人结肠癌裸鼠原位种植癌及转移模型的建立

目的 建立人结肠癌裸鼠原位种植瘤模型，为研究结肠癌的转移机制和抗转移治疗提供动物模型。方法 采用人结肠腺癌细胞株SWlll6接种于裸鼠皮下，形成稳定传代的皮下种植瘤。再取该肿瘤组织块原位种植于裸鼠结肠壁，建立类似于临床的结肠癌模型。观察原位种植肿瘤的成瘤率，生长情况，转移率和腹水出现率。结果 原位种植成瘤率为l00％(24／24)，区域淋巴结转移率l00％(24／24)，腹膜转移率为9l.7％(22／24)，肝转移率为75．0％(19／24)，腹水出现率为25．0％(6／24)。荷瘤裸鼠晚期出现消瘦和全身衰竭，中位生存期为l0周。结论 该实验的裸鼠原位种植转移模型的生物学行为与临床病程非常相似，为研究结肠癌转移机制和抗转移治疗提供理想的动物模型。     

Small Intestinal Transit Time and Intraluminal pH in Ileocecal Resected Patients with Crohn's Disease

The pH and transit times of the gut areimportant for the delivery of active drug from severaltablets used in the treatment of Crohn's disease (CD).Many patients with CD undergo an ileocecal resection, which might influence small intestinal pH andtransit time. The effect of ileocecal resection on thesevariables has not previously been studied. IntraluminalpH and transit time were measured in nineileocecal-resected CD patients and 13 healthy volunteers usingpH-sensitive radiocapsules. Small intestinal transittime (SITT) was significantly shorter inileocecal-resected patients (5.2 hr, controls 8.0 hr).The pH levels of the small intestine were identical inpatients and controls, whereas cecal pH was 0.9 pH unitshigher in resected CD patients. The time spent with pHhigher than 5.5, 6.0, 6.5, and 7.0 was significantly shorter in patients than in controls. There wasno correlation between the SITT and the length ofresected ileum or between the SITT and the time elapsedsince the resection. We conclude that ileocecal resection decreases the SITT and the time withpH higher than 5.5-7.0. The study indicates that thisreduction of the SITT is mainly due to the resection ofthe ileocecal valve and is, to a certain extent, independent of the length of resected ileum. Anileocecal resection might therefore affect the deliveryof active drug from tablets with pH-dependentdelivery.     

Late Sigmoid Colon Internal Herniation into the Jejuno-Jejunostomy Mesenteric Defect after Laparoscopic Roux-en-Y Gastric Bypass

A 49-year-old female with morbid obesity (BMI 42) underwent laparoscopic Roux-en-Y gastric bypass (LRYGBP). 10 months after the operation, she presented to the hospital with intermittent mid-abdominal pain. An internal hernia of the sigmoid colon through a mesenteric defect of the jejuno-jejunostomy was found. Although small bowel internal herniation has been widely documented, the finding of large bowel internal herniation has not been previously reported. Maintaining a high index of suspicion and a low threshold for urgent intervention are required when evaluating patients with vague abdominal complaints after LRYGBP.     

Reliability Block Diagrams to Model the Management of Colorectal Cancer

The present study aims to show how variousmedical and nonmedical components contribute to successand failure in the management of colorectal cancer. Thefirst encounter, subsequent diagnosis, and surgical therapy of a patient with Dukes B sigmoidcancer is modeled as a reliability block diagram with aserial and parallel arrangement of various components.The overall probability of a patient with new-onset colorectal cancer to visit a physician, becorrectly diagnosed, and undergo successful therapy is69%. The reduction in the overall success, despite thefact that the majority of components are assumed to function with failure rates of 5% or less,is a reflection of the multitude of serial subsystemsinvolved in the management of the patient. In contrast,the parallel arrangement of subsystems results in a relative insensitivity of the overallsystem to failure, a greater stability, and an improvedperformance. Since no medical system functionsperfectly, redundancy associated with parallelsubsystems assures a better overall outcome. Systemanalysis of health care provides a means to improve itsperformance.     

溃结2号方对溃疡性结肠炎大鼠溃疡组织中IL-1β及IL-10 mRNA表达的影响

【目的】观察溃结2号方对实验性溃疡性结肠炎(ulcerative colitis,UC)模型大鼠结肠溃疡组织白细胞介素1β(IL-1β)、白细胞介素10(IL-10)mRNA表达的影响。【方法】采用2,4,6-三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acidTNBS)及免疫诱导法复制UC大鼠模型,将造模成功的36只大鼠随机分为模型组、中药组(剂量为16.76 g.kg-1.d-1)、柳氨磺吡啶(SASP)组(剂量为0.206 g.kg-1.d-1),每组各12只。观察各组大鼠治疗14 d及21 d后结肠组织的病理改变,采用逆转录—聚合酶链反应(RT-PCR)方法检测大鼠结肠组织中IL-1βmRNA、IL-10 mRNA的表达。【结果】给药14 d时,中药组大鼠结肠组织中IL-1βmRNA、IL-10 mRNA表达与模型组及SASP组比较差异均无统计学意义(P>0.05);给药21 d时,中药组大鼠结肠组织中IL-1βmRNA表达量显著低于模型组(P<0.01),IL-10 mRNA表达显著高于模型组(P<0.01)。中药组对UC大鼠结肠组织病理损伤具有修复作用,且效果优于SASP组。【结论】溃结2号方对UC的治疗作用与其能调节结肠组织IL-1βmRNA、IL-10 mRNA表达水平有关。     

In Vivo Alterations of Fluid and Electrolyte Fluxes in Rat Colon by Gamma Irradiation

Colonic function in rats was investigated up to14 days following exposure to whole-body gammairradiation (8 Gy) using a combination of in vivo and invitro approaches. Water and electrolyte fluxes were measured in vivo under anesthesia by insertionof an agarose cylinder into the descending colon.Short-circuit current responses (I_sc; basal,agonist-stimulated) of distal colon were measured invitro as were mannitol and sodium fluxes. Water andelectrolyte absorption (Na, Cl) was markedly reduced atfour days after irradiation but returned to normal atseven days. Potassium secretion was increased from one to seven days after exposure. There were nodifferences in basal I_sc, Na, or mannitolfluxes at four days but responses to secretagogues(5-hydroxytryptamine, forskolin, carbachol) wereattenuated. No morphological alterations were associatedwith these functional modifications.     

Sigmoid Afferent Mechanisms in Patients with Irritable Bowel Syndrome

Up to 60% of patients with IBS have loweredperception thresholds in the rectum to balloondistension. The current study sought to test thehypothesis that IBS patients with normal perceptionthresholds in the rectum show hypersensitivity of afferentpathways in the sigmoid colon. Eleven healthy normalsubjects and eight IBS patients with normal rectalperception thresholds underwent a balloon distension protocol in the sigmoid and rectum. Discomfortthresholds, receptive relaxation, compliance, andreferral patterns were measured. Although IBS patientshad significantly lower discomfort thresholds in the sigmoid when measured as volume, pressure, andwall tension, thresholds were similar to normals.Receptive relaxation and dynamic compliance weresignificantly decreased in IBS patients in the sigmoid. Referral patterns were similar during sigmoiddistention in IBS patients in comparison to normals.Despite normal perception thresholds in rectum andsigmoid, IBS patients show evidence for alterations in rectosigmoid afferent mechanisms. In thesigmoid, this is seen in the form of reduced reflexrelaxation and compliance and in the rectum in the formof altered viscerosomatic referral.     

Carbonic Anhydrase I Reduction in Colonic Mucosa of Patients with Active Ulcerative Colitis

Ulcerative colitis (UC) is associated with lowintracolonic pH and unbalanced transmucosal ionicexchanges. Along the gastrointestinal tract carbonicanhydrase isoenzyme I (CA-I) is specifically expressed in colon epithelium and is involved in mucosalcontrol of ion, fluid, and acid- base balance. Sincealtered CA-I expression may play some role in UC, CA-Iwas measured at the mRNA and protein level and carbonic anhydrase (CA) enzyme activity wasdetermined in colon biopsies of 14 UC patients (6remission, 4 mild, 4 moderate UC) and of 12 healthysubjects. Patients with mild or moderate UC showed asignificant reduction of CA-I mRNA and protein and of totalCA activity in the inflamed mucosa compared to controls.Patients with UC in remission showed a pattern of CA-Iexpression and CA activity similar to controls. This is the first report showing a reduction inthe expression of CA-I in active UC.     

Analysis of Signaling Protein Kinases in Human Colon or Colorectal Carcinomas

Extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) mitogenactivated protein (MAP) kinases are highly activated in an in vivo rat model of colorectal carcinogenesis. In addition, other protein kinases such as c-Src and c-Yes have been shown to be up-regulated in some human colon cancers. To evaluate the activity of these kinases in human colorectal carcinomas, we examined colon cancers and adjacent normal intestinal mucosa from 11 patients. Moderate increases in ERK and JNK activities, in addition to up-regulation of c-Src, p125^FAK, and tyrosine-phosphorylated proteins, were observed in a subset of the colorectal carcinomas. There was a significant correlation found between levels of c-Src, p125^FAK, and tyrosine-phosphorylated proteins, as well as between c-Src protein levels and JNK activity. This is the first report that examines several different kinases as markers to characterize colorectal cancers in the same carcinoma sample, allowing the determination of correlations between markers in the same tumors.     

长期应用番泻叶对大鼠结肠电及Cajal间质细胞的影响

[目的]观察长期灌服番泻叶对大鼠结肠电及Cajal间质细胞(ICC)的影响。[方法]SD大鼠40只,随机分为2组: 正常对照组(饲以普通饲料)、番泻叶组(饲以含番泻叶粉的干饲料,起始剂量为200mg·kg-1·d-1,以100mg·kg-1·d-1剂量递增,保持对半数以上动物有泻下作用,连续3个月,终剂量为2 800mg·kg-1·d-1),检测大鼠结肠慢波的频率及振幅, 采用碘化锌-锇酸法(ZIO)观察肌间神经丛及ICC变化。[结果]长期灌服番泻叶后,大鼠结肠慢波频率及振幅明显下降(P<0.05);肌间神经丛及ICC分布不均匀,突起连接杂乱。[结论]长期灌服番泻叶所导致的大鼠结肠慢波频率减慢可能与肌间丛神经及ICC变性有关。