大肠癌和腺瘤细胞凋亡的特征和意义

目的　观察大肠癌和腺瘤组织细胞凋亡的特征,探讨细胞凋亡和增殖在大肠癌和腺瘤组织中的意义。方法　采用脱氧核糖核酸末端转移酶介导的ｄＵＴＰ缺口末端标记（ＴＵＮＥＬ）法检测凋亡细胞,以凋亡细胞百分率作为凋亡指数（Ａｐｏｐｔｉｃｉｎｄｅｘ,ＡＩ）对１５例大肠癌、１０例腺瘤、５例正常大肠粘膜进行凋亡细胞原位观察。结果　ＴＵＮＥＬ阳性物质位于细胞核内,常聚集于核膜附近,呈新月状和块状。大肠正常粘膜ＴＵＮＥＬ阳性细胞全部位于表层上皮中,数量很少（ＡＩ＝１．７４±１．０１）,腺瘤组织中ＴＵＮＥＬ阳性细胞相对较多（ＡＩ＝３３．４６±１１．３９）,大肠癌组织ＴＵＮＥＬ阳性细胞散在分布,与腺瘤相比数量明显减少（ＡＩ＝１１．０８±４．２７）（Ｐ＜０．０１）。结合增殖细胞核抗原（ＰＣＮＡ）实验结果可见,腺瘤组织中ＡＩ,ＰＩ（ＰＩ＝２７．２４±７．６６）均高,而大肠癌组织中则以细胞增殖（ＰＩ＝５４．１８±１０．４１）占优势。结论　大肠肿瘤癌变过程中不仅存在活跃的细胞增殖,而且有大量的细胞凋亡,因而增加了粘膜上皮的不稳定性,高的增殖能力通过选择而占优势,从而导致癌变的发生。     

中毒剂量锌对大鼠小肠粘膜超微结构的影响

目的：阐明中毒剂量锌对肠粘膜免疫屏障结构的影响及其机理。方法：通过建立常锌（ＺＮ）、中毒剂量锌（ＺＰ）大鼠模型,应用病理形态学手段（电镜）对大鼠肠道粘膜的超微结构进行研究。结果：第４周末和第７周末血浆、红细胞膜和肠组织的锌含量ＺＰ组明显高于ＺＮ组（Ｐ＜０．０５）。第四周末和第七周末ＺＰ组光镜下肠粘膜未见异常改变;但是电镜下见肠道粘膜超微结构的严重损害。结论：中毒剂量锌可以引起肠道粘膜超微结构的严重损害;屏障功能削弱,大鼠小肠粘膜的免疫防御能力降低。     

The effect of polycythemic hyperviscosity on ischemic bowel necrosis

It is known that polycythemia decreases the fluidity of the blood and impairs tissue perfusion due to red-cell sludging in the microcirculation. In this study, the effect of polycythemic hyperviscosity (PH) on bowel necrosis was evaluated in an experimental model of intestinal ischemia. Twenty-eight Wistar albino rats (90–170 g) were divided into two groups: group 1 was transfused to create hyperviscosity and then intestinal ischemia was produced (n = 16); in group 2 ischemia was produced without transfusion (n = 12). Intestinal ischemia was produced by clamping the superior mesenteric artery and the collateral arcades of the right colic artery for 30 min. Gross and histopathologic evaluations were performed by either immediate necropsy or relaparotomy 24 h later. Microscopic findings were graded from 0 to 3 according to the degree of ischemic changes. In group 1, 2 animals (12.5%) died before 24 h postoperatively; coagulation necrosis with grade 2 or 3 ischemic changes was observed in 10 animals (62.5%). In group 2 only a few hypertrophied Peyer's patches and capillary dilation were found, and all histopathologic changes were between grades 0 and 1. The difference between the histopathologic gradings of the two groups was significant (P < 0.001). It appears that in addition to reduced splanchnic blood flow, a secondary effect of PH is needed to induce ischemic coagulation necrosis. PH of the newborn must be considered a risk factor for necrotizing enterocolitis, so-called spontaneous intestinal perforations, and even intestinal atresia.Presented at the 1st European Congress of Pediatric Surgery, Graz/Austria, May 4–6, 1995     

Interactions of Phosphodiester and Phosphorothioate Oligonucleotides with Intestinal Epithelial Caco-2 Cells

Purpose. Oral bioavailability for antisense oligonucleotides has recently been reported but the mechanistic details are not known. The proposed oral delivery of nucleic acids will, therefore, require an understanding of the membrane binding interactions, cell uptake and transport of oligonucleotides across the human gastro-intestinal epithelium. In this initial study, we report on the cell-surface interactions of oligonucleotides with human intestinal cells. Methods. We have used the Caco-2 cell line as an in vitro model of the human intestinal epithelium to investigate the membrane binding interactions of 20-mer phosphodiester (PO) and phosphorothioate (PS) oligonucleotides. Results. The cellular association of both an internally [³H]-labelled and a 5end [³²P]-labelled PS oligonucleotide (3.0% at 0.4 µM extracellular concentration) was similar and was an order of magnitude greater than that of the 5end [³²P]-labelled PO oligonucleotide (0.2%) after 15 minutes incubation in these intestinal cells. The cellular association of PS was highly saturable with association being reduced to 0.9% at 5 µM whereas that of PO was less susceptible to competition (0.2% at 5 µM, 0.1% at 200 µM). Differential temperature-dependence was demonstrated; PS interactions were temperature-independent whereas the cellular association of PO decreased by 75% from 37°C to 17°C. Cell association of oligonucleotides was length and pH-dependent. A decrease in pH from 7.2 to 5.0 resulted in a 2- to 3-fold increase in cell-association for both backbone types. This enhanced association was not due to changes in lipophilicity as the octanol:aqueous buffer distribution coefficients remained constant over this pH range. The ability of NaCl washes to remove surface-bound PS oligonucleotides in a concentration-dependent manner suggests their binding may involve ionic interactions at the cell surface. Cell-surface washing with the proteolytic enzyme, Pronase^®, removed approximately 50% of the cell-associated oligonucleotide for both backbone types. Conclusions. Binding to surface proteins seems a major pathway for binding and internalization for both oligonucleotide chemistries and appear consistent with receptor (binding protein)-mediated endocytosis. Whether this binding protein-mediated entry of oligonucleotides can result in efficient transepithelial transport, however, requires further study.     

Mucoadhesive Polymers in Peroral Peptide Drug Delivery. VI. Carbomer and Chitosan Improve the Intestinal Absorption of the Peptide Drug Buserelin In Vivo

Purpose. To evaluate the effect of the crosslinked poly(acrylate) carbomer 934P (C934P) and its freeze-dried neutralized sodium salt (FNaC934P) as well as chitosan hydrochloride on the intestinal absorption of the peptide drug buserelin. Methods. Buserelin was applied intraduodenally in control buffer, 0.5% (w/v) C934P, 0.5% (w/v) FNaC934P, 1.5% (w/v) chitosan hydrochloride or FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture in rats. Results. All polymer preparation showed a statistically significant improvement of buserelin absorption compared to the control solution. The absolute bioavailabilities for the different polymer preparations were: control, 0.1%; 0.5% FNaC934P, 0.6%; 0.5% C934P, 2.0%; chitosan hydrochloride, 5.1% and FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture, 1.0%. The higher bioavailability with chitosan hydrochloride compared to C934P and FNaC934P indicates that for buserelin the intestinal transmucosal transport enhancing effect of the polymer plays a more dominant role than the protection against proteases such as -chymotrypsin. Conclusions. The mucoadhesive polymers carbomer 934P and chitosan hydrochloride are able to enhance the intestinal absorption of buserelin in vivo in rats, and may therefore be promising excipients in peroral delivery systems for peptide drugs.     

Jejunal duplication cyst displaying peristalsis and a five-layered appearance of the wall: a preoperative ultrasound diagnosis

A case of preoperatively diagnosed jejunal duplication cyst displaying the characteristic five-layered appearance of the gastrointestinal tract wall and peristaltic activity is reported. Both these rare features allowed a specific diagnosis of enteric duplication to be made.     

The Use of the Biliopancreatic Diversion as a Treatment for Failed Gastric Partitioning in the Morbidly Obese

The dilemma with which every bariatric surgeon is confronted is: What to do with the inevitable failures? In vertical gastric partitioning, revising the gastroplasty results in a high second failure rate. In an effort to improve the Success rate in failed gastroplasty patients who request revisionary surgery, the biliopancreatic bypass (classic Scopinaro procedure) was carried out on 57 patients. They have been followed for up to 10 years. The long-term weight loss has averaged 69.4 lb, which is 87% of the pregastroplasty excess weight. The price paid by these patients, in terms of complications, has been significant. Twenty-two Percent have developed hypoalbuminemia with its accompanying peripheral edema; 24% have required i.v. hyperalimintation because Of malnutrition. Sixteen percent of the patients developed a late post-op bowel obstruction, one resulting in death. Osteomalacia, spontaneous fractures have occurred. The biliopancreatic diversion procedure (BPD) is an effective weight-loss operation in the failed gastroplasty patients, but a significant price must be paid in terms of careful follow-up, nutritional deficiencies, and rehospitalizations.     

胆管结石乳头局部组织中血管活性肠肽和一氧化氮合酶表达的改变及意义

目的 探讨胆管结石患者乳头局部组织中血管活性肠肽(VIP)和一氧化氮合酶(NOS)表达的改变及意义。方法 选择68例进行逆行胰胆管造影和/或乳头括约肌切开术的胆管结石患者,采用内镜下活检乳头局部组织。常规石蜡包埋,连续切片,免疫组化SABC法检测VIP及NOS。对照组为门诊胃镜检查胃粘膜大致正常者。结果 结石组乳头粘膜内 VlP和NOS阳性产物与对照组相比较显著降低(P相似文献