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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to explore the cellular source(s) and the behaviour of the collagenolytic activity previously described in rat liver homogenates, in the reversibility of experimental cirrhosis of the liver, enriched suspensions of hepatocytes and of sinusoidal liver cells were obtained by a procedure which employs low EDTA concentrations and no bacterial collagenase. Cell suspensions were prepared from three different groups of animals: 1) normal controls, 2) rats with CCl4-induced cirrhosis of the liver, and 3) rats with swine serum-induced cirrhosis of the liver. Animals were sacrificed in each group upon completion of treatment and also after 3, 6 and 12 months. In each liver wet weight and collagen concentration were determined, and collagenolytic activity of both enriched cell suspensions was measured separately. In addition, histological studies of liver tissue and ultrastructural examination of cell suspensions were performed by standard procedures. Enriched suspensions of both normal hepatocytes and sinusoidal liver cells display Ca2(+)-dependent collagenolytic activities. Both cell suspensions obtained from each of the two types of cirrhotic livers show normal or slightly increased average levels of collagenase activity at the time of treatment discontinuation, when average liver collagen content ranges from 6 to 10-fold over normal, suggesting that the normal collagenase/collagen ratio is disturbed and that collagenolytic activity is deeply decreased in relation to the actual liver collagen load.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Collagenase of hepatocytes and sinusoidal liver cells in the reversibility of experimental cirrhosis of the liver. 198 May 58

Previous work has shown that lactic acid, and to a lesser extent pyruvic acid, is able to increase collagen synthesis significantly in liver slices of CCl4-treated rats but not normal rats. The purpose of this report is to document which cells in the cirrhotic liver are responsible for the lactate-stimulated increase in collagen synthesis. It was found that (a) incorporation of 3H-proline into protein-bound 3H-hydroxyproline is increased threefold to fourfold in hepatocytes from CCl4-treated rats as compared with normal rat hepatocytes; (b) neither the hepatocytes from normal nor those from CCl4-treated rats modify their collagen synthesizing capacity when 30 mmol/L lactic acid was added to the incubation medium; (c) nonparenchymal cells obtained from livers of CCl4-treated rats synthesize much less collagen than hepatocytes, but their synthesis is stimulated twofold by lactic acid; (d) from the different nonparenchymal cells, only fat-storing (Ito) cells increase collagen synthesis when lactic acid is present in the incubation medium. These results suggest that the increased lactic acid levels observed in patients with alcoholic hepatic cirrhosis may play an important role in the development of fibrosis by stimulating collagen production by fat-storing (Ito) cells.
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PMID:Regulation of collagen production in freshly isolated cell populations from normal and cirrhotic rat liver: effect of lactate. 199 24

It has been suggested that perisinusoidal liver cells (PSC) play a pivotal role in the pathogenesis of fibrocontractive changes. Using light and electron microscopic immunolocalization techniques, a series of 207 normal and pathologic human liver specimens were evaluated for the expression of alpha smooth muscle (SM) actin and desmin in this and other nonparenchymal cell types. In normal adult liver tissue, PSCs were practically devoid of desmin and exceptionally stained for alpha-SM actin, whereas this actin isoform frequently was encountered in PSCs from the embryonic to the adolescent period. A broad spectrum of pathologic conditions was accompanied by the presence of alpha-SM actin containing PSCs; these were detected preferentially in periportal or perivenular zones according to the predominant location of the underlying hepatocellular damage. The occurrence of this PSC phenotype generally was associated with fibrogenesis and was in some cases detected earlier than overt collagen accumulation. Fibrous bands subdividing liver tissue in cirrhosis and focal nodular hyperplasia, as well as desmoplastic reaction to malignant tumors, contained alpha-SM actin-rich cells admixed with variable proportions of cells coexpressing desmin. In end stages, this population was less numerous than in active fibrotic or cirrhotic processes. Using immunogold electron microscopy, alpha-SM actin was localized in microfilament bundles of typical PSCs. Our results are compatible with the assumption that the appearance of alpha-SM actin and desmin-expressing myofibroblasts results at least in part from a phenotypic modulation of PSCs.
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PMID:Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers. 202 9

To many people it may be disappointing that many uncertainties remain with respect to the assessment of PHT. Only a few findings such as increased WHVPG and varices prove PHT. However, we have gained considerable knowledge. PHT is the consequence of a number of changes which involve the intrahepatic and extrahepatic circulation. Alcohol, viruses and drugs may disturb parenchymal architecture and cause cellular swelling, collagen and fibrin deposition and invasion with inflammatory cells. These processes finally may evolve into cirrhosis. Although in initial stages the parenchymal disturbance per se may account for PHT, increasingly impaired liver function results in metabolic changes which cause altered haemodynamics. Advanced PHT in parenchymal liver disease is the result of the complex interaction between local and systemic changes. The current techniques for the assessment of PHT are helpful for the qualitative aspects: increase in pressure can be assessed directly or indirectly; the portal venous system can be visualized even without arteriography. Gastroscopy remains a standard procedure for diagnosing PHT. Ultrasound-endoscopy is particularly helpful to confirm fundic varices and to assess changes after sclerotherapy. Increasingly, non-invasive methods to quantify PHT have become available such as the Duplex scanner. However, limitations and pitfalls need to be realized. The quantitative assessment remains (as yet?) a technique for research centres. It is obvious that the clinician in general practice can do without most of the more sophisticated techniques which have been discussed here. For the time being, PHT, and particularly variceal bleeding, is most often treated with endoscopic sclerotherapy. For that reason, only in a minority of the cases very detailed studies are required. However, the increasing knowledge opens new perspectives for the treatment and prevention of PHT on various levels. This may be a rather specific treatment of parenchymal liver disease (antivirals, d-penicillamine for Wilson's disease or venesections for haemochromatosis), drugs which may reduce local tissue damage via more general pathways (colchicine, steroids) and drugs which influence flow. Undoubtedly one of these years a more selective blocker of portal venous pressure will become available. Optimal assessment for that type of therapy makes it mandatory to master at least a few more advanced techniques. With respect to noncirrhotic PHT with causes which may vary from congenital or acquired clotting abnormalities to anatomical malformations (oesophageal web) and 'natural healthy herb tea', measures can be taken. It is clear that before treating any of the more rare causes, a proper diagnostic work-up is required.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Assessment of portal hypertension: understanding will improve treatment. 203 36

In the mitochondria nine antigens and their corresponding antibodies are already known. They can be subdivided in three groups. The first one (M2-M4-M6-M8) appears during the evolution of primary biliary cirrhosis. The antibody against M2 is practically pathognomic for this disease. The M9-antibody is found in PBC with a slow and favourable evolution. The antibodies against M4-M8 are signs of a worse prognosis and a more rapid evolution into terminal cirrhosis. The second group is connected with infections and collagen diseases. The M1-antibody is directed against cardiolipin and diagnostic for syphilis. The M5-antibody appears in definite collagenoses. The M7-antibody is found in certain forms of acute and chronic cardiomyopathy. The third group of antibodies is induced by drugs: the anti-M3 by Venocuran containing a.o. phenopyrazone and the anti-M6 by Iproniazid. The role of the antigens and their antibodies concerning the aetiology and pathogenesis of the relevant diseases, especially primary biliary cirrhosis, is not known.
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PMID:[Mitochondrial antigens and their antibodies]. 205 46

To test further the competence of the cirrhotic liver to metabolize xenobiotics, hepatocytes were isolated from control and CCl4-induced cirrhotic male or female rats. Histologically micronodular cirrhosis was present in all CCl4-treated rats, while control rats had normal livers. Portal perfusion pressure and intrahepatic collagen content were also significantly increased by CCl4 administration. In male rats, no significant differences in levels of circulating transaminases nor in alkaline phosphatase was observed between cirrhotic and control rats, while CCl4-treated females had slightly higher than normal serum transaminase levels at the time of the studies. Hepatocytic cytochrome P-450 and basal xenobiotic biotransformation were unaffected by micronodular cirrhosis in both genders; calculation of the aminopyrine and 7-ethoxycoumarin intrinsic clearances (Cli) revealed, however, a slightly decreased transformation potential in hepatocytes obtained from cirrhotic females, a phenomenon not observed in cirrhotic male rats. It is speculated that the observed reduction in Cli may have been independent of cirrhosis per se, owing to the perduring cytotoxic effect of CCl4 as evidenced by the higher than normal level of transaminases in female rats. Finally, male rats were subjected to in vivo administration of phenobarbital or 3-methylcholanthrene; both compounds led to significant induction of the mixed-function oxidase system, which was similar in magnitude and in selectivity in control and cirrhotic rats as illustrated by calculation of the Michaelis-Menten kinetic parameters for aniline p-hydroxylation, aminopyrine-N-demethylation, 7-ethoxycoumarin-O-deethylation, and p-nitrophenol UDP-glucuronyl transferase. We conclude that in well-established but compensated and hepatolysis-free micronodular cirrhosis, hepatocytes are fully able to transform xenobiotics and to respond normally and selectively to inducers of drug metabolism.
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PMID:Unimpaired induction of drug-metabolizing enzymes in hepatocytes isolated from rats with micronodular cirrhosis. 205 6

Sera from 64 patients with HBsAg-negative chronic liver disease with or without cirrhosis were investigated for aminoterminal peptide of type III procollagen (sP-III-P) as a suitable marker of hepatic fibrosis; 244 healthy control subjects were included in the study. A close correlation (p less than 0.01) between sP-III-P levels and histological activity was observed; on the contrary, no correlation was found between the same serum marker of liver fibroplasia and biochemical activity or clinical severity of the disease. We conclude that sP-III-P as a suitable marker of liver overload of collagen fibers is strongly correlated with the histological activity of the disease. Local immune reactions produce soluble substances that might stimulate fibroblastic activity. The test has a significant sensitivity and a very high specificity as a marker of chronic liver disease with histological activity.
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PMID:Cryptogenic chronic active liver disease. Evaluation of serum aminoterminal peptide of type III procollagen as a marker of histological activity. 207 77

An ultrastructural morphometric study was carried out to detect differences in parenchymal structures between chronic viral hepatitis and hepatitic cirrhosis for more reliable diagnosis of cirrhosis in needle biopsy. Five human liver biopsy specimens were selected from each of the following five groups: chronic persistent hepatitis (CPH), mild chronic active hepatitis (MCAH), severe chronic active hepatitis (SCAH), active hepatitic cirrhosis (AHC) and inactive hepatitic cirrhosis (IHC). The ultrastructural changes in hepatitic cirrhosis which differed from those in chronic hepatitis were: (1) increase in the volume fraction (Vv) of hepatic intercellular space with increased Vv of collagen fibers and less microvilli in the space; (2) decrease in the Vv of perisinusoidal space with more collagen fibers and less microvilli; (3) decreased Vv and surface density (Sv) of RER in hepatocytes; (4) decreased Vv without change in Sv of mitochondria of hepatocytes.
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PMID:[Ultrastructural morphometry of liver parenchyma in hepatitic cirrhosis]. 208 47

The aim of the study was to evaluate the effects of D-penicillamine (cuprenil), encorton and both drugs in combination on fibrotic processes in the rat liver damaged by chronic use of CCl4. The studies comprised 80 white Wistar rats divided into 8 experimental groups. Group I receiving every day oral methylocellulose for 12 weeks was a control group. In group II the rats were given only CCl4 for 12 weeks. In the remaining experimental groups beside CCl4 the animals received drugs in various doses and for various periods. At 12 weeks all animals were killed and post-mortem studies were performed. The liver sections for histopathological studies were fixed in 10% buffered formaline. Paraffin specimens were stained with hematoxylin and eosine. Colour reactions to collagen fibers were performed by using Heidenhein's method and to reticuline fibers by Gomori's method. In the assessment of the severity of fatty degeneration, inflammatory infiltrates and fibrosis the 3-point scale was used, ranging from + for minor changes, ++ for moderate changes, for severe changes, and 0 for no changes. Morphological analysis of the liver showed that chronic administration of CCl4 produced an experimental model of cirrhosis of the liver in rats. Concomitant use of CCl4 and cuprenil revealed its inhibiting action on the fibrotic process in the rats' liver. Inhibition of fibrosis varied and was related to the dose and time of its action. The most optimal was a low dose, 10 mg kg of body weight, whereas a double dose used during the experiment appeared less favourable. Similarly less effective action was exhibited after encorton. After combined use of both drugs the inhibitory effect was negligible. In addition hepatotoxic effects were found manifested by marked fatty degeneration of hepatocytes.
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PMID:[Effects of D-penicillamine and encorton on the fibrotic processes in experimental liver cirrhosis in rats]. 210 Jul 93

Subclinical alveolitis is a frequent finding in immunologic systemic disorders. However the significance of subclinical alveolar inflammation does not seem to be univocal and varies according to the disease. The fact that pulmonary involvement is rare during the course of extrathoracic granulomatosis like Crohn's disease or primary cirrhosis and that subclinical alveolitis is frequent suggests that alveolar inflammation may be the expression in the lung of a systemic immune disorder. In contrast subclinical alveolitis in collagen-vascular diseases, particularly progressive systemic sclerosis, is frequently associated with abnormalities of lung parenchyma as assessed by CT scan supporting the hypothesis that subclinical alveolitis is associated with development of ILD. Close follow-up of these patients is needed to better determine whether subclinical alveolitis precedes ILD and whether early detection of subclinical alveolitis in immunologic systemic disorders may identify those patients that are at risk for the development of ILD in the future.
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PMID:Subclinical alveolitis in immunologic systemic disorders. 211 18


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