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S Matern

Publications and source records attributed to S Matern.

At least 73 records · Page 4Linked to original sources
PubMed1998

Glutathione status in liver and plasma during development of biliary cirrhosis after bile duct ligation.

We do not know much about the changes that occur in reduced (GSH) and oxidized (GSSG) glutathione in the development of liver cirrhosis. Therefore, we investigated the glutathione redox system during development of liver cirrhosis after bile-duct ligation in rats. We compared the GSH and GSSG content of liver and plasma between bile-duct-ligated rats and sham-operated controls 6 and 24 h and 5, 15, 23, and 38 days after operation. Compared to controls (x +/- SD: 6.07 +/- 0.52 mumol/g wet wt.), liver GSH significantly increased 24 h (+ 37%) and 5 days (+ 53%) after bile-duct ligation. Thereafter, GSH continuously declined to 4.25 +/- 0.64 mumol/g (-31%; P < 0.001) at the end of the observation period after 38 days. The GSH turnover in 5-day bile-duct-ligated rats with high GSH concentrations was not significantly different than in sham-operated controls (16 nmol/min per g after bile-duct ligation and 15 nmol/min per g in controls). GSSG (211 +/- 42 nmol/g wet wt. in controls) was significantly lower 6 and 24 h after bile-duct ligation (-34% and -43%, respectively). Thereafter, GSSG increased and was about 100% higher than in controls after 23 and 38 days. The relation of GSSG to GSH in liver continuously increased from 3.4 to 20.5% after bile-duct ligation. The course of plasma GSH (9.57 +/- 0.79 mumol/l) paralleled hepatic GSH on a lower level: + 14% at day 5, -41% at day 15 and -51% at the end of the observation period. Plasma GSSG (0.99 +/- 0.31 mumol/l) was inversely related to liver GSSG: there were increased concentrations early after bile duct ligation (day 5: + 91%) and reduced concentrations (-44%) at the end of the observation period. Dynamic changes of the glutathione status occur in the development of liver cirrhosis after bile-duct ligation. These changes are consistent with increased oxidative stress in the liver and a deficit of transporting GSSG from the cells into plasma.

Animals↗
PubMed1998

Biliary secretory immunoglobulin A is a major constituent of the new group of cholesterol crystal-binding proteins.

BACKGROUND & AIMS: Recently we described a new group of lectin-bound biliary proteins that bind to cholesterol crystals, modify crystal morphology, and inhibit cholesterol crystallization. The aim of the current study was to characterize and identify individual members of this group of cholesterol crystal-binding proteins. METHODS: Crystal-binding proteins were purified from human gallbladder bile by lectin affinity chromatography and preparative gel electrophoresis. Purified crystal-binding proteins were characterized by using cholesterol crystal-growth assays, immunoblotting, and amino acid analysis. For comparison, identified biliary proteins were isolated from gallbladder bile by lectin affinity and immunoaffinity chromatography. RESULTS: The individual crystal-binding proteins with molecular weights of 74, 63, and 28 kilodaltons inhibited cholesterol crystallization in a dose-dependent manner (2.5-10 micrograms/mL). Immunoblotting with specific antibodies and N-terminal amino acid sequences revealed that the 74-kilodalton crystal-binding protein is the secretory component, the 63-kilodalton protein is the heavy chain, and the 28-kilodalton protein is the light chain of human secretory immunoglobulin (Ig) A. Isolated biliary IgA showed a potent inhibitory effect on cholesterol crystallization in model bile even at levels less than physiological concentrations (1-100 micrograms/mL). CONCLUSIONS: Biliary secretory IgA is a major constituent of the previously described group of cholesterol crystal-binding proteins. Crystal-binding IgA may be an important modulator of crystal agglomeration into stones and stone growth in vivo.

Amino Acid Sequence↗
PubMed1997

[Hepatic diseases caused by drugs].

Drug-induced hepatotoxicity covers the clinical and pathological expressions of almost any acute or chronic liver disease. Liver damage is due to intrinsic toxicity of the drug (paracetamol) and/or immunoallergic mechanisms (halothane). Acute injury may be cytotoxic or cholestatic. Cytotoxic injury is characterized by necrosis (paracetamol, halothane) or steatosis (valproate). Cholestatic injury can be associated with immune-mediated portal inflammation (chlorpromazine) or solely attributed to inhibition of transport systems (cyclosporin A). Chronic drug-induced disorders include chronic active hepatitis (methyldopa), autoimmune hepatitis (tienilic acid), alcoholic steatohepatitis-like reactions (amiodarone), indolent fibrosis (methotrexate), chronic cholestatic diseases, vascular lesions, and hepatic neoplasms. The clinical and morphological picture of many drug-induced liver diseases is nonspecific. Diagnosis is based on thorough drug history, temporal relationship, time-course of liver dysfunction, and the exclusion of other causes. Treatment consists of instant withdrawal of the suspected drug and administration of acetylcysteine as early as possible in case of paracetamol intoxication. Drug-induced liver diseases are usually reversible, but prolonged treatment leads to progression and liver cirrhosis.

Chemical and Drug Induced Liver Injury↗
PubMed1997

Purification and characterization of a microsomal bile acid beta-glucosidase from human liver.

A human liver microsomal beta-glucosidase has been purified to apparent homogeneity in sodium dodecyl sulfate-polyacrylamide gel electrophoresis where a single protein band of Mr 100,000 was obtained under reducing conditions. The enzyme was enriched about 73, 000-fold over starting microsomal membranes by polyethylene glycol fractionation, anion exchange chromatographies on DEAE-Trisacryl, and Mono Q followed by affinity chromatography on N-(9-carboxynonyl)-1-deoxynojirimycin-AH-Sepharose 4B. The purified enzyme had a pH optimum between 5.0 and 6.4, was activated by divalent metal ions, and required phospholipids for exhibition of activity. The enzyme catalyzed the hydrolysis of 3beta-D-glucosido-lithocholic and 3beta-D-glucosido-chenodeoxycholic acids with high affinity (Km, 1.7 and 6.2 microM, respectively) and of the beta-D-glucoside (Km, 210 microM) and the beta-D-galactoside of 4-methylumbelliferone. The ratio of relative reaction rates for these substrates was about 6:3:11:1. No activity was detectable toward 6beta-D-glucosido-hyodeoxycholic acid, glucocerebroside, and the following glycosides of 4-methylumbelliferone: alpha-D-glucoside, alpha-L-arabinoside, beta-D-fucoside or beta-D-xyloside. Immunoinhibition and immunoprecipitation studies using antibodies prepared against lysosomal glucocerebrosidase showed no cross-reactivity with microsomal beta-glucosidase suggesting that these two enzymes are antigenically unrelated.

Bile Acids and Salts↗
PubMed1997

Study of human isoursodeoxycholic acid metabolism.

BACKGROUND/AIMS: The aim of this study was to examine the metabolism of isoursodeoxycholic acid (isoUDCA) in humans. METHODS: IsoUDCA was synthesized of >99% purity and administered orally for 1 week, 3 x 250 mg/day, to six healthy male subjects. Bile acids were extracted from duodenal bile, serum, and 24-h urine samples collected before and at the end of the study period, separated into groups of conjugates, and analyzed by gas chromatography-mass spectrometry and fast atom bombardment mass spectrometry. RESULTS: IsoUDCA was tolerated without any side effect. Liver function tests did not change. Bile acid concentrations (mean+/-SEM) increased from 11.9+/-1.87 to 15.3+/-1.37 mmol/l in bile (n.s.), and from 3.4+/-0.10 to 6.8+/-0.43 micromol/l in serum (p<0.05). Urinary excretion of bile acids increased from 5.3+/-0.29 to 82.2+/-7.84 micromol/24 h (p<0.01). All changes were due to significant increases of isoUDCA and UDCA in bile, serum and urine, and of 3-dehydro-UDCA, the 3-oxo intermediate of isomerization, in bile and in serum. The relative enrichments of isoUDCA, UDCA, and 3-dehydro-UDCA, were: in bile, 2.2%, 25.7%, and 0.7%; in serum, 24.7%, 23.5%, and 6.1%; and in urine, 83.7%, 2.0%, and 2.4%. Whereas 78% of serum isoUDCA was unconjugated, 93-94% of biliary and urinary isoUDCA was conjugated with N-acetylglucosamine. CONCLUSIONS: This study indicates good tolerance and significant intestinal absorption of orally administered isoUDCA. IsoUDCA is extensively isomerized, probably both by intestinal and hepatic enzymes to yield UDCA which became the major biliary compound. In vitro, using the human hepatoblastoma cell line Hep G2, isoUDCA was found to be cytoprotective towards ethanol-induced cell injuries.

Adult↗
PubMed1997

TIMP expression in toxic and cholestatic liver injury in rat.

BACKGROUND/AIMS: Hepatic fibrosis is a dynamic pathological process with a net accumulation of extracellular matrix proteins. Recent evidence suggests that besides their increased synthesis, inhibition of matrix degradation plays a significant role. ECM degradation occurs via metalloproteinases which are inhibited in situ by specific tissue inhibitors of metalloproteinases (TIMPs). The aim of our studies was to determine the expression of TIMPs during toxic liver injury and cholestatic liver injury leading to fibrosis. METHODS: We examined the expression of TIMP-1, -2 and -3 in two different rat models for liver injury (intraperitoneal CCl4 injection and bile duct ligation) by Northern blot analysis and in situ hybridization. For comparison, the mRNA expression of the acute phase protein haptoglobin was measured. RESULTS: TIMP-1 was increased during the early phase of toxic liver injury and in cholestasis. Its expression occurred predominantly in areas of inflammation, in hepatocytes, and in mesenchymal and endothelial cells. There was a slight upregulation of TIMP-2 expression during cholestasis. TIMP-3 was not detected at all. CONCLUSIONS: Our results emphasize an involvement of TIMP-1 in matrix homeostasis, indicating its possible participation in liver fibrosis.

Animals↗
PubMed1997

Abnormal postprandial duodenal chyme transport in patients with long standing insulin dependent diabetes mellitus.

BACKGROUND: Patients with long standing diabetes mellitus frequently have upper gut dysmotility. Gastroparesis has been well studied, whereas detailed data on duodenal motor function are limited. AIMS: To characterise postprandial duodenal chyme transport in such patients. METHODS: Intraluminal multiple impedance measurement, recently introduced as a novel technique for investigation of chyme transport, was used to study postprandial duodenal chyme flow in 10 patients with long standing insulin dependent diabetes mellitus with gastroparesis, and 10 healthy volunteers. RESULTS: Four distinct transport patterns of chyme, termed bolus transport events (BTEs), were found in both groups and could be characterised as: short distance propulsive; simple long distance propulsive; retrograde; and complex long distance propulsive. Diabetic patients had significantly lower numbers of propulsive BTEs (p < 0.01), and higher proportions of retrograde BTEs and complex long distance BTEs (p < 0.05) than control subjects, whereas the proportion of simple long distance BTEs was significantly lower (p < 0.05). The mean propagation velocities of the BTEs were similar in both groups. CONCLUSION: Abnormal postprandial duodenal chyme transport was found in patients with long standing insulin dependent diabetes mellitus. This is characterised by transport disorganisation and may result in disturbed chyme clearance.

Adult↗
PubMed1997

Dynamics of esophageal bolus transport in healthy subjects studied using multiple intraluminal impedancometry.

The dynamics of a bolus transport through the esophagus are largely unexplored. To study this physiological process, we applied multiple intraluminal impedancometry in 10 healthy subjects. Three different protocols were used: 1) liquid bolus administered with subject supine, 2) liquid bolus with subject upright, or 3) semisolid bolus with subject supine. Transit of different parts of a bolus (bolus head, body, and tail) was analyzed at different anatomic segments, namely the pharynx and the proximal, middle, and distal thirds of the esophagus. A characteristic pattern of bolus transport was seen in all subjects. Impedance changes related to air were observed preceding the bolus head. The bolus head propelled significantly faster than did the bolus body and tail. Pharyngeal bolus transit was significantly faster than esophageal bolus transit. Within the esophagus, bolus propulsion velocity gradually decreased. Bolus transport was significantly accelerated in the upright position and delayed with increase of bolus viscosity. In conclusion, the dynamics of a bolus transport from the pharynx into the stomach are complex. It varies within both different anatomic segments and different parts of the bolus and depends on bolus characteristics and test conditions. The spatial and temporal resolution of a bolus transport can be obtained by the impedance technique.

Adult↗
PubMed1996

[Lemierre's post-tonsillitis sepsis with meningitis and intravascular consumption coagulopathy as complication of infectious mononucleosis with pansinusitis].

HISTORY AND CLINICAL FINDINGS: 24 days after the onset of infectious mononucleosis, clinically and serologically confirmed, an otherwise healthy 18-year-old schoolboy developed a fulminant septicaemia with acute meningitis and loss of consciousness, consumptive coagulopathy and acute renal failure. INVESTIGATIONS: Computed tomography demonstrated pansinusitis. Lumbar puncture produced purulent cerebrospinal fluid with 11,500 cells/microliters, predominantly granulocytes, protein 205 mg/dl, glucose 19 mg/dl, indicating bacterial meningitis. The suspected diagnosis of posttonsillitis septicaemia (Lemierre's syndrome) was confirmed by repeated demonstration of fusiform gram-negative bacteria in anaerobic blood cultures, identified as Fusobacterium necrophorum. Anaerobic CSF culture grew Prevotella bivia of the Bacteroidaceae family. TREATMENT AND COURSE: Both the consumptive coagulopathy and the renal failure were successfully treated and the patient's condition stabilized. The sinuses were surgically drained under high doses of piperacillin/sulbactam and chloramphenicol. Despite the sensitivity of the cultured bacteria to the administered antibiotics the septic temperature continued, but disappeared within 4 days of metronidazole having been added. After 5 weeks of antibiotic treatment, three of them in an intensive care unit, the patient was discharged in good general condition. CONCLUSION: This case illustrates that severe septicaemia caused by rare bacteria may follow an attack of infectious mononucleosis which had taken an uncomplicated course.

Acute Kidney Injury↗
PubMed1996

Staphylococcal scalded skin syndrome in an immunocompromised adult.

Staphylococcal scalded skin syndrome, a generalized exfoliative dermatitis complicating infections by exfoliative toxin-producing strains of Staphylococcus aureus, is rarely observed in adults. In contrast to mortality in infants, mortality in adults is usually high. A case of generalized staphylococcal scalded skin syndrome in an immunocompromised woman is reported. Culture of skin biopsy and pleural fluid yielded identical strains of staphylococcus aureus belonging to phage group II. Exfoliative toxins A and B were detected in both isolates. As far as can be determined, this is the first reported case of generalized staphylococcal scalded skin syndrome in an adult with detection of exfoliate toxins A and B in which the patient was treated successfully.

Adult↗
PubMed1996

Stimulation of bile acid 6 alpha-hydroxylation by rifampin.

BACKGROUND: Rifampin was shown to relieve pruritus in cholestatic liver diseases. There has been much speculation about the origin of pruritus, but it has not yet been comprehensively explained. The role of bile acids in producing pruritus is obscure and still under debate. Since rifampin both inhibits the uptake of bile acids into the hepatocyte and strongly induces mixed-function oxidases in the liver, the beneficial effects of this drug might be a consequence of altered bile acid metabolism. METHODS: We investigated the influence of rifampin on urinary bile acid excretion with special respect to glucuronide and sulphate conjugates in 14 healthy volunteers before and after administration of rifampin, 600 mg x 7 days, using each subject as his or her own control. RESULTS: Bile acid glucuronide excretion increased from 0.55 to 1.19 mumol/24 h. This was in particular due to a significant increase of the urinary excretion of the 6 alpha-hydroxylated hyocholic and hyodeoxycholic acids, the relative amounts of which accounted for about two thirds of the urinary bile acid excretion. Excretion of sulphates, however, decreased from 1.40 to 0.86 mumol/24 h due to a significantly reduced excretion of lithocholic acid sulphate. No changes in the excretion rates of other primary and secondary bile acids and no changes in their conjugation patterns were observed. CONCLUSIONS: The results provide evidence that rifampin induces 6 alpha-hydroxylation of bile acids. The products are subsequently glucuronidated at the 6 alpha-hydroxy group, thus stimulating renal excretion of potentially toxic bile acids.

Adult↗
PubMed1995

Tissue inhibitor of metalloproteinases-2 (TIMP-2) in rat liver cells is increased by lipopolysaccharide and prostaglandin E2.

To explore the functional role of TIMP-2 in liver, we determined TIMP-2 mRNA levels in primary rat hepatocytes and in total rat liver. Rat hepatocytes constitutively express TIMP-2 mRNA at a low level. Incubation with dexamethasone, prostaglandin E2 and a combination of inflammatory cytokines leads to an up-regulation of TIMP-2 mRNA. In rats in vivo we found a dramatic increase of TIMP-2 expression after intraperitoneal injection of lipopolysaccharide. Compared to our previous findings on TIMP-1 we conclude that TIMP-2 mRNA expression is regulated in a distinct and partially opposite manner. Over-production of TIMP-2 could inhibit the activity of metalloproteinases and thus lead to matrix accumulation. Dysregulation of TIMP-2 synthesis might be involved in the development of liver fibrosis.

Animals↗
PubMed1995

The influence of rifampin treatment on caffeine clearance in healthy man.

BACKGROUND/AIMS: Since cytochrome P450IA2 is involved in the metabolism of procarcinogens and carcinogens, there is debate about whether induction of this enzyme system by pharmaceuticals leads to a higher risk of malignancy. We investigated rifampin as a potent inducer of the hepatic mixed function oxygenase system and its effect on caffeine metabolism which can be taken as an in vivo marker of cytochrome P450IA2 activity. METHODS: Caffeine clearance was measured in ten healthy volunteers before and after a 7-day treatment with 600 mg rifampin. Urinary 6 beta-hydroxycortisol output was used as endogenous marker of microsomal enzyme function. RESULTS: 6 beta-hydroxycortisol increased from 7.6 to 26.0 micrograms/24 h per kg after treatment with rifampin, consistent with the induction of mixed function oxidases in the liver. There were significant changes in caffeine plasma half-life (6.2 vs. 3.5 h; p < 0.004) and caffeine plasma clearance (1.3 vs. 2.2 ml/kg per min; p < 0.004) with rifampin. CONCLUSIONS: The hypothesis that induction of cytochrome P450IA2 entails accelerated activation of procarcinogens would predict rifampin to be associated with a higher risk of malignancy. As with other inducers of cytochrome P450IA2, such as phenytoin or omeprazole, no such linkage is known. Therefore the role of pharmaceutical induction of cytochrome P450IA2 in tumor promotion remains unclear.

Caffeine↗
PubMed1995

Chyme transport patterns in human duodenum, determined by multiple intraluminal impedancometry.

To get information about the mechanisms involved in chyme transport during the fasting and postprandial states, the novel procedure of multiple intraluminal impedancometry was evaluated in 14 healthy subjects (6 during fasting, 8 after a test meal). All main features of the migrating motor complex (MMC) cycle were determined. During phase II of the MMC cycle and the postprandial period, different transport patterns of chyme, termed bolus transport events (BTEs), were determined. These were 1) simple long-distance propulsive transport (spreading distance > 16 cm), 2) short-distance propulsive transport, and 3) retrograde transport. A significantly lower number of BTEs was recorded during fasting than postprandially. Short-distance propulsive BTEs predominated during fasting (72%), and long-distance propulsive BTEs predominated after the test meal (76%). Retrograde BTEs were recorded during fasting (4%) and postprandially (8%). In the latter state, complex long-distance propulsive BTEs were also observed (5%), consisting of multiple components. A major proportion of gastric contents was found to be continuously transported to jejunum. In conclusion, impedancometry enables us to determine patterns and parameters of chyme transport during fasting and postprandial states.

Adult↗
PubMed1995

A new subgroup of lectin-bound biliary proteins binds to cholesterol crystals, modifies crystal morphology, and inhibits cholesterol crystallization.

Biliary proteins inhibiting or promoting cholesterol crystallization are assumed to play a major role in cholesterol gallstone pathogenesis. We now report a new group of biliary proteins that bind to cholesterol crystals, modify crystal morphology, and inhibit cholesterol crystallization. Various glycoprotein mixtures were extracted from abnormal human gallbladder bile using lectin affinity chromatography on concanavalin A, lentil, and Helix pomatia columns and were added to supersaturated model bile. Independent of the protein mixtures added, from the cholesterol crystals harvested, the same four GPs were isolated having molecular masses of 16, 28, 63, and 74 kD, respectively. Each protein was purified using preparative SDS-PAGE, and influence on cholesterol crystallization in model bile was tested at 10 microg/ml. Crystal growth was reduced by 76% (GP63), 65% (GP16), 55% (GP74), and 40% (GP28), respectively. Thus, these glycoproteins are the most potent biliary inhibitors of cholesterol crystallization known so far. Evidence that the inhibiting effect on cholesterol crystallization is mediated via protein-crystal interaction was further provided from scanning electron microscopy studies. Crystals grown in presence of inhibiting proteins showed significantly more ordered structures. Incidence of triclinic crystals and regular aggregates was shifted from 30 to 70% compared with controls. These observations may have important implications for understanding the role of biliary proteins in cholesterol crystallization and gallstone pathogenesis.

Analysis of Variance↗
PubMed1994

TIMP-1 protein expression is stimulated by IL-1 beta and IL-6 in primary rat hepatocytes.

Degradation of extracellular matrix proteins is performed by metalloproteinases which are inhibited by tissue inhibitors of metalloproteinases (TIMP). We expressed the murine TIMP-1 protein in E. coli and prepared a polyclonal antiserum against the recombinant protein. Using this antiserum we studied the biosynthesis and glycosylation of murine TIMP-1 protein in COS-7 cells transfected with a TIMP-1 expression plasmid by metabolic labeling and indirect immunofluorescence studies. In primary rat hepatocytes we show for the first time that TIMP-1 protein expression is up-regulated upon stimulation with IL-1 beta and IL-6. Since TIMP-1 is induced during the acute phase reaction it could possibly be involved in the pathogenesis of liver fibrosis.

Acute-Phase Reaction↗