Role of neutrophils in gastric damage induced by platelet activating factor

Summary Platelet-activating factor (PAF) has recently been shown to be a potent ulcerogenic agent in the stomach and intestinal mucosa. Its exact mechanism of action is not yet known although histological studies suggest that vasocongestion is an important feature of PAF-induced damage. We have therefore studied the activity of various agents with different modes of action toward PAF-induced gastrointestinal lesions in the rat (PAF 2 g/kg i.v. ; macroscopic lesions of tissues scored 20 min later; arbitrary scale from 0 to 4). Drugs were administered either i. m., s. c. (5 min) or orally (30 min) before PAF injection. PAF-induced gastric lesions were strongly inhibited by the natural PAF-antagonist BN 52021 as well as by atropine sulphate and cimetidine which implicates cholinergic stimulation in the ulcerogenic activity of PAF. The somatostatin analog BIM 23014 was also very potent against PAF, perhaps by reducing the parasympathetic stimulation in the gastric wall as described for somatostatin. Allopurinol, which is a free radical scavenger also almost totally inhibited PAF-induced gastric damage, suggesting that neutrophils are involved in the mucosal lesions. The considerable inhibition of the gastric effects of PAF found in neutrophil-depleted animal supports this hypothesis. Theophylline and disodium cromoglycate, mast cell stabilizing drugs which were also active in our model, could act by protecting mast cell degranulation induced by free radicals released from activated neutrophils. A multifunctional process seems to determine the mucosal gastric damage induced by PAF, but parasympathetic stimulation and neutrophil activation play a major role in this pathology.Send offprint requests to A. Etienne at the above address     

A cAMP-activated chloride channel in the plasma membrane of cultured human gastric cells (HGT-1)

Hydrochloric acid (HCl) secretion by gastric parietal cells involves an apical Cl^– conductance, the properties of which have not been defined. In the present study, forskolin and histamine [agonists that increase intracellular cyclic adenosine monophosphate (cAMP)], and dibutyryl cAMP, activated channels in previously quiescent cell-attached membrane patches on cultured human gastric cells (HGT-1). In the cell-attached configuration (Cl^–149 mmol/ 1 in bath and pipette), channels exhibited outward rectification, voltage dependence, inward current (–0.7 pA) at zero holding potential and a reversal potential of +24 mV, consistent with the presence of a Cl^– conductive pathway. In excised inside-out patches, channels (i) exhibited degrees of outward rectification and voltage dependence that were comparable to those seen in cell-attached patches, (ii) demonstrated a –21 mV shift of their reversal potential when bath Cl^– was decreased from 149 mmol/l to 53 mmol/l (calculated Cl^–:cation permeability ratio 171), and (iii) were highly sensitive to the Cl^– channel blocker diphenylamine-2-carboxylic acid (DPC, 10^–3 mol/l). This cAMP-activated Cl^– channel bears many similarities to other Cl^– channels within intestinal epithalia, and may represent the apical Cl^– channel operating in HCl-secreting gastric parietal cells.     

Vagotomy fails to block the satiating effect of food in the stomach

Normal rats and rats with bilateral subdiaphragmatic vagotomy, each equipped with a pyloric noose, ate liquid food after 3-hr food deprivation. When the noose was open, ingested food accumulated in the stomach and entered the intestine in normal fashion. When the noose was closed, ingested food was trapped in the stomach and did not enter the intestine. Normal and vagotomized rats ate the same size meal with the noose closed as they ate with the noose open and all rats displayed a postprandial sequence of satiety behavior that culminated in resting. Thus, vagotomy failed to block the satiating effect of food in the stomach. This result suggests that gastric distension mediated by vagal afferents is not a necessary stimulus for satiety elicited by food in the stomach.     

Expression of CDX2 and MUC2 in Barrett's mucosa

Barrett's mucosa is a risk factor for esophageal adenocarcinoma and should be detected at an early stage. It is defined by the presence of columnar epithelium with goblet cells in the lower esophagus, but histologic diagnosis can be uncertain in the absence of distinct goblet cells. We investigated 55 biopsies from 48 patients with endoscopically plain Barrett's esophagus and performed immunohistochemistry for CDX2 and MUC2. In addition, alcian blue (pH 2,5)/PAS staining was done. In histologically unequivocal Barrett's mucosa, nuclear expression of CDX2 in goblet cells and many columnar cells, as well as cytoplasmic positivity for MUC2 in goblet cells, could be observed. Alcian blue (pH 2,5)/PAS stained acidic mucins in goblet cells and in some non-goblet columnar cells. In six cases, no definite Barrett's mucosa was present, and no expression of MUC2 could be observed. In these biopsies, there was granular cytoplasmic and/or focal nuclear staining for CDX2 in non-goblet columnar epithelial cells, indicating their intestinal differentiation. We suggest that this peculiar mucosa is the precursor of unequivocal Barrett's mucosa and would designate it early Barrett's mucosa. Alcian blue for acidic mucins is inconsistent in this epithelium and does not reliably indicate early intestinal differentiation.     

Lipopolysaccharide Induces CD25-Positive, IL-10-Producing Lymphocytes Without Secretion of Proinflammatory Cytokines in the Human Colon: Low MD-2 mRNA Expression in Colonic Macrophages

Despite the huge number of colonized Gram-negative bacteria in the colon, the normal colon maintains its homeostasis without any excessive immune response. To investigate the potential mechanisms involved, human colonic lamina propria mononuclear cells (LPMCs) obtained from uninflamed mucosa were cultured with lipopolysaccharide (LPS) prepared from Bacteroides vulgatus (BV-LPS) or Bacteroides fragilis (BF-LPS), as representatives of indigenous flora, or pathogenic Salmonella minnesota (SM-LPS). Colonic LPMCs failed to produce inflammatory cytokines in response to any type of LPS. Colonic macrophages barely expressed mRNA for MD-2, an essential association molecule for LPS signaling via Toll-like receptor 4. Further, BV-LPS induced CD25 and Foxp3 expression in lymphocytes and CD4(+)CD25(+) cells expressed IL-10 mRNA. Thus, the low expression of functioning LPS receptor molecules and induction of IL-10-producing CD4(+)CD25(+) lymphocytes by indigenous LPS may play a central role in the maintenance of colonic immunological homeostasis.     

Three familial cases of fundic gland polyposis without polyposis coli

We report three cases of fundic gland polyposis in the stomach identified in three patients who were related. Grossly the numerous polyps covered an area limited to the body and fundus of the stomach, no polyps were found in the antrum, duodenum, colon, or rectum, and histologically, the gastric lesions consisted of numerous hamartomatous polyps, characterized by proliferation of the fundic and cystic glands. The gastric lesions were identified in families without polyposis coli. This type of fundic gland polyposis has never been documented before in the literature.     

血清可溶性上皮钙粘蛋白，CA724和CA199联合检测对胃癌诊断的临床意义

目的探讨血清sE—cad、CA724、CA199联合检测在胃癌诊断中的价值。方法应用酶联免疫吸附法（ELISA）技术检N30例正常对照组、35例良性胃病、45例胃癌患者血清sE—cad的含量，CA724和CA199则采用电化学发光技术检测。结果胃癌患者血清sE—cad、CA724和CA199的含量明显高于正常对照组和良性胃病组，差异有显著性（P〈0．01），三者联合检测敏感性、准确性均显著提高（P〈0．05）。结论血清sE—cad、CA724和CA199联合检测有助于提高胃癌诊断的敏感性和特异性。     

消化道癌症患者血浆纤维连接蛋白的变化及其与微血管的关系

分析27例消化道癌症患者(其中胃癌18例,食道癌与结肠癌9例)和6例胃溃疡病人的血浆纤维连接蛋白(Fn)的变化。结果发现三者间无明显差异(P>0.05),但胃癌病人中有转移病灶者(n=7)及伴胃炎者(n=10)与相应对照组比,血浆Fn有非常明显降低(p<0.01)。胃癌组织中Fn免疫荧光主要集中在胃癌病人胃壁组织多形核白细胞浸润的炎症区及微血管周围,癌变区Fn免疫荧光很弱,甚至消失。对上述变化的意义进行了讨论。     

组胺H_2受体阻断剂对大鼠失血性应激反应时胃功能和溃疡指数的影响

用反射光谱法,研究了组胺H_2受体阻断剂Famotidine对急性失血大鼠胃粘膜血液量及血氧饱和度的影响。同时观察了胃液量和酸排出量的变化,并计量了溃疡指数。Famotidine(3mg/kg及8mg/kg,iv)对失血前大鼠胃粘膜血液量和血氧饱和度均未见有影响;对失血后胃粘膜血液量和血氧饱和度的降低有明显保护作用,对胃液量和酸排出量均有显著抑制作用,溃疡指数减小。     

Reversibility of Effects of Very Hypotonic Fluids on in Vitro Frog Gastric Mucosa: A Functional and Morphological Study

Functional and morphological properties of the in vitro frog gastric mucosa were studied during and after exposure to very hypotonic (? 25 mOsM) solutions. Within 20 min the acid secretory rate decreased to zero, but it returned to normal levels after isotonic fluids had been restored. The potential difference (PD) dropped within the first minutes after the exposure to hypotonic solutions, and became inverted. Following the return of isotonic conditions the PD increased to levels higher than in the controls. The electrical resistance increased about 10–fold during the hypotonic period, but decreased to near normal values when isotonic conditions were restored. By light and electron microscopy the cells of the hypotonic mucosae appeared greatly swollen, and the alterations were assessed by morphometric methods. The gland lumina were almost obliterated, and the lamina propria was reduced to about 60% of its former volume. After the return to isotonic conditions normal morphology was restored. It is conceivable that the great increase in resistance during the hypotonic period was caused by the occlusion of the gland lumina. Quantitative analyses of the Na, K, and C1 tissue concentrations indicated a large loss of these ions during the hypotonic state. Presumably the epithelial cells in the hypotonic mucosae avoid bursting by rapidly letting large numbers of ions exit, which results in a cellular osmolarity close to that of the bathing fluids.