Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.

Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.     

Oral trimethoprim-sulfamethoxazole in the treatment of cerebral toxoplasmosis in AIDS patients--a prospective study.

Toxoplasma encephalitis is the commonest cause of intracranial mass lesions in AIDS patients. Effective therapy includes pyrimethamine plus sulfadiazine, clindamycin with pyrimethamine, and co-trimoxazole. This study examines the efficacy of oral co-trimoxazole in 20 AIDS patients with toxoplasmosis and seeks to confirm the experience of Torre et al.     

New South Wales Nurse Education Project

Abstract: The development of a teaching package for nurse educators on drug and alcohol problems is described and the contents of its 16 modules outlined.     

Nonexclusive solute transport thru protein channels model of the Na,K ATPase complex and similar channels as general transport routes

In earlier work this author put forward a model of the Na,K ATPase complex as a general transport channel. Detailed treatment was limited to anion and monovalent cation transport. Here the functional mechanisms of the Na,K ATPase and similar protein channels as transport routes for all ionic fluxes and also amino acid, sugar and other solutes are presented. Anions, monosaccharide -OH groups and amino acid carboxyls bind to common arginyls and lose hydration water. They combine with cations which bind to adjacent side chain carboxyls, forming neutral ion pairs or positively charged complexes which have minimums in size, hydration and free polar groups. The smaller size and polarity facilitate entry into the tight, structured water channel of some 8-10 A outer bore. Solute fluxes depend on membrane redox activity which maintains channel sulfhydryls in reduced state required for proper transport. ATP binding at channels contributes to transport conformation while ATP hydrolysis gives high efflux of Na+, H+ and Ca2+ as phosphate ion pairs. This cation efflux current clears cations from inner membrane sites, increases negative potential and provides Na+ and H+ about the outer combining sites, while maintaining their inward gradients. Binding of many agents widens the outer bore to give larger, less selective influx.     

低位前外侧入路微创全髋置换术

目的:评价低位前外侧入路微创全髋关节置换术的可行性和早期临床效果.方法:17位患者18例髋关节进行前外侧入路微创全髋关节置换术,仰卧位,自大转子上2 cm为顶向前下切口,纵行切开髂胫束和臀中肌前部着点,由髋关节囊前方分离至髋臼前外缘.不脱位,经股骨颈截骨和取头,处理髋臼植入假体.患髋内收外旋股骨颈基底脱出切口外,股骨扩髓后植入假体.结果:手术切口平均长(10.5±2.1)cm.切口长短与体重正相关,髋臼病理改变和翻修者更长.手术时间平均为(101.7±14.6)min,术中出血量110～600ml,平均(302.2±77.3)ml;双侧髋关节置换1例.术后2～5 d患髋均可负重行走.随访7～22个月,Harris评分平均:术前44;术后6个月85.假体位置理想.无并发症.结论:经低位的前外侧入路行微创全髋关节置换术,需要特殊的髋关节拉钩和牵开技术.有创伤小、不损伤臀上神经、假体位置理想、术中可以处理较复杂病理改变、准确测量两侧下肢体长度、术后外展肌有力、早期康复等优点.