槟榔碱促结肠平滑肌细胞收缩及对胞内钙离子浓度的影响

目的:观察氢溴酸槟榔碱(Ah)促进培养的结肠平滑肌细胞收缩作用及对胞内游离Ca2 浓度的影响．方法:培养大鼠结肠平滑肌细胞,分为4组:正常对照组、Ah刺激组、乙酰胆碱(Ach)刺激组、阿托品预处理组．应用特异性Ca2 荧光批示剂Fluo-3／AM负载细胞,激光共聚焦显微镜检测游离Ca2 浓度和细胞收缩率．结果:正常对照组细胞未发生自主性收缩,因指示剂的衰减,荧光强度(FI)有递减的趋势; Ah刺激组在加药后短时间内胞内钙离子浓度迅速升高,出现一个波峰,FI平均基础值与峰值有差异(P<0．05),而后胞内钙离子浓度再缓慢攀升,在484．0±47．6 s达到高峰,而后有一个较长时间的平台期,在1 400 s左右恢复至静息水平,FI基础值与峰值有显著差异 (P<0．01),细胞收缩百分数为20．70％±0．07％; Ach刺激组在加药后胞内钙离子浓度升高,形成一个小波峰,FI基础值和峰值差异有显著性(P<0．01)．随后胞内钙离子浓度缓慢攀升, 在600 s左右达到高峰,而后有一个较长时间的平台期．FI基础值与峰值差异有显著性 (P<0．001);经阿托品预孵育处理后的细胞,加入Ah后,其收缩效应被完全抑制．结论:Ah可引起结肠平滑肌细胞收缩,升高细胞内游离Ca2 浓度．其收缩效应可以被M受体阻断剂阿托品所抑制．     

钌红、丁卡因对肺动脉高压模型大鼠肺动脉平滑肌细胞[Ca2+]i释放功能的影响

目的:分析肺动脉高压时肺动脉平滑肌细胞雷诺定(Ryanodine)受体[Ca2+]i释放功能的改变及钌红(Rutheniumred)、丁卡因对肺动脉高压模型大鼠肺动脉平滑肌细胞[Ca2+]i释放功能的影响.方法:清洁级Wister大白鼠25只,腹腔注射野百合碱,建立大鼠肺动脉高压模型,死亡2只,最终23只;原代培养肺动脉平滑肌细胞;Fura-2/AM(钙离于荧光指示剂)负载培养细胞;荧光测钙技术比较雷诺定诱导的野百合碱组(n=15)及对照组(n=8)[Ca2+]i数值,观测钌红、丁卡因对雷诺定受体激动剂雷诺定诱导的[Ca2+]i变化的影响.结果:10 nmol/L雷诺定使对照组[Ca2+]i平均增加(93.31±12.41)nmoL/L,使野百合碱组[Ca2+]i平均增加(141.71±13,59) nmol/L;两组样本[Ca2+]i增加的数值比较差异有统计学意义(P＜0.01).钌红浓度为o.5～ 10 μmol/L、丁卡因浓度为2～40 μnoL/L时,可使雷诺定受体激动剂雷诺定诱导的[Ca2+]i值最大下降(115.32±7.47) nmol/L和(107.97±7.11) nmol/L.结论:肺动脉高压大鼠肺动脉平滑肌细胞对雷诺定受体激动剂雷诺定的敏感性增强;钌红、丁卡因对雷诺定诱导的肺动脉高压大鼠肺动脉平滑肌细胞[Ca2+]i上升有明显的抑制作用.     

急性缺氧对环匹阿尼酸诱导的大鼠远端肺静脉平滑肌细胞内钙浓度升高的影响

目的:研究急性缺氧对Ca2+-ATPase抑制剂——环匹阿尼酸(CPA)诱导的大鼠远端肺静脉平滑肌细胞(PVSMC)内钙浓度([Ca2+]i)升高的影响及机制。方法:选用6只雄性SD大鼠(体重200~250 g),培养大鼠PVSMC,运用荧光显微镜和细胞内钙浓度检测系统观测CPA及急性缺氧(4%O2)对PVSMC的[Ca2+]i影响及钙池操纵性钙通道(SOCC)阻断剂氯化镍(Ni Cl2)和SKF96365的干预作用。结果:含5μmol/L硝苯地平(电压依赖钙通道阻断剂)的无钙Krebs溶液孵育PVSMC,10μmol/L CPA使PVSMC的[Ca2+]i小幅度升高,急性缺氧能使[Ca2+]i升高幅度增加;恢复细胞外Ca2+至2.5 mmol/L后,10μmol/L CPA使[Ca2+]i显著升高,急性缺氧可导致CPA诱导的[Ca2+]i升高显著增强;SOCC阻断剂Ni Cl2(500μmol/L)和SKF96365(50μmol/L)均能明显抑制急性缺氧条件下CPA诱导的[Ca2+]i升高,但对高钾(60 mmol/L KCl)Krebs溶液引起的[Ca2+]i反应无影响。结论:急性缺氧能够使CPA诱导的大鼠远端PVSMC的[Ca2+]i升高增强,[Ca2+]i升高可被SOCC阻断剂阻断,提示急性缺氧能够增强SOCC活性,使细胞外Ca2+通过SOCC内流增强,从而导致大鼠远端PVSMC的[Ca2+]i升高。     

槲皮素对家兔主动脉血管平滑肌细胞胞内游离钙浓度的影响

目的: 探讨槲皮素(Que)对血管平滑肌细胞胞内游离钙浓度([Ca2+]i)的影响.方法:采用新一代钙荧光探剂Fluo-3/AM检测Que对培养的兔主动脉血管平滑肌细胞(ASMC) [Ca2+]i 在高K+、去甲肾上腺素(NE)、血管紧张素Ⅱ(AngⅡ)刺激作用下的改变,并与Verapamil进行对照研究.结果:Que(10-6、 10-5、10-4mol/l)呈剂量依赖性抑制高K+去极化引起的[Ca2+]i 升高,与Verapamil作用相似,但弱于Verapa mil;Que (10-6～10- 4mol/L)对NE,AngⅡ通过受体介导引起的[Ca2+]i 增高也具有明显的抑制作用.但Que对静息状态的ASM C[Ca2+]i 无明显影响.结论:Que通过对血管平滑肌细胞电压依赖性钙通道和受体操纵性钙通道双重抑制作用,降低细胞内游离钙水平,这可能是其舒血管降压机制之一.     

环孢霉素A对心肌细胞结构和胞内钙离子浓度的影响

目的:探讨不同浓度的环孢霉素A(cyclosporine,CsA)在不同时间点对心肌细胞形态及胞内钙离子浓度([Ca2+]i)的影响。方法:分别将1×10-3g/L、1×10-2g/L、2×10-2g/L的CsA与原代培养的Wistar乳鼠(1~3 d)心肌细胞(n=6)共孵育,于2 h、4 h、6 h、8 h和12 h后,采用相差显微镜观察各组心肌细胞的结构及收缩性;应用激光共聚焦显微镜观察心肌细胞内[Ca2+]i的变化。结果:不同浓度的CsA作用2 h后,与对照组相比较,各组心肌细胞的形态及收缩性无明显变化。1×10-3g/L和1×10-2g/L CsA组心肌细胞内的[Ca2+]i与对照组比较无明显差异;但2×10-2g/L CsA组心肌细胞内的[Ca2+]i较其他3组明显增加(P0.01)。作用4 h后,随着CsA浓度的增加,CsA组细胞的收缩性逐渐减弱,胞浆内可见小颗粒逐渐增多;各CsA组心肌细胞内的[Ca2+]i与对照组比较显著增加(P0.05);与1×10-3g/L CsA和对照组相比较,1×10-2g/L和2×10-2g/L CsA组增加明显(P0.05)。作用6 h后,随着CsA浓度的增加,各浓度CsA组与对照组比较,可见细胞内小空泡逐渐增多,细胞的收缩性逐渐减弱。各组心肌细胞内的[Ca2+]i随着CsA浓度的增加逐渐升高,各组组间具有显著差异(P0.05)。作用8 h和12 h后,1×10-3g/L CsA组的心肌细胞出现部分溶解,1×10-2g/L和2×10-2g/L CsA组心肌细胞的损伤严重,出现大面积死亡、溶解。结论:CsA可引起原代培养的心肌细胞损伤,收缩性减弱,且具有剂量和时间依赖性,可能与其引起的细胞内[Ca2+]i的增加有关。     

地塞米松快速抑制气道平滑肌内游离钙升高实验初探

目的 通过对平滑肌细胞行地塞米松快速预处理,拟证实糖皮质激素对平滑肌细胞内游离钙离子浓度[Ca2+]i升高有快速抑制作用.方法 原代培养的大鼠平滑肌细胞,比较不同浓度地塞米松预处理后10 min与对照组之间游离钙上升情况的区别.利用Fura-2/AM显微荧光检测技术,检测肌细胞内[Ca2+]i在受到激动剂刺激后的浓度变化;同时设立RU486及CHX对照组,排除基因组作用在该反应中的影响.结果 地塞米松温浴10 min,能够明显降低Ach引起的气道平滑肌细胞内[Ca2+]i峰值.以上反应均不能被RU486和CHX影响或者逆转.结果 地塞米松能够通过非基因组作用快速抑制Ach引起的气道平滑肌细胞内[Ca2+]i浓度升高.     

神经肽Y对大鼠血管平滑肌细胞内钙离子浓度的影响

目的 应用激光共聚焦显微镜动态观察神经肽Y(NPY)受体激动剂[Leu31, Pro34]-NPY干预大鼠血管平滑肌细胞(VSMC)产生的细胞内钙离子([Ca2 ]i)浓度变化,以确定NPY对大鼠VSMC[Ca2 ]i浓度的影响.方法 用分散细胞培养法培养VSMC.用10 μmol/L的Fluo-3孵育细胞.使其与细胞内的游离[Ca2 ]i相结合,从而能够在525 nm的激发光激发下产生荧光.分别用正常细胞外液、无钙细胞外液稀释的10-6 mol/L[Leu31, Pro34 ]-NPY、1 μmol/L硝苯地平、10-6 mol/L[Leu31, Pro34 ]-NPY 1 μmol/L硝苯地平灌流细胞,同时用激光共聚焦显微镜扫描、记录图像.用Leica图像分析系统分析图像,定量分析不同情况下的[Ca2 ]i荧光强度.结果 正常细胞外液灌流时[Ca2 ]i变化不明显,最高值为57.3±3.1,最低值为53.7±2.9,无明显差异(P＞0.05). [Leu31, Pro34]-NPY干预细胞时,[Ca2 ]i明显地升高,随后又开始下降.最高值为86.4±2.7,最低值为58.1±3.0,有非常显著差异(P＜0.01).无钙细胞外液 [Leu31, Pro34 ]-NPY灌流VSMC时[Ca2 ]i浓度变化不明显,最高值为52.5±3.5,最低值为48.0±1.2(P＞0.05);[Leu31, Pro34 ]-NPY 硝苯地平组[Ca2 ]i变化不明显,最高值为52.6±2.1,最低值为51.7±2.7,差异无统计学意义(P＞0.05).硝苯地平组[Ca2 ]i呈下降趋势,最高值为52.8±2.2,最低值为37.5±2.1,有非常显著差异(P＜0.01).结论 NPY能够通过NPY-Y1受体使细胞内的[Ca2 ]i浓度升高,这种升高是依赖于细胞外的[Ca2 ]i由L型[Ca2 ]i通道进入细胞的.     

神经肽Y对大鼠血管平滑肌细胞内钙离子浓度的影响

目的应用激光共聚焦显微镜动态观察神经肽Y(NPY)受体激动剂[Leu31,Pro34]-NPY干预大鼠血管平滑肌细胞(VSMC)产生的细胞内钙离子([Ca2 ]i)浓度变化,以确定NPY对大鼠VSMC[Ca2 ]i浓度的影响。方法用分散细胞培养法培养VSMC。用10μmol/L的Fluo-3孵育细胞。使其与细胞内的游离[Ca2 ]i相结合,从而能够在525nm的激发光激发下产生荧光。分别用正常细胞外液、无钙细胞外液稀释的10-6mol/L[Leu31,Pro34]-NPY、1μmol/L硝苯地平、10-6mol/L[Leu31,Pro34]-NPY 1μmol/L硝苯地平灌流细胞,同时用激光共聚焦显微镜扫描、记录图像。用Leica图像分析系统分析图像,定量分析不同情况下的[Ca2 ]i荧光强度。结果正常细胞外液灌流时[Ca2 ]i变化不明显,最高值为57.3±3.1,最低值为53.7±2.9,无明显差异(P>0.05)。[Leu31,Pro34]-NPY干预细胞时,[Ca2 ]i明显地升高,随后又开始下降。最高值为86.4±2.7,最低值为58.1±3.0,有非常显著差异(P<0.01)。无钙细胞外液 [Leu31,Pro34]-NPY灌流VSMC时[Ca2 ]i浓度变化不明显,最高值为52.5±3.5,最低值为48.0±1.2(P>0.05);[Leu31,Pro34]-NPY 硝苯地平组[Ca2 ]i变化不明显,最高值为52.6±2.1,最低值为51.7±2.7,差异无统计学意义(P>0.05)。硝苯地平组[Ca2 ]i呈下降趋势,最高值为52.8±2.2,最低值为37.5±2.1,有非常显著差异(P<0.01)。结论NPY能够通过NPY-Y1受体使细胞内的[Ca2 ]i浓度升高,这种升高是依赖于细胞外的[Ca2 ]i由L型[Ca2 ]i通道进入细胞的。     

高糖和高胰岛素对影响血管平滑肌细胞舒缩信号分子的作用

目的观察高糖和高胰岛素对几个调控血管平滑肌细胞(VSMC)舒缩功能信号分子的作用,探讨糖尿病并发高血压的分子机制。方法将培养的大鼠主动脉VSMC随机分成对照组、高糖组(葡萄糖浓度25 mmol/L)、高胰岛素组(胰岛素浓度50μU/ml)、高糖+高胰岛素组、生理浓度胰岛素组(胰岛素浓度10μU/ml)、高糖+生理浓度胰岛素组。蛋白免疫印迹法测定细胞诱导型一氧化氮合酶(iNOS)、内皮型一氧化氮合酶(eNOS)、小分子鸟苷酸蛋白A(RhoA)、Rho激酶-1(ROCK-1)蛋白表达,比率荧光倒置显微镜检测细胞内钙水平([Ca2+]i)。结果高糖组iNOS、eNOS表达减少,[Ca2+]i升高,RhoA、ROCK-1表达明显升高;高胰岛素组iNOSe、NOS表达明显升高,[Ca2+]i明显降低,RhoA、ROCK-1无明显改变;生理胰岛素组iNOSe、NOS表达明显升高,[Ca2+]i、RhoA、ROCK-1无明显改变;当同时给予胰岛素和葡萄糖刺激时,胰岛素可拮抗高糖对上述4种分子的蛋白表达及[Ca2+]i的增加。结论高糖损害VSMC正常收缩舒张功能,而胰岛素可拮抗高糖对VSMC收缩舒张功能的损害作用。     

钙稳态失衡在致结肠平滑肌收缩性改变中的作用

目的:应激可影响胃肠运动,是肠易激综合征(IBS)的重要发病因素之一。钙离子(Ca2+)在平滑肌收缩运动中起重要作用,肌细胞收缩时,胞浆内游离Ca2+浓度([Ca2+]i)增加来源于细胞外Ca2+内流或肌浆网贮存钙释放;Ca2+可通过肌浆网再摄取或通过细胞膜排出胞外,导致[Ca2+]i降低,平滑肌舒     

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.