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)

BACKGROUND AND AIM: Thymosin-alpha1 (T-alpha1) influences T-cell maturation, production of Th1-type cytokines, and activity of NK cell-mediated cytotoxicity. The aim of this study is to evaluate the types of lymphocytes that contribute to the reduction in viral load in patients with chronic hepatitis B (CHB) following T-alpha1 treatment. METHODS: Seven patients with CHB were treated with 1.2 mg of T-alpha1 for 24 weeks. Peripheral blood lymphocytes (PBL) and intrahepatic lymphocytes were analyzed by flow cytometry. Serum cytokines (IL-4 and IFN-gamma) were measured by ELISA. RESULTS: Forty-eight weeks after T-alpha1 treatment, two patients (28.6%) showed normalized alanine aminotransferase and decreased HBV-DNA to undetectable level from serum. The histology activity index score significantly decreased (P<0.05). Although elevated serum interferon (IFN)-gamma was not observed, IFN-gamma producing Th1-type CD4(+) PBL appeared to be increased. CD56(+) natural killer T (NKT) cells in PBL did not increase, these cells in the liver remained significantly augmented even at the end of treatment (P<0.05). CD57(+) NKT cells slightly increased and the ratio of CD4(+) T/CD8(+) T cells decreased in the liver. T-alpha1 did not influence either double-positive CD4(+)8(+) T or double-negative CD4(-)8(-) cell subsets. CONCLUSION: NKT cells and CD8(+) cytotoxic T lymphocytes augmented in the liver by T-alpha1 may eliminate hepatitis B virus infected hepatocytes.
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PMID:Thymosin-alpha1 increases intrahepatic NKT cells and CTLs in patients with chronic hepatitis B. 1247 32

The biochemical, virologic, and histologic spectrum of hepatitis C virus (HCV) in 66 consecutive patients with HIV-HCV coinfection and 119 HCV controls was compared: 86% of coinfected patients had CD4 counts >200 cells/mm3, 51% had a normal alanine aminotransferase (ALT) value, the mean HCV RNA titer was 5.7 log IU/mL, 92% of coinfected patients were of genotype 1, and the mean histologic activity index was 6.86 with advanced fibrosis in 32% of patients. The biochemical, virologic, and histologic findings of HCV in coinfected patients were similar to those observed in HCV controls. For both groups of patients, no clinical, biochemical, or virologic factors could reliably identify patients with advanced fibrosis or cirrhosis, underscoring the importance of liver biopsy in the evaluation of these patients. The spectrum of liver disease in coinfection includes a significant proportion of patients with normal ALT values, and excluding these patients from previous studies has led to an overestimation of HCV disease severity.
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PMID:The clinical spectrum of hepatitis C virus in HIV coinfection. 1251 11

BACKGROUND/AIMS: Bovine lactoferrin (bLF) has been shown to prevent the infection of cultured hepatocytes by hepatitis C virus (HCV). The present study attempted to clarify the effects of long-term administration of bLF on serum parameters, including immunomodulatory cytokines, in patients with chronic hepatitis C (CHC). METHODS: Sixty-three CHC patients were randomly assigned into 2 groups. At an oral dose of 600 mg/day, bLF was administered for 12 months to 36 patients (bLF group), while no bLF was given to the remaining 27 patients (control group. Serum levels of alanine aminotransferase, HCV-RNA, IL-10, and IL-18 were evaluated, as well as CD4-positive T cell subsets in the peripheral blood. RESULTS: The serum IL-18 level was increased by bLF administration, but not in the control group. After 3 months of bLF treatment, it was significantly higher than before bLF administration, but it decreased gradually thereafter. The percentage of interferon (IFN)-gamma+ and IL-4- (Th1) cells in the peripheral blood increased along with the serum IL-18 level, although the change was not statistically significant. The other parameters did not change significantly during the study period in both groups. CONCLUSIONS: These results suggest that oral administration of bLF to CHC patients for up to 3 months can produce a Th1-cytokine dominant environment in the peripheral blood that favors the eradication of HCV by IFN therapy.
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PMID:Long-term follow-up of chronic hepatitis C patients treated with oral lactoferrin for 12 months. 1269 43

Chronic hepatitis C virus (HCV) is an independent risk factor for antiretroviral-related hepatotoxicity, but little is known about the frequency of severe liver toxicity in patients with HIV-HCV coinfection first treated for HCV (pretreated). The aim of this prospective study of 105 patients was to compare the incidence of progression to severe antiretroviral-related liver toxicity in 66 patients pretreated (36 with interferon-alpha [IFNalpha], 30 with IFNalpha plus ribavirin), and 39 patients not pretreated. The subjects could choose whether to receive anti-HCV therapy. Severe liver toxicity was defined as alanine aminotransferase (ALT) level > or =5-times the upper limit of normal in patients with normal baseline levels and > or =3.5-times in those with increased baseline levels. The authors also estimated the hepatotoxicity-related risk of discontinuing antiretroviral therapy. During antiretroviral therapy, 10 subjects (9.5%) experienced severe hepatotoxicity: 4 of 66 pretreated patients and 6 of 39 untreated patients (24-month survival: 94% +/- 2.9% vs. 85% +/- 5.8%). After adjusting for baseline CD4 cell counts, ALT levels, histologic scores, HCV and HIV viremia, HCV genotype (genotype 1 in 29% of pretreated patients and 20% of patients not pretreated), and previous anti-HCV therapy, the risk of discontinuing anti-HIV treatment was significantly higher in the anti-HCV untreated patients (RR = 10.4; 95% CI: 1.6-66; p =.0127) and in those with increased baseline ALT levels (RR = 1.014; 95% CI: 1.006-1.021; p =.0005). The authors' data suggest that previous treatment of chronic active HCV is an independent factor associated with a decrease of severe liver toxicity as the result of a subsequent antiretroviral regimen. The authors also confirm that the baseline level of ALT is an important prognostic factor for increased liver damage during antiretroviral therapy.
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PMID:Pretreatment of chronic active hepatitis C in patients coinfected with HIV and hepatitis C virus reduces the hepatotoxicity associated with subsequent antiretroviral therapy. 1279 46

We reported a case of non-Hodgkin's lymphoma where liver involvement was the predominant clinical manifestation. A 27-year old man presented with markedly elevated serum aspartate aminotrasferase, alanine aminotransferase and lactate dehydrogenase, reduced prothrombin activity, thrombocytopenic purpura and hepato-splenomegaly without adenopathy. Viral, toxic, autoimmune and metabolic liver diseases were excluded. Bone marrow biopsy showed an intracapillary infiltration of T-lymphocytes with no evidence of lipid storage disease. Because of a progressive spleen enlargement, splenectomy was performed. Histological examination showed lymphomatous intrasinuses invasion of the spleen. Immunohistochemical investigation revealed the T phenotype of the neoplastic cells: CD45+, CD45RO+, CD3+, CD4-, CD8-, TIA1-. About 50 % of the lymphoid cells expressed CD56 antigen. The diagnosis of hepatosplenic T cell lymphoma was done. The patient was treated with chemotherapy, which induced a complete remission. Eighteen months later, he had a first relapse with increased aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, thrombocytopenic purpura and blast in the peripheral blood. In spite of autologous bone marrow transplantation, he died twenty months after the diagnosis. Even in the absence of a mass lesion or lymphoadenopathy, hepatosplenic T-cell lymphoma should be considered in the differential diagnosis of a patient whose clinical course is atypical for acute hepatic dysfunction.
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PMID:Hepato-splenic lymphoma: a rare entity mimicking acute hepatitis: a case report. 1280 Feb 62

We conducted a prospective cohort study to describe the association between alcohol use, HIV disease progression, and drug toxicity and to determine health care provider awareness of excessive alcohol use by recruiting 881 HIV-infected veterans (median age, 49 years; 99% male; 54% African American) from 3 VA HIV clinics. Twenty percent of patients were hazardous drinkers by the Alcohol Use Disorders Identification Test, 33% were binge drinkers, 32% had a chart ICD-9 alcohol diagnosis, and 12.5% and 66.7%, respectively, were described by their health care providers as currently and ever drinking "too much." Hazardous/binge drinkers more often had detectable viral loads (P < 0.001). Patients with alcohol diagnoses more often had elevated alanine transaminase or aspartate transaminase levels (P </= 0.02), anemia (P < 0.001), and elevated mean corpuscular volume (P < 0.001). Health care providers missed hazardous drinking in patients with undetectable viral loads (P = 0.01), patients without hepatitis C (P = 0.09), and patients with normal aspartate transaminase levels (P = 0.07) and missed alcohol diagnoses in patients without hepatitis and those with CD4 cell counts of >200/mL. We conclude that in HIV-positive veterans, hazardous drinking and alcohol diagnoses were common and associated with HIV disease progression and/or hepatic comorbidity and anemia. Health care providers more often missed alcohol problems in patients with less severe HIV infection and those without evidence of liver disease. Health care providers should routinely screen and counsel patients regarding alcohol problems as part of standard of care to minimize disease progression and bone marrow and hepatic toxicity.
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PMID:How harmful is hazardous alcohol use and abuse in HIV infection: do health care providers know who is at risk? 1286 42

Mercury is a well-recognized health hazard and an environmental contaminant. Mercury modulates immune responses ranging from immune suppression to autoimmunity but the mechanisms responsible for these effects are still unclear. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm mercury in drinking water for 14 days. Body weight was reduced at the highest dose of mercury whereas the relative kidney and spleen weights were significantly increased. The dose range of mercury used did not cause hepatotoxicity as indicated by circulating alanine aminotransferase and aspartate aminotransferase levels. Circulating blood leukocytes were elevated in mice treated with the highest dose of mercury. Mercury ranging from 1.5 to 37.5 ppm dose-dependently decreased CD3(+) T lymphocytes in spleen; both CD4(+) and CD8(+) single-positive lymphocyte populations were decreased. Exposure to 7.5 and 37.5 ppm mercury decreased the CD8(+) T lymphocyte population in the thymus, whereas double-positive CD4(+)/CD8(+) and CD4(+) thymocytes were not altered. Mercury altered the expression of inflammatory cytokines (tumor necrosis factor alpha, interferon gamma, and interleukin-12), c-myc, and major histocompatibility complex II, in various organs. Results indicated that a decrease in T lymphocyte populations in immune organs and altered cytokine gene expression may contribute to the immunotoxic effects of inorganic mercury.
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PMID:Oral exposure to inorganic mercury alters T lymphocyte phenotypes and cytokine expression in BALB/c mice. 1292 68

An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carrier containing doxorubicin and human immunoglobulin as an actively/passively targeting moiety was used in four patients with generalized breast cancer resistant to standard cytotoxic chemotherapy. The dose and time schedule were deduced from a Phase I clinical trial in which doxorubicin bound to HPMA copolymer carrier (PK1) was tested. It was confirmed that the Dox-HPMA-HuIg conjugate is stable and doxorubicin remains in the peripheral blood with a small amount also in the urine, mostly in its polymer-bound form. More than 116 biochemical, immunological and hematological parameters were determined for blood samples taken from patients 24 h, 48 h, 72 h and 1 to 11 weeks after treatment. Depending on the patient, some parameters decreased permanently or temporarily to the normal level (CRP, C3, CA 72-4, beta(2)-microglobulin, ferritin, CEA, CA 125, CD4, CD8, CE19, CD16(+)56(+), leu, ery) and some moved markedly towards physiological values (AST, ALT, ALP, GMT, CA 15-3, NSE, AFP). While the number of peripheral blood reticulocytes was significantly decreased after treatment with the classical free drug, their number was not affected or was even elevated after treatment with Dox-HPMA-HuIg. Increased absolute numbers of CD16(+)56(+) and CD4(+) cells in the peripheral blood and activation of NK and LAK cells in all patients support data obtained in experimental animals, pointing to a dual, i.e. cytostatic and immunomobilizing character of Dox-HPMA conjugates containing a targeting immunoglobulin moiety.
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PMID:Cytostatic and immunomobilizing activities of polymer-bound drugs: experimental and first clinical data. 1293 33

All classes of antiretroviral (ARV) therapy have been associated with asymptomatic elevations of alanine aminotransferase/aspartate aminotransferase (ALT/AST) levels, and much less frequently with serious, and at times life threatening, clinical liver hepatotoxicity. The relationship between the risk of developing serious clinical liver injury and the rate and severity of elevated asymptomatic ALT/AST levels is poorly understood. Boehringer Ingelheim has recently completed the Viramune Hepatic Safety Project; its primary objective was to identify risk factors for antiretroviral-associated hepatotoxicity. Data from 1731 nevirapine-treated patients and 1912 control patients who took part in Boehringer Ingelheim-controlled clinical trials as well as 814 nevirapine-treated patients in uncontrolled trials were analyzed. Risk factors for asymptomatic ALT/AST elevations during nevirapine therapy included baseline elevations of ALT/AST levels > 2.5x upper limit of normal (RR = 4.3, p < .01) and co-infection with hepatitis B (RR = 2.3, p < .01) or hepatitis C (RR = 5.2, p < .01). An analysis of ALT/AST elevations > 5x ULN for patients stratified by baseline CD4 cell count demonstrated that men with > or = 400 CD4 cells/mm3 were at increased risk of asymptomatic transaminase elevations while taking nevirapine (RR = 1.6, p < .01). No consistent CD4 cell count cutoff could be identified in women that was associated with an increased risk of ALT/AST elevations. Analyses from five large observational cohorts (N = 8711) demonstrated no significant differences in the rate of serious hepatic events among antiretroviral regimens, including between the non-nucleoside reverse transcriptase inhibitors nevirapine and efavirenz. Use of nevirapine was not associated with a significantly increased risk of clinical hepatotoxic events, including liver failure or liver related death, compared to therapy with other antiretroviral drugs.
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PMID:A comprehensive hepatic safety analysis of nevirapine in different populations of HIV infected patients. 1502 21

BACKGROUND/AIMS: To examine whether or not activated Kupffer cells play an important role in intra-hepatic Th1-associated necro-inflammation in Concanavalin A (Con A)-induced hepatic injury in mice. METHODS: Con A was administered to Balb/c mice pretreated with or without gadolinium chloride (GdCl(3)). Kupffer cell activation was evaluated by their ability to produce superoxide anions in situ under liver perfusion with nitro blue tetrazolium (NBT). Hepatic concentration of cytokines was measured by ELISA and the mRNA expression of CXC chemokine receptor 3 (CXCR3) was evaluated by RT-PCR. Immunohistochemical detection of CD4 positive lymphocytes in the liver was also performed. RESULTS: GdCl(3)-pretreatment significantly (P<0.01) reduced the serum levels of alanine aminotransferase (ALT) in Con A-treated mice. Formazan deposition in Kupffer cells, the hepatic concentration of tumor necrosis factor-alpha and interferon-gamma, the mRNA expression of CXCR3 and the CD4 positive lymphocytes in the liver were decreased in GdCl(3)-pretreated mice as compared with those without GdCl(3)-pretreatment (P<0.05, respectively). CONCLUSIONS: Activated Kupffer cells, which produce superoxide anions, are involved in Con A-induced hepatic necro-inflammation in mice possibly through the activation of Th1-associated immune response mediated by CD4 and/or CXCR3 positive cells recruited into the liver.
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PMID:Activated Kupffer cells play an important role in intra-hepatic Th1-associated necro-inflammation in Concanavalin A-induced hepatic injury in mice. 1456 29


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