葛根素对大鼠糖尿病牙周炎的疗效及血清AGEs的影响

目的:通过动物实验,观察中药葛根素注射液对糖尿病牙周病大鼠的血清糖基化终产物AGEs及牙槽骨吸收的影响,探讨中药葛根素注射液对糖尿病牙周炎的疗效。方法:将50只健康雄性SD大鼠随机分为健康对照组(D组)10只、模型组40只。模型组采用四氧嘧啶及正畸结扎丝固定诱导糖尿病牙周炎模型,将成模的30只大鼠随机分为A组(葛根素注射液用药组),B组(氨基胍用药组),C组(空白对照组),每组10只。分别对A、B、C组大鼠干预处理6周,在用药第4及6周时分别观测大鼠血糖,牙周软组织状况,荧光分光光度计测量血清的AGEs的含量,苏木精—伊红染色观察牙周组织的病理改变,牙科CT观测牙槽骨的吸收情况。观察应用葛根素注射液后,大鼠的牙周组织的改变。结果:实验结束时,A组血糖较B组略高,但是差异不大(P>0.05),较C组明显降低(P<0.05),但是仍高于D组。大鼠血清AGEs含量在用药4周时,A、B组较C组明显降低(P<0.05),但是仍高于D组,A组略高于B组(P<0.05)。6周时,A、B组较C组降低(P<0.05),但是A组B组之间差异不大,无统计学意义(P>0.05)。牙周状况,4周时,A、B组较C组牙周组织炎症减轻,附着丧失,及探诊出血减轻,牙槽骨吸收降低并出现新生骨基质。用药6周时,状况较4周明显改善。结论:中药葛根素注射液可降低糖尿病牙周炎大鼠外周血血清中AGEs的含量,并抑制糖尿病大鼠牙周炎的发展。     

糖尿病牙周炎大鼠模型的构建

目的:通过对糖尿病牙周炎大鼠模型的构建以及分析,以利后续研究。方法:40只大鼠随机分成模型组(n=20)和健康对照组(n=20)。模型组链脲佐菌素(STZ)腹腔注射,并用正畸结扎丝结扎双侧上颌第一磨牙;对照组不做处理。第4周处死两组大鼠,观察牙周组织学变化。结果:模型组大鼠出现糖尿病和牙周炎的典型症状;对照组无相应表现。两组大鼠牙周袋深度值比较有显著差异(P0.05)。结论:该实验创建了糖尿病牙周动物的稳定模型,为将来的研究打下了坚实的基础。     

90例慢性牙周炎临床分析

目的评价不同治疗方法对慢性牙周炎的临床效果。方法对90例慢性牙周炎患者,随机分成三组:龈上洁治术 抗生素组(A组),单纯龈上洁治术组(B组)和单纯抗生素组(C组)。分别给予不同的治疗,在治疗后1周、2周和4周记录牙周袋探诊深度(PPD)、探诊附着水平(PAL)、菌斑指数(PLI)、龈沟出血指数(SBI)。结果治疗1周和2周后各指标显著减轻(P<0.05),2周比1周减轻更明显(P<0.05),4周与2周比较无明显差异(P>0.05),A组各指标减轻比B组显著(P<0.05);B组比C组疗效显著(P<0.05)。结论A组作用优于B组(P<0.05),B组优于C组(P<0.05)。     

盐酸米诺环素原位凝胶的药效学研究

目的探讨盐酸米诺环素原位凝胶治疗牙周炎的药效学作用。方法以大鼠为模型动物,建立了与临床病理特征相一致的稳定的大鼠实验牙周炎模型,并以此模型进行了药效学研究。结果对比给药组与正常对照组、牙周炎组、空白对照组对牙周病各项临床指标(探诊出血、牙龈指数、牙周袋深度)的改善和病理照片表明,盐酸米诺环素原位凝胶在给药第1周内探诊出血、牙龈指数、牙周袋深度逐渐减小,4周时与正常对照组各项指标差异无统计学意义。结论盐酸米诺环素原位凝胶能有效地改善牙周炎炎症反应,是一种理想的治疗牙周炎的药物传递系统。     

二甲双胍对2型糖尿病模型大鼠肾组织AGEs表达的影响

目的观察二甲双胍(MET)对2型糖尿病(T2DM)模型大鼠肾组织非酶糖基化终末产物(AGEs)及其受体(RAGE)mRNA表达的影响,探讨MET对糖尿病肾病的保护机制。方法用高脂饲料喂养结合腹腔注射小剂量链脲佐菌素(STZ)建立2型糖尿病大鼠模型。模型大鼠随机分组,给予二甲双胍干预治疗(MET组,300 mg·kg~(-1)·d~(-1))、格列本脲干预(GLY组,5 mg·kg~(-1)·d~(-1)),并设立糖尿病模型组(T2DM组)和正常对照组(NC组)。给药8周后,观察各组大鼠血糖(BG)、糖化血红蛋白(Hb A1c)、尿素氮(BUN)、尿白蛋白和尿AGEs排泄的情况;免疫组化测肾小球AGEs蛋白表达;Real-time PCR检测肾组织RAGE mRNA表达。结果 8周末,MET组及GLY组BG、Hb A1c、FINS、尿白蛋白/尿肌酐(UACR)、基底膜厚度(GBMT)明显低于T2DM组,高于NC组(P<0.05),MET组与GLY组BG、Hb A1c和FINS差异无统计学意义(P>0.05);MET组尿AGEs/尿肌酐(UGCR)、肾组织AGEs蛋白和RAGE mRNA表达明显低于糖尿病模型组(P<0.05),但比NC组高(P<0.05);MET组UGCR、肾组织AGEs和RAGE mRNA表达低于GLY组(P<0.05)。结论 MET可减少AGEs在糖尿病大鼠肾组织的积累,并下调糖尿病大鼠肾组织RAGE mRNA的过度表达,该作用可能与其肾脏保护作用有关。     

米诺环素治疗中重度慢性牙周炎合并2型糖尿病的临床观察

目的:探讨米诺环素对中重度慢性牙周炎合并2型糖尿病患者的临床指标、炎症因子和血糖的影响。方法:选取我院2013年2月-2015年8月收治的中重度慢性牙周炎合并2型糖尿病患者125例,按照随机数字表法分为对照组(63例)和观察组(62例)。两组患者均给予洁治术和根面平整术等牙周基础治疗;对照组患者术后给予碘甘油注满牙周袋,2~4次/d;观察组患者术后给予盐酸米诺环素软膏注满牙周袋,每周1次。两组患者均治疗4周。观察两组患者治疗前和治疗后3个月的临床指标[探诊深度、临床附着水平(CAL)和探诊出血率]、血清炎症因子(C反应蛋白和肿瘤坏死因子α)、血糖(空腹血糖和糖化血红蛋白)水平,并记录不良反应发生情况。结果:治疗前,两组患者临床指标、血清炎症因子和血糖水平比较,差异均无统计学意义(P>0.05)。治疗后3个月,两组患者探诊深度、探诊出血率和血清炎症因子水平均明显降低,且观察组明显低于对照组,差异均有统计学意义(P<0.05);两组患者CAL均较治疗前增加,但治疗前后比较、组间比较差异均无统计学意义(P>0.05);两组患者空腹血糖均明显降低,差异有统计学意义(P<0.05),但组间比较差异无统计学意义(P>0.05);对照组患者糖化血红蛋白水平较治疗前降低,但差异无统计学意义(P>0.05);观察组患者糖化血红蛋白水平明显降低,且观察组明显低于对照组,差异有统计学意义(P<0.05)。观察组患者不良反应发生率(3.23%)与对照组(0)比较,差异无统计学意义(P>0.05)。结论:米诺环素治疗中重度慢性牙周炎合并2型糖尿病可有效改善患者牙周炎的临床指标,降低血清炎症因子和血糖水平,且安全性较高。     

派丽奥治疗慢性牙周炎的临床疗效观察

目的观察派丽奥抗生素软膏治疗慢性牙周炎的临床疗效。方法选择临床诊断为慢性牙周炎的患者58例,采用随机单盲自身对照方法,以单纯牙周基础治疗为对照,实验组基础治疗后在牙周袋内置入派丽奥软膏,每周1次,共4次。记录基线、用药后1、4及8周的牙龈指数(GI)、牙周探诊深度(PD)和探诊出血(BOP)的变化并进行统计学分析。结果第4周、第8周2组临床指标均较基线时有明显改善(P<0.05),实验组改善优于对照组,差异有显著性(P<0.05)。结论派丽奥是治疗牙周炎有效、安全的局部治疗药物。     

大鼠实验性牙周炎动物模型的建立

目的 采用一种综合的方法建立大鼠实验性牙周炎动物模型。方法 将SD大鼠44只分为3组：①正常对照组(N组)；②牙龈炎组(P组)和③牙周炎组(DP组)。P组和DP组肌注醋酸强的松龙，丝线缝扎牙颈部，高糖加自身粪便水喂养。显微镜下观察牙周组织的组织学改变。结果 N组实验全过程中未见明显炎症的出现。P组实验1周出现龈炎表现；4周牙龈上皮明显增生，结缔组织内有比1周时更多的大量炎症细胞浸润，牙龈指数显著增大。DP组实验7周可观察到牙周主纤维断裂，破骨细胞和牙槽骨吸收，以及牙周袋等典型的牙周炎表现。结论 以SD大鼠为实验动物，采用全身因素和局部因素的共同作用，4-7周可以造成明显的牙周炎。     

糖尿病大鼠阴茎组织中糖基化终产物、诱导型一氧化氮合酶的表达分析

目的：探讨糖尿病大鼠阴茎组织糖基化终产物（AGEs）、诱导型一氧化氮合酶（iNOS）的表达变化及它们表达的相关性。方法64只雄性Wistar大鼠随机分为糖尿病模型组（DM组）和对照组（NC组）,各32只。在DM组大鼠模型制备成功后的4、8、12、20周,两组各杀检8只大鼠。使用免疫组织化学法观察阴茎组织中AGEs、iNOS的表达定位同时分析其含量变化,使用Real-time PCR检测阴茎组织中AGEs、iNOSmRNA的表达情况。结果大量AGEs和iNOS阳性细胞分别出现于4、8、12、20周DM模型大鼠阴茎组织内,其累计光密度（IOD）值高于对照组,并随病程进展而增高（P<0.05,P<0.01）。 Real-time PCR结果显示,NC组大鼠在造模后4、8、12、20周AGEs和iNOS的表达量差异无统计学意义（P>0.05）,DM模型大鼠阴茎组织AGEs和iNOS mRNA表达水平随着病程进展逐渐增加（P<0.01）,且高于相同时间点的NC组（P<0.01）,Pearson相关分析显示,DM大鼠阴茎组织AGEs与iN-OS的表达水平呈显著正相关（r=0.845,P<0.01）。结论高血糖状态下,阴茎组织内AGEs和iNOS的表达显著增加并呈正相关,可能共同参与了DM阴茎损害的发生。     

槲皮素脂质体对糖尿病大鼠肾脏糖基化终产物及其受体表达的影响

摘要： 目的 观察槲皮素脂质体 （LQ） 对糖尿病大鼠肾脏糖基化终产物 （AGEs） 及其受体 （RAGE） 表达的影响。方法 采用旋转蒸发法制备槲皮素脂质体, 高糖高脂饲料联合腹腔注射链脲佐菌素 （STZ） 建立 2 型糖尿病大鼠模型, 并随机分为糖尿病模型组 （DM 组）, 槲皮素脂质体低 （LQ-L）、 中 （LQ-M）、 高 （LQ-H） 剂量组, 氨基胍 （AG） 对照组（AG 组）, 另设正常组 （N 组）。灌胃治疗 8 周后测定各组大鼠血糖、 体质量、 肾脏肥大指数 （KI）、 血尿素氮 （BUN）、 血肌酐 （Scr）, ELISA 法测血清 AGEs 表达和 24 h 尿微量白蛋白, PAS 染色观察肾脏病理改变, 免疫组化测肾组织 AGEs 表达, RT-PCR 检测肾皮质 RAGE mRNA 表达水平。结果 与 N 组比较, DM 组大鼠血糖、 KI、 BUN、 Scr、 血清 AGEs 和 24 h 尿微量白蛋白显著升高, 体质量明显降低; 肾小球体积萎缩, 基底膜增厚; 肾组织 AGEs 和 RAGE mRNA 表达增高 （均 P < 0.05）。与 DM 组比较, LQ 各剂量组大鼠血糖、 KI、 BUN、 Scr、 血清 AGEs 和 24 h 尿微量白蛋白均降低, 体质量增加; 病理改变明显减轻; 肾组织 AGEs 和 RAGE mRNA 表达降低, 以中剂量组作用更明显 （均 P < 0.05）。结论 LQ 可抑制蛋白质非酶糖基化反应, 从而减少肾组织 AGEs 生成及 RAGE mRNA 表达水平, 对糖尿病大鼠肾脏具有保护作用。     

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.