Clinical factors influencing liver stiffness as measured by transient elastography (Fibroscan(R)) in patients with chronic liver disease / 대한간학회지

BACKGROUND/AIMS: Transient elastography as performed using the Fibroscan(R) is a useful noninvasive method for evaluating hepatic fibrosis. However, recent studies have found that liver stiffness measurement (LSM) values are inappropriately elevated in acute hepatitis or in the acute flare state of chronic hepatitis, suggesting that the LSM value obtained by the Fibroscan(R) is not a reliable marker for fibrosis. We retrospectively evaluated the clinical factors influencing the LSM value obtained using transient elastography as performed using the Fibroscan(R) in patients with chronic liver disease. METHODS: A total of 298 patients who were followed in Kungpook National University Hospital from November 2007 to May 2008 due to previously established liver cirrhosis or chronic liver disease were investigated using the Fibroscan(R), laboratory test, ultrasound, and/or abdominal computed tomography. RESULTS: The 298 patients were aged 47.8+/-12.9 years (mean+/-SD). The cut-off value for a diagnosis of liver cirrhosis was 12.5 kPa (as used in previous studies). Thirty-six patients (15%) and 202 patients (85%) with chronic liver disease without clinical manifestation of cirrhosis had LSMs of >12.5 kPa and <12.5 kPa, respectively. Multivariate analysis revealed that LSM values were unusually increased in patients with chronic liver disease who were older (P=0.007) or who had increased gamma gultamyltranspetidase (GGT) (P=0.022), decreased albumin (P=0.015), or increased total bilirubin (P=0.009). CONCLUSIONS: This study reveals that age, GGT, and albumin are clinical factors influencing LSM values. This reinforces the need to interpret LSM values in the context of a defined diagnosis, biochemical data, radiologic examination, and other clinical findings.

Estradiol transdérmico e perfil lipídico: efeitos em um grupo específico de mulheres brasileiras pós-menopausadas / Transdermal estradiol and lipid profile: effects on a specific group of brazilian postmenopausal women / Estradiol transdérmico y perfil lipídico: efectos en un grupo específico de mujeres brasileñas posmenopáusicas

Fundamento: Em mulheres pós-menopausadas, mudanças significantes ocorrem, que podem induzir doenças cardiovasculares, tais como o perfil lipídico aterogênico devido a um aumento nos níveis de colesterol total e LDL, e uma diminuição nos níveis de HDL. A terapia de reposição hormonal (TRH) pode evitar essas mudanças no perfil lipídico. Objetivo: Determinar os efeitos da TRH constituída por estradiol transdérmico e acetato de medroxiprogesterona nos parâmetros bioquímicos e lipídicos de mulheres brasileiras pós-menopausadas. Métodos: Este é um estudo prospectivo, longitudinal, aberto, no qual trinta mulheres pós-menopausadas receberam estradiol em gel transdérmico (1 mg/dia) de forma contínua, combinado com acetato de medroxiprogesterona (MPA) (5 mg/dia) por 12 dias/mês. Os seguintes parâmetros foram determinados: colesterol total, triglicérides, lipoproteína de alta densidade (HDL-colesterol), lipoproteína de baixa densidade (LDL-colesterol), lipoproteína de muito baixa densidade (VLDL-colesterol), glicose, aspartato aminotransferase (AST), alanina aminotransferase (ALT), gama-glutamil transferase (GGT) e hormônio folículo estimulante (FSH). Resultados: Os parâmetros do perfil lipídico mostraram uma diminuição não-significante, enquanto os níveis de GGT e FSH apresentaram uma diminuição estatisticamente significante. Conclusões: O tratamento com estradiol em gel transdérmico não mostrou um impacto significante no perfil lipídico, de forma que não resultou em um efeito benéfico nos marcadores de doenças cardiovasculares, sugerindo que a dose, modo de administração e o tempo de tratamento foram importantes para esses resultados. Além disso, o tratamento com dose baixa e modo de administração transdérmico também demonstrou um significante efeito hepático nessa população. Dessa forma, esse tratamento pode fornecer efeitos interessantes sobre o perfil lipídico em mulheres brasileiras pós-menopausadas.

Background: In postmenopausal women, significant changes occur that can induce cardiovascular diseases, such as atherogenic lipid profile, due to an increase in total cholesterol and LDL levels, and a decrease in HDL cholesterol levels. The hormone replacement therapy (HRT) can prevent these changes in lipid profile. Objective: Verify the effects of HRT consisting of transdermal estradiol gel associated with medroxyprogesterone acetate on the lipid profile and biochemical parameters in Brazilian postmenopausal women. Methods: This study is an open prospective longitudinal study, in which thirty postmenopausal women received transdermal estradiol gel (1 mg/day) continuously combined with oral medroxyprogesterone acetate (MPA) (5 mg/day) for 12 days/month. The following parameters were determined: total cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gama glutamyl transferase (GGT) and follicle-stimulating hormone (FSH). Results: The parameters of the lipid profile did not show a significant decrease, while the levels of GGT and FSH had a statistically significant decrease. Conclusions: the treatment with transdermal estradiol gel did not have a significant impact on the lipid profile, thus not resulting in a beneficial effect on cardiovascular disease markers, suggesting that the dose, administration route and the time of treatment were important for these results. Moreover, the treatment using small dose and the transdermal administration route also had a significant hepatic effect in this population. Therefore, this treatment might provide interesting effects on the lipid profile in Brazilian postmenopausal women.

Fundamento: Cambios significantes ocurren en las mujeres posmenopáusicas que pueden inducir enfermedades cardiovasculares, tales como el perfil lipídico aterogénico debido a un aumento en los niveles de colesterol total y LDL y una disminución en los niveles de HDL. La terapia de reemplazo hormonal (TRH) puede evitar esos cambios en el perfil lipídico. Objetivo: Determinar los efectos de la TRH constituida por estradiol transdérmico y acetato de medroxiprogesterona en los parámetros bioquímicos y lipídicos de mujeres brasileñas posmenopáusicas Métodos: Este es un estudio prospectivo, longitudinal, abierto, en el que treinta mujeres posmenopáusicas recibieron estradiol en gel transdérmico (1 mg/día) de forma continua, combinado con acetato de medroxiprogesterona (MPA) (5 mg/día) por 12 días/mes. Se determinaron los seguientes parámetros: colesterol total, triglicéridos, lipoproteína de alta densidad (HDL-colesterol), lipoproteína de baja densidad (LDL-colesterol), lipoproteína de muy baja densidad (VLDL-colesterol), glucosa, aspartato transaminasa (AST), alanina aminotransferasa (ALT), Gammaglutamiltranspeptidasa (GGT) y hormona foliculoestimulante (FSH). Resultados: Los parámetros del perfil lipídico mostraron una disminución insignificante, mientras los niveles de GGT y FSH presentaron una disminución estadísticamente significante. Conclusiones: El tratamiento con estradiol en gel transdérmico no mostró un impacto significante en el perfil lipídico, causando un efecto benéfico en los marcadores de enfermedades cardiovasculares, sugiriendo que la dosis, el modo de administración y el tiempo de tratamiento fueron importantes para esos resultados. Además, el tratamiento con dosis baja y modo de administración transdérmico también demostró un significante efecto hepático en esa población. Así pues, ese tratamiento puede surtir efectos interesantes sobre el perfil lipídico en las mujeres brasileñas posmenopáusicas.

Effect of gallic acid on alkaline phosphatase and peptidase activities in rat intestine.

Gallic acid is a normal constituent of many edible foods, thus directly interacts with epithelial tissue in intestine. In the present study, the effect of gallic acid on intestinal alkaline phosphatase (IAP) and peptidase activities in rat intestine was evaluated. Gallic acid (0.27-0.5 mM) inhibited activities of leucine aminopeptidase (LAP) and -glutamyl transpeptidase (-GTP) by over 90%, compared to controls in rat intestine. In contrast, 0.1-0.6 mM gallic acid either had no effect or stimulated the activity of IAP in rat intestine. The observed inhibition of peptidases by gallic acid was reversible in nature. Kinetic analysis revealed no change in Vmax of LAP (0.42-0.44 units/mg protein) and -GTP (0.22-0.24 units/mg protein), while the values of apparent Km were increased 6-7 fold, exhibiting competitive-type of enzyme inhibition by gallic acid. The values of Ki for LAP and -GTP were 0.037 mM and 0.017 mM, respectively. These observations indicate that gallic acid is a potent inhibitor of brush border peptidases, and thus may interfere in the digestion and absorption of proteins in the intestine.

Influência dos fatores sexuais e etários sobre a proteína total, fração albumina e atividade sérica de aspartato-aminotransferase e gama-glutamiltransferase de ovinos da raça Santa Inês / Influence of age and sex on total serum protein and albumin and aspartato-aminotransferas and gama-glutamiltransferase serum activities on Santa Inês sheep

O presente estudo estabelece valores de referência dos teores séricos de proteínas totais, albumina, AST e GGT em ovinos da raça santa Inês e avalia a interferência de fatores sexuais e etários sobre estas variáveis. Foram colhidas amostras de sangue de 161 ovelhas. O resultado encontrado para os valores padrões séricos foram 5,86 +0,96 g/dL para proteínas totais, 2,33+0,43 g/dL para albumina, 63,25+27,52 U/L para AST e 28,45+14,53 U/L para GGT. A análise dos resultados permite afirmar que os valores referentes à concentração sérica de albumina e à atividade sérica de AST sofrem influência de fatores sexuais e etários, e os valores referentes à atividade sérica de GGT sofrem influência somente de fatores etários. Não foram encontradas influências dos fatores sexuais e etários para os outros parâmetros estudados.

This work establishes reference values for serum protein and albumin and serum activities of AST and GGT of Santa Inês sheep and evaluates the sexual and age influence on these values. Blood samples were collected from 161 clinically healthy sheep. The results allowed to establish the following reference values 5,86 + 0,96 g/dL (P>0,05)for serum protein, 2,33+0,43 g/dL (P>0,05) for albumin, 63,25+27,52 U/L (P>0,05) for AST and 28,45+14,53 U/L (P>0,05)for GGT. The result’s analysis also allowed concluding that age and sex influence on albumin serum concentrations and AST serum activity and that GGT serum activity suffer age influence

Redifferentiation of human hepatoma cells (SMMC-7721) induced by two new highly oxygenated bisabolane-type sesquiterpenes.

Bisabolane-type sesquiterpenes are a class of biologically active compounds that has antitumour,antifungal, antibacterial,antioxidant and antivenom properties.We investigated the effect of two new highly oxygenated bisabolane-type sesquiterpenes (HOBS)isolated from Cremanthodium discoideum (C.discoideum) on tumour cells. Our results showed that HOBS induced morphological differentiation and reduced microvilli formation on the cell surface in SMMC-7721 cells.Flow cytometry analysis demonstrated that HOBS could induce cell-cycle arrest in the G1 phase. Moreover,HOBS was able to increase tyrosine-alpha ketoglutarate transaminase activity,decrease alpha- foetoprotein level and gamma-glutamyl transferase activity. In addition,we found that HOBS inhibited the anchorage- independent growth of SMMC-7721 cells in a dose-dependent manner.Taken together,all the above observations indicate that HOBS might be able to normalize malignant SMMC-7721 cells by inhibiting cell proliferation and inducing redifferentiation.

Screening of hepatoprotective effect of a herbal mixture against CCl4 induced hepatotoxicity in Swiss albino mice.

The hepatoprotective potential of a herbal mixture was evaluated against CCl4 induced liver injury in Swiss albino mice. Liv 52, a commercially available polyherbal hepatoprotective drug was evaluated for comparison. The potential toxicity of the above herbal hepatoprotective agents was also compared. It was observed that there was a reduction in the enzyme biomarkers (Aspartate and Alanine Transaminase) of liver injury in the herbal mixture treated groups, which was similar to the reduction initiated by Liv 52. An increase in glutathione was observed in the herbal mixture treated groups and it was assumed that the herbal mixture protects the liver by virtue of its antioxidant nature along with high regeneration initiation potential. From the study it is also concluded that the herbal mixture is safer than Liv 52.

Short-term zinc deficiency in diet induces increased oxidative stress in testes and epididymis of rats.

In order to determine the effects of Zinc deficient diet on oxidative stress in testis and epididymis, various parameters viz: total proteins, lipid peroxidation, hydroperoxides, antioxidant capacity and enzymatic activities are evaluated in rats fed on zinc deficient diet for 2, 4 and 6 weeks. Total proteins, water and lipid solouble antioxidant capacity decreased while lipid peroxidation (TBARS) and hydroperoxides concentration increased in testes, caput and cauda epididymis except in 2ZD (testes) where hydroperoxides revealed a significant decrease. GSH decreased in testes and caput and cauda epididymis. GPx and gamma-GT activities increased in testes and caput and cauda epididymis of zinc deficient rats. Further, GST increased in testes but exhibited decreases after 2 and 4 weeks and an increase after 6 weeks in caput and cauda epididymis of zinc deficient rats. GR activities decreased in testes but it increased in caput and cauda epididymis of zinc deficient rats. Thus, zinc deprivation results in increased sensitivity to oxidative stress. All these may have been as a consequence of increased ROS generation and/or decreased zinc dependent antioxidant processes.

Effect of pretreatment of Cassia fistula Linn. leaf extract against subacute CCl4 induced hepatotoxicity in rats.

CCl4 alone treatment (0.lml of liquid paraffin/100g body weight, ip) for 7 days followed by 0.l ml of CCl4 (in liquid parafiin/100g body weight, ip) from day 8 till day 14, caused a 16 fold increase in lipid peroxidation and a 50% reduction in catalase and glutathione reductase in liver tissue of rats accompanied by an increase in the activities of transaminases. alkaline phosphatase, lactate dehydrogenase and gamma - glutamyl transpeptidase in serum as compared to liquid paraffin treated control. Pretreatment of ethanolic leaf extract of C. fistula (500mg/kg body weight/day for 7 days) followed by CCl4 treatment (0.1 ml/100g body weight from day 8 till day 14) completely reversed back lipid peroxidation and the activities of catalase and glutathione reductase in the liver tissue towards normalcy. This treatment also reversed the elevated levels of the enzymes in the serum. Ethanolic leaf extract alone treatment did not produce any change in all the parameters studied. The results suggest antioxidant and hepatoprotective properties of C. fistula during its pretreatment against CCl4 induced hepatotoxicity.

Análise sérica das enzimas aspartato aminotransferase, alanina aminotransferase e gama glutamiltranspeptidase de coelhos adultos tratados com extrato bruto de própolis / Serum activities of aspartate aminotransferase, alanine aminotransferase and gamma glutamyl transpeptidase enzymes in rabbits treated with crude extract of propolis

Diversos trabalhos têm atribuído a própolis inúmeras propriedades farmacológicas, dentre elas podemos citar, como exemplo, efeitos antibacteriano, antiviral, antiinflamatório, regenerador do tecido cartilaginoso, inibidor da formação de radicais livres e redutor de níveis sangüíneo de glicose e triacilglicerol. Alguns efeitos colaterais são atribuídos à própolis principalmente em doses elevadas. Muitos efeitos tóxicos da própolis são atribuídos ao álcool etílico presente no extrato. Dentre alguns efeitos tóxicos citados em literatura como realmente da própolis temos a dermatite e o aumento da uréia sangüínea. O presente estudo teve como objetivo investigar se o extrato bruto de própolis ocasiona algum efeito adverso nos níveis séricos de alanina aminotransferase, aspartato aminotransferase e gama – glutamiltranspeptidase de coelhos saudáveis. O experimento teve 30 dias de duração, sendo as dosagens dos constituintes do sangue (alanina aminotransferase, aspartato aminotransferase e gama – glutamiltranspeptidase) realizadas a 0, 15 e 30 dias. Os resultados indicaram que, de o extrato bruto de própolis na forma testadea, não ocasionou alteração relevante nos níveis séricos das enzimas marcadoras de metabolismo hepático

Macrophage Activation Syndrome in a Child with Systemic Juvenile Rheumatoid Arthritis

Macrophage activation syndrome (MAS) is a rare and potentially fatal complication of rheumatic disorders in children. We describe a 13-month-old boy in whom MAS developed as a complication of systemic juvenile rheumatoid arthritis (S-JRA). He suffered from fever and generalized rash followed by multiple joints swelling for four months before admission. Physical examination revealed cervical lymphadenopathy and hepatosplenomegaly. Laboratory findings were: abnormal liver enzymes, increased triglyceride and ferritin levels, coagulopathies resembling disseminated intravascular coagulation, anemia and thrombocytopenia. Hyperplasia of hemophagocytic macrophages was remarkable in his bone marrow. Methylprednisolone and cyclosporin therapy resulted in clinical and laboratory improvements. This is the third case of MAS associated with S-JRA in Koreans, and the first one, in which hemophagocytic macrophages were proven in bone marrow.

Fatores preditivos de coledocolitíase em doentes com litíase vesicular / Predictors of choledocholithiasis in patients sustaining gallstones

OBJETIVO: Identificar fatores clínicos, bioquímicos e ultra-sonográficos preditivos de coledocolitíase no período pré-operatório de doentes portadores de litíase vesicular avaliados por colangiografia. MÉTODOS: Analisamos prospectivamente 148 doentes portadores de litíase vesicular, relacionando critérios pré-operatórios clínicos, bioquímicos e ultra-sonográficos. Todos estes doentes foram submetidos à colangiografia, podendo esta ser endoscópica pré-operatória ou realizada pelo cirurgião durante a colecistectomia. Foram calculados os valores da sensibilidade, especificidade, valores preditivos positivo (VPP) e negativo (VPN), e acurácia para cada um dos critérios estudados, além da correlação de Spearman, Odds ratio e análise de regressão logística para a variável coledocolitíase. RESULTADOS: Os resultado obtidos mostraram que na análise univariada, a presença de icterícia na internação, a elevação de fosfatase alcalina, gama glutamiltransferase (gamaGT), aspartato aminotransferase, alanina aminotransferase, bilirrubina total, e ultra-sonografia (USG) com presença de dilatação de vias biliares e visibilização de cálculo na via biliar principal (VBP) tiveram diferença estatisticamente significante para coledocolitíase em nossa amostra (p<0,001). Na análise de regressão logística, obtivemos como fatores na equação para coledocolitíase: a icterícia na internação, a USG com visibilização de cálculo na VBP e a gamaGT, nessa ordem. A gamaGT obteve o maior VPN, sendo considerado o melhor critério isoladamente para se descartar coledocolitíase. Todos os doentes com coledocolitíase em nossa amostra apresentavam ao menos um dos critérios pré-operatórios analisados. CONCLUSÕES: A presença de icterícia e a visibilização de cálculo na VBP foram os melhores fatores para predizer coledocolitíase e a gamaGT foi o melhor exame para descartar o diagnóstico de coledocolitíase.

Hipertensão portal esquistossomótica: influência do fluxo sangüíneo portal nos níveis séricos das enzimas hepáticas / Schistosomal portal hypertension: influence of the portal blood flow in serum levels of hepatic enzymes

OBJETIVO: Avaliar a relação entre o fluxo sangüíneo portal e o perfil laboratorial hepático em pacientes com hipertensão portal esquistossomótica. PACIENTES E MÉTODOS: Estudaram-se 64 pacientes com hipertensão portal esquistossomótica, sendo 19 não-operados, 23 submetidos a desconexão ázigo-portal com esplenectomia e 22 submetidos a derivação esplenorrenal distal. Avaliou-se o perfil laboratorial hepático através da dosagem sérica de albumina, transaminases glutâmico-oxalacética e glutâmico-pirúvica, bilirrubinas direta e indireta, fosfatase alcalina, gama-glutamil transferase e avaliação do tempo de protrombina. O fluxo portal foi avaliado por Doppler. Os resultados foram analisados através de regressão linear, coeficiente de correlação de Pearson, teste do Qui-quadrado e análise de variância de um via com pós-teste de Tukey. RESULTADOS: Evidenciou-se que somente a gama-glutamil transferase teve correlação significativa com o fluxo portal. No cotejo dos quartis, também, somente a gama-glutamil transferase mostrou resultado significativo, em que se constatou que o quarto quartil, de maior fluxo portal e formado em sua maioria por pacientes não operados, também foi o de maior valor médio de gama-glutamil transferase e significativamente maior que o primeiro e terceiro quartis. CONCLUSÕES: Estes dados sugerem que: quanto maior o fluxo sangüíneo portal, maior o nível sérico de gama-glutamil transferase; a gama-glutamil transferase é a variável da avaliação do perfil hepático mais representativa da influência do fluxo portal na atividade funcional hepática nos pacientes com esquistossomose hepatoesplênica, e é possível que as cirurgias, através de suas modificações hemodinâmicas (diminuição da congestão), sejam também benéficas por diminuírem o grau de colestase presente ou em regredirem a indução microssomal.

Preliminary studies on acute and subacute toxicity of an antidiabetic herbal preparation, Dianex.

Dianex, a polyherbal formulation intended to use for diabetic patients, has been screened for toxic effects. For acute toxicity studies, Dianex was administered orally in graded doses of 0.75-10 g/kg to the mice. For subacute toxicity studies, different doses of Dianex (1.0, 1.5 and 2.5 g/kg) were administered orally to the rats once daily for 30 days. Animals were observed for physiological and behavioural responses, mortality, food and water intake and body weight changes. Hematological evaluation was performed weekly. All the animals were sacrificed on 31st day and changes in organ weights and histology were examined. Biochemical studies were done in liver and serum. No mortality was observed up to 10 g/kg of Dianex in acute toxicity study. Daily administration of as high as 2.5 g/kg dose of Dianex did not result in any mortality or changes in gross behaviour, body weight, weight and histology of different organs or serum and liver biochemistry. However, significant increase in RBC count and hemoglobin level was observed in the treated animals at all doses. Other peripheral blood constituents were in the normal range. The dose of Dianex to produce significant antidiabetic activity in mouse, 0.25-0.5 g/kg, is much lower than the doses used in the present study. Therefore such doses may be safe for daily administration without causing any serious side effects.

DL-methionine supplementation of rice-and-bean diets affects gamma-glutamyltranspeptidase activity and glutathione content in livers of growing rats

Gamma-glutamyltranspeptidase (GGT-EC 2.3.2.2) activity and glutathione (GSH) content were measured in livers of female weanling Wistar rats (N = 5-18), submitted to rice-and-bean diets (13 and 6 per cent w/w protein), both supplemented or not with DL-methionine (0.5 and 0.23 g/100 g dry diet, respectively). After 28 days, the rats on the rice-and-bean diets showed significantly higher levels (four times higher) of liver GGT activity and a concomitant 50 per cent lower concentration of liver GSH in comparison with control groups feeding on casein. The addition of DL-methionine to rice-and-bean diets significantly increased the liver GSH content, which reached levels 50 per cent higher than those found in animals on casein diets. The increase in GSH was accompanied by a decrease in liver GGT activity, which did not reach levels as low as those observed in the control groups. No significant correlation could be established between GGT and GSH changes under the present experimental conditions. Linear correlation analysis only revealed that in animals submitted to unsupplemented rice-and-bean diets GSH concentration was positively associated (P<0.05) with weight gain, food intake and food efficiency. GGT, however, was negatively correlated (P<0.05) with food intake only, and exclusively for supplemented rice-and-bean diets. The high levels of GGT activity observed in the present study for rats receiving a rice-and-bean mixture could be a result of the poor quality of these diets associated with their deficiency in sulfur amino acids. The results also suggest that diet supplementation with methionine could be important in the reduction of the deleterious effects of GSH depletion by restoring the intracellular concentration of this tripeptide.

Enhancement of aflatoxin B1-induced enzyme altered hepatic foci in rats by treatment with carbon tetrachloride

The effect of carbon tetrachloride (CCl4) on aflatoxin B1 (AFB1)-induced enzyme altered hepatic foci has been examined in young male Fischer rats given AIN-76A diet. A single i.p. dose of AFB1 (0.2 mg/kg body wt) was given to rats 24 h after partial hepatectomy. Two weeks later, CCl4 (0.8 ml/kg body wt) was injected i.p. once a week for 9 weeks. Animals were sacrificed 24 h after the last dose of CCl4 and glutathione S-transferase placental form (GST-P) and gamma-glutamyl transpeptidase (GGT) positive hepatic foci were analyzed by immunohistochemical and histochemical methods, respectively. Ten weeks after AFB1 dosing, treatment with CCl4 increased the number of AFB1-induced enzyme altered foci several fold and produced a ten to twenty-fold increase in area and volume. GST-P was more sensitive than GGT in detecting AFB1-induced enzyme altered foci. Treatment with AFB1 or CCl4 produced mild hepatic fibrosis in zones 1 and 3 respectively, whereas both treatments produced severe fibrosis in zones 1 to 3 areas. Treatment with CCl4 after AFB1 dosing lowered hepatic GSH levels by 20% and increased lipid peroxidation by 40%. It appears that CCl4, by being an effective enhancer of AFB1-induced enzyme altered hepatic foci in the rat, may mimic cirrhosis observed in human hepatocellular carcinoma.

Modulation of gamma glutamyl transpeptidase activity in lymphoid system by organochlorine pesticides in rats.

Effects of 1,1,1,-trichloro-2,2-bis (p-chlorophenyl) ethane (DDT) and lindane were studied on gamma glutamyl transpeptidase (GGT) activity in different tissues of the lymphoid system in rats. DDT (100 or 200 ppm) and lindane (30 or 80 ppm) exposure for 8 weeks suppressed the GGT activity in a dose dependent manner in thymus and macrophage. In spleen, significant decrease in the enzyme activity was observed at higher exposure (200 ppm DDT or 80 ppm lindane) levels. Lindane suppressed GGT activity at both 30 or 80 ppm dose levels, while DDT reduced the GGT activity at 200 ppm but not at 100 ppm exposure in lymphocyte. The study indicates the possibility of using GGT as an effective and consistent biochemical marker for immunotoxicity of xenobiotics and other environmental stressors.

Anti-oxidant enzymes, gamma-glutamyl transpeptidase and lipid peroxidation in kidney of rats exposed to cigarette smoke.

Glutathione reductase (GR), glutathione peroxidase (GSH Px) and catalase (Cat) were determined in the kidneys of rats exposed to cigarette smoke for 3 months. Activity of the brush-border enzyme gamma-glutamyl transpeptidase (GGT), glutathione (GSH) and lipid peroxide levels (LPX) were also estimated in both, kidney homogenates and urine. Activities of GR, Cat, GGT and the levels of GSH were decreased in the kidney. However, the activities of GSH Px and LPX levels were increased. Urinary excretion of GGT, GSH and LPX were also higher. Fall in the activity of GR and rise in the activity of GSH Px, may perturb the reduced glutathione/oxidised glutathione ratio, which in turn could lead to increased LPX seen in chronic cigarette smoke exposure.

Lack of functional correlation between gamma-glutamyl transpeptidase and amino acid transport in the lactating mouse mammary gland.

Gamma-glutamyl transpeptidase (EC 2.3.2.2) in lactating mouse mammary gland was inhibited by affinity labelling of the tissue with 6-diazo-5-oxo-L-norleucine. Amino acid (L-alanine, L-methionine) uptake by the affinity labelled mammary gland tissue and the control tissue was measured in vitro. Uptake of amino acids by the affinity-labelled tissue was comparable to that of control tissue. These findings suggest that gamma-glutamyl cycle is not involved in amino acid uptake by the mammary gland.

Differential effects of protein restriction on gamma-glutamyltranspeptidase [EC 2.3.2.2] activity in young and mature rats

Gamma-glutamyltranspeptidase (GGT, EC 2.3.2.2) activity was determined in the plasma and liver of 40 young (50 days old) and 40 mature (300 days old) male Wistar rats, after a protein restriction period of 28 days. Casein protein levels used were: 1 percent, 3 percent, 5 percent, 7 percent and 28 percent (control). Weanling rats submitted to protein-free diet and adult rats submitted to that and other low-protein diets (1 percent, 3 percent or 5 percent casein) presented weight reductions (-0.38 +/- 0.07 g/day and -0.98 +/- 0.19 g/day, respectively). Only in young animals did these weight reductions parallel those of food consumption (37 +/- 12 percent of control), plasma protein (52 +/- 11 percent of control), plasma albumin (70 +/- 12 percent of control), hepatic RNA (68 +/- 7 percent of control) and protein (71 +/- 8 percent of control). A marked effect of the protein restriction, increasing the GGT activity, was also observed only in young rats. A significant (P<0.05) rise was promoted by the protein-free diet in the plasma GGT (2.83 +/- 1.39 vs 0.69 +/- 0.50 mU/ml for control) and by both the protein-free and 3 percent casein diets, in the liver GGT (respectively, 16.00 +/- 6.72 and 7.75 +/- 3.49 vs 0.94 +/- 0.57 U/g protein for control). The different results obtained for young in relation to mature animals could be explained by the reduction of both protein and sulfur-containing amino acid requirements with aging.