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)

Perindopril has been studied in groups of normal young and elderly subjects, in patients with hepatic cirrhosis and in hypertensive patients. Plasma concentrations of perindoprilat are increased and renal clearance reduced in elderly subjects, resulting in an increase in the acute pharmacodynamic effect of perindopril. Compensated hepatic cirrhosis does not have any independent effect on the pharmacokinetics of perindopril. After intravenous administration, perindoprilat concentrations show multiexponential decay with a terminal half life of over 30 hours associated with sustained inhibition of ACE. During repeated dosing there is little accumulation of drug, and no evidence of increased haemodynamic effect after chronic treatment in hypertensives. The therapeutic consequences of these findings are: binding of perindoprilat to ACE prolongs the haemodynamic effect, giving the option of once daily administration; despite the long terminal elimination half life of the drug, significant accumulation is not a problem during chronic treatment; increased plasma concentrations of active metabolite in the elderly and reduced renal elimination may require reduced doses to be used; further dose adjustment in compensated hepatic cirrhosis is not routinely necessary.
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PMID:Pharmacokinetics of perindopril: therapeutic consequences. 250 11

1. Perindopril, a new ACE inhibitor, is a prodrug requiring conversion into its active form perindoprilat by hydrolysis in the liver. 2. The pharmacodynamics and pharmacokinetics of perindopril (8 mg oral) and perindoprilat (2 mg intravenously) were studied in a double-blind randomised crossover study in a group of patients with compensated biopsy-proven hepatic cirrhosis. 3. Blood pressure and heart rate responses were similar after the two routes of administration as were plasma renin activity and aldosterone levels following dosing. 4. The AUC of perindoprilat after oral administration of perindopril represented 46 +/- 4% of the total AUC of perindopril and its metabolite when expressed in molar terms. Comparison with the AUC of perindoprilat after its intravenous administration suggested that 30 +/- 6% of the oral dose of perindopril was converted to its active metabolite. 5. The findings are comparable with those in healthy subjects. It appears that the presence of relatively mild hepatic cirrhosis does not significantly alter the pharmacokinetics of perindopril.
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PMID:The pharmacokinetics and pharmacodynamics of perindopril in patients with hepatic cirrhosis. 255 45

Eleven patients with newly diagnosed Wilson's disease were treated with zinc acetate as their sole anticopper therapy. Treatment duration was 8 to 37 months. Three of the patients had symptoms; in eight who were presymptomatic, diagnosis was made because of affected siblings who had symptoms. All patients did well clinically. Copper absorption was suppressed, as reflected by blockade of absorption of orally administered copper 64. Values for 24-hour urine copper and nonceruloplasmin plasma copper (freely available copper) were reduced. Values for liver-derived serum enzymes were also generally reduced in patients who had pretreatment elevations. Percutaneous liver biopsies were done initially and repeated in seven of the patients after 12 to 35 months of zinc therapy. In five of these patients a second biopsy specimen showed higher levels of copper than the first. In three of these five a third biopsy 6 to 23 months after the second revealed liver copper values that either had returned to the baseline value or were lower. One patient's initial biopsy specimen showed active inflammation, which subsided with therapy. All of the biopsies revealed histologic scarring typical of cirrhosis, and this did not appear to change over the course of therapy. We conclude that hepatic copper may increase temporarily during early zinc therapy but that the accumulated copper is sequestered in a nontoxic form. On the basis of animal studies we postulate that this sequestered copper is primarily bound to the high levels of hepatic metallothionein induced by zinc. Zinc appears to be a reasonable option for the initial treatment of patients with Wilson's disease, particularly those with presymptomatic disease.
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PMID:Treatment of Wilson's disease with zinc. VI. Initial treatment studies. 259 53

Hypercalcemic crisis represents a medical emergency. If conservative treatment is ineffective, low calcium bath or zero calcium bath hemodialysis are good alternatives. We report 4 patients treated with calcium free acetate hemodialysis because of hypercalcemic crisis due to breast cancer, hepatocellular carcinoma, cirrhosis of the liver and immobilisation with hydrochlorothiazids' medication. Following 3 h of hemodialysis, serum calcium concentrations fell from a mean value of 3.96 (range 3.53-4.46) mmol/l to 2.71 (2.28-3.12) mmol/l. In 2 patients rapid clinical improvement was achieved and in one oliguric patient diuresis started spontaneously during hemodialysis. One patient died from gram-negative sepsis. In 3 cases the subsequent conservative treatment was sufficient to maintain serum calcium levels within the normal range. Together with the previously reported cases (5 patients treated by hemodialysis with low dialysate calcium and 3 patients by hemodialysis with calcium free dialysate) our experience indicates that hemodialysis is an effective and safe therapy for hypercalcemic crisis.
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PMID:Calcium free hemodialysis: an effective therapy in hypercalcemic crisis--report of 4 cases. 260 Feb 93

Perindopril has been studied in groups of normal young and elderly subjects, in patients with hepatic cirrhosis and in hypertensive patients. Plasma concentrations of perindoprilat are increased and renal clearance reduced in elderly subjects, resulting in an increase in the acute pharmacodynamic effect of perindopril. Compensated hepatic cirrhosis does not have any independent effect on the pharmacokinetics of perindopril. After intravenous administration, perindoprilat concentrations show multiexponential decay with a terminal half-life of over 30 hours, associated with sustained inhibition of ACE. During repeated dosing, there is little accumulation of the drug and no evidence of increased hemodynamic effect after chronic treatment in hypertensives. The therapeutic consequences of these findings are: (1) Binding of perindoprilat to ACE prolongs the hemodynamic effect, giving the option of once daily administration. (2) Despite the long terminal elimination half-life of the drug, significant accumulation is not a problem during chronic treatment. (3) Increased plasma concentrations of active metabolite in the elderly and reduced renal elimination may require reduced doses to be used. (4) Further dose adjustment in compensated hepatic cirrhosis is not routinely necessary.
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PMID:Pharmacokinetics of perindopril: therapeutic consequences. 260 99

We have used the gamma-glutamyltransferase (GGT) isoenzyme pattern in serum as a means for discriminating between hepatobiliary diseases, including neoplasias. The reference pattern, determined in 142 normal subjects with a simplified conventional cellulose acetate electrophoretic procedure, contained two GGT bands, alpha 1-GGT and alpha 2-GGT, in proportions of 60-80% and 20-40%, respectively. Sera from 95 hepatobiliary patients showed typical isoenzyme features: (a) a beta-migrating GGT form that was less than 10% of the total GGT in chronic hepatitis and cirrhosis, and less than or equal to 30% of the total GGT in cirrhosis with intrahepatic cholestasis and in cases of extra- and intrahepatic obstructive jaundice, including liver neoplasias; (b) a gamma-migrating GGT band and (or) a "dep-GGT" (nonmigrating) band in cases of extrahepatic jaundice; and (c) an albumin-migrating GGT band that had a diagnostic sensitivity of 75% for hepatic tumors. The diagnostic specificity of this last band is 92% toward other hepatic disorders and 91% toward nonhepatic neoplasias; we consider it a potential specific marker for primary or metastatic liver neoplasias.
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PMID:The gamma-glutamyltransferase isoenzyme pattern in serum as a signal discriminating between hepatobiliary diseases, including neoplasias. 289 71

If conservative treatment of hypercalcemic crises is ineffective, low calcium bath or zero calcium bath hemodialysis represent good alternatives. We report 5 patients (from 54 to 82 years old) treated with calcium free acetate hemodialysis because of hypercalcemic crises due to breast cancer with bone metastases, thiazids' medication and immobilisation, liver cirrhosis, hepatocellular carcinoma and hyperparathyroidism. By 3 hours' therapy calcium concentration could be reduced from a mean value of 3.74 mmol/l (3.13-4.46) to 2.47 mmol/l (1.38-3.12). In 3 cases rapid clinical improvement was achieved and in 4 cases the subsequent conservative therapy was sufficient to maintain serum calcium levels within reference range. In accordance to other investigators we consider hemodialysis as an effective method of low risk in hypercalcemic crises. Calcium rebound may occur in patients with hyperparathyrodism.
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PMID:[Calcium-free hemodialysis--value in therapy of hypercalcemic crisis]. 292 46

The effect of therapy with a microsomal enzyme-inducing drug on the cirrhotic liver in male Wistar rats was investigated by morphological and biochemical means. The cirrhotic animals were treated with medroxyprogesterone acetate (MPA) 100 mg/kg body wt, i.p. daily for a week. In the cirrhotic rats liver weight was enhanced, liver protein content was increased while total liver DNA content remained unchanged upon MPA treatment. The hepatic regenerative nodule size increased, as determined by morphological means. Hepatic microsomal metabolic activity was improved, as seen by increases in NADPH-cytochrome P-450 reductase and aminopyrine N-demethylase activities and cytochrome P-450 content. Since the increases in liver protein content and metabolic activity were relatively greater in the cirrhotic than intact animals upon MPA treatment, it was suggested that the spontaneous regeneration associated with liver cirrhosis may affect the induction phenomenon. The results demonstrate that an enzyme inducer may have beneficial effects on the cirrhotic liver by elevating metabolic activity and parenchymal mass.
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PMID:Treatment of liver cirrhosis with microsomal enzyme-inducing compound in the rat. 293 1

Part of the hyaluronic acid (HA) synthesized in peripheral tissues enters the blood circulation through the lymph. It is rapidly taken up by the endothelial cells in the liver (half-life in blood is 2.5-5.5 minutes) and degraded. Pure primary cultures of liver endothelial cells were obtained by a newly developed technique and used to follow the metabolism of the polysaccharide on the cell surface. At 37 degrees C the HA is effectively endocytosed and degraded to acetate and lactate. A radioassay specific for HA and sensitive in the nanogram range has been developed to follow the concentration of HA in serum. The normal level in man is 10 to 100 micrograms/l. Elevated serum levels of HA are seen in liver cirrhosis, rheumatoid arthritis and scleroderma indicating that both an impaired catabolism in the liver and an increased synthesis in the peripheral tissues can modify the HA level.
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PMID:The catabolic fate of hyaluronic acid. 294

The relaxation times of water protons in rat liver tissue were measured with a NMR spectrometer at 20 MHz. The paramagnetic trace elements Cu, Fe, and Mn were determined by neutron activation analysis. No shortening of T1 could be observed when liver Cu or Fe concentration was increased in the microgram range. T1 was strongly correlated with the liver Mn concentration of untreated animals and animals whose liver Mn concentration was artificially increased or decreased by intravenous injection of manganous acetate or a metal chelating agent with high affinity for hepatobiliary excretion. Deviations from this Mn-T1 correlation were found in the initial phase of liver cirrhosis induced by thioacetamide (elongated T1, normal Mn concentration) and after stimulation of liver growth by phenobarbital (normal T1, decreased Mn concentration). An increased or decreased enhancement factor for Mn may have contributed to the observed deviations during phenobarbital and thioacetamide treatment.
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PMID:Contribution of paramagnetic trace elements to the spin-lattice relaxation time in the liver. 299 26


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