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Biomedical subjects

J Svanvik

Publications and source records attributed to J Svanvik.

At least 37 records · Page 2Linked to original sources

Inflammation reduces mucosal secretion of hydrogen ions and impairs concentrating function and luminal acidification in feline gallbladder.

BACKGROUND: The gallbladder mucosa normally absorbs fluid and secretes H+ ions. The fluid secretion in inflamed gallbladders is induced by prostaglandins and mediated by intramural vasoactive intestinal peptide (VIP)-ergic nerves. METHODS: The influence of inflammation on gallblader contents due to secretion of H+ into the lumen. In animals with inflamed gallbladder this acid secretion was reduced; there was secretion of HCO3- and no evident acidification of the gallbladder contents. Injection of VIP antiserum or indomethacin restored H+ secretion and inhibited HCO3- and fluid secretion by the inflamed gallbladder mucosa. An impaired acidification of the gallbladder contents due to mucosal inflammation may reduce the solubility of calcium salts in gallbladder bile and increase the risk of their precipitation in the lumen. CONCLUSION: Mucosal inflammation reduces H+ secretion and impairs acidification of the gallbladder contents.

Amiloride↗

A comparative retrospective study of thoracoscopy versus thoracotomy for the treatment of spontaneous pneumothorax.

Thoracoscopic surgery has been claimed to reduce patient disability, recovery time, and hospital costs compared with open surgery. We analyzed 25 patients who had undergone thoracoscopic surgery and compared the outcome to 24 patients who had undergone conventional surgery for spontaneous pneumothorax. The thoracoscopic group was able to return to work and daily activities earlier and had less impairment of shoulder movement. There was a loss of sensation corresponding to the dermatomes where the thoracoscopic ports were placed, which could have resulted from compression of the intercostal nerves by the instruments. However, a similar loss of sensation was found in the thoracotomy group. We conclude that thoracoscopy may be the method of choice for the treatment of spontaneous pneumothorax, although further methodological development should be done.

Activities of Daily Living↗

VIP-antiserum inhibits fluid secretion by the inflamed gallbladder mucosa.

The inflammatory fluid secretion by the gallbladder mucosa in experimental cholecystitis is induced by an increased prostaglandin formation and is mediated by intramural nerves. In the present study the effect of VIP-antiserum on the inflammatory fluid secretion in the gallbladder was tested in a validated experimental model in cats. The animals were studied in acute experiments 6 weeks after a procedure when the cystic duct was tied and gallstones were implanted in the gallbladder. During basal conditions there was a continuous secretion of fluid into the lumen of the inflamed gallbladder averaging 0.43 +/- 0.18 ml/h. Injection of VIP antiserum, obtained from immunized rabbits and diluted with saline 1:10 in a bolus of 4 ml into the coeliac artery reversed this secretion into an absorption of 1.72 +/- 0.44 ml h-1 (P < 0.001). VIP-antiserum did not affect the fluid adsorption in control animals with an intact gallbladder and injection of control serum from rabbits not immunized to VIP did not affect fluid secretion in the inflamed gallbladders. The results support the idea that the inflammatory fluid secretion in the gallbladder mucosa is mediated by VIP-ergic nerve fibres.

Animals↗

Raised pressure in the bile ducts after orthotopic liver transplantation.

Biliary complications are common after orthotopic liver transplantation. Bile leakage in the immediate postoperative period and on removal of the T-tube could possibly be caused by a raised bile duct pressure. In order to test this hypothesis, bile duct pressure was studied in seven consecutive liver transplant patients. During the operation, the common bile duct was anastomosed end-to-end over a T-tube. The initial bile duct pressure measurement was performed a median of 12 days (range 10-17 days) after the transplantation and on one or two more occasions during the following 3 months. Seven cholecystectomized gallstone patients with indwelling T-tubes were used as controls. The bile duct pressure at the level of the xiphoid process in the transplanted group was 7.7 +/- 1.4 cm H2O and in the control group 0.5 +/- 0.8 cm H2O (P < 0.001). The initially increased bile duct pressure after liver transplantation decreased with time (P < 0.05) towards normal during the following 3 months. The raised pressure may increase the risk of bile leakage in the postoperative period.

Adult↗

A possible role of ursodeoxycholic acid in liver transplantation.

There are many different causes of graft dysfunction and cholestasis after liver transplantation. These include non-primary function, preservation and reperfusion injury, acute rejection, artery thrombosis, drug toxicity, bile leakage, and bile duct stenosis. Medication with ursodeoxycholic acid (UDCA) has beneficial effects in different cholestatic conditions. The initial rationale for its use after liver transplantation was to alter the bile acid pool to a more atoxic composition, as liver transplantation can be associated with cholestasis and can stimulate the initial bile production. We have consecutively treated 41 patients with primary graft function with UDCA. During the first postoperative month, 17% of the UDCA treated patients had an episode of acute rejection compared with 75% of a historical control group of 8 patients. The results suggest that adjuvant treatment with UDCA reduces acute liver graft rejection. This has to be confirmed by controlled prospective trials; one is presently being carried out in the Nordic countries. Several studies have indicated an immunomodulating capacity of this bile acid and we have recently reported our results from a heart transplant model in the rat, where treatment with UDCA prolonged graft survival. Improvement in surgical technique and postoperative care as well as immunosuppressive treatment has improved the results of liver transplantation. Acute rejection is nowadays a dominating problem after liver transplantation and the inclusion of UDCA may reduce morbidity.

Animals↗

Isolation and characterization of a cholesterol crystallization promoter from human bile.

BACKGROUND: Recent studies on the pathogenesis of cholesterol gallstone disease have focused on the potential importance of an imbalance between biliary proteins having either inhibitory or promoting activities on nucleation and/or growth of cholesterol crystals as the initial stage in stone formation. The current study describes the purification and partial characterization of a 42-kilodalton biliary glycoprotein that shows concentration-dependent cholesterol crystallization-promoting activity. METHODS: Chromatographic methods were used for separation and purification. Characterization steps included electrophoresis, deglycosylation, amino acid and carbohydrate analysis, and activity analysis by crystal growth assay. RESULTS: The 42-kilodalton purified glycoprotein is an extensively glycosylated (37%) monomer with an acidic isoelectric point (pl < 4.1) that is probably based on the sialic acid content of the carbohydrate moiety. Enzymatic N-deglycosylation removes the carbohydrate moiety and inactivates the promoting activity. Furthermore, enzymatic proteolysis results in both its complete structural degradation and functional inactivation. Although the glycoprotein was isolated from normal human gallbladder biles, its presence in gallstone-associated samples is clearly shown. CONCLUSIONS: This report outlines biochemical features of a human biliary glycoprotein that may be of major pathophysiological significance in gallstone disease.

Amino Acids↗

Hepatic excretion and metabolism of polyethylene glycols and mannitol in the cat.

The biliary clearances of fluid phase markers like erythritol and mannitol have been used to estimate canalicular bile flow. Larger fluid phase marker molecules like polyethylene glycol (PEG) 900 are excreted more extensively into bile, and it has been suggested that the biliary clearance of these give a more accurate measure of canalicular water flux than those of erythritol and mannitol. In this study, the biliary excretion of PEG 900 was compared with that of mannitol during choleresis induced by either sodium taurocholate or secretin. The biliary excretion of PEG 900 exceeded that of mannitol by a factor of 94. The biliary clearance of these markers was not influenced by secretin-induced choleresis. Using ion-exchange chromatography and fast atom bombardment mass spectrometry (FABMS) it was demonstrated that 26% of the PEG molecules are excreted into bile after oxidation to carboxylic acids, whereas sulphate conjugation is negligible. The majority of the PEG molecules (74%) were secreted unchanged, which supports the hypothesis of a mainly passive movement of PEG with the water flux into bile. FABMS showed an enrichment of larger PEG molecules in bile, which supports a previous finding that among differently sized PEGs the 1074-Da molecules have the highest biliary excretion.

Animals↗

In vivo regulation of mucosal transport of H+ and HCO3- in the feline gall bladder.

In the gall bladder of a fasting subject, a decline in the pH of the contents occurs due to secretion of H+ from the mucosa. In this study in anaesthetized cats, the gall bladder lumen was perfused with a bicarbonate buffer bubbled with 4% CO2 in air. During basal conditions, the PCO2 always rose while the pH and [HCO3-] fell in the buffer when passing through the gall bladder lumen, indicating a continuous secretion of H+ by the mucosa. This H+ secretion was enhanced by stimulation of the respective sympathetic nerves and was blocked by intraluminal amiloride. Intravenous infusion of vasoactive intestinal peptide (VIP) raised the pH and [HCO3-] in the buffer during the passage through the gall bladder lumen, indicating a secretion of bicarbonate from the mucosa. In view of the presence of sympathetic and VIP immunoreactive nerve fibres in the gall bladder wall and VIP receptors on the luminal epithelial cells, the study demonstrates that there are functional grounds for physiological variations in the secretion of H+ and HCO3- by the gall bladder mucosa. These variations may be important for the solubility of calcium salts in the gall bladder contents.

Amiloride↗

Contraction and evacuation of the gallbladder studied simultaneously by ultrasonography and 99mTc-labeled diethyl-iminodiacetic acid scintigraphy.

Emptying of the gallbladder was studied by the simultaneous use of 99mTc-labeled diethyl-iminodiacetic acid [HIDA] scanning and real-time ultrasonography. In response to a liquid test meal the gallbladder volume was reduced for 80 min and then increased again, but the radionuclide evacuation continued and was more complete than could be explained by the reduction of gallbladder volume. In response to intravenous infusion of cholecystokinin, a maximal contraction of the gallbladder to 35% of the basal volume was obtained at 40 min, and 36% of the HIDA then remained in the gallbladder. In a separate series repeated intravenous injections of 99mTc-HIDA were given after the test meal, and the isotope was found to enter the gallbladder even when the gallbladder contracted. The results support the view that the gallbladder acts like a 'bellows' when contracting and that postprandial fluid secretion by the gallbladder mucosa may help to evacuate its contents.

Adult↗

Location of enkephalinase and functional effects of [Leu5]enkephalin and inhibition of enkephalinase in the feline main pancreatic and bile duct sphincters.

1. Morphological studies have demonstrated enkephalinergic nerve fibres in proximity to the sphincter of Oddi, and opiates are known to contract this sphincter. In this study, the flow resistances in the common bile duct and main pancreatic duct sphincters were studied simultaneously in anaesthetized cats using a perfusion technique. 2. Naloxone did not affect the activity of these sphincters under basal conditions, indicating that there is no basal enkephalinergic tone. 3. The response to [Leu5]enkephalin (0.015-15 micrograms/kg), morphine (1 mg/kg) and ketamine (10 mg/kg) was a naloxone-sensitive increased activity in the sphincters with a raised frequency of phasic contractions. The threshold dose for an effect of [Leu5]enkephalin on the sphincter of Oddi was 0.015 microgram/kg and a maximal response was observed at 0.75 microgram/kg. There were no differences in the response of the main pancreatic duct sphincter and the bile duct sphincter to the different drugs. 4. Immunoautoradiographic studies demonstrated enkephalinase in the sphincter++ of Oddi. 5. Acetorphan (3 mg/kg intravenously), which inhibits endogenous enkephalinase both in the peripheral and the central nervous system when administered parenterally, caused a naloxone-sensitive contraction, whereas thiorphan (3-20 mg/kg), an enkephalinase inhibitor that does not easily penetrate the blood-brain barrier, had no effect on the sphincter of Oddi. 6. These results show that endogenous and exogenous opiates influence the function of the feline sphincter of Oddi and that enkephalins may be involved in the physiological control of this sphincter, although not under basal conditions.

Animals↗