甲醛染毒对大鼠生殖发育毒性的实验研究

目的探讨甲醛对大鼠生殖发育的影响。方法按两代一窝繁殖法进行生殖毒性试验。选用体重110~130gW istar大鼠120只,随机分为4组,每组雌鼠20只、雄鼠10只。采用静式吸入法染毒,雌、雄大鼠每天染毒1h,各组的甲醛浓度分别为,高浓度组:119.6±15.4mg/m3、中浓度组:25.2±4.6mg/m3、低浓度组:4.8±1.3 mg/m3、对照组:室内空气,同时观察大鼠各项生殖发育指标。结果F2代高剂量组仔鼠有17只畸形,占活胎数的32.1%(17/53),与对照组比较差异有显著性(P<0.05);F1代高浓度组雌鼠受孕率、死胎率、胎盘总重及胎窝总重与对照组比较差异均有显著性(P<0.05),F2代高浓度组大鼠活产率、4天存活率、21天存活率与对照组比较差异均有统计学意义(P<0.05),在哺乳期F1代出生14天后和F2代出生后体重均明显低于同时期对照组大鼠的体重。结论甲醛可影响大鼠生殖及子代发育,并具有致畸作用。     

氟对大鼠睾丸生殖细胞增殖细胞核抗原表达的影响

目的了解氟对大鼠睾丸生殖细胞增殖功能的影响。方法对雄性大鼠腹腔注射NaF溶液建立氟中毒模型,观察睾丸的病理学、生殖细胞数量及生精功能的改变,免疫组化法测定睾丸生殖细胞中增殖细胞核抗原(PCNA)的表达。结果高剂量染毒组(20mg/kg)与低剂量染毒组(10mg/kg)大鼠的睾丸生殖细胞数分别为(161.00±16.16)和(268.00±12.13),低于对照组(P<0.05),其生殖细胞PCNA表达率分别为(0.60±0.81)%和(0.71±0.05)%,亦低于对照组(P<0.05);其精子数目、精子活动度比对照组显著降低(P<0.05),精子畸形率比对照组显著升高(P<0.05)。结论氟可能通过抑制PCNA的表达,从而减少生殖细胞的数量,对雄性生殖系统造成损害。     

不同剂量亚砷酸钠染毒大鼠唾液砷水平及其与血砷、尿砷间关系研究

目的 探讨不同剂量砷暴露大鼠唾液中含砷量变化及其与血砷、尿砷间的关系.方法 将32只雄性SD大鼠按体质量随机分为4组,分别为对照组(生理盐水)及低(0.2 mg/kg)、中(2.0 mg/kg)、高(20.0mg/kg)剂量亚砷酸钠染毒组,每组8只.采用经口灌胃染毒方法,隔日1次,连续2周后收集唾液、血液、尿液及脏器,计算脏器系数,应用原子荧光分光光度计(AFS-230)检测血砷、尿砷,应用电感耦合-等离子体质谱(ICP-MS)检测唾液砷.结果 亚砷酸钠染毒组大鼠体质量增长值均低于对照组,其中高剂量组[(76.13±17.19)g]与对照组[(103.00±12.31)g]比较,差异有统计学意义(P＜0.05).高剂量组大鼠肝脏及肾脏脏器系数[(3.92±0.54)％、(0.96±0.15)％]与对照组[(3.27±0.35)％、(0.76±0.05)％]比较,差异有统计学意义(P＜0.05或＜0.01).低、中、高染毒组大鼠唾液砷[(0.044±0.019)、(0.211±0.071)、(1.128±0.380)mg/L]、血砷[(11.832±1.887)、(45.032±7.216)、(121.839±17.323)mg/L]及尿砷[(0.138±0.085)、(0.874±0.328)、(8.843±1.754)mg/L]与对照组[(0.018±0.014)、(2.267±0.370)、(0.025±0.011)mg/L]比较,差异有统计学意义(P均＜ 0.05),且各染毒组之间比较差异有统计学意义(P均＜0.05).大鼠唾液砷与血砷、尿砷之间存在显著正相关,相关系数分别为0.934、0.960(P均＜0.01).结论 高砷暴露可抑制大鼠体质量增长,并对肝脏及肾脏有较强毒性.砷在唾液中存在良好的剂量-反应关系,且唾液砷与血砷、尿砷间存在明显的正相关关系,提示唾液砷也是一种良好的砷暴露标志物.     

表没食子儿茶素没食子酸酯改善高脂饮食大鼠体重及相关代谢研究

目的:观察不同剂量表没食子儿茶素没食子酸酯(EGCG)对高脂饮食大鼠体重、糖脂代谢及肝脏氧化应激状态的影响,为深入研究EGCG防治肥胖的机制探索最佳干预剂量。方法:40只雄性SD大鼠随机分为正常对照组、高脂饮食组、EGCG低剂量组[100 mg/(kg·d)]、EGCG中剂量组[200 mg/(kg·d)]、EGCG高剂量组[400 mg/(kg·d)],每组8只。正常对照组喂饲基础饲料,高脂饮食组喂饲高脂饲料,EGCG各组喂饲高脂饲料的同时给予各剂量EGCG灌胃。喂养8周末处死大鼠。测定体重、内脏脂肪重量、肝脏重量、血清空腹血糖(FBG)、三酰甘油(TG)、总胆固醇(TC)、肝脏总超氧化物歧化酶(T-SOD)活性、谷胱甘肽过氧化物酶(GPx)活性、丙二醛(MDA)含量。结果:高脂饮食组实验末体重、肝脏重量、血清FBG均显著高于正常对照组(P<0.05)。与高脂饮食组相比,EGCG各剂量组能有效降低高脂饮食大鼠体重、肝脏重量、血清FBG和TG水平(均P0.05)。与高脂饮食组相比,低剂量EGCG可升高肝脏GPx活力(P<0.05)。中剂量EGCG可降低肝脏MDA含量(P0.05)。结论:中剂量EGCG对控制高脂饮食大鼠体重、改善糖脂代谢及肝脏氧化应激状态更为适宜,而高剂量EGCG可能反而会促进机体氧化应激水平。     

铝对大鼠海马组织形态学及细胞凋亡相关基因表达的影响

目的 研究三氯化铝对大鼠海马组织形态学及细胞凋亡相关基因表达的影响.方法 选择雄性SD大鼠,按体重随机分为4组,在基础饲料中添加三氯化铝,Al3+剂量分别为0、11.2、55.9和111.9 mg/kg体重,连续染毒3个月.采用流式细胞仪检测大鼠海马Bcl-2 、Bax、p53表达,原子吸收法检测海马铝含量,并观察海马病理形态学变化.结果 与对照组相比,各染毒组大鼠海马Bcl-2表达明显减少(P＜0.05)、Bax、p53表达明显增加(P＜0.05),且随剂量增加渐趋明显.各染毒组大鼠海马铝含量均显著增高(P＜0.05),并与染毒剂量呈明显正相关(r=0.805,P＜0.01);病理检查发现111.9 mg/kg组大鼠海马颗粒空泡变性细胞明显增多,海马和皮质锥体细胞明显减少,并可见神经原纤维缠结样病理改变.结论 铝诱导大鼠出现AD典型的病理改变,其机制可能与Bcl-2表达下调及Bax、p53表达上调有关.     

不同剂量的氯解磷定联合阿托品对急性敌敌畏中毒大鼠的治疗效果

目的:探讨不同剂量的氯解磷定联合阿托品对急性敌敌畏中毒大鼠模型的治疗效果。方法 :将204只健康雄性大鼠按照随机数字表法分为对照组(n=12)、染毒组(n=48)、治疗组(n=144)。对照组给予1 mL生理盐水一次性灌胃。染毒组和治疗组按照30 mg/kg敌敌畏一次性灌胃。治疗组在灌胃后立即腹腔注射阿托品15 mg/kg,同时加以30、45、60 mg/kg的氯解磷定腹腔注射。观察动物中毒表现和存活情况,分别于染毒后2、24、48和72 h处死大鼠,取血标本和肺组织。测定血清中乙酰胆碱酯酶(AChE)、丙二醛(MDA)、超氧化物歧化酶(SOD)的含量;苏木素-伊红(HE)染色观察肺组织病理变化。结果:与染毒组相比,治疗组大鼠翘尾、流涎、肌束震颤、翻正反射消失发生率明显降低,同时存活率增加,且差异具有统计学意义(均P<0.05);与染毒组相比,治疗组大鼠动脉血中AChE、SOD含量增加,MDA含量明显减少,高剂量的氯解磷定效果更明显(均P<0.05)。HE结果显示,氯解磷定治疗组大鼠肺组织损害减轻,炎细胞减少,且高剂量的氯解磷定效果更显著。结论:氯解磷定联合阿托品对急性敌敌畏中毒大鼠具有治疗作用,且高剂量的氯解磷定效果更加明显。     

铜负荷大鼠脑组织Cu、Zn、Fe分布及其对神经元细胞损伤的机制

目的 观察铜负荷大鼠不同脑区脑组织Cu、Zn、Fe分布,并探讨其对神经元细胞损伤的机制.方法 选择雄性Wistar大鼠50只,随机均分模型组和对照组,模型组给予含硫酸铜1 g/kg的粉状饲料和0.185％硫酸铜水,对照组正常喂饲.第12周结束时,取血、脑组织标本,检测血和不同脑区Cu、Zn、Fe及Cu/Zn-SOD、MDA含量.结果 模型组各脑区脑组织Cu含量均较对照组明显升高(P均＜0.05),Zn、Fe含量无明显变化;血清、大脑皮层及基底节区Cu/Zn-SOD活力均较对照组减低(P均＜0.05),MDA含量均较对照组明显升高(P均＜0.05).结论 Cu负荷大鼠脑组织Cu含量明显增高,其对神经元细胞的损伤可能与Cu/Zn-SOD活力减低、MDA含量升高有关.     

宫内慢性缺氧对子代大鼠血压的影响

目的 探讨宫内慢性缺氧对子代大鼠血压的影响.方法 SD大鼠孕鼠于妊娠第7～21天,每日置于氧气浓度为10%±1%的低压氧舱3 h,待分娩后观测其子代大鼠体重、主要脏器重量及血压的变化.结果 宫内缺氧组仔鼠出生后第1天体重显著低于对照组(P<0.01),但出生后第20天体重与对照组无显著性差异;宫内缺氧组仔鼠肝脏于出生后第1、20天以及雄性仔鼠肾脏于出生后3月、7月的重量显著低于对照组(P<0.05);5月龄、7月龄宫内缺氧组子代雄性大鼠血压均比同性别对照组显著升高(P<0.05),且呈现随年龄增长而逐渐加重趋势,但宫内缺氧子代雌性大鼠血压与对照组相比无显著性差异.结论慢性宫内缺氧可能是引起大鼠肝、肾、血管组织程序控制的应激因素之一.它可诱发子代雄性大鼠血压升高,呈现性别依赖现象,并随年龄增长有逐渐加重倾向.     

甲醛对大鼠的致突变研究

目的研究甲醛对大鼠睾丸生殖细胞的一般毒性及致突变作用.方法采用不同浓度的甲醛(0 mg/m3, 4.8 mg/m3, 25 mg/m3, 118 mg/m3)经呼吸道染毒Wistar大鼠,8w后颈椎脱臼法处死.观察甲醛对骨髓嗜多染红细胞的致微核作用及对大鼠精子形态的影响.结果各剂量组致微核作用和精子畸形率均随浓度的增大而升高,呈现剂量-反应关系.结论甲醛对大鼠有生殖毒性并具有一定的致突变作用.     

红花提取物对急性心肌梗死犬血清微量元素和心肌形态学的影响

目的 观察红花提取物对急性心肌梗死犬血清微量元素和形态学的影响.方法 取杂种犬24只,随机分为4组,每组6只,分别为模型组、阳性药物对照组(地奥心血康胶囊,52.0 mg/kg)、及红花提取物低剂量组(5.5 mg/kg)、红花提取物高剂量组(11.0 mg/kg).结扎犬左冠状动脉前降支,制备急性心肌梗死模型,观察红花提取物对血清微量元素(Cu2+、Zn2+、Ca2+、Mg2+)含量的影响;通过HE染色,观察心肌细胞形态学的变化.结果 与模型组比较,红花提取物各剂量组血清微量元素Cu2+含量降低(P<0.05),Zn2+、Ca2+、Mg2+含量增加(P<0.05,P<0.01),缺血心肌细胞的病理形态学损伤程度减轻.结论 红花提取物对实验性心肌梗死犬的心肌具有明显的保护作用.     

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.     

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.