The effect of 2,4-diamino-6-hydroxy-pyrimidine on postburn Staphylococcus aureus sepsis in rats

GTP-cyclohydrolase I (GTP-CHI) is the first and rate-limiting enzyme for the de novo biosynthesis of biopterin. The present study was to observe the effect of 2,4-diamino-6-hydroxy-pyrimidine (DAHP),an inhibtor of GTP-CHI, on the development of postburn Staphylococcus aureus sepsis. Methods: 56 male Wistar rats were randomly divided into four groups as follows: normal control group (n= 10), scald control group(n= 10),pos tburn sepsis group (n= 20) and DA HP treatment group (n= 16). In the scald control group, rats were subjected to a 20% total body surface area (TBSA) Ⅲ° scald injury, then sacrificed at 24 hrs. In the postburn sepsis group (n=20), rats were inflicted with 20% TBSA Ⅲ° scald followed by Staphylococcus aureus challenge, and they were further divided into 2 and 6 hrs groups. In the DAHP treatment group (n= 16), animals were intraperitoneally injected with a dose of 1g/kg DAHP prior to Staphylococcus aureus challenge, and then further divided into 2, 6 hrs groups. Tissue samples from liver, kidneys, lungs and heart were collected to determine GTP-CHI, inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) mRNA expression. Meanwhile, biopterin and nitric oxide (NO) levels in these tissues were also measured. Results: After the scald injury followed by Staphylococcus aureus challenge, GTP-CHI mRNA expression and biopterin levels significantly elevated in various tissues such as liver, heart, kidneys and lungs, so did the values of iNOS mRNA expression and NO formation (P＜0.01). Pretreatment with DAHP could significantly reduce GTP-CHI/biopterin induction (P＜0. 05～0. 01), and the up-regulation of iNOS/NO was also suppressed. Furthermore, DAHP administration could also inhibit the gene expression of TNF-α. 2 hrs after septic challenge, TNF-α mRNA expression in liver, kidneys and lungs in DAHP-treated group were 35.7%, 37.3% and 33.0% of those in postburn septic group, respectively. Additionally, in animals without DAHP treatment, the 6-hour mortality was 55.6% (20/36), while it was only 25.0% in DAHP-treated animals (4/16, P=0. 08). Conclusions: Early treatment with DAHP might be a potential strategy to prevent the development of postburn Staphylococcal sepsis, which appears to be associated with down-regulation of biopterin and NO formation by DAHP.     

D4S1647、D6S2414基因座在中国汉族、蒙古族、藏族的遗传多态性

目的 调查D4S1647、D6S2414基因座在中国汉族、蒙古族、藏族群体中的遗传分布规律。方法 采集308份血及唾液标本应用PCR技术，扩增产物用非变性聚丙酰胺凝胶电泳分离，银染显色分析。结果 两位点各群体基因型频率分布均符合Hardy-Weinberg平衡，每一位点等位基因频率分布在各群体间无显著差异；通过对10个汉族家系的遗传模式分析，证实了两位点等位基因传递遵循孟德尔遗传规律。结论 D4S1647、D6S2414基因座在中国汉族，蒙古族，藏族群体均具有高度遗传多态性。     

异丙酚对MPTP损伤的小鼠黑质多巴胺神经元的保护作用

目的　观察异丙酚对 1 甲基 4 苯基 1,2 ,3 ,6 四氢吡啶 (1 methyl 4 phenyl 1,2 ,3 ,6 tetrahydropyridineMPTP)损伤的小鼠纹状体多巴胺神经元的影响以及可能的作用机制。方法　给予Propofol 10 0mg/ (kg·d)后注射MPTP 2 0mg/ (kg·d) ,用药 6d。 12d后分离纹状体应用高效液相 -电化学方法检测纹状体多巴胺、二羟基苯乙酸及高香草酸的含量水平 ,应用12 5I- β-CIT放射性配基和免疫组化的方法检测多巴胺转运蛋白的活性和黑质神经元的损伤情况。结果　异丙酚可增加MPTP模型鼠多巴胺及其代谢产物的含量 ,异丙酚处理组DA ,DOPAC ,HVA的含量分别为 (8.2 417± 1.692 ) μg/ g、(1.3 81± 0 .486) μg/g和 (1.63 3 9± 0 .5 73 ) μg/ g ,与MPTP损伤组比较 ,明显增加。异丙酚亦可抑制黑质酪氨酸羟化酶 (TH)阳性神经元的减少。MPTP组注射MPTP 6d后 ,纹状体DAT为 (5 .3 13± 0 .64 2 )与正常组 (6.992± 0 .5 48) μg/ g比较显著下降 (P <0 .0 1) ,P +M组纹状体DAT为 (6.5 65± 0 .40 5 ) ,明显高于MPTP组 (P <0 .0 1) ,即减轻纹状体内多巴胺转运蛋白密度下降。结论　异丙酚对MPTP损伤的DA神经元具有一定的保护作用 ,其保护作用可能与抑制多巴胺转运蛋白活性有关     

潮汕地区健康青年H9、H6、H5亚型甲型流感病毒血清抗体调查

目的：调查潮汕地区健康青年中H9、H6、H5三种甲型流感病毒亚型的隐性感染情况，以期了解上述三种禽类甲型流感病毒亚型是否能够或已经从禽类直接或间接传染给人。方法：潮汕地区健康青年血清946份，通过HI实验进行抗体检测。结果：H9亚型抗体阳性率达37．2％；同时发现有三份血清存在H5抗体；未见H6亚型抗体的存在。结论：H9亚型在健康青年中的隐性感染率非常高；H5亚型抗体的存在也应值得注意。     

利培酮治疗与细胞色素P4502D6/C188T酶基因多态性的关联分析

目的　研究利培酮临床效应的个体差异与其代谢酶细胞色素P4 5 0 2D6 (cytochromeP4 5 02D6 ,CYP2D6 )酶基因多态性的相关性。方法　对 88例符合CCMD 3精神分裂症诊断标准的患者和 96例健康对照者作病例 -对照分析。精神分裂症患者给予利培酮治疗 8周 ,用阳性和阴性症状量表 (posi tiveandnegativesymptomscale ,PANSS)评分评价利培酮疗效。采用聚合酶链反应扩增及限制性片段长度多态性 (PCR RFLP)技术对CYP2D6exonⅠ的C188T位点突变进行检测 ,分析利培酮临床效应与其主要代谢酶CYP2D6 /C188T酶基因多态性的相关性。结果　中国上海地区人群的CYP2D6 /C188T突变率(弱代谢型 )为 36 .3% ,病例组和正常对照组间基因型频率总体分布比较无显著差异 (χ2 =1.15 ,df=2 ,P >0 .0 5 ) ,两组间的等位基因频率之间比较也无显著性差异 (χ2 =0 .78,df=1,P >0 .0 5 )。进行性别及有否家族史分组后分析 ,亦无差异存在 ,且CYP2D6 /C188T突变与利培酮临床效应之间并无相关性 (χ2 =1.12 ,df=2 ;χ2 =0 .0 3,df=1,P >0 .0 5 )。结论　未发现中国人CYP2D6 /C188T多态性与利培酮临床效应的个体差异有相关性。     

钙调素拮抗剂E6对大鼠脑一氧化氮合酶活性和突触体谷氨酸释放的影响

目的 探讨钙调素拮抗剂E6的抗脑缺血作用机制。方法 用[3H]-L-Glu（glutamic　acid,Glu）标记大鼠脑突触体,测定突触体的Gln释放量和用一氧化氮合酶（nitric oxide synthase,NOS）试剂盒测定成年大鼠脑匀浆上清中NOS活性。结果　E6促进Glu释放（与对照组比,10-5mol·L-1组增加81.0％）,但对KCl（50 mmol·L-1）引起的Glu释放有抑制作用,10-5mol·L-1E6的抑制率为23.2％。E6浓度依赖性地抑制NOS活性。钙调素（calmodulin,CaM）（30μg·ml-1）可逆转E6的抑制作用（10-6mol·L-1E6的抑制率为13.7％）,N-硝基-精氨酸（（N-nitro-arginine,L-NNA）（10μmol·L-1）可加强E6的抑命作用（10-6mol·L-1的抑制率为76.5％）。结论 E6是与CaM结合后发挥抑制 NOS活性效应的,E6对Glu 释放的影响可能与其对NOS活性及其对神经细胞内Ca2+影响有关。     

病毒性心肌炎患者血清IL-6的检测及其临床意义

为了观察病毒性心肌炎患者血清 IL-6的水平变化 ,我们对 1 8例病毒性心肌炎患者血清 IL -6水平进行了检测 ,并与正常对照组进行比较 ,现报告如下。对象与方法1　对　象　健康对照组 48例 ,男 2 5例 ,女2 3例 ,年龄 2 5～ 58岁 ,平均年龄 44 .0 5± 1 1 .76岁。病毒性心肌炎组 1 8例 ,男 7例 ,女 1 1例 ,年龄1 8～ 45岁 ,平均年龄 3 9.4± 8.56岁。按 1 995年全国心肌炎、心肌病专题会议诊断参考标准入选 ,排除急、慢性肝病 ,其中急性心肌炎 1 5例 ,慢性心肌炎 3例。2　方　法　正常对照组、心肌炎组均空腹抽静脉血 3 ml,分离血清后置于 -2…     

白花前胡甲素对心肌缺血再灌注大鼠血清IL-6水平的影响

目的　探讨白花前胡甲素 (Pd Ia)抗缺血再灌注损伤的机制 ,为寻找高效、低毒及安全的防治缺血再灌注损伤的药物提供理论基础。方法　采用放射免疫分析测定血清IL— 6水平 ,并通过常规HE染色比较中性粒细胞等炎性细胞的心肌浸润情况。结果　Pd Ia低、中、高三个剂量组IL— 6水平分别由对照组的 (15 2 88±15 2 5 ) pg/ml降至 (12 8 45± 18 37)pg/ml、 (119 6 6± 15 72 ) pg/ml和 (116 13± 10 45 )pg/ml (P <0 0 1) ,其作用强度与硝苯地平相近 (12 3 5 5± 18 6 2 )pg/ml。 结论　Pd Ia明显抑制缺血再灌注大鼠血清IL— 6水平 ,提示Pd Ia可能通过抑制NF—kB途径实现再灌注性损伤的防治     

Interactions Between Cytomegalovirus, Human Herpesvirus-6, and the Recurrence of Hepatitis C After Liver Transplantation

Recurrence of hepatitis C (HCV) following liver transplantation is common. Herpesvirus reactivation following transplant may have an immunomodulatory effect resulting in increased HCV replication. We studied whether cytomegalovirus (CMV) and human herpesvirus-6 (HHV-6) may be associated with HCV recurrence and viral load after transplant. We prospectively followed 66 HCV liver-transplant recipients with serial viral load testing for CMV and HHV-6. Infection and viral load were correlated with the development of biopsy-proven HCV recurrence and HCV viral loads. Histologic recurrence of HCV occurred in 41/66 (62.1%) patients. In the primary analysis, CMV infection and disease, and HHV-6 infection were not associated with HCV recurrence. Peak CMV and HHV-6 viral loads were not significantly different in patients with and without recurrence. No correlation was observed between HCV viral loads at 1 and 3 months post-transplant and peak HHV-6 or CMV viral loads. In a subgroup analysis, HHV-6 infection was associated with the development of more severe recurrence (hepatitis and/or fibrosis score > or = 2) (p = 0.01). Also, fibrosis scores at last follow up were higher in patients with CMV disease (1.67 vs. 0.56; p = 0.016) and in patients with HHV-6 infection (1.18 vs. 0.55; p = 0.031). In conclusion, HHV-6 and CMV infection and viral load were not associated with increased overall rates of HCV recurrence or HCV viral load after liver transplantation but may be associated with more severe forms of recurrence.     

脑胶质瘤白细胞介素-6自分泌或旁分泌环路的研究

目的　研究白细胞介素 6(IL 6) /IL 6受体 (IL 6R)自分泌或旁分泌环路与脑胶质瘤的关系。方法　采用逆转录 聚合酶链反应 (RT PCR)方法检测IL 6和IL 6R基因在 4株脑胶质瘤细胞株、62例脑胶质瘤组织标本、5例良性脑膜瘤组织和 5例人正常脑胶质细胞中的表达 ;将IL 6单抗 (McAb)或IL 6RMcAb与脑胶质瘤细胞共同孵育 ,四甲基偶氮唑蓝 (MTT)比色法检测对细胞生长的抑制作用。结果　脑胶质瘤细胞株C6、9L、U 2 5 1和SHG44均有IL 6和IL 6R的表达 ,脑胶质瘤组织标本中 47例 (75 .81% )表达IL 6、5 2例 (83 .87% )表达IL 6R、41例 (66.13 % )同时表达IL 6和IL 6R ;良性脑膜瘤组织 4例表达IL 6,人脑正常胶质细胞仅有IL 6弱表达 ,两者均无IL 6R表达。IL 6McAb和IL 6RMcAb能够显著抑制脑胶质瘤细胞的增殖 ,并存在剂量依赖关系(P <0 .0 1)。结论　脑胶质瘤很可能存在IL 6/IL 6R自分泌或旁分泌环路 ,阻断此环路可以明显抑制胶质瘤细胞的恶性增殖