Genetic variations in five genes involved in the excitement of cardiomyocytes

We provide here 29 genetic variations, including 28 novel ones, in five genes that are potentially involved in the excitement of cardiomyocytes: we found 4 in KCNA10, 2 in KCNK1, 8 in KCNK6, 11 in SLC18A1 (VMAT1), and 4 in SLC6A2 (norepinephrine transporter). We also examined their allelic frequencies in a Japanese population of long QT syndrome-affected and nonaffected individuals. These data would be useful for genetic association studies designed to investigate acquired arrhythmias. Received: May 22, 2001 / Accepted: June 8, 2001     

Effectiveness and limits of antimicrobial treatment on seminal leukocyte concentration and related reactive oxygen species production in patients with male accessory gland infection

To evaluate whether bacteriological cure, sperm outcome, spontaneous pregnancy rate and white blood cell (WBC)-related reactive oxygen species (ROS) production were related to the extent of the infection and to an intermittent and repetitive antimicrobial treatment, 122 patients with bacterial [>10(5) colony-forming units (CFU)/ml] male accessory gland infections (MAGI) were studied. According to ultrasound criteria, patients had prostatitis (PR, n = 52), prostatovesiculitis (PV, n = 32) or prostatovesiculoepididymitis (PVE, n = 38). Each group was further subdivided into two subsets: one subset (PR, n = 40; PV, n = 20; PVE, n = 25) was given ofloxacin or doxycycline for 14 consecutive days per month for 3 months; the other subset (PR, n = 12; PV, n = 12; PVE, n = 13) received no treatment. The female partners were also treated. All patients were evaluated before, during (1 and 3 months) and after (3 months) treatment. The bacteriological cure rate was the highest (92.5%) after the third antibiotic course in PR, followed by PV (70.4%), and the lowest in PVE (52.0%). At 3 months after therapy discontinuation, some sperm parameters, seminal WBC concentration and ROS generation (assessed in the 45% Percoll fraction) were ameliorated in PR and PV, whereas no improvement occurred in patients with PVE, except for the percentage of coiled tails. Antibiotic treatment in PR and PV patients led to positive effects on sperm output and spontaneous pregnancy rate (40%) by removing pro-oxidant noxae (microbial and/or WBC-related ROS production). The persistent infertility, dyspermia and sperm-derived ROS overproduction in PVE may relate to a significant percentage of antibiotic-independent re-infection and/or to low antioxidative epididymal properties, which persisted following antimicrobial treatment.     

A contribution to the pathogenesis of respiratory disturbances associated with subarachnoid haemorrhage; an experimental approach using an animal model

Summary The present experimental work focuses on the mechanisms involved in respiratory distress observed in the course of subarachnoid haemorrhage. For this purpose, respiratory disturbances were induced in rabbits by injecting fresh autologous blood into the subarachnoid space. For six hours after this artificially induced SAH, blood PO₂ and PCO₂ as well as expiratory air CO₂ were regularly determined, while during the same period cerebral blood flow and cerebrospinal fluid pressure measurements were recorded.The results of this study suggest that pressure effects acting the brain structures that support respiration are principally involved in the pathogenesis of respiratory disturbances following SAH. A decrease in CBF and hypoxia with hypercapnia play a contributing secondary role adding to a vicious cycle phenomenon.     

Differences in diazepam pharmacokinetics in Chinese and white Caucasians – Relation to body lipid stores

Summary We have compared diazepam pharmacokinetics in 16 Chinese and 18 white Caucasian healthy male volunteers, resident in Hong Kong and have correlated them with physical attributes. Serum concentrations of diazepam and desmethyldiazepam were measured in venous blood by an enzyme-linked immunoassay (0–3 h samples) and HPLC (3–72 h samples). Pharmacokinetic parameters were derived assuming a two compartment model, distribution phase <6 h, and 100% oral systemic availability. Compared with the Chinese the white Caucasians were older, heavier, taller, and fatter, as judged by skin fold thickness (SFT) and total body weight to Ideal body weight (TBW/IBW) ratio; respective mean differences being 16%, 27%, 4%, 26%, and 15% (p<0.05). Mean diazepam apparent volume of distribution (V) and V/IBW were larger in the white Caucasians (52% & 39% respectively, p=0.002). SFT and TBW/IBW ratio yielded the best correlations with V, V/TBW and V/IBW (0.50–0.75, p<0.05). Obesity indices contributed most to the overall regressions (R² up to 0.52), and for V there was a further small effect (2%, partial F test) due to ethnic group, possibly reflecting stature. Mean peak diazepam concentration (C_max) was similar in both ethnic groups. Time to C_max (t_max) was more often prolonged in the Chinese (X ² test, p=0.01). Body fat and stature may thus account for these inter-ethnic differences in the apparent volume of distribution of diazepam, a highly lipid-soluble drug.     

Ocular pharmacokinetic models of clonidine-3H hydrochloride

A single topical instillation of clonidine-³H HCl solution (0.2%) was administered to the rabbit eye (30 μl) in order to study the drug's ocular pharmacokinetics. Seven different tissues and plasma were excised and assayed for drug over 180min. By 45–60 min pseudoequilibrium is reached for the cornea, iris/ciliary body, and aqueous humor. Thereafter, drug levels in these tissues decline in parallel. The data are fit separately to a physiological model and a classical diffusion model for which seven ocular tissue compartments and a plasma reservoir are constructed for each model. Clearance terms and distribution equilibrium coefficients are determined from the tissue level data and used as parameters in fitting the mass balance differential equations representing the physiological model. The model parameters can also be fit to a 0.4% single dose. In a separate experiment, a topical infusion technique was designed to provide a constant rate input to the cornea until an apparent steady state was reached in aqueous humor at 55 min. Aqueous humor levels were assayed for clonidine over the infusion and postinfusion periods. The physiological model parameters are fit to the topical infusion data and show good agreement between the predicted and experimental data. The classical model is too complex to fit the data to integrated exponential equations primarily because the method of residuals is inadequate in determining a sufficient set of initial estimates. This is overcome by dividing the eight-compartment model into seven fragmental models, each representing one to five compartments. A stepwise procedure is developed in which initial estimates are obtained for each separate fragmental model and refined. The refined parameter values can then be used as initial estimates for the complex model. Differential equations for the complex model are fit simultaneously to tissue levels representing each compartment. By observation, the classical model fit the data more closely than the physiological model. Statistical moment theory is also applied to the topical infusion data to determine ocular pharmacokinetic parameters for clonidine. The calculated values are: corneal absorption rate constantk _a , 0.00139 min^?1; aqueous humor elimination rate constantk ₁₀ , 0.0658min^?1; mean residence timeMRT _d , 35.6 min; apparent steadystate volume of distributionV _ss, 0.530 ml; and ocular clearanceQ _e , 14.9 =μl/min. The fraction absorbed from the single instillation is estimated as 0.0163.     

Outbreak of Rabbit Hemorrhagic Disease Virus 2 Infections,Ghana

In September 2019, high mortality in commercial rabbits was reported in the Greater Accra Region of Ghana. Rabbit hemorrhagic disease virus 2 phylogenetically related to isolates from 2015–2017 outbreaks in the Netherlands was confirmed as the causative agent. The virus has not yet been detected in native rabbits in Ghana.     

颅脑创伤急性期外周血白细胞变化的临床意义

目的 探讨颅脑创伤急性外周血白细胞（PWBC）数及中性粒细胞（PMN）比例与病情及预后的关系。方法 回顾性分析总结50例颅脑创伤急性期外周血白细胞数及性粒细胞比例,根据病情或预后分组分别进行比较。结果 颅脑创伤病情重者较病情轻者PWBC数与PWM比例显著提高（P＜0．05,P＜0．001）;恢复不良组及死亡组与恢复良好组相比,PWBC数显著增高（P＜0．05,P＜0．01）。结论 临床监测PWBC数及PMN比例可作为颅脑创伤患者的病情判断和预后估计的一项辅助指标。     

幼兔近视模型及大光明护眼液的疗效

目的 :探讨学生近视眼的发病机制和有效治疗药物。方法 :选用 2 0只新西兰纯种幼兔建立近视模型 ,然后分别采用2种药物和生理盐水治疗。结果 :大光明护眼液治疗组的平均屈光度 (D)值为 (+ 2 5 0± 0 6 8)、平均裸眼觅食距离 (cm)值为(2 80 0 0± 2 7 30 )、平均体重 (g)增长值为 (72 6 0 0± 31 30 ) ;而珍视明滴眼液治疗组和生理盐水治疗组近视屈光度 (D)值分别为(+ 1 6 6± 0 2 9)和 (+ 0 85± 0 42 ) ,平均裸眼觅食距离 (cm)分别为 (2 5 6 0 0± 5 4 48)和 (196 0 0± 76 48) ,平均体重 (g)增长分别为 (6 2 2 0 0± 31 94)和 (5 6 0 0 0± 6 2 85 )。结论 :(1)长期限制视距、微弱光线照射和经常习惯性近距离视物是造成近视眼的直接因素 ;(2 )采用大光明护眼液治疗近视眼的疗效明显 ,优于珍视明滴眼液和生理盐水治疗组 (P <0 0 1)。