褪黑素对内毒素血症大鼠肺动脉形态及舒张功能的影响

目的探讨褪黑素(MT)对脂多糖(LPS)诱导的内毒素血症大鼠肺动脉血管反应性紊乱的作用及相关机制。方法雄性SD大鼠分组如下:①溶剂对照组;②LPS组;③LPS+MT组;④MT组。检测各组大鼠血清总抗氧化能力;制备离体肺动脉血管环,应用血管张力检测技术检测各组血管环在iNOS抑制剂氨基胍、非特异性NOS抑制剂L-硝基精氨酸和血红素加氧酶-1抑制剂锌原卟啉孵育前后对苯肾上腺素和乙酰胆碱的反应性变化;应用HE染色和扫描电镜技术观察血管及内皮超微形态学改变。结果 LPS+MT组血清总抗氧化能力虽仍低于对照组水平(P0.01),但是与LPS组相比明显增高(P0.01);HE和电镜观察结果显示MT可减轻内毒素诱导的肺动脉组织的形态学改变;MT可显著改善LPS诱导的肺动脉对内皮依赖性舒张剂的低反应性,氨基胍和锌原卟啉孵育后,LPS组舒张反应继续下降,LPS组和LPS+MT组对PE的收缩反应均增高。结论 MT可以逆转肺动脉内皮依赖性舒张反应受抑,并能减少血管组织的结构损伤。     

L-精氨酸和氨基胍对糖尿病大鼠一氧化氮、一氧化氮合酶及肾功能的影响

目的探讨L-精氨酸和氨基胍对早期糖尿病大鼠一氧化氮、一氧化氮合酶活性及肾功能的影响。方法Wistar大鼠60只,检测其24 h尿蛋白排泄量、血清一氧化氮水平、总一氧化氮合酶和诱导型一氧化氮合酶及结构型一氧化氮合酶活性等5项指标。然后用链脲佐菌素60 mg/kg制备糖尿病大鼠模型,将糖尿病鼠随机分为糖尿病对照组、L-精氨酸组和氨基胍组。于8周末时再检测大鼠上述5项指标并进行统计分析。结果与造模前比较,糖尿病对照组在8周末时24 h尿蛋白排泄量(43.92±7.38 mg)、一氧化氮水平(42.2±6.92μmol/L)和诱导型一氧化氮合酶活性(19.75±3.85 kU/L)升高(P<0.01,P<0.05);L-精氨酸组24 h尿蛋白排泄量(100.47±43.42 mg)和一氧化氮水平(67.34±18.87μmol/L)显著升高(P<0.01);氨基胍组24 h尿蛋白排泄量(22.33±3.47 mg)增加(P<0.01),总一氧化氮合酶(23.34±3.10 kU/L)、诱导型一氧化氮合酶(14.84±1.98 kU/L)和结构型一氧化氮合酶(8.50±2.25 kU/L)降低(P<0.01,P<0.05)。与糖尿病对照组比较,8周末时L-精氨酸组24 h尿蛋白排泄量和一氧化氮均升高(P<0.05),总一氧化氮合酶、诱导型一氧化氮合酶和结构型一氧化氮合酶活性差异无显著性;氨基胍组与L-精氨酸组比较,上述5项指标均下降(P<0.05)。结论在糖尿病肾病早期应用L-精氨酸可增加血一氧化氮的合成,使24 h尿蛋白排泄量增加,损害肾功能;而早期应用氨基胍可降低血一氧化氮、一氧化氮合酶及24 h尿蛋白排泄量,保护肾功能。     

尾加压素Ⅱ对大鼠胸主动脉及肠系膜动脉各部分产生一氧化氮的影响

目的取离体大鼠胸主动脉和肠系膜动脉,将UⅡ与血管各层(内、中、外膜)组织共同孵育,观察UⅡ对NOS活性及NO生成的影响,以探讨UⅡ的血管活性效应的机理.材料与方法分离雄性SD大鼠胸主动脉和肠系膜动脉,将胸主动脉各层分离,上述组织分别加入不同浓度尾加压素Ⅱ在37 ℃、通以95%O2～5%CO2气体条件下进行血管组织孵育,孵育时间为2小时和4小时.测定孵育液中亚硝酸盐含量及组织中一氧化氮合酶活性.取最适浓度及最佳时间点,孵育血管后进行诱导型一氧化氮合酶免疫组织化学染色进行表达定位.结果尾加压素Ⅱ(10-9、10-8 mol/L)可以引起胸主动脉外膜一氧化氮生成增加,一氧化氮合酶活性增强,P<0.05,免疫组化证实血管外膜诱导型一氧化氮合酶表达呈强阳性,孵育2小时和4小时没有显著性差异,P>0.05;10-10～10-8 mol/L浓度尾加压素Ⅱ可以浓度依赖性、时间依赖性刺激肠系膜动脉一氧化氮生成,免疫组化证实诱导型一氧化氮合酶在血管外膜和中膜表达增加,但NOS活性没有明显变化.结论 UⅡ可以刺激胸主动脉和肠系膜动脉血管外膜产生NO.UⅡ对胸主动脉及肠系膜动脉NO/NOS系统影响不同,可能是UⅡ作用于血管引起不同生物学效应的机制之一.     

尾加压素Ⅱ对大鼠胸主动脉及肠系膜动脉各部分产生一氧化氮的影响

目的　取离体大鼠胸主动脉和肠系膜动脉 ,将UⅡ与血管各层 (内、中、外膜 )组织共同孵育 ,观察UⅡ对NOS活性及NO生成的影响 ,以探讨UⅡ的血管活性效应的机理。材料与方法　分离雄性SD大鼠胸主动脉和肠系膜动脉 ,将胸主动脉各层分离 ,上述组织分别加入不同浓度尾加压素Ⅱ在 37℃、通以 95 %O2 ～ 5 %CO2 气体条件下进行血管组织孵育 ,孵育时间为 2小时和 4小时。测定孵育液中亚硝酸盐含量及组织中一氧化氮合酶活性。取最适浓度及最佳时间点 ,孵育血管后进行诱导型一氧化氮合酶免疫组织化学染色进行表达定位。结果　尾加压素Ⅱ (1 0 - 9、1 0 - 8mol/L)可以引起胸主动脉外膜一氧化氮生成增加 ,一氧化氮合酶活性增强 ,P <0 0 5 ,免疫组化证实血管外膜诱导型一氧化氮合酶表达呈强阳性 ,孵育 2小时和 4小时没有显著性差异 ,P >0 0 5 ;1 0 - 1 0 ～ 1 0 - 8mol/L浓度尾加压素Ⅱ可以浓度依赖性、时间依赖性刺激肠系膜动脉一氧化氮生成 ,免疫组化证实诱导型一氧化氮合酶在血管外膜和中膜表达增加 ,但NOS活性没有明显变化。结论　UⅡ可以刺激胸主动脉和肠系膜动脉血管外膜产生NO。UⅡ对胸主动脉及肠系膜动脉NO/NOS系统影响不同 ,可能是UⅡ作用于血管引起不同生物学效应的机制之一。     

利拉鲁肽对离体大鼠胸主动脉环的血管舒张效应及其机制研究

目的：研究利拉鲁肽对离体大鼠胸主动脉环的血管舒张效应及其作用机制。
　　方法：分离32只SD雄性大鼠的胸主动脉环,分成去内皮组（n=16）和内皮完整组（n=16）。采用离体血管环实验方法,经生物信号采集与分析系统测定血管环张力的变化,观察利拉鲁肽（1×10-5 mol/L）对去甲肾上腺素（1×10-6 mol/L）预收缩的胸主动脉环的舒张作用。随后内皮完整组又分为左旋硝基精氨酸甲酯干预亚组（n=8）和格列苯脲干预亚组（n=8）,分别接受一氧化氮合酶抑制剂左旋硝基精氨酸甲酯（1×10-4 mol/L）和非特异性ATP敏感性钾通道（KATP）抑制剂格列苯脲（1×10-5 mol/L）的预处理,预处理后利拉鲁肽分别作用于预处理过的去甲肾上腺素预收缩的胸主动脉环,观察利拉鲁肽对离体大鼠胸主动脉环作用的影响。
　　结果：利拉鲁肽对基础状态的胸主动脉环无作用。去甲肾上腺素预收缩胸主动脉环后,当利拉鲁肽浓度达到1×10-5 mol/L时,利拉鲁肽对去内皮组和内皮完整组胸主动脉环均有舒张作用,但对内皮完整组舒张作用更强,胸主动脉环最大舒张幅度达17%（P<0.05）,差异有统计学意义。经左旋硝基精氨酸甲酯和格列苯脲预处理后,左旋硝基精氨酸甲酯干预亚组利拉鲁肽对胸主动脉环舒张幅度为4%（P<0.05）,与预处理前相比差异有统计学意义。格列苯脲干预亚组利拉鲁肽对胸主动脉环舒张幅度为14%（P>0.05）,与预处理前相比差异无统计学意义。
　　结论：利拉鲁肽对去甲肾上腺素预收缩的胸主动脉环有明显的舒张作用,其机制与内皮细胞一氧化氮合酶有关。而KATP未能阻断利拉鲁肽的血管舒张作用。     

模拟失重大鼠胸主动脉收缩功能的变化可能与Rho激酶改变有关

目的:观察模拟失重大鼠胸主动脉收缩功能的变化及Rho相关的蛋白激酶（Rho-associated protein kinase,ROCK）表达的改变,并探讨二者之间的关系。方法: 以尾部悬吊4周建立模拟失重大鼠模型并观察模拟失重对胸主动脉的主要生理的影响。采用离体血管环功能实验检测大鼠胸主动脉的收缩反应性变化;通过蛋白印迹技术检测大鼠胸主动脉ROCK II蛋白的表达。结果: 与对照组相比,悬吊组氯化钾、苯肾上腺素诱导的大鼠胸主动脉收缩功能均明显增强（P<0.05）。用ROCK特异性抑制剂Y-27632孵育1 h后,两组胸主动脉的收缩反应均显著降低至同一水平,两组间无统计学差异。蛋白印迹结果显示,悬吊组ROCK II的表达增加。结论: ROCK表达的改变可能在模拟失重大鼠胸主动脉收缩功能增强中发挥重要作用,去除ROCK的作用可消除模拟失重大鼠与正常大鼠胸主动脉收缩功能的差异。     

替米沙坦对代谢综合征大鼠血管反应性及解偶联蛋白-2表达的影响

目的:探讨血管紧张素Ⅱ受体拮抗剂替米沙坦(Telm)对代谢综合征(MS)大鼠血管功能和解偶联蛋白-2(UCP-2)表达的影响。方法:将45只2月龄的雄性Wistar大鼠,随机分为普食对照组、MS组和MS+Telm组,每组15只,喂养6月,测定鼠尾的血压。硝酸还原酶法检测血浆一氧化氮(NO)浓度,羟胺法测定超氧化物歧化酶(SOD)浓度,硫代硫酸巴比妥法(TBA法)测定丙二醛(MDA)水平,检测采用相应的试剂盒。取大鼠胸主动脉,利用体外血管环张力测定技术,检测其对苯肾上腺素(PE)、乙酰胆碱(Ach)和硝普钠(SNP)的反应。应用Westernblot法检测胸主动脉UCP-2和内皮型一氧化氮合酶(eNOS)的表达。结果:MS+Telm组体外胸主动脉对PE诱导的收缩反应明显低于MS组(P0.05),对Ach诱导的舒张反应明显高于MS组(P0.05)。MS+Telm组血浆SOD、NO的水平高于MS组,MDA的水平低于MS组(P0.05),其胸主动脉UCP-2、eNOS的表达明显高于MS组(P0.05)。结论:Telm能促进主动脉中UCP-2和eNOS的表达,有效改善MS大鼠血管的反应性。     

糖基化终产物对人脐静脉内皮细胞一氧化氮合酶活性和表达的影响及二甲双胍的保护作用

目的 探讨糖基化终产物及二甲双胍对人脐静脉内皮细胞一氧化氮合酶活性和表达的影响.方法 用胶原酶法分离人脐静脉内皮细胞并加以培养.将内皮细胞与不同浓度的糖基化终产物和二甲双胍分别孵育3、6、12、24 h,CCK-8法测定人脐静脉内皮细胞增殖活性.硝酸还原酶法测定一氧化氮含量,分光光度法测定一氧化氮合酶活性,蛋白免疫印迹法检测内皮型一氧化氮合酶蛋白表达水平.结果 糖基化终产物抑制人脐静脉内皮细胞增殖,二甲双胍促进人脐静脉内皮细胞增殖.糖基化终产物抑制人脐静脉内皮细胞的一氧化氮生成和一氧化氮合酶活性(P<0.01),呈剂量、时间依赖关系.二甲双胍(与对照组相比)或与糖基化终产物共同干预(与糖基化终产物组相比)均增加人脐静脉内皮细胞一氧化氮生成和一氧化氮合酶活性(P<0.01).糖基化终产物与人脐静脉内皮细胞共同孵育24 h后,内皮型一氧化氮合酶表达水平明显下降;二甲双胍上调内皮型一氧化氮合酶的表达;与糖基化终产物组相比,糖基化终产物与二甲双胍共同干预组内皮型一氧化氮合酶表达上调(P<0.01).结论 二甲双胍能够改善糖基化终产物导致的人脐静脉内皮细胞损伤.     

脂多糖对大鼠不同组织中一氧化氮合成酶基因表达的影响

通过Northernblot和NADPH－心肌黄酶染色显示一氧化氮合成酶活性的组织化学分析方法，观察了脂多糖对大氧心脏、主动脉和肾组织中诱导型一氧化氮合成酶基因表达的影响及诱导型一氧化氮合成酶被脂多糖诱导表达的动力学。结果表明，未经脂多糖处理的大鼠诱导型一氧化氮合成酶基因在所检测的三种组织中表达活性很低，脂多糖作用于大鼠2h，心、肾和主动脉中的诱导型一氧化氮合成酶mRNA开始增加，6h达到峰值，此后，逐渐下降，24h回复到对照水平。一氧化氮合成酶组织化学染色显示，对照大鼠的组织细胞内存在较低的组成型一氧化氮合成酶活性，被脂多糖处理不同时间后，三种组织中的一氧化氮合成酶活性均显著升高，到24h仍维持在较高水平，提示诱导型一氧化氮合成酶被合成后，在组织细胞内较为稳定。     

掌叶大黄水提取物对大鼠离体胸主动脉的舒张作用

目的 观察掌叶大黄水提取物的大鼠离体胸主动脉的舒张作用及其机制.方法 采用大鼠胸主动脉环张力测定法,观察掌叶大黄水提取物对内皮完整和去除内皮血管的舒张作用.应用一氧化氮合成酶抑制剂左旋硝基精氨酸甲酯、鸟苷酸环化酶抑制剂亚甲蓝、环氧化酶抑制剂吲哚美辛、钙激活钾通道阻滞剂四乙铵、ATP敏感钾通道阻滞剂格列本脲和电压依赖钾通道阻滞剂4-氨基吡啶研究掌叶大黄水提取物舒张血管的作用机制.结果 掌叶大黄水提取物能舒张由苯肾上腺素预收缩的大鼠胸主动脉环.在内皮完整的血管环中,0.03、0.1 g/mL的掌叶大黄水提取物预孵育后,能抑制去甲肾上腺素对大鼠胸主动脉的收缩作用;在去除内皮的血管环中,掌叶大黄水提取物舒张血管的作用无改变(P＞0.05).与对照组比较,左旋硝基精氨酸甲酯、亚甲蓝、吲哚美辛、格列本脲和4-氨基吡啶对掌叶大黄水提取物的舒张血管作用无抑制(P均＞0.05),而四乙铵可使掌叶大黄水提取物的舒张血管作用降低(P＜0.05).结论 掌叶大黄水提取物舒张血管的作用可能不依赖于血管内皮功能,而与激活钙激活钾通道有关.     

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.