Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma cyclic AMP concentration during glucagon infusion at various time intervals was determined in 8 normal subjects, 9 patients with extrahepatic obstructive jaundice and 10 patients with cholestatic hepatitis (hepatitis A and B). Plasma cyclic AMP concentrations (pmol/ml) during glucagon infusion in patients with both obstructive jaundice and cholestatic hepatitis were found to be greater than those in control subjects. In addition, a significant difference in plasma cyclic AMP concentrations was found between patients with cholestatic hepatitis and obstructive jaundice at the 10th minute of glucagon infusion. These results indicate that plasma cyclic AMP levels at the 10th minute of glucagon infusion represent a reliable diagnostic index of cholestatic jaundice.
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PMID:Effect of glucagon infusion on plasma cyclic AMP in patients with cholestatic hepatitis and obstructive jaundice. New test of hepatic cholestasis. 19 91

The 2'-fluorinated arabinosyl-pyrimidine nucleosides, 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC) and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methyluracil (FMAU), are new antiviral compounds with in vitro inhibitory activity against the DNA polymerase of hepadnaviruses. Those compounds also induced permanent inhibition of viral replication in woodchucks chronically infected by woodchuck hepatitis virus. The effects of these antiviral compounds were assessed in ducks chronically infected by duck hepatitis B virus (DHBV). Following intraperitoneal administration for 5 days, FMAU (2 mg/kg/day) and FIAC (10 mg/kg/day) induced a transient decrease in DHBV replication, as shown by the decrease in both the serum and liver DHBV DNA level. After stopping therapy, DHBV replication rebounded immediately to the pretreatment level. The supercoiled form of liver viral DNA was found to be less affected by the therapy. By contrast, no obvious antiviral effect was observed with vidarabine monophosphate (ara-AMP) (80 mg/kg/day) therapy. No sign of toxicity was observed during the course of the treatment. These preliminary results confirmed in the DHBV model the higher efficacy of FIAC and FMAU as compared to ara-AMP. Pharmacokinetic studies are needed to explain the differences observed in viral replication in these 2 models of HBV infection.
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PMID:Effects of 2'-fluorinated arabinosyl-pyrimidine nucleosides on duck hepatitis B virus DNA level in serum and liver of chronically infected ducks. 162 11

Corticosteroid metabolism in the liver and the level of c-AMP in the liver and spleen of rats with experimental toxic hepatitis were investigated after splenin administration. Hydrocortisone metabolites were isolated by a method of two-dimensional thin-layer chromatography. It was shown that their production and the level of c-AMP in the liver and spleen after simulation of experimental hepatitis were considerably reduced. The administration of this drug returned the indices under study to normal. The results obtained demonstrated that humoral factors could produce protective action in toxic liver lesion.
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PMID:[The effect of splenic humoral factors on corticosteroid metabolism and the cAMP content in the liver of rats with experimental toxic hepatitis]. 215 58

With the aim of improving the chemotherapeutic index of 9-beta-D-arabinofuranosyl-adenine 5' monophosphate (ara-AMP) in the treatment of chronic hepatitis B, this drug was conjugated with lactosaminated serum albumin (L-SA), a neoglycoprotein which only enters into hepatocytes. We used a L-SA-ara-AMP conjugate which, in contrast to those previously employed, has the advantage of remaining soluble after lyophilization. We found in mice that: (I) this new conjugate was quite stable in the bloodstream where only a small part of ara-AMP was released; (II) after administration of the conjugate labelled in the drug moiety both acid insoluble and soluble radioactivities were several times higher in liver than in other organs; (III) in mice with Ectromelia virus hepatitis, the conjugate inhibited virus DNA synthesis in liver without affecting cellular DNA synthesis in intestine and bone marrow; (IV) the conjugate did not display any recognizable sign of acute toxicity even at doses several fold higher than those pharmacologically active; and (V) when prepared with homologous albumin it was not immunogenic.
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PMID:Drug targeting in antiviral chemotherapy. A chemically stable conjugate of 9-beta-D-arabinofuranosyl-adenine 5'-monophosphate with lactosaminated albumin accomplishes a selective delivery of the drug to liver cells. 242 Mar 34

The correlation of collagen metabolism to liver contents of cyclic AMP and GMP as well as blood level of hormones was investigated in 105 patients with chronic hepatitis and liver cirrhosis. In patients with active hepatitis and cirrhosis showing the highest intensity of collagen metabolism there appeared elevated levels of cyclic AMP, somatotropic hormone and insulin against low levels of hydrocortisone and thyroxin. The relations between characteristics of plasma protein-bound oxyproline (PBOP), circadian oxyprolinuria and regulatory mechanisms under study suggest a competitive control of hepatic connective tissue metabolism maintained by hormones via cyclase systems. In high levels of blood PBOP and low ones of hydrocortisone, glucocorticoids unlike D-penicillamine promoted inhibition of liver collagen synthesis.
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PMID:[Various characteristics of collagen metabolism in patients with chronic diseases of the liver]. 262 62

Levels of plasma cyclic AMP, serum immunoreactive insulin (IRI), serum c-peptide immunoreactivity (CPR) and blood sugar (BS) were determined 0, 15, 30, 45 and 60 min after a glucagon injection (0.01 mg per kg body weight) in normal controls, patients with acute hepatitis and liver cirrhosis. Plasma cyclic AMP responses to glucagon in liver disease patients varied widely in peak value, and only in patients with fulminant hepatitis and decompensated liver cirrhosis with poor prognosis was the response suppressed. The peak response of BS was found significantly later in liver cirrhosis patients than in normal controls. IRI and CPR responses to glucagon were lower in acute hepatitis patients than in normal controls and liver cirrhosis patients. IRI levels and their sum were also lower in acute hepatitis patients, although CPR levels were not significantly different. Thus, the ratio of the sum of CPR from 0 to 60 min to that of IRI was significantly higher in acute hepatitis, indicating impaired pancreatic secretion of insulin to glucagon stimulation as well as increased uptake of insulin by the liver in acute hepatitis.
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PMID:Responses of plasma cyclic AMP, serum immunoreactive insulin, C-peptide immunoreactivity and blood sugar levels to glucagon in patients with liver diseases. 300 Jan 42

With the aim of improving the chemotherapeutic index of adenine arabinoside 5-monophosphate (ara-AMP) in the treatment of chronic hepatitis B, this drug was conjugated with lactosaminated serum albumin (L-SA), a neoglycoprotein which only enters into hepatocytes where it is digested in lysosomes. In mice, the L-[3H]SA-ara-AMP conjugates, intravenously injected, selectively penetrated the liver, only small quantities were taken up by cells of spleen, bone marrow, intestine, and brain. After administration of the conjugate to mice with Ectromelia virus hepatitis, ara-AMP was selectively concentrated in liver in a pharmacologically active form. If L-SA-ara-AMP conjugates behave in man as in mouse, their administration to patients with chronic hepatitis B should result in a selective concentration of ara-AMP in liver with a more efficient inhibition of virus replication accompanied by lower toxicity for other tissues.
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PMID:Selective penetration and pharmacological activity of lactosaminated albumin conjugates of adenine arabinoside 5-monophosphate (ara-AMP) in mouse liver. 621 Feb 32

Following an intravenous bolus of 1 mg glucagon plasma level time profiles of glucagon, cyclic AMP and glucose were monitored for two hours in 6 healthy adult volunteers, 6 patients with decompensated cirrhosis, 6 patients with acute viral hepatitis and at recovery, 6 patients with extrahepatic and 4 patients with intrahepatic cholestasis. Elimination half-livers of glucagon (controls = 22.5 +/- 5.6 min) were significantly prolonged in patients with cirrhosis (52.2 +/- 30.8 min) amd acute hepatitis (58.6 +/- 26.3 min). The glucagon - induced rise in cyclic AMP was similar in all subjects but independent of the phase of the hepatitis (acute or recovery) maximal cyclic AMP values were significantly higher in those patients compared to controls. In contrast glucose response was much lower (p less than 0.001) in patients with hepatitis (acute and recovery). All measured parameters, demonstrated considerable individual variations and a large overlap between the different groups of subjects. Therefore it is concluded that these observations negate the diagnostic and functional usefulness of the glucagon test as a predictive liver function index.
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PMID:Glucagon-induced alterations of plasma levels of cyclic AMP and glucose in patients with liver disease. 632 1

In order to obtain hepatotropic conjugates of antiviral drugs suitable for intramuscular administration, three nucleoside analogs (adenine arabinoside monophosphate, ribavirin and azidothymidine) were coupled to a high molecular mass lactosaminated poly-L-lysine. The conjugates had a high molar ratio drug/conjugate and after intramuscular administration to mice, were selectively taken up by the liver and eliminated by the kidney only in minute quantities. The high molar ratio and low renal elimination are important properties not possessed by conjugates previously prepared by using a small molecular mass lactosaminated poly-L-lysine. The conjugate with adenine arabinoside monophosphate (ara-AMP) was found to be devoid of acute toxicity for mice and in spite of its high molecular dimension (Mn = ca. 72,500) did not induce antibodies in this animal after repeated intramuscular injections. This conjugate could have two advantages over a similar complex of ara-AMP with lactosaminated human albumin currently under clinical trials for the treatment of chronic type B hepatitis which must be injected intravenously: it might provide better patient compliance since it is injectable intramuscularly and could introduce larger amounts of ara-AMP into hepatocytes due to its higher drug/carrier molar ratio.
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PMID:Selective delivery to the liver of antiviral nucleoside analogs coupled to a high molecular mass lactosaminated poly-L-lysine and administered to mice by intramuscular route. 754 Dec 3

The 2',3'-cyclic phosphate termini are produced, as either intermediates or final products, during RNA cleavage by many different endoribonucleases. Likewise, ribozymes such as hammerheads, hairpins, or the hepatitis delta ribozyme, generate 2',3'-cyclic phosphate ends. Discovery of the RNA 3'-terminal phosphate cyclase has indicated that cyclic phosphate termini in RNA can also be produced by an entirely different mechanism. The RNA 3'-phosphate cyclase converts the 3'-terminal phosphate in RNA into the 2',3'-cyclic phosphodiester in the ATP-dependent reaction which involves formation of the covalent cyclase-AMP and the RNA-N3' pp5' A intermediates. The findings that several eukaryotic and prokaryotic RNA ligases require the 2',3'-cyclic phosphate for the ligation of RNA molecules raised a possibility that the RNA 3'-phosphate cyclase may have an anabolic function in RNA metabolism by generating terminal cyclic groups required for ligation. Recent cloning of a cDNA encoding the human cyclase indicated that genes encoding cyclase-like proteins are conserved among Eucarya, Bacteria, and Archaea. The protein encoded by the Escherichia coli gene was overexpressed and shown to have the RNA 3'-phosphate cyclase activity. This article reviews properties of the human and bacterial cyclases, their mechanism of action and substrate specificity. Possible biological functions of the enzymes are also discussed.
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PMID:Cyclases of the 3'-terminal phosphate in RNA: a new family of RNA processing enzymes conserved in eucarya, bacteria and archaea. 1039 37


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