P38MAPK抑制剂SB202190体外抑制细粒棘球蚴原头节生长的研究*

【摘要】 目的 探讨P38MAPK抑制剂SB202190体外抑制细粒棘球蚴原头节生长的作用。 方法 将体外培养的细粒棘球蚴原头节分别加入12.5、25、50、100μmol/L的 SB202190中体外孵育。利用伊红染色的方法,在光镜下观察原头节的活力变化。实验重复三次;扫描电子显微镜下（SEM）下观察SB202190作用后原头节表面超微结构改变;不同浓度SB202190作用24小时后,半胱氨酸天冬氨酸蛋白酶-3（caspase-3）活性检测试剂盒检测caspase-3酶活性。结果 50μmol/L和100μmol/L 的SB202190作用1天后,头节活力开始下降。作用14天后,100μmol/LSB202190组无存活的头节,50mol/LSB202190组的头节活力仅为13.8%。超微结构显示100μmol/LSB202190作用6d后,原头节顶突外翻、变形,顶突界面缺损,吸盘变形,体表出现虫蛀样损害。不同浓度SB202190作用24h后,与正常对照组比较,SB202190抑制剂高浓度组原头节的caspase-3表达明显增高。结论 P38MAPK抑制剂SB202190在体外有明显的抑制细粒棘球蚴原头节生长的作用。     

ERK抑制剂PD98059体外抗细粒棘球绦虫原头蚴作用的研究

目的探讨ERK1/2抑制剂PD98059体外抗细粒棘球绦虫原头蚴作用。方法体外培养细粒棘球绦虫原头蚴,分组后分别加入100、50、25、12.5μmol/L的PD98059后继续培养7d,利用伊红染色方法在倒置显微镜下观察原头蚴的活力,实验重复3次,绘制原头蚴活力曲线;扫描电子显微镜(SEM)下观察不同浓度PD98059组原头节表面结构改变。结果 PD98059作用1d对细粒棘球蚴原头节具有杀伤作用,第7d100μmol/L PD98059组原头节的活力仅为(12.4±0.9)%。超微结构显示原头节顶突外翻、变形,顶突界面缺损,吸盘变形,甚至出现虫蛀样损害。结论 PD98059在体外有显著的抗细粒棘球蚴原头节的作用,可认为是一种新型的抗包虫药物。     

石蒜碱及其与阿苯达唑联合体外抗细粒棘球蚴原头节的作用研究

目的观察比较石蒜碱、阿苯达唑及石蒜碱联合阿苯达唑体外抗细粒棘球蚴原头节的作用。方法从感染羊肝上提取细粒棘球蚴原头节,体外培养3d后,分别用石蒜碱(100、500、1 000μmol/L)、阿苯达唑(50μmol/L)、石蒜碱联合阿苯达唑(100μmol/L+50μmol/L)处理细粒棘球蚴原头节,在处理后的第1、3、5、7、9d,用1%伊红染色后显微镜下观察原头节的活性,使用多因素重复测量方差分析检验各组间原头节活性率的差异。结果经100、500、1 000μmol/L的石蒜碱体外作用9d后,原头节的活性分别为72.70%、14.09%和0。石蒜碱不同剂量组处理后的原头节的活性与对照组比较,差异有统计学意义(P0.05);石蒜碱高、中、低剂量组之间比较,差异有统计学意义(P0.05);在相同浓度石蒜碱处理组内,不同测量时间点之间比较,差异具有统计学意义(P0.05)。石蒜碱联合阿苯达唑(100μmol/L+50μmol/L)、阿苯达唑(50μmol/L)及低剂量石蒜碱(100μmol/L)体外作用9d后,原头节的活性分别为50.20%、90.22%和72.70%,差异有统计学意义(P0.05)。结论石蒜碱具有体外抗细粒棘球蚴原头节的作用,并表现出时间和浓度依赖性,且与阿苯达唑具有协同作用。     

黄腐酚对体外泡状棘球蚴原头节活性的影响

目的探讨不同浓度黄腐酚在体外对泡状棘球蚴原头节活性及形态学影响。方法将体外培养的泡状棘球蚴原头节随机分为6组:空白对照组,溶剂对照组和黄腐酚10、20、40、80μmol/L组,培养7 d,每24 h用0.1%伊红染色后在倒置显微镜下观察原头节的活性并计算成活率;黄腐酚作用泡状棘球蚴原头节3 d后,应用半胱天冬氨酸蛋白酶-3(caspase-3)检测试剂盒检测caspase-3活性;Western blot检测体外培养3d后的原头节Bcl-2、Bax蛋白表达量;使用活性氧检测试剂盒检测体外作用24 h后6组原头节内活性氧(ROS)变化水平。结果随着药物浓度升高,泡状棘球蚴原头节活力降低,空白对照组、溶剂对照组泡状棘球蚴原头节在第7 d的活力分别为(97.26±0.208)%、(97.33±0.305)%,第7 d 10μmol/L、20μmol/L、40μmol/L黄腐酚组泡状棘球蚴原头节的活力分别为(42.06±0.404)%、(24.10±0.200)%、(11.83±0.416)%,均低于对照组(P均0.05)。80μmol/L黄腐酚组杀伤作用较强,原头蚴的活力为(0.96±0.208)%。不同浓度黄腐酚组作用原头蚴3 d, caspase-3活性与对照组相比显著增高(P0.05)。黄腐酚不同浓度作用原头蚴3 d后,凋亡抑制蛋白Bcl-2表达下降,而凋亡蛋白Bax表达随着药物浓度的增加而显著上调(P0.05)。不同浓度黄腐酚作用24 h后原头节体内活性氧(ROS)水平与对照组相比显著升高(P0.05)。结论黄腐酚在体外具有一定杀灭泡球蚴原头节作用,并表现出时间依赖性和浓度依赖性。其机制可能与caspase-3活性增强、Bax表达水平升高、Bcl-2表达水平降低、ROS水平增高诱导头节细胞的凋亡有关。     

羟基喜树碱对细粒棘球蚴原头节的生长抑制作用及其机制

目的观察羟基喜树碱(HCPT)对体外培养的细粒棘球蚴原头节生存抑制作用及其机制,寻找减少肝脏包虫病术后复发和术中头节外溢的安全高效的可行性药物,并探索其药物作用靶点,为肝脏包虫病的治疗用药提供更多的选择。方法体外培养细粒棘球蚴原头节,分别加入浓度为2.5μmol/L和5μmol/L的HCPT中,37℃恒温孵育2 d和4 d后伊红染色检测原头节生长活力;采用酶标法检测ROS,GSH和caspase-3活性;Western blot检测GRP78和Caspase-12蛋白表达水平。结果 HCPT对细粒棘球蚴生长有抑制作用,HCPT2.5μmol/L和5μmol/L作用4 d,细粒棘球蚴原头节的活力分别为28.2%和7.5%,差异有统计学意义(P0.05)。高浓度HCPT组ROS和caspase-3含量与对照组比较增高,GSH含量降低(P0.05);高浓度HCPT作用组GRP78和Caspase-12表达量与对照组比较增加(P0.05)。结论 HCPT体外可抑制细粒棘球蚴原头节存活,内质网应激机制可能参与其中。     

羟基喜树碱对细粒棘球蚴原头节的生长抑制作用及其机制北大核心CSCD

目的观察羟基喜树碱(HCPT)对体外培养的细粒棘球蚴原头节生存抑制作用及其机制,寻找减少肝脏包虫病术后复发和术中头节外溢的安全高效的可行性药物,并探索其药物作用靶点,为肝脏包虫病的治疗用药提供更多的选择。方法体外培养细粒棘球蚴原头节,分别加入浓度为2.5μmol/L和5μmol/L的HCPT中,37℃恒温孵育2 d和4 d后伊红染色检测原头节生长活力;采用酶标法检测ROS,GSH和caspase-3活性;Western blot检测GRP78和Caspase-12蛋白表达水平。结果 HCPT对细粒棘球蚴生长有抑制作用,HCPT2.5μmol/L和5μmol/L作用4 d,细粒棘球蚴原头节的活力分别为28.2%和7.5%,差异有统计学意义(P<0.05)。高浓度HCPT组ROS和caspase-3含量与对照组比较增高,GSH含量降低(P<0.05);高浓度HCPT作用组GRP78和Caspase-12表达量与对照组比较增加(P<0.05)。结论 HCPT体外可抑制细粒棘球蚴原头节存活,内质网应激机制可能参与其中。     

过氧化氢体外诱导细粒棘球蚴原头节细胞Caspase-3表达及超微结构改变的影响

目的探讨过氧化氢(H2O2)体外诱导细粒棘球蚴原头节细胞凋亡、Caspase-3表达和细胞超微结构的影响。方法RPMI1640添加谷氨酰胺组即体外培养细粒棘球蚴原头节,用5mmol/L H2O2诱导8h,使其发生细胞凋亡。用原位末端脱氧核糖核苷酸转移酶标记技术(TUNEL法)检测原头节细胞凋亡情况,用过氧化物酶标记链霉卵白素(SP)染色半胱天冬氨酸蛋白酶-3(caspase-3)。在透射电镜下观察原头节细胞超微结构的变化。结果过氧化氢诱导原头节细胞凋亡细胞增加,caspase-3表达增加,电镜观察原头节细胞异染色质增加,部分细胞染色质异常浓缩呈现凋亡细胞征象。结论H2O2可诱导细粒棘球蚴原头节细胞凋亡,且caspase-3参与原头节细胞的凋亡。     

达克罗宁对细粒棘球蚴原头节体外作用及其ROS水平的影响

目的初步探究达克罗宁对细粒棘球蚴原头节体外生长的影响以及原头节内ROS的表达情况。方法用达克罗宁与细粒棘球蚴原头节体外共培养,采用0.1%曙红排斥试验观察原头节的形态,统计存活率并绘制原头节的生存曲线;将DCFH-DA探针加入孵育原头节的培养基以检测其ROS活性;用SOD和Caspase-3试剂盒测定SOD和Caspase-3的活性。结果 40μg/ml达克罗宁可使体外培养的原头节在第4d全部死亡;达克罗宁以剂量依赖的方式使原头节的ROS和Caspase-3表达量增加,同时降低SOD的活性。结论达克罗宁具有体外抗细粒棘球蚴原头节作用,通过激活ROS诱导氧化应激导致Caspase-3被激活从而引起细粒棘球蚴原头节的凋亡。     

去氢骆驼蓬碱体外诱导细粒棘球蚴原头节凋亡过程中caspase-3及抗氧化酶活性检测分析

目的观察不同浓度去氢骆驼蓬碱体外诱导细粒棘球蚴原头节生长凋亡过程中虫体活力、Caspase-3及相关抗氧化酶活性变化。方法将体外培养的细粒棘球蚴原头节分为空白对照组、溶剂组、阿苯达唑(ABZ)阳性对照组及不同浓度去氢骆驼蓬碱(25、50μmol/L)处理组进行体外干预试验,于48、96、144、192、240、288h后取样,经0.1%伊红染色后置于倒置显微镜下观察原头节活力。试验重复验证3次,绘制活力曲线图。用ELISA试剂盒检测作用48h、96h后各浓度组原头节caspase-3及抗氧化酶HO-1和NQO-1的活性变化。结果去氢骆驼蓬碱处理组从作用第48h开始原头节活力开始下降,培养至第240h时25μmol/L组原头节死亡率为97.9%,50μmol/L组原头节均死亡。ELISA法测定25、50μmol/L去氢骆驼蓬碱作用原头节48h后caspase-3活性分别为(32.776±8.437)ng/ml和(52.129±5.949)ng/ml,与空白对照组比较差异有统计学意义(P0.05);ELISA法测定25、50μmol/L去氢骆驼蓬碱作用48、96h后原头节抗氧化酶HO-1和NQO-1活性分别为(0.563±0.031)ng/ml、(1.832±0.10)ng/ml和(0.425±0.011)ng/ml、(1.288±0.05)ng/ml,差异均有统计学意义(P0.05),且呈时间及剂量依赖性。结论去氢骆驼蓬碱能抑制体外培养的细粒棘球蚴原头节的生长,并能降低caspase-3及抗氧化酶活性,具体机制有待进一步研究。     

阿霉素体外抗细粒棘球蚴原头节作用研究

目的研究阿霉素(Dox)对细粒棘球蚴原头节的体外抑制作用。方法 4 800个原头节随机分为空白对照组、 1%DMSO组、 Dox组(25、 50、 100、 200、 400、 600μmol/L),每组200个原头节,设3个平行组,体外干预24 h。伊红拒染实验检测Dox干预后原头节活力,统计存活率。扫描电镜观察Dox干预后原头节表面超微结构变化。单细胞凝胶电泳实验检测Dox干预后原头节DNA损伤程度。实时荧光定量PCR (qRTPCR)检测Dox干预后DNA损伤相关基因共济失调毛细血管扩张症突变激酶(ATM)、 p53、 DNA拓扑异构酶2A (Topo2a)的mRNA表达水平。结果伊红拒染实验结果显示,空白对照组、 1%DMSO组、 25、 50、 100、 200、 400、600μmol/L Dox组细粒棘球蚴原头节的存活率分别为(99.0±0.5)%、(98.6±0.3)%、(96.0±1.4)%、(80.3±4.8)%、(75.6±6.2)%、(53.2±3.0)%、(26.4±8.1)%和0, IC50为(267.9±7.1)μmol/L。与空白对照组相比,1%DMSO组、 25μmol/L Dox组原头节存活率差异无统计学意义(P 0.05), 50、 100、 200、400、 600μmol/L Dox组原头节存活率差异有统计学意义(P 0.01)。扫描电镜结果显示,空白对照组、 1%DMSO组原头节表面光滑,头节呈球形或椭圆形,顶突完整,微毛清晰可见;400μmol/L Dox组原头节吸盘变形,体部塌陷严重,顶突轻微变形,微毛明显脱落,虫体表层发生皱缩。单细胞凝胶电泳实验结果显示,100μmol/L Dox组原头节出现拖尾现象,彗星尾距(OTM)为16.6±1.7,与空白对照组(0.1±0.0)相比,差异有统计学意义(P 0.01)。qRTPCR结果显示,1%DMSO组原头节ATM、 p53和Topo2a mRNA相对表达量分别为1.0±0.1、 1.1±0.1、 1.3±0.9,与空白对照组(1.0±0.1、 1.0±0.4、 1.0±0.1)相比,差异无统计学意义(P 0.05)。100μmol/L Dox组原头节ATM、 p53和Topo2a mRNA相对表达量分别为38.6±3.5、 10.0±2.5、 54.0±0.8,与空白对照组相比,差异有统计学意义(P 0.05)。结论Dox具有体外抗细粒棘球蚴原头节作用,可引起虫体DNA损伤,可能与ATM、 p53、Topo2a的mRNA相对表达量变化相关。     

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.