Biomedical subjects

J Svanvik

Publications and source records attributed to J Svanvik.

At least 91 records · Page 5Linked to original sources

PubMed1987

Direct measurements of enterohepatic circulation of bile acids in the cat. Influence of contraceptive steroids and oophorectomy.

Contraceptive steroids that increase the risk of gallstones reduce the bile acid pool size and increase the cholesterol saturation in bile. To analyze mechanisms behind these effects, bile acid enterohepatic circulation was studied with direct methods in cats treated with peroral contraceptive steroids for 3 months, cats oophorectomized 1-2 months before study, and female control animals. Both administration of contraceptive steroids and oophorectomy reduced the bile acid pool size and bile acid synthesis rate. Contraceptive steroids increased water secretion by the liver at low bile acid secretion rates, reduced bile acid accumulation in the gallbladder, and increased the recycling rate of the bile acid pool. Oophorectomy did not significantly change the relation between bile acid and water secretion by the liver. The reduced bile acid pool size in animals receiving contraceptive steroids can be explained by an increased recycling rate induced by an enhanced water secretion by the liver. The possibility of a direct effect on the hepatic synthesis of bile acids by both administration of contraceptive steroids and oophorectomy cannot be excluded.

Animals↗

PubMed1987

Cholecystokinin secretion in pregnancy.

The gallbladder volume is increased in pregnancy, and its contraction during a meal is impaired. This is of importance for the increased risk of gallstones in pregnancy, since it may cause retention of cholesterol crystals in the gallbladder lumen. Cholecystokinin (CCK) is responsible for the food-induced gallbladder contraction. We have consequently measured the plasma concentrations of CCK in the fasting and the stimulated state in pregnant women and in age-matched non-pregnant controls. In a subset of pregnant women and controls the gallbladder volume was measured with ultrasound. The results show that whereas basal CCK concentrations were normal, the response to an oral preparation that contracts the gallbladder was increased in pregnancy. Moreover, the secretion of CCK correlated well with gallbladder emptying. We conclude that the behaviour of the gallbladder in pregnancy is not due to impaired secretion of CCK.

Adult↗

PubMed1987

The secretion of cholecystokinin in the gallstone patient before and after removal of a functioning gallbladder.

Cholecystectomy will not always relieve the abdominal symptoms of the patient with gallstones. The functional effects of gallbladder removal in a patient with a patent cystic duct are not known in detail. Studies of the function of the gallbladder and pancreas have suggested feedback mechanisms for the release of cholecystokinin (CCK). A disturbed regulation of CCK release after cholecystectomy might induce pancreaticobiliary and gastrointestinal dysfunctions. In our study the concentrations of CCK in plasma were measured in 17 patients with gallstones. The measurements were taken with gallbladders opacified at cholecystography and with patent cystic ducts at the operation, in the fasting state, and during stimulation before and 17 weeks after the cholecystectomy. The CCK assay used measures sulfated CCK-8, CCK-22, and CCK-33 with equimolar potency but neither nonsulfated CCK nor any gastrins. Emtobil (containing peanut oil and sorbitol) was used for peroral stimulation of the CCK release. The basal concentration of CCK was 4 pmol/L and rose five times during a "test meal." No significant differences were seen in fasting or stimulated concentrations of plasma CCK before and after the cholecystectomy. Thus cholecystectomy in gallstone patients with functioning gallbladders does not seem to influence the regulation of CCK release.

Adult↗

PubMed1986

Loperamide inhibits gallbladder inflammatory fluid secretion in experimental cholecystitis.

Fluid secretion by the gallbladder mucosa is suggested to have a key pathophysiological role in acute cholecystitis, since it causes distension of the obstructed gallbladder. The present study investigates the actions of loperamide on the gallbladder function in experimental cholecystitis. Gallbladder fluid transport and motility were studied in vivo with a continuous perfusion technique. A net fluid secretion by the gallbladder mucosa was seen in cats in which cholecystitis was induced whereas there was a net fluid absorption from the gallbladder lumen in the control animals. The net fluid secretion in experimental cholecystitis was inhibited by loperamide (1 mg/kg), an effect that was blocked by naloxone (1 mg/kg), suggesting an involvement of specific opiate receptors. Loperamide (1 mg/kg) relaxed the normal gallbladder but had no significant effects on its fluid absorption. Since loperamide reduces mucosal fluid secretion in experimental cholecystitis without contracting the gallbladder wall, it is suggested that this peripherally acting opiate agonist could be useful in the treatment of patients with acute cholecystitis.

Animals↗

PubMed1986

Reflex regulation of flow resistance in the feline sphincter of Oddi by hydrostatic pressure in the biliary tract.

Despite wide variations in bile secretion and biliary tract capacitance, the pressure in the bile ducts is fairly constant. Recent studies have demonstrated that both inhibitory and excitatory nerves regulate the activity of the sphincter of Oddi. In the present study, it was consistently found that the resistance by the choledochoduodenal junction to a constant flow, within the physiologic range of hepatic bile output, is reduced when the hydrostatic pressure in the gallbladder and bile ducts is increased from 0 to 10, 0 to 15, and 0 to 20 cmH2O. This response was eliminated by tetrodotoxin or infiltration of the junction between the common bile duct and the cystic duct by mepivacaine, a local anesthetic. The results suggest a homeostatic mechanism during the interprandial periods, when the activity of the sphincter of Oddi is regulated by the distending pressure in the biliary tract. This reflex regulation is mediated by modulation of the activity of inhibitory nerves running along the common bile duct.

Ampulla of Vater↗

PubMed1986

Transport of fluid and biliary lipids in the canine gallbladder in experimental cholecystitis.

In acute cholecystitis the cystic duct is usually obstructed by a gallstone and the gallbladder is often tensely distended with clear fluid. Because these findings suggest that fluid absorption in the gallbladder may be reversed in cholecystitis, we examined the effect of inflammation on the gallbladder mucosal function in dogs. In 20 dogs cholecystitis was induced by ligating the cystic duct and allowing inflammation to develop from bile stasis and the presence of a chronic indwelling cannula in the gallbladder. Every morning an aliquot of normal hepatic bile was infused into the gallbladder through a cannula in the gallbladder fundus. After either 4 or 24 hr the gallbladder contents were aspirated, the volume was measured, and the concentrations of bile acids, cholesterol, phospholipids, and protein were determined. Changes in volume were checked using [14C]PEG as a nonabsorbable tracer. A net absorption of fluid, bile acids, cholesterol, and phospholipids occurred during the first 24 to 48 hr after ligation of the cystic duct. Thereafter, fluid, cholesterol, and protein were secreted into the lumen, but absorption of bile acids continued. The lithogenic index of bile placed in the inflamed gallbladder was always greater when the bile was removed 24 hr later. The rate of fluid secretion into the lumen of the inflamed gallbladder increased after a meal and decreased after indomethacin. These findings demonstrate that inflammation can stimulate the gallbladder mucosa to secrete fluid, a process that may be important in the pathophysiology of acute cholecystitis in man. Since inflammation also resulted in an increased cholesterol saturation of gallbladder bile, cholecystitis per se may contribute to the formation of cholesterol gallstones.

Animals↗

PubMed1986

Antibodies to Escherichia coli and anti-adhesive activity in paired serum, hepatic and gall bladder bile samples.

Human bile contains a mixture of immunoglobulins excreted through the liver and produced in the biliary tract. This study examines the specific antibody activity of the biliary immunoglobulins against Escherichia coli antigens. Paired samples of serum, hepatic bile, and gall bladder bile were obtained from 23 patients with gallstones and five patients with healthy gall bladders. Antibody activity against E. coli antigens was found in all the sera and most of the bile samples. The levels of IgA, IgM, IgG, and secretory component (SC)-combined antibodies were lower in bile than in serum. Selective treatment of IgA by the liver was suggested by the finding of a correlation between the serum and the bile IgA antibody activity. IgG antibodies were only found in inflamed gall bladders. The bile was shown to have antibacterial activity against E. coli, i.e. an ability to inhibit the attachment to epithelial cells, but the inhibitory activity was not restricted to the immunoglobulin fraction of the bile.

Adhesiveness↗

PubMed1986

The influence of morphine, loperamide and naloxone on gallbladder response to prostaglandin E2 in the anaesthetized cat.

In experimental cholecystitis there is a net fluid secretion into the gallbladder lumen and an increased release of prostaglandins. Indomethacin and opiates are known to inhibit this mucosal fluid secretion. Intraluminal or intra-arterial administration of prostaglandin E2 reduces basal gallbladder fluid absorption or induces a net fluid secretion to the lumen and also contracts the normal gallbladder. The use of a continuous perfusion technique in anaesthetized cats in this study shows that the effects of prostaglandin E2 on gallbladder function are blocked by intravenous morphine and loperamide. Naloxone does not affect the gallbladder responses to PGE2 administration. As a mechanism of action it is suggested that opiates inhibit secretory and contractile nerves that are activated by prostaglandins in the gallbladder wall. The findings suggest that the pain relieving effects of opiates in cholecystitis and biliary pain partly are due to blocking of the effects by prostaglandins on gallbladder function.

Animals↗

PubMed1986

Release of immunoreactive vasoactive intestinal peptide (VIP) from the gallbladder in response to vagal stimulation.

Immunoreactive VIP was detected in the gallbladder lumen and in the arterial blood and venous effluent from the gallbladder in fasting cats. During perfusion of the gallbladder in vivo there was a constant basal intraluminal secretion of VIP. The VIP concentration in the luminal effluent exceeded that in plasma supporting the notion that there was a release from the gallbladder tissue. The rate of secretion was significantly increased during efferent electrical stimulation of the peripheral cut end of the cervical vagal nerves, after blockade with atropine. A similar increase in concentration of VIP was seen in the venous effluent from the gallbladder. The results suggest a local release of VIP from intrinsic neurons within the gallbladder wall. This release is increased in response to activation of non-cholinergic fibres in the vagus nerves, suggesting a role for VIP in regulation of gallbladder functions.

Animals↗

PubMed1986

Influence of pregnancy, oophorectomy and contraceptive steroids on gall bladder concentrating function and hepatic bile flow in the cat.

Pregnancy and contraceptive steroids are associated with a raised incidence of cholesterol gall stone disease. In pregnancy there is an increase in the size of the gall bladder. Investigation of hepatobiliary function in man and mammals has not established if the enlarged gall bladder is simply dilated, or if the absorptive capacity of the mucosa has changed. In the present study the concentrating function of the gall bladder and bile secretion from the liver were studied in pregnant animals, oophorectomised animals and animals treated for three months with contraceptive steroids. The effects of intravenous administration of prolactin, progesterone and oestrogen were studied in oophorectomised animals. It was found that the net rate of water absorption in the gall bladder of pregnant animals was doubled, while oophorectomy and contraceptive steroids did not affect this variable. The volume outflow of bile was enhanced in pregnant animals and in animals treated with contraceptive steroids. Intravenous infusions of prolactin, oestrogen or progesterone were found not to influence gall bladder concentrating function, nor hepatic bile secretion in oophorectomised animals.

Absorption↗

PubMed1986

Prostaglandin E2 formation by the gall bladder in experimental cholecystitis.

Both experimental cholecystitis and luminal distension inhibit fluid absorption and stimulate motor activity in the gall bladder. These functional alterations are mimicked by exogenous prostaglandins (PGs) and inhibited by potent cyclooxygenase inhibitors, but direct evidence of a primary role of endogenous PGs is not available. Therefore, experiments in the cat were carried out in which the effects of lyso-phosphatidylcholine (lysoPC; 0.5-2.0 mmol/l), implantation of cholesterol stones, and raised intraluminal pressure in the gall bladder lumen were assessed. The gall bladder was perfused in vivo at a constant rate by a buffer solution. PGE2 was determined in the effluent by a radioimmunological method validated by gas chromatography-mass spectrometry. PGE2 output was markedly (p less than 0.01) raised (13.9 +/- 2.6 vs 1.1 +/- 0.5 ng/h; n = 10) during lysoPC perfusions and this response was inhibited by 66% (p less than 0.02) after indomethacin administration (2 mg/kg iv). A significant (p less than 0.05) increase in PGE2 output occurred six weeks after implantation of gall stones (3.7 +/- 1.5 ng/h; n = 6) and in response to distension of the normal gall bladder wall (3.6 +/- 1.2 ng/h; n = 6). These findings support the theory that PGs play an important pathophysiologic role in biliary tract disease.

Animals↗

PubMed1986

Adrenergic influence on gallbladder function in experimental cholecystitis.

In experimental cholecystitis a net secretion of fluid to the gallbladder lumen is seen in animals with morphological signs of acute inflammation. This fluid secretion, which increases the intraluminal pressure in the obstructed gallbladder, is suggested to be influenced by non-cholinergic intramural gallbladder nerves activated by prostaglandins. In the present study in vivo we show that this fluid secretion, measured by a perfusion technique, is markedly inhibited by electrical activation of the splanchnic nerves that contain adrenergic fibres to the gallbladder and by intravenous administration of an alpha 2-adrenergic agonist, demonstrating that this fluid secretion can be modulated by activation of alpha 2-adrenergic receptors. In patients with an obstructed gallbladder outlet, inhibition of this secretion may reduce gallbladder distension and thus relieve biliary pain. The results suggest that pharmacological activation of adrenergic mechanisms could be useful in the treatment of cholecystitis and biliary pain.

Adrenergic Fibers↗

PubMed1986

Gallstones, cholecystectomy, and duodenogastric reflux of bile acid.

It has earlier been suggested that cholecystectomy, by eliminating the reservoir function of the gallbladder, will induce reflux of bile to the stomach. In the present study 23 patients were studied for duodenogastric reflux of bile acid before and 3 months after cholecystectomy. At the test the gastric contents were continuously aspirated via a nasogastric tube, collected at 15-min intervals for 2 h in the fasting patient, and analyzed for volume and bile acid concentration. The results were compared with those in 14 control subjects. Significant duodenogastric reflux of bile acid (greater than 100 mumol/h) was seen more frequently in gallstone patients than in controls. This is explained by a high prevalence of bile acid reflux in patients with a reduced or absent opacification of the gallbladder at cholecystography. Cholecystectomy increased the prevalence of bile acid reflux in the patients with well-opacified gallbladders at cholecystography. The duodenogastric reflux of bile acid in patients with a poor filling of the gallbladder at cholecystography was not further enhanced by cholecystectomy. It is concluded that gallstone patients have an increased tendency to duodenogastric reflux of bile acid. This tendency is further enhanced by removal of a functioning gallbladder. The findings may explain some of the symptoms in patients with gallstones. The reflux may also be responsible for symptoms in the so-called postcholecystectomy syndrome.

Adult↗

PubMed1986

Cholecystokinin secretion after oral Emtobil, a gallbladder-contracting formula.

Oral Emtobil, a liquid preparation of sorbitol and peanut oil, has been used in roentgenological practice for several years. Emptying of an opacified gallbladder is seen within 15 min after intake of 100 ml of this solution. The main physiological factor responsible for contraction of the gallbladder is cholecystokinin (CCK). In the present study plasma concentrations of CCK in fasting, healthy subjects were studied in response to oral Emtobil. The radioimmunoassay used measures sulphated CCK-8 and CCK-33 with equimolar potency. Neither non-sulphated CCK nor any gastrins are measured. The average concentration, after an overnight fast in nine healthy subjects without gallstones, was 1.2 pmol/l. A peak concentration was seen within 30 min after 'the test meal' and averaged 8 pmol/l. It is suggested that oral Emtobil contracts the gallbladder by release of CCK. Since Emtobil induces a fast and marked rise in the plasma concentration of CCK, it may be used in test procedures to estimate the secretion of CCK.

Administration, Oral↗

PubMed1986

Enzyme substitution in chronic pancreatitis: effects on clinical and functional parameters and on the hydrogen (H2) breath test.

Ten patients with chronic pancreatitis (with abdominal pain and/or diarrhoea) were treated in a double-blind multiple cross-over trial with Pankreon granules 20 g per day or placebo during three periods of one month each. Pain and bowel habits were recorded. Faecal fat and breath hydrogen (H2) excretion were analyzed during the last days of each treatment period. The pain score was initially low in all patients and was not affected by enzymes. The number of daily bowel movements was reduced from 3.16 to 2.32 (n.s.). Faecal fat excretion per 72 hrs was reduced from 357 +/- 158 mmol free fatty acid to 226 +/- 98 mmol (p less than 0.05). With placebo treatment H2 excretion (from 60 and 180 min after a standard breakfast) was significantly increased compared with 19 healthy volunteers (p less than 0.05). It was not significantly reduced by enzymes. In 28 comparisons the H2 output between 60 and 180 min was correlated to faecal fat. In eight patients the oro-coecal transit-time could be determined by the H2 breath test. The transit-time did not differ from that of ten healthy volunteers and remained unchanged by enzymes. Carbohydrate maldigestion occurs parallel to fat maldigestion in chronic pancreatitis, and is not sufficiently reduced by 20 g of pancreatic enzymes.

Adult↗

PubMed1985

Adrenergic vasoconstriction in peripheral nerves of the rabbit.

The blood flow in the sciatic nerve of the rabbit was estimated from the wash out of intraneurally injected 133Xe. To avoid diffusion of the tracer into the surrounding muscular tissue, the nerve was covered by a gas-tight plastic film. Using this technique, the basal blood flow in the sciatic nerve was estimated to 35 ml X min-1 X 100 g-1. It was found that intraarterial norepinephrine and electrical stimulation of the lumbar sympathetic chain strongly reduced the wash out of 133Xe, which only can be explained by a pronounced reduction of the blood flow in the nerve itself. The blood flow again increased within 4 min of stopping the infusion of norepinephrine or the sympathetic stimulation. The prolonged effect and higher neurotoxicity of local anesthetics containing adrenaline may be explained by an alpha receptor-mediated vasoconstriction of the microvessels of peripheral nerves.

Animals↗

PubMed1985

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.

Animals↗

PubMed1985

Indomethacin reduces raised intraluminal gallbladder pressure in acute cholecystitis.

Indomethacin was recently shown to have a potent analgesic effect on biliary pain. The underlying mechanism is not fully clear, although reduction of increased gallbladder pressure by inhibition of prostaglandin synthesis had been suggested. For further clarification of this mechanism, the effect of intravenous indomethacin on the intraluminal gallbladder pressure was investigated in patients undergoing operation for acute cholecystitis. After laparotomy, gallbladder pressure was measured continuously during 25 min in 20 patients, 10 of whom received 100 mg indomethacin intravenously, while 10 were untreated controls. High intraluminal gallbladder pressure was found in all patients. Indomethacin reduced the average pressure by 11% in 20 min, whereas the corresponding pressure in the controls was constant. The results indicate that acute cholecystitis is associated with substantially raised intraluminal pressure, and that the analgesic action of indomethacin on biliary pain may be attributable to a local effect on gallbladder function, resulting in reduction of intraluminal pressure.

Acute Disease↗