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Biomedical subjects

I Sobhani

Publications and source records attributed to I Sobhani.

At least 37 records · Page 2Linked to original sources

Helicobacter pylori stimulates gastric acid secretion via platelet activating factor.

Platelet activating factor (PAF) is a phospholipid mediator known as potent ulcerogenic agent but its physiological role is still unknown in the gastrointestinal tract. Lyso PAF the immediate PAF procursor has no deleterious effect in the gastrointestinal tract. We have previously reported that lyso PAF is produced by gastric mucosa in basal condition and in response to gastrin in healthy men. Helicobacter pylori metabolises lyso PAF to produce PAF. The aim was to study the effect of PAF on the gastric acid secretion. Isolated rabbit glands were used as a model and acid secretion was assessed by (14C) Aminopyrine (AP) uptake. PAF and histamine stimulated AP accumulation time- and dose-dependently. PAF-induced AP accumulation was supressed by omeprazole and Fura 2. BN50727 a specific PAF antagonist inhibited PAF-induced AP accumulation. The presence of a PAF receptor transcript was investigated by reverse transcriptase polymerase chain reaction (RT-PCR) from total mRNA using two primers in which oligonucleotides were synthetized from the human leucocyte PAF receptor cDNA. A single RT-PCR band of the transcript with expected size was detected in the crude isolated cell fraction. These results and others from our laboratory suggest that PAF stimulates gastric acid secretion via specific receptor on the parietal cells and H. pylori produces PAF which may induce mucosal injury directly or indirectly via acid pathway.

Aminopyrine↗

[Helicobacter pylori, a rediscovered bacterium. Implication in gastroduodenal diseases].

Helicobacter pylori is a microaerophilic bacterium initially found in the gastric antrum of patients with peptic ulcer disease. As a result, H. pylori is now believed to have a pathophysiologic role in gastritis as well as in peptic ulcer disease. Several recent studies showed that it may be associated with duodenal ulcer relapse and that eradication therapy using antibiotics may significantly decrease the ulcer recurrence rate in duodenal ulcer patients. Moreover, epidemiological studies suggest that it may increase the relative risk of carcinoma in the stomach and preliminary studies seem to indicate that some low-grade lymphoma in the stomach may regress after H. pylori eradication. Although the mechanisms by which H. pylori induces mucosal injury and/or neoplasm is not clearly understood, several modifications in gastric functions have been reported. The most specific way of detecting H. pylori in tissue is a combination of culture and histologic staining of mucosal biopsy specimens obtained by endoscopy. Rapid urease test, cytology and PCR procedures performed on biopsies may give rapid, sensitive and specific results. Breath test using 13C- or 14C-radiolabelled urea and serology tests are of particular importance when H. pylori diagnosis is needed via no invasive procedures. Helicobacter pylori is supposed to interact with G and D cells. Gastrin and somatostatin are synthetized and released from antral G and gastric D cells respectively. The gastric D cells are in close contact with either G and parietal cells. Gastrin stimulates gastric acid secretion and epithelial gastric cell proliferation (parietal and EC-L cells) while somatostatin inhibits these effects. Chronic gastritis is associated with fundic duodenal ulcer disease. In this situation, basal gastrin and meal- or bombesin-stimulated gastrin in the serum (especially gastrin G17) have been found to be higher in H. pylori positive than in negative patients. Moreover, gastrin decreases up to normal levels after eradication of H. pylori. The long term effect of a such hypergastrinemia is not so far established. The mechanism underlaying hormonal modification is poorly understood. Since no G/D cell ratio modification could be found after H. pylori eradication while the amount of somatostatin increases, one would suggest functional alteration of either G or D cells in the H. pylori-related chronic gastritis. The role of inflammatory mediators on the gastrin release and the processing of progastrin induced by the bacterium need further investigations.

Duodenal Diseases↗

Quantitative analysis of the immune cells in the anal mucosa.

The prevalence of anoperineal diseases, i.e. sexual transmitted infections, is increasing particularly in AIDS, a fact which is likely due to the alteration of mucosal immunity. However, no data were available on normal anal status. In order to study anal immunity in man, we characterized lymphocytes subtypes and Langerhans' cells (LC) using quantitative morphometric analysis and immunohistochemistry. Anal normal mucosal samples obtained from surgical specimens of 45 patients (30 suffering from hemorrhoids and 15 from fissurations) were analyzed. Immunohistochemistry was performed on frozen sections with antibodies recognizing CD1a (LC), CD3 (T lymphocytes), CD4 (T4), CD8 (T8) and CD22 (B-lymphocytes). Immunostained cells were counted per square millimeter of mucosal epithelium. The surface of CD1a cells was measured using a computerized software program and a percentage of CD1a immunostained area was calculated in comparison to the whole mucosal surface. LC and T-Lymphocytes were found in the squamous epithelium in all analyzed samples. The mean values of LC number were 84.13 +/- 9.6 and 64.77 +/- 9.8 in hemorroid- and fissure-patients, respectively. The mean values of LC area (% of CD1a stained area over total mucosal surface) were 3.89 +/- 0.44 and 4.84 +/- 0.64, respectively. In the two groups, the number of intraepithelial CD8 lymphocytes was higher than that of CD4 lymphocytes. These data suggest for the first time that anal mucosa could be considered as a part of MALT system.

Adult↗

Platelet-activating factor stimulates gastric acid secretion in isolated rabbit gastric glands.

We examined the effect of platelet-activating factor (PAF) on gastric acid secretion by isolated rabbit gastric glands as determined by [14C]aminopyrine ([14C]AP) uptake. PAF, histamine, and carbachol time- and concentration-dependently stimulated [14C]AP uptake, with estimated half-maximal effective concentrations of 60 pM, 0.25 microM, and 0.1 microM, respectively. PAF-induced [14C]AP uptake was inhibited by the specific PAF antagonists BN-50727 and SR-27417 and by the proton pump inhibitors omeprazole and lansoprazole. However, the H2-receptor antagonist famotidine had no effect. Buffering extracellular Ca2+ by ethylene glycol-bis(beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid resulted in a shift to the right of the time-course effect of PAF without altering the maximal response, whereas buffering intracellular Ca2+ by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid 2-acetoxymethyl ester, as well as blocking Ca2+ channels by verapamil, inhibited PAF-induced [14C]AP uptake. Intracellular Ca2+ concentration in isolated rabbit gastric glands, as measured by fura 2-acetoxymethyl ester, concentration-dependently increased in response to PAF, to a maximum of 1.5-fold for 0.1 microM. These results suggest that PAF stimulates gastric acid secretion via specific receptors activating intracellular Ca2+ mobilization, which could be located on the parietal cells.

Aminopyrine↗

Antibiotic versus maintenance therapy in the prevention of duodenal ulcer recurrence. Results of a multicentric double-blind randomized trial.

OBJECTIVES: Reduction of gastric acid secretion by maintenance therapy and eradication of Helicobacter pylori by antibiotic treatment have been shown to reduce duodenal ulcer relapse. This study compared the effect of two regimens, a 6-month maintenance on an H2 receptor antagonist versus a one-week antibiotic therapy, on the rate of duodenal ulcer relapse in duodenal ulcer patients with gastric H. pylori infection. METHODS: We conducted a 30-week, double-blind, double-dummy, multicentric clinical trial involving 119 patients (97 M, 22 F, mean age 39 +/- 14 years) randomly assigned to a daily dose of 40 mg famotidine for 6 weeks supplemented with, during the first week, either antibiotics (500 mg amoxicillin q.i.d. and 500 mg tinidazole t.i.d.-antibiotic group) or their placebo (maintenance group). Healed patients after 6 weeks entered the 6-month maintenance phase: the maintenance group received 20 mg famotidine at bedtime and the antibiotic group, a placebo. Endoscopy with antral biopsies was performed to allow a rapid urease test, culture and histological examination upon entry, after 6 weeks, 3 months, and 6 months and, whenever symptoms recurred. H. pylori status was regarded as positive if any one of these three tests was positive, and negative if all tests were negative. RESULTS: The 2 treatment groups were well balanced for all baseline characteristics. After 6 weeks, H. pylori was eradicated in 25 (45%) patients in the antibiotic group, and in 1 (2%) in the maintenance group (P < 0.01). In term of intention-to-treat, there was no significant difference in the healing rate after 6 weeks (93 and 83% in the antibiotic and maintenance groups, respectively; P = 0.15) or in the relapse rate after 6 months (13 and 28% in the antibiotic and maintenance groups, respectively; P = 0.17 Log-rank test). However, the overall failure rate (absence of healing, relapse) was lower (P = 0.04, Log-rank test) in the antibiotic group in which all relapses but one were observed in H. pylori positive patients. The rate of ulcer relapse (1/20) in patients of antibiotic group who remained free of H. pylori during the study, was significantly (P < 0.01) lower compared with that of H. pylori positive patients in the maintenance group (11/44). During the first 6-week period, more side effects were observed in the antibiotic group than in the maintenance group (4 vs 1 patient, respectively). CONCLUSIONS: Our results indicate no significant difference between ulcer relapse rates after 6 months following a one-week antibiotic therapy or long-term maintenance therapy. Short-term antibiotic therapy should be considered as a valuable alternative to the long-term maintenance therapy.

Adult↗

[Female dyschesia, functional associations and pelvic disorders].

OBJECTIVES: Although the usual methods of exploring anorectal disorders give information on specific aspects of defecation, they do not take into account the related effect of disorders involving the pelvic contents including the genital and urinary tract. We therefore used physical examination and global imaging to demonstrate the effect of urinary and genital anomalies in female patients with dyschesia. METHODS: A prospective study was conducted in 50 consecutive female patients (age range 21-83) who consulted for dyschesia. The following protocol was used. History taking included a search for urinary and gynaecology surgery or medical treatment and the number of pregnancies and instrumental deliveries as well as a precise scoring of defecation disorders. The general physical examination included a search for signs of prolapsus or ulcerations. A rectocolpocystogram was performed in all patients. RESULTS: There were 7 patients under 40 years of age, 25 from 41 to 61 years and 18 over 61. Urinary incontinence was the most frequent functional complaint (80%). In 92% of the patients, the rectocolpocystogram revealed associated anatomic anomalies. Dynamic stimulation was associated with cervicocystoptosis (72%), hysteroptosis (50%) and rectocele (66%). CONCLUSION: Female dyschesia is a complex phenomena involving the anatomic status of the urinary, genital and anorectal tracts. Therapeutic management should be based on a complete examination including an evaluation of the pelvic contents and the perineum.

Adult↗

Polymerase chain reaction assay for the detection of Helicobacter pylori in gastric biopsy specimens: comparison with culture, rapid urease test, and histopathological tests.

Ulcer recurrence is probably related to residual Helicobacter pylori (H pylori). Histological examination and culture are considered to be the most specific tests. CLO test is a rapid but less specific test, which is usually used as an alternative test to culture. The aim of this study was to investigate the efficiency of a simplified polymerase chain reaction (PCR) assay as a procedure for the diagnosis of gastric H pylori infection of patients. Biopsy specimens were obtained from antral mucosa of 58 patients at endoscopy and submitted to four tests for detection of H pylori. The bacteria were found in 53%, 43%, 48%, and 50% of patients according to the results of PCR, CLO test, culture, and histological examination. Twenty three patients had both negative histology and negative culture and PCR was negative in all of these. Thirteen patients were not classified because only histology or culture was positive and 10 of these had a positive PCR test. When the diagnosis of H pylori was established by agreement with both histology and culture or three positive tests out of four, 29 patients were H pylori positive (28 having had three positive tests and one displaying positive histology and culture), and 26 were negative, and three undetermined. PCR proved the most sensitive and specific test. These results suggest the simplified PCR assay may be a valuable test for the detection of H pylori.

Adult↗

Chronic endogenous hypergastrinemia in humans: evidence for a mitogenic effect on the colonic mucosa.

BACKGROUND: Information concerning the influence that gastrin may exert on the colon is fragmentary and somewhat controversial. This study analyzed the effect of chronic endogenous hypergastrinemia on cell proliferation and tumor occurrence in the human colonic mucosa. METHODS: Twenty-three consecutive hypergastrinemic patients presenting with the Zollinger-Ellison syndrome and 18 normogastrinemic subjects were studied. All had fasting serum gastrin determination, colonoscopy, and cell kinetic measurement in two colonic sites using in vitro 5'-bromodeoxyuridine incorporation. RESULTS: Macroscopic tumors, one endocrine and five adenomas, were found in 5 of 23 hypergastrinemic patients, without apparent relationship with the level of gastrin. The labeling indices were significantly higher in hypergastrinemic than in normogastrinemic individuals in the right and left colon, (P < 0.002 to P < 0.001) without resulting in colonic cell hyperplasia. There was no correlation between labeling indices and serum gastrin concentrations or duration of hypergastrinemia. The DNA labeling distribution along the crypt was normal in the two groups, without expansion of the proliferative zone towards the surface. CONCLUSIONS: These results showed for the first time that long-lasting endogenous hypergastrinemia is accompanied by increased in vivo cell proliferation in the human colonic mucosa. However, the prevalence of adenomas (17.4%) in patients, all more than 50 years old, may not be different from that in the general population.

Adenoma↗

Gastric secretion of platelet activating factor and precursors in healthy humans: effect of pentagastrin.

The release of platelet activating factor (PAF-ACETHER or PAF) and its precursors in the gastric lumen was assessed in 13 normal subjects in basal condition and after stimulation by gastrin. Acid, pepsin, and sialic acid outputs were determined under the same conditions. Gastric juice was collected using a nasogastric tube after overnight fast in basal condition for 60 minutes, then under pentagastrin infusion (6 micrograms/kg/hr for 60 minutes). Platelet activating factor was detected at low concentration in 4/13 subjects under basal condition (mean (SEM) 1.2 (0.6) pg/hr) while high concentrations of lyso platelet activating factor (6.1 (1.8) microgram/hr) and of alkyl-acyl-glycerophosphocholine (AAGPC) (11.5 (3) micrograms/hr) were found in 13 and 11 subjects, respectively. Platelet activating factor was not detected during pentagastrin infusion, while lyso platelet activating factor and alkyl-acyl-glycerophosphocholine were detected in 13 and in 12 subjects, respectively. Compared with the basal condition these platelet activating factor precursors increased significantly (p < 0.001) going up to fivefold baseline (31.8 (6.8) micrograms/hr and 53 (9.3) micrograms/hr respectively) in response to pentagastrin. There was a positive correlation between platelet activating factor precursors and acid or pepsin output but not between platelet activating factor precursors and sialic acid. As sialic acid may be considered an index of mucus glycoprotein degradation, it seems that gastrin stimulation of gastric epithelial cells results in a concomittant secretion of platelet activating factor precursors, acid, and pepsin irrespective of mucus glycoprotein degradation.

Acetylation↗

[Increase of resting energy expenditure during flare-ups in Crohn disease].

Crohn's disease is an inflammatory process commonly characterized by phases of flare-up. Weight loss and malnutrition are prominent features in the course of the disease, especially during acute episodes. It is therefore important to define energy needs. Curiously, resting energy expenditure (REE) has rarely been studied in Crohn's disease, and never in relation with the activity of the disease. We therefore determined REE together with body composition (fat free mass, FFM), Crohn's disease activity index (CDAI) and plasma acute phase proteins in 70 patients: during flare-up in 41 and during clinical remission (CDAI < 150) in 29. We found an increase in REE in patients with active disease (CDAI > 150), as compared with patients in remission, when REE was expressed as a function of FFM: 31.7 +/- 2.7 versus 29.4 +/- 3.3 kcal/kg FFM/day (P < 0.01). The mean REE/FFM was 8% higher during flare-up than during remission, and was correlated to both clinical (CDAI; P = 0.011) and biological inflammatory activity indices (C reactive protein, P = 0.018; orosomucoid, P = 0.024). In some patients, the REE was in the normal range, despite an increase in REE/FFM, because of a decrease in FFM due to hypermetabolism. In 8 patients treated successfully by total parenteral nutrition for a massive flare-up, REE/FFM was increased before TPN (36.6 +/- 3.0 kcal/kg/day), and decreased after 4 weeks of TPN (31.4 +/- 1.8 kcal/kg/day; P < 0.001), returning within normal values in 7 patients.

Adult↗

[Budd-Chiari's syndrome with caval membranous web treated by liver transplantation].

In this paper, the case of a 30 year-old Asiatic man with a Budd-Chiari syndrome secondary to a caval membranous web, associated with cirrhosis is presented. After unsuccessful percutaneous dilatation, liver transplantation associated with membranotomy treated the venous obstacle and ensured satisfactory recovery. Orthotopic liver transplantation is the most effective treatment in this setting.

Adult↗

[Diarrhea in AIDS. Group AIDS GIT].

Gastrointestinal (GI) infections are frequent in AIDS patients. The frequency and type of opportunistic GI infections are exactly the same in homosexuals and heterosexuals. Diarrhoea is the usual sign of GI infection, and its mechanism seems to combine a secretory component and a malabsorption. Although a number of pathogens can be isolated, in many cases the diarrhoea cannot be explained by an infection or a lesion. The hypothesis of a primary HIV infection in the epithelium of the small bowel and colon has not been confirmed by immunofluorescence and molecular hybridization. The HIV virus has been found in the GI mucosa, but it was probably carried by the immune cells in general circulation (CD4 lymphocytes and macrophages) which subsequently colonize the chorion of the mucosa.

Acquired Immunodeficiency Syndrome↗

Significance and regulation of gastric secretion of platelet-activating factor (PAF-acether) in man.

Platelet-activating factor (PAF) has been implicated in the pathogenesis of acute inflammatory and ulcerative diseases of the upper gastrointestinal tract. In the present study, we compared the gastric output of PAF and its precursors with gastric acid output, in patients with various upper gastrointestinal tract diseases and healthy controls. PAF and precursors were also extracted from gastric biopsies from subjects with chronic gastritis and/or gastric colonization by Helicobacter pylori. Under basal conditions, hourly gastric PAF output increased in esophagitis and erosive gastritis, but not in duodenal ulcer or Zollinger-Ellison syndrome. In the gastric juice of duodenal ulcer patients, PAF output rose after secretin, but in patients with Zollinger-Ellison syndrome, PAF was only detected when gastric acid secretion had been reduced by antisecretory drugs and no concurrent changes were observed in serum gastrin levels. After pentagastrin, patients and controls exhibited a significant decrease in PAF output and a negative correlation was found between PAF and acid outputs (r = -0.57, p < 0.01). When PAF was incubated with gastric juice in vitro, it underwent degradation irrespective of the medium pH. We found no relation between the outputs of PAF and precursors and the severity of gastritis or gastric colonization by H. pylori. Overall, these results suggest that PAF might be released in the stomach by gastric epithelial cells and could be responsible for mucosal injury of the upper gastrointestinal tract.

Adult↗

Raised concentrations of platelet activating factor in colonic mucosa of Crohn's disease patients.

Platelet activating factor (PAF-ACETHER or PAF) and precursors of platelet activating factor were investigated in 26 patients with acute Crohn's disease and in 10 healthy controls. Platelet activating factor, lyso platelet activating factor, and alkyl acyl glycerophosphocholine, were determined in colonic mucosal biopsies in patients with acute Crohn's disease, during prednisolone therapy, and in remission. Biopsy specimens were submitted to histopathology examination and to phospholipid extraction. Platelet activating factor, lyso platelet activating factor, and alkyl acyl glycerophosphocholine were found in patients with acute Crohn's disease and in remission as well as in controls. Whatever the site of the biopsy, the level of platelet activating factor in colonic mucosa was higher (p < 0.01) in Crohn's disease than in controls. There was no correlation between the level of colonic PAF-ACETHER and age, sex, Crohn's disease activity index, and biological parameters in sera. Although concentrations of colonic platelet activating factor content were higher (p < 0.01) when colonic mucosa displayed cell infiltration, they were neither related to the severity nor the type of inflammatory cells. Platelet activating factor decreases with prednisolone therapy and might return to normal concentrations in quiescent patients. Lyso platelet activating factor and alkyl acyl glycerophosphocholine were not significantly higher in Crohn's disease than in controls. These data suggest that platelet activating factor may be involved in the pathogenesis of Crohn's disease and that it could be used as a marker of the mucosal activity of the disease.

Adult↗

Detection of gastrin mRNA in human antral mucosa and digestive endocrine tumors by in situ hybridization: a correlative study with immunocytochemistry and electron microscopy.

In gastrinomas, as well as in other endocrine tumors whose hormone overproduction is responsible for clinical syndromes, antibodies against the bioactive form(s) of hormones can fail to detect immunoreactivity. Moreover, tumor secretory granule morphology may fail to allow tumor type identification. The use of anti-pre-pro-gastrin antibodies has been proposed as an alternative to identify gastrinomas. The aim of the present study was to demonstrate that in situ detection of gastrin mRNA may represent another possibility. A 35S-labeled cDNA probe encoding the human gastrin pre-pro-hormone was used to localize gastrin gene transcripts in antral mucosa and digestive endocrine tumors from patients with a Zollinger-Ellison syndrome characterized by high serum gastrin levels. In situ hybridization was combined with light and electron microscopic immunostaining of the bioactive gastrin 17/34 form and morphological study of secretory granules. Gastrin mRNAs were detected in antral gastrin cells and in a variable proportion of tumor cells in all endocrine tumor studied. Transcript expression correlated well with immunohistochemical staining and granule ultrastructure for most of the tumors, and provided crucial evidence for identifying as gastrinomas two tumors with weak immunoreactivity and poorly granulated cells. Our data show that in situ hybridization is a sensitive method for gastrin mRNA detection and represents a valuable tool for the identification of gastrinomas.

Digestive System Neoplasms↗

Human jejunal secretion induced by prostaglandin E1: a dose-response study.

1. Intraluminally infused prostaglandins induce jejunal secretion of water and electrolytes in man, and a receptor-mediated process in the intestinal epithelial cells has been suggested to explain this secretion. In an attempt to obtain data under basal conditions for pharmacological studies, we tested the dose-response effect of PGE1 on jejunal hydroelectrolytic movements in 10 healthy volunteers. 2. Accordingly, a solution with or without PGE1 was infused via a four-lumen tube with a proximal occluding balloon and jejunal water and electrolyte transport were determined. The segment tested was 40 cm long. Seven randomized doses of PGE1 ranging from 0.01 to 1.3 micrograms kg-1 min-1 (2.83 to 364 pmol kg-1 min-1) were infused in an isotonic control saline solution. The secretion induced by PGE1 was evaluated in each subject as the difference between fluxes in response to the control saline solution and to PGE1. 3. Whatever the dose, PGE1 induced secretion of water, Na+, K+ and Cl- which was dose-dependent and saturable, with a mean Km of congruent to 6-8 pmol kg-1 min-1, suggesting that at the pharmacological doses used, enterocytes have a saturable membrane site similar to a single class of receptor for PGE1. 4. These findings may be of great importance if prostaglandins are administered as drugs or used as jejunal secretory agents in vivo when the antisecretory effect of another drug is studied.

Adult↗