storage sites for unchanged cyclosporine. Elimination half-lives were slower for most tissues than for blood and increased with multiple dosing. The amount of unchanged drug was negligible in urine and bile.(ABSTRACT TRUNCATED AT 250 WORDS)     

Einsatz von Bone-morphogenetic Protein-7 (BMP-7) in der Behandlung von Pseudarthrosen der oberen und unteren Extremität

Bone morphogenetic proteins (BMPs) are bone growth factors, which regulate bone formation during fetal development and bone repair after injury in postfetal life. Since 1992 BMP-7 has been produced by recombinant technique (rhBMP-7). Numerous animal models and clinical trials have shown that rhBMP-7 can induce de novo bone formation in segmental defects of bones and in cases of nonunion. Since 2001 rhBMP-7 has been approved for treatment of tibial nonunion in Europe. The effect of rhBMP-7 is comparable to the clinical and radiological results achieved with bone autografts. The problem of donor site morbidity (which occurs in up to 20% of all cases) is eliminated by the use of BMP-7. Long-term results and experience in clinical practice are not yet available.     

Clinicopathologic analysis of eight cases of pancreatic carcinoid tumors

Carcinoids of the pancreas are exceedingly rare tumors that orieinate from the enterochromaffin cells of the gastroenteropancreatic neuroendocrine system. According to a recent report,1 pancreatic carcinoids are found in only 0.58% (79/13 715 cases) of the entire carcinoid group. Todate, very limited information regarding the detection and diagnosis of this entity has been reported in the available literature. Although pancreatic carcinoid tumors grow.     

多沙唑嗪与特拉唑嗪治疗原发性高血压的疗效比较

目的:比较甲磺酸多沙唑嗪和特拉唑嗪治疗原发性高血压的疗效和安全性.方法:采用随机单盲平行对照试验,将符合条件的轻、中度高血压患者63例随机分为试验组(多沙唑嗪)和对照组(特拉唑嗪).试验剂量从2 mg开始逐渐递增至2～8 mg/d,疗程4周.治疗前后分别行心电图、常规体检、血尿常规和生化检查.结果:①治疗4周后,多沙唑嗪组降压总有效率80.7%,特拉唑嗪组降压总有效率70.0%.两组间无显著性差异.②多沙唑嗪组治疗前后收缩压、舒张压的下降幅度分别为10.81%、10.70%,特拉唑嗪组为10.01%、11.47%.两组间无显著性差异.③多沙唑嗪组有效剂量2～6 mg/d,平均3.04 mg/d,特拉唑嗪组有效剂量2～8 mg/d,平均4.19 mg/d.④每组不良事件发生率相似,多沙唑嗪组25.8%,特拉唑嗪组33.3%(P>0.05).最常见的不良反应为头晕、头痛、心悸、体位性低血压等,多为轻度,可迅速缓解,多沙唑嗪组未发生体位性低血压.结论:甲磺酸多沙唑嗪2～6 mg/d,一天一次口服治疗轻、中度高血压安全有效.     

自身免疫性白内障的晶状体代谢与生理改变研究

目的 :探讨自身免疫性白内障 (AIC)的病理生理学机制。　方法 :采用酶组织化学方法以及晶状体生理功能检查 ,观察AIC模型动物晶状体生理功能与组织内主要酶活性的变化。　结果 :晶状体组织内Na K ATP酶活性降低与晶状体调节力下降、裂隙灯下显微镜混浊改变之间存在着相关性。　结论 :自身免疫性晶状体损伤 ,进而造成晶状体组织内相关酶代谢异常是AIC的病理基础     

EMPACT syndrome

Background: Seizure prophylaxis with phenytoin is a common measure in oncologic patients with brain metastases. In these patients, generalized severe adverse drug reactions such as erythema multiforme (EEM) may occur. However, in a subgroup of patients with brain radiation therapy, EEM‐like lesions develop particularly in the radiation field. Most recently, the acronym EMPACT ( E rythema M ultiforme associated with P henytoin A nd C ranial radiation T herapy) was proposed to specifically describe this syndrome. Patient/Method: Here, we report on EMPACT syndrome in a 46‐year‐old woman. Therapeutic measures included seizure prophylaxis with phenytoin and total brain radiation therapy of brain metastases from bronchial carcinoma. Three weeks after introduction of phenytoin, the patient presented with EEM‐like skin lesions restricted to the original radiation field and facial mucocutaneous involvement. After a few days, the rash spread to the upper part of the body. She was also in poor general condition. Results: The immediate cessation of phenytoin therapy, combined with administration of systemic corticosteroids and high dose immunoglobulins along with intensive local treatment and pain medications, resulted in complete resolution of the skin eruption. Patch testing to phenytoin was positive after 72 hours. Conclusion: EMPACT should be classified as an specific entity among the EEM‐like drug reactions as it only appears after radiotherapy and seizure prophylaxis with the anticonvulsant phenytoin. We propose including specific type IV‐sensitization to phenytoin into the definition of EMPACT.     

海洛因依赖者戒毒中应用护理程序的研究

目的:探讨护理程序对戒毒病人的护理模式,以促进病人积极参与戒毒,减轻戒断症状及改善吸毒导致生理、心理、社会的危害。方法:对应用护理程序工作方法的护理效果进行SPSS11.5统计分析。结果:开展后住院病人意外事件及暴力行为的发生率比开展前显著性降低,实施心理卫生教育后病人对毒品危害性及相关知识认识水平显著提高。结论:通过应用护理程序的工作方法能帮助病人进步且朝向预定目标,为病人走上康复之道打下基础。     

耐药性癫(癎)患者颞叶中细胞周期依赖性蛋白激酶5的表达

目的 研究细胞周期依赖性蛋白激酶5(cyclin dependent kinases 5,CDK5)在耐药性癫(癎)患者颞叶中的表达,探索其在耐药性癫(癎)发病机制中的作用.方法 收集耐药性癫(癎)患者术后脑组织,用荧光定量PCR、免疫组化和Western blot 3种检测方法从基因和蛋白水平分别测定CDK5在耐药性癫(癎)患者颞叶中的表达,并与对照组进行比较.结果 荧光定量PCR发现CDK5 mRAN比对照组明显增加,免疫组化检测显示这种基因的蛋白表达产物主要分布在神经元轴突和胶质细胞中,Western blot检测在相对分子质量35 000处有一蛋白条带,并且可见实验组(颞叶和海马中分别为1.4293±0.1839和2.0733±0.4738)高于对照组(颞叶和海马中分别为0.9680±0.4147和1.403±0.6163,P＜0.05).结论 CDK5在耐药性癫(癎)患者颞叶中表达增强,提示他们可能参与了耐药性癫(癎)的形成.