乳果糖对大鼠非酒精性脂肪性肝炎模型形成的影响

目的　探讨肠道环境改变与非酒精性脂肪性肝炎的关系。方法　 4 2只SD大鼠随机分为模型组 (n =2 4 )、治疗组 (n =12 )和正常组 (n =6 )。模型组和治疗组大鼠以高脂饲料喂养。治疗组大鼠高脂饮食 8周后以乳果糖治疗。正常组大鼠以正常饲料喂养。实验 8周处死 12只模型组大鼠 ,16周处死模型组剩余大鼠和治疗组、正常组大鼠。测定血清转氨酶 ,HE染色观察肝脏病理改变。结果　 16周模型组大鼠血清ALT、AST明显升高 ,肝脏表现为脂肪性肝炎 ,治疗组大鼠血清ALT、AST明显下降 ,接近正常组水平 ,肝组织炎症活动计数也明显下降 (5 .83± 2 .0 2比 3.6 3± 0 .6 4 ) ,但仍显著高于 8周模型组大鼠水平 (3.6 3± 0 .6 4比 1.98± 0 .90 )。治疗组肝细胞脂肪变性程度无显著变化。结论　乳果糖可以改善高脂饮食诱发的脂肪性肝炎大鼠肝组织炎症损伤 ,但不能完全阻止炎症的进展 ,提示肠道细菌过度生长等肠道环境的改变是非酒精性脂肪性肝炎发病的重要机制之一     

熊去氧胆酸对高脂饮食大鼠脂肪性肝炎形成的影响

目的 探讨熊去氧胆酸对高脂馀食诱发的大鼠非酒精性脂肪性肝炎模型形成的影响。方法 29只SD大鼠随机分为3组：模型组予高脂饮食饲养;治疗组在高脂饮食饲养2周后同时加用熊去氧胆酸;正常组予标准饮食饲养,12周处死,结果 所有造模大鼠均出现肥胖、高脂血症和血清转氨酶升高,伴典型的脂肪性肝炎;与模型组相比,治疗组仅血清转氨酶、肝组织脂肪变和炎症坏死等指标有改善趋势,但两组间并无统计学差异。结论 熊去氧胆酸对高脂饮食诱发的肥胖、高脂血症性脂肪性肝炎可能并无防治作用。     

饮食调整治疗大鼠非酒精性脂肪性肝炎

目的:观察单纯饮食改变治疗大鼠非酒精性脂肪性肝炎(NASH)的作用。方法:30只SD大鼠随机分为3组(每组n=10):正常组喂普通饲料;模型组喂高脂饲料;饮食治疗组在高脂饮食12周后恢复正常饲料喂养。16周后处死动物。结果:正常饮食能显著降低造模大鼠的体重、肝指数、转氨酶,还能改善肝脏脂肪变性和炎症坏死的程度。结论:单纯恢复正常饮食即可治疗大鼠NASH。     

二甲双胍干预大鼠非酒精性脂肪性肝炎疗效观察

目的观察二甲双胍对非酒精性脂肪性肝炎大鼠模型的干预作用。方法实验动物分3组,模型组和治疗组各12只雄性SD大鼠给予高脂肪高胆固醇饲料喂养,另设6只普通饲料喂养大鼠作为对照组。治疗组从高脂饮食第4周起在饮水中加用二甲双胍(每天250mgkg)。所有大鼠均于实验24周后处死,进行血清生化和肝脏组织学检测。结果与模型组相比,治疗组肝脏指数和腹腔脂肪含量显著减少(P均<0.001),且体重呈下降趋势;血清天冬氨酸转氨酶[(162.45±11.2)UL比(115.9±29.3)UL,P=0.01]、三酰甘油(1.10±0.24比0.75±0.30,P=0.01)水平显著下降;治疗组肝脏组织学炎症评分(1.20±1.14比4.83±1.05,P<0.01)和肝纤维化评分(0.70±0.48比1.42±0.45,P<0.05)显著下降,伴肝脂肪变程度减轻(P<0.05)。结论二甲双胍早期干预可显著改善高脂饮食大鼠脂肪性肝炎和纤维化程度,伴肝重、腹部脂肪含量及血清三酰甘油水平下降。     

壳脂胶囊对非酒精性脂肪性肝炎大鼠肝组织PPAR-γ、IR的作用研究

[目的]探讨壳脂胶囊对非酒精性脂肪性肝炎大鼠肝组织PPAR-γ、IR的影响.[方法]高脂饮食饲喂SD大鼠以制备非酒精性脂肪性肝炎模型,造模同时进行药物干预.干预8周后,自动生化分析仪检测血清谷草转氨酶（AST）、谷丙转氨酶（ALT）、总胆固醇（CHO）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、甘油三酯（TG）水平,苏木精-伊红染色、油红O染色观察肝组织病理,RT-PCR检测PPAR-γmRNA和IR mRNA,Western-blot检测PPAR-γ和IR蛋白表达.[结果]与模型组比较,壳脂胶囊能明显降低血清TG、CHO、LDL、AST、ALT水平（P＜0.01）;壳脂胶囊组脂肪变性和炎症反应程度均较模型组有一定的减轻;壳脂胶囊组大鼠PPAR-γ和IR的蛋白和基因表达水平均高于模型组（P＜0.05）.[结论]壳脂胶囊可能通过上调肝组织PPAR-γ、IR蛋白及PPAR-γ mR-NA、IR mRNA的表达,改善胰岛素抵抗,进而调解脂肪代谢,改善肝脏功能,达到防治NASH的目的.     

牛磺酸、金牡蛎对大鼠酒精性肝损伤的防治作用

目的探讨牛磺酸、金牡蛎对酒精性肝病的防治作用。目的３２只雄性Ｗｉｓｔａｒ大鼠随机分为４组,模型组以高脂饮食加酒精饲养６个月,牛磺酸组和金牡蛎组分别在造模２周后予１％牛磺酸或１％金牡蛎水溶液口服,并以正常饮食组作对照。结果成功地建立了大鼠慢性酒精性肝损伤模型,牛磺酸和金牡蛎可显著改善其肝病理学变化,肝组织脂肪含量和血清转氨酶水平均较模型组显著下降,但肝组织胶原蛋白含量及肝纤维化程度无明显改善。结论金牡蛎及其提取物牛磺酸可有效防治大鼠酒精性脂肪肝,但对酒精性肝纤维化的防治无效。     

牛磺酸,金牡蛎对大鼠清性肝损伤的防治作用

目的 探讨牛磺酸、金牡蛎对酒精性肝病的防治作用。目的 ３２只雄性Ｗｉｓｔａｒ大鼠随机分为４组，模型组以高脂饮食加酒精饲养６个月，牛磺酸组和金牡蛎组分别在造模２周后予１％牛磺酸或１％金牡蛎水溶液口服，并以正常饮食组作对照。结果 成功地建立了大鼠慢性酒精性肝损伤模型，牛磺酸和金牡蛎可显著改善其肝病理学变化，肝组织脂肪含量和血清转氨酶水平均较模型组显著下降，但肝组织胶原蛋白含量及肝纤维化程度无明显改善。     

吡格列酮对大鼠非酒精性脂肪性肝炎干预的实验研究

目的　用吡格列酮对试验动物进行干预 ,探讨胰岛素抵抗与非酒精性脂肪性肝炎的关系。方法　雄性SD大鼠 5 0只随机分组。正常对照组喂饲普通饮食 ,高脂模型组喂饲高脂饮食 ,给药组分别在喂饲高脂饮食 4周后、9周后分别给予吡格列酮灌胃 ,并分别在 9周末及 14周末处死各组大鼠 ,测定血清转氨酶、血糖、血脂、胰岛素及FFA水平 ,观察肝组织学改变。结果　 9周后模型组大鼠呈现明显腹型肥胖 ,产生脂质代谢紊乱及胰岛素抵抗 ,肝脏出现肝细胞脂肪变性 ,给药组各项指标均有明显改善 ;14周后模型组大鼠血清转氨酶水平升高 ,肝脏出现炎细胞浸润 ,除肝组织炎症外 ,给药组其他指标均有不同程度的改善。结论　胰岛素抵抗在大鼠肝脏脂肪变的发生中起到关键作用 ,与脂肪肝发生炎症坏死关系甚密切 :吡格列酮可明显改善高脂饮食诱发大鼠肝脏的脂肪变性 ,对炎症变化作用不明显     

丹参对大鼠非酒精性脂肪性肝炎和脂质代谢的作用

目的观察丹参注射液对大鼠非酒精性脂肪性肝炎(NASH)脂质代谢和糖代谢的干预作用。方法高脂饲料建立大鼠NASH模型,设正常组,模型组,复方甘草甜素对照组,低剂量丹参组和高剂量丹参组,检测大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ-谷氨酰转肽酶(GGT)、甘油三酯(TG)、总胆固醇(TC)、血糖(GLU)水平,参照2006年2月NAFLD诊疗指南中脂肪肝分度和炎症分级的组织病理学标准进行量化计分。结果高、低剂量丹参组比模型组及对照组血清GGT、AST水平显著下降;与对照组及低剂量丹参组比较,高剂量丹参组血清TC、GLU及肝组织炎症计分水平均显著下降。结论高剂量丹参注射液对高脂饮食诱发的大鼠脂肪性肝炎和脂肪代谢紊乱有一定的防治作用。     

脂炎消煎剂防治大鼠非酒精性脂肪性肝炎的实验研究

目的研究脂炎消煎剂对大鼠非酒精性脂肪性肝炎防治作用的机制。方法采用高脂饲料喂养,建立大鼠非酒精性脂肪性肝炎模型,随机分正常组、模型组和脂炎消煎剂大、小剂量组(剂量按体重计20g/kg和10g/kg),第24周检测大鼠肝功能、血脂并观察肝脏形态学改变,检测肝组织超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、丙二醛(MDA)和羟脯氨酸(Hyp)含量。结果与模型组比较,脂炎消煎剂组血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)下降,血清甘油三酯(TG)、总胆固醇(CHOL)减低,高密度脂蛋白胆固醇(HDLC)升高;肝组织SOD活力和GSH含量升高,MDA和Hyp下降;肝脏形态学明显改善。结论脂炎消煎剂具有降低血脂、抗脂质过氧化和保护肝细胞的作用,对非酒精性脂肪性肝炎具有一定的防治作用。     

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.     

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.