Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven healthy macaques were inoculated with the GBV-C/HGV-RNA serum from a non-A-E hepatitis patient. The serology and pathology of the liver in the animals were observed. The results indicated that all inoculated animals were infected with a GBV-C/HGV-RNA viremia and had mildly abnormal alanine transaminase levels during the infectious period. The histology, immuno-histochemistry, and in situ hybridization in the liver tissues of the inoculated animals also showed that there was a very mild hepatitis with the positive antigenic expression and the genome of GBV-C/HGV-NS5 in hepatocytes. The pathological changes in the infected animals appeared to become normal whether or not GBV-C/HGV-RNA viremia persisted. There is a possibility that the mild virulence of the GBV-C/HGV to the host became harmless with time after inoculation. Infection and the transmission of the GBV-C/HGV virus in the macaques provides an appropriate animal model and new information about GBV-C/HGV infection in both humans and animals. It is possible that this virus is a mild and self-limited pathogenic agent to the hepatic cells of primates.
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PMID:Serological and histological findings in infection and transmission of GBV-C/HGV to macaques. 1056 59

The aim of our study was to assess the clinical, biochemical and virological profile of patients with atypical viral hepatitis A (protracted, relapsed and cholestatic forms). Five patients with the relapsed form and 2 patients with the cholestatic form were studied among 95 patients hospitalized in our Division of Infectious Diseases for viral hepatitis A during the years 1988 to 1998. A relapse was defined by a decrease in serum alanine transaminase levels > or = 50% followed by a > or = 50% increase in the minimal value. The protracted form was defined by elevated serum alanine transaminase levels for more than 6 months. The cholestatic form was defined by the highest value of bilirubinemia above 15 mg/dL or by a persistent jaundice for more than 8 weeks. All 5 of the protracted-relapsed forms had a biphasic course: the median time between onset and relapse of the disease was 8 weeks, and serum aminotransferase activities returned to the normal range within an average of 45 weeks after relapse. The two cholestatic forms were characterized by a very high level of bilirubinemia (24.58 and 19.03 mg/dL) and by protracted jaundice with itching (3 and 8 months). All patients were tested for hepatitis B and C, Cytomegalovirus and Epstein-Barr virus, with negative results. In short, viral hepatitis A is a benign, self-limiting disease which usually resolves in a few weeks. In a non-negligible percentage of cases (3-21%), however, it can assume atypical forms, which are more serious in patients with chronic liver diseases.
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PMID:[Viral hepatitis A with atypical course. Clinical, biochemical, and virologic study of 7 cases]. 1063 16

The clinical usefulness of injectable biapenem (BIPM) was examined for various infectious diseases in the fields of internal medicine, urology, surgery, orthopedics, obstetrics and gynecology, otorhinolaryngology, ophthalmology, dermatology, oral surgery, and plastic surgery. BIPM was administered by intravenous drip infusion at a dose of 150, 300, or 600 mg twice a day. The concentrations in various body fluid and tissues were also examined. 1. In the total enrollment of 256 cases, the numbers subjected to the analyses for clinical efficacy, bacteriological efficacy, side effects and abnormal laboratory findings were 214, 170, 252 and 251 cases, respectively. 2. The clinical efficacy rate was 85.5% (183/214 cases) as a whole, being 2/2 for sepsis, 6/8 for cellulitis and lymphangitis, 76.2% (16/21) for traumatic, operative wound and burn infections, 4/6 for osteomyelitis and arthritis, 92.9% (13/14) for peritonsillar abscess and peritonsillitis, 83.3% (15/18) for chronic lower respiratory tract infection, 7/7 for pneumonia, 83.3% (30/36) for complicated urinary tract infection, 100% (14/14) for cholecystitis and cholangitis, 88.2% (15/17) for peritonitis, 86.5% (32/37) for internal genital infection, 8/9 for pelvic peritonitis, 2/4 for corneal ulcer, orbital infection and panophthalmitis, 1/2 for otitis media, 4/4 for sinustitis, 93.3% (14/15) for osteitis of jaw and cellulitis of mouth floor. The efficacy rate in the poor responders to the pretreatment by other antibiotics was 86.4% (70/81). 3. 300 strains of causative organisms were isolated from 170 cases which contained polymicrobial infections. The elimination rate of causative organisms was 85.3% (256/300 strains), in terms of bacteriological efficacy. 4. Side effects were noted in 11 of 252 cases (4.4%) with 11 events. The signs and symptoms were the skin symptoms (5 cases), gastro-intestinal symptoms (3 cases), interstitial pneumonia (2 cases), and feeling bad (1 case), all of which disappeared during treatment or after the discontinuation of treatment. The abnormal laboratory findings were observed in 31 of 251 cases (12.4%) with 50 events, and major ones were an increase in eosinophils, and elevations of AST, ALT, gamma-GTP and Al-p. 5. The concentrations of BIPM in body fluid and tissues were determined in 46 cases (212 samples) most of which were administered 300 mg of BIPM by intravenous drip infusion for 60 minutes. The concentrations in the sputum within 6 hours after administration were 0.1-2.5 micrograms/g. The maximum concentrations in body fluid and tissues were 0.2-1.8 micrograms/g or ml in the bile, middle ear mucosa, tonsillar tissue, aqueous humor and bone tissues and were 2.0-5.7 micrograms/g or ml in the gallbladder, maxillary sinus mucous membrane, ethmoidal sinus mucous membrane, oral tissues, skin, woman genitals, synovia, joint tissue, and the eschar. The concentrations in the uterine arterial plasma and retroperitoneal fluid were almost similar to those in the cubitl vein plasma. From the above-mentioned results of clinical efficacy, bacteriological efficacy, and safety, injectable BIPM was confirmed to be useful in the treatment of moderate, severe and/or refractory infections in various fields.
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PMID:[Clinical evaluation of biapenem in various infectious diseases]. 1065 41

Data were collected from 104 infected children who were followed up from birth for a mean of 49 (range, 6-153) months in 22 European centers, to outline the natural history of perinatal hepatitis C virus (HCV) infection. Fifty-four children were persistently HCV RNA positive, 44 were occasionally positive, and 6 never had detectable viremia. At least 90% of the children had evidence of ongoing infection at the latest analysis. Eighteen children became HCV RNA negative at their last assessments, but 40% of these had high alanine aminotransferase (ALT) concentrations. Infection was asymptomatic in all but 2 children, who developed hepatomegaly. Mean ALT concentrations decreased substantially after the first 2 years of life; 14 children had persistently normal ALT values. Signs of minimal to moderate inflammation were noted in all 20 patients who underwent liver biopsy. Perinatal HCV infection is usually asymptomatic in the first years of life, but the virus persists in most children, even in the absence of elevated ALT activity.
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PMID:Persistence rate and progression of vertically acquired hepatitis C infection. European Paediatric Hepatitis C Virus Infection. 1066 21

Immunity to allogeneic MHC Ags is weak in rodent livers, raising questions as to the mechanisms that might control responses in this organ. Infection with an adenovirus vector reveals that T cell-mediated immunity to nonself-Ags in the liver is self-limiting. Virus-induced liver injury decreases and coincides with disappearance of virus-specific CTL, concomitant to an increase of apoptotic T cells early after infection. But whereas death in CD4 cells is independent of Fas, perforin, and TNF-alpha, that of CD8 cells requires Fas and not perforin or TNF-alpha pathways. Fas ligand is expressed on liver-infiltrating cells, pointing to death by fratricide that causes almost complete disappearance of virus-specific CTL 4 wk after infection. CTL elimination is virus dose dependent, and high doses induced high alanine aminotransferase values, elevated expression of Fas ligand on CD8 cells, and increased CD8 cell migration into the infected liver.
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PMID:Fas-mediated apoptosis causes elimination of virus-specific cytotoxic T cells in the virus-infected liver. 1120 53

An 11-year-old Thai boy who had received multiple blood transfusions from 12 different donors for treatment of Dengue shock syndrome presented with symptoms of acute hepatitis 5 weeks thereafter. He was found positive for antibodies to hepatitis C virus (HCV) and HCV-RNA was detected by reverse transcription PCR (RT-PCR). When his alanine aminotransferase (ALT) level peaked at 1,879 U/l in the 8th week, interferon therapy (3 million units, thrice weekly for 6 months ) was initiated. After initially decreasing to tenfold the normal level, the ALT dropped to fivefold the normal level at 6 months. HCV RNA is still detectable in his serum 6 months later. Using RT-PCR and subsequent restriction fragment length polymorphism (RFLP) analysis we identified one of the donors as harboring HCV genotype 3a, identical to that found in the patient. Moreover, polymorphism analysis on the hypervariable region employing five distinct restriction endonucleases suggested this donor as the source of infection. We hence recommend thorough screening of all blood donors as the only means of prevention presently feasible.
Infection
PMID:Acute posttransfusion hepatitis C: identification of a common hepatitis C virus strain in donor and recipient using polymorphism analysis. 1126 58

A 69-year-old male was hospitalized in January 1999 because of visceral leishmaniasis. He had also suffered from anti-hepatitis C virus (HCV)-positive chronic hepatitis for years. All serum hepatitis B virus (HBV) antigens and antibodies were negative except for anti-HBc. The patient was treated with amphotericin B cholesteryl sulfate (2 mg/kg twice a day for 7 days, iv). Fever disappeared on the 3rd day of treatment, the clinical condition improved rapidly and the patient recovered. In May 1999 the patient developed icteric HBsAg-negative acute hepatitis (aspartate aminotransferase 722 U/l; alanine aminotransferase 988 U/l). Anti-HBc IgM was positive and HBV-DNA was detected in serum by PCR. Anti-HAV IgM was negative. A serum sample obtained on presentation and stored at -80 degrees C was retrospectively tested and found positive for HBV-DNA. In July 1999, complete remission of acute hepatitis and seroconversion to anti-HBs was observed. We suppose that a moderate depression of the immune system, probably associated with leishmaniasis, may have enhanced HBV replication in the patient who had an HBsAg-negative 'silent' HBV infection. Restoration of the immune system after successful antiprotozoan therapy might have induced cell-mediated necrosis of the HBV-infected hepatocytes and seroconversion to anti-HBs.
Infection
PMID:Clinical expression of 'silent' hepatitis B virus infection in a patient with visceral leishmaniasis. 1144 Mar 89

A retrospective analysis of data from a cohort of patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were treated with highly active antiretroviral therapy (HAART) at 3 infectious diseases units in northern Italy was performed. While the patients were receiving HAART, CD4(+) cell counts significantly increased and HIV RNA serum levels decreased. However, no significant overall changes in alanine aminotransferase (ALT) levels and HCV RNA serum levels were observed. Fifteen (4.6%) of 323 patients died within 3 years of follow-up; death was related to cirrhosis in 5 patients (1.6%). No significant difference was observed between cirrhosis-related mortality and mortality related to other causes. Patients with ALT levels >4 times the normal values at initiation of HAART showed a significant decrease in ALT levels, whereas patients with normal ALT levels at initiation of HAART showed a significant increase over time, suggesting that HAART may have long-term beneficial or detrimental effects, depending on patient characteristics.
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PMID:Evolution of coinfection with human immunodeficiency virus and hepatitis C virus in patients treated with highly active antiretroviral therapy. 1158 1

The aetiological agent of chronic hepatitis C is the hepatitis C virus. The hepatitis C virus is spread by parenteral transmission of body fluids, primarily blood or blood products. In 1989, after more than a decade of research, HCV was isolated and characterised. The hepatitis C viral genome is a positive-sense, single-stranded RNA molecule approximately 9.4 kb in length, which encodes a polyprotein of about 3100 amino acids. There are 6 main genotypes of HCV, each further stratified by subtype. In 1994, a cohort of women was identified in Ireland as having been iatrogenically exposed to the hepatitis C virus. The women were all young and exposed as a consequence of the receipt of HCV 1b contaminated anti-D immunoglobulin. The source of the infection was identified as an acutely infected female. As part of a voluntary serological screening programme involving 62,667 people, 704 individuals were identified as seropositive for exposure to the hepatitis C virus; 55.4% were found to be positive for the viral genome 17 years after exposure. Of these women 98% had evidence of inflammation, but surprisingly, a remarkable 49% showed no evidence of fibrosis. Clinicopathology and virological analysis has identified associations between viral load and the histological activity index for inflammation, and, between inflammation and levels of the liver enzyme alanine aminotransferase. Infection at a younger age appears to protect individuals from progression to advanced liver disease. Molecular analyses of host immunogenetic elements shows that particular class II human leukocyte associated antigen alleles are associated with clearance of the hepatitis C virus. Additional class II alleles have been identified that are associated with stable viraemia over an extended period of patient follow-up. Although, investigation of large untreated homogeneous cohorts is likely to become more difficult, as the efficacy of anti-viral therapy improves, further investigation of host and viral factors that influence disease progression will help provide an evidence based approach were realistic expectations regarding patient prognosis can be ascertained.
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PMID:The Irish paradigm on the natural progression of hepatitis C virus infection: an investigation in a homogeneous patient population infected with HCV 1b (review). 1178 30

OBJECTIVE: To evaluate the pharmacokinetics of cefetamet pivoxil and possible interaction with N-acetylcysteine and cisapride in healthy volunteers. METHODS: In a double-blind, randomized three-way crossover study with 12 healthy male volunteers, serum and urine concentrations of cefetamet were determined over 12 h by a validated bioassay method after oral administration of 0.5 g cefetamet pivoxil and, randomly, placebo, 5x20 mg cisapride, or 0.6 g N-acetylcysteine. RESULTS: The study medications were well tolerated, although there were 10 cases of altered bowel movements, two cases of mild, transient headache and one case of increased serum transferase levels (AST and ALT). The mean peak serum level of cefetamet pivoxil in the placebo group was 4.86plus minus1.35 mg/L. The urine recovery/24 h in the placebo group was 41.9plus minus3.8% of the oral dose. The elimination half-life was 3.56plus minus0.92 h. N-Acetylcysteine had no effect on the pharmacokinetics of cefetamet pivoxil. With concomitant administration of cisapride there was an accelerated absorption of cefetamet pivoxil and a slightly increased Cmax of cefetamet. The Cmax values differed significantly (p<0.05) only between the cisapride group (5.76plus minus1.50 mg/L) and the N-acetylcysteine group (4.53plus minus1.18 mg/L). CONCLUSION: None of the small pharmacokinetic differences between the three groups is expected to have any relevance in the treatment of infectious diseases with cefetamet pivoxil.
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PMID:Pharmacokinetics of cefetamet pivoxil and interaction with cisapride and N-acetylcysteine. 1186


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