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Biomedical subjects

M Ligumsky

Publications and source records attributed to M Ligumsky.

At least 55 records · Page 3Linked to original sources
PubMed1986

Histamine and chondroitin sulfate E proteoglycan released by cultured human colonic mucosa: indication for possible presence of E mast cells.

An association between the release of histamine and chondroitin sulfate E proteoglycan (PG) was demonstrated in human colonic mucosa (HCM). Colonic biopsy samples incorporated [35S]sulfate (2.7 X 10(6) +/- 188 X 10(3) cpm/mg of wet tissue; mean +/- SEM, n = 5) into PG, which was partially released into the culture medium during the incubation period. Ascending thin-layer chromatography of the released 35S-labeled PG after its digestion by chondroitin ABC lyase (chondroitinase, EC 4.2.2.4) followed by autoradiography yielded three products that migrated in the position of monosulfated disaccharides of N-acetylgalactosamine 4-sulfate and N-acetylgalactosamine 6-sulfate and of an oversulfated disaccharide possessing N-acetylgalactosamine 4,6-disulfate. Cultured colonic mucosa released 23.6 +/- 3.7 ng of histamine per mg of wet tissue (mean +/- SEM, n = 16) without any specific trigger. Comparison by linear regression analysis of the release of histamine and chondroitin [35S]sulfate E PG revealed a correlation coefficient (r) of 0.7 (n = 16; P less than 0.005). Histological examination of the colonic biopsies revealed the presence of many mast cells in various degrees of degranulation in the mucosa and submucosa, most of which were found in the submucosa. Incubation of the HCM biopsies in the presence of anti-human IgE revealed 58% +/- 12% (mean +/- SEM, n = 3) enhancement in the release of chondroitin [35S]sulfate E PG and 64% +/- 10% (mean +/- SEM, n = 4) of histamine release. The above correlation, the observation that most of the mast cells showed various degrees of degranulation, and the lack of heparin synthesis as opposed to the synthesis and immunological release of chondroitin sulfate E strongly suggest that the E mast cell exists in the human colon.

Cells, Cultured↗
PubMed1986

Sucralfate protection against gastrointestinal damage: possible role of prostanoids.

The protective effect of sucralfate against gastric and intestinal mucosal damage was studied in rats. Sucralfate (125 mg) significantly reduced gastric mucosal lesion formation induced by s.c. administration of indomethacin (30 mg/kg) or intragastric administration of aspirin (100 mg/kg), HCl (0.6 N), NaOH (0.2 N) or sodium taurocholate (30 mM). Furthermore, when given in three doses of 125 mg each, sucralfate significantly decreased the development of small intestinal lesions induced by indomethacin in the re-fed rat. Gastric mucosal cyclooxygenase activity in sucralfate-treated rats expressed as prostaglandin E2 formation--388 +/- 140 (ng/g wet weight; mean +/- SE)--was significantly higher (P less than 0.01) than its activity in the control--264 +/- 62 (ng/g wet weight). Sucralfate also slightly, but significantly, decreased indomethacin-induced gastric mucosal cyclooxygenase inhibition. Intestinal mucosal cyclooxygenase activity was not affected by sucralfate. The results suggest that gastric and intestinal mucosal damage induced by various ulcerogens is significantly reduced by sucralfate. Sucralfate-induced stimulation of endogenous gastric mucosal prostanoid formation may in part explain its effective protective properties.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Protection by mild irritants against indomethacin-induced gastric mucosal damage in the rat: role of prostaglandin synthesis.

"Mild irritants" have been shown to protect rat gastric mucosa from damage induced by noxious topical agents, supposedly by induction of mucosal prostaglandin (PG) biosynthesis. The protective effect of NaCl 5%, ethanol 20%, NaOH 0.075 N, HCl 0.35 N, salicylic acid 100 mg/kg and paracetamol 200 mg/kg was investigated in rats treated with an ulcerogenic dose (25 mg/kg) of indomethacin; mucosal PG synthesis was simultaneously determined. Significant protection was achieved only with NaCl 5%, salicylic acid and paracetamol. Salicylic acid and paracetamol significantly decreased acid secretion and enhanced PGE2 or 6-keto PGF1 alpha generation in control rats, while a small but significant change in the indomethacin-inhibited PG synthesis was observed after treatment with NaCl 5% or salicylic acid. We conclude that protection by "mild irritants" against indomethacin-induced mucosal damage may involve increased cytoprotective PG generation, as shown for paracetamol and salicylic acid, or partial blocking of indomethacin binding at the cyclooxygenase receptor site, as shown for NaCl 5% and salicylic acid.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Dietary fat, adipose tissue composition, and the development of carcinoma of the colon.

Dietary fat and plasma lipids have been implicated in the development of carcinoma of the colon. Because of the difficulties in obtaining accurate dietary histories, subcutaneous adipose tissue fatty acids were analyzed to compare fat intake in 3 groups of patients undergoing colonoscopy: patients with carcinoma of the colon (n = 53; average age, 64 yr; 47% male), patients with neoplastic polyps (n = 34; age 63 yr; 71% male), and patients with normal findings (controls; n = 68; age 58 yr; 40% male). The groups were similar with regard to body mass index and coffee and egg consumption. One-way analysis of variance of the plasma total cholesterol, triglycerides, high-density lipoprotein cholesterol, 9 adipose fatty acids, groups of polyunsaturated fatty acids (vegetable origin), saturated fatty acids (animal origin), or the ratio of polyunsaturated to saturated fatty acids did not show any significant differences across the 3 groups. The quality of dietary fat does not appear to be associated with the development of carcinoma of the colon or of neoplastic polyps in this population.

Adipose Tissue↗
PubMed1986

Pouch ileitis--recurrence of the inflammatory bowel disease in the ileal reservoir.

"Pouchitis" is an inflammation of the ileal pouch that has been described as occurring after Kock's procedure--the continent ileal pouch. The case presented herein demonstrates clinical and histological features that resemble ulcerative colitis, implying that this disorder may be a recurrence of the patient's original inflammatory bowel disease and not merely a local and nonspecific process as previously suggested.

Adult↗
PubMed1985

Naloxone is protective against indomethacin-induced intestinal ulceration in the rat.

Naloxone, an opiate antagonist, was reported to protect against stress ulcers in dogs and rats. We studied its possible protective effect against indomethacin-induced intestinal ulceration in the rat. Naloxone was indeed found to possess a marked protective effect on the intestinal mucosa (ulcer index 73.3 +/- 13.6 vs. 273.8 +/- 21.8, p less than 0.001). Naloxone was found to elevate basal intestinal mucosal prostaglandin E2 (p less than 0.001) and cyclic adenosine monophosphate levels (p less than 0.005) but was unable to overcome the inhibition of prostaglandin E2 caused by indomethacin. An increase of cyclic adenosine monophosphate levels was seen, however, even in the presence of indomethacin, suggesting that cyclic adenosine monophosphate, but not prostaglandins, may play a role in the protective effect of naloxone.

Animals↗
PubMed1985

Salicylic acid blocks indomethacin-induced cyclooxygenase inhibition and lesion formation in rat gastric mucosa.

Salicylic acid has been shown to decrease gastric mucosal lesions induced by indomethacin in the rat. In vitro, it has also been shown to counteract the inhibitory effect of indomethacin and aspirin on the cyclooxygenase enzyme system in seminal vesicle microsomes and in platelets and vascular tissue. The hypothesis that the mechanism of salicylic acid "protection" against indomethacin-induced gastric lesions involves interference with indomethacin-induced mucosal cyclooxygenase inhibition was tested. Male, fasted rats were treated with intragastric salicylic acid in doses of 50, 100, 200, 300, or 400 mg/kg concomitantly with a sc injection of 20 mg/kg of indomethacin. Gastric mucosal lesions and mucosal cyclooxygenase activity (as measured by ex vivo prostaglandin F2 alpha synthesis) were examined 3 hr later. Intragastric salicylic acid, 200-400 mg/kg, significantly reduced indomethacin-induced lesion formation, while counteracting significantly indomethacin inhibition of prostaglandin synthesis. Salicylic acid alone did not significantly change cyclooxygenase activity. It is concluded that topical salicylic acid can decrease indomethacin-induced gastric mucosal lesion in the rat, in part, by counteracting the inhibitory effect of indomethacin at the cyclooxygenase level.

Animals↗
PubMed1985

Comparison of misoprostol and cimetidine in the treatment of duodenal ulcer.

The efficacy of misoprostol (a synthetic analogue of prostaglandin E1) and cimetidine in the treatment of duodenal ulcer was evaluated. Seventy-one patients with endoscopically proven duodenal ulcer were randomized in a double-blind manner in one of three groups that received four daily doses of either misoprostol, 50 or 200 micrograms, or cimetidine, 300 mg. Ulcer healing was assessed endoscopically after 4 weeks of treatment. The mean age, sex distribution, and tobacco, alcohol and caffeine consumption were similar in all treatment groups. Only one patient was lost to follow-up. On the misoprostol low dose, healing of the ulcer was observed in 60.9% of the patients. In contrast, healing on the higher dose of misoprostol was not significantly different to that with cimetidine. No significant clinical or laboratory side effects were observed in any of the patients. We found that the daily dose of 800 micrograms misoprostol is safe and effective in the treatment of duodenal ulcer.

Adult↗
PubMed1985

Comparison of misoprostol and cimetidine in the treatment of gastric ulcer.

The efficacy of misoprostol (a synthetic analogue of prostaglandin E1) and cimetidine in the treatment of gastric ulcer was evaluated. Thirty-two patients with endoscopically proven gastric ulcer were randomized, in a double-blind manner, in one of three groups that received four daily doses of either misoprostol, 50 or 200 micrograms, or cimetidine, 300 mg. Ulcer healing was assessed endoscopically after 4 weeks of treatment. The three groups were fairly comparable in their alcohol and caffeine intake, previous ulcer history and ulcer size. A relatively high proportion of patients in the cimetidine-treated group was smokers. Only one patient was withdrawn from the study. On the misoprostol low dose, healing of the ulcer was observed in 20% of the patients. In contrast, healing on the high dose of misoprostol (70%) was not significantly different from that on cimetidine (73%). No important clinical side effects were observed in any of the patients. These results (part of a multicenter, international study) suggest that the divided daily dose of 800 micrograms misoprostol is safe and effective in the short-term treatment of gastric ulcer.

Adolescent↗
PubMed1984

Stimulation of gastric prostaglandin synthesis by refeeding in the rat. Role in protection of gastric mucosa from damage.

The purpose of the present study was to determine whether feeding stimulates prostaglandin (PG) synthesis in the gastric mucosa and whether this might play a role in the defensive mechanism of the gastric mucosa. The effect of refeeding on the formation of gastric lesions induced by nonsteroidal antiinflammatory drugs and on the generation of prostaglandin in the gastric mucosa was investigated. In the fasted rat aspirin and indomethacin produced many lesions in the corpus, but few or no lesions in the antrum. Refeeding of chow pellets before aspirin or indomethacin significantly decreased the corpus lesions, but provoked lesions in the antrum. When each drug was given before the refeeding, the protection against corpus lesions by refeeding was reduced and the lesions in the antrum were significantly increased. Mucosal generation of 6-keto-PGF 1 alpha (a stable metabolite of PGI2) and PGF2 alpha was measured ex vivo by the method of Whittle. The generation of 6-keto-PGF1 alpha and PGF2 alpha in the fasted rat deprived of food for 24 hr was 1761 +/- 170 and 217 +/- 7 ng/min/g tissue in the corpus mucosa, and 2958 +/- 217 and 453 +/- 33 ng/min/g tissue in the antral mucosa, respectively. Refeeding of chow pellets significantly increased the generation of both prostaglandins in the antral mucosa and of PGF2 alpha in the corpus mucosa, but did not affect the generation of PGI2 in the corpus mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Prostaglandins mediate inhibition of gastric acid secretion by somatostatin in the rat.

Somatostatin, a tetradecapeptide with potent inhibitory actions on gastric acid secretion, potentiated carbamylcholine-induced synthesis and release of prostaglandin E2 from isolated perfused rat stomachs. The ability of somatostatin to inhibit acid secretion was blocked by indomethacin, an inhibitor of prostaglandin synthesis. These results suggest that prostaglandins mediate gastric acid inhibition by somatostatin in the rat.

Animals↗
PubMed1983

Prostanoid synthesis by cultured gastric and duodenal mucosa: Possible role in the pathogenesis of duodenal ulcer.

Cultured duodenal mucosa obtained from normal subjects synthesized and secreted significantly less prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, and thromboxane B2 (TXB2) than cultured gastric mucosa obtained from the same subjects. Accumulation of PGE2, 6-keto-PGF1 alpha, and TXB2--the stable metabolites of prostacyclin I2 and thromboxane A2, respectively--by cultured gastric mucosa obtained from 21 untreated patients with active duodenal ulcer was significantly lower than their respective accumulation by cultured gastric mucosa obtained from 14 normal subjects. Accumulation of all three prostanoids by cultured duodenal mucosa obtained from patients with active duodenal ulcer and from normal subjects was not significantly different. PGE2, 6-keto-PGF1 alpha, and TXB2 accumulation was five to six times higher than their respective content in fresh tissue before culture and was inhibited by flufenamic acid. These results suggest that a decrease in endogenous gastric prostanoid synthesis may have a role in the pathogenesis of peptic ulcer disease.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Aspirin can inhibit gastric mucosal cyclo-oxygenase without causing lesions in rat.

Dose-response relationships between aspirin-induced cyclo-oxygenase inhibition and gastric mucosal injury were studied in rats. Oral or parenteral aspirin, 25 mg/kg, inhibited prostaglandin generation by 87%-95% at 1, 3, and 6 h with no lesion formation. Aspirin, 100 mg/kg, inhibited prostaglandin generation by 95%-98% at 1, 3, and 6 h, but lesions were observed only when aspirin was given orally. Three-hour pretreatment with intraperitoneal aspirin, 12.5 mg/kg, did not enhance the mucosal injury caused by 10 mM acidified taurocholate, although prostaglandin generation was inhibited by 80%. Pretreatment with 25 mg/kg aspirin inhibited prostaglandin generation by 89% and was associated with significant mucosal injury by acidified taurocholate. We conclude that aspirin-induced 95% inhibition of gastric mucosal cyclo-oxygenase is not, by itself, sufficient to produce lesions and inhibition by greater than 80% is required to predispose the gastric mucosa to injury by otherwise mild irritants.

Administration, Oral↗
PubMed1982

Endogenous gastric mucosal prostaglandins: their role in mucosal integrity.

These studies were designed to determine the role of endogenous gastric mucosal prostaglandins (PG) in maintaining mucosal integrity. Vagally denervated, separated pouches of gastric fundic mucosa in unanesthetized dogs were irrigated with either acetylsalicylic acid (ASA) or salicylic acid (SA) (0, 2.5, 5.0, 10.0, 20.0, and 40.0 mM) in 150 mM HCl. Transmucosal potential difference (PD) and net H+, Na+, and K+ flux were measured. Mucosal ex vivo generation of 6-oxo-PGF1 alpha, PGE2, and PGF2 alpha was measured by radioimmunoassay in mucosal biopsies taken after exposure to each agent. No difference in PD or net H+, Na+, or K+ flux was observed between pouch irrigation with ASA or SA at 2.5-20.0 mM concentrations. Net H+ and Na+ flux was significantly greater (P less than 0.01) after irrigation with 40 mM SA than with 40 mM ASA. No significant reduction in gastric mucosal ex vivo generation of 6-oxo-PGF1 alpha (range, 65-98 ng.g-.min-1), PGE2 (range, 250-326 ng.g-1.min-1), or PGF2 alpha (range, 115-156 ng.g-1.min-1) was observed after pouch irrigation with all concentrations of SA. In comparison, gastric mucosal ex vivo generation of 6-oxo-PGF1 alpha (range, 75-2 ng.g-1.min-1), PGE2 (range, 22-3 ng.g-1.min-1), and PGF2 alpha (range, 40-2 ng.g-1.min-1) was significantly reduced after irrigation with all concentrations of ASA. From these data, we conclude that the activity of endogenous gastric prostacyclin, PGE2 alpha, and PGF2 alpha is not a prerequisite for mucosal integrity as measured by PD and net cationic flux.

Animals↗
PubMed1982

Salicylic acid blocks indomethacin- and aspirin-induced cyclo-oxygenase inhibition in rat gastric mucosa.

Salicylic acid reduces gastric mucosal lesions induced by aspirin and indomethacin. Aspirin and indomethacin reduce gastric mucosal cyclo-oxygenase activity. These studies were designed to determine whether or not salicylic acid interacts with gastric mucosal cyclo-oxygenase, decreasing the inhibitory effect of aspirin and indomethacin as has been observed in platelets and vascular tissue. The interaction between salicylic acid and two cyclo-oxygenase inhibitors, indomethacin and aspirin, was assessed on ex vivo prostaglandin generation in the rat gastric mucosa. Salicylic acid (100 mg/kg) was administered orally 30 min before the subcutaneous injection of either indomethacin (0.5-10 mg/kg) or aspirin (5.0-20 mg/kg). Pretreatment produced a shift of the mean 50% inhibitory dose for PGF2 alpha formation from 0.92 to 7.6 mg/kg for indomethacin and from 7.8 to 20 mg/kg for aspirin. Similar results were achieved with ex vivo prostacyclin synthesis as measured by the level of 6-keto-PGF 1 alpha. These data are consistent with competitive enzyme kinetics, and may, in part, explain the protective effect of salicylic acid against the ulcerogenicity of aspirin and indomethacin on the gastric mucosa.

Animals↗
PubMed1982

Prostanoid synthesis by cultured peripheral blood mononuclear cells in inflammatory diseases of the bowel.

Prostanoid synthesis by cultured peripheral blood mononuclear cells and monocytes in inflammatory bowel disease patients was determined because monocytosis was reported in inflammatory bowel diseases and prostanoids are synthesized by peripheral blood mononuclear cells in response to inflammatory stimuli. Prostaglandin E2 and thromboxane B2 accumulation in the medium of cultured peripheral blood mononuclear cells isolated from patients with active Crohn's disease was two and three times higher than their respective accumulation by peripheral blood mononuclear cells isolated from normal subjects or patients in remission. In ulcerative colitis, prostaglandin E2 and thromboxane B2 accumulation was not enhanced. 6-Keto-prostaglandin F1 alpha was not detected in any of the cultured medium. The absolute number of monocytes was determined according to their adherence to plastic surfaces, and the percent of phagocytic cells was significantly higher among peripheral blood mononuclear cells in patients with Crohn's disease and ulcerative colitis as compared with peripheral blood mononuclear cells isolated from normal subjects. However, prostaglandin E2 secretion, by the same number of cultured monocytes isolated from all groups of patients, was similar. Flufenamic acid, methylprednisolone, and 5-aminosalicylic acid significantly inhibited prostaglandin E2 and thromboxane B2 accumulation. These results suggest that in Crohn's disease enhanced prostanoid synthesis is probably due to the monocytosis, whereas in ulcerative colitis the monocytosis is not accompanied by a significant increase in prostanoid synthesis in vitro.

6-Ketoprostaglandin F1 alpha↗