川芎嗪对大鼠肾缺血-再灌注后核因子-kB表达与一氧化氮合酶活性的影响

目的 研究川芎嗪对肾脏缺血-再灌注后肾功能、核因子-κB(NFκB)的表达及一氧化氮合酶(NOS)活性的影响.方法 将30只SD大鼠随机分为假手术组、缺血-再灌注模型组和川芎嗪处理组,化学法检测血清肌酐(Cr)和尿素氮(BUN)浓度以及左肾组织中一氧化氮合酶活性,HE染色后镜下观察肾脏病理变化,免疫组化测定肾组织NF-KB的表达水平.结果 川芎嗪15,30,45 mg·kg-1剂量于缺血前静脉注射均能降低再灌注时肾脏组织中NF-κB的表达.抑制诱生型NOS(iNOS)活性、降低尿素氮和肌酐水平,其中以15 mg·kg-1作用最为显著.结论 川芎嗪15,30,45mg·kg-1剂量均能减轻肾缺血损伤,其机制可能与抑制NF-κB的表达、降低iNOS活性有关,且该作用与川芎嗪的剂量相关,以15 mg·kg-1剂量的效果最好.     

褪黑素对急性肾脏缺血再灌注损伤模型小鼠血红素加氧酶-1表达的影响

目的:研究褪黑素(MT)对急性肾脏缺血再灌注损伤模型小鼠的保护作用及其机制。方法:将昆明种小鼠40只,随机分成MT高、低剂量(10、1 mg.kg~(-1))组,假手术组,缺血再灌注组,造模前30 min各组分别腹腔注射相应药物,后2组注射等容量的3%乙醇生理盐水。造模24 h后测定小鼠血清肌苷(Cr)与尿素氮(Bun)水平,观察肾脏组织的病理学改变,免疫组织化学方法观察小鼠肾脏血红素加氧酶-1(HO-1)的表达。结果:与假手术组相比,缺血再灌注组肾小管上皮细胞呈明显的缺血性改变,血清Cr与Bun水平均显著性升高(P<0.01),肾脏HO-1表达明显增强;与缺血再灌注组相比,MT高、低剂量组肾小管上皮细胞缺血性改变减轻,血清Cr与Bun水平均显著性降低(P<0.01),肾脏HO-1表达明显增强。结论:MT可能通过上调HO- 1的表达而促进其合成从而发挥对急性肾脏缺血再灌注损伤模型小鼠的保护作用。     

川芎嗪对小鼠急性肾缺血再灌注损伤的保护作用研究

目的 :探讨川芎嗪 (LT)对小鼠急性肾缺血再灌注损伤的保护作用。方法 :夹闭右肾肾蒂阻断血流 30min,然后放开动脉夹再灌注 0 .2 5、1、2 4h ,造成小鼠急性缺血再灌注模型 ,于手术前分别腹腔注射川芎嗪 1 0 0mg·kg- 1和等量生理盐水。化学法观察小鼠血清肌酐 (Scr)、尿素氮 (Bun)、丙二醛 (MDA)含量和超氧化物歧化酶 (SOD) ,肾组织MDA含量和SOD ,并观察肾组织WBC滞留数、肾小管计分等病理变化。结果 :与模型组比较 ,川芎嗪使肾缺血再灌注 1、2 4h小鼠肾组织MDA含量、肾小管计分明显降低 ,血、肾中SOD活性增强 ,使肾缺血再灌注 2 4h血中Scr、Bun、MDA含量、肾中WBC滞留数明显降低。结论 :川芎嗪对急性肾缺血再灌注损伤有保护作用 ,其机制可能与抗自由基损伤、抑制WBC粘附有关     

川芎嗪改善缺血再灌注诱导的大鼠急性肾损伤

目的探讨川芎嗪对缺血再灌注(I/R)诱导的大鼠急性肾损伤的保护作用及其与线粒体自噬的相关性。方法 48只Wistar大鼠分为正常对照组、模型组、模型+TMP(10,15和20 mg·kg^-1)组和正常+TMP(15 mg·kg^-1)组。通过夹闭双侧肾动脉45 min再灌注30 min制备大鼠急性肾损伤模型;模型+TMP(10,15和20 mg·kg^-1)组大鼠于夹闭双侧肾动脉45 min再灌注30 min后一次性ip给予不同剂量的TMP;正常+TMP(15 mg·kg^-1)组于开腹刺激75 min后一次性ip给予TMP 15 mg·kg^-1。给予TMP 24 h后,肌氨酸氧化酶法检测血清中肌酐(Cr)含量;尿素酶-谷氨酸脱氢酶法检测血清中尿素氮(BUN)含量;ELISA法检测血清中肿瘤坏死因子α(TNF-α)含量;WST-1法检测肾组织匀浆中超氧化物歧化酶(SOD)活性;TBA法检测肾组织匀浆中丙二醛(MDA)含量。HE染色检测肾组织病理变化,免疫组织化学法检测大鼠肾组织中磷酸...     

川芎嗪对大鼠肾缺血-再灌注后核因子-κB表达与一氧化氮合酶活性的影响

目的 研究川芎嗪对肾脏缺血－再灌注后肾功能、核因子-κB（NF-κB）的表达及一氧化氮合酶（NOS）活性的影响.方法 将30只SD大鼠随机分为假手术组、缺血－再灌注模型组和川芎嗪处理组,化学法检测血清肌酐（Cr）和尿素氮（BUN）浓度以及左肾组织中一氧化氮合酶活性,HE染色后镜下观察肾脏病理变化,免疫组化测定肾组织NF-κB的表达水平.结果川芎嗪15,30,45 mg&#8226;kg-1剂量于缺血前静脉注射均能降低再灌注时肾脏组织中NF-κB的表达,抑制诱生型NOS（iNOS）活性、降低尿素氮和肌酐水平,其中以15 mg&#8226;kg-1作用最为显著.结论 川芎嗪15,30,45 mg&#8226;kg-1剂量均能减轻肾缺血损伤, 其机制可能与抑制NF-κB的表达、降低iNOS活性有关,且该作用与川芎嗪的剂量相关,以15 mg&#8226;kg-1剂量的效果最好.     

单核细胞趋化蛋白-1与大鼠肾脏缺血再灌注损伤的实验研究

目的 研究肾脏缺血再灌注损伤的发病机制。方法 雄性Wisrar大鼠50只，随机分为5组，即假手术组（n=10）、肾缺血再灌注0h组（n=10）、再灌注4h组（n=10）、再灌注12h组（n=10）、再灌注24h组（n=10）。夹闭肾动脉建立大鼠肾缺血再灌注模型，在再灌注不同时点检测肾组织单核细胞趋化蛋白-1（MCP-1）的含量（ELISA方法）；肾功能指标：血肌酐（Cr）、血尿素氮（BUN）；光镜下观察肾脏的病理改变并进行肾小管评分。结果 正常情况下，肾脏组织中MCP-1蛋白含量很少．缺血再灌注0h（单纯缺血）即可观察到肾脏组织中MCP-1含量升高，至4h达到峰值．随后其水平逐渐下降；缺血再灌注各时段组大鼠血Cr、BUN与假手术组相比明显升高（均P〈0．01），且随再灌注时间延长．血Cr、BUN的水平逐渐增高；光镜下观察见缺血再灌注组肾小管和肾间质有不同程度的损伤，肾小球无明显变化。结论 单核细胞趋化蛋白．1在肾脏缺血再灌注损伤中含量升高且呈动态变化，说明MCP-1参与了肾脏缺血再灌注损伤。     

马来酸罗格列酮对肾缺血再灌注损伤模型小鼠的保护作用及其机制研究

目的:探讨马来酸罗格列酮对肾缺血再灌注损伤模型小鼠的保护作用及其机制。方法:小鼠30只随机分为假手术组(生理盐水)、模型组(生理盐水)和马来酸罗格列酮组(5 mg.kg-1.d-1),灌胃给予相应药物,连续10 d,末次给药40 min后除假手术组外建立肾缺血再灌注损伤模型,术后检测肾脏指数,血清尿素氮(BUN)、肌酐(Cr)、肾组织中丙二醛(MDA)的含量及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力,常规HE染色观察肾组织病理变化。结果:与模型组比较,马来酸罗格列酮组小鼠肾脏指数降低(P<0.01),血清BUN、Cr、肾组织中MDA含量均减少(P<0.01),SOD和GSH-Px活力增加(P<0.01或P<0.05)。结论:马来酸罗格列酮对小鼠肾缺血再灌注损伤具有保护作用,其机制可能与减轻自由基引起的肾组织脂质过氧化反应有关。     

富硒木耳水提物对链脲佐菌素诱导的小鼠糖尿病肾损伤的保护作用

目的研究富硒木耳水提物(aqueous of Se-enriched Auricularia auricular,AESAA)对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病肾损伤的保护作用及机制。方法给予小鼠高脂饮食联合STZ (80 mg·kg~(-1))建立糖尿病肾病(diabetic nephropathy,DN)模型。将60只C57B/6J小鼠随机分为空白组、模型组、二甲双胍组(metformin,Met,400 mg·kg~(-1))、AESAA低剂量组(500 mg·kg~(-1))、AESAA高剂量组(1 000 mg·kg~(-1))、普通木耳水提物组(aqueous extracts of Auricularia auricular,AEAA,1 000 mg·kg~(-1)),灌胃给药8周后,取血及肾脏组织。检测小鼠血清中总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low density lipoprotein cholesterol,LDL-C)、尿素氮(blood urea nitrogen,BUN)、肌酐(creatinine,Cr)及尿酸(uric acid,UA)的含量;HE染色评价肾脏组织病理学变化;Western blot检测肾脏组织中高迁移率族蛋白1(high mobility group box 1 protein,HMGB1)、晚期糖基化终产物受体(the receptor of advanced glycation end products,RAGE)和核因子-κB(NF-κB)磷酸化的表达。结果与模型组相比,AESAA能改善肾脏病理性损伤;降低血清中TC、TG、LDL-C、Cr、BUN的含量(P<0.01)和UA的含量(P<0.05);抑制肾组织HMGB1、RAGE蛋白表达(P<0.01)和p-NF-κB蛋白表达(P<0.05)。结论 AESAA能逆转STZ诱导的糖尿病肾损伤,其机制可能与其调控HMGB1/RAGE/NF-κB信号通路有关。     

气腹预处理与肾动脉间断阻断预处理对大鼠孤立肾脏缺血再灌注损伤的影响

目的 比较15 mm Hg气腹预处理(pneumoperitoneum preconditioning,PP)与肾动脉间断阻断预处理(arterial occlusion preconditioning,AOP)这两种缺血预处理方法对大鼠孤立肾脏缺血再灌注损伤的影响.方法 将40只雄性Wistar大鼠切除右肾建立孤立肾模型.2周后再随机平均分为四组:假手术组(Sham组),缺血再灌注组(I/R组),15mm Hg气腹预处理组(PP组)以及肾动脉间断阻断预处理组(AOP组).经过不同方式的缺血预处理及缺血再灌注损伤后,采血检测各组大鼠的肾损伤分子-1(Kim-1)、血肌酐(Cr)、血尿素氮(BUN),同时切除左肾,取肾组织测定丙二醛(MDA)的含量.结果 PP组及AOP组这两种缺血预处理方式均能有效地减轻缺血再灌注导致的肾脏损害;但该保护作用只能一定程度上减轻而并不能完全消除缺血再灌注导致的肾脏损害.结论 在腹腔镜保留肾单位手术中,15 mm Hg气腹预处理方式有可能成为一种有效减轻肾脏缺血再灌注损伤的方法.     

银杏叶提取物对急性缺血-再灌注损伤小鼠肾脏的保护作用研究

目的观察银杏叶提取物对急性缺血-再灌注损伤小鼠肾脏的保护作用。方法取昆明种小鼠30只,随机分为假手术组、模型组和给药组各10只。给药组小鼠腹腔注射银杏叶提取物,0.1 mg.g-1;模型组与假手术组均腹腔注射等量0.9%氯化钠注射液。30 m in后将所有小鼠麻醉,切除给药组与模型组小鼠右侧肾脏,游离左侧肾脏,夹闭左侧肾蒂45 m in,然后去除血管夹,再灌注24 h;将假手术组小鼠麻醉后只切除右肾,缝合切口。24 h后处死小鼠,测定血清肌酐(Cr)和尿素氮(BUN)并观察肾脏组织的病理学改变。结果模型组小鼠血清Cr[(49.90±12.02)μmol.L-1]与BUN[(26.36±7.41)mmol.L-1]均明显高于假手术组[分别为(21.40±2.67)μmol.L-1和(7.20±0.84)mmol.L-1](均P<0.01);给药组小鼠血清Cr[(30.20±6.30)μmol.L-1]与BUN[(15.37±3.77)mmol.L-1]均较模型组明显降低(均P<0.01),与假手术组相比,均差异无显著性。模型组小鼠肾小管上皮细胞缺血性改变明显,给药组小鼠肾小管上皮细胞缺血性改变较模型组明显减轻。结论银杏叶提取物对急性肾缺血-再灌注损伤小鼠肾脏有明显的保护作用。     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Tramadol concentrations in blood and in cerebrospinal fluid in a neonate

Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood–brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.     

Disease control in asthmatic children seen in private practice in Switzerland

ABSTRACT

Background: Asthma is the most common chronic childhood disease in Switzerland with a prevalence of 10%. Asthma has a high economic burden accounting for high medical costs. Assessment of disease control is likely to be of help in the implementation of strategies to improve asthma. Therefore, we aimed to evaluate asthma control and therapy regimens among children in private practice.

Methods: We assessed asthma control as well as therapy regimens in 575 asthmatic children in an experience programme in Switzerland by using an abbreviated questionnaire based on the asthma control questionnaire and the child health questionnaire on Visit 1 and Visit 2.

Results: Good asthma control at Visit 1 was only present in 25.7% of asthmatic children. Occasional asthma symptoms, limitation of physical activity, nocturnal awakening and anxiety of the parent was present in 80.5%, 41.2%, 46.8% and 57% of the children, respectively. After adjustment of therapy regimens at Visit 1, mainly by adding a leukotriene receptor antagonist, asthma control was reported to be much better in 53.4% of the children at Visit 2.

Conclusions: As asthma control is inadequately achieved within a major portion of asthmatic children, it is imperative to find measures to improve asthma control and hence, to reduce the burden of disease.