Influence of age and of desmotropic drugs on the step phenomenon observed in rat skin

Summary Comprehensive analysis of the mechanical properties of rat skin revealed the step phenomenon. This particular observation was made after constant strain rate (analysis of stress strain curves) as well as after constant load (creep experiments). Relative low extensions or low loads were necessary to provoke the steps. In most cases two, sometimes three steps were observed. The step phenomenon was found mainly in skin strips punched out perpendicularly to the body axis. Probably some bonds in the fibrous network are broken giving way to additional elongation whereafter stronger links take over the stress. Since earlier studies demonstrated a pronounced influence of age and of desmotropic drugs on mechanical properties at ultimate load, e.g., tensile strength, ultimate modulus of elasticity, and ultimate strain, also the step phenomenon was studied under these conditions. In stress-strain experiments most of the steps were found at the ages of 2 and 4 months. Total stress loss and total work loss due to the steps were the highest at the age of 4 months. If, however, these values were calculated as percentage of ultimate values, the highest figures were found in young animals. Elongation gain due to the steps also showed a maximum at time of maturation, e.g., 4 months. Similar findings were achieved in creep experiments at medium load (200 g). After treatment with prednisolone acetate more steps and after treatment with d-penicillamine fewer steps were observed. In stress-strain experiments total stress loss and total work loss due to steps were more than twice as high than controls after prednisolone treatment and only one half after d-penicillamine. If calculated as percentage of ultimate stress or percentage of work input, these changes disappeared because of similar changes at ultimate load. However, elongation gain due to steps, which was not significantly influenced by prednisolone acetate but significantly decreased by d-penicillamine, showed the same changes when calculated as percentage of ultimate strain. Under all conditions the step phenomenon mainly influenced the extension parameters. The data presented here confirm earlier observations that mechanical properties at low loads or low and medium extensions show at least to some extent a different pattern under the influence of maturation and age and after treatment with desmotropic drugs compared to the mechanical parameters at ultimate load.     

Effect ofβ-adrenergic blockade on haemodynamic responses to dynamic and isometric exercise in angina pectoris

Summary The effect of treatment for 1–4 weeks with metoprolol, a ₁-selective blocking agent, or alprenolol, on the heart rate and blood pressure response to isometric exercise was studied in two groups of 12 patients with angina. Measurements were made during the peak effect of metoprolol 10, 40 or 50 mg, and alprenolol 200 mg as Aptin^® Durules^®. After 1 min of sustained handgrip at 50% of maximal voluntary contraction, systolic (6–15%) and diastolic (8–12%) blood pressure after both drugs was significantly lower than without any -blockade; Heart rate was decreased by 19–22% by metoprolol but not by alprenolol. The blood pressurerise during handgrip was not attenuated by either drug. The rise in heart rate was significantly reduced (by 36–50%) by metoprolol 40 and 50 mg and alprenolol 200 mg. No patient experienced angina during handgrip. In contrast, all but one were restricted by angina during bicycle exercise without treatment, at a level that produced the same increase in heart rate as the handgrip test, viz. 3 min at a load of 33 W). The cardiovascular response to sustained handgrip is too small to provide a useful challenge for determination of the anti-anginal efficacy of drugs. However, slight ECG changes of ischaemia did occur during handgrip, which were reversed by -blockade.     

非线性混合效应模型法估算癫(间)患者苯妥英群体药物动力学参数

目的 应用非线性混合效应模型法(NONMEM),估算癫癇患者苯妥英群体药物动力学参数,考察各因素对最大消除速率常数Vm(mg·d-1)及米氏常数Km(mg·L-1)的影响。方法 回顾性搜集56例门诊及住院癫癇患者服用苯妥英钠日剂量和血药浓度数据96对,并运行SAS程序进行计算。结果 患者的性别、年龄、体重、合并用药等对药物动力学参数均无显著性影响,Vm=(522.40±10.25)mg·d-1(513.14～630.63 mg·d-1),Km=(11.05±9.62)mg·L-1(1.90～34.83 mg·L-1)。血药浓度预测值与实测值相关性良好。结论 用非线性混合效应模型法估算癫癇患者苯妥英群体药物动力学参数方法可靠,值得推广。     

抗菌药物的药动学及药效学相关研究的临床意义

通过对抗菌药物的药动学(PK)、药效学(PD)的相关研究，发现了抗菌药物不同的PK/PD特性；提出了预测抗菌药物疗效的重要PD参数为AUC0-24/MIC，Cmax/MIC，t＞MIC和抗生素后效应(PAE)等；而且对评价药物有效性。指导合理用药，提高药物疗效，避免产生耐药性都有指导性的作用。因此，PK/PD研究是抗菌药合理应用的基础，在研究、设计和制定抗菌药物治疗方案、制定敏感性临界值以及推荐用药指南等方面都具有重要价值。     

卵巢上皮性癌BRCA1和p53基因表达的临床意义及相互关系研究

目的：探讨BRCA1、p53基因蛋白在卵巢上皮性癌中的表达情况及相互关系。方法：应用S-P免疫组织化学法检测50例卵巢上皮性癌组织中BRCA1和p53蛋白的表达。采用Kaplan—Meier法分析两种蛋白表达情况与患者预后的关系。结果：1)BRCA1蛋白在卵巢癌组织中的阳性表达率仅为30％，明显低于正常卵巢组织(100％)和良性肿瘤组织(90％)(P＜0．01)；BRCA1在低分化癌、有淋巴结转移的卵巢癌组织中表达减少甚至缺失。2)p53蛋白在卵巢癌组织中的表达率为64％，而在正常卵巢及良性肿瘤组织中无表达；其表达仅与病理学分级有关。3)两种基因蛋白表达比较呈显著负相关(P＜0．01)。4)患者生存随访表明，有BRCA1表达的患者平均生存期长于无表达者；而p53对生存时间无影响。结论：BRCA1基因在转录后水平的下调对卵巢上皮性癌的发生发展有重要的作用．同时BRCA1基因与p53基因协同促进肿瘤的演进恶化。     

Simultaneous display of MRA and MPR in detecting vascular compression for trigeminal neuralgia or hemifacial spasm: comparison with oblique sagittal views of MRI

A new technique, simultaneous display of magnetic resonance angiography (MRA) and multiplanar reconstruction (MPR), was performed by a workstation to identify the involved vessels in patients with trigeminal neuralgia (TN) or hemifacial spasm (HFS), and the results were compared with those of oblique sagittal MRI technique. Twelve patients with either HFS or TN were prospectively assessed by simultaneous display of MRA and MPR, and oblique sagittal techniques, to point out the neurovascular compression and to identify the involved vessels. Three-dimensional (3D) time-of-flight (TOF) spoiled gradient-echo (SPGR) images were acquired to create MRA and MPR. Oblique sagittal views were also created and displayed on films. A total of 15 vessels in 12 patients were identified as compressing vessels during surgery. Simultaneous display of MRA and MPR technique pointed out the presence of vessels at and/or around root entry/exit zone (REZ) in all 12 patients, but proper identification by the name of the individual vessel was correct in 13 of 15 cases. However, oblique sagittal technique indicated the presence of vessels at and/or around REZ in 11 patients, but only 8 of 14 vessels were correctly identified. Our new method, simultaneous display of MRA-MPR, facilitated correct identification of the involved vessels compared with the oblique sagittal view method. Received: 30 June 1999; Revised: 9 September 1999; Accepted: 23 November 1999     

糖尿病酮症酸中毒患儿氧化应激状况及影响因素分析

Objective To investigate the oxidative stress state in children with diabetic ketoacidosis (DKA),and analyze whether any observed abnormalities were related to metabolic disturbances.Methods Four groups of subjects were studied,comprising with 22 patients with DKA(group 1),18 diabetic children with medium metabolic control,whose glycated hemoglobin(HbAlc) below 9%(group 2),22 children with poorly controlled diabetes,whose Hbal c above 9%(group 3),and 36 healthy control children(group 4).Malondialdehyde(MDA),nitrate oxidase(NO),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),and metabolic parameters such as fasting blood glucose,HbAlc,blood gas analysis,serum ion,renal function of the subjects were measured.Results Mean serum MDA value was significantly higher in group 1 than in group 2(P ＜0.01) and group 4(P ＜0.01),but was not different from that in group 3 (P ＞0.05).Serum levels of NO were significantly higher in group 1,2 and 3 compared with group 4(P＜0.01).Serum levels of GSH-Px were significantly lower in group 1,2 and 3 than in group 4(P＜0.01).There were no significant differences of serum SOD value among the four groups(P＞0.05).Both serum MDA and NO values in the diabetic patients(groups 1 +2 +3) were positively related to HbAlc(r=0.375,P ＜0.01;r=0.250,P ＜0.05),and serum SOD values in the DKA patients were negatively related to HbAlc(r= -0.507,P＜0.05),there were not any significant relationship between the other oxidative markers and metabolic parameters.Conclusion There is an increase of oxidative stress and decrease of antioxygenic ability in DKA children,and these changes tend to correlate more with markers of diabetic imbalance than with parameters of acute metabolic disturbances of DKA.     

亚热带气候环境下西藏小型猪部分血液生理生化指标的比较

目的比较研究西藏小型猪在亚热带气候环境下的部分血液生理生化指标。方法常规方法测定原代和F1代西藏小型猪血液的9项生理和9项生化指标,比较两代之间以及雌、雄之间的不同,并与其他实验动物及人类的同类指标进行对比分析。结果在生化指标中,原代雌雄之间AST差异显著;F1代雌雄之间TG、ALB有差异,BUN、CHOL有显著性差异。在生理指标中,原代雌、雄间无差异,F1代雌雄间MONO有显著性差异。结论西藏小型猪已经基本适应亚热带地区的环境。与其他实验动物相比西藏小型猪许多生理生化指标更接近人类,非常适合替代犬、猴用于生物医学研究。     

L-肉毒碱体外对人精子活率及运动参数的影响

目的：研究L-肉毒碱体外对人精子活率及运动参数的影响，分析L-肉毒碱对维持和提高精子质量的效果，并探讨其在男性不育症治疗中的作用。方法：选取10例精液质量参数正常、健康的生育男性和20例弱精子症不育患者精液，分别加入不同浓度的L-肉毒碱并于37℃孵育，镜检观察精子的形态变化，并采用计算机辅助精液分析系统检测各组精子的活率、活力（a＋b级精子百分率）、前向性（STR）、直线性（LIN）、直线速度（VSL）、曲线速度（VCL）以及平均路径速度（VAP）参数，同时对检测结果进行统计学分析。结果：正常生育男性精子体外加入L-肉毒碱后，可明显减缓精子活率、活力及VSL、VCL以及VAP的下降趋势，且随着L-肉毒碱加入浓度的增加，这种减缓作用增强。但当L-肉毒碱浓度超过1200μmol／L时，减缓作用减小。较为适宜的L-肉毒碱浓度为400μmol／L。弱精子症患者精液体外加入L-肉毒碱浓度在400μmol／L～1200μmol／L、孵育时间为30min～60min时，差异有统计学意义（P〈0．05或P（0．01）地提高体外精子的活率、活力及VSL、VCL以及VAP等参数。体外加入L-肉毒碱，能显著提高固精浆L-肉毒碱水平低下所致弱精症患者精子的活率、活力及运动参数，并可显著减缓正常生育精子活率、活力及运动参数的降低。结论：体外添加适宜浓度的L-肉毒碱，能显著提高因精浆L-肉毒碱水平低下所致弱精症患者精子的活率、活力及运动参数，并可显著减缓正常生育精子活率、活力及运动参数的降低。