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)

An epizootic of fatal diarrhea occurred in mice which were approximately 10 days of age. The enteric lesions were similar to those reported in lethal intestinal virus of infant mice, but many diseased mice also had necrotic hepatitis. Mouse hepatitis virus antigen was demonstrated in the affected intestine and liver, and a virus that produced syncitium formation in mouse brain tumor cell culture was isolated from the intestines, livers, and brains. The virus was capable of producing intestinal and hepatic lesions similar to the naturally occurring disease after inoculation into suckling mice. Electron microscopy revealed viral particles within affected intestinal epithelial cells of the inoculated mice.
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PMID:Isolation of mouse hepatitis virus from infant mice with fatal diarrhea. 21 Mar 27

Five patients with documented recurrences of glioblastoma multiforme were given continuous infusions of methotrexate delivered intratumorally using implantable catheters and subcutaneous refillable pumps. A continuous infusion of methotrexate (1 mg/d) was begun with concomitant oral administration of folinic acid. The methotrexate dose was increased every 2 weeks to 3, 10, 30, and, ultimately, 75 mg/d in two patients. Samples of serum and ventricular cerebrospinal fluid (CSF) were obtained to determine the levels of methotrexate and total bioactive folates, and brain tissue was obtained from two patients for determination of methotrexate concentration. The patients survived from 7 to 49 weeks after the implantation of the infusion device. Neither the clinical examination nor sequential radiological studies gave clear evidence of reduction in tumor size. Pneumonia developed in one patient, and mild hepatitis and increased seizure frequency in another. Methotrexate was stable in the delivery system over 12 days, and ventricular CSF reached steady-state levels by 5 days. Steady-state ventricular CSF levels of methotrexate were higher than serum levels in some patients, while the reverse was true in others. Levels of total bioactive folates in the CSF did not increase above the normal range. Methotrexate concentrations were highest at the center of the tumor, but measurable amounts of methotrexate were detectable in all areas of the brain. At autopsy in four patients, variable liquefactive necrosis of the brain tumors was seen, and viable tumor was found at the periphery of the tumor bed. These preliminary results suggest that it is technically feasible to infuse methotrexate into brain tumor cavities, and show that little central nervous system or systemic toxicity was encountered in five patients. Better delineation of the safety and efficacy of this therapeutic approach will require further clinical trials.
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PMID:Continuous intratumoral infusion of methotrexate for recurrent glioblastoma: a pilot study. 165 12

The case presented documents HSV hepatitis in a 41 year old caucasian male with a history of prolonged steroid treatment and recent irradiation for brain tumor recurrence. The fulminant nature of the hepatitis, accompanied by gastric ulcer hemorrhage, lead to his death within 24 hours of symptomatic manifestation. The diagnosis of HSV hepatitis was made postmortem. The etiology of the hepatitis was established by light microscopic identification of Cowdry type A intranuclear inclusion bodies, electron microscopic identification of virus particles, and the immunohistochemical detection of herpes simplex virus antigens.
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PMID:A case of fulminant herpes simplex hepatitis in an adult. 609 88

The stems of Bougainvillea spectabillis Wild (Nyctaginaceae) have been used in folk medicine for hepatis, and spinasterol and quercetin were isolated and characterized from the plant leaves in this study. These constituents have not been previously isolated from Bougainvillea spectabillis W. Quercetin, the flavonoid, was found as active principle because it showed a strong activity on xanthine oxidase inhibition (IC50 = 7.23 microM) in this study as well as in the literature. Since xanthine oxidase serum levels are increased in hepatitis and tumoral brain tissues, quercetin may be used for remission of hepatitis or brain tumor. In order to study the structure-activity relationship of the flavonoids as regards xanthine oxidase inhibition, nine naturally occurring flavonoids have been tested the inhibitory effects on xanthine oxidase, such as baicalein, baicalin, capillarisin, d-catechin, d-epicatechin, hesperidin, liquiritin, puerarin and wogonin. The results showed that baicalein displayed the strongest activity (IC50 = 9.44 microM), followed by wogonin (IC50 = 52.46 microM) and then baicalin (IC50 = 71.73 microns). Baicalein induced uncompetitive inhibition of the enzyme with respect to xanhtine and the apparent inhibition constant (Ki) was 2.48 x 10(-6) M.
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PMID:Inhibitory effects of flavonoids on xanthine oxidase. 829 30

Persistent infection with mouse hepatitis virus (MHV) strain A59 in murine DBT (delayed brain tumor) cells resulted in the emergence of host range variants, designated V51A and V51B, at 210 days postinfection. These host range mutants replicated efficiently in normally nonpermissive Chinese hamster ovary (CHO), in human hepatocarcinoma (HepG2), and to a lesser extent in human breast carcinoma (MCF7) cell lines. Little if any replication was noted in baby hamster kidney (BHK), green African monkey kidney (COS-7), feline kidney (CRFK), and swine testicular (ST) cell lines. By fluorescent antibody (FA) staining, persistent viruses V10B and V30B, isolated at days 38 and 119 days postinfection, also demonstrated very low levels of replication in human HepG2 cells. These data suggest that persistence may rapidly select for host range expansion of animal viruses. Pretreatment of HepG2 cells with a polyclonal antibody directed against human carcinoembryonic antigens (CEA) or with some monoclonal antibodies (Col-1, Col-4, Col-12, and Col-14) that bind human CEA significantly inhibited V51B infection. Under identical conditions, little or no blockade was evident with other monoclonal antibodies (kat4c or Col-6) which also bind the human CEA glycoproteins. In addition, an antibody (EDDA) directed against irrelevant antigens did not block V51B replication. Pretreatment with the Col-4 and Col-14 antibodies did not block Sindbis virus replication in HepG2 cells or MHV infection in DBT cells, suggesting that one or more CEA glycoproteins likely functioned as receptors for V51B entry into human cell lines. To test this hypothesis, the human biliary glycoprotein (Bgp) and CEA genes were cloned and expressed in normally nonpermissive BHK cell lines by using noncytopathic Sindbis virus replicons (pSinRep19). By growth curves and FA staining, human CEA and to a much lesser extent human Bgp functioned as receptors for V51B entry. Furthermore, V51B replication was blocked with polyclonal antiserum directed against human CEA and Bgp. Under identical conditions, the parental MHV strain A59 failed to replicate in BHK cells expressing human Bgp or CEA. These data suggest that MHV persistence may promote virus cross-species transmissibility by selecting for virus variants that recognize phylogenetic homologues of the normal receptor.
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PMID:Persistent infection promotes cross-species transmissibility of mouse hepatitis virus. 984 69

Xanthine oxidase inhibitors are known to be therapeutically useful for the treatment of hepatitis and brain tumor. Baicalein, baicalin and wogonin, isolated from Scutellaria rivularis, have been reported to exhibit a strong activity on xanthine oxidase inhibition. In this study, their antioxidant activity was evaluated by modified xanthine oxidase inhibition and cytochrome c reduced methods. The results showed that the order of activity on xanthine oxidase inhibition was baicalein > wogonin > baicalin, IC50 = 3.12, 157.38 and 215.19 microM, respectively, whereas the activity on cytochrome c reduction was baicalin > wogonin > baicalein (IC50 = 224.12, 300.10 and 370.33 microM, respectively). In another study, an electron spin resonance (ESR) technique was used to further confirm the direct free radical scavenging activity. Both baicalein and baicalin demonstrated a strong activity on eliminating the superoxide radical (.O2-) (baicalein: 7.31 x 10(4) u/g; baicalin: 1.19 x 10(5) u/g). The IC50 of baicalein was 2.8 fold higher than that of baicalin. However they had no significant effect on scavenging hydroxyl radical (.OH). The present results demonstrated that baicalein and baicalin posed a different pathological pathway. The antioxidant function of baicalin was mainly based on scavenging superoxide radical whilst baicalein was a good xanthine oxidase inhibitor.
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PMID:Antioxidant and free radical scavenging effects of baicalein, baicalin and wogonin. 1106 94

The coronavirus mouse hepatitis virus (MHV) directs the synthesis of viral RNA on discrete membranous complexes that are distributed throughout the cell cytoplasm. These putative replication complexes are composed of intimately associated but biochemically distinct membrane populations, each of which contains proteins processed from the replicase (gene 1) polyprotein. Specifically, one membrane population contains the gene 1 proteins p65 and p1a-22, while the other contains the gene 1 proteins p28 and helicase, as well as the structural nucleocapsid (N) protein and newly synthesized viral RNA. In this study, immunofluorescence confocal microscopy was used to define the relationship of the membrane populations comprising the putative replication complexes at different times of infection in MHV-A59-infected delayed brain tumor cells. At 5.5 h postinfection (p.i.) the membranes containing N and helicase colocalized with the membranes containing p1a-22/p65 at foci distinct from sites of M accumulation. By 8 to 12 h p.i., however, the membranes containing helicase and N had a predominantly perinuclear distribution and colocalized with M. In contrast, the p1a-22/p65-containing membranes retained a peripheral, punctate distribution at all times of infection and did not colocalize with M. By late times of infection, helicase, N, and M each also colocalized with ERGIC p53, a specific marker for the endoplasmic reticulum-Golgi-intermediate compartment. These data demonstrated that the putative replication complexes separated into component membranes that relocalized during the course of infection. These results suggest that the membrane populations within the MHV replication complex serve distinct functions both in RNA synthesis and in delivery of replication products to sites of virus assembly.
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PMID:Mouse hepatitis virus replicase protein complexes are translocated to sites of M protein accumulation in the ERGIC at late times of infection. 1141 2

Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults. Its established first-line adjuvant treatment is radiotherapy in combination with temozolomide (TZM). Hematotoxicity is listed as a frequent adverse drug reaction in the US prescribing information and hepatotoxicity has been reported infrequently in the postmarketing period. We here present the case of a patient diagnosed with GBM who developed severe sustained cholestatic hepatitis following treatment with TZM. The cholestasis was not reversible after withdrawal of TZM during 6 months before the patient's death. Another 2 published case reports of sustained cholestasis following TZM treatment were identified; however, the sustained nature of cholestasis was not emphasized in these reports. Sixteen cases of cholestatic hepatitis/cholestasis associated with TZM were identified in the FDA spontaneous reporting system between 2007 and 2010. Information on the course of the cholestasis in these cases could not be retrieved. In the literature there are other published reports of hepatotoxicity associated with TZM that have reported reversibility upon withdrawal of the drug. Thus, TZM appears to cause different types of hepatotoxicity. Particular attention should be paid to sustained cholestasis as a very serious type of TZM-associated liver toxicity.
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PMID:Severe sustained cholestatic hepatitis following temozolomide in a patient with glioblastoma multiforme: case study and review of data from the FDA adverse event reporting system. 2239 96

Liver cirrhosis, a devastating liver fibrosis caused by hepatitis/inflammation or tumors, is a major comorbid factor in known surgery fields, such as cardiovascular and abdominal surgeries. It is important to review possible comorbid results in neurosurgical procedures in cirrhotic patients. In the reviewed literature, Child-Pugh and model for end-stage liver disease scores are commonly used in the assessment of surgical risks for cirrhotic patients undergoing abdominal, cardiovascular or neurosurgical procedures. The major categories of neurosurgery are traumatic brain injury (TBI), spontaneous intracranial hemorrhage (SICH), brain tumors, and spinal instrumentation procedures. TBI was reported with surgical mortality as high as 34.5% and a complication rate of 87.2%. For SICH, mortality ranged from 22.7% to 47.0%, while complications were reported to be 43.2%. Less is discussed in brain tumor patients; still the postoperative hemorrhage rate approached 26.7%. In spinal fusion instrumentation procedures, the complication rate was as high as 41.0%. Preoperative assessment and correction could possibly decrease complications such as hemorrhage, wound infection and other cirrhosis-related complications (renal, pulmonary, ascites and encephalopathy). In this study, we reviewed the neurosurgical-related literature with regard to liver cirrhosis as a prognostic factor influencing neurosurgical outcomes.
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PMID:Neurosurgical procedures in patients with liver cirrhosis: A review. 2641 25