蒜油对急性模拟高原条件下大鼠血气的影响

目的:探讨蒜油对急性高原条件下大鼠血气的影响及机制.方法:低压氧舱复制急性高原大鼠模型,观察蒜油对其部分生化指标及血流动力学指标的作用.结果:蒜油引起急性高原大鼠模型动脉血氧分压(PaO2)、血氧饱和度(SaO2)增高(P＜0.05),肺动脉压(PAP)降低(P＜0.01),主动脉收缩压(SAP)、左室收缩压(LVSP)、左心室压力最大上升速率(＋dp/dtmax)降低(P＜0.01),血浆超氧化物歧化酶(SOD)含量增加(P＜0.01),血浆NO水平部分提高.结论:蒜油可阻止急性高原大鼠模型PaO2、SaO2降低,降低肺动脉高压(HPAP)及心肌耗氧量,纠正自由基代谢失衡,增加血浆一氧化氮浓度可能是其作用机制.     

实验性结肠炎中氧化过度及褪黑素的保护作用

目的　探讨褪黑素对大鼠免疫性结肠炎的影响及有关机制。方法　应用三硝基苯磺酸和乙醇制备大鼠免疫性结肠炎模型。实验设正常对照组、模型对照组、阳性药物对照组 (5 氨基水杨酸 ,1 0 0mg·kg- 1 )、褪黑素给药组 (2 5 ,5 0 ,1 0 0mg·kg- 1 ) ,每天灌肠给药 1次 ,给药时间从制备模型 1wk后开始至实验结束共 3wk。观察大鼠结肠黏膜损伤指数 (CMDI)、粪便隐血实验 (OB)、髓过氧化物酶 (MPO)含量和黏膜病理组织学 (HS)情况 ,并检测结肠组织丙二醛(MDA)、谷胱甘肽过氧化物酶 (GSHPx)、过氧化氢酶(CAT)、超氧化物歧化酶 (SOD)、血浆和结肠组织一氧化氮(NO)含量。结果　模型组大鼠结肠CMDI、HS、OB程度和MPO水平均比正常组升高 ,褪黑素可改善结肠炎大鼠CM DI和HS ,降低MPO水平和粪便OB程度 ,改善结肠黏膜病理损伤 ,大鼠结肠MDA、血浆和结肠NO含量增加 ,结肠SOD、GSHPx和CAT水平降低 ,MT可降低MDA、NO含量 ,增加GSHPx、SOD和CAT水平。结论　MT对大鼠结肠黏膜损伤具有保护作用     

注射用生脉对感染性休克的影响

目的考察注射用生脉对感染性休克的保护作用及可能机制。方法采用盲肠结扎穿孔法复制大鼠感染性休克模型,测量大鼠血压、全血乳酸(LD)、血浆一氧化氮(NO)、血浆丙二醛(MDA)含量和血浆超氧化物歧化酶(SOD)活力;同时,对大鼠心脏进行病理组织学检查。结果注射用生脉显著升高感染性休克大鼠的平均动脉压(MAP),降低全血LD、血浆NO和MDA含量,提高血浆的SOD活力;且注射用生脉可减轻感染性休克大鼠心肌的损伤。结论注射用生脉对感染性休克具有保护作用。     

平原与急进高原后(4100m)氨茶碱在大鼠体内药动学比较

目的:探讨平原组(P)与急进高原组(H)大鼠体内氨茶碱的药动学特征.方法:Wistar大鼠于平原地区禁食12 h后将0.003 8 g(约含氨茶碱3.6 mg)氨茶碱片剂灌胃给药,一周清洗期后急进高原,灌胃给药.平原组及急进高原组于给药前(0 h)及给药后0.33,0.66,1,1.5,2,3,4,6,8,12,24 h由眼眶后静脉丛取血,采用液相-串联质谱方法测定血药浓度.结果:急进高原后,氨茶碱血浆超滤液浓度显著减低,因此蛋白结合率增高明显,平原组与高原组分别为37.05%和74.17%.氨茶碱急进高原组与平原组相比药动学参数发生显著变化,房室模型参数K_a显著增大,与高原组相比半衰期从(2.365±0.448)h 增大到(2.944±0.694)h,体内平均驻留时间延长,峰浓度增大,达峰时间缩短,总清除率降低.结论:急进高原后,氨茶碱在大鼠体内代谢过程发生显著变化,研究结果为平原和急进高原后临床合理应用氨茶碱提供参考依据.     

己酮可可碱对新生大鼠缺血缺氧性脑病的干预作用

目的 :观察己酮可可碱 (pentoxifylline,PTX )对新生大鼠缺血缺氧性脑病 (hypoxic- ischemicencephalopathy,HIE)模型的干预作用。方法 :建立新生大鼠 HIE模型 ,72只出生 7d的 Wistar大鼠随机分为假手术组、HIE模型组和 PTX组 ,于缺血缺氧后 72 h取左脑 ,测定脑组织水含量、大脑皮层神经细胞内游离钙离子浓度、超氧化物歧化酶 (SOD)、丙二醛 (MDA)、一氧化氮合酶 (NOS)及一氧化氮 (NO)。结果 :与 HIE模型组相比 ,PTX组脑组织含水量、游离钙离子浓度和 MDA、NOS以及 NO水平显著降低 (P <0 .0 5、0 .0 1、0 .0 5、0 .0 5、0 .0 5 ) ,SOD水平显著升高 (P <0 .0 5 )。结论 :PTX对新生大鼠缺血缺氧后脑组织有保护作用 ,其机制可能与 PTX改善能量代谢及减少局部细胞毒性物质有关。     

奥美拉唑对大鼠反流性食管黏膜损伤后氧化应激反应的影响

目的：观察奥美拉唑对反流性食管黏膜损伤后大鼠血浆和食管组织中MDA、SOD、NOS和NO的影响,探讨奥美拉唑治疗反流性食管炎的作用机制。方法选用健康雄性SD大鼠,体重220～250 g,随机将动物分为假手术组、单纯胃食管反流动物模型组（模型组）、模型组＋奥美拉唑低剂量组、中剂量组、高剂量组。分别取食管标本肉眼观察黏膜状况,检测大鼠血浆和食管组织中MDA、SOD、NOS和NO的变化。结果假手术组大鼠食管颜色淡红,有光泽,黏膜光滑。模型组大鼠食管颜色变淡白,黏膜粗糙、增厚、皱襞灰白色斑块状增生。与模型组比较,奥美拉唑低、中、高剂量治疗组大鼠食管病变明显减轻。与假手术组比较,模型组大鼠血浆和食管黏膜组织中MDA、NO含量及NOS活性明显升高,SOD活性显著降低。与模型组比较,奥美拉唑治疗组大鼠血浆和食管黏膜组织中MDA、NO含量及NOS活性明显降低,SOD活性显著升高。结论奥美拉唑明显降低反流性食管黏膜损伤后大鼠血浆和食管黏膜组织中MDA、NO的含量和NOS的活性,显著升高SOD活性,改善氧化应激,可能是其减轻食管局部及外周炎性反应、治疗反流性食管炎的重要作用机制。     

魔芋葡甘聚糖对动脉粥样硬化家兔血清一氧化氮、血浆内皮素和脂质过氧化物的影响

目的 :观察魔芋葡甘聚糖预防用药对动脉粥样硬化 (AS)家兔血清一氧化氮 (NO) ,血浆内皮素(ET)、脂质过氧化物 (MDA)和超氧化物歧化酶(SOD)的影响。方法 :采用高胆固醇饲料喂饲另加牛血清白蛋白一次注射方法 ,建立家兔AS模型 ,随机分为对照组 (n =8) ,模型组 (n =8)和魔芋葡甘聚糖用药组 (n =8) ,各组在实验第 8周取血清标本测定血清NO ,血浆ET、MDA和SOD。结果 :与模型组比较 ,魔芋葡甘聚糖预防用药 8周 ,能提高NO和SOD活性 (P <0 .0 1) ,降低ET和MDA含量 (P <0 .0 1)。结论 :魔芋葡甘聚糖具有抗氧化、保护内皮功能和维持NO/ET平衡的作用     

高原肺水肿患者血浆ET和SOD测定及其意义

目的 :探讨高原肺水肿 (HAPE)患者血浆ET和SOD的水平及在发病中的作用 ,方法 :采用放射免疫法测定血浆ET、SOD、AⅡ 的含量 ,用Griss反应法检测NO水平。结果 :HAPE患者血浆NO和SOD水平显著低于高原健康组 (P <0 0 1 ) ,ET和AⅡ 水平显著高于高原健康组 (P <0 0 1 ) ,结论 :血管活性物质平衡失调及血管内皮细胞损伤是HAPE发病的重要原因之一。     

参茸益精片对急性高原缺氧脑损伤的保护作用研究

目的观察参茸益精片对急性高原缺氧脑损伤的保护作用,并探讨其分子机制。方法将SD大鼠随机分为空白对照组(对照组)、高原急性缺氧模型组(模型组)和参茸益精片治疗组(治疗组),每组6只。建立急性高原缺氧脑损伤大鼠动物模型,治疗组灌胃参茸益精片。观察大鼠脑组织SOD活性和MDA水平的变化,Western blot和RT-PCR检测胆碱乙酰转移酶(Choline acetyltransferase,ChAT)和蛋白激酶C(Protein kinase C,PKC)表达水平的变化。结果与对照组比较,模型组大鼠脑组织SOD活性显著降低(P<0.01),MDA水平显著增加(P<0.01);治疗组大鼠脑组织SOD活性显著增加(P<0.01),MDA水平显著降低(P<0.01)。模型组大鼠脑组织ChAT和PKC表达水平显著降低(P<0.05),治疗组ChAT和PKC表达水平显著升高(P<0.05)。结论参茸益精片可以保护急性高原缺氧引起的脑损伤,可能与其调节ChAT和PKC的表达水平有关。     

慢性氟中毒对大鼠血清氧化应激反应的影响

目的 探讨不同剂量氟化钠对大鼠血清抗氧化系统的影响.方法 给4组Wistar大鼠分别饮用含0、125、250、500mg/L的氟化钠去离子水溶液6个月,复制慢性氟中毒大鼠模型.6个月后眶静脉取血,测定血清抗氧化酶谷胱甘肽过氧化物酶(GPX)、超氧化物歧化酶(SOD)活力,丙二醛(MDA)和一氧化氮(NO)的含量.结果 与对照组相比,染氟组大鼠血清GPX、SOD活力显著下降,MDA和NO含量显著增加.结论 高剂量氟可以破坏大鼠的抗氧化系统,使其处于氧化应激状态.     

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.     

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 x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 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.     

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.     

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。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.