The role of prostaglandins E and F in acalculous gallbladder disease

Prostaglandins have been postulated to be involved in the formation of gallstones and the pain and inflammation of calculous gallbladder disease. This report evaluated prostaglandin E and F levels in patients with acalculous gallbladder disease. Control gallbladders were obtained from patients undergoing cholecystectomy during insertion of hepatic artery catheters for regional, hepatic chemotherapy. Patients without gallstones and with long-standing post-prandial biliary colic with abnormal cholecystokinin administration underwent cholecystectomy for chronic acalculous cholecystitis. A third group of patients underwent cholecystectomy for acute acalculous cholecystitis. Gallbladder mucosa and muscle were separated, and prostaglandin E and F concentrations in mucosal and muscle or mucosa were identified in gallbladders from patients with chronic acalculous cholecystitis compared to gallbladders from patients without biliary tract symptoms. In gallbladders from patients with acute acalculous cholecystitis a seven-fold increase in PGE production by muscle tissue and mucosal cells was found. The more histologically inflamed gallbladders had higher mucosal and muscle prostaglandin E concentrations than were found in less inflamed gallbladders. Prostaglandin F levels were not significantly changed or were decreased, resulting in a significant increase in the ratio of PGE/PGF in acutely diseased gallbladders when compared to normal gallbladders. Prostaglandin E may be a manipulatable intermediary in the sequence of events that results in the development of acute acalculous cholecystitis.     

Prostaglandin E2 and prostaglandin F2 alpha biosynthesis in human gastric mucosa: effect of chronic alcohol misuse.

BACKGROUND AND AIMS: The results of experimental studies support the hypothesis that decreased prostaglandin production might play a part in the gastric mucosal injury induced by alcohol. In this study, it was investigated whether alcohol misuse impairs the synthesis of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) in gastric mucosa. PATIENTS: Fifty six alcoholic patients and 66 subjects without alcohol misuse were included in the study. METHODS: Mucosal biopsy specimens were obtained from the antrum and body of the stomach. Maximal synthesis rates of PGE2 and PGF2 alpha were determined in the microsomal fraction of the biopsy specimens. RESULTS: The rates of synthesis of both prostaglandins in biopsy specimens from the antrum were not significantly different from those obtained in the body. Synthesis of both prostaglandins was significantly reduced in alcoholic patients who abstained less than five days compared with the non-alcoholic group with normal mucosa (PGE2-40%, PGF2 alpha-42% respectively). In non-alcoholic patients with severe gastritis PGE2 synthesis was increased (+30%, p < 0.05) and PGF2 alpha synthesis was decreased (-42.5%, p < 0.025). In alcoholic patients with severe gastritis PGE2 synthesis was depressed by almost 60% (p < 0.001) compared with the non-alcoholic group with severe gastritis. Neither colonisation of Helicobacter pylori nor smoking had a significant influence on the prostaglandin synthesis. CONCLUSIONS: Chronic alcohol misuse is associated with significantly reduced capacity for prostaglandin synthesis in gastric mucosa and this alcohol induced decrease in prostaglandin synthesis is modulated by the presence and degree of gastritis.     

A significant increase in the in-vitro production of prostaglandin E by ovine cervical tissue at delivery [proceedings]

A study of prostaglandin production in vitro by cervical tissue was conducted using a continuous superfusion technique. Prostaglandin F (PGF) and prostaglandin E (PGE) production rates have been obtained from cervical tissue of late-pregnant animals and animals killed after delivery. Highest PGE production rates were found at delivery rather than in tissue from late-pregnant animals; however, there was no production rate difference for PGF. At delivery, PGE production by the cervix is comparable with the production by fetal cotylelon which was known previously to be the major uterine source of PGE. Whether prostaglandins are associated in cervical ripening during labor in unknown, but if prostaglandins are involved then the prostaglandin source may be the cervix.     

Regulation of eicosanoid production in rabbit colon by interleukin-1

Prostaglandins and thromboxanes are increased in human and experimental colitis, but the factors that regulate this enhanced production are unclear. The present studies evaluate the effects of the monokines, interleukin-1 alpha and beta on eicosanoid production in rabbit colon. In tissue incubations the peak dose response of eicosanoid release to human recombinant interleukin-1 is 50 ng/ml. Interleukin-1 alpha increases prostaglandin E2 (PGE2) by 4.5 +/- 1.9 ng/g tissue, 6-keto PGF1 alpha by 6.2 +/- 2.7 ng/g, and thromboxane B2 by 2.1 +/- 0.3 ng/g compared to placebo. In isolated rabbit colons perfused with Krebs' solution, 10-h infusion of interleukin-1 alpha (50 ng/ml) progressively increases production of PGE2, 6-keto PGF1 alpha, and thromboxane B2. Bolus injections of bradykinin increase production of PGE2, but not 6-keto PGF1 alpha and thromboxane B2, and these responses are markedly augmented by interleukin-1 alpha: at 10 h bradykinin-stimulated PGE2 production is 518 +/- 104 vs. 95 +/- 18 ng/5 min (p less than 0.005), 6-keto PGF1 alpha is 172 +/- 88 vs. 8 +/- 2 ng/5 min (p less than 0.02), and thromboxane B2 is 60 +/- 14 vs. 13 +/- 4 ng/5 min (p less than 0.02) for interleukin-treated colons vs. placebo-treated colons, respectively. The response is greater with interleukin-1 alpha than interleukin-1 beta. This study demonstrates that interleukin-1 stimulates prostaglandin and thromboxane production in normal colon tissue. These data are consistent with the concept that interleukin-1 production by inflammatory cells may augment prostaglandin and thromboxane production in colitis.     

Relationship between the production of prostaglandins and progesterone by luteinizing human granulosa cells.

Luteinizing granulosa cells synthesize high concentrations of progesterone, prostaglandin (PG) E(2) and PGF(2 alpha). The objective of this study was to explore the relationship between prostaglandin and progesterone output from human granulosa cells as they undergo functional luteinization in culture. Granulosa cells were partially purified from ovarian follicular aspirates and cultured at a density of 10(5) cells/ml in serum-supplemented DMEM:Ham's F(12) medium for 0, 1 or 2 days. Cells were then switched to serum-free medium for 24 h before measuring hormone concentrations in this spent medium by specific radioimmunoassays. Over the first 3 days in culture, PGF(2 alpha) and PGE(2) production declined progressively by up to 82+/-3% coincident with a 55+/-11% increase in progesterone output. In subsequent experiments, cells were treated for 24 h on the second day of culture with either 0.01 to 10 microM meclofenamic acid or with 10 microM and 100 microM aminoglutethimide. Meclofenamic acid inhibited synthesis of PGF(2 alpha) and PGE(2) by up to 70+/-9% and 64+/-7% respectively without affecting progesterone output. Likewise, 100 microM aminoglutethimide inhibited progesterone production by 62+/-6% without affecting concentrations of either PGF(2 alpha) or PGE(2). We have concluded that the progressive decline in prostaglandin production and the rise in progesterone output from luteinizing human granulosa cells occur independently of each other.     

Skeletal muscle PGF(2)(alpha) and PGE(2) in response to eccentric resistance exercise: influence of ibuprofen acetaminophen

PGs have been shown to modulate skeletal muscle protein metabolism as well as inflammation and pain. In nonskeletal muscle tissues, the over the counter analgesic drugs ibuprofen and acetaminophen function through suppression of PG synthesis. We previously reported that ibuprofen and acetaminophen inhibit the normal increase in skeletal muscle protein synthesis after high intensity eccentric resistance exercise. The current study examined skeletal muscle PG levels in the same subjects to further investigate the mechanisms of action of these drugs in exercised skeletal muscle. Twenty-four males (25 +/- 3 yr) were assigned to 3 groups that received the maximal over the counter dose of ibuprofen (1200 mg/d), acetaminophen (4000 mg/d), or a placebo after 10-14 sets of 10 eccentric repetitions at 120% of concentric 1 repetition maximum using the knee extensors. Preexercise and 24 h postexercise biopsies of the vastus lateralis revealed that the exercise-induced change in PGF(2alpha) in the placebo group (77%) was significantly different (P < 0.05) from those in the ibuprofen (-1%) and acetaminophen (-14%) groups. However, the exercise-induced change in PGE(2) in the placebo group (64%) was only significantly different (P < 0.05) from that in the acetaminophen group (-16%). The exercise-induced changes in PGF(2alpha) and PGE(2) were not different between the ibuprofen and acetaminophen groups. These results suggest that ibuprofen and acetaminophen have a comparable effect on suppressing the normal increase in PGF(2alpha) in human skeletal muscle after eccentric resistance exercise, which may profoundly influence the anabolic response of muscle to this form of exercise.     

Effect of bradykinin on feline gallbladder water transport and prostanoid formation

Continuing evaluation of the pathophysiology of gallbladder disease has demonstrated significant relationships between gallbladder mucosal fluid transport, gallbladder inflammation, and prostanoid formation. Inflamed gallbladder mucosa secretes, rather than absorbs, fluid, a process associated with prostaglandin formation. Bradykinin has been previously implicated in the pathogenesis of cholecystitis and, in the intestine, bradykinin stimulates mucosal fluid secretion by a prostaglandin-mediated mechanism. Bradykinin was infused into the gallbladder lumen and administered intraarterially into the hepatic artery of perfused cat gallbladders. Both methods of bradykinin administration reversed the mucosal absorption present during control experiments as measured by concentration changes in a nonabsorbable marker. Perfusate and gallbladder tissue prostaglandin E concentrations were significantly increased by bradykinin when compared to control values. Concentrations of 6-ketoPGF ₁ in perfusate solutions and in gallbladder tissue were significantly increased, suggesting bradykinin increased prostacyclin formation.Bradykinin administration significantly increased inflammation, as evaluated by a histologic scoring system. Indomethacin was administered intravenously along with luminalperfusion of the gallbladder with bradykinin. Indomethacin significantly decreasedgallbladder fluid secretion and prostanoid formation, but not histologic inflammation,when compared to values produced by bradykinin alone. An increase in systemic vascularand bile kinin concentrations produces gallbladder mucosal water secretion, a processwhich may be mediated by prostanoids. Histologic inflammation produced by bradykininwas not prevented by indomethacin.Supported by USPHS grant DK 27695-06.     

Effect of prostaglandins(PGs) on progesterone production by human cultured luteal cells and their ability of PGs production

The present study was designed to investigate whether or not prostaglandins(PGs) were produced by human luteal cells(HLC) and their effects on the luteal cells by monolayer culture. The following results were obtained. Cultured HLC secreted progesterone(P), prostaglandin F(PGF) and prostaglandin E(PGE) into a medium at concentrations of 276.6 +/- 38.6, 1.95 +/- 0.36, 2.44 +/- 0.45 ng/ml/1 X 10(5) cells/day (mean +/- SE), respectively. Cultured HLC was able to convert 14C-arachidonic acid to 14C-PGF2 alpha, 14C-PGE2. These two results indicated that HLC had the ability to produce PGF and PGE. Cultures were carried out in the presence of indomethacin (Ind), PGF2 alpha and PGE2 alone as well as in a combination. P production by HLC was reduced in the presence of Ind. P production in the presence of Ind+PGE2 was more than that in the presence of Ind alone. There was no significant difference in P production between the presence of Ind and Ind+PGF2 alpha. It was concluded that HLC had the ability to produce PGs and that PGE2 significantly stimulated P production in as low concentrations as HLC could produce physiologically while PGF2 alpha did not.     

Neurogenic Inflammation in Cholecystitis

Neurogenic inflammation implies stimulation ofnerves with resultant inflammation in tissue surroundingthe nerve terminals. We hypothesized that neurogenicinflammation has a role in cholecystitis. Capsaicin (stimulant of afferent, nociceptive neurons),6-hydroxydopamine (stimulates release of peptides fromsympathetic nerve terminals), bradykinin,lipopolysaccharide, and saline were instilled intoguinea pig gallbladders for 24 hr (N = 5 in each group).In parallel, test agents were instilled with 1%lidocaine. Water transport across gallbladder mucosa,myeloperoxidase and interleukin-1 release fromgallbladder tissue, and prostaglandin E in luminal fluidwere measured. Capsaicin caused water secretion andsignificant 2 release of myeloperoxidase, interleukin-1,and prostaglandin-E₂, effects that wereblocked by lidocaine. 6-Hydroxydopamine did not affectwater transport or prostaglandin E₂, but didcause myeloperoxidase and interleukin-1 release.Bradykinin- and lipopolysaccharideinduced inflammationwere partially inhibited by lidocaine. Taken together, theseresults suggest that neurogenic inflammation has a rolein the pathophysiology of cholecystitis.     

Prostanoids and leukotrienes in experimental feline cholecystitis

Current information suggests that arachidonic acid metabolites are involved in the development of cholecystitis. The purpose of this study was to evaluate eicosanoid formation during the development of experimental cholecystitis in cats. Lysophosphatidylcholine is found in the gallbladders of patients with cholecystitis and is known to be a cytolytic, membrane-damaging substance. Anesthetized cats underwent gallbladder perfusion with and without 1.5 mmol/L lysophosphatidylcholine. Additional experiments were performed when calcium ionophore were added to the perfusates and experiments were performed when cats were treated with indomethacin and underwent perfusion with lysophosphatidylcholine. Changes in the gallbladder were determined by evaluating mucosal water transport as measured by determining the changes in concentration in a nonabsorbable marker, by protein secretion and by beta-glucuronidase accumulation in gallbladder tissue as an index of inflammation. Eicosanoid formation was evaluated by measuring perfusate concentrations and gallbladder homogenate concentrations by radioimmunoassay of prostaglandin E, 6 keto prostaglandin F1 alpha, leukotriene B4 and leukotriene C4. Lysophosphatidylcholine perfusion reversed the control patterns of absorption and produced water exsorption, produced an efflux of protein into the perfusate and increased beta-glucuronidase activity. These changes were accompanied by increased production of prostaglandin E and 6 keto prostaglandin F1 alpha in gallbladder perfusate and homogenate. The concentration of leukotriene C4 in gallbladder effusate was increased by lysophosphatidylcholine when compared with control values. Indomethacin inhibited the protein efflux, decreased beta-glucuronidase levels and decreased prostaglandin E and 6 keto prostaglandin F1 alpha formation when compared with values produced by lysophosphatidylcholine alone. Cyclooxygenase inhibition did not alter the secretion of water into the gallbladder or perfusate leukotriene C4 concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostaglandin production by intra-uterine tissues from periparturient sheep: use of a superfusion technique

A technique for the continuous superfusion of small tissue samples in vitro has been applied to the study of prostaglandin production by ovine intra-uterine tissues. Basal and oxytocin-stimulated production of prostaglandins was studied at 120-125 days of pregnancy and after dexamethasone-induced delivery. In general, the relative rate of prostaglandin production by tissues was: foetal cotyledon = maternal cotyledon greater than myometrium and in quantitative order the prostaglandins produced were prostaglandin E (PGE) greater than prostaglandin F (PGF) = 13,14-dihydro-15-oxo-prostaglandin F (PGFM). Considerable variations was found between the rates of prostaglandin production in individual sheep. Oxytocin had no effect on the production of prostaglandins by tissues obtained before labour but myometrium and maternal cotyledon obtained at delivery exhibited a significant increase in production of PGE and PGF (though not PGFM) in response to oxytocin. Administration of arachidonic acid increased the production of PGE and PGF by the foetal cotyledon.     

Effect of calcium channel blocker diltiazem on cytoprotection and prostaglandin and sulfhydryl production by rat gastric epithelial cells

The calcium channel blockers verapamil and diltiazem protect gastric mucosa against exogenous injury in vivo. Whether this protection is mediated by systemic factors, such as blood flow, is due to inhibition of gastric acid secretion, or is associated with stimulation of endogenous protective agents such as prostaglandins or sulfhydryls, is unknown. We have evaluated whether diltiazem protects rat gastric epithelial cells in tissue culture (a model which excludes the influence of systemic factors) against damage induced by sodium taurocholate, indomethacin, or ethanol. Further we have assessed the effect of diltiazem on prostaglandin and sulfhydryl production. 51Chromium release assay and phase contrast microscopy have been used to assess cell damage. Sodium taurocholate, indomethacin, and ethanol-damaged cultured cells in a dose-dependent manner. Pretreatment with diltiazem did not prevent the drug-induced damage. Diltiazem did not increase PGE2 and 6-keto PGF1a production by cultured cells nor did it affect the cellular level of endogenous sulfhydryls. In conclusion, the calcium channel blocker diltiazem is not directly protective to rat gastric mucosal cells in vitro. Diltiazem does not stimulate prostaglandin production by gastric cells nor does it increase the cellular level of protective sulfhydryls.     

Inter-relationships between inflammatory mediators released from colonic mucosa in ulcerative colitis and their effects on colonic secretion.

Metabolites of arachidonic acid have been implicated in the pathophysiology of ulcerative colitis-they can stimulate intestinal secretion, increase mucosal blood flow, and influence smooth muscle activity. The influence on the mucosal transport function of culture medium in which colonic mucosal biopsy specimens had been incubated was investigated using rat stripped distal colonic mucosa in vitro as the assay system. Colonic tissue from patients with colitis and from control subjects was cultured. Medium from inflamed tissue contained more prostaglandin E2 (PGE2) and leukotriene D4 (LTD4) and evoked a greater electrical (secretory) response in rat colonic mucosa than control tissue medium. In inflamed tissue, cyclo-oxygenase inhibition (indomethacin) attenuated PGE2 but increased LTD4 production; conversely lipoxygenase inhibition (ICI 207968) inhibited LTD4 production but enhanced PGE2 output. Each inhibitor alone enhanced the electrical response in the rat colon. Inhibition of both enzymes (indomethacin plus ICI 207968) caused a fall in both PGE2 (82%) and LTD4 (89%) production and in the electrical response (57%). Inflamed tissue treated with a phospholipase A2 inhibitor (mepacrine) produced less PGE2, LTD4, and electrical responses when compared with inflamed tissue, either untreated (91%, 92%, and 79% respectively) or treated with cyclo-oxygenase and lipoxygenase inhibition. Incubation with bradykinin stimulated eicosanoid release and electrical response, while a bradykinin antagonist caused a modest inhibition. Analysis of these observations suggests that a combination of arachidonic acid derivatives accounts for about half the secretory response. Other products of phospholipase A2 activity are probably responsible for much of the remainder, leaving up to 20% the result of types of mediator not determined in this study.     

Determination of prostaglandin synthetase activity in rectal biopsy material and its significance in colonic disease.

A method is described for determining prostaglandin synthetase activity in milligram amounts of tissue. The procedure is based on the conversion of 14C-arachidonic acid to prostaglandin E2 and F2alpha-like substances. High levels of prostaglandin synthetase activity occurred in the inflamed mucosa of patients with ulcerative colitis and fell during successful drug therapy, but it is not yet known whether the cause of the inflammation first involves increased PG synthetase activity, or whether inflammation caused increase of PG synthetase.     

Specific change in the direction of prostaglandin synthesis by intra-uterine tissues of the rhesus monkey (Macaca mulatta) during late pregnancy.

The rates of production of prostaglandin E (PGE), prostaglandin F (PGF) and 13, 14-dihydro-15-oxo-prostaglandin F (PGFM) by intra-uterine tissues from pregnant monkeys in vitro have been determined using a method of tissue superfusion. The amnion, chorion, placenta, decidua basalis, decidua parietalis and myometrium were obtained at Caesarean section during late pregnancy. Production of PGE by all tissues was significantly lower at term than during late pregnancy, whereas production of PGF by the amnion, chorion, decidua parietalis and myometrium was significantly greater. All tissues produced significantly more PGE than PGF and also, excepting the decidua basalis and decidua parietalis, more PGFM than PGF. Close to parturition the amnion was quantitatively (per unit weight) the major source of prostaglandins. It is suggested that a specific change in the direction of prostaglandin synthesis by intra-uterine tissues occurs near parturition in the rhesus monkey.     

Inhibitory action of follicular fluid on progesterone and prostaglandin synthesis in bovine follicles.

The present studies examined the inhibitory effect of mid-cycle and preovulatory bovine follicular fluid (bFF) on the secretion of progesterone and prostaglandin F 2 alpha (PGF 2 alpha) by bovine theca and granulosa cells cultured in tissue culture Medium 199. The inhibitory effect of bFF on the secretion of PGF 2 alpha by incubated and cultured hemipituitary glands of male rats was also studied. Addition of 5, 10 or 20% charcoal-extracted, mid-cycle bFF to the culture medium caused a twofold decrease in the accumulation of both progesterone and PGF 2 alpha by the cultured granulosa cells (P less than 0.01). In contrast, when preovulatory bFF was used, there was no inhibitory effect on secretion of progesterone and PGF 2 alpha. The addition of 10% mid-cycle bFF to the culture medium caused a two- to fourfold decrease in the accumulation of both PGF 2 alpha and progesterone by the cultured theca (p less than 0.008). However, in the presence of 1 microgram LH/ml, the inhibitory effect of mid-cycle bFF on progesterone and PGF 2 alpha secretion was abolished. The secretion of PGF 2 alpha was significantly (p less than 0.03) decreased in male rat hemipituitary glands after 5 h of incubation or 18 h of culture. These findings suggest that bFF from mid-cycle follicles inhibits prostaglandin synthetase as well as luteinization. The inhibition disappeared with bFF from preovulatory follicles.     

Association between gallstone-evoked pain, inflammation and proliferation of nerves in the gallbladder: a possible explanation for clinical differences

OBJECTIVE: To investigate whether enhanced neuroproliferation could be involved in the pathogenesis of gallstone pain. MATERIAL AND METHODS: Gallbladders from 117 patients with gallstones and 43 controls were examined. The gallbladder samples were immunostained against the pan-neuronal marker PGP 9.5 and the number of nerves and nerve area per tissue area estimated. RESULTS: More nerves and an increased nerve area per tissue area were found in uncomplicated symptomatic gallstone disease. In comparison, acute cholecystitis displayed a significantly (p=0.01) decreased number of nerves and nerve area per tissue area. In both categories, the gallbladder neck contained more nerves (p=0.06 and 0.04, respectively) and an increased nerve area per tissue area (p=0.034 and 0.008, respectively) than the body. CONCLUSIONS: Uncomplicated disease showed enhanced neuroproliferation, significantly more in the gallbladder neck, whereas significantly fewer nerves were observed in acute cholecystitis. Nerve growth alteration may play a role in uncomplicated gallstone pain but the pathology may be different in inflammation.     

Effects of prostaglandin F2 alpha on bone formation and resorption in cultured neonatal mouse calvariae: role of prostaglandin E2 production

Although most studies show that prostaglandin E2 (PGE2) is the most potent and effective of the prostanoids in bone, recent data in cell culture suggest that PGF2 alpha may have unique effects, particularly on cell replication. The present study was undertaken to compare the effects of PGF2 alpha and PGE2 in cultured neonatal mouse parietal bones by simultaneous measurement of bone resorption as release of previously incorporated 45Ca, bone formation as incorporation of [3H]proline into collagenase-digestible (CDP) and noncollagen protein, and DNA synthesis as incorporation of [3H]thymidine. PGF2 alpha was less effective than PGE2 as a stimulator of bone resorption, and its effects were partially inhibited by indomethacin and markedly inhibited by glucocorticoids. In contrast, the resorptive response to PGE2 was unaffected by indomethacin and only partially inhibited by cortisol. PGF2 alpha had little effect on bone formation, in contrast to the biphasic effect of PGE2, which inhibited labeling of CDP in the absence of cortisol and stimulated CDP labeling in the presence of cortisol. PGF2 alpha increased thymidine incorporation into DNA, but the effect was smaller than that of PGE2 and was inhibited by indomethacin. These observations suggested that PGF2 alpha might act in part by stimulating PGE2 production. By RIA, PGE2 concentrations were increased in the medium of bones treated with PGF2 alpha, and this increase was blocked by indomethacin. By HPLC, bones prelabeled with [3H]arachidonic acid showed an increase in labeled PGE2 release, and RIA showed an increase in PGE2 after PGF2 alpha treatment. These results indicate that PGF2 alpha is a relatively weak agonist in bone compared to PGE2 and that some of the effects of PGF2 alpha on bone resorption, formation, and cell replication may be mediated by an increase in endogenous PGE2 production.     

The effects of morphine and enkephaline on gallbladder function in experimental cholecystitis. Inhibition of inflammatory gallbladder secretion

Administration of morphine or its derivatives is the traditional way to treat biliary pain. Despite the common use of morphine and its analogues in patients with cholecystitis and biliary pain, their effects on the function of the inflamed gallbladder are not known. In the present study it is demonstrated that morphine usually contracts the normal gallbladder but does not influence the fluid transport across the mucosa. In experimental cholecystitis morphine and enkephaline do not further contract the gallbladder but, by specific opioid receptors, reduce the inflammatory fluid secretion by the mucosa. In case of obstruction of the gallbladder, fluid secretion by the mucosa will distend its wall and induce biliary pain. It is suggested that the pain-relieving effect of morphine in cholecystitis and attacks of biliary pain is mediated not only by a central analgesic effect but also by an influence on the function of the inflamed gallbladder.     

Interrelationship between stimulation of prostaglandin e and hyaluronate production by poly (i).Poly (c) and interferon in synovial fibroblast culture

The interferon-inducer, polyinosinate. Polycyctidylate [Poly (I). Poly (C)] stimulated both prostaglandin E (PGE) and hyaluronic acid (HA) production by human cultured synovial fibroblasts. Increased accumulation of PGE in the medium was noted within 3 hours of culture, while accumulation of HA was observed only after a 24 hour lag period. The stimulation of PGE and HA production by Poly (I) Poly (C) was prevented by aspirin and indomethacin. Human interferon was also effective in stimulating both PGE and HA production. Concomitant addition of cortisol to culture medium abrogated the stimulatory effect of Poly (I). Poly (C) and interferon on both PGE and HA production. Exogenous PGE₂, however, overcame the inhibitory effect of cortisol on HA production. The present results suggest that the stimulatory effect of both interferon and Poly (I). Poly (C) on HA production may be mediated by PGE. Prostaglandins may thus play a role in the inflammatory process associated with viral infections.