Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration

The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers.After the sublingual spray C_max was higher (39.0 ng·ml^-1) and t_max was shorter (3.9 min) than after the sublingual (22.8 ng·ml^-1 and 13.8 min) and peroral (16.9 ng·ml^-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng·ml^-1·min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively.The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions. For the a/b ratio of the finger pulse, the maximal effect was higher (e_max=130%) and the time to e_max (t_emax) shorter (16.6 min) after the spray than the sublingual tablet (84.4% and 25.5 min) or peroral tablet (90.2 and 31.3 min). The onset of effect was within 3, 5 and 7.5 min after the spray, sublingual and peroral tablets, respectively. A larger change in the orthostatically-induced decrease in systolic blood pressure and increase in heart rate was obtained following peroral than sublingual administration despite the similar plasma concentrations of ISDN. This probably reflects the larger amount of pharmacodynamically active mononitrate metabolites formed after oral dosing. The integrated effect following administration of 2.5 mg ISDN as spray was similar to that of a sublingual tablet of 5 mg.     

Levodopa improves physical fatigue in Parkinson's disease: a double-blind, placebo-controlled, crossover study.

We quantitatively investigated the effect of carbidopa/levodopa (25/100) on physical fatigue during finger tapping and force generation in a double-blind, placebo-controlled crossover study. Parkinson's disease (PD) subjects were randomly assigned to carbidopa/levodopa or placebo for Visit 1 or 2 and participated in the following two studies: (1) Finger tapping. Twenty-five PD patients used their index fingers to strike two keys 20 cm apart on a musical instrument digital interface (MIDI) keyboard. The slopes of the regression line of dwell time and movement time were used to assess the rate of fatigue development. (2) Force generation. Twelve PD patients contracted the wrist extensors maximally to obtain a baseline maximum voluntary contraction (BMVC) force. Then they repetitively contracted the wrist extensors at 50% of the BMVC for 7 seconds and rested for 3 seconds. An interval maximum voluntary contraction (IMVC) was measured every three repetitions. Fatigue was defined as an IMVC of less than 60% of the BMVC. The slope of the regression line of IMVC was used to assess the rate of force decline. These two studies were repeated 1 hour after carbidopa/levodopa (25/100) or placebo. Subjects filled out the Multidimensional Fatigue Inventory (MFI) at the beginning of the first visit. Results showed that the slope of dwell time decreased with levodopa but not with placebo (P = 0.004). The rate of force decline also decreased with levodopa but not with placebo (P = 0.01). The subscores in the dimension of physical fatigue in the MFI did not correlate with the rate changes in dwell time or the rate changes in force decline. We concluded that (1) levodopa improves physical fatigue in finger tapping and force generation, (2) physical fatigue in Parkinson's disease is at least partially related to dopamine deficiency, and (3) the MFI measures different aspects of physical fatigue compared with those measured by finger tapping and force generation.     

环指屈肌腱损伤吻接术前、后力学性能测试研究

研究正常环指屈肌腱拉伸力学性能和模拟屈肌腱损伤后吻接术后屈肌腱的力学性能,为临床提供生物力学参数。取10个手环指标本,解剖后暴露环指,将标本固定于电子万能试验机底座上,由钢丝绳吊钩沿屈肌腱纵行方向钩住、钢丝绳上端固定于试验机上夹头上,驱动机器,对标本进行拉伸实验,施加拉应力,直至屈肌腱断裂。对断裂后的屈肌腱模拟临床手术进行移位吻接,对10个标本做了腱与腱移位吻接。再对吻接后的标本进行拉伸实验。分别得出了正常组标本和吻接术后标本的拉伸最大载荷、应力、应变等数据。表明:屈肌腱腱与腱吻合组最大载荷、应力、应变均小于正常对照组,但模拟末端编织法吻接术腱与腱吻合组标本,仍具有较好的拉伸力学性能指标。     

静脉动脉化再植拇指完全离断

目的 报道静脉动脉化再植拇指完全离断的新方法。方法 1999—2002年在5例拇指完全离断再植手术中，因指动脉严重损伤或多次吻合指动脉失败后，将近侧动脉与断指的一条静脉吻合作为供血通路，近侧的静脉与断指的另几条静脉吻合作为回血通路。结果 5例再植拇指全部成活，早期病例完全恢复了良好的功能。结论 静脉动脉化是一种拇指离断再植的新方法，操作简便，效果可靠，值得推广应用。     

手指离断再植术后护理

目的 探讨断指再植护理措施。方法 采用指体的摆放，病房适宜温度20～25℃，烤灯局部保温，术后观察血运指标，小儿特殊护理及康复指导。结果 成活优良率91．6％，住院天数平均16天，功能恢复满意率75％。结论 护理措施恰当，可显降低并发症的发生，提高治愈率。     

Prevalence of vibration-induced white finger and assessment of vibration exposure among travertine workers in Italy

Summary Among 76 stonedrillers and stonecutters/chippers working in the Rapolano travertine quarries (Tuscany, Italy), 27 subjects (35.5%) were affected with vibration-induced white finger (VWF). The median latent period for VWF was ten years (range 0.1–26 years). A VWF prevalence of 8% was found among 60 comparable controls (P < 0.0001). Vibration measurements showed that the frequency-weighted accelerations for two rock-drills and two small chipping hammers ranged from 19.7 to 36.4 m/s². Weighted accelerations between 2.4 and 4.1 m/s². were measured on the handles of a vertical grinder and a hand cutter. Vibration data, daily exposure time and total duration of exposure period were used to calculate two indicators of vibration dose such as the four-hour, energy-equivalent, frequency-weighted acceleration (m/s²) and the vibration exposure level (dB). A significant association between the vibration exposure level and the severity of VWF stages was observed among the travertine operators. The dose-effect relationship proposed by ISO 5349 was not suitable for the data of the present study because it overestimates the risk due to hand-transmitted vibration in the travertine workers. Finally, the results of a cold test indicated that the rewarming time of fingertips to room temperature was more prolonged in the operators with VAT than in those without VWF and in the controls.     

手部烧伤后重度虎口挛缩虎口重建术

自１９８９年２月～１９９５年３月，对２３例手部烧伤后重度虎口挛缩行瘢痕切除及虎口开大后，选用带旋髂浅血管蒂的腹股沟皮瓣移植重建虎口，术后均取得了满意效果。虎口挛缩的程度为０°～２５°。虎口开大后达８０°～９０°。虎口区瘢痕切除后皮肤缺损最小８ｃｍ×５ｃｍ，最大１２ｃｍ×６ｃｍ，平均１０ｃｍ×５ｃｍ。皮瓣切取面积最小１４ｃｍ×７ｃｍ，最大１８ｃｍ×８ｃｍ，平均１６ｃｍ×７ｃｍ。术后皮瓣断蒂时间为２～３周，２３例皮瓣均完全成活。对重度虎口挛缩应用带旋髂浅血管蒂的腹股沟皮瓣移植重建虎口是一种简单易行、成功率高的方法。因其具有供区部位隐蔽，皮肤质量好，不损伤肢体重要血管及可早期断蒂等优点，极易被患者接受。     

中指近节背侧岛状皮瓣

介绍中指近节背侧岛状皮瓣的应用解剖,该皮瓣的营养动脉为第2掌背动脉,位置表浅,解剖容易,安全可靠。自1990年11月以来,应用该皮瓣修复手部软组织缺损共6例,均获成功。     

锌指蛋白440在人膝关节OA软骨细胞损伤中的促进作用及机制

探讨锌指蛋白440（ZNF440）在膝关节（Knee）骨性关节炎（OA）软骨细胞损伤和退化变性病理生理学中的作用。方法 Knee软骨中分离人软骨细胞,分为对照组、Knee OA组、ZNF440-GFP（绿色荧光蛋白）组、ZNF440-siRNA组和Scriptaid组。通过免疫组化和Western blotting测定ZNF440在Knee OA软骨中的表达。用ZNF440-GFP过表达和ZNF440-siRNA转染细胞,并给予白细胞介素-1β(IL-1β)刺激。分别用qPCR和WB检测分解代谢、合成代谢和凋亡相关标志物的mRNA和蛋白表达水平。生物信息学分析有可能抑制ZNF440表达的化合物。结果 与对照组相比,ZNF440在Knee OA软骨中的表达有所增加(P＜0.05);ZNF440过表达明显增加基质金属蛋白酶（MMP）13和PARP p85的表达,并降低COL2A1表达(P＜0.05);siRNA敲除ZNF440可部分逆转IL-1β刺激诱导的人Knee OA软骨细胞的分解代谢和细胞凋亡(P＜0.05)。通过生物信息学分析和验证实验,确定Scriptaid是一种有可能下调ZNF440表达的化合物。Scriptaid处理可降低OA软骨细胞中ZNF440的表达,同时降低过表达ZNF440的人Knee OA软骨细胞中MMP13和PARP p85的表达(P＜0.05)。结论 ZNF440在人Knee OA软骨中的表达明显增加,可能通过调节细胞中炎症、分解代谢和凋亡标志物的表达参与软骨退行性机制。此外,Scriptaid可降低ZNF440的表达,并抑制其在OA软骨细胞中的破坏作用