Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous our studies showed that some steroid hormones, as pure crystalline Progesterone (pPc) and 17-alpha-hydroxyprogesterone capronate (17 alpha HPC) heightened the cirrhogenic action produced in rat liver by carbon tetrachloride. Medroxyprogesterone (MPA), however, did not appear to promote cirrhosis, but increased just steatosis. In the present paper, we have studied the above mentioned steroid hormones for their possible capability of inducing changes in plasma fibronectin concentration. For this purpose, the soluble plasma fibronectin level was measured in female rats 45 days after CCl4-induced cirrhosis, and it was compared with the insoluble fibronectin of liver (detected by immunostaining) and the collagen content in the organ. The results obtained show that, after treatment with CCl4 and MPA, both plasma and liver fibronectin content strongly increases, whereas liver collagen content lowers. However, after treatment with CCl4 alone or in association with the other two steroid hormones, any changes in fibronectin content is not observable, but, on the contrary, is evident a heightened collagen production associated with a cirrhotic change of liver.
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PMID:Changes in fibronectin production in rat liver during cirrhotic evolution due to treatment with CCl4 and steroid hormones: correlation with plasmatic fibronectin. 146 20

MAP, RPF, GFR, V and UNaV were measured in nine conscious control and in 11 conscious cirrhotic rats with ascites before and following two bolus injections (100 and 600 pmol/kg body wt) of endothelin (ET). PRA and plasma concentration of aldosterone and ANP were measured in basal conditions and following the high dose ET. ET induced similar increase in MAP and decrease in RPF and GFR in control and cirrhotic rats. High-dose ET produced a significant reduction in UNaV in control rats (from 2.22 +/- 0.46 to 1.14 +/- 0.28 microEq/min, P less than 0.01). By contrast, it induced marked natriuresis in cirrhotic rats (from 0.76 +/- 0.18 to 2.31 +/- 0.70 microEq/min, P less than 0.05). ET significantly increased aldosterone (control rats: 59.3 +/- 2.2 vs. 85.4 +/- 7.4 ng/dl, P less than 0.025; cirrhotic rats: 115.0 +/- 15.8 vs. 163.9 +/- 30.8, ng/dl, P less than 0.05) and ANP (control rats: 20.1 +/- 3.4 vs. 42.7 +/- 7.7, fmol/ml, P less than 0.025; cirrhotic rats: 107.5 +/- 17.3 vs. 214.2 +/- 41.1, fmol/ml, P less than 0.025) and significantly suppressed PRA (control rats: 2.5 +/- 0.5 vs. 0.2 +/- 0.04, ng/ml.hr, P less than 0.025; cirrhotic rats: 16.6 +/- 2.9 vs. 5.0 +/- 1.1, ng/ml.hr, P less than 0.01) in both groups of animals. These results indicate that ET has marked natriuretic properties in cirrhosis with ascites due to inhibition of tubular sodium reabsorption.
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PMID:Doses of endothelin have natriuretic effects in conscious rats with cirrhosis and ascites. 194 66

Central nervous system (CNS)-induced natriuresis was investigated in nonascitic rats with CCl4-induced cirrhosis (CTC rats) under pentobarbital anesthesia. At baseline, urine sodium output (UNa+V, in mumol.min-1.100 g body wt-1) (-30%, P less than 0.01) and mean arterial pressure (MAP, in mmHg) (-12%, P less than 0.001) were significantly reduced in CTC rats (n = 32) compared with matched controls (n = 34). In response to intracerebroventricular infusion of sodium-rich (349 mM) artificial cerebrospinal fluid (Na(+)-CSF infusion), UNa+V was significantly higher in CTC rats (2.8 +/- 0.3; n = 15) than in controls (1.7 +/- 0.2; n = 17; P less than 0.01); no differences were found in pressor changes (24 +/- 3 vs. 19 +/- 2). A similar but normal sodium CSF (150 mM) infusion did not influence UNa+V or MAP in any group (n = 12, both). In contrast, CTC rats (n = 5) showed, compared with controls (n = 5), significantly reduced natriuretic (UNa+V, 6.9 +/- 0.5 vs. 12.4 +/- 0.9; P less than 0.001) and pressor (+16 +/- 3 vs. +31 +/- 2; P less than 0.01) responses to an intravenous hypertonic sodium overload. Natriuresis induced by Na(+)-CSF infusion was related to increases in creatinine clearance (similar in both groups) and in fractional sodium excretion, which was significantly higher in CTC rats (5.90 +/- 0.15%) than in controls (3.65 +/- 0.14%; P less than 0.01). In summary, CNS-dependent efferent natriuretic mechanisms were preserved in CTC rats and were able to reverse renal tubular sodium retention in these animals. It is proposed that Na(+)-CSF infusion may be a useful tool for the study of renal sodium retention in experimental liver cirrhosis.
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PMID:Enhanced responsiveness to CNS-induced natriuresis in anesthetized nonascitic cirrhotic rats. 205 81

Recent work indicates that nitric oxide (NO) plays an important role in the systemic and renal alterations of liver cirrhosis. This study used aminoguanidine (AG), a preferential inhibitor of inducible nitric oxide synthase (iNOS), to evaluate the role of this NOS isoform in the systemic and renal alterations of an experimental model of liver cirrhosis with ascites (carbon tetrachloride/ phenobarbital). Experiments have been performed in anesthetized cirrhotic rats and their respective control rats prepared for clearance studies. Administration of AG (10 to 100 mg/kg, iv) elevated dose-dependent mean arterial pressure (MAP, in mm Hg) in the cirrhotic rats from a basal level of 79.3 +/- 3.6 to 115.0 +/- 4.7, whereas in the control animals, MAP increased only with the highest dose of the inhibitor (from 121.8 +/- 3.6 to 133.3 +/- 1.4). In the cirrhotic group, AG also significantly increased sodium and water excretion, whereas these effects were very modest in the control group. Plasma concentration of nitrates+nitrites, measured as an index of NO production, were significantly increased in the cirrhotic animals in the basal period and decreased with AG to levels not significantly different from the control animals. Similar experiments performed with the nonspecific NOS inhibitor N omega-nitro-L-arginine (NNA) also demonstrated an increased pressor sensitivity of the cirrhotic rats, but the arterial hypotension was completely corrected. These results, in an experimental model of liver cirrhosis with ascites, show that AG exerts a beneficial effect as a result of inhibition of NO production, increasing blood pressure and improving the reduced excretory function. Because NNA, but not AG, completely normalized the arterial hypotension, it is suggested that the constitutive NOS isoform is also contributing in an important degree. It is concluded that the activation of both inducible and constitutive NOS isoforms plays an important role in the lower systemic blood pressure and associated abnormalities that characterize liver cirrhosis.
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PMID:Renal and pressor effects of aminoguanidine in cirrhotic rats with ascites. 898 51

Although the fertility status of women with Wilson's disease may be preserved, contraceptive method choice is complicated by the tendency for some methods to have an adverse effect on hepatic function and, conversely, for liver disease to compromise the efficacy of some contraceptives. This paper presents the case of a 28-year-old woman diagnosed with Wilson's disease at 13 years of age. She presented to an Israeli hospital at 9 weeks' gestational age with bleeding esophageal varices, cirrhosis, and portal hypertension. Although the patient had been oligomenorrheic, with menses every 2-3 months, she had experienced 3 spontaneous first-trimester abortions. Due to the urgent need for a portal decompression shunt procedure and the risk of further bleeding, the patient opted to terminate the current pregnancy. To prevent conception until the patient's liver condition stabilized, she was injected with Depo-Provera and penicillamine treatment was resumed. Although IUDs and estrogen-containing oral contraceptives are relatively contraindicated in women with liver dysfunction, spermicide and barrier contraceptives are highly recommended and progesterone-only preparations can be safely prescribed.
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PMID:The contraceptive choice for a Wilson's disease patient with chronic liver disease. 940 5

The purpose of this study was to investigate the therapeutic effects of terlipressin (TP) alone or in combination with tetramethylpyrazine (TMP) on anesthetized portal hypertensive rats. Portal hypertension was induced by either partial portal vein ligation (PVL, without cirrhosis) or bile duct ligation (BDL, with cirrhosis) in Sprague-Dawley rats. Each PVL or BDL rat received only one of the two regimens: vehicle for 3 min followed by TP (0.017 mg x kg(-1) x min(-1) for 3 min) or TMP (10 mg x kg(-1) x min(-1) for 3 min) followed by TP. In PVL rats, infusion of vehicle followed by TP induced significant reduction of portal venous pressure (PVP, -15.0+/-1.0%) and prominent elevation of mean arterial pressure (MAP, 57.3+/-8.1%) as well as total peripheral resistance (TPR, 113+/-11%) from baseline, and there was a cardiodepressant response (cardiac index, CI, -26.3+/-1.1%). Infusion of TMP followed by TP induced significant reduction of PVP (-20.3+/-0.4%) and CI (-9.9+/-1.2%) and significant elevation of MAP (31.3+/-2.5%) and TPR (46.0+/-4.1%) from baseline. In BDL rats, infusion of vehicle followed by TP also induced significant reduction of PVP (-13.8+/-1.7%) but an increase in MAP (57.1+/-2.2%) and TPR (101+/-6%) from baseline, and there also was a cardiodepressant response (CI, -21.4+/-2.3%). Infusion of TMP followed by TP induced significant reduction of PVP (-18.9+/-1.4%) and CI (-11.9+/-2.1%), but an increase in MAP (36.2+/-2.5%) and TPR (55.0+/-5.2%). Compared with vehicle followed by TP, TMP not only significantly enhanced portal hypotensive (PVP reduction) effects of TP but also attenuated the systemic pressor (MAP and TPR elevation) and cardiodepressant (CI reduction) effects of TP in both PVL and BDL rats. Our results suggest that TP, alone or in combination with TMP, induced portal hypotensive effects in two models of portal hypertensive rats. Combination of TP and TMP was beneficial in enhancing portal hypotensive effects of TP and ameliorating the systemic pressor and cardiodepressant effects of TP.
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PMID:Beneficial effects of combined terlipressin and tetramethylpyrazine administration on portal hypertensive rats. 1054 25

Chronic hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. The HCV capside core is a multifunctional protein with regulatory functions that affects transcription and cell growth in vitro and in vivo. Here, we show that both HCV genotype 1a and 3 core proteins activate MEK1 and Erk1/2 MAP kinases and that the costitutive expression of the HCV core results in a high basal activity of Raf1 and MAP/kinase/kinase, as determined by endogenous Raf1 in vitro kinase assay and immunodetection of hyperphosphorylated Erk1 and Erk2 even after a serum starvation. Moreover, the activation of both Erk1/2 and the downstream transcription factor Elk-1 in response to the mitogenic stimulus EGF is significantly prolonged. The sustained response to EGF in cells expressing the HCV core occurs despite a normal induction of the MAP phosphatases MKP regulatory feedback and is likely due to the costitutive activation of Raf-1 activity. The ability of HCV core proteins to directly activate the MAP kinase cascade and to prolong its activity in response to mitogenic stimuli may contribute to the neoplastic transformation of HCV infected liver cells.
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PMID:Sustained activation of the Raf/MEK/Erk pathway in response to EGF in stable cell lines expressing the Hepatitis C Virus (HCV) core protein. 1142 Jun 71

This article discusses the potential availability of Cyclo-Provera, a monthly injectable similar to Depo-Provera that is being considered for approval by the US Food and Drug Administration (FDA). A new drug application was filed by its marketing company, Pharmacia and Upjohn of Kalamazoo, Michigan, in September 1997. The company wants mutual recognition by the FDA in US and European markets. The Jones Institute for Reproductive Medicine at the Eastern Virginia Medical School in Norfolk recently completed a company-sponsored clinical trial of the drug. This Institute is 1 of 44 sites conducting nationwide clinical trials among a total sample of 1200 women over 5 years. Cyclo-Provera is comprised of depomedroxyprogesterone acetate (DMPA), which is the same ingredient in Depo-Provera. Cyclo-Provera has a lower dose of DMPA (25 mg) combined with 5 mg of estradiol cypionate. The ingredients are expected to provide improved monthly menstrual cycle control. Cyclo-Provera is marketed outside the US under the name Cyclofem. Cyclofem is mainly used in China and Latin America. Germany produces a similar drug. The World Health Organization (WHO) has conducted multinational studies on both drugs. WHO recommends Cyclofem for most women who desire effective, reversible contraception and who are not at risk for most cardiovascular complications. The estrogen in Cyclofem is less potent and has a shorter life span than the estrogen in combined contraceptives. WHO guidelines suggest that Cyclofem has advantages that outweigh disadvantages for smokers under 35 years old, light smokers older than 35, women with mild hypertension (160/100), women with current or medically treated gall bladder disease, or women with mild cirrhosis. Cyclofem is not recommended for heavy smokers over 35 years old, women with a history of hypertension, and women with severe cirrhosis.
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PMID:New year, new option: Cyclo-Provera awaits word. 1234 12

Alcohol abuse reduces response rates to IFN therapy in patients with chronic hepatitis C. To model the molecular mechanisms behind this phenotype, we characterized the effects of ethanol on Jak-Stat and MAPK pathways in Huh7 human hepatoma cells, in HCV replicon cell lines, and in primary human hepatocytes. High physiological concentrations of acute ethanol activated the Jak-Stat and p38 MAPK pathways and inhibited HCV replication in several independent replicon cell lines. Moreover, acute ethanol induced Stat1 serine phosphorylation, which was partially mediated by the p38 MAPK pathway. In contrast, when combined with exogenously applied IFN-alpha, ethanol inhibited the antiviral actions of IFN against HCV replication, involving inhibition of IFN-induced Stat1 tyrosine phosphorylation. These effects of alcohol occurred independently of i) alcohol metabolism via ADH and CYP2E1, and ii) cytotoxic or cytostatic effects of ethanol. In this model system, ethanol directly perturbs the Jak-Stat pathway, and HCV replication. Infection with Hepatitis C virus is a significant cause of morbidity and mortality throughout the world. With a propensity to progress to chronic infection, approximately 70% of patients with chronic viremia develop histological evidence of chronic liver diseases including chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The situation is even more dire for patients who abuse ethanol, where the risk of developing end stage liver disease is significantly higher as compared to HCV patients who do not drink 12.Recombinant interferon alpha (IFN-alpha) therapy produces sustained responses (ie clearance of viremia) in 8-12% of patients with chronic hepatitis C 3. Significant improvements in response rates can be achieved with IFN plus ribavirin combination 456 and pegylated IFN plus ribavirin 78 therapies. However, over 50% of chronically infected patients still do not clear viremia. Moreover, HCV-infected patients who abuse alcohol have extremely low response rates to IFN therapy 9, but the mechanisms involved have not been clarified.MAPKs play essential roles in regulation of differentiation, cell growth, and responses to cytokines, chemokines and stress. The core element in MAPK signaling consists of a module of 3 kinases, named MKKK, MKK, and MAPK, which sequentially phosphorylate each other 10. Currently, four MAPK modules have been characterized in mammalian cells: Extracellular Regulated Kinases (ERK1 and 2), Stress activated/c-Jun N terminal kinase (SAPK/JNK), p38 MAP kinases, and ERK5 11. Interestingly, ethanol modulates MAPKs 12. However, information on how ethanol affects MAPKs in the context of innate antiviral pathways such as the Jak-Stat pathway in human cells is extremely limited. When IFN-alpha binds its receptor, two receptor associated tyrosine kinases, Tyk2 and Jak1 become activated by phosphorylation, and phosphorylate Stat1 and Stat2 on conserved tyrosine residues 13. Stat1 and Stat2 combine with the IRF-9 protein to form the transcription factor interferon stimulated gene factor 3 (ISGF-3), which binds to the interferon stimulated response element (ISRE), and induces transcription of IFN-alpha-induced genes (ISG). The ISGs mediate the antiviral effects of IFN. The transcriptional activities of Stats 1, 3, 4, 5a, and 5b are also regulated by serine phosphorylation 14. Phosphorylation of Stat1 on a conserved serine amino acid at position 727 (S727), results in maximal transcriptional activity of the ISGF-3 transcription factor complex 15. Although cross-talk between p38 MAPK and the Jak-Stat pathway is essential for IFN-induced ISRE transcription, p38 does not participate in IFN induction of Stat1 serine phosphorylation 1416171819. However, cellular stress responses induced by stimuli such as ultraviolet light do induce p38 MAPK mediated Stat1 S727 phosphorylation 18. In the current report, we postulated that alcohol and HCV proteins modulate MAPK and Jak-Stat pathways in human liver cells. To begin to address these issues, we characterized the interaction of acute ethanol on Jak-Stat and MAPK pathways in Huh7 cells, HCV replicon cells lines, and primary human hepatocytes.
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PMID:Effect of ethanol on innate antiviral pathways and HCV replication in human liver cells. 1632 17

The main goal for treatment of chronic hepatitis B is to prevent complications such as liver cirrhosis or hepatocellular carcinoma. Knowledge from population studies of the long-term risk of chronic HBV infection, as well as the recent introduction of pegylated interferon and additional nucleoside analogues has changed the therapeutic situation. Recently, a Swedish expert panel convened to update the national recommendations for treatment. The panel recommends treatment for patients with active HBV infection causing protracted liver inflammation or significant liver fibrosis, verified by liver histology. In general, pegylated interferon alpha-2a is recommended as first-line treatment, in particular for HBeAg-positive patients with HBV genotypes A or B. Among nucleoside analogues, entecavir is the first choice and adefovir or tenofovir can be used as alternatives. Lamivudine monotherapy is not recommended due to the high risk of resistance development. Combinations of nucleoside analogues such as tenofovir and lamivudine or emtricitabine are alternatives for patients with non-response or infection with resistant variants, or as first choice for patients with advanced liver disease. Nucleoside analogue treatment should be monitored to detect primary non-response and virological breakthrough. Special recommendations are given for HBV/HIV coinfected patients, immunosuppressed patients, children, and for treatment before and after liver transplantation. The present guideline is translated from Swedish, where it is published on the MPA and RAV websites (www.mpa.se and www.rav.nu.se) including 7 separate papers based on thorough literature search. The complete reference list can be received from the Medical Products Agency upon request.
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PMID:Treatment of chronic hepatitis B infection: an update of Swedish recommendations. 1858 30


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