厄贝沙坦通过核转录因子κB信号通路减轻高糖诱导的H9C2细胞炎症反应及凋亡的研究

目的探讨厄贝沙坦通过抑制核转录因子κB(NF-κB)的表达减轻高糖诱导的H9C2细胞炎症反应及凋亡。方法将H9C2细胞分为:对照(Con)组(5.5 mmol/L葡萄糖)、甘露醇(Man)组(5.5 mmol/L葡萄糖+27.5 mmol/L甘露醇)、二甲基亚砜(DMSO)组(5.5 mmol/L葡萄糖+1‰二甲基亚砜)、高糖(HG)组(33 mmol/L葡萄糖)、厄贝沙坦(Ir)组(33 mmol/L葡萄糖+1μmol/L厄贝沙坦),每组3个细胞。检测细胞增殖抑制率;IL-6、单核细胞趋化蛋白1(MCP-1)、TNF-α、Bax、Bcl-2 mRNA;核转录因子κB(NF-κB)、caspase-3蛋白表达及细胞凋亡率。结果 Ir组低于高糖诱导的Bax[(50.31±2.18)vs(61.96±4.08)]、IL-6[(7.67±1.53)vs(25.33±4.16)]、MCP-1[(26.67±6.11)vs(43.33±3.06)]、TNF-α[(35.33±3.06)vs(44.67±4.16)]、NF-κB[(2.19±0.52)vs(3.58±0.53)]及caspase-3[(2.28±0.10)vs(2.86±0.12)]表达及细胞凋亡[(10.73±1.78)vs(16.46±2.24)],差异均有统计学意义(P0.05);上调高糖抑制的Bcl-2[(0.62±0.04)vs(0.45±0.06)]的表达(P0.05)。结论厄贝沙坦通过NF-κB信号通路,可减轻高糖诱导的H9C2细胞炎症反应及凋亡。     

苦瓜蛋白通过阻止核因子κB核转位抑制炎性因子生成

目的 研究苦瓜蛋白对载脂蛋白E基因敲除(ApoE-/-)小鼠炎症因子核因子κB(NF-κB)蛋白核转位的影响,探讨苦瓜蛋白抗炎的分子机制.方法 40只6周龄雄性ApoE-/-小鼠,随机分为普食组、高脂高胆固醇组、高脂高胆固醇苦瓜蛋白组、普食苦瓜蛋白组.12周后眼球采血,ELISA测定血浆中炎性因子NF-κB、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)、IL-6和γ干扰素(IFN-γ)及抗炎因子IL-10的水平,免疫组织化学检测主动脉壁IκB表达,RT-PCR和Western blot检测NF-κB和IκB表达.结果 ApoE-/-小鼠经高脂高胆固醇饲料喂养12周后,血液中炎症因子NF-κB、IL-1β、TNF-α、IL-6、IFN-γ水平均显著高于普食组(P＜0.01,n=5),但抗炎因子IL-10仍维持较高水平.经苦瓜蛋白干预后,血清中炎症因子水平下降,而抗炎因子IL-10水平并不上升.RT-PCR以及Western blot检测结果表明,苦瓜蛋白显著降低高脂高胆固醇饲料喂养小鼠动脉血管壁细胞核内NF-κB蛋白水平,阻止其核转位.与普食组比较,高脂高胆固醇组IκB被显著降解(0.19±0.05比0.74 +0.15,P＜0.05,n=5),但其经苦瓜蛋白干预后,这种降解作用得到显著的抑制(0.19±0.05比0.36±0.07,P＜0.01,n=5).结论 苦瓜蛋白通过减少IκB降解抑制NF-κB蛋白核转位而发挥抑制炎性因子生成的作用.     

Protective effect of osteoprotegerin in vascular endothelial cells cultured with high glucose and its possible mechanism

目的 探讨护骨素对高糖诱导的血管内皮细胞保护作用及机制.方法 人脐静脉内皮细胞分别在正糖(5 mmol/L葡萄糖)、高糖(25 mmol/L葡萄糖)、高糖+护骨素(25 mmol/L葡萄糖+2 μg/ml护骨素)、高渗(5mmol/L葡萄糖+20 mmol/L甘露醇)环境下培养72小时.以流式细胞术测定各组细胞的凋亡;Western blot法分析各组细胞磷酸化核转录因子(NF-κB)抑制蛋白激酶β (p-IκKβ)、NF-κB抑制蛋白激酶β(IκKβ)、NF-κB抑制蛋白α(IκBα)、bcl-2及bax表达水平.结果 (1)与正糖组相比,高糖组内皮细胞凋亡率显著增加(P＜0.01);高糖+护骨素组细胞凋亡明显低于高糖组,而又高于正糖组(P＜0.05);(2)与正糖组相比,高糖组p-IκKβ表达显著增高(P＜0.01),IκBo和bcl-2表达显著降低(P＜0.01);高糖+护骨素组p-IκKβ明显低于高糖组,而又高于正糖组(P＜0.05),IκBα和Bcl-2表达水平明显高于高糖组,而又低于正糖组(P＜0.05).结论 高糖通过激活IκKβ/NF-κB信号通路引起血管内皮细胞凋亡;护骨素具有抗高糖诱导的IκKβ/NF-κB活性作用,从而降低内皮细胞凋亡,保护内皮细胞.     

心外膜脂肪细胞核因子-κB信号途径抑制在抗动脉粥样硬化中的作用

目的研究心外膜脂肪细胞核因子(NF)-κB信号途径抑制在抗动脉粥样硬化中的作用。方法建立泡沫细胞模型,分为空白组,转染试剂组,siRNA干扰组,高脂组,高脂+SRT1720组,高脂+SRT1720+siRNA干扰组。采用油红O染色判断模型的建立,采用Western印迹方法进行蛋白表达的分析。结果建立模型成功;与高脂组比较,高脂+SRT1720组SIRT1蛋白表达量升高显著,NF-κB及其下游靶分子肿瘤坏死因子(TNF)-α蛋白表达量下降显著(P0.05)。与高脂+SRT1720组比较,高脂+SRT1720+siRNA干扰组SIRT 1蛋白表达量下降显著,NF-κB及其下游靶分子TNF-α蛋白表达量升高显著(均P0.05)。结论泡沫细胞中SIRT1是NF-κB信号通路的上游,通过抑制心外膜脂肪组织NF-κB炎症信号途径,参与调节泡沫细胞从动脉粥样硬化斑块中移出,可为防治冠状动脉粥样硬化的治疗提供新的手段。     

沉默信息调节因子1对高糖诱导的系膜细胞内皮素-1和转化生长因子β1的影响

目的探讨沉默信息调节因子1(SIRT1)对高糖诱导的系膜细胞内皮素-1(ET-1)和转化生长因子β1(TGF-β1)的影响。方法体外培养系膜细胞分为:(1)高糖组(高糖培养液);(2)SIRT1激动剂(白藜芦醇)+高糖组,含1μmol/L白藜芦醇的高糖培养液;(3)SIRT1 RNAi干扰+高糖组,加入pTRC-shSIRT1慢病毒感染;(4)正常对照(NC)组。检测各组细胞SIRT1基因表达,以及ET-1和TGF-β1水平。结果高糖组、SIRT1激动剂+高糖组、SIRT1RNAi干扰+高糖组及NC组ET-1含量分别为(56.1±6.3)、(31.9±5.1)、(105.63±8.2)和(17.3±3.4)pg/ml;TGF-β1含量分别为(43.3±5.7)、(27.5±4.9)、(87.4±7.3)和(15.6±3.6)ng/ml。高糖抑制SIRT1表达,上调ET-1和TGF-β1表达(P0.05);SIRT1激动剂可改善高糖对SIRT1的抑制,下调ET-1和TGF-β1表达(P0.05);沉默SIRT1,可上调ET-1和TGF-β1表达(P0.05)。结论 SIRT1基因对高糖诱导的系膜细胞ET-1和TGF-β1可能起负调控作用。     

沉默信息调节因子1在具核梭杆菌诱导肠上皮细胞炎症和凋亡中的作用

目的探讨沉默信息调节因子1(SIRT1)在具核梭杆菌(Fn)诱导肠上皮细胞炎症和凋亡中的作用。方法建立Fn感染肠上皮细胞模型并分为3组,即Fn感染组、Fn+Sirtinol组(SIRT1抑制剂)、Fn+白藜芦醇组(SIRT1激动剂),另设未感染对照组。在Fn感染肠上皮细胞6 h后,采用qRT-PCR、ELISA、Western blot、流式细胞术检测4组细胞中SIRT1基因mRNA和蛋白表达情况、炎症因子的量、NF-κB信号通路的表达、凋亡率、凋亡相关蛋白的表达。结果与Fn感染组相比,Fn+白藜芦醇组细胞中SIRT1 mRNA和蛋白质的表达升高,Fn+Sirtinol组细胞中SIRT1 mRNA和蛋白质的表达降低(P0.01)。Fn+Sirtinol组上清液中4种炎症因子含量[IL-1β:(35.975±2.995)pg/ml,IL-6:(954.250±37.340)pg/ml,IL-8:(598.500±23.014)pg/ml,TNF-α:(398.296±20.663)pg/ml]显著高于Fn+白藜芦醇组[IL-1β:(6.925±1.053)pg/ml,IL-6:(242.009±18.850)pg/ml,IL-8:(5.375±6.067)pg/ml,TNF-α:(79.537±8.334)pg/ml]和Fn感染组[IL-1β:(11.125±1.374)pg/ml,IL-6:(525.425±21.247)pg/ml,IL-8:(262.000±14.071)pg/ml,TNF-α:(180.412±11.826)pg/ml](P0.01)。Fn+Sirtinol组细胞中3种NF-κB信号通路相关蛋白质的表达量与其余3组比较差异有统计学义(P0.01);Fn感染组细胞中3种蛋白质的表达量明显高于Fn+白藜芦醇组和对照组(P0.01,P0.05)。Fn+Sirtinol组细胞在Fn感染6 h后凋亡率达峰值[(27.028±3.319)%],与其余3组的细胞的凋亡率比较差异有统计学义(P0.01);Fn感染组细胞的凋亡率[(16.864±2.213)%]明显高于Fn+白藜芦醇组[(5.584±1.148)%]和对照组[(2.510±0.763)%](P0.01)。Fn+Sirtinol组细胞中Bax、Cleaved caspase-3、Cleaved caspase-9蛋白高表达,与其余3组比较差异有统计学义(P0.01)。Fn+Sirtinol组细胞中Bcl-2蛋白低表达,与Fn+白藜芦醇组和对照组表达量比较差异有统计学义(P0.01或P0.05),Fn+白藜芦醇组组细胞中Bcl-2蛋白的表达量则明显高于对照组(P0.01)。结论在Fn感染的体外模型中,SIRT1可抑制肠上皮细胞分泌炎症因子,下调NF-κB信号通路的表达,可能通过线粒体凋亡途径抑制细胞的凋亡。     

过氧化物酶体增殖物激活受体α的激活可以减轻高糖高脂诱导的心肌细胞凋亡

目的 探讨激活过氧化物酶体增殖物激活受体α(PPARα)对高糖高脂诱导的心肌细胞凋亡的影响.方法 将培养的心肌细胞分为:1)正常组(N组);2)高糖高脂组(H组);3)高糖高脂 PPARα特异性激动剂匹尼尼酸(Wy14643)组(S组).TUNEL法检测细胞凋亡,免疫细胞化学法检测各组细胞PPARα蛋白的表达.结果 H组凋亡细胞较N组增多[(71.34±0.01)% vs (2.50±0.01)%,P＜0.01];H组PPARα蛋白表达下降(0.08±0.02),与N组(0.12±0.02)比较,P＜0.01;PPARα激活剂匹尼尼酸可抑制高糖高脂引起的心肌细胞凋亡,同时伴有培养液中 PPARα蛋白的表达增高(0.16±0.0119 vs 0.08±0.02,P＜0.01).结论 胞核PPARα的表达增高可抑制高糖高脂培养的心肌细胞凋亡,有可能参与机体对高糖高脂血症的自我保护过程.     

过氧化物酶体增殖物激活受体α的激活可以减轻高糖高脂诱导的心肌细胞凋亡

目的探讨激活过氧化物酶体增殖物激活受体α(PPARα)对高糖高脂诱导的心肌细胞凋亡的影响。方法将培养的心肌细胞分为:1)正常组(N组);2)高糖高脂组(H组);3)高糖高脂 PPARα特异性激动剂匹尼尼酸(Wy14643)组(S组)。TUNEL法检测细胞凋亡,免疫细胞化学法检测各组细胞PPARα蛋白的表达。结果H组凋亡细胞较N组增多[(71.34±0.01)%vs(2.50±0.01)%,P<0.01];H组PPARα蛋白表达下降(0.08±0.02),与N组(0.12±0.02)比较,P<0.01;PPARα激活剂匹尼尼酸可抑制高糖高脂引起的心肌细胞凋亡,同时伴有培养液中PPARα蛋白的表达增高(0.16±0.0119vs0.08±0.02,P<0.01)。结论胞核PPARα的表达增高可抑制高糖高脂培养的心肌细胞凋亡,有可能参与机体对高糖高脂血症的自我保护过程。     

异鼠李素对高糖高脂诱导胰岛β细胞损伤保护作用的研究

目的探讨异鼠李素(ISO)对高糖高脂诱导小鼠胰岛β细胞株MIN6细胞损伤的保护作用及机制。方法不同浓度ISO预处理MIN6细胞后高糖高脂培养48 h,CCK8法筛选ISO最佳干预浓度。细胞分为正常对照(Con)组(11. 1 mmol/L葡萄糖)、高糖高脂损伤模型(M)组(33. 3 mmol/L葡萄糖+0. 25 mmol/L棕榈酸)及ISO预处理(ISO+M)组(10μmol/L ISO+33. 3 mmol/L葡萄糖+0. 25 mmol/L棕榈酸)。流式细胞术测定各组细胞凋亡率;硝酸还原酶法检测一氧化氮(NO)含量;RT-PCR测定IL-1β、IL-6、肿瘤坏死因子α(TNF-α)mRNA表达;Western blot法检测磷酸化核因子κB(NF-κB)抑制蛋白(IκB)激酶β(p-IKKβ)、磷酸化NF-κB抑制蛋白α(p-IκBα)、诱导型一氧化氮合酶(iNOS)及NF-κB p65蛋白的表达。结果细胞凋亡及NO含量M组高于Con组,ISO+M组低于M组(P0. 01)。IL-1β、IL-6、TNF-αmRNA,p-IKKβ、p-IκB、iNOS蛋白与NF-κB p65蛋白表达M组高于Con组,ISO+M组低于M组(P0. 05)。结论 ISO可减轻高糖高脂诱导的胰岛β细胞损伤,可能与抑制IκB激酶(IKK)/IκB/NF-κB/iNOS通路活性有关。     

细胞因子信号转导抑制因子3表达下调抵抗高脂饮食诱导肥胖的作用机制研究

目的 探讨RNA干扰下丘脑弓状核细胞因子信号转导抑制因子3(SOCS3)对饮食诱导大鼠肥胖的防治作用.方法 利用慢病毒介导的RNA干扰技术建立大鼠下丘脑弓状核SOCS3基因沉默的动物模型,然后给予高脂饲料喂养8周处死,采用放射免疫法测定血清瘦素和胰岛素的含量,免疫组化及实时定量PCR方法检测大鼠下丘脑注射部位SOCS3的表达.结果 干扰组大鼠下丘脑注射部位的SOCS3蛋白表达明显降低,SOCS3 mRNA表达量下调49％ (P＜0.01),干扰组大鼠体重增长缓慢,血清瘦素[(8.18±2.10对10.85±2.23)ng/ml]、胰岛素[(18.89±4.88对26.78±6.01)mU/L]、血糖[(4.89±0.91对6.26±1.41) mmol/L]及甘油三酯[(0.47±0.10对0.62±0.16)mmol/L]水平均明显降低(P＜0.05或P＜0.01).结论 利用RNA干扰下调下丘脑弓状核SOCS3基因的表达能够抵抗高脂饮食诱导的肥胖、改善瘦素抵抗和相关的代谢紊乱.     

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.