Selective proteasomal dysfunction in the hippocampal CA1 region after transient forebrain ischemia.

Delayed neuronal death in the hippocampal CA1 region after transient forebrain ischemia may share its underlying mechanism with neurodegeneration and other modes of neuronal death. The precise mechanism, however, remains unknown. In the postischemic hippocampus, conjugated ubiquitin accumulates and free ubiquitin is depleted, suggesting impaired proteasome function. The authors measured regional proteasome activity after transient forebrain ischemia in male Mongolian gerbils. At 30 minutes after ischemia, proteasome activity was 40% of normal in the frontal cortex and hippocampus. After 2 hours of reperfusion, it had returned to normal levels in the frontal cortex, CA3 region, and dentate gyrus, but remained low for up to 48 hours in the CA1 region. Thus, the 26S proteasome was globally impaired in the forebrain during transient ischemia and failed to recover only in the CA1 region after reperfusion. The authors also measured 20S and 26S proteasome activities directly after decapitation ischemia (at 5 and 20 minutes) by fractionating the extracts with glycerol gradient centrifugation. Without adenosine triphosphate (ATP), only 20S proteasome activity was detected in extracts from both the hippocampus and frontal cortex. When the extracts were incubated with ATP in an ATP-regenerating system, 26S proteasome activity recovered almost fully in the frontal cortex but only partially in the hippocampus. Thus, after transient forebrain ischemia, ATP-dependent reassociation of the 20S catalytic and PA700 regulatory subunits to form the active 26S proteasome is severely and specifically impaired in the hippocampus. The irreversible loss of proteasome function underlies the delayed neuronal death induced by transient forebrain ischemia in the hippocampal CA1 region.     

Population differences in the pattern of familial aggregation for sex hormone‐binding globulin and its response to exercise training: The HERITAGE family study

Familial influences were investigated for baseline sex hormone‐binding globulin (SHBG) and its response (post‐training minus baseline) to a 20‐week endurance exercise training program. One hundred, eighty‐four participants from 85 Black families in the HERITAGE Family Study (HERITAGE) were analyzed using a familial correlation model. Baseline SHBG values and the training response were adjusted for the effects of age, baseline BMI, testosterone, estradiol, and fasting insulin levels (plus baseline SHBG values for the training response) within four sex‐by‐generation groups prior to genetic analysis. Baseline SHBG levels were influenced by appreciable familial effects (maximum heritability h² = 54%) with neither spouse resemblance nor sex and generation differences in the correlations. This estimate is only slightly, but not significantly, smaller than the heritability of 64% reported previously in 428 participants from 99 White families in HERITAGE. In contrast to the modest familial effects for the training response in White participants in HERITAGE (h² = 25%), there were no evidence of familial resemblance in Blacks in the current study. Furthermore, there was heterogeneity for both baseline SHBG and the training response between Blacks and Whites in the pattern of familial aggregation. In conclusion, baseline SHBG levels are influenced by significant familial effects in both Blacks and Whites, independent of the effects of age, sex, and baseline values of BMI, testosterone, estradiol, and fasting insulin levels. Whereas modest familial effects were detected for the training response in Whites, the lack of similar effects in Blacks may be due to the smaller sample size. Am. J. Hum. Biol. 13:832–837, 2001. © 2001 Wiley‐Liss, Inc.     

合并各类危险因素的2型糖尿病患者冠状动脉病变影像学特征

背景随着 2型糖尿病患病率的上升,人们应重视其心血管并发症的早期干预,以降低其并发症的发病率. 目的观察 2型糖尿病合并冠心病危险因素及冠状动脉造影情况. 设计以患者为研究对象,横断面的观察对比研究. 单位一所市级医院的内科病房. 对象实验于 1998- 05/2003- 05在哈尔滨市第一医院内分泌科完成.纳入标准符合 1997年 ADA确定的糖尿病诊断标准及 1979年 WHO制定的<缺血性心脏病的命名和诊断标准>的大于 30岁的 2型糖尿病合并冠心病患者;排除标准患有严重心、肝、肾疾病及严重的感染,风湿性心脏病、肺源性心脏病者. 98例住院患者符合上述纳入标准,设为糖尿病组,男 56 例,女 42例,年龄为 35～ 70岁.对照组为同期住院的非糖尿病冠心病患者 85例,男 53 例,女 32例,年龄为 40～ 75岁. 方法观察血糖(葡萄糖氧化酶法)、空腹胰岛素和 C肽(放免法)、糖化血红蛋白(亲和层析微柱法)血清三酰甘油、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇(全自动生化仪)及应用 JUDKINS方法行选择性左右冠状动脉造影. 主要观察指标① 2组冠状动脉造影结果比较;②糖尿病病程与冠状动脉病变支数关系的比较. 结果 2组冠状动脉造影结果比较 ,糖尿病组的左主干病变、回旋支病变者与对照组相比,差异无显著性意义( P >0.05);而前降支和右冠状动脉的病变者糖尿病组多于对照组( P< 0.05),并且糖尿病组的病变表现为 3支病变和单支病变为主,呈现为弥漫性改变. 2型糖尿病患者的冠状动脉病变多数是 3支血管病变,其病变弥漫,且随病程越长,越易发生多支血管病变. 结论 2型糖尿病患者随着病程的延长,冠心病的发生逐渐增多,且病变范围广,病情较严重.     

免疫胶体金标记电镜技术及其在病毒形态学研究中的应用

根据免疫胶体金电镜技术(IGEM),以不同方法制备了几种不同大小的胶体金颗粒,经SPA包被后对EHFV感染的Vero E-6细胞、轮状病毒感染的Ma 104细胞和CMV感染的人胚肺细胞分别进行免疫胶体金细胞表面标记、细胞穿透标记和超薄切片标记实验,并着重讨论了IGEM的优越性,适用范围和存在的问题。     

曲伏前列腺素对培养人眼睫状肌细胞基质金属蛋白酶-2表达的影响

【目的】研究曲伏前列腺素作用下,基质金属蛋白酶-2（MMP-2）在人睫状肌细胞的表达。【方法】在人睫状肌细胞无牛血清培养基中加入1μmol/L曲伏前列腺素（travoprost）,根据曲伏前列腺素孵育时间的不同,分为4个时间组,即0 h组（对照组）、6 h、12 h、24 h组。Real-time PCR和ELISA法分别检测上述各时间组人睫状肌细胞MMP-2在基因和蛋白水平的表达,每种方法分别重复做3次。Zymography技术分别检测4组细胞MMP-2的活性,重复4次。【结果】设定对照组mRNA相对表达量为1做作标准,6 h、12 h、24 h组MMP-2 mRNA相对表达量为0.58±0.04、1.20±0.05、1.95±0.11,MMP-2 mRNA表达呈逐渐升高趋势（P=0.000）;ELISA检测MMP-2的A值分别为0.0503±0.0021、0.0627±0.0017、0.0673±0.0025、0.0783±0.0039,MMP-2的表达随travoprost作用时间延长逐渐升高（P=0.000）。Zymography技术检测MMP-2校正光密度值分别为10±5,52±7,104±21,237±40;MMP-2活性随travoprost作用时间延长而逐渐增强（P=0.000）。【结论】曲伏前列腺素作用于人睫状肌细胞后,MMP-2表达随药物作用时间延长逐渐增加,活性逐渐增强。     

肩胛舌骨肌上颈清扫术在临床N0口腔癌治疗中的应用

目的探讨肩胛舌骨肌上颈清扫术在口腔癌治疗中的应用价值。方法对27例临床N0(T1~3)口腔鳞状细胞癌患者行肩胛舌骨肌上颈清扫,清扫范围为第Ⅰ、Ⅱ、Ⅲ区淋巴结。记录颈清扫手术时间、术后淋巴结病理检查结果、术后肩功能及随访结果。结果手术时间平均(x±s)为(16±02)h。术后病理检查证实5例出现颈淋巴转移(19%),转移发生于第Ⅰ区2例(7%)、第Ⅱ区4例(15%),其中1例同时存在第Ⅰ、Ⅱ区转移。肩功能在术后3个月内基本恢复。术后随访2~4年,随访率100%,未见原发灶复发及颈淋巴转移。结论肩胛舌骨肌上颈清扫术是临床颈部N0口腔癌的合适术式,它既能达到治疗目的,又能最大程度地保留肩颈部外形与功能。     

天麻素注射液的稳定性研究

作者用化学动力学方法测得天麻素注射液的水解反应速度与天麻素浓度的一次方成正比,属假一级反应;测得天麻素水解反应的活化能:pH≤2.5的酸性介质中E_a=29.54±0.55kcal·mol~(-1),pH≥10.5的碱性介质中E_a=14.79±1.74kcal·mol~(-1);天麻素注射液稳定的pH值约为6.8,稳定的pH范围为5.5～7.5。     

Gold(III) porphyrin complex is more potent than cisplatin in inhibiting growth of nasopharyngeal carcinoma in vitro and in vivo

Nasopharyngeal carcinoma (NPC) is a common neoplasm in Southeastern Asia, and cisplatin‐containing regimens for combinational chemotherapy are widely used for treating locally recurrent or metastatic diseases. However, resistance to cisplatin is not infrequently seen and its associated side effects may be life‐threatening. In this report, another metallo‐pharmaceutical agent gold(III) porphyrin complex [Au(TPP)]Cl was investigated in comparison to cisplatin for its in vitro and in vivo anticancer effects. Through induction of the intrinsic apoptosis pathway, [Au(TPP)]Cl exhibited 100‐fold higher potency than cisplatin in killing NPC cells, including cisplatin‐sensitive and cisplatin‐resistant variants, and also an variant harboring the Epstein‐Barr virus. In addition, a safety concentration window was demonstrated, allowing [Au(TPP)]Cl to kill tumors with minimal cytotoxicity to noncancerous cells. More importantly, weekly intraperitoneal injection of 3 mg/kg [Au(TPP)]Cl was more effective than the same dose of cisplatin in inducing tumor apoptosis in vivo and remarkably inhibited tumor growth in animals without any noticeable side effect. [Au(TPP)]Cl therefore is a promising chemotherapeutic agent that deserves further development as a novel drug for the treatment of advanced NPC, in particular, for cases with cisplatin‐resistance. © 2008 Wiley‐Liss, Inc.     

“三管一孔一脏器”显露在预防腹腔镜胆囊切除术胆管损伤的价值

目的研究胆囊各种病理形态、胆囊动脉变异和胆囊管变异情况下，腹腔镜胆囊切除术（ＬＣ）胆管损伤防治预案．方法ＬＣ患者１０６５例，急诊ＬＣ２０７例，择期ＬＣ８５８例，在全麻、ＣＯ２气腹状态下，采用经Ｃａｌｏｔ’ｓ三角后侧径路方法，显露“三管一孔一脏器”（ＴＯＯ）作为胆囊切除术的安全标志．结果“ＴＯＯ”显露１０２１例，占９５８６％，未显露４４例，占４１４％．胆囊动脉变异１４０例，胆囊管变异１５２例，均经ＬＣ顺利完成．全组无胆管损伤等并发症和死亡．结论“三管一孔一脏器”显露在ＬＣ预防胆管损伤起着重要作用．