Activation of ion transport by combined effects of ionomycin,forskolin and phorbol ester on cultured HT-29cl.19A human colonocytes

The differentiated clone 19A of the HT-29 human colon carcinoma cell line was used as a model to study the intracellular electrophysiological effects of interaction of the cAMP, the protein kinase C (PKC) and the Ca²⁺ pathways, (a) A synergistic effect between ionomycin and forskolin was observed. From intracellular responses it was concluded that the synergistic effect is caused by activation of an apical Cl^– conductance by protein kinase A and a basolateral K⁺ conductance by Ca²⁺. (b) A transient synergistic effect of ionomycin and the phorbol ester phorbol dibutyrate (PDB) was found. The decrease of the response appeared to be due to PKC-dependent inactivation of the basolateral K⁺ conductance. The synergism is caused by PKC-dependent increase of the apical Cl^– conductance and Ca²⁺-dependent increase of the basolateral K⁺ conductance. (c) The effects of carbachol and PDB were not fully additive presumably because of their convergence on PKC activation, (d) Forskolin and PDB, when added in this order, had a less than additive effect. Results of cell-attached patch-clamp studies, presented in the accompanying paper, showed a synergistic effect of forskolin and PDB on non-rectifying small-conductance Cl^– channels. Assuming that these channels are involved in the transepithelial responses it is suggested that forskolin and PDB induce a modulatory, synergistic increase of the apical Cl^– conductance when both pathways are activated simultaneously. (e) The HT-29cl.19A cells differ from T₈₄ cells in that the latter did not respond with an increase of the short-circuit current to addition of phorbol ester. This may be due to a very low expression of PKC.     

Nitric oxide mediates intestinal hyperaemic responses to intraluminal bile-oleate

It has long been recognized that intestinal blood flow increases at mealtimes. Mesenteric hyperaemia is also evoked by activation of sensory peptidergic nerves. Our studies explored the possible role of endogenous nitric oxide (NO) in the rat intestinal vasodilator response to luminal instillation of an oleic acid plus bile mixture before and after acute intrajejunal instillation of capsaicin and after chronic pretreatment with capsaicin. In anaesthetized rats we measured jejunal blood flow (BF) with an ultrasonic Doppler flowmeter and systemic arterial pressure (AP) with a pressure transducer. Intestinal perfusion with 80 mM oleic acid in bile increased BF by 98±12%. Instillation of 4 mg of capsaicin into the jejunal lumen initially increased BF by 42±9% but was followed by vasoconstriction. Inhibition of NO synthase with 25 mg/kg i.v. N-nitro-L-arginine (L-NNA) decreased BF by 27±5% and increased AP by 37±11%. After treatment with L-NNA and after acute and chronic administration of capsaicin, the bile-oleate-induced maximal increases in BF above control levels were 42±7%, 65±12%, and 58±8%, respectively. The observed inhibitory effect of L-NNA on the intestinal hyperaemic response to the bile-oleate mixture was reversed by pretreatment with L-arginine (100 mg/kg i.V.). In capsaicin pretreated rats the subsequent bile-oleate-induced hyperaemia was reduced in magnitude but the inhibitory effects of L-NNA were proportionately the same as in animals not receiving capsaicin. These findings support the hypothesis that NO is involved with bile-oleate-induced mesenteric hyperaemia.     

Expression of alpha-amylase isoenzymes and trypsin by the proliferating epithelium of large intrahepatic bile ducts and intrahepatic peribiliary glands in hepatolithiasis

The expression of alpha-amylase isoenzymes (pancreatic and salivary) and trypsin by the epithelium of large intrahepatic bile ducts and peribiliary glands was examined immunohistochemically in hepatolithiasis ( n = 22), extrahepatic biliary obstruction ( n = 20) and normal liver ( n = 22). Hepatolithiasis was associated with marked proliferation of bile duct cells and peribiliary glands. Expression of pancreatic and salivary amylase was observed in the proliferating bile duct cells and peribiliary glands of all livers, and trypsin was found in 68% of the livers. In extrahepatic biliary obstruction, proliferation of the biliary epithelium was less marked, but expression of amylase isoenzymes was observed in all livers and trypsin was found in 50%. All normal livers showed expression of amylase isoenzymes in large intrahepatic bile ducts, septal bile ducts and peribiliary glands, and trypsin was found in 73%. The density of enzyme-containing acini was highest in hepatolithiasis, intermediate in extrahepatic biliary obstruction and lowest in normal liver. These results show that the proliferating biliary epithelium in hepatolithiasis contains amylase isoenzymes and trypsin and that biliary epithelium retains the ability to produce these enzymes after proliferation, suggesting that a large amount of amylase isoenzymes and trypsin may be secreted into the bile ducts in hepatolithiasis. These enzymes may play an important role in the pathophysiology of hepatolithiasis.     

Treatment of mice with the anticoccidial drug Toltrazuril does not interfere with the development of a specific cellular intestinal immune response to Eimeria falciformis

Immunity against Eimeria-infections is highly specific and it depends on cell-mediated effector mechanisms. Infections of BALB/c mice with 1000 sporulated oocysts of Eimeria falciformis led to protection against challenge infections. Treatment with the anticoccidium Toltrazuril, during primary infection, terminated the ongoing disease and did not interfere with the establishment of protective immunity against challenge infections. Mesenteric lymph node cells of infected, treated as well as non-treated and challenged BALB/c mice, showed a similar proliferation upon stimulation with parasite antigen. In contrast, neither cells of the Peyers patches, intraepithelial lymphocytes, nor spleen cells responded to stimulation with parasite antigens. Cells from all compartments and of all investigated groups proliferated and released the cytokines IFN- and IL-4 in response to the mitogen Concanavalin A. The number of cells releasing IFN- or IL-4 was not dependent on the status of infection or previous treatment with Toltrazuril. The serum IgG response against total sporozoite antigens of individual mice showed that in addition, a systemic humoral response developed in infected mice, independent of a previous drug treatment, although the specific IgG antibody concentration was higher in non-treated mice. Thus, Toltrazuril does not impair the parasite specific intestinal cellular and systemic antibody response and does not prevent the development of protection against challenge infection.     

激光泪道成形术治疗泪道阻塞的临床观察

目的 观察激光泪道成形术治疗泪道阻塞的效果及复发病例再次激光联合插管治疗的效果。方法 采用Nd：YAG激光泪道成形术治疗泪道阻塞102例。132眼。对复发病例。再次行激光联合插管治疗。结果 113眼一次治愈，有效9眼。术后10眼复发，再次行激光联合插管治疗，7眼治愈，3眼未愈。本组总治愈率90．9％，有效率97．7％。结论 Nd：YAG激光泪道成形术治疗泪道阻塞操作简单，安全有效，复发病例联合插管治疗可以提高治愈率。     

Immune aspects of intestinal metaplasia of the stomach: An immunohistochemical study

Summary Immune characteristics of intestinal metaplasia of the stomach were analyzed by the immunoperoxidase technique in frozen and paraffin-embedded specimens. In fetal and minimally inflamed adult gastric mucosa, secretory component (SC) was absent from epithelial cells. Non-intestinalized gastric mucosa with evident inflammatory changes showed weak SC immunoreactivity at the generative cell zone. Enhanced immunoreactivity of SC with evidence of transepithelial transport of IgA and IgM, but not of IgG, was demonstrated in intestinalized glands of either the complete or incomplete type. The number of inflammatory cells and lymphoid follicles was decreased in intestinalized mucosa when compared with that in non-intestinalized gastritic mucosa; J chain-negative IgG plasma cells and T cells, both of which were fairly abundant in the latter mucosa, were remarkably decreased in the former mucosa, whereas the decrease of J chain-positive IgA or IgM plasma cells was slight or equivocal. In either mucosa, IgA was the most popular immunoglobulin class in plasma cells. IgD plasma cells were very rare. In the germinal centers of lymphoid follicles which were preferentially distributed in non-intestinalized gastritic mucosa, IgM or IgG germinocytes predominated over IgA germinocytes, and a few T cells and NK cells also were present. Intraepithelial lymphoid cells with a T-suppressor phenotype were detected in intestinalized glands. The possibility that intestinal metaplasia is an adaptation to long-standing chronic gastritis is discussed.     

Apamin distinguishes two types of relaxation mediated by enteric nerves in the guinea-pig gastrointestinal tract

Summary Eight smooth muscle preparations from the stomach, small intestine and large intestine of the guinea-pig were used to compare apamin's actions in reducing the effectiveness of transmission from enteric inhibitory nerves and in reducing responses to inhibitory agonists ,-methylene ATP, VIP and isoprenaline. The effects of apamin on inhibitory reflexes in the ileum and colon were also evaluated. Apamin had little or no effect on responses to VIP and isoprenaline in any region, but consistently and substantially reduced responses to ,-methylene ATP. Responses to stimulation of enteric inhibitory neurons were substantially reduced by apamin in the antrum circular muscle, ileum longitudinal and circular muscle, taenia coli and distal colon longitudinal muscle, but it was ineffective in the fundus circular muscle, proximal colon longitudinal muscle and distal colon circular muscle. It caused a small reduction of the relaxation of the ileal circular muscle caused reflexly by distension, but did not modify the similar descending inhibitory reflex in the circular muscle of the colon. It is concluded that apamin can be used to distinguish two types of non-noradrenergic transmission from enteric inhibitory nerves to gastrointestinal muscle. Furthermore, neither VIP nor ATP can be the sole transmitter chemical released from enteric inhibitory neurons throughout the gastrointestinal tract.     

Survival of Patients with Multi-Level Malignant Bowel Obstruction on Total Parenteral Nutrition at Home

Home parenteral nutrition (HPN) may improve the survival in selected patients with malignant bowel obstruction. This retrospective, medical registry-based study aimed to identify clinical and laboratory markers predicting short survival, which would allow a more accurate selection of patients that would benefit from HPN in inoperative bowel obstruction. In a retrospective analysis of 114 patients receiving HPN, the median survival was 89 days after discharge home, and the three and six-month survival probability was 48% and 26%, respectively. Parenteral nutrition was provided during 98% of overall survival time and ended on a median of one day before the patient’s death. Discontinuing chemotherapy, anemia, severe hypoalbuminemia, and water retention appeared correlated with survival shorter than three months. In these cases, routine initiation of HPN should be discouraged, as it may not bring any benefits to the patient. The decision on the initiation of HPN should be made along with continuing or initiating chemotherapy.     

急症一期切除吻合术治疗左半结肠癌梗阻36例体会

目的：探讨左半结肠癌致急性肠梗阻的手术处理方法。方法：回顾性分析1995－2000年间36例左半结肠癌致肠梗阻一期切除吻合术的外科临床效果。结果：全组36例病人均采用梗阻近端肠管减压灌洗,并留置盲肠造瘘管术后接负压吸引,术后均一期愈合,未出现吻合口漏。随访12例中,半年死亡1例,1年死亡4例,3年死亡5例,5年死亡例。结论：只要病情允许,严格掌握手术适应症和基本操作,对左半结肠癌急性肠梗阻行一期切除吻合手术是可行的。