Effect of Renal Impairment on the Pharmacokinetics and Tolerability of Tiagabine

Summary: Purpose: We wished to determine the effect of renal impairment on the pharmacokinetics and tolerability of the new antiepileptic drug tiagabine (TGB).
Methods: We assessed TGB pharmacokinetics and tolerability in 25 subjects with various degrees of renal function (based on creatinine clearance, n = 4–6 per group) from healthy (group I) to requiring hemodialysis (group V) in a single and multiple dose (every 12h), one-period (groups I-IV) or a single dose, two-period (group V) study (4-mg oral doses of TGB · HCl). Blood samples were collected after the first dose (both periods for group V) and after the last dose on day 5 (groups I-IV). TGB plasma concentrations and plasma protein binding were determined by high-performance liquid chromatography (HPLC) and ultrafiltration, respectively.
Results: TGB was well tolerated by all study subjects. The pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic parameter (based on either total or unbound concentrations) was statistically correlated with creatinine clearance. For total TGB in plasma, single-dose mean values of the maximum plasma concentration, clearance, and half-life (t1/2) ranged from 52 to 108 ng/ml, from 7.14 to 11.02 I/h, and from 6.4 to 8.4 h, respectively.
Conclusions: TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment.     

Glycopyrrolate vs. atropine during anaesthesia for laryngoscopy and bronchoscopy

As glycopyrrolate has been reported superior to atropine with respect to reduction of salivation, stability of cardiac rate and rhythm, and recovery, a comparison of these properties of the two drugs and placebo was made in 45 patients undergoing direct laryngoscopy and 45 patients undergoing bronchoscopy, in most cases followed by mediastinoscopy. When given i.m. 30 min before anaesthesia (midazolam, alfentanil, thiopentone, and suxamethonium), the two test drugs were found to be equally potent regarding the antisialogogic effect. The same increase in heart rate after the test drugs was seen before induction, and during anaesthesia heart rate rose to the same level in the placebo group as the test groups. During anaesthesia, blood pressure was lowest in the atropine group. No differences could be demonstrated with respect to cardiac arrhythmias, possibly due to the small size of the material. The present study gives no reason for preferring either drug, and only the efficacy of both test drugs in controlling airway secretions provides an argument for using any anticholinergic drug when laryngoscopy or bronchoscopy is performed under the conditions of the present study.     

Endocrinology: Two cases of ovarian tumours in women who had undergone multiple ovarian stimulation attempts

Concerns have been raised recently about the possible associationbetween superovulation and ovarian cancer. In order to contributeto the limited literature on this important issue, two casesof ovarian tumours in women who had undergone multiple ovulationinductions are presented. In the first case, the patient hadsecondary anovulatory infertility. She was treated with humanmenopausal gonadotrophin (HMG) alone and in combination withclomiphene citrate or buserelin for six cycles. She then underwentovarian stimulation with buserelin/HMG in the long protocolfor in-vitro fertilization (IVF) and embryo transfer. In preparationfor a new IVF/embryo transfer attempt, 8 months later, the screeningultrasound revealed a cystic formation of the left ovary andan enlargement of the right. During laparotomy, both ovarieswere found to bear large tumours (approximately 6x5x4 cm) whichwere removed. Histological examination showed that they wereepithelial tumours (serous-papillary cystadenomas) of borderlinemalignancy. The patient conceived spontaneously 1.5 years afterthe operation. In the second case, the patient presented withsecondary anovulatory infertility. She underwent ovulation inductionwith clomiphene/HMG and with buserelin/HMG in the long protocol,and intra-uterine insemination with husband's spermatozoa andconceived (singleton pregnancy). She was delivered by Caesareansection, during which a cystic tumour of the left ovary wasremoved. Histological examination revealed a benign mucous cystadenomaof the ovary. In conclusion, the clinical information from thesetwo cases does not support a causal association between ovarianstimulation and ovarian tumours but does potntially supporta facilitating one.     

补肾方剂对去势大鼠骨代谢影响的实验研究

使用补肾方剂(补肾健骨胶囊)对切除卵巢的雌性成年大鼠进行了不同剂量的药物治疗，并与正常对照组、模型组和尼尔雌醇治疗组的大鼠进行了对比。统计学结果显示，补肾健骨腔囊治疗可有效改善卵巢切除大鼠骨质疏松症，各项骨检测指标明显好于模型组，差异有显著性和非常显著性(P＜0．05～0．001)。补肾健骨腔囊治疗后大鼠骨载荷、骨桡度、骨强度等生物力学指标明显好于模型组(P＜0．05～0．001)。说明补肾健骨胶囊治疗可明显的改善骨质疏松大鼠的骨质丢失状态，提高骨骼抵抗外力冲击的能力，有效的防治骨质琉松症，避免骨折的发生。     

肉桂挥发油对“虚证”模型环核苷酸系统反应性的影响

本实验用纯系CFW小鼠与Wistar大鼠建立“虚证”模型。以环核苷酸系统反应性为指标观察了肉桂挥发油的作用。通过气相色谱及气质联用等方法研究表明,本实验所提取的挥发油中桂皮醛含量约为92％。肉桂挥发油可显著降低“阳虚”——甲状腺素缺乏(甲减)模型升高了的cGMP系统反应性而使其降低了的耗O_2率升高;这是一种治疗作用。肉桂挥发油可显著升高“阴虚”——甲状腺素过多(甲亢)模型已升高了的cAMP系统反应性并使其升高了的耗O_2率进一步升高,这是一种恶化作用。这两种作用与中医对症治疗的原则是一致的。     

Selective inhibition of MAO-A,not MAO-B,results in antidepressant-like effects on DRL 72-s behavior

The effects of monoamine oxidase inhibitors (MAOIs) that selectively inhibit the MAO-A or MAO-B forms of MAO were studied in rats performing under a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement. Clorgyline and CGP11305A, irreversible and reversible MAO-A inhibitors, respectively, increased the reinforcement rate, decreased the response rate, and enhanced temporal discrimination. The irreversible MAO-B inhibitor (–)-deprenyl did not produce similar effects. Pargyline did not increase the reinforcement rate at low doses that selectively inhibit MAO-B, but did increase the reinforcement rate at doses that inhibit MAO-A by more than 90%. The present results are in accord with clinical data demonstrating that MAO-A inhibitors are effective therapeutic agents in treating depression while MAO-B inhibitors are of questionable antidepressant efficacy. The present findings provide further evidence that the DRL 72-s schedule may be useful both as a screen for identifying new antidepressants and for investigating the neurochemical effects of antidepressant drugs that are responsible for their therapeutic effects.     

Dose-response curves of homovanillic acid in pre-frontal cortex and caudate following antipsychotic drugs: relation to clinical potencies

Dose-response curves for the elevation of homovanillic acid (HVA) levels, determined by high performance liquid chromatography using electrochemical detection, in the pre-frontal cortex and caudate of rats after acute treatment with 12 antipsychotic drugs are presented. The order of potency in both brain regions was: haloperidol fluphenazine > loxapine > trifluoperazine > thiothixene > molindone > clopenthixol > chlorpromazine > metoclopramide > thioridazine > clozapine > sulpiride. This ranking is roughly correlated with that based on clinical potencies. The relative elevation of the content of HVA was weaker in the pre-frontal cortex than in the caudate for all drugs tested, except clozapine at a high dose.     

肥胖相关性肾病诊疗研究进展

肥胖相关性肾病已呈流行发展趋势,已成为终末期肾病的主要原因之一。目前认为其发病机制主要与肥胖所致肾小球血流动力学改变和脂质异位沉积等相关,但其机制仍未完全阐明。减轻体重是治疗肥胖相关性肾病的重要方法,但常因环境、个人执行情况的影响而收效甚微,且有部分患者体重控制后肾病仍持续进展。综合应用有效的肥胖相关性肾病治疗方法,对控制其进展十分重要。该文综述肥胖相关性肾病的致病机制和诊疗进展,探讨中药在肥胖相关性肾病治疗中的价值,旨在为临床提供参考,提高肥胖相关性肾病一体化管理水平。     

调和阴阳法针灸对老年不寐患者睡眠质量及MT、NE、5-HT水平的影响

目的 探讨调和阴阳法针灸对老年不寐患者睡眠质量及褪黑素（MT）、去甲肾上腺素（NE）、5-羟色胺（5-HT）水平的影响。方法 选取2020年7月—2022年7月河北医科大学第一医院收治的老年不寐患者120例,采用随机数表法分为观察组和对照组,每组60例。对照组采取常规药物治疗,观察组在对照组基础上联合调和阴阳法针灸。比较两组临床疗效,同时评估其中医证候积分和匹兹堡睡眠质量指数（PSQI）评分,测定MT、NE、5-HT、多巴胺（DA）、γ-氨基丁酸（GABA）水平,观察记录不良反应发生情况。结果 观察组总有效率高于对照组（P <0.05）;观察组治疗前后入睡困难、多梦易醒、神疲食少、目赤口苦、舌红少津、脉弦数、舌苔黄评分的差值均高于对照组（P <0.05）。观察组与对照组治疗前及治疗后2、4周的PSQI评分比较,结果 ①不同时间点PSQI评分比较,差异有统计学意义（F =17.894,P =0.000）;②两组PSQI评分比较,差异有统计学意义（F =26.894,P =0.000）,观察组PSQI评分较低,相对睡眠质量较好;③观察组与对照组PSQI评分变化趋势比较,差异有统计学意义（F =45.247,P =0.000）。观察组治疗前后睡眠总时间、快速眼动睡眠期、睡眠潜伏期、醒觉时间、睡眠效率的差值均高于对照组（P <0.05）;观察组治疗前后MT、NE、5-HT的差值均高于对照组（P <0.05）;观察组治疗前后DA、GABA的差值均高于对照组（P <0.05）;两组不良反应总发生率比较,差异无统计学意义（P >0.05）。结论 调和阴阳法针灸治疗老年失眠症疗效显著,不仅能有效改善患者中医症状、睡眠质量及睡眠结构,还能改善血清MT、NE、5-HT、DA、GABA水平,安全性较高。     

Differential potentiation by calcium antagonists of neuromuscular blockade induced by pancuronium and succinylcholine in cats in vivo

Summary The effects of several calcium antagonists (verapamil, nicardipine and two diltiazem isomers, d-cis and l-cis diltiazem) alone and associated to non-depolarizing (pancuronium) and depolarizing (succinylcholine) neuromuscular blockers, were evaluated on sciatic nerve-tibialis anterior muscle preparations from cats in vivo. The calcium antagonists used (at 0.1 and 0.5mg/kg iv) did not modify the height of muscular twitches elicited indirectly. However, these agents potentiated in a dose-dependent way the neuromuscular blockade induced by iv pancuronium (2–40g/kg) and succinylcholine (6–200g/kg). The order of potency in increasing the effects of pancuronium was nicardipine d-cis diltiazem verapamil, whereas the order of potency in enhancing succinylcholine effects was d-cis diltiazem verapamil nicardipine. The effects of diltiazem were stereoselective, thus the potentiation induced by d-cis diltiazem was significantly greater in all cases than that induced by l-cis diltiazem, which suggests that calcium channel blockade plays a role in these interactions. However, other mechanisms such as calcium antagonists-induced nicotinic receptor desensitization may also be involved.