绝对不应期电刺激对正常豚鼠心室肌细胞舒缩的影响

为探讨绝对不应期电刺激对正常豚鼠心室肌细胞舒缩的影响 ,酶解分离心室肌细胞 ,在 0 .5Hz的基础刺激S1 (脉宽 4ms,电压 60V)的绝对不应期内给予刺激S2 (与S1 延迟 1 0ms,脉宽 1 0ms ,电压 60V) ,应用单细胞收缩动缘检测仪 ,同步观察细胞收缩幅度和钙瞬变的变化。结果 :①心室肌细胞收缩幅值增高 1 5 .45± 6.48% ,收缩速度峰值增加 1 5 .97± 8.37% ,舒张速度峰值增加 2 1 .63± 8.0 6% (n =1 0 ) ;②以荧光强度的比值 (F360 /F380 )反映细胞内Ca2 +浓度变化 ,即钙瞬变。心室肌细胞收缩过程其幅值增加 2 2 .5 5± 9.0 8% ,增高速度与减少速度分别增加36.75± 9.77%和 2 3.62± 4.47% (n =6)。结论 :适宜的绝对不应期电刺激可增强正常豚鼠心室肌细胞舒缩能力。     

绝对不应期电刺激对心力衰竭豚鼠心室肌细胞钙离子流的影响

目的探讨绝对不应期电刺激(ARPES)对心力衰竭(简称心衰)心室肌细胞收缩和钙离子流的作用。方法应用单细胞收缩动缘检测仪,在单纯基础刺激和一定延时后同时给予ARPES,观察细胞收缩并测定以F360/F380反映细胞内钙瞬变。应用膜片钳技术中记录单纯基础刺激和ARPES(延迟后10ms刺激)所诱发动作电位(APSA1,APARPES),并比较动作电位时程(APD)。分别以APSA1和APARPES为测试电压,记录AP电压钳下的细胞膜L型钙通道电流(ICa-L)。结果①ARPES使单个心衰心室肌细胞收缩幅值增高15.53%±5.31%(P<0.05),收缩和舒张速度峰值均增加(分别增加10.60%±3.02%,23.2%±8.26%,P<0.05或0.01,n=6);F360/F380幅值增加16.82%±7.03%(P<0.01,n=6)。②ARPES延长动作APD。③与APSA1电压钳记录的ICa-L相比,APARPES电压钳记录的ICa-L减弱程度明显减少,其单位膜电容下的电流强度的整合值增加(P<0.01)。结论ARPES提高衰竭心肌收缩力与增强单个心室肌细胞钙瞬变相关。     

氯卡胺对人体心室肌复极化的影响

采用心脏程序刺激方法和单相动作电位记录技术研究静脉注射氯卡胺(2mg/kg)对12例房室折返心动过速患者右室肌复极化过程的影响。每例患者测定给药前后右室肌有效不应期和记录固定右房起搏频率(120ppm)时右室肌单相动作电位。结果显示氯卡胺明显缩短单相动作电位复极化90％、50%间期(MAPD_(90)、MAPD_(50)),加速心室肌复极化过程;心肌有效不应期改变不明显,右室有效不应期与MAPD_(90)比值显著增加,由此提示氯卡胺可增加心肌的膜稳定性。     

实验性甲状腺机能减退犬的心室电生理效应及其抗颤动作用

应用心脏电刺激和单相动作电位记录技术，观察了实验性甲状腺机能减退犬的在体心室电生理效应。结果表明，甲状腺机能减退状态呈现出与胺碘酮相似的电生理效应。包括同步均一地延长心室复极化（且主要是复极化前期），延长心室有效不应期，并具有抗心室纤颤作用。研究结果为深入认识甲状腺机能减退状态的心电生理效应及其潜在的抗心律失常作用提供了实验依据。     

兔心肌心室间复极离散的电生理学机制研究

目的观察生理和缺血状态下兔心室间复极离散,探讨临床缺血心肌发生室性心律失常的电生理机制。方法酶解法急性分离兔心室肌细胞,采用细胞膜片钳技术,分别观察对照组(正常心室内膜动作电位时程)和缺血组(缺血心室内膜动作电位时程)在不同刺激频率下[即基础循环周长(basic cycle length,BCL)=2000、1000、500及250 ms]左右心室肌心内膜细胞的动作电位时程变化。结果对照组生理心肌的室间离散分别为(47.70±7.89)ms,(45.50±7.00)ms,(40.30±7.33)ms,(37.90±6.45)ms;缺血后心室间离散则分别为(91.90±7.67)ms,(91.40±7.62)ms,(88.60±7.78)ms,(89.20±6.91)ms。结论生理状态的心肌左右心室间存在复极离散,缺血状态下心室间复极离散增大。这种心室间的复极异质性可能是缺血心肌发生室性心律失常的电生理机制之一。     

心脏兴奋收缩偶联

在参与心脏活动的离子中，Ca^2＋被认为可能是最重要的。人体内存在一种促使心脏收缩舒张的关键机制，这一机制即为兴奋收缩偶联。充分了解Ca^2＋如何在各种细胞器间的转运并引发兴奋收缩偶联，对于深入理解心脏功能的生理基础具有十分重要的意义。心脏兴奋收缩偶联是指由心肌电兴奋开始到心脏收缩并泵血这一过程。在心电活动中，Ca^2＋作为普遍存在的第二信使，起着关键的作用。它能够直接兴奋肌丝，从而引起心脏收缩。心肌Ca^2＋失调是引起心脏收缩功能障碍和心律失常等病理生理状态的关键原因。在心肌动作电位中，Ca^2＋通过去极化兴奋Ca^2＋进入细胞形成Ca^2＋内流（ICa），参与心电活动周期中平台期的形成。Ca^2＋内流会触发肌浆网（SR）释放Ca^2＋。这种Ca^2＋的内流和释放，使得细胞内Ca^2＋浓度迅速升高，随后Ca^2＋与肌纤蛋白-肌钙蛋白C结合，引发收缩机制。若是心脏发生舒张活动，[Ca^2＋]i必须下降，从而使得Ca^2＋由肌钙蛋白上释放出来。这一过程需将Ca^2＋转运出胞浆，主要通过以下四条途径来实现：①肌浆网（SR）Ca^2＋-ATPase；②肌纤维膜Na^＋-Ca^2＋交换（NCX）；③肌纤维膜Ca^2＋-ATPase；④线粒体Ca^2＋单向转运。本文将着重论述心肌细胞Ca^2＋转运体系及其调节机制。     

肥厚心肌细胞Na^＋／Ca^2＋交换活性对β—肾上腺素能药物的反应性降低

目的 探讨肥厚心肌细胞Na^ /Ca^2 交换对β-类肾上腺素能药物刺激的反应及发生这种改变的可能机制。方法 采用胶原酶消化的高血压大鼠单个心室肌细胞及全细胞膜片钳技术，记录Na^ /Ca^2 交换电流并观察药物对它的影响。结果 (1)异丙肾上腺患可浓度依赖性地增加正常及肥厚大鼠心室肌细胞的Na^ /Ca^2 交换电流，但其对肥厚心室肌细胞Na^ /Ca^2 交换电流的增强作用要弱于正常心室肌细胞(P＜0．05)。(2)cAMP可浓度依赖性地增加正常及肥厚大鼠心室肌细胞的Na^ /Ca^2 交换电流，其对正常及肥厚大鼠心室肌细胞Na^ /Ca^2 交换电流的增强作用无差别(P＞0．05)。结论 高血压大鼠心室肌细胞Na^ /Ca^2 交换对β-类肾上腺患能药物的反应性降低，可随与翘厚心肌细胞的g—受体数目及功能、G蛋白及腺昔酸环化酶的活性改变等环节有关，此种反应可能是肥厚心肌收缩及舒张功能障碍的机制之一。     

低血钾与室性心律失常发生

低血钾可直接快速抑制心肌细胞快速激活的延迟整流钾电流、内向整流钾电流和瞬时外向钾电流等多种复极化电流,降低心肌细胞膜电位复极储备,延缓动作电位复极,并导致细胞膜电位超极化。细胞外K~+水平明显影响细胞膜Na~+-K~+ATP酶活性,低血钾状态可减慢该酶的转换速率,使细胞内Na~+增多,继之增强反向Na~+-Ca~(2+)交换并引起细胞内Ca~(2+)蓄积,激活Ca-钙调蛋白激酶Ⅱ,并且进一步增加平台期的L型Ca电流和晚Na电流。通过正反馈调节过程,引起细胞膜电位震荡早期后除极和触发激动,并使心室不应期缩短,增加心室间的复极梯度,延缓兴奋传导,严重时引起恶性心律失常。     

pcDNA3-HERG转染抑制苯肾上腺素诱导的心肌细胞肥大的动物实验

目的 探讨HERG基因真核表达质粒pcDNA3-HERG（编码人快激活延迟整流钾通道α亚单位）转染抑制α1肾上腺素能受体激动剂苯肾上腺素（phenylephrine，PE）诱导的乳兔心室肌细胞肥大的电生理机制。方法 培养乳兔心室肌细胞，观察10μmol／LPE作用6h和48h心肌肥大指标（细胞体积、总蛋白含量及膜电容）、动作电位时限（APD）及钙调神经磷酸酶（CaN）活性的变化；以真核表达质粒pcDNA3-HERG转染心室肌细胞，观察转染细胞经PE诱导48h后上述指标的变化。结果 PE作用6h，心室肌细胞动作电位复极达90％时限（APD90）延长14．3％（P〈0．05），而此时并无心肌肥大和CaN活性增加。PE作用48h，心室肌细胞APD90延长18．8％（P〈0．05），细胞体积、总蛋白含量、膜电容以及CaN活性分别增加40．0％、41．8％、36．4％、124．1％（P〈0．01）；pcDNA3-HERG转染可过度表达ⅠHERG，其尾电流密度约为未转染HERG组快激活延迟整流钾电流（ⅠKr）尾电流密度的4倍（P〈0．05），可促进复极，明显缩短PE引起的APD90延长（P〈0．05），显著抑制PE诱导心肌肥大和CaN活性增加。结论 PE诱导乳兔心室肌细胞肥大过程中，APD延长并非继发于而是早于心肌肥大。APD延长，继而导致Ca^2＋内流和胞内Ca^2＋增加，激活CaN信号通路可能在PE诱导心肌肥大中起重要作用。     

降钙素基因相关肽拮抗垂体后叶素引起心肌缺血性电生…

用浮置微电极技术观察垂体后叶素对兔心肌细胞的异常电生理学效应及降钙素基因相关肽的保护作用。结果表明：静脉注射Ｐｉｔ后，心率减慢，心外膜电图ＳＴ段招高，Ｔ波倒置，心室肌细胞跨膜动作电位的静息电位及动作电位振幅明显降低。复极化至３０％、５０％和９０％的动作电位过程亦明显缩短。静脉注射Ｐｉｔ同时注射ＣＧＲＰ，可见ＣＧＲＰ明显拮抗以上异常改变，从而起到保护心肌和稳定心肌的电生理作用。     

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.