Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon-alpha-2a is a recombinant interferon with antiviral, antitumour and immunomodulatory properties. Clinical studies have demonstrated that the drug offers therapeutic benefit in patients with some forms of chronic viral hepatitis. Remission, as measured by clearance of viral DNA and hepatitis B 'e' antigen (HBeAg), and normalisation of serum alanine aminotransferase levels, is observed in approximately 30 to 45% of patients with chronic hepatitis B receiving interferon-alpha-2a (2.5 to 18MU administered 3 times/week); about 5 to 15% of untreated controls remit spontaneously every year. Complete recovery [with loss of hepatitis B surface antigen (HBsAg)] is usually noted in < 20% of treated individuals. Similar response rates have been reported in the relatively small number of children evaluated to date. Although numerous studies have shown that interferon-alpha-2a (at various dosages) induces biochemical amelioration of chronic hepatitis C in approximately 50 to 75% of patients, relapse is common. Thus, long term remission may only be observed in about 15 to 30% of treated patients. On the other hand, this disorder remits spontaneously in only a few patients. The role of interferon-alpha-2a in the treatment of chronic hepatitis D remains unclear. Although preliminary data suggest it may be beneficial, cessation of therapy is generally followed by relapse. As with other types of interferons, most patients receiving interferon-alpha-2a experience an 'influenza-like' syndrome, which tends to diminish with continuing therapy. Other effects such as fatigue, lethargy, anorexia and weight loss are usually dose-limiting. Serum neutralising antibodies develop in approximately 10 to 20% of treated patients. Thus, although response rates are less than optimal, interferon-alpha-2a is a drug of first choice amongst the limited therapeutic options available for the management of well-compensated chronic viral hepatitis B or C.
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PMID:Interferon-alpha-2a. A review of its pharmacological properties and therapeutic use in the management of viral hepatitis. 858 31

A 51-year-old female was admitted with complaints of fever and general fatigue. Chest X-ray showed diffuse bilateral fine nodular shadows and infiltrates. Complication of hepatic and muscular injury was suspected from increased levels of GOT, GPT and CPK in the serum. Arterial blood gas analysis revealed hypoxemia. Because hypoxemia aggravated despite treatment with intravenous minocycline (200 mg/day), corticosteroids and mechanical ventilation were started, and the administration of minocycline (400 mg/day) and sparfloxacin was added. Consequent, chest X-rays and several laboratory data improved gradually. The final diagnosis was established with a significant rise of both IgG and IgM antibody against Chlamydia psittaci with MIF and identification of Chlamydia with the cell culture method. Chlamydia was successfully isolated from BALF of this patient obtained 5 days after commencement of minocycline treatment. Psittacosis should be considered as a possible cause of severe respiratory failure necessitating emergency care including mechanical ventilation.
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PMID:[A case of fulminant psittacosis necessitating mechanical ventilation diagnosed by chlamydial isolation form BALF]. 858 93

Ribavirin is a guanosine analogue that normalizes serum liver enzymes in most nontransplant patients with chronic hepatitis C virus (HCV) infection. We conducted an uncontrolled pilot study of ribavirin in 9 liver transplantation recipients that had persistently elevated liver enzymes, active hepatitis by liver biopsy, and HCV RNA in serum by polymerase chain reaction. Ribavirin was given orally at dosages of 800-1200 mg per day for 3 mo. All 9 patients promptly responded to ribavirin: mean (+/- SD) ALT decreased from 392 +/- 377 IU/L immediately before treatment to 199 +/- 185 and 68 +/- 37 IU/L after 1 and 12 weeks of treatment, respectively, complete normalization of enzymes occurred in 4 patients. None of the patients cleared the virus from their serum during therapy, and biochemical relapse occurred in all patients 4 +/- 4.2 weeks after cessation of therapy. The hepatitis activity index of liver biopsy specimens obtained before and at the cessation of therapy was similar. Ribavirin treatment was resumed in 4 patients because of increasing fatigue (2 patients), rising bilirubin (3), or increasing necroinflammation on liver biopsy (2); the biochemical response to the second course of therapy was similar to the first course in all 4 patients. Ribavirin caused reversible hemolysis in all patients, including symptomatic anemia in 3 patients that resolved after reduction of drug dosage. These results suggest that ribavirin may be of benefit in the treatment of HCV infection after liver transplantation. Further studies are needed to determine the optimal dosage and duration of therapy.
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PMID:A pilot study of ribavirin therapy for recurrent hepatitis C virus infection after liver transplantation. 863 76

LY188011 (Gemcitabine hydrochloride) is a new derivative of deoxycytidine. Phase I study was carried out by a cooperative study group. LY188011 was administered weekly for 3 consecutive weeks starting with an initial dose of 60 mg/m2 (1n) and then increasing the dosage to 1,000 mg/m2 (16.7n). Dose limiting factor was found to be myelosuppression (decreases of WBC, neutrophils and platelet), and MTD was considered to be 1,000 mg/m2. The nadir of WBC and platelet were observed after about 1-3 weeks. It took 1-2 weeks for their recovery. Other adverse reactions included fever, fatigue, anorexia, nausea/vomiting, anemia and transient elevations of GOT and GPT. However, those adverse reactions were mild. T1/2 rho of plasma concentration was about 19 min and the C5min was dependent on the dose. Anti-cancer effects were observed in one gastric cancer and two colon cancer patients. It is recommended that the dosing schedule for an early phase II study is 800 mg/m2 weekly for 3 weeks with 1 week of rest as one cycle, in multiple cycles.
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PMID:[LY188011 phase I study. Research Group of Gemcitabine (LY188011)]. 868 15

Twenty-one HIV negative Japanese patients with chronic hepatitis C who had congenital bleeding disorders, 15 hemophilia A, 3 hemophilia B, 1 von Willebrand's disease, 1 afibrinogenemia and 1 thrombasthenia, were treated with 9 million units 3 times a week of natural interferon (IFN)-alpha for 6 months. They were followed, biochemically and virologically, for at least 18 months after therapy discontinuation to evaluate the long-term results. Liver biopsy, hepatitis C virus (HCV) genotyping and quantification of viral load by polymerase chain reaction (PCR) were performed to identify the predictors of a favorable response to IFN treatment. One male patient with hemophilia A dropped out because of general fatigue and was excluded from evaluation. Ten (50.0%) patients continued to be HCV RNA negative in serum together with normal ALT levels throughout the study. Subtype 1b and a high level of viremia significantly associated with an unfavorable outcome on the response to IFN although liver histology was not definitive for predicting the response. We concluded that a 6-month treatment with high doses of natural IFN-alpha was effective in inducing a long-term response without relapse of viremia in 50% of chronic hepatitis C patients with congenital bleeding disorders and that HCV subtype and pretreatment level of viremia were useful predictors of the response to IFN in treating such patients.
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PMID:A long-term follow-up study of interferon treatment for chronic hepatitis C in Japanese patients with congenital bleeding disorders. 885 94

Fatigue of night duty workers in different divisions of a newspaper office was investigated by physiological methods such as the Blinker, Flicker and grip methods. The relationship between fatigue and hematological parameters such as hemoglobin (Hb), the hematocrit (Ht), serum-free amino acid levels, and indices of liver function such as the GOT and GPT levels were also examined. The composing and press room workers mainly complained of the subjective symptom of muscle fatigue, while workers in the photo-engraving and editorial departments mainly complained of mental fatigue. The overall rate of fatigue in the newspaper office was about 38.1%, but varied from one division to another, being especially high in the photo-engraving and editorial departments. The subjects with fatigue had low levels of serum GOT and GPT and high levels of serum-gluconeogenic amino acids, such as aspartic acid, glutamic acid, prolin, glycine, and alanine. These altered levels of serum-free amino acids and GOT and GPT seemed to be due to increased secretion of adrenal corticoid hormone caused by the stress of fatigue.
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PMID:Studies on fatigue of night duty workers at a newspaper office. 885 78

Interferon-alpha is currently the only available treatment for HCV hepatitis. We assessed the safety and efficacy of 6 month course of interferon therapy in 18 consecutive liver transplant recipients with recurrent HCV hepatitis and report the long-term response with maintenance interferon. Median follow-up after the institution of interferon was 24 months. Complete response was defined as normalization of both aspartate and alanine aminotransferase. Complete response after 6 months of interferon was observed in 28% (5/18); an additional 33% (6/18) of the patients were late responders. Overall, 61% (11/18) of the patients had long-term sustained normal response at a median follow-up of 24 months. Long-term sustained response was observed in 73% (8/11) of the patients who continued interferon beyond 6 months vs. 43% (3/7) in those who received 6 months of interferon. Fatigue, headache and cytopenia were the most commonly observed side-effects occurring in 39%, 22% and 28% of the patients, respectively. Discontinuation of interferon, however, was not required in any of the patients. Rejection was documented in 6% (1/18) patients receiving interferon; this incidence was not higher than rejection episodes occurring > 6 months post-transplant in other recipients transplanted during the same period and who did not receive interferon. Responders had a trend towards later recurrence of HCV hepatitis after transplantation. In conclusion; maintenance interferon was well tolerated and appeared to improve the long-term outcome in our patients; however, future studies should evaluate this in a controlled trial.
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PMID:Interferon-alpha therapy for hepatitis C virus recurrence after liver transplantation: long-term response with maintenance therapy. 888 7

Therapy with ribavirin for 6-12 months is associated with decreases in serum aminotransferases in some patients with chronic hepatitis C. We have assessed the practicality and safety of prolonged therapy with ribavirin. Six patients with chronic hepatitis C were given 1000-1200 mg of ribavirin daily for 24 months. Serum aminotransferases and hepatitis C virus (HCV) RNA levels were monitored during and after therapy. Liver biopsies were carried out before and at the end of treatment. With therapy, mean serum alanine aminotransferase (ALT) levels fell from 161 U/L to 45 U/L at 12 months and to 39 U/L at 24 months. HCV RNA levels did not change. Liver histology improved in five and was unchanged in one patient. When therapy was stopped, aminotransferases rose to pretreatment levels. Side effects included mild fatigue and headaches. Two patients developed gallstones during therapy, perhaps caused by the chronic haemolysis that occurred in all patients. In conclusion, prolonged therapy with ribavirin can result in sustained improvements in serum aminotransferases and hepatic histology in a proportion of patients with chronic hepatitis C. Ribavirin therapy does not cause decreases in viraemia and, therefore, probably must be continued indefinitely to provide lasting benefit. The advantages of such therapy must be weighed against possible long-term side-effects.
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PMID:Prolonged therapy of chronic hepatitis C with ribavirin. 891 4

Hepatitis C is a common cause of chronic liver disease that may progress to cirrhosis. We conducted a multicenter double-blind placebo-controlled trial of ribavirin 600 mg given orally twice daily for 36 weeks with follow-up off therapy for an additional 16 weeks. Fifty-nine patients with compensated chronic hepatitis C were entered. Efficacy was measured at the end of therapy and after follow-up by normalization of alanine aminotransferase (ALT), improvement in liver histology, reduction in hepatitis C virus (HCV) RNA level and improvement of symptoms. Among the ribavirin recipients, 12 of 29 (41.4%) had normal ALT values at 36 weeks compared with only 1 of 30 (3.3%) placebo recipients (P < .001). No patient maintained a normal ALT when therapy was stopped. No significant decrease in level of HCV RNA was observed during the study. Histological improvement among subjects who normalized ALT (-1.67 Knodell index) was significantly greater than that in other treated patients (+0.33 Knodell index; P < .05). Fatigue improved in 19.2% of ribavirin-treated subjects and in 8.3% of placebo recipients whereas no worsening of fatigue was reported by ribavirin recipients compared with 16.7% of controls. This difference in fatigue was significant at weeks 36 and 52 (P < .05; .02, respectively). Adverse events were generally comparable between treatment groups except for a reversible hemolytic anemia experienced by ribavirin recipients. Chest pain was noted in four patients on ribavirin. Ribavirin was well tolerated and improved aminotransferase values and reduced fatigue in patients with hepatitis C viral infection while treatment was being administered. Because this action was produced without change in viral level, the mechanism of action of this agent requires further investigation.
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PMID:Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: a multicenter trial. 925 61

Twenty relapsing-remitting (RR) clinically definite MS patients were treated with 9 MIU intramuscular recombinant interferon alpha-2a (rIFNA) (Roferon-A, Roche) (n = 12) or placebo (n = 8) every other day for 6 months and followed up for a further 6 months after stopping treatment. Numbers of active lesions at MRI and of patients with clinical-MRI signs of disease activity and lymphocyte interferon gamma production, which were decreased during treatment, returned to values similar to baseline and placebos after stopping treatment. rIFNA chronic therapy seems therefore needed in order to maintain drug efficacy. Side effect profile was monitored, too, for over 1 year in the same 20 patients plus 25 additional RR MS patients. Besides the typical side effects of type I interferon therapy (fever, fatigue, depression, lymphopenia, hepatic enzyme elevation), occurrence of serum autoAbs was noted in 30% patients (in 60% antinuclear and in 80% antithyroid autoAbs). In two patients rIFNA treatment was stopped, in one case for antithyroid autoAbs and hypothyroidism, in the other for antinuclear autoAbs and a five-fold increase of ALT. A careful monitoring of serum autoAbs and of signs of thyroid or liver damage must always precede and accompany longterm type I IFN therapy.
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PMID:Long term recombinant interferon alpha treatment in MS with special emphasis to side effects. 934 19


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