Prostaglandin E2 Content Research Articles

EFFECT OF LANSOPRAZOLE ON GASTRIC SECRETION, PROSTAGLANDIN E, AND PLASMA GASTRIN IN INDOMETHACIN-INDUCED ULCER IN RATS

The effect of lansoprazole (lansoprazole) (40, 80 mg/kg) daily orally for three weeks on gastric luminal release of prostaglandin E2 (PGE2), pH, sodium and potassium ion contents of gastric juice, as well as plasma gastrin level was investigated on indomethacin-induced ulcer in rats. Daily administration of lansoprazole (40 or 80 mg/kg) significantly elevated the intragastric pH and K+ ion concentration after one, two and three weeks. Sodium ion concentration was only elevated by lansoprazole 80 mg/kg after the same time intervals. Plasma gastrin level was significantly elevated by lansoprazole in a dose dependent manner. On the other hand, lansoprazole in either doses failed to elevate the reduced level of PGE, in the gastric lumin induced by indomethacin. In conclusion, lansoprazole caused elevation in intragastric pH value, Na+ and K+ ions concentration, it also raised plasma gastrin level in a dose dependent manner, these effects would be related to inhibition of acid secretion. On the other hand lansoprazole failed to elevate the gastric luminal PGE2 level indicating that it has no cytoprotective effect.

Effect of 10% ethanol and sofalcone on prostaglandin E2 content, mucus gel thickness, and experimental ulcers in the stomach of developing rats.

We studied the effects of a mild irritant, 10% ethanol, and sofalcone on the gastric mucosal defense mechanisms in newborn rats, comparing the effects to those seen in adult rats. The results indicated (1) that both mucosal prostaglandin E2 (PGE2) content and mucus gel layer thickness increased with age, (2) that sofalcone, but not 10% ethanol, increased mucosal PGE2 content and mucus gel thickness in 1- and 8-week-old rats, (3) that both sofalcone and 10% ethanol decreased mucosal damage induced by 50 or 75% ethanol in both age groups, and (4) that 10% ethanol, but not sofalcone, decreased ethanol-induced mucosal damage in rats pretreated with indomethacin. We concluded that 10% ethanol and sofalcone increase gastric mucosal defence mechanisms in newborn rats as in older rats.

Both prostaglandin E2 and nitric oxide sequentially mediate the tumor necrosis factor alpha-induced inhibition of surfactant synthesis by human type II pneumocytes.

Tumor necrosis factor alpha (TNF-alpha)-induced inhibition of surfactant synthesis seems to participate in the pathogenesis of the adult respiratory distress syndrome. To examine the ability of human type II pneumocytes to produce nitric oxide (NO) in the presence of TNF-alpha and, in addition, to explore the role of this radical in the transduction of the cytokine signal. Multiple organ donors were the source of lung tissue specimens. Type II pneumocytes were isolated by enzymatic digestion, adherence separation of macrophages, and gradient purification. After 24-hour preculture, cells were cultured for 24 hours in the presence or absence of TNF-alpha (100 ng/mL), sodium nitroprusside (100 mumol/L), N omega-nitro-L-arginine methyl ester (NAME) (1 mmol/L), methylene blue (10 mumol/L),8-bromo-3',5'-cyclic guanosine monophosphate (8-Br-cGMP) (1 mmol/L), prostaglandin E2 (PGE2) (0.1 mumol/L), indomethacin (30 mumol/L), and combinations. The NO release to the medium and cGMP and PGE2 contents of the cells were measured. The incorporation of 14C-labeled glucose (D-[U-14C]glucose) into phosphatidylcholine and phosphatidylglycerol was selectively inhibited either by 8-Br-cGMP or in the presence of TNF-alpha, PGE2, or nitroprusside, all of which caused an increase in the intracellular levels of cGMP. The inhibitory effect of TNF-alpha was partially reverted by indomethacin, NAME, N-monomethyl arginine, or methylene blue. The inhibitory effect of PGE2 was partially reverted by NAME, while that of nitroprusside was reverted by methylene blue, but not by indomethacin. Tumor necrosis factor alpha induced an increase in PGE2 (4.31 +/- 0.27 vs 1.65 +/- 0.17-pg/microgram protein, n = 10, P < .01) and cGMP (0.238 +/- 0.012 vs 0.109 +/- 0.014-pmol/microgram protein, n = 10, P < .01) cell content and in the NO release to the medium (3.10 +/- 0.14 vs 1.19 +/- 0.11-nmol/microgram protein, n = 10, P < .01). The basal NO release to the medium was also increased in the presence of PGE2. The NAME, which blocked NO generation and cGMP increase, did not affect PGE2 production in response to TNF-alpha. However, indomethacin, which blocked PGE2 production, also blunted NO generation and cGMP increase. The NO generation, secondary to PGE2 production, seems responsible for the TNF-alpha-induced inhibition of phosphatidylcholine synthesis by human type II pneumocytes. Nitric oxide seems to exert this effect through activation of guanylyl cyclase.

Decreased hypothalamic prostaglandin D2 and prostaglandin E2 contents during isoflurane anaesthesia in rats

This study was undertaken to evaluate the effect of isoflurane anaesthesia on the hypothalamic contents of both prostaglandin D2 and E2 which affect the sleep-wakefulness cycle. Sixty-three Wistar rats were divided into three equal groups, control, isoflurane and recovery groups. Twenty-one rats of the control did not receive isoflurane. In the other groups 21 rats received isoflurane 2% for 30 min and 21 received isoflurane 2% for 30 min and were allowed to recover their usual behaviours, including righting reflex, spontaneously. The hypothalamus was removed and the contents of PGD2 and PGE2 were measured by enzyme immunoassay. The PGD2 content in the hypothalamus was 397.9 +/- 226.0 pg.g-1 for the control group, 134.2 +/- 41.2 pg.g-1 for the isoflurane group and 269.1 +/- 124.6 pg.g-1 for the recovery group, respectively. The hypothalamic PGE2 contents were 381.4 +/- 139.0 pg.g-1 for the control group, 183.3 +/- 26.4 pg.g-1 for the isoflurane group and 312.2 +/- 96.0 pg.g-1 for the recovery group, respectively. The hypothalamic PGD2 and PGE2 contents in the isoflurane group were lower (P < 0.05) than those in the control and recovery groups, while both the PGD2 and PGE2 contents of the control and the recovery groups were similar. We conclude that decreased hypothalamic PGD2 and PGE2 contents may be related to some manifestations of general anaesthesia with isoflurane.

EFFECTS OF DIETARY FIBRE ON DIMETHYLHYDRAZINE‐INDUCED CHANGES IN PROSTANOID CONCENTRATIONS IN RAT COLONIC MUCOSA

1. This study was designed to elucidate the effects of guar gum, a dietary fibre, on changes in prostanoid contents induced by 1,2-dimethylhydrazine, a carcinogenic agent, in rat colonic mucosa. 2. Prostanoid contents were determined using high performance liquid chromatography; five prostanoids, namely 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, prostaglandin E2, prostaglandin D2 and thromboxane B2, were detected. 3. Four subcutaneous injections of dimethylhydrazine, 60 mg/kg every 6 days, increased the mucosal concentrations of prostaglandin E2 and thromboxane B2 by approximately 50%. Other prostanoids did not change significantly throughout the experiments. 4. In rats treated with dimethylhydrazine and a fibre diet a significant increase in thromboxane B2 content was not observed, although a significant increase in prostaglandin E2 content was observed. These effects were observed in rats fed with fibre diet over 20 days but not observed in rats fed with fibre diet over 10 days. 5. From these results and the report that aspirin use at low doses is effective in the reduction of the risk of fatal colonic cancer, inhibiting thromboxane B2 synthesis by fibre diet might be involved in the protective effect against the occurrence of colonic cancer.

Intestinal site-dependent susceptibility to chronic indomethacin in the rat: a morphological and biochemical study.

The cyclo-oxygenase inhibitor indomethacin induces a pattern of gastrointestinal injury in the rat that is site-dependent. This study compared the extent of injury to different regions of the rat intestine (small intestine, caecum and colon) with the corresponding changes in arachidonic acid metabolism in these areas, following long-term, low-dose indomethachin. Rats (eight per group) received either indomethacin (3 mg.kg/day) or control diet for either 6 or 12 weeks. At termination animals were bled, examined both macroscopically and microscopically for ulcers, and assayed for blood thromboxane B2, intestinal tissue prostaglandin E2 content and production of leukotriene B4. In a further eight animals luminal indomethacin concentrations from the small intestine, caecum and colon were measured following 6 weeks of chronic drug ingestion. At 6 weeks, macroscopic ulcers were observed in 2/8 (small intestine), 3/8 (caecum) and 1/8 (colon) animals. The corresponding ratios at 12 weeks were 5/8, 8/8 and 0/8. In control animals, a site-dependent gradient of the prostaglandin E2 concentration was found. In indomethacin-dosed animals the intestinal prostaglandin E2 content was reduced significantly in the caecum at 6 weeks, and in all tissues at 12 weeks. An increased leukotriene B4 production was observed in the caecum only, at 12 weeks (P < 0.01), and the blood thromboxane B2 was reduced at both time points (P < 0.05). There is a site-dependent gradient of the prostaglandin E2 concentration in the rat intestine. The rat caecum is particularly sensitive to long-term low-dose indomethacin, both in terms of chronic intestinal inflammation and changes in prostanoid metabolism. This site-dependent degree of injury may be associated with a local cyclo-oxygenase inhibition.

Association of Increased Prostaglandin E2 Content in Bronchoalveolar Lavage Fluid and Intrathoracic Malignancy

Prostaglandin E2 (PGE2), a metabolite of arachidonic acid, plays an important role in immunoregulation. We have previously reported an increased PGE2 content in bronchoalveolar lavage fluid (BALF) in 18 patients who had primary lung cancer as compared with 6 patients who had benign lung diseases and 10 normal smokers. In this article, we report our further observation, including additional 73 patients with primary lung cancer, 11 patients who had carcinoma other than lung cancer with and without lung metastases, and 24 patients with various benign lung diseases. Prostaglandin E2 content of BALF in patients with primary lung cancer and patients with extrathoracic cancer with lung metastases was markedly increased to 283.7 +/- 423.8 and 278.3 +/- 303.4 pg/ml, respectively. In contrast, patients who had extrathoracic cancer without lung metastases and patients with benign lung diseases had PGE2 content in BALF of 22.6 +/- 6.6 and 27.2 +/- 12.4 pg/ml, respectively. Values between the subgroups of patients with lung cancer (primary and metastatic) and patients with benign diseases or extrathoracic cancer without lung metastasis were significantly different (p < .001). Follow up of eight patients who successfully underwent surgical resection of cancer showed decreased levels of PGE2 in all but two patients. Although the exact cause and mechanism of the observed increase of PGE2 in BALF of patients with lung cancer are not clear at this point, current study together with our previous observations clearly indicates that the presence of lung cancer, both primary and metastatic, is associated with an elevated PGE2 content of BALF. The clinical significance of this observation is not known. However, an increased amount of PGE2 in BALF might adversely affect the course of lung cancer, because PGE2 is a down regulator of immune response against infection and neoplasm. Further investigations into the mechanism(s) and the role of PGE2 in BALF are warranted.

Induction of cyclooxygenase-2 in rat vascular smooth muscle cells in vitro and in vivo.

Prostaglandins are synthesized from arachidonic acid by the rate-limiting enzyme cyclooxygenase (prostaglandin G/H synthase). Active cyclooxygenase is encoded by two distinct and independently regulated genes, termed cyclooxygenase-1 (cox1) and cyclooxygenase-2 (cox2). In this investigation, we examined the expression of cox1 and cox2 mRNA in rat aorta following balloon deendothelialization (BDE) in vivo and in rat aortic smooth muscle cells (SMC) after serum stimulation in vitro. Two h after BDE, rat aortic cox2 mRNA levels increased greater than 50-fold relative to the lowest detectable levels on days 2 and 14. No message was detectable in non-BDE control rat aortas. Similar to the results found in vivo, cultured SMC exhibited a greater than 45-fold increase in cox2 mRNA levels after a 2-h exposure to serum. This increase was transient because cox2 levels declined at 4 and 8 h. In contrast, minimal changes in cox1 mRNA levels were observed after BDE or serum treatments. Increased levels of cox2 mRNA and corresponding protein synthesis led to an accumulation of total cyclooxygenase protein, which remained elevated 24 h after serum stimulation. Serum-treated SMC also generated greater amounts of cyclooxygenase-dependent metabolites than quiescent SMC as evidenced by marked increases in prostaglandin E2 content in conditioned media. This increase is associated with a 2.5-3.0-fold increased rate of arachidonic acid conversion to prostaglandin E2. Our data indicate that injury and serum stimulation differentially regulate mRNA and protein expression of two distinct cox genes in vascular SMC in vivo and in vitro. The findings suggest that the prostanoid responses after vascular injury are, in part, mediated by acute increases in cox2 mRNA and cyclooxygenase-2 protein.

Alteration of biological properties of bacterial lipopolysaccharide by calcium hydroxide treatment

Bacterial lipopolysaccharide (LPS) plays a major role in the development of periapical bone resorption. Although the chemical properties of LPS are altered by treatment with an alkali such as calcium hydroxide, the effects of calcium hydroxide on the biological properties of LPS are not known. The purpose of this study was to investigate whether treatment of LPS with calcium hydroxide alters its biological action as measured by human monocyte secretion of prostaglandin E2. Monocyte cell cultures were stimulated with LPS or calcium hydroxide-treated LPS and culture supernatants were analyzed for prostaglandin E2 content using gas chromatography-mass spectrometry. Prostaglandin E2 was identified in supernatants of LPS-stimulated monocytes but not in those stimulated with calcium hydroxide-treated LPS. It was concluded that the treatment with calcium hydroxide may alter biological properties of bacterial LPS.

Acute indomethacin-induced jejunal injury in the rat: Early morphological and biochemical changes

Background/Aims: Gastrointestinal injury induced by nonsteroidal anti-inflammatory drugs includes smooth muscle contraction, endothelial cell injury, and neutrophil infiltration. The aim of this study was to correlate early morphological changes with those in the metabolism of arachidonic acid. Methods: Rats administered a single oral dose of indomethacin (15 mg/kg) or vehicle were killed and their intestines perfusion-fixed at 1, 2, 3, 6, and 48 hours after dosage. Serial sections of affected small intestine were immunostained for neutrophils, macrophages, actin, and fibrinogen. In addition, rats receiving either indomethacin (15 mg/kg) or vehicle were killed at 1 and 6 hours after dosage; blood and small intestinal tissue were assayed for blood thromboxane B2, intestinal tissue prostaglandin E2, and the intestinal production of leukotriene B4. Results: At 2–6 hours, both intravascular and extravascular fibrin deposition were evident at the villus tip, and vertical alignment of villus smooth muscle cells was prominent. Significant neutrophil infiltration associated with a significant increase in leukotriene production was observed 6 hours after dosage. The extracted prostaglandin E2 content that was suppressed at 1 hour had recovered by 6 hours, whereas the blood thromboxane B2 levels were suppressed throughout the experiment. Conclusions: This study identifies an early neutrophil-independent phase of indomethacin-induced enteropathy that involves rapid cyclooxygenase inhibition and both microvascular and smooth muscle changes.

The effects of orally administered calcium pentosan polysulfate on inflammation and cartilage degradation produced in rabbit joints by intraarticular injection of a hyaluronate-polylysine complex.

To determine the antiinflammatory and cartilage-protecting activities of orally administered calcium pentosan polysulfate (CaPPS) in a rabbit model of inflammatory arthritis. A single intraarticular injection of a preformed polycation complex (PC) of poly-D-lysine and hyaluronan was used to induce joint inflammation; saline was injected into the contralateral joint as a control. Animals were killed 1, 4, 7, or 10 days post-PC injection. CaPPS, at 5 mg/kg, 10 mg/kg, or 75 mg/kg, was given every 48 hours commencing 7 days prior to PC injection. Serum interleukin-6 (IL-6), synovial fluid (SF) prostaglandin E2, cell numbers, and cartilage proteoglycan (PG) content, composition, and biosynthesis were determined for PC- and saline-injected joints. In PC-injected, non-drug-treated animals, serum IL-6 activity, SF leukocyte numbers, and prostaglandin E2 levels were elevated, while cartilage PG content and biosynthesis were reduced. CaPPS at 10 mg/kg, but not at 5 mg/kg, decreased serum IL-6 levels but maintained cartilage PG concentration and biosynthesis. However, SF leukocyte counts and prostaglandin E2 levels (except on day 1) were not reduced. The ability of CaPPS to attenuate serum IL-6 levels and preserve cartilage PGs in inflamed rabbit joints suggests that this substance could be of value as an effective orally administered chondroprotective, antiarthritic drug.

DEVELOPMENTAL CHANGES IN MUCUS GEL THICKNESS AND ITS RESPONSIVENESS TO PROSTAGLANDIN E2 IN THE RAT STOMACH

The author investigated developmental changes in the thickness of the mucosal gel layer and its responsiveness to prostaglandins in the stomach of developing rats. The results showed that (1) both mucus gel thickness and mucosal hexosamine content increased with age, (2) oral administration of 16, 16-dimethyl prostaglandin E2 increased mucosal prostaglandin E2 content and mucus gel thickness, and reduced ethanol-induced mucosal damage in 8-wk-old rats, none of which were observed in 1-wk-old rats, (3) oral 2'-carboxymethoxy-4, 4'-bis (3-methyl-2-butenyloxy) calchone increased mucosal prostaglandin E2 content and mucus gel thickness, and reduced ethanol-induced mucosal damage both in 1-wk-old and 8-wk-old rats, and (4) oral low-dose ethanol did not increase mucosal prostaglandin E2 content nor mucus gel thickness, but it did reduce ethanol-induced mucosal damage in both 1-wk-old and 8-wk-old rats. The author concluded that the mucosal susceptibility of the stomach of newborn rats may be due to the smaller amount of mucus gel found at that age.

Prostaglandin E2 in gastric mucosa of children with Helicobacter pylori gastritis: relation to thickness of mucus gel layer.

To evaluate the changes in mucus gel layer thickness and prostaglandin E2 (PGE2) content caused by Helicobacter pylori infection in the antral mucosa of children: to assess whether decreased mucus gel thickness is related to PGE2 production. Antral biopsy specimens were taken at endoscopy from 153 children. H pylori gastritis was evident in 45 and normal mucosa in 59. The other 49 children were studied one month after antibiotic treatment that eradicated the infection in 37 of them had been stopped. One antral specimen was immersed in ice-cold saline, put under an inverse microscope with an eyepiece graticule. Mucus gel thickness was measured and then the processed for histological examination; another specimen was weighed and processed for in vitro prostanoid generation. Mucus gel layer thickness was significantly decreased in children with H pylori gastritis (90 (SD) 29) microns v 120 (58) microns in controls, p < 0.01) but returned to control values after H pylori had been eradicated. PGE2 generation was significantly increased in children with H pylori gastritis (1022 (811) ng/g v 641 (473) ng/g in controls, p < 0.01). One month after treatment PGE2 generation significantly decreased in children without infection (880 (534), p < 0.01), but was still high where infection persisted. A significant inverse correlation was found between PGE2 generation and mucus gel layer thickness (p < 0.05). These data suggest that H pylori damages the mucus gel layer, and that the gastric mucosa increases generation of PGE2 in response to back diffusion of acid and pepsin.

Mechanism of muscle protein degradation in cancer cachexia.

Depletion of skeletal muscle mass in animals bearing an experimental model of cachexia, the MAC16 adenocarcinoma, occurs by a reduction in protein synthesis accompanied by a large increase in protein degradation. Serum from mice bearing the MAC16 tumour produced an increased protein degradation in isolated gastrocnemius muscle, as measured by tyrosine release, with a maximal effect occurring with serum from animals with a weight loss of between 11 and 20%. The response was specific to the cachectic state, since serum from mice bearing the MAC13 adenocarcinoma, which does not produce weight loss, did not increase tyrosine release from gastrocnemius muscle above that observed with serum from non tumour-bearing animals. The circulatory proteolysis-inducing factor was stable to heating at 60 degrees C for 5 min and was not inhibited by phenylmethylsulfonyl fluoride, suggesting that it was not a serine protease. The level of prostaglandin E2 (PGE2) in gastrocnemius muscle was significantly elevated after incubation with serum from cachectic mice bearing the MAC16 tumour. Both indomethacin and the polyunsaturated fatty acid eicosapentaenoic acid (EPA) inhibited the rise in muscle PGE2 content in response to serum from cachectic mice and also inhibited muscle protein degradation. These results suggest that muscle protein degradation in cancer cachexia is associated with a rise in PGE2 content.

Virus-induced Changes in Airway Responsiveness, Morphology, and Histamine Levels in Guinea Pigs

A significant increase in airway responsiveness to histamine was observed in vitro and in vivo 4 days after intratracheal inoculation of parainfluenza Type 3 (PI-3) virus to guinea pigs. Light microscopic and ultrastructural examination of the central airways of animals inoculated with virus revealed stratification of the epithelial lining, with pronounced loss of cilia and granule-depleted goblet cells. In the peripheral airways, typical lesions of patchy alveolitis and bronchiolitis were found. The alveolar epithelium often lacked Type I alveolar cells and was lined merely by cells containing osmiophilic lamellar bodies typical of Type II alveolar cells. PI-3 virus inoculation resulted in a reduction in the number of airway mucosal mast cells, particularly in the bronchioles, and in a change of density of the granules of mast cells. Further, a significant rise (100%) in histamine concentration was observed in lung lavage fluid after virus inoculation. The prostaglandin E2 (PGE2) content in the lavage fluid was not changed. After stimulation with histamine, the tracheae of animals inoculated with control solution or PI-3 virus produced similar amounts of PGE2. These data indicate that PI-3 virus activates airway mast cells and increases the histamine content in the respiratory tract. Neither the virus-induced lung damage nor the increased levels of histamine in the airways influence the release of the epithelially derived relaxing factor PGE2. It is suggested that mast cell-derived products, in particular histamine, are involved in virus-induced airway hyperresponsiveness.

Glycogenolytic and haemodynamic responses to bovine serum albumin in isolated perfused livers from sensitized rats

Infusion of BSA into isolated perfused livers of rats sensitized by intraperitoneal injection of BSA led to rapid increases in portal-vein pressure, glucose output and the lactate/pyruvate ratio in the effluent perfusate, with concomitant decreases in oxygen consumption and lactate+pyruvate efflux. The responses were attenuated at low (approximately 7 microM) perfusate Ca2+, but were restored on re-addition of normal Ca2+ concentration. Co-infusion of the cyclo-oxygenase inhibitor ibuprofen (50 microM) or of the platelet-activating factor receptor antagonist WEB 2170 (1.2 microM) inhibited haemodynamic responses to BSA (5 micrograms/ml) by 48% and 59% respectively. Responses to BSA were also attenuated by prior infusion of the beta-adrenergic agonist isoprenaline. Glycogen phosphorylase a activity was increased by 26% in livers freeze-clamped 2 min after onset of BSA infusion; tissue prostaglandin E2 content was increased at 2 min, but returned to control levels at 5 min. Homologous desensitization of hepatic responses to BSA was observed, but heterologous desensitization with heat-aggregated IgG did not take place. It is concluded that livers from rats sensitized to antigen respond directly to subsequent antigen administration by vasoconstriction and glycogenolysis, and that autacoid mediators are involved in these responses.

Role of gastric mucosal prostaglandin E2 in the inhibitory action of secretin and somatostatin on gastric acid secretion in the rat.

We investigated the effect of indomethacin on secretin- and somatostatin-induced inhibition of gastric acid secretion stimulated by intravenous infusion of pentagastrin (0.3 microgram/kg.h) in anesthetized rats. Intravenous administration of a prostaglandin synthesis inhibitor, indomethacin (2 mg/kg + 1 mg/kg.h), completely abolished the inhibition of gastric acid secretion induced by intravenous infusion of secretion (0.05 CU/kg.h). The inhibitory effect of intravenous infusion of somatostatin (Sandostatin; 0.2 micrograms/kg.h). The inhibitory the gastric acid was not significantly changed by indomethacin. Secretin significantly increased the gastric mucosal content of prostaglandin E2, and the increase was completely blocked by indomethacin. Somatostatin, however, had no significant effect on gastric mucosal prostaglandin E2. The results suggest that endogenous prostaglandin is involved in the mechanism of inhibition of gastric acid secretion by secretin, but not by somatostatin.

Anti-ulcer activity and mode of action of the polysaccharide fraction from the leaves of Panax ginseng.

The effects of a weakly acidic polysaccharide fraction, GL-4, from the leaves of Panax ginseng C. A. Meyer on various experimental gastric ulcer models in mice and rats have been studied. Oral administration of GL-4 at doses of 50 to 200 mg/kg inhibited the formation of the gastric lesions induced by necrotizing agents such as HCl/ethanol and ethanol in a dose-dependent manner. This protective effect was observed not only upon oral but also upon subcutaneous administration of GL-4 (50-100 mg/kg). GL-4 also inhibited the formation of gastric ulcers which were induced by water immersion stress, indomethacin, or pylorus-ligation. The contents of prostaglandin E2 in the gastric juice from rats were not influenced by oral administration of GL-4. The protective action of GL-4 against HCl/ethanol-induced gastric lesions was not abolished by pretreatment with indomethacin. When GL-4 (100 mg/kg, p.o.) was administered into pylorus-ligated rats, both gastric acidity and pepsin activity in the gastric juice decreased significantly.

Alterations in murine macrophage arachidonic acid metabolism following ingestion of nonviable Histoplasma capsulatum.

The effect of ingestion of heat-killed Histoplasma capsulatum yeast cells on the metabolism of arachidonic acid (20:4) to prostenoids and leukotrienes was examined in murine peritoneal macrophages (M phi s). H. capsulatum-containing M phi s exhibited a metabolite profile similar to that of zymosan-challenged phagocytes; however, there were differences with respect to the relative and total amounts of products produced. While proteose peptone-elicited M phi s exposed to H. capsulatum released quantitatively less prostaglandin E2 (PGE2) and leukotriene C4 than zymosan-treated M phi s, they metabolized a greater percentage of total product to prostenoids. In addition, whereas in vitro priming with gamma interferon increased both the PGE2 and leukotriene C4 contents of zymosan-stimulated M phi supernatants, similarly primed M phi s challenged with H. capsulatum selectively increased only PGE2 production. The immunosuppressive effect of a relative excess of prostenoids in H. capsulatum-containing M phi s may contribute to the overall disturbance in cell-mediated immunity characteristic of disseminated histoplasmosis.

Eicosanoids Content in Small Intestinal Mucosa of Children with Celiac Disease

SummaryCeliac disease (CD) is characterized by diarrhea, growth retardation, and weight loss in genetically susceptible subjects on a gluten‐containing diet. The exact pathogenesis of CD is still obscure, but it is considered to be immunologically mediated. We have previously shown elevated prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) content in small intestinal mucosa obtained from active celiac children. In the present study, we found significantly elevated PGE2, leukotriene B4 (LTB4), and leukotrienes C4,D4, and E4 (LTC4D4E4) content in small bowel mucosa from children suffering from CD on a gluten‐containing diet in comparison to control subjects. PGE2 was 25,278 ± 7,761 vs. 4,478 ± 426 pg/mg of protein (mean ± SEM), respectively. LTB4 was 8,807 ± 3,706 vs. 403 ± 63 pg/mg of protein (mean ± SEM), respectively. LTC4D4E4 was 15,369 ± 4,085 vs. 2,998 ± 279 pg/mg of protein (mean ± SEM), respectively. We conclude that the elevated content of arachidonic acid metabolic products via cyclooxygenase and lipoxygenase pathways may contribute to the diarrhea and may be involved in the pathogenesis of mucosal injury.