微粒子载体携反义MCP-1基因的转染抑制腹主动脉瘤生长的实验研究

目的　探讨微粒子携反义单核细胞趋化蛋白 1(MCP 1)基因局部定位转染对大鼠腹主动脉瘤生长的影响及机制。　方法　将大鼠制成腹主动脉瘤模型后 ,分成微粒子 DNA组和空载粒子对照组、生理盐水对照组 ,分别进行腹主动脉局部定位转染 ,2周后观察腹主动脉直径的变化 ,应用聚合酶链反应 (PCR)观察微粒子作为基因转染载体的可行性 ,应用原位杂交、Western蛋白质印迹等方法观察反义基因转染后对内源性MCP 1基因表达的抑制作用。　结果　基因转染后 2周 ,微粒子 DNA组腹主动脉直径为 (1 79± 0 12 )mm ,明显小于 2个对照组 (P <0 0 1) ,PCR扩增见该组动脉组织提取的DNA中有特异性条带出现 ,动脉壁中MCP 1基因的mRNA和蛋白表达水平明显低于对照组 (P <0 0 1)。　结论　微粒子可有效地用作基因转染的载体 ;反义MCP 1基因的转染可通过抑制内源性MCP 1基因的表达和动脉壁巨噬细胞的浸润而达到抑制腹主动脉瘤生长的作用。     

趋化素样因子1在大鼠腹主动脉瘤病情发展中的作用

目的探讨氢气抑制趋化素样因子1(Cklf1)在大鼠腹主动脉瘤病情发展中的作用。方法取雄性SD大鼠20只,随机分为腹主动脉瘤组和腹主动脉瘤干预组(腹腔注射氢气饱和生理盐水),建立腹主动脉瘤模型。术后28 d开腹取材,观察腹主动脉扩张情况,采用苏木素-伊红(HE)染色和弹力纤维染色检测炎症浸润和腹主动脉中膜弹力纤维破坏情况,免疫组化法检测Cklf1(r Cklf1)、金属蛋白酶(MMP2)蛋白表达情况,RT-PCR检测r Cklf1、MMP2基因表达情况。结果腹主动脉瘤组大鼠腹主动脉扩张率明显高于腹主动脉瘤干预组(P0.01)。腹主动脉瘤组大鼠瘤壁r Cklf1 mRNA、MMP2 mRNA表达量均明显高于腹主动脉瘤干预组(P0.01);r Cklf1、MMP2主要在腹主动脉瘤壁中层病变严重区域表达上调;与腹主动脉瘤组相比,干预组r Cklf1、MMP2阳性表达明显减弱,炎症浸润、弹力纤维破坏程度明显减轻。结论氢气可通过抑制r Cklf1表达,抑制炎性细胞向腹主动脉受损区域聚集,降低MMP2表达合成,减缓中膜弹力纤维降解,干预腹主动脉瘤进展。     

核因子κB的反义和诱骗性寡核苷酸对大鼠球囊损伤后血管狭窄和新生内膜形成的影响

探讨核因子κB p65亚基的反义和诱骗性寡核苷酸单独或联合作用对大鼠颈动脉球囊损伤细胞间粘附分子、单核细胞趋化因子的作用. SD大鼠随机分为7组,每组分为6个时相点(6 h和1、3、5、7、14 d),每个时相点3只大鼠.制作血管球囊损伤模型.相应时间点处死动物.模型组、正义组、诱骗对照组血管内膜面积、中膜面积、内膜/中膜在第5天增加,14 d达到高峰.管腔面积随时相点减小.反义组、诱骗组、反义组+诱骗组干预后,血管上述病理指标明显改善(P<0.05),反义组+诱骗组较反义组、诱骗组治疗效果更明显(P<0.05).内皮细胞间粘附分子、单核细胞趋化因子mRNA表达在血管损伤后6 h即可检测到,3、5、7 d后持续表达增加,14 d后表达降低.免疫组织化学检测显示,内皮细胞间粘附分子1、单核细胞趋化因子1蛋白质表达在6个时相点均为阳性染色,14 d达到高峰;反义组、诱骗组、反义组+诱骗组治疗后,与模型组、正义组、诱骗对照组相比,内皮细胞间粘附分子、单核细胞趋化因子mRNA表达和蛋白合成在各时相点均降低(P<0.05).免疫印迹法检测核蛋白抽提物显示,核因子κB p65在血管损伤后6 h有一定蛋白表达,1 d后蛋白表达明显增加,至7 d达高峰,14 d后蛋白表达略降低.反义组、诱骗组、反义组+诱骗组干预后,各时相点蛋白质表达均较模型组、正义组、诱骗对照组减弱(P<0.05).核因子κB调控内皮细胞间粘附分子、单核细胞趋化因子基因表达和蛋白质合成;球囊损伤后血管壁细胞增殖在不同时相点有动态变化;脂质体介导局部转染反义、诱骗性寡核苷酸可抑制核因子κB激活对下游基因的调控,两者联合作用效果更为显著.     

核因子κB的反义和诱骗性寡核苷酸对大鼠球囊损伤后血管狭窄和新生内膜形成的影响

探讨核因子κBp6 5亚基的反义和诱骗性寡核苷酸单独或联合作用对大鼠颈动脉球囊损伤细胞间粘附分子、单核细胞趋化因子的作用。SD大鼠随机分为 7组 ,每组分为 6个时相点 (6h和 1、3、5、7、1 4d) ,每个时相点 3只大鼠。制作血管球囊损伤模型。相应时间点处死动物。模型组、正义组、诱骗对照组血管内膜面积、中膜面积、内膜 中膜在第 5天增加 ,1 4d达到高峰。管腔面积随时相点减小。反义组、诱骗组、反义组 +诱骗组干预后 ,血管上述病理指标明显改善 (P <0 .0 5 ) ,反义组 +诱骗组较反义组、诱骗组治疗效果更明显 (P <0 .0 5 )。内皮细胞间粘附分子、单核细胞趋化因子mRNA表达在血管损伤后 6h即可检测到 ,3、5、7d后持续表达增加 ,1 4d后表达降低。免疫组织化学检测显示 ,内皮细胞间粘附分子 1、单核细胞趋化因子 1蛋白质表达在 6个时相点均为阳性染色 ,1 4d达到高峰 ;反义组、诱骗组、反义组 +诱骗组治疗后 ,与模型组、正义组、诱骗对照组相比 ,内皮细胞间粘附分子、单核细胞趋化因子mRNA表达和蛋白合成在各时相点均降低 (P <0 .0 5 )。免疫印迹法检测核蛋白抽提物显示 ,核因子κBp6 5在血管损伤后 6h有一定蛋白表达 ,1d后蛋白表达明显增加 ,至 7d达高峰 ,1 4d后蛋白表达略降低。反义组、诱骗组、反义组     

氧化型脂蛋白诱导血管平滑肌细胞表达单核细胞趋化蛋白-1

为了解脂蛋白对平滑肌细胞的单核细胞趋化蛋白-1mRNA和蛋白表达的影响，在牛主动脉平滑肌细胞培养基中分别加入低密度脂蛋白、氧化型低密度脂蛋白、极低密度脂蛋白和氧化型极低密度脂蛋白，培养24h，用异硫氰酸胍法提取细胞的总RNA，用γ-32P末端标记的单核细胞趋化蛋白-1的寡核苷酸探针进行狭缝杂交分析，检测平滑肌细胞的单核细胞趋化蛋白-1mRNA的表达。同时用夹心酶联免疫吸附试验检测条件培养基中单核细胞趋化蛋白-1的蛋白含量。结果发现。培养的牛主动脉平滑肌细胞能表达单核细胞趋化蛋白-1mRNA及蛋白，氧化型低密度脂蛋白和氧化型极低密度脂蛋白使其单核细胞趋化蛋白-1mRNA的表达明显增强，同时也使其条件培养基中单核细胞趋化蛋白-1的蛋白水平增加，而低密度脂蛋白和极低密度脂蛋白仅使平滑肌细胞中单核细胞趋化蛋白-1mRNA和蛋白的表达轻度增加。提示氧化型低密度脂蛋白和氧化型极低密度脂蛋白能诱导平滑肌细胞表达高水平的单核细胞趋化蛋白-1。     

糖基化终产物对大鼠主动脉平滑肌细胞单核细胞趋化蛋白1基因表达的影响

为探讨糖基化终产物对大鼠主动脉平滑肌细胞表达单核细胞趋化蛋白 1基因的影响 ,体外分离培养大鼠主动脉平滑肌细胞 ,然后用不同浓度葡萄糖 (0、5、2 0、5 0和 80mmol L)制备的糖基化终产物 BSA(2 0 0mg L)干预 2 4h和用葡萄糖浓度为 5 0mmol L孵育的糖基化终产物 BSA干预 0、12、2 4和 36h ,逆转录聚合酶链反应检测细胞中单核细胞趋化蛋白 1mRNA表达水平。结果发现 ,葡萄糖浓度 2 0mmol L、5 0mmol L和 80mmol L孵育的糖基化终产物都增加单核细胞趋化蛋白 1mRNA的表达 ,其中 5 0mmol L组作用最明显 (P <0 .0 0 5 ) ,干预 12h、2 4h、36h后单核细胞趋化蛋白 1mRNA表达均较未干预组明显增加 (P <0 .0 0 1)。结果提示 ,糖基化终产物促进大鼠主动脉平滑肌细胞单核细胞趋化蛋白 1基因的表达     

脂质过氧化诱导培养的内皮细胞表达单核细胞趋化蛋白-1

在人脐静脉和牛主动脉内皮细胞培养基中加入联胺，引发其脂质过氧化损伤，观察能否诱导内皮细胞表述单核细胞起化蛋白河。用斑点杂交法检测内皮细胞暴露于联胺后其单核细胞趋化蛋白-1mRNA的表达，杂交用的探针为了r32P5’末端标记的寡核苷酸探针。同时，用酶联免疫反应检测内皮细胞暴露于联胺后．其条件培养基中的单核细胞趋化蛋白-1蛋白含量。斑点杂交显示．培养的内皮细胞可表达单核细胞趋化蛋白-1mRNA，暴露于联胺后．其单核细胞趋化蛋白-1mRNA表达水平明显升高。而且，单核细胞趋化蛋白-1mRNA表达水平与联胺的作用时间和浓度均呈正相关。酶联免疫反应显示，各组条件培养基中的单核细胞趋化蛋白-1蛋白含量亦与联胺作用的时间和浓度呈正相关。提示内皮细胞的脂质过氧化损伤可诱导其产生单核细胞起化蛋白-1增加，在动脉粥样硬化发生过程中单核细胞的聚集可能起重要作用。     

核转录因子NF-κB对血管损伤和新生内膜形成的影响

目的:探讨核转录因子NF-κB对血管平滑肌细胞增殖以及大鼠颈动脉球囊损伤后血管新生内膜的作用。方法:原代培养大鼠胸主动脉血管平滑肌细胞。检测增殖的平滑肌细胞内增殖细胞核抗原(PCNA)和NF-κB水平。制作大鼠血管球囊损伤模型,检测血管新生内膜形成及单核细胞化学趋化因子(MCP-1)、NF-κBp65和细胞外信号调节激酶(ERK2)的表达。结果:增殖的平滑肌细胞PCNA和NF-κBp65蛋白水平表达增加。NF-κBp65反义和诱骗寡核苷酸抑制PCNA表达。大鼠血管球囊损伤后第7天,正义组、诱骗对照组、模型组的内膜面积、中膜面积、内膜/中膜比值达到高峰。反义组、诱骗组和反义诱骗组显著降低内膜与中膜比值(P<0.05)。球囊损伤后3d、5d、7d,MCP-1mRNA和蛋白质水平持续而明显的表达增强,14d后略为降低。反义组、诱骗组、反义诱骗组在各时间点均能减少MCP-1mRNA和蛋白质表达。Western Blot检测显示血管球囊损伤后7d,NF-κBp65、ERK2的蛋白合成达到高峰。反义组、诱骗组、反义诱骗组较模型组、正义组、诱骗对照组各时相点蛋白合成均减弱。结论:增殖的平滑肌细胞NF-κBp65基因表达增加。NF-κB调控PCNA、MCP-1、ERK2的基因表达和蛋白质水平。局部转染NF-κB反义和诱骗寡核苷酸能抑制血管新生内膜的形成。     

表达反义单核细胞趋化蛋白-1的重组逆转录病毒对家兔动脉平滑肌单核细胞趋化蛋白-1基因表达的影响

为研究反义单核细胞趋化蛋白－１ 转基因表达对单核细胞进入动脉壁的作用,首先构建了表达反义单核细胞趋化蛋白－ １ 基因的逆转录病毒重组体,并观察它在培养的细胞中的表达。将家兔单核细胞趋化蛋白－ １ ｃＤＮＡ 反向插入到ｐＬＮＣＸ,构成ＬＮＣＸ－ａｎｔｉ－ ＭＣＰ－１ 重组病毒质粒。再将重组质粒转染φ－２ 细胞,继以φ－ ２ 细胞产生的病毒上清感染ＰＡ３１７细胞,取得Ｇ４１８ＰＡ３１７ 抗细胞克隆。上述细胞经扩增培养,收集病毒上清并感染ＮＩＨ３Ｔ３ 细胞后进行检测。结果发现,病毒的滴度为５．６×１０７ ＣＦＵＬ,感染的ＮＩＨ３Ｔ３ 细胞中有重组病毒的整合。重组病毒感染培养的家兔动脉平滑肌细胞后,用聚合酶链反应检测发现,感染的平滑肌细胞基因组ＤＮＡ中有重组病毒整合;ＲＮＡｓｌｏｔ 杂交结果显示,感染的平滑肌细胞中有反义单核细胞趋化蛋白－１ 的表达,与未感染的平滑肌细胞相比,感染的平滑肌细胞中单核细胞趋化蛋白－ １ ｍＲＮＡ 的表达明显受到抑制。结果提示,反义单核细胞趋化蛋白－ １ 逆转录病毒表达载体在培养的动脉平滑肌中能表达反义基因并抑制靶基因的表达,为进一步开展体内实验研究奠定了基础     

血凝素样氧化型低密度脂蛋白受体1基因沉默抑制人脐静脉内皮细胞表达分形趋化因子和单核细胞趋化蛋白1

目的探讨血凝素样氧化型低密度脂蛋白受体1基因沉默后能否抑制氧化型低密度脂蛋白诱导的分形趋化因子和单核细胞趋化蛋白1的表达。方法分别用不同浓度的氧化型低密度脂蛋白与人脐静脉内皮细胞共孵育,及预先对人脐静脉内皮细胞转染pGenesil-1 LOX-1 shRNA后再用氧化型低密度脂蛋白刺激,半定量RT-PCR、Western blot及酶联免疫吸附法检测血凝素样氧化型低密度脂蛋白受体1、分形趋化因子和单核细胞趋化蛋白1的mRNA和蛋白表达。结果氧化型低密度脂蛋白能呈浓度依赖性诱导血凝素样氧化型低密度脂蛋白受体1、分形趋化因子和单核细胞趋化蛋白1的mRNA和蛋白表达(P<0.01)。用RNA干扰抑制血凝素样氧化型低密度脂蛋白受体1的表达后,显著抑制了氧化型低密度脂蛋白诱导的分形趋化因子和单核细胞趋化蛋白1的mRNA和蛋白表达(P<0.01)。结论氧化型低密度脂蛋白能呈浓度依赖性诱导人脐静脉内皮细胞中分形趋化因子和单核细胞趋化蛋白1表达;这种诱导作用可以被血凝素样氧化型低密度脂蛋白受体1基因沉默抑制。     

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.