Cl-通道在小牛血清引起的血管平滑肌细胞增殖中的作用

为探讨Cl^-通道在小牛血清引起的血管平滑肌细胞增殖中的作用,采用细胞计数和氚标胸腺嘧啶脱氧核苷掺入实验,并结合fura-2荧光测定细胞浆Ca^2 浓度等技术,研究了Cl^－通道阻断剂对大鼠血管平滑肌细胞增殖的影响。结果发现,Cl^-通道阻断剂4,4－二异硫氰酸二乙丙烯2,2－二磺酸（DIDS,0．01μmol/L－0．1mmol/L)可抑制5％小牛血清引起的血管平滑肌细胞增殖,其作用具有时效性和量效性,其它Cl^-通道阻断剂如茚满羟基丙酸（IAA－94,0．1μmol/L-1mmol/L)、二苯丙氨基－2,2－二羧酸（DPC,0．1μmol/L-1mmol/L)和速尿（10μmol/L-mmol/L)等均无此作用,且DIDS对电压依赖性钙通道没有直接的影响。结果提示小牛血清可以开放DIDS敏感的Cl^-通道,且该通道可能在小牛血清引起的小牛血清引起的血管平滑肌细胞增殖的调控上起着一定的作用。     

氯通道参与脑血管平滑肌细胞Ca2+池操纵性Ca2+内流

研究Cl-通道在牛脑血管平滑肌细胞Ca2+池操纵性Ca2+内流中的作用.采用培养的脑血管平滑肌细胞,在生物荧光双波长影像分析系统用Fura-2/Am荧光探针测定单个细胞内游离Ca2+浓度.结果发现① Cl-通道阻断剂DIDS(0.75 μmol/L)能降低内皮素1(10-7 mol/L)刺激引起的脑血管平滑肌细胞Ca2+内流,抑制率为29.6%±3.9%,随后加入Cl-通道阻断剂NPPB(10 μmol/L)能继续降低平台相,抑制率为44.9%±8.7%;交换加药顺序,NPPB能降低内皮素1刺激引起的Ca2+内流,DIDS能进一步降低Ca2+内流.②DIDS(0.75 μmol/L)能降低三磷酸腺苷(10 μmol/L)刺激引起的脑血管平滑肌细胞Ca2+内流,抑制率为26.7%±10.5%,随后加入NPPB(10 μmol/L)能继续降低平台相,抑制率为54.3%±9.6%;交换加药顺序,NPPB能降低三磷酸腺苷刺激引起的Ca2+内流,DIDS能进一步降低Ca2+内流.③DIDS(0.75 μmol/L)能降低环匹阿尼酸(10 μmol/L)刺激引起的脑血管平滑肌细胞Ca2+内流,抑制率为26.5%±5.0%,随后加入NPPB(10 μmol/L)能继续降低平台相,抑制率为46.1%±4.2%;交换加药顺序,NPPB能降低环匹阿尼酸刺激引起的Ca2+内流,DIDS能进一步降低Ca2+内流.提示对DIDS、NPPB敏感的非同一性Cl-通道参与内皮素1、三磷酸腺苷、环匹阿尼酸触发的脑血管平滑肌细胞 Ca2+池操纵性Ca2+内流.     

辣椒素对高盐致大鼠血管平滑肌细胞增殖的抑制作用

目的研究辣椒素对高盐诱导的大鼠血管平滑肌细胞(VSMC)增殖的抑制作用。方法组织贴壁法培养原代大鼠血管平滑肌细胞,根据MTT结果绘制大鼠血管平滑肌细胞的生长曲线,大鼠血管平滑肌细胞传至第4代去血清同步化24 h,不同浓度辣椒素(0.01μmol/L、0.1μmol/L、1μmol/L、10μmol/L、100μmol/L)进行高盐培养72 h,MTT比色法检测大鼠血管平滑肌细胞增殖情况,选取抑制血管平滑肌细胞增殖的辣椒素浓度进行后续实验。CCK-8检测渗透压对大鼠血管平滑肌细胞增殖的影响,流式细胞仪分析细胞增殖周期,免疫荧光染色法和Western blot检测增殖细胞核抗原(PCNA)的表达,实时荧光定量PCR检测瞬时受体电位家族香草醛1型受体(TRPV1)mRNA的表达,Western blot检测瞬时受体电位家族香草醛1型受体的蛋白表达。结果 MTT结果显示,辣椒素浓度为10μmol/L时大鼠血管平滑肌细胞增殖开始受抑制,100μmol/L时抑制作用增强(P0.05),选取10μmol/L辣椒素进行后续实验。CCK-8结果显示,高盐组细胞明显增殖,而甘露醇组、正常组和高盐+辣椒素组无差异。流式细胞仪测得高盐组G0/G1、G2/M期细胞比例减少(P0.05),S期细胞比例增多(P0.05);与高盐组比较,高盐+辣椒素组G0/G1、G2/M期细胞比例增加(P0.05),S期细胞比例下降(P0.05)。免疫荧光及Western blot结果显示,高盐组增殖细胞核抗原阳性细胞核增多,蛋白表达增加(P0.05),而高盐+辣椒素组增殖细胞核抗原阳性细胞核减少,蛋白表达减少(P0.05)。实时荧光定量PCR和Western blot结果显示高盐组瞬时受体电位家族香草醛1型受体mRNA及蛋白表达减少(P0.05),辣椒素组则增加(P0.05)。结论辣椒素可抑制高盐所致的大鼠血管平滑肌细胞增殖,其作用机制可能与激活瞬时受体电位家族香草醛1型受体表达有关。     

肾上腺素诱导的血管平滑肌细胞C1~-电流及其与Ca~(2 )运动的关系

为观察肾上腺素对主动脉平滑肌细胞C1- 电流的影响及其与Ca2 内流的关系 ,采用膜片钳单离子通道(细胞贴附式 )技术和Fura 2荧光法测定细胞内游离Ca2 浓度变化。结果发现 ,10 μmol L肾上腺素可引起氯通道开放概率由对照组的 0 .0 6 1± 0 .0 0 4 2增加到 0 .6 90± 0 .0 11;平均开放时间由 1.0 8± 0 .2 3ms延长到 6 .4 4± 0 .5 7ms。此Cl- 电流可被硝苯地平和EGTA抑制。肾上腺素可引起平滑肌细胞内游离Ca2 浓度由静息时 77± 13nmol L快速升高达峰值随后维持在高水平的内流平台相 ,达 2 16± 2 7nmol L。Cl- 通道阻断剂尼氟灭酸在一定范围内呈浓度依赖性抑制肾上腺素诱发的Cl- 电流及Ca2 内流 ,8μmol L尼氟灭酸对细胞内游离Ca2 浓度的抑制率达 2 7%± 8%。结果表明 ,Cl- 通道开放在调节平滑肌细胞Ca2 内流中起重要作用。     

替米沙坦对大鼠离体胸主动脉环的舒张机制研究

目的 观察替米沙坦对大鼠离体胸主动脉环张力的影响,并探讨其作用机制.方法 采用离体血管张力实验方法 .观察替米沙坦在1×10-9 mol/L,1×10-8 mol/L,1×10-7 mol/L,1×10-6 mol/L,1×10-5 mol/L浓度时,对去甲肾上腺素(NE,1×10-6 mol/L)、氯化钾(KCl,60 mmol/L)诱发大鼠离体胸主动脉环收缩的影响.观察Na+/Ca2+交换体阻断剂KB-R7943(1×10-6 mol/L)、KV通道阻断剂四胺基吡啶(4-AP,1×10-3 mol/L)、KATP通道阻断剂格列苯脲(Gli,1×10-5 mol/L)、KCa通道阻断剂四乙胺(TEA,1×10-2 mol/L)、KiR通道阻断剂氯化钡(BaCl2,1×10-3 mol/L)对替米沙坦作用的影响.结果替米沙坦对KCl(60 mmol/L) 预收缩的离体胸主动脉环张力无影响,对NE(1×10-6 mol/L) 预收缩的离体胸主动脉环产生浓度依赖性的舒张作用.用KB-R7943、4-AP、Gli预处理的血管环对替米沙坦的舒张反应与未经处理时比较无统计学意义(P>0.05).TEA及BaCl2可减弱替米沙坦对血管环的舒张作用(P<0.05).结论 替米沙坦对NE预收缩的大鼠胸主动脉环具有浓度依赖性的舒张作用,其舒张反应与Na+/Ca2+交换体、KV通道和KATP通道无关,可能与KCa通道及KiR通道有关.     

咪达唑仑对大鼠离体胸主动脉环的舒张机制研究

目的 观察咪达唑仑对大鼠离体胸主动脉环张力的影响,并探讨其作用机制.方法 采用离体血管张力试验方法.观察咪达唑仑在3×10-6t mol/L、1×10-5 mol/L,3×10-5 mol/L、1×10-4 mol/L浓度时,对去甲肾上腺素(NE,1×10-6 mol/L)、氯化钾(KCI,60mmol/L)诱发大鼠离体胸主动脉环收缩的影响.观察Na+/Ca2+交换体阻断荆KB-R7943(1×10-5 mol/L)、Kv通道阻断剂4-AP(4-AP,1×10-3 mol/L)、KATP通道阻断剂格列苯脲(Gli,1×10-5 mol/L)、KCa通道阻断剂四乙胺(TEA,1×10-2 mol/L)、K1R通道阻断剂氯化钡(BaCl2,1×10-3 mol/L)对咪达唑仑作用的影响.结果 各浓度咪达唑仑对预收缩的大鼠离体胸主动脉环有舒张作用.用KB-R7943、4-AP、TEA及BaCl2预处理的血管环对咪达唑仑的舒张反应与未经处理时比较无统计学意义(P>0.05).Gli可减弱咪达唑仑对血管环的舒张作用(P<0.05).结论 咪这唑仑对大鼠胸主动脉环具有浓度依赖性的舒张作用,其舒张反应与Na+/Ca2+交换体、Kv通道、KCa通道和K1R通道无关,可能与KATP通道有关.     

罗格列酮对血管紧张素Ⅱ诱导血管平滑肌细胞增殖的影响

目的 探讨罗格列酮对血管紧张素Ⅱ诱导血管平滑肌细胞增殖的影响及可能的机制.方法 原代培养大鼠血管平滑肌细胞,取第4～8代细胞进行实验.用终浓度为1 μmol/L血管紧张素Ⅱ诱导6 h,随机分成对照组(含10% FBS的DMEM培养基)、1 μmol/L血管紧张素Ⅱ组、不同浓度罗格列酮(20、30、40及50μmol/L) 干预组,30 μmol/L罗格列酮干预不同时间组 (6、12、18及24 h).分别采用MTT和流式细胞术观察血管平滑肌细胞增殖和增殖周期的变化;逆转录聚合酶链反应和免疫印迹法测定不同干预条件下血管平滑肌细胞血管紧张素Ⅱ2型受体mRNA和蛋白的表达水平.结果 血管紧张素Ⅱ组吸光值明显高于对照组(P<0.01),20、30、40及50μmol/L罗格列酮干预12 h及30μmol/L 罗格列酮干预6、12、18及24 h后,吸光值明显降低(P<0.05或P<0.01);血管紧张素Ⅱ组增殖指数和S期细胞分数明显高于对照组(P<0.01).随着罗格列酮干预浓度的增加或干预时间的延长,增殖指数、S期细胞分数及处于S期分数均明显下降(P<0.05或P<0.01).与血管紧张素Ⅱ组相比,不同浓度(20、30及50μmol/L)罗格列酮干预12 h及同一浓度(30μmol/L)干预不同时间(6、12及24 h)显著升高血管紧张素Ⅱ2型受体mRNA和蛋白的表达(P<0.05或P<0.01).结论 罗格列酮至少部分通过上调血管紧张素Ⅱ2型受体表达,阻止血管平滑肌细胞从G0/G1期向S期、G2/M期转化,从而抑制血管紧张素Ⅱ诱导血管平滑肌细胞的增殖、迁移,发挥血管保护作用.     

吲哚布芬舒张血管的作用及机制研究

目的研究吲哚布芬对离体大鼠胸主动脉张力的影响,并探讨其作用机制。方法采用离体血管张力记录法,观察吲哚布芬对大鼠主动脉血管环的作用及不同工具药的影响。结果吲哚布芬（0.3μmol/L、1μmol/L、3μmol/L、10μmol/L和30μmol/L）对KCl（30mmol/L）预收缩的血管环具有浓度依赖性舒张作用,去内皮组舒张作用弱于内皮完整组,说明此舒张作用具有部分内皮依赖性。在KCl预收缩基础上,非特异性NOS抑制剂L-NAME（100μmol/L）处理大鼠胸主动脉后,吲哚布芬的舒张血管作用部分被抑制;加入钾通道阻滞剂4-氨基吡啶4-AP（1mmol/L）、氯化钡BaCl2（1mmol/L）、格列苯脲Gli（10μmol/L）和四乙胺TEA（10mmol/L）,吲哚布芬舒张血管作用均被抑制。结论吲哚布芬具有浓度依赖的舒张血管作用且具有部分内皮依赖性;而其舒血管作用可被反向钠钙交换体阻滞剂KB-R7943增强。吲哚布芬对大鼠胸主动脉的舒张作用可能与KATP通道、Kv通道、KCa通道和KiR通道有关。     

波动性高糖对血管平滑肌细胞增殖及凋亡蛋白表达的影响

目的探讨波动性高葡萄糖对血管平滑肌细胞增殖及凋亡蛋白表达的影响。方法以持续高糖和波动性高糖分别孵育大鼠胸主动脉平滑肌细胞24 h,采用MTT法检测血管平滑肌细胞增殖活性,流式细胞术检测细胞周期改变,Western bloting检测胞浆中Bcl-2、Bax蛋白的表达。结果波动性高浓度葡萄糖(5.5 mmol/L和25mmol/L交替)培养较持续高浓度葡萄糖(25 mmol/L)培养可明显增加血管平滑肌细胞增殖活性,促进其由G0/G1期向S期转变,上调Bcl-2/Bax比值。结论波动性高葡萄糖可能通过干预细胞周期及对凋亡蛋白的调控,进一步促进血管平滑肌细胞增殖,诱导其凋亡,因而较持续性高葡萄糖更能促进糖尿病动脉粥样硬化的发生发展。     

同型半胱氨酸干扰胰岛素样生长因子2和H19的印迹表达及其与血管平滑肌细胞增殖的关系

目的采用动脉粥样硬化的独立危险因子同型半胱氨酸刺激脐静脉血管平滑肌细胞,观察同型半胱氨酸对血管平滑肌细胞胰岛素样生长因子2和H19表达的干扰作用,分析二者与血管平滑肌细胞增殖的关系及其在动脉粥样硬化发病中的可能作用。方法将培养的脐静脉血管平滑肌细胞分为0、50、100、200、500及1000μmol/L同型半胱氨酸组,以0μmol/L同型半胱氨酸组为空白对照组。用不同浓度的同型半胱氨酸刺激血管平滑肌细胞48 h后,MTT法检测血管平滑肌细胞的增殖水平;半定量逆转录聚合酶链反应法检测血管平滑肌细胞胰岛素样生长因子2和H19的mRNA表达水平,Western Blotting法检测血管平滑肌细胞胰岛素样生长因子2的蛋白表达水平。结果与空白对照组相比较,同型半胱氨酸各浓度组血管平滑肌细胞的增殖活力明显增加,以高浓度(500及1 000μmol/L)组为著(P0.05)。同时,同型半胱氨酸组血管平滑肌细胞H19的mRNA表达水平增加,500及1000μmol/L浓度组(0.548 6±0.063 3及0.733 3±0.049 6)明显高于空白对照组(0.202 2±0.012 4)(P0.05);胰岛素样生长因子2的mRNA和蛋白表达均下降,尤以高浓度组为著,500及1 000μmol/L浓度组的mRNA(0.258 8±0.024 8及0.168 9±0.069 6)和蛋白(0.116 7±0.015 5及0.083 7±0.018 0)表达水平均明显低于空白对照组(0.515 8±0.018 9和0.244 3±0.042 3)(P0.05)。结论同型半胱氨酸能干扰胰岛素样生长因子2和H19的表达,并可能进一步促进血管平滑肌细胞的增殖。     

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。     

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。     

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。     

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.