糖尿病大鼠阴茎组织糖基化终产物含量的变化和糖基化终产物受体的表达情况

目的研究糖尿病阴茎组织糖基化终产物(AGEs)含量的变化和糖基化终产物受体(RAGE)的表达情况。方法用葡萄糖和血红蛋白(Hb)在体外孵育形成Hb-AGEs,免疫新西兰兔,制备AGEs抗血清,建立竞争性ELISA法,测定大鼠阴茎组织AGEs含量。应用RT-PCR研究RAGEmRNA表达。结果各组糖尿病大鼠未经治疗时阴茎组织AGEs水平均较对照(NC)组明显升高(P<0.01),8周时糖尿病用胰岛素治疗(DMI)组及糖尿病用胰岛素和二氨基酚嗪(DAP)治疗(DMID)组的AGEs水平较糖尿病未治疗(DM)组降低(P<0.05～0.01),至16周DMID组上述指标较DMI组明显降低(P<0.01)。RAGEmRNA在DM组大鼠阴茎组织的表达明显高于NC组(P<0.01)。结论糖尿病大鼠阴茎组织AGEs水平明显升高,RAGEmRNA高表达,胰岛素和DAP治疗可降低AGEs水平。     

温筋通对链脲佐菌素糖尿病大鼠坐骨神经糖化终产物受体mRNA表达的调节

目的：探讨中药复方温筋通对糖尿病大鼠坐骨神经糖化终产物(AGEs)受本（RAGE）mRNA表达的影响。方法：40只大鼠采用链脲佐菌素制备糖尿病大鼠模型。制模后将大鼠随分为模型组，氨基胍组，预防组和治疗组。预防组与治疗组分别在制模后不同时间给予温筋通灌胃。另选10只体重，鼠龄相匹配的大鼠作为正常对照组，采用逆转录聚酶链式反应（RT－PCR）检测病程12周各组大鼠坐骨神经RAGmRNA表达水平。结果：糖尿病大鼠坐骨神经RAGEmRNA表达较正常对照组增强（P＜0．01），温筋通预防组，治疗组及氨基胍预防组在鼠坐骨神经RAGEmRNA表达较糖尿病治疗组降低（P＜0．05－0．01）。结论：温筋通可能通过调节糖尿大鼠坐骨神经RAGEmRNA的异常表达，减轻AGEs对坐骨神经的损伤。     

吡格列酮减少链脲佐菌素诱导的糖尿病大鼠肾皮质糖基化终产物受体mRNA的表达

为探讨吡格列酮对链脲佐菌素诱导的糖尿病大鼠肾皮质糖基化终产物受体(RAGE)mRNA水平的影响,吡格列酮(20 mg·kg-1·d-1)灌胃8周后取肾皮质行RT-PCR半定量检测RAGE mRNA水平的变化,糖尿病吡格列酮治疗组、糖尿病对照组和正常对照组间RAGE表达差异有统计学意义(P＜0.01),结果表明吡格列酮能下调糖尿病大鼠肾皮质RAGE mRNA的表达,减轻高血糖和糖基化终产物对肾脏的损害.     

糖尿病大鼠局灶脑缺血AGEs及其受体的表达

目的 观察晚期糖基化终产物(Advanced glycation endproducts,AGEs)及其受体(Recepter of advanced glycation endproducts,RAGE)在糖尿病大鼠局灶脑缺血中的表达.方法 雄性Wistar大鼠50只,随机取25只应用链脲佐菌素(STZ)法制备DM模型后,正常组与DM组各取20只,应用线栓法制备局灶脑缺血模型即大脑中动脉阻塞(MCAO)模型.根据缺血不同时间又分为单纯缺血组(MCAO组)1、3、6、24 h组,DM局灶脑缺血组(DM+MCAO组)1、3、6、24 h组,每组5只.采用SP免疫组化检测AGEs、 RAGE在缺血不同时间脑组织中的表达.结果 正常对照组有较少AGEs和 RAGE表达,DM组及MCAO组表达增加,DM+MACO组明显增加,且在缺血1 h逐渐开始增加,6 h略有下降,24 h表达再次增加.结论 AGEs及 RAGE的表达参与了DM大鼠局灶脑缺血损伤.     

糖基化终产物受体介导高血压机械牵张力协同促进糖基化终产物激活小鼠血管平滑肌细胞ERK1/2加速血管重构

目的为证实糖基化终产物受体(RAGE)是否介导了机械牵张力和/或糖基化终产物(AGE)对小鼠主动脉血管平滑肌细胞(VSMC)的细胞外信号调节激酶(ERK1/2)的协同激活并加速血管重构。方法①正常血糖小鼠下腔静脉分别连接到正常血糖小鼠和STZ诱导的糖尿病小鼠右颈总动脉形成静脉桥,术后不同时间点(0、4、8周)收获移植静脉作常规切片HE染色,观察移植静脉在动脉压力作用下的血管构筑情况。②体外静息培养的血管平滑肌细胞分别给予机械牵张力和/或糖基化终产物刺激,用Western Blotting法检测细胞内ERK1/2磷酸化水平。③糖基化终产物受体基因沉默(siRNA-RAGE)或过表达(overexpression-RAGE)预处理VSMC后给予机械牵张力和/或糖基化终产物刺激,观察ERK1/2活性的变化。结果高血压(动脉压)可明显改变移植静脉的血管构筑,但移植到高血糖组的比正常血糖组的血管构筑改变更加明显(术后4周和术后8周高血糖组与正常血糖组移植血管厚度分别为73.99±4.45μm比49.67±11.62μm和117.06±17.62μm比88.97±15.78μm,P均<0.05)。机械牵张力和糖基化终产物...     

T细胞介导的小鼠免疫性肝纤维化形成过程中细胞因子mRNA表达水平

目的　研究刀豆蛋白A诱导下T细胞介导的小鼠免疫性肝纤维化模型形成过程中细胞因子mRNA表达水平的变化。方法　Balb/c小鼠随机分为正常对照组、模型组。模型组小鼠静脉注射刀豆蛋白A 15mg/kg ,每周 1次 ,共 2 0周 ,正常对照组给予等量生理盐水。于第 1、5、12和 2 0次注射后 2 4h分别处死 8只小鼠 ,取肝脏组织低温保存 ,常规苏木精 伊红染色、果莫里法 (Gomori)纤维染色及冰冻切片CD4 、CD8 T细胞染色。抽提小鼠肝脏组织总RNA ,RT PCR扩增肝组织IL 2、IL 4、IL 10、转化生长因子 (TGF) β1和 β 肌动蛋白 (β actin)的mRNA ,凝胶图像分析系统扫描扩增产物的灰度值 ,以 β actin作为内参照 ,计算细胞因子mRNA的相对表达量。 结果　模型组小鼠苏木精 伊红染色和Gomori染色提示实验中晚期发生肝纤维化 ,冰冻切片免疫组织化学染色提示肝组织内淋巴细胞浸润以CD4 细胞为主。IL 2mRNA水平仅在第 1次注射后上升 ,随后迅速降低 ;IL 4、IL 10和TGF β1mRNA表达水平则在模型形成过程中保持较高的表达水平。结论　反复刀豆蛋白A刺激可以诱导T淋巴细胞介导的小鼠免疫性肝纤维化模型的发生 ,IL 4、IL 10和TGF β1等细胞因子mRNA在模型形成过程中持续高水平表达 ,在模型的发病过程中起着重要作用。     

晚期糖基化终产物受体阻断剂FPS-ZM1减缓ApoE-/-小鼠动脉粥样硬化进展的作用

目的 研究晚期糖基化终产物受体(receptor for advanced glycation end products,RAGE)阻断剂FPS-ZM1对ApoE-/-小鼠高脂喂养后动脉粥样硬化(atherosclerosis,AS)进展的干预作用.方法 ApoE-/-小鼠随机分成对照组(普通喂养),AS模型组(高脂喂...     

当归四逆汤对大鼠DPN抑制作用及AGEs/RAGE的调节

目的观察当归四逆汤对糖尿病大鼠坐骨神经传导速度的影响及糖基化终末产物(AGEs)和AGEs受体(RAGE)的调节作用。方法采用链脲佐菌素(STZ)复制糖尿病大鼠模型,模型鼠随机分为中药组、西药组、模型组,另设健康鼠为正常组。分别干预8 w后,检测糖尿病大鼠坐骨神经传导速度、坐骨神经病理形态、AGEs含量、RAGE mRNA表达水平。结果与模型组相比,中药能够保护坐骨神经结构,显著降低AGEs含量、下调RAGE mRNA水平(P0. 05)。结论当归四逆汤能够通过下调AGEs/RAGE含量提高坐骨神经传导速度、保护坐骨神经结构,进而抑制大鼠糖尿病周围神经病变(DPN)的发生发展。     

补阳还五汤对阿尔茨海默病小鼠海马晚期糖基化终产物受体的影响

目的探讨补阳还五汤(BYHWD)对阿尔茨海默病(AD)小鼠海马晚期糖基化终产物受体(RAGE)的影响。方法选用30只APP/PS1转基因小鼠,随机分成模型组,治疗组(多奈哌齐0.001 g/kg),BYHWD高、中、低剂量组(BYHWD 37.06、18.53、9.26 g/kg),另选6只C57BL/16J小鼠分为对照组,各组连续治疗35 d后取材。采用酶联免疫吸附法(ELISA)测定海马APP、Aβ_(1 ~ 42)、Aβ_(1 ~ 40)和血清Aβ_(1 ~ 40)水平,采用HE染色和尼氏染色观察各组小鼠海马CA1区神经元组织形态病理改变,采用免疫组化检测海马RAGE表达,采用RT-PCR和Western印迹检测海马RAGE、VCAM和ICAM-1基因和蛋白表达。结果与模型组比较,BYHWD高、中剂量组可明显改善海马形态结构,明显降低海马APP、Aβ_(1 ~ 42)和Aβ_(1 ~ 40)水平,明显升高血清Aβ_(1 ~ 40)水平(P0.05),明显降低海马RAGE、VCAM和ICAM-1基因和蛋白表达(P0.05)。结论 BYHWD通过抑制RAGE表达来改善AD小鼠海马的形态结构。     

辛伐他汀抑制糖基化终产物诱导心肌微血管内皮细胞炎性反应及机制探讨

目的观察羟甲基戊二酰辅酶A还原酶抑制荆辛伐他汀对糖基化终产物(AGEs)诱导心肌微血管内皮细胞(CMECs)表达单核细胞趋化因子1(MCP-1)、细胞间黏附分子1(ICAM-1)的抑制作用,探讨辛伐他汀在早期糖尿病心肌微血管炎性病变中的保护机制。方法将培养的CMECs用辛伐他汀预孵育6 h,加入400mg/L的外源性糖基化牛血清白蛋白共培养72 h,分为AGEs组和BSA对照组,分别采用ELISA法测定McP-1的表达;流式细胞仪测定ICAM-1的表达;RT-PCR法测定糖基化终产物特异性受体mRNA的表达;Western blot法检测内皮细胞表面特异性受体(RAGE)蛋白表达。结果与BSA对照组比较,AGEs组MCP-1、ICAM-1、RAGE mRNA及其蛋白表达明显增强,差异有统计学意义(P<0.05)。辛伐他汀预孵则显著抑制AGEs诱导的MCP-1、ICAM-1的表达,并在mRNA及蛋白水平下调RAGE蛋白的表达。结论辛伐他汀可能通过抑制AGEs-RAGE信号途径来发挥对糖尿病心肌微血管病变的保护作用。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

Angiographic diagnosis of the degree of serosal invasion of carcinoma of the colon

Angiography using Prostaglandin El^® was performed on 38 patients with carcinoma of the colon in order to diagnose the degree of serosal cancer invasion. The findings at angiography were classified into four groups:1) AG-S3, abnormal change (irregularity and/or encasement) up to marginal vessels; 2) AG-S2, abnormality up to vasa recta; 3) AG-S1, abnormality of penetrating branches of vasa recta within the wall of the colon; and 4) AG-S0, no distinct findings of abovementioned vessels. These angiographic findings were compared with both macroscopic and microscopic serosal cancer invasion. Angiographic diagnosis is in accord with the macroscopic findings in 84.2 percent of cases. Angiographic diagnosis is in accord with the microscopic findings in 32.4 percent of cases. Macroscopic findings confirm the angiographic diagnosis precisely but the conflict with microscopic findings should not be overlooked. This may be the result of inflammatory change, adhesion, and fibrosis around carcinoma of the colon.     

Study of constancy of hydrogen-consuming flora of human colon

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H₂-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.Supported in part by the Department of Veterans Affairs and NIDDKD RO1 DK 13309-25.