Evidence for nitric oxide participation in down-regulation of CYP2B1/2 gene expression at the pretranslational level

Septic or inflammatory stimuli suppress drug metabolism by cytochrome P-450 in the liver, presumably at the pretranslational level. We have shown previously that nitric oxide is responsible at least in part for the inhibition by bacterial lipopolysaccharide of phenobarbital-induced CYP2B1/2 activity in vivo. This was attributed to the interaction of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report that endogeneous nitric oxide also contributes to LPS-induced suppression of CYP2B1/2 in vivo by down-regulating the expression of CYP2B1/2 protein and mRNA.     

健康人血清叶酸和维生素B_(12)水平的测定

本文对14岁以下健康小儿171名,成人30名及初生儿脐带血30份进行了血清叶酸和维生素B_(12)含量测定,171名小儿于采血前均经补足叶酸和维生素B_(12)。结果:血清叶酸(nmol/L)的正常值低限,<4岁者为6.1,4～14岁为8.4,成人为5.0;血清维生素B_(12)(pmol/L)的正常值低限,<1岁为459,1岁～成人为107。     

核因子-κB与创伤的关系及其在法医病理学中的应用

损伤时间推断是法医病理学的一个研究热点和难点。核因子-κB(NF-κB)是一种核转录调节蛋白,参与多种炎性介质的转录和调控。近年来研究发现NF-κB与机体创伤后的反应密切相关,其在损伤后的时序性表达可望在法医病理学用于损伤时间推断。     

氯胺酮对脂多糖诱导下人脐静脉内皮细胞活化的影响

目的 观察氯胺酮和N-甲基-D-天门冬氨酸(NMDA)受体非竞争性拮抗剂MK-801对脂多糖(LPS)刺激下人脐静脉内皮细胞(HUVECs)胞间粘附分子-1(ICAM-1)表达及核因子-kappa B(NF-kB)易位表达的影响。方法 采用Jaffe方法培养的HUVECs随机分为10组:对照组(C组,RPMI-1640),LPS组(L组,LPS1μg/ml),氯胺酮组(K组,依浓度不同分为KⅠ、KⅡ、KⅢ、KⅣ亚组,即氯胺酮12.5、25.0、100、300μmol/L LPS1μg/ml),MK-801组(M组,依浓度不同分为MⅠ、MⅡ、MⅢ、MⅣ亚组,即MK-801 1.25、2.50、10、30μmol/L LPS1μg/ml)。在37℃、5％CO_2中孵育18h后,用流式细胞仪检测ICAM-1的表达阳性率。NF-kB易位表达的测定分组处理同上,在LPS1μg/ml刺激2h后,用免疫组化(SP)方法测定内皮细胞中NF-kB p65亚基的表达。结果 KⅡ、KⅢ、KⅣ亚组可抑制LPS作用下HUVECs表面ICAM-1的表达和细胞内部NF-kB的易位表达(P<0.05),且两者的变化呈正相关(r=0.985,P<0.01)。M组各亚组对LPS作用后HUVECs表面ICAM-1的表达和NF-kB的易位表达无明显影响(P>0.05)。结论 氯胺酮对炎症反应中内皮细胞的活化具有抑制作用,但并非通过NMDA受体途径。     

慢性肾功能衰竭病人高同型半胱氨酸血症及其影响因素

目的 :研究慢性肾衰 (CRF)病人血浆同型半胱氨酸 (Hcy)水平及其影响因素。方法 :采用荧光偏振免疫分析法测定 16 0例CRF病人血浆总同型半胱氨酸 (tHcy)水平 ,同时用离子夺获分析法和微离子酶免疫分析法分别检测血浆叶酸(FA)和维生素B12 (VB12 )浓度。结果 :CRF病人血浆tHcy水平 (2 2 6 9± 12 16 ) μmol/ )明显高于正常对照组 (7 97±2 6 5 ) μmol/L ,CRF病人高同型半胱氨酸血症的发生率为 82 5 0 % ,其中血液透析组血浆tHcy水平 (2 4 13± 12 6 8μmol/L ,n =73)明显高于持续性非卧床腹膜透析 (CAPD)组 (16 4 3± 5 5 8μmol/L ,n =19)和非透析治疗组 (19 79± 10 5 7)μmol/L ,(n =6 8) ,但血浆FA和VB12 与正常对照组均无明显差别 (P >0 0 5 )。CRF病人血浆tHcy水平与血浆FA浓度均呈负相关关系 ,未经透析的CRF病人血浆tHcy水平与内生肌酐清除率和血浆FA水平呈负相关 ;透析治疗组血浆tHcy水平与血浆FA浓度呈负相关。血透 4h使血浆tHcy下降约 4 0 0 % ,透析后 2 0h回复到透析前水平的 76 0 %～86 0 % ,但在采用血仿膜和聚砜膜透析的病人之间 ,血浆tHcy水平无明显差异。结论 :CRF病人普遍存在高同型半胱氨酸血症 ,但没有明显的FA和VB12 缺乏 ,CRF时肾脏损害削弱了对Hcy的代谢或清除能力 ,     

Optimized and combined T1 and B1 mapping technique for fast and accurate T1 quantification in contrast-enhanced abdominal MRI.

Fast T(1) mapping techniques are a valuable means of quantitatively assessing the distribution and dynamics of intravenously or orally applied paramagnetic contrast agents (CAs) by noninvasive imaging. In this study a fast T(1) mapping technique based on the variable flip angle (VFA) approach was optimized for accurate T(1) quantification in abdominal contrast-enhanced (CE) MRI. Optimization methods were developed to maximize the signal-to-noise ratio (SNR) and ensure effective RF and gradient spoiling, as well as a steady state, for a defined T(1) range of 100-800 ms and a limited acquisition time. We corrected B(1) field inhomogeneities by performing an additional measurement using an optimized fast B(1) mapping technique. High-precision in vitro and abdominal in vivo T(1) maps were successfully generated at a voxel size of 2.8 x 2.8 x 15 mm(3) and a temporal resolution of 2.3 s per T(1) map on 1.5T and 3T MRI systems. The application of the proposed fast T(1) mapping technique in abdominal CE-MRI enables noninvasive quantification of abdominal tissue perfusion and vascular permeability, and offers the possibility of quantitatively assessing dilution, distribution, and mixing processes of labeled solutions or drugs in the gastrointestinal tract.     

缺血性脑血管病患者血清基质金属蛋白酶水平及影响因素分析

目的 比较急性脑梗死、短暂脑缺血发作(TIA)和陈旧脑梗死患者血清基质金属蛋白酶-9(MMP-9)水平并分析其影响因素.方法 缺血性脑血管病患者136例,分为急性脑梗死组57例,TIA组22例,陈旧脑梗死组57例,进行神经功能评分及血压、血常规、血脂、血糖检查.依据ELISA法进行血MMP-9测定.结果 MMP-9水平分别为急性脑梗死患者(444.13±418.46)ng/ml,TIA患者(374.36±278.31)ng/ml,陈旧脑梗死患者(231.11±367.43)ng/ml.急性脑梗死和TIA患者血MMP-9水平明显高于陈旧脑梗死患者(P＜0.05).MMP-9水平与血白细胞水平(r=0.192,P=0.025)、低密度脂蛋白(r=0.261,P=0.002)、收缩压(r=0.232,P=0.006)呈正相关;与高密度脂蛋白(r=-0.219,P=0.011)和血糖(r=-0.254,P=0.003)呈负相关.MMP-9与收缩压(β=0.259,P=0.001)、血白细胞(β=0.209,P=0.008)、低密度脂蛋白(β=0.586,P=0.000)、胆固醇(β=-0.458,P=0.007)和血糖(β=-0.200,P=0.014)具有线性关系.结论 MMP-9水平在急性脑梗死及TIA时升高,收缩压、血白细胞和低密度脂蛋白均可能为其影响因素.     

湖南省乙肝病毒基因型分布及临床意义

目的 :研究湖南省乙肝病毒 (HBV)基因型分布及临床意义。方法 :选择湖南省HBVDNA阳性慢性乙肝病人共 185例 ,其中病毒携带者 (ASC) 4 2例 ,慢性轻、中度肝炎 (CH) 38例 ,重型肝炎 (FHF) 80例 (伴有肝硬化者 4 9例 ) ,肝细胞癌 (HCC) 2 5例 ,采用聚合酶链反应 限制性片段长度多态性 (PCR RFLP)方法检测HBV基因型。结果 :基因型B136例 (73.5 % ) ,基因型C 4 9例 (2 6 .5 % )。基因型B在FHF中占绝对优势 (83.7% ) ,其次为HCC(76 % ) ,与ASC(5 7.1% )比较 ,差异有显著性 (P <0 .0 1)。与基因型B相比 ,基因型C在垂直传播感染者中多见 (38.8%与 13.2 % ,P <0 .0 0 1) ;HBeAg阳性率明显增高 (5 7.1%与 30 .9% ,P <0 .0 0 1) ;抗HBe阳性率明显下降 (36 .9%与 6 6 .2 % ,P <0 .0 0 1)。与基因型C相比 ,基因型B感染者ALT水平明显增高 (2 6 4 .5± 2 5 6 .5与 10 0± 12 0 .6 ,P <0 .0 0 1)。结论 :湖南省存在乙肝病毒基因型B和基因型C ;基因型B为优势基因型并与肝脏疾病活动性相关 ,基因型C与母婴垂直传播感染有关     

Immunogenicity study of low-dose administration of hepatitis B virus vaccine in newborn infants: A cost reduction trial

Different doses of hepatitis B virus vaccine—prepared by Korea Green Cross Corporation, were given to healthy infants born to HBsAg-negative mothers at birth, 1 and 6 months of age. A dose of 2 μg was administered intradermally in Group A and, in the three other groups, the vaccine was given intramuscularly (i.m.). An adequate follow-up observation was possible for 9 months after birth in 22, 25, 23 and 21 infants in Groups A, B, C and D, respecvely.
Group C (5 μg, i.m.) produced seroconversion most rapidly, showing the highest rate (96%) at 9 months of age. The lowest seroconversion rate (5%) was found at the age of 1 month in Group A subjects, but the rate increased to 91% after a booster dose was given at 6 months of age.
While it can be concluded that a 5 μg i.m. dose of vaccine at 0, 1 and 6 months of age is optimum for the immunization of infants in efficacy and economy, a 2 μg intradermal dose can also be considered as an immunogenic and economical regimen, though the immune response is slower and a special technique is required for immunization.     

对拉米夫定耐药的慢性乙型肝炎病人治疗研究现状

核苷类似物拉米夫定于1998年在我国上市，为乙型肝炎的抗病毒治疗带来了新的希望。然而持续的拉米夫定治疗会使病人产生耐药从而导致严重后果。本文对这部分病人的抗病毒治疗进展进行综述。