葛根素对血管内皮剥脱术后Ⅰ型胶原增生的影响

为研究血管内皮剥脱术后血清Ⅰ型前胶原羧基端肽（PIP）浓度的变化及葛根素对其影响，将18只Wistar大鼠随机分为3组（均为6只）：内皮剥脱（BD）组，内皮剥脱加葛根素（BDP）组和假手术（SO）组。以大鼠胸主动脉球囊内皮剥脱法建立血管内皮剥脱模型。放射免疫分析测定血清PIP浓度。结果：术后2周和4周时BD组血清PIP浓度显著高于SO组（P＜0．01）；BDP组血清PIP浓度明显低于BD组（P＜0．01）。提示：血管内皮剥脱可致体内Ⅰ型胶原合成增加，葛根素对其具有抑制作用。     

葛根素对糖尿病大鼠心功能及心肌细胞内钙离子的影响

目的探讨葛根素对糖尿病大鼠心功能及心肌细胞内钙离子的影响。方法 40只SD大鼠随机分成空白对照组、糖尿病模型组、葛根素低剂量组和葛根素高剂量组,每组10只。测定大鼠心脏功能、心室重量指数、心脏重量指数和心肌细胞内钙离子瞬间变化。结果与糖尿病模型组比较,葛根素低剂量组和葛根素高剂量组心脏功能明显改善,心室重量指数、心脏重量指数及钙瞬变峰幅度下降,钙瞬变时程缩短,且高剂量组改善更加明显。结论葛根素可以改善糖尿病大鼠心功能、心室重量指数和心脏重量指数,其机制可能与调节心肌细胞内钙离子水平有关。     

葛根素对大鼠心肌细胞离子通道的影响

目的：探讨葛根素对大鼠心肌细胞离子通道的影响及其抗心律失常的电生理学机制．方法：采用Langendoff胶原酶灌注加浸泡法分离大鼠心室肌细胞，据不同细胞外灌流液将实验分5组：对照组；葛根素1．2，2．4，4．8和9．6mmol／L组．分别用膜片钳全细胞记录各组内向整流钾通道（Ikl）、瞬时外向钾通道（Ito）的电流．结果：在500ms去极化的实验条件下，葛根素使不同去极化水平时的Ikl瞬间电流及稳态电流均明显下降．随着药物剂量的增加，这种抑制作用也增强．结论：葛根素对大鼠心肌细胞离子通道的作用主要是抑制Ikl且抑制呈浓度依赖性．     

钙拮抗剂对大鼠肝硬化模型门脉高压的实验研究

本文旨在观察细胞膜和细胞内钙拮抗剂单独与联合使用对正常大鼠和肝硬化门脉高压大鼠门脉压力的影响。实验分两部分进行：（一）钙拮抗剂对钙离子诱导大鼠门脉压力升高的影响；（二）钙拮抗剂预防及阻止鼠肝硬化门脉高压症的研究。结果表明，硫氮酮（ＤＩＬ）能有效地预防ＣＣｌ４诱发的鼠肝硬化门脉高压；联合使用尼卡地平（ＮＩＣ）和ＤＩＬ可有效地降低肝硬化门脉高压和抑制钙离子所引起的门脉压升高，与二者单独使用差异有非常显著性统计学。     

雌激素对血管平滑肌细胞内游离钙的调节作用

目的：动态观察雌二醇（Ｅ２）对单个血管平滑肌细胞内游离钙离子浓度及血管紧张素Ⅱ引致的细胞内钙离子浓度变化的影响，以探讨雌激素对平滑肌细胞内储存钙释放的调节作用。方法：体外培养健康雌性兔胸主动脉中层平滑肌，细胞接种在５７０型粘附式细胞仪专用的培养皿中，加入１０－５、１０－７、１０－９ｍｏｌ／Ｌ３种不同浓度的Ｅ２处理。另用３种不同浓度的Ｅ２预处理细胞１小时后，加入血管紧张素Ⅱ。实验分单纯血管紧张素Ⅱ处理组和血管紧张素Ⅱ＋不同浓度Ｅ２预处理组，用ｆｕｒａ－３法测定细胞内钙离子浓度。结果：３种浓度Ｅ２对平滑肌细胞内游离钙离子浓度的基础水平无影响，但１０－５、１０－７ｍｏｌ／Ｌ的Ｅ２预处理细胞后血管紧张素Ⅱ未能激发细胞内游离钙离子浓度升高。结论：雌激素可能参与血管紧张素Ⅱ诱导的血管平滑肌细胞内钙离子浓度变化的调节     

5种黄酮醇类化合物对大鼠心肌细胞内钙离子的影响

目的研究山萘酚（Kaempferol，KA）、杨梅素（Myricetin，MY）、二氢杨梅素（Dihydromyricetin，DMY）、槲皮素（Quercetin，Qu）、二氢槲皮素（Dihydroquercetin，DQU）5种黄酮醇类化合物对大鼠心肌细胞内游离钙离子（[Ca^2＋]i）的影响。方法采用Fluo-3／AM同时加入PluronicF-127作为细胞内游离钙离子的荧光探针，负载H9C2心肌细胞系，应用激光扫描共聚焦显微技术，测定5种黄酮醇类化合物（50μmol／L）在静息状态和加入60mmol／L氯化钾（KCl）时心肌细胞胞浆内游离钙离子的荧光强度（FI）。结果静息状态下，KA和Qu能够明显降低心肌细胞内[Ca^2＋]i（P〈0．05），MY能够短暂而明显升高[Ca^2＋]i（P〈0．05），而DMY和DQU对心肌细胞内[Ca2＋li无明显影响（P〉0．05）；KA、MY、DMY、Qu和DQU对KCl介导的高钙有抑制作用（P〈0．05）。结论5种黄酮醇类化合物对电压依赖性钙通道（VDC）有明显抑制作用，这可能是产生药理活性机制之一．有利于进一步研究其对心肌的保护作用和探讨其构效关系。     

骨髓间质干细胞心肌分化过程中细胞内钙离子浓度的变化

目的研究骨髓间质干细胞心肌分化前、后钙离子浓度变化。方法用5-杂氮胞苷(5-azacytidine)体外诱导猪骨髓间质干细胞使之向心肌分化；ELASA法测定分化前、后细胞内心肌肌钙蛋白Ⅰ(cTnⅠ)变化；应用离子图像分析系统测定分化前、后细胞内钙离子浓度变化。结果(1)经5-杂氮胞苷诱导后细胞形态发生变化；(2)诱导后第3周起细胞内cTnⅠ明显增高；(3)诱导组细胞内钙离子浓度较对照组高，且诱导前后细胞内钙释放机制不同。结论骨髓间质干细胞体外经5-杂氮胞苷诱导后可具有心肌细胞的某些特性，这一过程与钙信号有关。     

纳洛酮对缺血再灌注海马细胞线粒体功能保护作用的研究

目的观察缺血再灌注期间海马细胞内游离钙离子、线粒体膜电位的变化以及纳洛酮对细胞的保护作用。方法20只新西兰大白兔随机分成4组对照组、缺血组、再灌注组、纳洛酮组,每组5只,然后以荧光染色流式细胞仪检测各实验组海马细胞内游离钙离子浓度和线粒体膜电位的变化。结果缺血组、再灌注组海马细胞内游离钙离子浓度显著高于对照组和纳洛酮组;其线粒体膜电位则低于对照组和纳洛酮组;再灌注组游离钙离子浓度明显高于缺血组;其线粒体膜电位则低于缺血组;对照组与纳洛酮组间各指标无显著差异。结论纳洛酮对缺血再灌注引起的海马细胞内钙离子浓度升高有抑制作用,对线粒体膜电位下降有一定的保护作用。     

玉郎伞多糖对Aβ25-35所致PC12细胞损伤细胞内钙离子浓度的影响

目的观察Aβ25-35诱导PC12细胞凋亡损伤模型胞内钙浓度的变化及YLSP的影响。方法采用Aβ25-35诱导PC12细胞凋亡损伤模型,石杉碱甲作为对照药,给予YLSP预处理后,加入Flu-3/AM,用流式细胞仪（FCM）测定各组细胞的平均荧光强度。结果各组PC12细胞内钙离子含量存在显著性差异（F=14.051,P〈0.01）,其中,Aβ25-35作用PC12细胞后,PC12细胞内钙离子含量显著升高（P〈0.01）,经YLSP处理后,PC12细胞内钙离子含量较模型组细胞显著降低（P〈0.01）,其中,YLSP高剂量组的PC12细胞内钙离子含量显著低于石杉碱甲组（P〈0.01）。结论 YLSP能对抗Aβ引起的细胞内钙离子浓度升高,防止钙超载的发生。     

细胞内活性氧在甲基乙二醛促人腹膜间皮细胞分泌血管内皮生长因子中的作用

目的：观察葡萄糖降解产物甲基乙二醛（MGO）对人腹膜间皮细胞（HPMC）分泌血管内皮生长因子（VEGF）的影响及细胞内活性氧（ROS）在其中的作用。方法：分别用不同浓度的MGO及抗氧化剂N-酰-L-半胱氨酸（NAC）作用于细胞，用RT-PCR和ELISA方法测定HPMC中VEGF的表达；再以氧化敏感的荧光染料2、7-二氢二氯荧光素（DCFH）染色，流式细胞仪测定细胞内ROS强度。结果：MGO能使细胞内ROS水平明显升高，呈浓度依赖效应；MGO同时以时效和量效方式促进HPMC中VEGF的表达；而NAC能够明显抑制MGO导致的细胞内ROS升高，同时抑制HPMC中VEGF的分泌。结论：MGO可能部分通过诱导细胞内ROS，促进HPMC表达VEGF，从而引起腹膜新生血管的增加，最终导致腹膜失超滤现象。     

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.     

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.     

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.     

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。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

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.     

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.