Salbutamol disposition and dynamics in conscious rabbits: Influence of the route of administration and of the dose

This study assessed the influence of dose and route of administration on salbutamol kinetics and hypokaliemic effect. Salbutamol plasma kinetics were studied in a first group of 6 rabbits who received 60, 800, and 60 g/kg by the intravenous (iv), oral (po), and intratracheal (it) routes, respectively, at 1-week intervals. A second group of 6 rabbits received 120, 2400, and 120 g/kg of salbutamol by the same three routes. Multiple blood samples were withdrawn to assay salbutamol and potassium. Following iv salbutamol (60 g/kg), total plasma clearance was 82±5 ml/min per kg, apparent volume of distribution was 5.0±0.5 l/kg, and terminal half- life was 41±2 min. Similar values were estimated when 120 g/kg of salbutamol was administered iv or was given po or it. The bioavailability of po and it salbutamol was approximately 1 and 20%, respectively. For the first group, the maximal decrease in plasma potassium elicited by salbutamol was 0.80±0.19, 0.48±0.22, and 0.78±0.46 mmol/l, and for the second group, maximal decrement was 1.31±0.37, 0.70±0.24, and 0.84±0.17 mmol/l for the iv, po, and it routes, respectively. Compared to salbutamol peak plasma concentrations, maximal decrease in plasma potassium appeared between 60 and 108 min later for the iv route, 90 and 25 min later for po and it routes, and for this reason, the hypokaliemic effect was not associated to salbutamol plasma concentrations. The hypokaliemic effect was dependent upon the route, e.g., po>it>iv. It is concluded that (i) salbutamol plasma kinetics are first-order independently of the route of administration, and (ii) salbutamol hypokaliemic effect is modulated by the dose and the route of administration.List of abbreviations AUC Area under salbutamol plasma concentration-time curve - cl_INT Salbutamol intrinsic clearance - cl_T Salbutamol total plasma clearance - c_MAX Salbutamol maximal plasma concentration - F Fraction of the dose of salbutamol reaching the systemic circulation - iv Intravenous route of administration - it Intratracheal route of administration - po Oral route of administration - V_area Salbutamol apparent volume of distribution - T ₂ ¹ Salbutamol half-life of the terminal phase - t_MAX Time to observe the maximal decrease in plasma potassium - e_MAX Predicted maximal effect of salbutamol - EC₅₀ Concentration of salbutamol eliciting 50% of e_MAX Supported by the Medical Research Council of Canada (MT-10874). Sylvie Perreault is recipient of a Bourse Formation de troisième cycle des Fonds de la Recherche en Santé du Québec.     

金粉蕨素抑制大鼠主动脉平滑肌增殖作用及机制

目的 :观察金粉蕨素对牛血清刺激的大鼠主动脉平滑肌细胞增殖的抑制作用 ,并对其作用机制进行初步探讨。方法 :体外培养大鼠主动脉平滑肌细胞 ,以终浓度为 10 %的新生牛血清 (NCS)作为刺激因素 ,用噻唑蓝 (MTT)比色法和细胞计数法观察细胞增殖状况 ,用流式细胞仪分析细胞周期 ,用Westernblot实验测定蛋白表达。结果 :与 10 %牛血清组相比 ,不同浓度金粉蕨素组的MTT测定值与细胞数目均明显下降 (P <0 .0 5 ) ,其下降幅度呈浓度依赖性 ;10 μmol·L-1时达峰值 (P <0 .0 1) ;细胞周期分析显示 ,金粉蕨素组G1期百分比 (85 .1% )高于10 %牛血清组 (70 .0 % ) ,而S期比例 (4 .3% )低于10 %牛血清组 (16.4 % ) ;Westernblot结果显示给药组P ERK1 2蛋白表达明显低于同时间点牛血清组。结论 :金粉蕨素能阻止细胞周期由G0 G1期向S期推进 ,抑制血管平滑肌细胞增殖 ,此作用与其抑制ERK1 2磷酸化、影响MAPK ERK通路激活有关。     

Flow characteristics past jellyfish and St. Vincent valves in the aortic position under physiological pulsatile flow conditions

Thrombus formation and hemolysis have been linked to the dynamic flow characteristics of heart valve prostheses. To enhance our understanding of the flow characteristics past the aortic position of a Jellyfish (JF) valve in the left ventricle, in vitro laser Doppler anemometry (LDA) measurements were carried out under physiological pulsatile flow conditions. The hemodynamic performance of the JF valve was then compared with that of the St. Vincent (SV) valve. The comparison was given in terms of mean systolic pressure drop, back flow energy losses, flow velocity, and shear stresses at various locations downstream of both valves and at cardiac outputs of 3.5 L/min, 4.5 L/min, and 6.5 L/min respectively. The results indicated that both valves created disturbed flow fields with elevated levels of turbulent shear stress as well as higher levels of turbulence in the immediate vicinity of the valve and up to 1 diameter of the pipe (D) downstream of the valve. At a location further downstream, the JF valve showed better flow characteristics than the SV in terms of velocity profiles and turbulent shear stresses. The closure volume of the SV valve was found to be 2.5 times higher than that of the JF valve. Moreover, the total back flow losses and mean systolic pressure drop also were found to be higher in the SV than the JF valve.     

Aortic aneurysm and dissection are not associated with an increased risk for giant cell arteritis/ polymyalgia rheumatica

It has recently been claimed that giant cell arteritis (GCA) is associated with a markedly increased risk of aortic aneurysm formation or rupture. In the present study, the opposite approach was taken, by looking for the incidence of GCA and polymyalgia rheumatica (PMR) in patients with aortic aneurysm, aortic dissection, or both (AA/D). The records of 315 consecutive patients admitted with the diagnosis of AA/D were reviewed. In addition, follow up information was obtained in 82 patients by examination in the outpatient clinic. After careful examination and assessment of clinical and laboratory data, it was found that none of the 82 patients who survived hospitalisation and were available for examination had GCA or PMR. Moreover, review of the retrospective data available from hospital records of the total consecutive 315 patients with AA/D failed to find any patient with a diagnosis of GCA/PMR. In conclusion, the present study did not find an increased prevalence of GCA/PMR among a cohort of Israeli patients with AA/D. Therefore, it is suggested that a thorough investigation aiming to diagnose GCA/PMR is not cost effective in most of the elderly patients presenting with AA/D.     

Effects of exogenous sphinganine, sphingosine, and sphingosine-1-phosphate on relaxation and contraction of porcine thoracic aortic and pulmonary arterial rings.

Fumonisin mycotoxicosis in pigs causes a decrease in mean aortic pressure, an increase in mean pulmonary arterial pressure, and increases in serum concentrations of sphinganine (3.2 microM) and sphingosine (1.4 microM). To determine a causal relationship between the hemodynamic changes and sphingolipid alterations, we examined the in vitro effects of sphinganine, sphingosine, and sphingosine-1-phosphate on porcine aortic and pulmonary arterial rings. Both sphinganine and sphingosine relaxed un-contracted and phenylephrine-contracted aortic rings at > or = 10 microM and > or = 1 microM, respectively. Sphingosine (> or = 10 microM) relaxed un-contracted and phenylephrine-contracted pulmonary arterial rings, whereas sphingosine-1-phosphate (10 microM) contracted pulmonary arterial rings. Sphingosine (3 microM) also impaired the contractile response of pulmonary artery rings to 60 mM KCl. The results suggested that the systemic hypotension caused by fumonisin is mediated, in part, by increases in serum sphinganine and sphingosine concentrations, and the pulmonary hypertension is mediated, in part, by increased sphingosine-1-phosphate concentrations.     

The effect of two low-dose propofol infusions on the relationship between six-pulse transcranial electrical stimulation and the evoked lower extremity muscle response

BACKGROUND: Transcranial stimulation of the motor cortex using high-voltage electrical stimuli given in train is a method of monitoring the integrity of the motor pathways during thoracoabdominal aortic aneurysm surgery. The purpose of this study was to assess the relationship between the stimulus intensity and the corresponding amplitude of the myogenic motor evoked potential (tcMEP) in response to six-pulse transcranial electrical stimulation during two levels of low-dose propofol infusion and stable fentanyl/nitrous oxide anaesthesia. METHODS: Nine patients (37-78 yr) scheduled to undergo surgery on the thoracoabdominal aorta were studied. After achieving a stable anaesthetic state the output voltage was decreased with 50 V intervals from 350 V to 200 V during a target propofol infusion aimed at a plasma steady-state concentration of 0.7 microg x ml(-1) and increased with 50 V intervals from 200 V to 450 V during a target propofol infusion aimed at a plasma steady-state concentration of 1.4 microg x ml(-1). TcMEPs were recorded from the right tibialis anterior muscle. RESULTS: Doubling the target propofol infusion to 1.4 microg x ml(-1) resulted in a 30-50% decrease in tcMEP amplitude. The largest tcMEP amplitude using the six-pulse paradigm was found during a propofol infusion aimed at a plasma concentration of 0.7 microg x ml(-1) and demanded a stimulus output of 350 V, corresponding to a charge density of 7.5 microC x cm(-2) per phase. CONCLUSION: Doubling the target propofol infusion to 1.4 microg x ml(-1) provides less robust, but still recordable tcMEPs in response to six-pulse electrical stimulation. Safety guidelines are discussed.     

Long-term survival following emergency abdominal aortic aneurysm repair

Survival following emergency surgery for ruptured abdominal aortic aneurysm remains poor and is in stark contrast to that for elective repair. We have carried out a 5-year retrospective observational study to determine the long-term (5-year) survival of patients following emergency surgery for ruptured abdominal aortic aneurysm at a district general hospital in East Anglia. A total of 99 patients presented to the operating theatre for emergency repair of ruptured abdominal aortic aneurysm in this 5-year study period. In-hospital mortality was 70% and was unchanged over the 5 years. Overall long-term survival in those patients discharged from hospital was good. The ICU cost per long-term survivor was calculated to be pound sterling 36750.     

吸毒人员吸毒方式、性行为特点与HBV感染的关系研究

目的 了解湖南省吸毒人员乙型肝炎病毒(HBV)感染情况以及吸毒方式、性行为特点与HBV感染的关系。方法 采用现况研究，通过整群抽样，随机抽取某男性戒毒所和某女性戒毒所中的吸毒人员，以问卷的方式调查吸毒人员的吸毒方式和性行为特点，并用酶联免疫吸附试验(ELISA)检测血清中HBsAg、抗-HB、HHcAg、抗-HBc、抗-HBc，采用Chi-square检验对数据进行统计分析。结果 吸毒人员HBV感染率为63．2％；静脉注射和非静脉注射吸毒者HBV感染率分别为64．0％和59．4％，两者差异无显著性(P＞0．05)；有婚外性行为和无婚外性行为的吸毒人员HBV感染率分别为65．4％和55．2％，两者差异有显著性(P＜0．05)；不同性伙伴个数HBV感染率比较有显著性差异(P＜0．01)。结论 吸毒人群是HBV的高危人群，静脉吸毒与非静脉吸毒对HBV的感染无显著性差异，婚外性行为是HBV感染的主要危险因素，性伙伴个数是影响HBV感染的重要因素之一。     

对新型农村合作医疗定点医疗机构监管的途径与程序

根据定点医疗机构不规范行为产生的规律、特点和表现形式,探讨对定点医疗机构监管的途径,即内部监管和外部监管、组织监督和社会监督、专项监管和综合监管、法律、法规、部门规章、行业条例等监管、内部及外部审计等;制定了对定点医疗机构监管的程序,即制定监管计划—实施监管行动—监管信息反馈—奖优罚劣。     

盐酸雷洛昔芬的合成改进

目的:优化盐酸雷洛昔芬的合成路线.方法:以3-甲氧基苯硫酚和4-甲氧基-α-溴代苯乙酮为起始原料,经取代反应,环合反应得到6-甲氧基-2-(4-乙酰氧基苯基)苯并[b]噻吩,再与4-[2-(1-哌啶基)乙氧基]苯甲酰氯盐酸盐发生Friedel-Crafts反应,然后发生脱甲基反应,最后经成盐反应,共5步主要反应制得目标产物.结果:目标化合物结构经红外光谱、核磁共振氢谱及质谱确证.结论:本方法反应条件温和,操作简便,并且提高了产率.