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

The pathogenic profiles of two heterologous animal rotaviruses, rhesus rotavirus strain MMU 18006 and bovine rotavirus strain WC3, were evaluated in mice with severe combined immunodeficiency (SCID mice) and normal BALB/c mice. Control animals were inoculated with homologous murine strain EDIM 5099 or a tissue culture-adapted murine rotavirus. Heterologous infection with rhesus rotavirus resulted in hepatitis in 84% of SCID and 21% of BALB/c mice, with mortality rates of 27 and 0%, respectively. Surviving SCID animals developed chronic liver disease, while symptoms in BALB/c mice resolved in 2 to 4 weeks after onset. Histopathologic examination revealed a diffuse hepatitis with focal areas of parenchymal necrosis. Rotavirus was detected in liver tissue from 100% of 29 SCID and 85% (11 of 13) BALB/c animals tested by cell culture infectivity, immunofluorescence, or electron microscopy. No extramucosal spread of virus or hepatitis was observed after infection with heterologous bovine strain WC3 or homologous murine rotaviruses. This finding of a novel rotavirus-induced disease manifestation suggests altered tissue tropism in a heterologous host for a group of viruses previously shown to replicate exclusively in the gut mucosa. The implications of our observations suggest that in human vaccine trials utilizing heterologous rotavirus strains, special attention should be paid to children with immunodeficiency disorders, and screening for hepatic function should be included in vaccine protocols.
 ...
PMID:Extramucosal spread and development of hepatitis in immunodeficient and normal mice infected with rhesus rotavirus. 215 22

Quinidine, procainamide and disopyramide are antiarrhythmic drugs in the class 1A category. These drugs have a low toxic to therapeutic ratio, and their use is associated with a number of serious adverse effects during long term therapy and life-threatening sequelae following acute overdose. Class 1A agents inhibit the fast inward sodium current and decrease the maximum rate of rise and amplitude of the cardiac action potential. Prolonged Q-T interval and, to a lesser extent, QRS duration may be observed at therapeutic concentrations of quinidine. With increasing plasma concentrations, progressive depression of automaticity and conduction velocity occur. 'Quinidine syncope' (a transient loss of consciousness due to paroxysmal ventricular tachycardia, frequently of the torsade de pointes type) occurs with therapeutic dosing, often in the first few days of therapy. Extracardiac adverse effects of quinidine include potentially intolerable gastrointestinal effects and hypersensitivity reactions such as fever, rash, blood dyscrasias and hepatitis. Procainamide produces electrophysiological changes that are similar to those of quinidine, although Q-T interval prolongation with the former is less pronounced at therapeutic concentrations. Hypersensitivity reactions including fever, rash and (more seriously) agranulocytosis are associated with procainamide, and a frequent adverse effect requiring cessation of therapy is the development of systemic lupus erythematosus. Of the 3 drugs, disopyramide has the most pronounced negative inotropic effects, which are especially significant in patients with pre-existing left ventricular dysfunction. As with quinidine, unexpected 'disopyramide syncope' at therapeutic concentrations has been described. Anticholinergic side effects are common with this drug and may require cessation of therapy. Disopyramide therapy may unpredictably induce severe hypoglycaemia. Severe intoxication with the class 1A agents may result from acute accidental or intentional overdose, or from accumulation of the drugs during long term therapy. Acute overdose can result in severe disturbances of cardiac conduction and hypotension, frequently accompanied by central nervous system toxicity. Decreased renal function can cause significant accumulation of procainamide and its active metabolite acecainide (N-acetyl-procainamide), resulting in severe intoxication. Mild to moderate renal dysfunction is less likely to lead to quinidine or disopyramide intoxication, unless renal failure is severe or concurrent hepatic dysfunction is present. Management of acute intoxication with class 1A drugs includes gut decontamination with provision of respiratory support and treatment of seizures as needed. Hypertonic sodium bicarbonate, by antagonising the inhibitory effect of quinidine on sodium conductance, may reverse many or all manifestations of cardiovascular toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Poisoning due to class IA antiarrhythmic drugs. Quinidine, procainamide and disopyramide. 228 95

Two physiologically based pharmacokinetic models A and B incorporating enterohepatic recycling, which succeeded previously in predicting the disposition of glycyrrhizin (GLZ) in normal rats and subjects, were applied to predict GLZ disposition in plasma and tissues of chronically CCl4-intoxicated rats, and serum of humans with hepatitis after i.v. dosing. The prediction by model A with the direct excretion of GLZ from liver into gut lumen gave fairly good agreement with the observed time courses of GLZ concentrations in blood and tissues in the intoxicated rats. The human serum disposition was predicted by model B, to which was added a gallbladder for the excretion from liver into gut lumen to model A by assuming continuous delaying transfer from the gallbladder. An attempt to predict the serum dispositions in five human subjects by considering individual differences in serum free fraction, biliary excretion ratio, and intestinal absorption clearance was successful in model B. Thus, scale-up of the disposition kinetics of GLZ from rat to man with liver failure was successful.
 ...
PMID:Prediction of glycyrrhizin disposition in rat and man with liver failure by a physiologically based pharmacokinetic model. 238 51

Suckling BALB-c mice, subjected to nutritional deprivation in artificially expanded litters (18 to 20 pups), were compared to normally nourished pups (7-9 per litter) in a series of experiments designed to provide data on morphologic and functional alterations of the small intestine during malnutrition and infection. The effects of protein calorie malnutrition (PCM) on the viral replication pattern and severity of clinical disease were examined in suckling mice infected with murine rotavirus (MRV). The infection in nutritionally deprived animals was characterized by a significant decrease in the minimal infectious dose and in the incubation period for the onset of diarrhea as well as increased severity of disease when compared to well nourished controls. Rotavirus-specific antibody, administered orally prior to virus inoculation, significantly reduced MRV replication in both groups but most strikingly in malnourished animals. Additional studies of the uptake of a macromolecule [ovalbumin (OVA)] following oral administration to experimental and control groups showed more rapid and complete absorption in the malnourished animals. Infection further enhanced the uptake of OVA, suggesting that both PCM and rotavirus infection alter the permeability of the small intestine. An unexpected observation of rotavirus-associated hepatitis in CB-17scid mice was also made in nearly 40% of malnourished mice inoculated with 10(6) PFU of Rhesus rotavirus (RRV). Mice with PCM exhibited a susceptibility to hepatitis between SCID mice (80%) and immunologically normal mice (18%). While these data are not sufficient to confirm a nutritionally-mediated immunoincompetence, they do suggest that either loss of immune competence and/or increased gut permeability in malnourished animals may allow a more severe homologous rotavirus infection as well as extraintestinal spread of heterologous rotavirus.
 ...
PMID:Effect of nutritional deprivation on mucosal viral infections. 254 24

The duration of challenge resistance in mice immunized with mouse hepatitis virus (MHV) strain JHM was examined as a model of immunity to corona-virus infection. Genetically susceptible BALB/cByJ mice were immunized by intranasal (i.n.) or per os (p.o.) inoculation with MHV-JHM or sterile tissue culture fluid (sham) then challenged i.n. with MHV-JHM or sterile tissue culture fluid 1, 6, or 12 months later. Four days after challenge, virus in nasal turbinates and liver was quantified, and prevalence of microscopic lesions in liver and gut-associated lymphoid tissue was tabulated as indices of challenge resistance. MHV-immunized and challenged groups were compared to sham-immunized and challenged groups. Mice immunized by i.n. inoculation were strongly resistant to challenge at 1, 6, and 12 months. Mice immunized by p.o. inoculation were resistant at 1 month, but became partially susceptible to reinfection at 6 and 12 months, based upon all indices. These data indicate that, depending upon route of immunization, mice can become susceptible to reinfection with the same coronavirus strain over time.
 ...
PMID:Duration of challenge immunity to coronavirus JHM in mice. 255 52

Subacute fascioliasis was diagnosed by pathomorphological and parasitological investigations on 13 dead moufflons (Ovis ammon musimon) from a herd of 21 animals (mortality 62%) which had succumbed between January and April 1988. The flock had been kept on meadow in the so-called Leipziger Auenwald. The main findings like severe hepatitis traumatica fasciolosa, fibrinous and fibrous perihepatitis, chronic interstitial hepatitis (pseudocirrhosis), cholangitis fasciolosa (X 13), wasting (X 8), heart dilatation (X 10), lung oedema (X 12), anemia (X 5), ascites (X 3), gut oedema (X 3) and occasionally observed lesions are described in detail and discussed with regard to diagnosis and pathogenicity. Beside severe infection with Fasciola hepatica (juvenile and adult flukes) the parasitological investigation demonstrated, in some cases, various additional but unimportant infections with protostrongylids, gastro-intestinal nematodes, coccidia (X 2) and Moniezia expansa (X 1). The analysis of meteorological data (January 1987 till March 1988) established optimal conditions for F. hepatica development stages and Galba truncatula so that high multiplication and infection rates of the snails and long surviving of metacercariae must be assumed.
 ...
PMID:[Fascioliasis in moufflons]. 278 70

Infectious mononucleosis, a systemic illness caused by the Epstein-Barr virus, is seen frequently by primary care physicians. Mononucleosis affects several organ systems, and, within the abdomen, there can be splenic involvement, hepatitis, mesenteric lymphadenopathy, hyperplasia of gut-associated lymphoid tissue, pancreatitis, and transient malabsorption. Life-threatening abdominal complications require prompt recognition and intervention. Other abdominal complications, though worrisome, are usually short-lived and resolve without sequelae.
 ...
PMID:Abdominal complications of infectious mononucleosis. 305 95

Sarcocystosis was studied in 37 sheep after oral inoculation with 10(4)-5 x 10(7) sporocysts of Sarcocystis tenella from canine feces. Two sheep inoculated with 2.5 x 10(7) and 5 x 10(7) sporocysts became moribund 16 and 19 days post-inoculation (DPI), respectively, due to occlusion of arteries of gut and mesentery by first generation meronts. Sheep inoculated with 10(7) sporocysts remained clinically normal until 21 DPI and those inoculated with 10(5)-10(6) became ill 24-28 DPI due to anemia coincident with maturation of second generation meronts. Inflammation, hepatitis and myocarditis were the main lesions of acute and subacute ovine sarcocystosis. Inflammation began to subside by the time (75 DPI) sarcocysts matured. Sarcocystis-induced encephalitis was distinguished from naturally occurring myelomalacia in sheep caused by an unidentified sporozoan.
 ...
PMID:Lesions in sheep inoculated with Sarcocystis tenella sporocysts from canine feces. 312 99

Transgenic mouse lineages were established that carry the normal (M) or mutant (Z) alleles of the human alpha 1-antitrypsin (alpha 1-Pi) gene. All of the alpha 1-Pi transgenic mice expressed the human protein in the liver, cartilage, gut, kidneys, lymphoid macrophages, and thymus. The human M-allele protein was secreted normally into the serum. However, the human Z-allele protein accumulated in several cell types, but particularly in hepatocytes, and was found in serum in tenfold lower concentrations than the M-allele protein. Mice in one lineage carrying the mutant Z allele expressed high levels of human alpha 1-Pi RNA and displayed significant runting (50% of normal weight) in the neonatal period. This lineage was found to have alpha 1-Pi-induced liver pathology in the neonatal period, concomitant with the accumulation of human Z protein in diastase-resistant cytoplasmic globules that could be revealed in the Periodic acid-Schiff reaction (PAS). The phenotype of mice in the strain expressing high levels of the Z allele is remarkably similar to human neonatal hepatitis, and this strain may prove to be a useful animal model for studying this disease.
 ...
PMID:Neonatal hepatitis induced by alpha 1-antitrypsin: a transgenic mouse model. 326 19

The antiviral drug, acyclovir, has been used in the treatment of chronic type B hepatitis. High serum concentrations of acyclovir are required to achieve inhibition of hepatitis B viral replication. Because only 15 to 20% of an oral dose is absorbed, it is necessary to administer acyclovir by intravenous infusion. 6-Deoxyacyclovir, an analog of acyclovir, is well absorbed when given orally, and is converted to acyclovir by xanthine oxidase which is present in the gut and liver. This study has examined the hepatic disposition of 6-deoxyacyclovir in a 100 ml recirculating (12 ml per min) perfused rat liver system. Following administration of a bolus dose of 5 mumoles 6-deoxyacyclovir to the reservoir, perfusate concentrations of 6-deoxyacyclovir declined monoexponentially, as the metabolite acyclovir appeared in the perfusate. Addition of the xanthine oxidase inhibitor allopurinol (5 mg) to the perfusate reservoir prior to the administration of 6-deoxyacyclovir resulted in impaired hepatic metabolism of 6-deoxyacyclovir, as demonstrated by a 47% reduction in systemic clearance rate (4.5 +/- 0.4 to 2.4 +/- 0.9 ml per min; p less than 0.05) (mean +/- S.E., n = 6) and a 1.8-fold increase in terminal elimination half-life of 6-deoxyacyclovir (23.5 +/- 2.7 to 42.7 +/- 4.1 min; p less than 0.05), accompanied by a 30% reduction in appearance of acyclovir. The efficient hepatic conversion of 6-deoxyacyclovir to the active antiviral drug, acyclovir, provides a rationale for trials of oral 6-deoxyacyclovir in the treatment of chronic type B hepatitis.
 ...
PMID:The disposition of 6-deoxyacyclovir, a xanthine oxidase-activated prodrug of acyclovir, in the isolated perfused rat liver. 355 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>