脑梗死患者血清可溶性黏附分子的变化及临床意义

目的　了解急性脑梗死患者血清可溶性黏附分子的变化及临床意义。　方法　采用双抗体夹心ELISA法测定了 77例脑梗死患者血清可溶性黏附分子 ,并与 36例脑出血和 30例健康人对照比较。　结果　脑梗死患者 2 4h内血清可溶性黏附分子水平〔sICAM 1:(4 80 3± 2 6 1) μg/L ,sVCAM 1:(1197± 81) μg/L ,sELAM 1:(5 0 4 4± 2 6 9) μg/L〕明显高于脑出血和健康对照组 (P <0 0 1) ,至第 14天仍高于脑出血组和健康对照组 ;大梗死灶组血清可溶性黏附分子水平〔sICAM 1:(5 0 81± 30 4 ) μg/L ,sVCAM 1:(12 2 3± 4 9) μg/L ,sELAM 1:(5 2 4 4± 2 89) μg/L)明显高于中梗死灶组和小梗死灶组。脑梗死后并发感染患者在 14d内血清可溶性黏附分子水平明显高于无并发感染者。　结论　可溶性黏附分子与急性脑梗死密切相关 ,可溶性黏附分子可作为脑梗死治疗时 ,特别是进展性卒中治疗的重要监测指标之一。     

脑梗死患者血浆对氧磷酯酶-1和氧化低密度脂蛋白水平的变化及意义

目的探讨脑梗死患者血浆对氧磷酯酶-1(PON-1)活性和氧化低密度脂蛋白(ox-LDL)含量变化以及它们在脑梗死发生发展过程中的作用。方法用对氧磷为底物的速率法和酶联免疫吸附法(ELISA)分别测定75例急性期脑梗死患者血浆PON-1活性和ox-LDL水平,并与35例脑出血患者及46例健康对照组比较。结果(1)脑梗死患者血浆PON-1活性为(138.2±25.3)U/L,明显低于脑出血组〔(168.2±28.2)U/L〕及健康对照组〔(171.1±28.5)U/L〕(P<0.01);脑梗死患者血浆ox-LDL水平为〔(615.3±253.2)μg/L〕,明显高于脑出血组〔(460.9±193.0)μg/L〕及健康对照组〔(437.7±187.4)μg/L〕(P<0.01)。(2)大梗死灶组血浆PON-1活性明显低于中梗死灶组和小梗死灶组。而大梗死灶组血浆ox-LDL水平明显高于中梗死灶组和小梗死灶组(P<0.01)。(3)相关分析表明,脑梗死时血浆PON-1活性与ox-LDL水平呈负相关(r=-0.556,P<0.01),而与血脂水平无明显的相关关系。结论脑梗死患者血浆PON-1活性降低和ox-LDL水平升高,提示血浆PON-1可能通过降低抗氧化能力机制参与了脑梗死的病理生理过程。     

老年脑梗死患者蛋白C系统及抗凝血酶系统测定的研究

目的　探讨老年脑梗死患者血浆抗凝系统蛋白C系统及抗凝血酶系统的水平变化及临床意义。方法　酶联免疫吸附测定 (ELISA)法测定蛋白C(PC)、总蛋白S(TPS)、游离蛋白S(FPS)及凝血酶 抗凝血酶Ⅲ复合物 (TAT)的含量 ,发色底物法测定活化蛋白C(APC)和抗凝血酶Ⅲ (ATⅢ )活性。结果　与对照组相比 ,老年脑梗死患者急性期PC、FPS、ATⅢ明显下降 [(2 .89± 1.0 4) μg/ml、(7.85± 2 .2 6 ) μg/ml、(77.2 1± 2 5 .43) % ;(3.42± 1.13) μg/ml、(9.34±3.0 1) μg/ml、(97.2 8± 2 0 .42 ) % ;P <0 .0 5 ],恢复期无差异(P >0 .0 5 ) ;APC、TAT在脑梗死急性期及恢复期明显增高 (P<0 .0 1)。随病情加重PC、FPS显著下降 ,而TAT明显升高 ;有TIA病史的脑梗死患者FPS水平明显低于无TIA病史者 [(6 .5 4± 2 .97) μg/ml,(7.99± 1.13) μg/ml;P<0 .0 1]。PC、FPS与血脂间无相关性。结论　老年脑梗死患者存在凝血的激活 ,抗凝系统的异常参与了老年脑梗死的病理过程     

脑梗死患者脑脊液和血清中脂蛋白(a)的变化

为观察脑梗死患者脑脊液和血清中脂蛋白 (a)含量的变化 ,选择 80例脑梗死患者和 40例对照者 ,用酶联免疫法测定脂蛋白 (a)在脑脊液及血清中的含量。结果发现 ,脑梗死患者与对照者脑脊液中脂蛋白 (a)含量分别为 2 34± 2 9μg/L及 2 11± 2 1μg/L ,血清中脂蛋白 (a)含量分别为 0 .2 99± 0 .0 2 8g/L及 0 .2 71± 0 .0 2 5g/L ,脑梗死组脑脊液及血清中脂蛋白 (a)含量明显高于对照组 (P <0 .0 1)。脑梗死患者和对照者脑脊液与血清中脂蛋白 (a)水平间均无相关关系 (P >0 .0 5 )。结果提示 ,脑梗死患者脑脊液及血清中脂蛋白 (a)水平明显高于对照者。     

颈动脉粥样硬化、C反应蛋白与急性脑梗死的关系

目的探讨颈动脉硬化和C反应蛋白与急性脑梗死的关系。方法采用彩色多普勒超声检测86例急性脑梗死患者的颈动脉内膜,免疫比浊法测定其血清C反应蛋白水平,并与40例同期住院的非脑血管疾病患者作对照。结果脑梗死组颈动脉内膜斑块明显多于对照组(P<0.01),且以软斑和混合斑为主,而对照组以硬斑为主;脑梗死组C反应蛋白水平为9.85±2.28 mg/L,显著高于对照组的5.28±1.23 mg/L(P<0.01);软斑、混合斑、硬斑、正常颈动脉、内膜毛糙组C反应蛋白水平分别为9.80±2.43 mg/L、10.72±2.55 mg/L、7.46±2.54 mg/L、6.15±1.71 mg/L及6.38±1.96 mg/L。前两组与后三组比较均有显著性差异(P<0.01),后三组之间比较没有显著性差异。结论急性脑梗死患者颈动脉斑块明显增多,C反应蛋白水平明显升高,C反应蛋白水平可以反应颈动脉斑块的性质和稳定性。     

微量白蛋白尿与脑梗死面积的关系探讨

目的探讨脑梗死患者微量白蛋白尿水平变化与脑梗死面积之间的关系。方法用比浊法测尿微量白蛋白值,比较大梗死组、中梗死组、腔隙性梗死组及对照组微量白蛋白尿的阳性率及尿微量白蛋白水平。结果微量白蛋白尿阳性率大梗死组62.4%、中梗死组58.9%、腔隙性梗死组54.5%,对照组32.6%。尿微量白蛋白水平大梗死组(22.56±14.28mg/L)、中梗死组(16.82±11.78mg/L)、腔隙性梗死组(11.76±10.28mg/L)、对照组(7.12±10.12mg/L)。3个脑梗死组与对照组比较差异均有统计学意义(P<0.05),大梗死组、中梗死组与腔隙性组比较有统计学意义(P<0.05)。结论脑梗死患者呈现微量白蛋白尿高发率;尿微量白蛋白水平越高,梗死面积越大。可为临床预后的预测因子。     

补体耗竭对心肌缺血再灌注的保护作用及机制

目的明确耗竭补体对心肌缺血再灌注的保护作用.方法12只小猪随机分为对照组和眼镜蛇毒因子(CVF)组,CVF组在结扎冠状动脉前6h按20U/kg注射CVF以耗竭补体.开胸结扎小猪左冠状动脉前降支60min,然后松扎5h.测定血流动力学、梗死面积、心肌组织髓过氧化物酶(MPO)等指标,并作免疫组织化学检查.结果(1)血流动力学两组左室内压上升最大速度(+ap/dtmax)在心肌缺血期间均有明显下降,再灌注5h后对照组回升至(326±42)kPa/s,而CVF组回升达(418±41)kPa/s(P<0.05);(2)心肌梗死面积(坏死区占左心室重量百分比)对照组为(13.2±4.0)%,CVF组仅为(7.6±2.8)%(P<0.05);(3)MPO活性(U/g)对照组坏死区为2.68±0.15,而CVF组为1.27±O.14(P<O.01);(4)免疫组化染色对照组坏死区心肌组织有明显Clq、C3、C5b-9的沉积.结论CVF耗竭补体对小猪心肌缺血再灌注有显著心肌保护作用,此可能与抑制粒细胞有关.     

慢性情绪应激对高脂饮食大鼠炎症反应和主动脉Toll样受体4表达的影响

目的通过观察慢性情绪应激对高脂饮食大鼠脂代谢、炎症反应和主动脉内皮细胞TLR4表达的影响,探讨慢性情绪应激在动脉粥样硬化病变形成中的作用、机制。方法雄性Wistar大鼠40只,随机分为正常对照组(NC)、无应激组(NS)、生理应激组(PS)和情绪应激组(ES),每组各10只,并制作慢性情绪应激模型。于末次应激结束后采集血标本,全自动生化分析仪检测血清TC、TG、HDL-C、LDL-C和hs-CRP,ELISA法测定血清ox-LDL、放免法检测TNF-α水平;HE染色观察大鼠主动脉形态学变化;免疫组化法(S-P)测定主动脉内皮细胞TLR4表达。结果 (1)ES组大鼠较其他3组出现了明显的脂代谢紊乱和炎症反应。与PS组、NS组、NC组比较,ES组TC、LDL-C、ox-LDL水平明显升高[TC:(5.30±0.69)mmol/L比(3.94±0.42)mmol/L、(3.82±0.48)mmol/L、(2.07±0.26)mmol/L;LDL-C:(1.57±0.22)mmol/L比(1.18±0.13)mmol/L、(1.11±0.11)mmol/L、(0.75±0.11)mmol/L;ox-LDL:(65.18±6.51)μg/dl比(45.65±2.70)μg/dl、(38.35±2.27)μg/dl、(14.99±1.46)μg/dl,均为P<0.01];ES组HDL-C[(0.94±0.14)mmol/L]低于NS组[(1.09±0.14)mmol/L,P<0.05],低于NC组[(1.16±0.18)mmol/L,P<0.01];与PS组、NS组、NC组比较,ES组hs-CRP、TNF-α水平升高[hs-CRP:(1.748±0.082)mg/L比(1.485±0.067)mg/L、(1.381±0.067)mg/L、(0.757±0.069)mg/L;TNF-α:(2.447±0.083)μg/L比(2.189±0.099)μg/L、(2.181±0.085)μg/L、(1.772±0.075)μg/L,均为P<0.01];(2)ES组大鼠主动脉出现早期动脉粥样硬化性改变;(3)ES组大鼠主动脉内皮细胞TLR4表达明显上调,其阳性细胞单位面积平均吸光度值(A)高于PS组、NS组和NC组[(0.334±0.010)比(0.250±0.012)、(0.238±0.015)、(0.082±0.008),均为P<0.01]。结论慢性情绪应激可能在动脉粥样硬化形成的早期,部分通过激活TLR4释放炎性细胞因子引起机体的炎症反应,进而导致动脉粥样硬化病变形成。     

哮喘儿童持续吸入低剂量糖皮质激素的全身性副作用

目的 探讨我国哮喘儿童吸入糖皮质激素的全身性副作用.方法 将30例14岁以下轻度哮喘儿童随机分为安慰剂组(A组)、二丙酸倍氯松(BDP)200 μg组(B组)、BDP 400 μg组(C组),每组10例,分别持续吸入安慰剂及BDP 200、400 μg/d 1年,观察患儿气道高反应性(BHR)、身高增长、骨密度(BMD)、钙磷代谢及下丘脑-垂体-肾上腺轴(HPAA)功能的影响.结果 B组及C组患儿吸入BDP后PD20-FEV1即一秒钟用力呼气容积下降20% 时累积吸入的组胺剂量[Log(PD20- FEV1)]分别为(2.70±0.13) μg及(3.15±0.18) μg,与治疗前[B组(2.04±0.47) μg,C组(1.94±0.46) μg]比较,差异有显著性(P均<0.01),而B组与C组间比较,差异有显著性(P<0.01).A、B及C组患儿吸入BDP后血骨钙素分别为(29±12) μg/L、(22±6) μg/L、(31±11) μg/L,血钙为(2.49±0.11) mmol/L、(2.39±0.28) mmol/L、(2.20±0.35) mmol/L, 血磷为(1.8±0.6) mmol/L、(1.7±0.7) mmol/L、(1.5±0.4) mmol/L,血碱性磷酸酶为(410±113) U/L、(337±99) U/L、(351±122) U/L(P>0.05),桡骨BMD为(0.40±0.10) g/cm2、(0.42±0.05 ) g/cm2、(0.44±0.02) g/cm2,尺骨BMD为(0.32±0.07) g/cm2、(0.36±0.08) g/cm2、(0.35±0.04) g/cm2,腰椎4～5BMD为(0.62±0.09) g/cm2、(0.59±0.08) g/cm2、(0.64±0.06) g/cm2,血皮质醇基础值为(350±86)nmol/L、(407±199) nmol/L、(365±71)nmol/L, 三组间比较差异无显著性(P均>0.05).但C组治疗后血皮质醇对促肾上腺皮质激素(ACTH)刺激的反应值为(482±97) nmol/L, 与治疗前(621±199 )nmol/L比较,差异有显著性(P<0.01),而A组和B组治疗后分别为 (566±203) nmol/L,(452±97)nmol/L,与治疗前[A组(534±204)nmol/L,B组(481±82)nmol/L]比较,差异无显著性(P均>0.05).A组患儿吸入BDP后身高标准差计分(SDS)为(1.2±0.9)分,B组为(1.3±0.9)分,C组为(1.0±0.7)分,三组比较差异均无显著性(P均>0.05).结论 14岁以下轻度儿童哮喘吸入200 μg/d的BDP即能有效降低BHR,且无明显全身性副作用.而当剂量达400 μg/d时,血皮质醇对ACTH刺激的反应性明显降低,有必要作进一步的研究.     

血浆巨噬细胞游走抑制因子和颈动脉斑块性质与进展性脑梗死的关系

目的探讨血浆巨噬细胞游走抑制因子(macrophage migration-inhihitory factors,MIF)水平、颈动脉斑块性质与进展性脑梗死患者的关系。方法选择急性前循环脑梗死患者106例,根据临床表现分为进展性脑梗死组(进展组)56例和非进展性脑梗死组(非进展组)50例;另选健康体检者40例为对照组。采用ELISA法检测血浆MIF,同时行颈动脉多普勒超声检查。根据斑块性质,脑梗死患者又分为无斑块26例、稳定斑块40例和不稳定斑块40例,并进行MIF比较。结果进展组症状相关侧颈动脉斑块以不稳定斑块为主,占44.6%;与非进展组MIF(19.50±4.66)μg/L和对照组(23.06±5.10)μg/L比较,进展组MIF(26.24±6.08)μg/L明显升高,差异有统计学意义(P<0.05);脑梗死不稳定斑块、稳定斑块、无斑块患者MIF分别为(26.48±6.12)μg/L(23.45±5.04)μg/L、(21.12±4.53)μg/L,差异有统计学意义(P<0.05)。结论血浆MIF水平的升高和颈动脉斑块不稳定性与进展性脑梗死的发生密切相关。     

近期感染与脑梗死发病的相关性研究

目的:探讨近期感染与脑梗死发病的关系,分析循环免疫复合物(circulatingimmunecomplex,CIC)、C反应蛋白(Creactiveprotein,CRP)、补体C4、C3、C1q与近期感染和脑梗死发病的关联。方法:调查了97例脑梗死患者与对照组83例,测定26例有近期感染史和71例无近期感染史的脑梗死病例及83例对照组的血清CIC、CRP、C4、C3、C1q含量,并进行分析。结果:经单因素Logistic回归显示:近期感染(OR,2.67;95%可信区间,1.2～5.9),CIC(OR,1.08;95%可信区间,1.03～1.12),CRP(OR,1.27;95%可信区间,1.16～1.39)水平升高,C1q(OR,0.88;95%可信区间,0.83～0.93),C3(OR,0.98;95%可信区间,0.96～0.99),C4(OR,0.93;95%可信区间,0.89～0.97)水平降低都是脑梗死的危险因素。但经多因素Logistic回归后仅CRP(OR,1.26;95%可信区间,1.12～1.43)水平升高,C1q(OR,0.88;95%可信区间,0.82～0.94),C3(OR,0.98;95%可信区间,0.96～0.99)水平降低是脑梗死的危险因素。经Spearman相关分析显示:感染与CIC有关(r=0.27,P=0.0008),与脑梗死发作有关(r=0.18,P=0.013)。脑梗死与CIC(r=0.3,P<0.0001),CRP(r=0.43,P<0.0001),C1q(r=-0.37,P=0.0001),C3(r=-0.26,P=0.0007),C4(r=-0.27,P=0.0004)水平有关。结论:感染是脑梗死的一个危险因素;循环免疫复合物CIC、CRP、补体C4、C3、C1q参与了脑梗死发病;循环免疫复合物既与感染有关联又参与了脑梗死的免疫损伤过程。     

The role of circulating immune complexes in the pathogenesis of Graves' disease

It has recently been reported that many immunological abnormalities including the presence of TSH-receptor antibody (TRAb) were found in Graves' disease (GD). Circulating immune complexes (CIC) have also been detected in the serum of patients with GD as observed in systemic lupus erythematosus, which is thought to be a typical model of immune complex disease. The role of CIC in pathogenesis of hyperthyroidism, however, remains to be elucidated. Therefore, to clarify pathophysiological functions of CIC in GD, the levels of it in those patients were compared with their symptoms, those of TRAb, and lymphoblastogenesis (LBG) induced by phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM). The subjects were forty patients with GD without any medication, one hundred and nine patients with GD on medication with methimazole (MMI), and fifteen healthy volunteers. CIC was measured by three different methods; polyethyleneglycol precipitation method (PEG), Clq binding assay (Clq), and Protein A binding assay (PA). The normal range was estimated with the mean plus or minus two times the standard deviation of normal controls. In untreated GD, CIC determined by PEG, Clq and PA widely distributed from normal range to high levels. The positive rates of CIC determined by PEG, Clq, PA, and any one method of these three were 17.5%, 22.5%, 30.0% and 52.5%, respectively. LBG using incorporation of tritiated thymidine showed the decreases in PHA and Con A, and the increases in PWM in patients with GD. The positive rates of CIC determined by PEG and PA were significantly higher in patients without goiter or with small one than those with large one (p less than 0.05). CIC measured by all three of PEG, Clq and PA showed negative correlation with TRAb significantly (p less than 0.05, p less than 0.01, p less than 0.01, respectively). On the other hand, CIC measured by Clq showed significant negative correlation with serum thyroxine concentration (p less than 0.01). The levels of CIC, TRAb and PWM-induced LBG decreased following the tapering dose of MMI sufficient to keep patients in euthyroid state. In consequence, there were no longer any correlations between CIC and TRAb after thyroid function was normalized. These observations suggest that CIC's which have huge molecular weight or have ability to bind Fc receptor on K cell, macrophage, neutrophil, and other immune cells may be one of the factors to inhibit the goitrogenic action of TRAb, and that CIC's which have ability to activate the complement system may be one of the factors to inhibit the stimulation of secretion of thyroid hormone by TRAb.(ABSTRACT TRUNCATED AT 400 WORDS)     

Circulating immune complexes in rheumatoid arthritis: a prospective study using five immunoassays

We evaluated 257 patients with rheumatoid arthritis (RA) to determine the frequency of circulating immune complexes (CIC) in the serum, relationships between the presence of CIC, clinical indices of disease activity and other laboratory features, and relationships between changes in CIC levels and changes in disease activity. CIC were detected by fluid phase Clq binding activity, conglutinin binding activity, anti-C3 assay, staphylococci protein A binding assay and the precipitation of cryoglobulins. CIC in the serum were found to correlate with indices of disease activity, extraarticular features and the presence of rheumatoid factor. A change in Clq binding activity correlated with a parallel change in the joint count.     

Increased preoperative glucose levels are associated with perioperative mortality in patients undergoing noncardiac, nonvascular surgery

OBJECTIVE: To determine the relationship between preoperative glucose levels and perioperative mortality in noncardiac, nonvascular surgery. RESEARCH DESIGN AND METHODS: We performed a case-control study in a cohort of 108 593 patients who underwent noncardiac surgery at the Erasmus MC during 1991-2001. Cases were 989 patients who underwent elective noncardiac, nonvascular surgery and died within 30 days during hospital stay. From the remaining patients, 1879 matched controls (age, sex, calendar year, and type of surgery) were selected. Information was obtained regarding the presence of cardiac risk factors, medication, and preoperative laboratory results. Preoperative random glucose levels <5.6 mmol/l (110 mg/dl) were normal. Impaired glucose levels in the range of 5.6-11.1 mmol/l were prediabetes. Glucose levels >or=11.1 mmol/l (200 mg/dl) were diabetes. RESULTS: Preoperative glucose levels were available in 904 cases and 1247 controls. A cardiovascular complication was the primary cause of death in 207 (23%) cases. Prediabetes glucose levels were associated with a 1.7-fold increased mortality risk compared with normoglycemic levels (adjusted odds ratio (OR) 1.7 and 95% confidence interval (CI) 1.4-2.1; P<0.001). Diabetes glucose levels were associated with a 2.1-fold increased risk (adjusted OR 2.1 and 95% CI 1.3-3.5; P<0.001). In cases with cardiovascular death, prediabetes glucose levels had a threefold increased cardiovascular mortality risk (adjusted OR 3.0 and 95% CI 1.7-5.1) and diabetes glucose levels had a fourfold increased cardiovascular mortality risk (OR 4.0 and 95% CI 1.3-12). CONCLUSIONS: Preoperative hyperglycemia is associated with increased (cardiovascular) mortality in patients undergoing noncardiac, nonvascular surgery.     

Acute Effects of Steroids On Immune Complex Profile of Patients with Systemic Lupus Erythematosus

Eleven patients with active systemic lupus erythematosus, previously untreated, were studied to 1) determine the acute effect of corticosteroids on circulating immune complex (CIC) levels and 2) correlate the initial CIC profile with the development of organ system involvement. Using serial measurements of CIC as detected by assays for cryoglobulins and binding to Clq, Raji cells, and rheumatoid factor, we found that levels of CIC change little during the first month of high dose daily steroid therapy, but they uniformly decrease to near normal by 6 to 12 months. High levels of CIC detected by Raji cell assay early in the course of systemic lupus erythematosus and before steroid therapy appear to be predictive of the development of chronic lupus nephritis (P < 0.005).     

Further description of early clinically silent lupus nephritis

Thirty silent lupus nephritis (SLN) patients were compared to 16 individuals bearing overt lupus nephritis (OLN). Results included: years of systemic lupus erythematosus (SLE) diagnosis were significantly earlier (4.6 +/- 2.8 years) in SLN than in OLN (7.18 +/- 3.61) (P < 0.05). Neurological compromise, hypertension, normocitic anemia and lymphopenia were significantly prevalent in OLN than in SLN (P < 0.05). Beside normal urinary sediment and renal function tests, the SLN group showed a moderate increase of both activity (AI) and chronicity (CI) renal pathology index when compared to highly increased AI and CI in OLN (P < 0.05). Seventy percent of SLN patients were ISN/RPS Classes I (6.6%) and II (63.3%) while 81% of OLN cases were Classes III, IV (37.5%) and V. IgG, IgA, IgM, lambda chain, C3 and fibrinogen immune deposits were found in 90% or over in both SLN and OLN individuals while in 60% or over, both groups also showed kappa chain, Clq and C4 deposits. While prevalence of ANA, anti-dsDNA and anti-C1q antibodies were similar in both groups, anti-histone, anti-RNP, CIC and CH50 serum levels were significantly different in OLN versus SLN (P < 0.05). We strongly suggest that indeed SLN is the earliest stage in the natural history of lupus nephritis.     

Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T〉C polymorphism in the bile salt export pump

AIM： To study the association of three common ABCB11 and ABCC2 polymorphisms （ABCB11： 1331T〉C→V444A; ABCC2： 3563T〉A → V1188E and 4544G 〉A → C1515Y） with intrahepatic cholestasis of pregnancy （ICP） and contraceptive-induced cholestasis （CIC）. METHODS： ABCB11 and ABCC2 genotyping data were available from four CIC patients and from 42 and 33 ICP patients, respectively. Allele-frequencies of the studied polymorphisms were compared with those in healthy pregnant controls and Caucasian individuals. Furthermore, serum bile acid levels were correlated with the presence or absence of the 1331 C allele. RESULTS： The ABCB11 1331T〉C polymorphism was significantly more frequent in cholestatic patients than in pregnant controls： C allele 76.2% （CI, 58.0-94.4） vs 51.3% （CI 35.8-66.7）, respectively （P = 0.0007）; and CC allele 57.1% （CI 36.0-78.3） vs 20% （CI 7.6-32.4）, respectively （P = 0.0065）. All four CIC patients were homozygous carriers of the C allele. In contrast, none of the studied ABCC2 polymorphism was overrepresented in ICP or CIC patients. Higher serum bile acid levels were found in carriers of the 1331CC genotype compared to carriers of the TT genotype. CONCLUSION： Our data support a role for the ABCB11 1331T〉C polymorphism as a susceptibility factor for the development of estrogen-induced cholestasis, whereas no such association was found for ABCC2. Serum bile acid and 7-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC.     

Evaluation of lipid peroxidation product, nitrite and antioxidant levels in newly diagnosed and two months follow-up patients with pulmonary tuberculosis

This case-control study followed by a longitudinal cohort study was undertaken to evaluate the level of lipid peroxidation product malondialdehyde (MDA) and nitrite as an indirect measurement of nitric oxide vis-à-vis the levels of antioxidants vitamin C and vitamin E in pulmonary tuberculosis. Fifty-six sputum smear-positive cases of pulmonary tuberculosis based on Ziehl-Neelsen (ZN) staining and 50 healthy controls without any systemic disease were included in this study. Thirty-five cases were longitudinally followed up with standard antituberculosis chemotherapy (ATT) for two months. Serum levels of malondiadehyde (MDA), nitrite, and plasma levels of vitamins C and E were measured. The mean serum MDA level was significantly higher (8.1 +/- 1.61 nmoles/ml) in PTB patients before commencement of ATT as compared to healthy controls (3.45 +/- 1.7 nmoles/ml) (p=0.0001) and decreased significantly after 2 months of ATT (3.84 +/- 1.28 nmoles/ml) (p=0.0001). The mean serum nitrite level (47.19 +/- 18.44 micromol/l) was significantly elevated before ATT compared to healthy controls (32.89 +/- 11.94 micromoles/l) and decreased significantly after 2 months of ATT (27.71 +/- 11.97 micromoles/l) (p=0.0001). The mean plasma levels of vitamins C (0.88 +/- 0.33 mg/dl) and E (0.79 +/- 0.24 mg/dl) in PTB patients before commencement of ATT were lower than healthy controls (1.42 +/- 0.38 mg/dl) and (1.35 +/- 0.35 mg/dl), respectively (p=0.001). There was a significant increase in vitamin C levels after 2 months of ATT (1.19 +/- 0.40 mg/dl) compared to before ATT (0.83 +/- 0.31 mg/dl) (p=0.0001), but no significant change in mean plasma vitamin E level before and after 2 months on ATT was found. Elevated malondialdehyde and nitrite levels with concomitant depressed vitamin C and E levels are indicative of lipid peroxidation and oxidative stress. The decrease in levels of malondialdehyde and nitrite with subsequent increase in vitamin C levels after two months of follow-up indicate a good response to treatment with standard ATT. Hence, the extent of oxidative stress in PTB can be evaluated by analyzing lipid peroxidation product, antioxidant and nitric oxide levels.     

Bleeding duodenal ulcer and association with polymorphism of endothelial constitutive nitric oxide synthase gene

Nitric oxide (NO) exerts both protective and proinflammatory actions in the gastrointestinal tract. Enhanced gastric NO synthase (NOS) activity has been shown in duodenal ulcer patients. Recently, intron-4 polymorphism of the endothelial constitutive (ec) NOS gene has been associated with some pathological conditions. Our aim was to determine the genotype and allele frequencies of the ecNOS4 polymorphism in peptic ulcer patients. The distribution of the polymorphism ecNOS4a/b was studied in 188 ulcer patients and 120 healthy controls, from genomic DNA. Genotypes ab, bb, and aa and allele frequency were similar in both peptic ulcer patients and controls, and no differences were found when patients and controls were analyzed according to the presence of several etiological factors. However, alelle a carrier status was associated with decreased risk of bleeding in duodenal ulcer patients (OR = 0.49; 95% CI = 0.25–0.95; P = 0.03). In conclusion, this ecNOS4 polymorphism gene could be related to susceptibility of duodenal ulcer patients to bleeding.     

Autoimmunity and normal immune functions in aged humans

The high frequency of ANA, A-LDL and RF in advanced age suggests that AABs are present in the majority of aged subjects. CIC incidence determined by three methods is far below AAB incidence; only the Clq solubility test suggests an increased CIC incidence in aged as compared to young subjects. Simultaneous occurrence of AABs of different specificities or CIC determined by two or three methods is rare and both AAB and CIC levels are usually low. AAB prevalence in CIC-positive individuals seems to depend on the specificity of the AAB. CIC positivity is associated with relatively low Clq concentrations; however, usually not with Clq concentrations below the normal range. Neither ANA nor CIC positivity seems to correlate with DNA synthetic response to PHA, but ANA positivity may be associated with low responses to allogeneic cells. ANA positivity and, to a lesser extent, CIC positivity seems to be connected with enhanced killer cell activity. The concept of some AABs and CIC as autoregulatory factors of the humoral immune system compensating for the thymus-dependent regulation in old age is stressed.