Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
1.
Diabetes ; 34(9): 911-6, 1985 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3896900

RESUMO

The reduction in blood glucose in non-insulin-dependent diabetes mellitus (NIDDM) brought about by the use of phenobarbital (PB), a hepatic microsomal enzyme inducer, suggests an improvement in insulin sensitivity. The effect of PB on insulin-mediated glucose metabolism was hence investigated using the euglycemic clamp technique in 10 women with NIDDM aged 56-75 yr. The addition of PB to sulfonylurea therapy, concurrently for 6 wk, reduced fasting blood glucose (BG, from 12.8 +/- 1.6 to 10.2 +/- 3.2 mmol/L, P less than 0.01) and immunoreactive insulin (IRI) levels (from 32.4 +/- 13.6 to 24.7 +/- 9.8 mU/L, P less than 0.01), whereas body weight remained unaltered. During the trial, there was a significant change in the glucose disposal rate (M, from 1.27 +/- 0.60 to 2.82 +/- 0.86 mg/kg/min, P less than 0.001), the metabolic clearance rate of glucose (from 0.89 +/- 0.41 to 2.24 +/- 1.27 ml/kg/min, P less than 0.01), the insulin sensitivity index (from 1.10 +/- 0.44 to 2.86 +/- 1.54 mg/kg/min: mU/L X 100, P less than 0.001), and the plasma antipyrine clearance rate (from 28.3 +/- 11.7 to 51.4 +/- 20.2 ml/min, P less than 0.001), an in vivo index of liver microsomal enzyme activity. The antipyrine clearance rate correlated with insulin-mediated glucose metabolism (r2 = 0.560, P less than 0.01). This correlation could be interpreted as indicating that, in NIDDM patients, peripheral glucose utilization and the liver microsomal enzyme system share common regulators. Our study suggests a new approach to the improvement of insulin sensitivity in NIDDM patients.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Indução Enzimática , Insulina/metabolismo , Idoso , Glicemia/análise , Feminino , Humanos , Insulina/sangue , Fígado/enzimologia , Testes de Função Hepática , Pessoa de Meia-Idade , Fenobarbital/farmacologia
2.
Clin Pharmacol Ther ; 61(3): 331-9, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9091249

RESUMO

OBJECTIVES: The effect of aging on drug metabolism in humans has not yet been completely described. METHODS: Two hundred twenty-six patients with equal histopathologic conditions were investigated. The cytochrome P450 contents in the liver biopsy samples, the plasma antipyrine clearance rates after oral administration and, as an independent control of vitality, serum testosterone levels were determined. RESULTS: Cytochrome P450 content in subjects from 20 to 29 years of age was 7.2 +/- 2.6 nmol.gm-1, increased during the fourth decade (+7.2%, p = NS), declined after 40 years (-16%, p < 0.01) to a level that remained unaltered up to 69 years, and declined further after 70 years (-32%, p < 0.001). The antipyrine (phenazone) clearance rate in young subjects was 46.4 +/- 18.5 ml.min-1, remained unaltered during the fourth decade, and declined after 40 years by a rate of 0.34 ml.min-1 per year toward old age (-29%, p < 0.001). The half-life in young subjects was 9.5 +/- 2.0 hours and increased after 30 years toward old age (+26%, p < 0.001). The volume of antipyrine distribution, 0.46 +/- 0.12 L.kg-1 in young subjects, decreased after 30 years (-11%). In line with the testosterone content, the decrease in drug metabolism was equal in both sexes. CONCLUSION: This study shows a reduction of in vitro and in vivo drug metabolism with age in humans. The data suggest that at least three age groups--young, middle-aged, and elderly--should be included in the evaluation of the pharmacokinetics of a new drug. The reduction of drug metabolism (-30%) after 70 years of age indicates that care is needed in the prescription of drugs for elderly subjects.


Assuntos
Envelhecimento/metabolismo , Anti-Inflamatórios não Esteroides/farmacocinética , Antipirina/farmacocinética , Sistema Enzimático do Citocromo P-450/fisiologia , Adulto , Idoso , Análise de Variância , Área Sob a Curva , Feminino , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Fumar/metabolismo
3.
Clin Pharmacol Ther ; 33(6): 826-35, 1983 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-6851415

RESUMO

Although treated adequately with antidiabetic drugs, diet, exercise, and education, patients with noninsulin-dependent diabetes mellitus (NIDDM) may develop resistance to treatment. In NIDDM hepatic microsomal enzyme activity is reduced and since postreceptional glucose metabolism is influenced by these enzymes, we treated the subjects with enzyme-inducing drugs. These inducers (phenobarbital and medroxyprogesterone acetate) when added as adjuvant therapy to sulfonyl urea regimen, reduced blood glucose and plasma insulin, and increased microsomal enzyme activity (as indicated by increased antipyrine metabolism). A trial with placebo did not alter serum glucose levels. Body weight fell and serum aminotransferase levels were normalized. These changes were reflected by reduction of liver fat content (determined by light microscopy), by increased surface density of smooth endoplasmic reticulum, and by repairation of the plasma cell membrane of hepatocytes, as seen in electron micrographs. Activation of postreceptional events in hepatocytes may thus be a new approach in the treatment of therapy-resistant type II diabetes.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Indução Enzimática/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Idoso , Antipirina/metabolismo , Glicemia , Feminino , Humanos , Fígado/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade
4.
Am J Clin Nutr ; 42(1): 147-51, 1985 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-4014064

RESUMO

Serum selenium was evaluated in relation to hepatic structure and function in 46 alcoholics with diagnostic liver biopsy classified into 4 groups by hepatic histology. Their serum selenium concentration varied from 12 to 88 micrograms/l and was lower (p less than 0.001) in all groups of alcoholics, ie patients with normal liver (53.0 +/- 20.7 micrograms/l, mean +/- SD), fatty liver (55.8 +/- 21.2 micrograms/l), alcoholic hepatitis (46.0 +/- 14.1 micrograms/l), and cirrhosis (41.1 +/- 12.8 micrograms/l), than in 25 healthy controls (88.7 +/- 11.0 micrograms/l). Serum selenium level was related to the severity of liver disease, and most reduced in subjects with decompensated alcoholic cirrhosis. Their serum selenium level (29.2 +/- 13.7 micrograms/l) was below (p less than 0.05) that obtained in alcoholics with normal liver and fatty liver respectively. Both inadequate dietary selenium intake and alcohol-induced changes in hepatic structure and function may have contributed to the decrease of serum selenium in the subjects studied.


Assuntos
Hepatopatias Alcoólicas/sangue , Testes de Função Hepática , Selênio/sangue , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Fígado/patologia , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/fisiopatologia , Masculino , Pessoa de Meia-Idade
5.
Pathol Res Pract ; 176(2-4): 115-24, 1983 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-6222294

RESUMO

Medroxyprogesterone acetate (MPA) induced morphological alterations in the normal female rat liver and after carbon tetrachloride exposure were assessed by light and electron microscopy and morphometry. Administration of MPA increased the smooth endoplasmic reticulum (SER) in normal rat. Carbon tetrachloride, injected intraperitoneally for four weeks, caused fatty accumulation, enlargement of the cell nucleus and decrease of the rough endoplasmic reticulum (RER) and increase of the SER. After one week of recovery, without treatment, the fatty infiltration and the SER membranes decreased and the RER increased. MPA, following injury, induced a decrease in the fatty accumulation and mitochondrial volume density and the hepatocyte nuclear and cytoplasm size normalized. The SER membrane volume density increased and the surface density decreased, the RER membrane volume density increased while the surface density did not alter significantly. The volume densities of the mitochondria and the peroxisomes decreased in the MPA treated CCl4 exposed groups. The results demonstrate that MPA induces a proliferation of the SER in normal rat liver and after hepatic injury the compound has a beneficial effect on the regeneration.


Assuntos
Antineoplásicos/farmacologia , Intoxicação por Tetracloreto de Carbono/patologia , Imunossupressores/farmacologia , Fígado/efeitos dos fármacos , Medroxiprogesterona/análogos & derivados , Animais , Feminino , Fígado/patologia , Fígado/ultraestrutura , Regeneração Hepática/efeitos dos fármacos , Medroxiprogesterona/farmacologia , Acetato de Medroxiprogesterona , Microscopia Eletrônica , Organoides/efeitos dos fármacos , Ratos , Ratos Endogâmicos
7.
Scand J Gastroenterol ; 16(7): 853-63, 1981.
Artigo em Inglês | MEDLINE | ID: mdl-7323715

RESUMO

Alpha-methyldopa-induced histologic alterations were investigated in 21 patients with hepatic injury after short- and long-term exposure. Seven patients developed liver injury within 6 months and 24 after several years (mean, 5 years) of exposure. Histologic findings and clinical and biochemical data differed significantly in the two groups. Morphologic analysis of the short-term-treated group revealed marked parenchymatous degeneration, focal, confluent and massive necrosis, and inflammation. Fatty accumulation and increased fibrous trabeculae were characteristic for the patients treated for long term. All patients in the short-term-exposed group had acute and severe hepatitis. Four of them had icterus. Two patients died of hepatic coma. Patients in the long-term-treated group had for several months initially mild but increasing discomfort, dyspepsia, nausea, and colics. Liver function tests in these groups revealed differences in serum albumin, bilirubin, and transferase levels. No changes were observed in alkaline phosphatase and Thrombotest. Fat accumulation and fibrous trabeculae suggest that the alterations precede the clinical symptoms and biochemical signs of hepatitis. The findings show that alpha-methyldopa may induce hepatocellular injury after short- and long-term exposure.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fígado/patologia , Metildopa/efeitos adversos , Adulto , Idoso , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fígado Gorduroso/induzido quimicamente , Feminino , Humanos , Fígado/efeitos dos fármacos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Necrose , Fatores de Tempo
8.
Scand J Gastroenterol ; 16(7): 865-72, 1981.
Artigo em Inglês | MEDLINE | ID: mdl-7323716

RESUMO

Alpha-methyldopa-induced liver injury was studied in six patients by clinical, biochemical, histologic, and morphometric methods. The patients, all women, developed hepatic injury after long-term therapy lasting 2 to 8 years. Withdrawal of the drug resulted in improvement of the symptoms. Hepatitis with fibrosis and moderate to severe fatty accumulation was seen in most of the liver biopsies at onset of symptoms. Follow-up ranged from 7 to 24.5 months, at the end of which the liver function test results were in the normal range. A second liver biopsy showed significant decrease in fatty infiltration. Three patients showed a decrease in lipid content from moderate to mild or normal and two other patients from severe to moderate. A 73-year-old patient had chronic aggressive hepatitis with massive necrosis of the parenchyma after 8 years of therapy, and follow-up biopsy 12 months later showed cirrhosis. In this study alpha-methyldopa withdrawal resulted in a reduction of lipid and fibrous trabeculae content, possibly caused by alpha-methyldopa-induced derangement of liver function.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/patologia , Fígado/patologia , Metildopa/efeitos adversos , Idoso , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , Seguimentos , Humanos , Fígado/efeitos dos fármacos , Testes de Função Hepática , Pessoa de Meia-Idade , Fatores de Tempo
9.
Scand J Clin Lab Invest ; 43(8): 671-5, 1983 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6665516

RESUMO

The association of serum LDL and HDL cholesterol with hepatic microsomal enzyme induction, assessed by plasma antipyrine kinetics was investigated in 30 epileptics. Patients on enzyme-inducing anticonvulsants had reduced LDL/HDL cholesterol ratios and elevated HDL cholesterol concentrations and HDL/total cholesterol ratios, indicating a cholesterol transfer from LDL to HDL. Strong hepatic microsomal enzyme induction was associated with reduced LDL cholesterol. The LDL/HDL cholesterol ratio was negatively proportional and the HDL/total cholesterol ratio positively proportional to the antipyrine clearance rate. Epileptics, particularly those with a high antipyrine clearance, had a cholesterol distribution pattern characteristic of a low probability of developing coronary atherosclerosis. The results support the view that hepatic microsomal enzyme induction favourably alters the cholesterol distribution in the body.


Assuntos
Antipirina/metabolismo , Colesterol/sangue , Indução Enzimática/efeitos dos fármacos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Microssomos Hepáticos/enzimologia , Adulto , Anticonvulsivantes/farmacologia , HDL-Colesterol , LDL-Colesterol , Doença das Coronárias/etiologia , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Risco
10.
Res Commun Chem Pathol Pharmacol ; 35(1): 121-35, 1982 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7058284

RESUMO

Therapy with enzyme inducing drugs may improve the clinical state of alcoholics with liver cirrhosis. The histological changes associated with the therapy were investigated by comparing liver biopsies before and after phenobarbital and medroxyprogesterone acetate treatment, known inducers of hepatic microsomal enzyme system, in eight alcoholics with cirrhosis and two control groups, subjects with normal liver and endstage alcoholic cirrhosis. Pericellular collagen, determined morphometrically, reduced from a point value of 87.6 +/- 28.3 to 63.4 +/- 16.7 (p less than 0.01), while the fibrous septa as well as the non-fatty and fatty parenchyma did not alter significantly. Antipyrine metabolism, an index of hepatic cell function, improved from 17.4 +/- 6.4 to 45.6 +/- 22.2 ml/min (p less than 0.01). Although direct correlation between the decrease of pericellular collagen fibres and antipyrine metabolism was not significant (r = 0.410) the findings suggest that accumulation of pericellular collagen prevents mechanically and availability of the compound to the cell, thus delaying its metabolism.


Assuntos
Colágeno/metabolismo , Cirrose Hepática Alcoólica/metabolismo , Adulto , Antipirina/sangue , Humanos , Fígado/patologia , Cirrose Hepática Alcoólica/patologia , Masculino , Medroxiprogesterona/farmacologia , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Fenobarbital/farmacologia
11.
Scand J Gastroenterol ; 18(6): 743-7, 1983 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-6669938

RESUMO

Twenty-four patients with steatotic liver underwent computerized tomography (CT) and ultrasound (US) examinations and liver biopsy, performed within a maximum interval of 6 weeks. The CT and US findings were compared with the fat and fibrous content of the biopsy specimens. A good linear inverse correlation between the CT findings and fat content was found. The ranges of CT values were 39-60 HU (mean, 52 HU) for mild fat content (less than or equal to 9.9%), 4-46 HU (mean, 27 HU) for moderate fat content (10.0-24.9%), and -6 to 19 HU (mean, 10 HU) for severe fat content (greater than or equal to 25.0%). With US it was possible to estimate roughly the fat and fibrous content of the liver. There was always the 'bright liver' finding in patients with 10.0% or more fat content, but it was impossible to estimate the content of fat more accurately. 'Bright liver' was also found in most patients with mildly and in all patients with severely increased fibrous content. It was impossible to differentiate the latter from each other or from the 'bright liver' caused by fatty degeneration.


Assuntos
Fígado Gorduroso/diagnóstico , Lipídeos/análise , Fígado/análise , Tomografia Computadorizada por Raios X , Ultrassonografia , Adulto , Idoso , Estudos de Avaliação como Assunto , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade
12.
Acta Med Scand ; 212(4): 207-15, 1982.
Artigo em Inglês | MEDLINE | ID: mdl-7148516

RESUMO

The hepatic injury developing during occupational exposure to chemicals was investigated in 23 male patients, aged 23-49 years, by comparing case histories, liver function tests, hepatic microsomal enzyme activities in vivo and in vitro with histology. The subjects, 15 chemical industry workers and 8 painters, had disturbed liver tests after years of exposure to solvents, paints and lacquers. Characteristic for the patients was a 2-4-fold increase in serum aminotransferases associated with normal liver or reactive hepatitis with or without fatty liver. All patients, except subjects with fatty change, had metabolically active liver which was reflected as adaptive and toxic changes in cellular ultrastructure. The biochemical liver tests normalized within 3-6 weeks after cessation of the exposure. The findings demonstrate that occupational exposure to chemical solvents may insidiously damage the liver. The injury is detectable by biochemical, metabolic and histological investigations in the early phase.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Doenças Profissionais/induzido quimicamente , Adulto , Humanos , Laca/intoxicação , Fígado/patologia , Hepatopatias/patologia , Testes de Função Hepática , Masculino , Microscopia Eletrônica , Microssomos Hepáticos/enzimologia , Pessoa de Meia-Idade , Pintura/intoxicação , Solventes/intoxicação
13.
Res Commun Chem Pathol Pharmacol ; 33(1): 163-74, 1981 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7268203

RESUMO

The relationship between liver histology and plasma high density lipoproteins (HDL) was investigated in 40 patients with diagnostic liver biopsy. The subjects with slight or marked changes in liver histology had low HDL cholesterol and apoprotein (A-I and A-II) levels, low HDL cholesterol/total cholesterol ratios and high triglyceride concentrations as compared with subjects with a normal liver. Plasma HDL cholesterol, HDL cholesterol/total cholesterol ratio and apoprotein A-I were directly proportional and triglycerides inversely proportional to the amount of non-fatty parenchyma in the livers. Conventional liver tests were not related to liver histology. The findings indicate that plasma HDL levels reflect alterations in hepatic parenchyma. Quantitative assessments of liver changes may hence be of significance when evaluating plasma HDL levels.


Assuntos
Lipoproteínas HDL/sangue , Fígado/patologia , Adulto , Idoso , Colesterol/sangue , Eletrocardiografia , Fígado Gorduroso/sangue , Fígado Gorduroso/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue
14.
Diabete Metab ; 9(2): 100-5, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6617929

RESUMO

The relationship between blood lactate levels, liver histology and microsomal enzyme activity (cytochrome P-450 content) was assessed in 32 non-insulin-dependent diabetics (NIDD) undergoing diagnostic liver biopsy. Fasting blood lactate was related to liver histology and the mean was in the low normal range in the diabetics with an intact liver, whereas higher values were noted in the diabetics with a fatty liver, inflammatory changes and an increase in fibrous trabeculae. Similarly, in the diabetics with an abnormal liver, there was a tendency for pyruvate to be elevated, and body weights and serum insulin concentrations were higher than in the NIDD with an intact liver. P-450 was inversely related to liver histology and its content was reduced in association with increases in fat and fibrous tissues. P-450 was significantly correlated with lactate (rs -0.79), pyruvate (rs -0.65) and serum insulin (rs -0.53). The results revealed close associations between blood lactate, hepatic structure and microsomal enzyme activity, and emphasize that liver function is an important consideration when lactate metabolism is evaluated in NIDD.


Assuntos
Diabetes Mellitus/sangue , Lactatos/sangue , Fígado/patologia , Microssomos Hepáticos/enzimologia , Idoso , Glicemia/análise , Sistema Enzimático do Citocromo P-450/sangue , Diabetes Mellitus/enzimologia , Diabetes Mellitus/patologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Ácido Láctico , Masculino , Pessoa de Meia-Idade , Piruvatos/sangue , Ácido Pirúvico
15.
J Hepatol ; 1(5): 501-11, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-2932501

RESUMO

The effect of therapy with a microsomal enzyme-inducing drug on the cirrhotic liver in male Wistar rats was investigated by morphological and biochemical means. The cirrhotic animals were treated with medroxyprogesterone acetate (MPA) 100 mg/kg body wt, i.p. daily for a week. In the cirrhotic rats liver weight was enhanced, liver protein content was increased while total liver DNA content remained unchanged upon MPA treatment. The hepatic regenerative nodule size increased, as determined by morphological means. Hepatic microsomal metabolic activity was improved, as seen by increases in NADPH-cytochrome P-450 reductase and aminopyrine N-demethylase activities and cytochrome P-450 content. Since the increases in liver protein content and metabolic activity were relatively greater in the cirrhotic than intact animals upon MPA treatment, it was suggested that the spontaneous regeneration associated with liver cirrhosis may affect the induction phenomenon. The results demonstrate that an enzyme inducer may have beneficial effects on the cirrhotic liver by elevating metabolic activity and parenchymal mass.


Assuntos
Cirrose Hepática/tratamento farmacológico , Medroxiprogesterona/análogos & derivados , Aminopirina N-Desmetilase/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Redutases do Citocromo/metabolismo , DNA/metabolismo , Indução Enzimática/efeitos dos fármacos , Testes de Função Hepática , Masculino , Medroxiprogesterona/uso terapêutico , Acetato de Medroxiprogesterona , Microssomos Hepáticos/enzimologia , Proteínas/metabolismo , Ratos
16.
J Hepatol ; 1(3): 277-90, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-2999223

RESUMO

Carbohydrate intolerance was investigated in 8 alcoholics with liver cirrhosis and in controls. Indices of carbohydrate metabolism, glucose and insulin levels after glucose loading, were compared with glucose phosphorylating (glucokinase, hexokinase) and releasing (glucose-6-phosphatase) enzymes. Comparison was also made with pericellular collagen in liver biopsies and with insulin sensitivity assessed by the euglycemic clamp technique and with conventional liver function tests including oral antipyrine test. Glucokinase activity was low or absent, hexokinase activity increased and the GK/HK ratio reduced. Glucose-6-phosphatase activity was lowered and insulin sensitivity decreased. Pericellular collagen was increased (P less than 0.001) and related to the fasting glucose (r0.593) and insulin levels (r0.526). Blood glucose was related to antipyrine metabolism (r-0.727) but not to the other liver tests. Glucose intolerance in cirrhosis seems to be associated with reduced glucose phosphorylating and liberating enzyme activities. Hyperinsulinaemia, developing secondarily, may then lead to insulin resistance.


Assuntos
Glicemia/metabolismo , Resistência à Insulina , Cirrose Hepática Alcoólica/metabolismo , Fígado/enzimologia , Adulto , Idoso , Antipirina/metabolismo , Colágeno/metabolismo , Glucoquinase/análise , Glucose/metabolismo , Glucose-6-Fosfatase/análise , Hexoquinase/análise , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação
17.
Res Commun Chem Pathol Pharmacol ; 53(2): 159-65, 1986 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3489965

RESUMO

Chemically induced liver cirrhosis in the rat was associated with an increased biosynthesis of the hepatic polyamines putrescine and spermidine and a reduction in the activities of the cytochrome P-450-associated monooxygenase enzymes aryl hydrocarbon hydroxylase, ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase. These parameters were normalized after a 4-week spontaneous regeneration period. The results suggest an independent regulatory mechanism of polyamine biosynthesis and monooxygenase expression.


Assuntos
Hidrocarboneto de Aril Hidroxilases/metabolismo , Cirrose Hepática Experimental/enzimologia , Oxirredutases/metabolismo , Oxigenases/metabolismo , Poliaminas/biossíntese , O-Dealquilase 7-Alcoxicumarina , Animais , Hidrocarboneto de Aril Hidroxilases/genética , Tetracloreto de Carbono/farmacologia , Citocromo P-450 CYP1A1 , Sistema Enzimático do Citocromo P-450/metabolismo , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/metabolismo , Ornitina Descarboxilase/metabolismo , Oxirredutases/genética , Oxigenases/genética , Putrescina/metabolismo , Ratos , Ratos Endogâmicos , Espermidina/metabolismo
18.
Scand J Gastroenterol ; 21(6): 737-43, 1986 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3529363

RESUMO

The role of the liver in glucose metabolism was investigated in 24 consecutive patients undergoing diagnostic liver biopsy by comparing hepatic morphometry and microsomal enzyme activity in vivo (antipyrine) with fasting blood glucose (BG) and immunoreactive insulin (IRI) levels and with the metabolic clearance rate of insulin and the insulin sensitivity index. The patients had elevated BG and IRI levels and reduced insulin-mediated glucose metabolism, insulin sensitivity index, and microsomal enzyme activity as compared with controls. The insulin metabolic clearance rate did not diverge among the groups. Patients with fatty liver had a high BG associated with a reduced glucose disposal rate, whereas fasting IRI did not diverge when compared with other liver patients. Glucose disposal rate was related to the amount of unaltered liver (r2 = 0.640; p less than 0.001) and antipyrine metabolism (r = 0.631; p less than 0.01) and inversely related to the amount of fat (r2 = 0.585; p less than 0.01). The findings demonstrate that insulin-mediated glucose metabolism is related to liver structure and microsomal function. Accumulation of fat in the liver seems to be a major factor associated with reduced insulin sensitivity and glucose tolerance.


Assuntos
Glicemia/metabolismo , Insulina/farmacologia , Hepatopatias/metabolismo , Fígado/patologia , Microssomos Hepáticos/enzimologia , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Aspartato Aminotransferases/metabolismo , Feminino , Humanos , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade
19.
Acta Med Scand ; 214(3): 181-9, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6660024

RESUMO

Three consecutive head nurses developed liver injury after years of handling cytostatic drugs. They had neurological symptoms associated with elevated serum alanine amino-transferase (ALAT) and alkaline phosphatase (ALP) levels. Liver histology showed portal hepatitis with piecemeal necrosis in one of them, the others had hepatic fibrosis and fat accumulation. The subjects' livers were metabolically active as reflected by adaptive and toxic changes in cellular ultrastructure. After withdrawal of the drugs, serum ALAT and ALP values fluctuated between normal and 2-3 times elevated. Follow-up biopsies demonstrated an increase in collagen fibres and a decrease in microsomal enzyme activity, as reflected by arylhydrocarbon hydroxylase activity in vitro. The findings suggest that handling of cytostatic drugs may insidiously damage the liver, which, with time, seems to lead to irreversible fibrosis.


Assuntos
Antineoplásicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fígado/efeitos dos fármacos , Enfermeiras e Enfermeiros , Doenças Profissionais/induzido quimicamente , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Feminino , Humanos , Fígado/patologia , Microssomos Hepáticos/enzimologia
20.
Acta Med Scand ; 214(2): 103-9, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6624542

RESUMO

The association of high-density lipoproteins (HDL) in plasma with liver lipids and proteins was investigated in 28 subjects with diagnostic liver biopsy. Lipids and proteins were evaluated in relation to hepatic histology and microsomal enzyme induction, assessed by liver cytochrome P-450. Moderate-severe hepatic parenchymal changes were associated with low liver phospholipids, protein and cytochrome P-450, low plasma HDL cholesterol (HDL-C), and high hepatic triglycerides. Liver microsomal induction accompanying anticonvulsant therapy was associated with high liver phospholipids and protein, high plasma HDL-C, apoproteins A-I and A-II, and high HDL-C/total cholesterol (T-C) ratio. HDL-C, A-I and the HDL-C/T-C ratio were directly proportional to liver phospholipids, protein and cytochrome P-450, inversely related to hepatic triglycerides. Increases in hepatic phospholipids and protein, characteristic of microsomal induction, may lead to the elevation of plasma HDL apoprotein and HDL-C levels and HDL-C/T-C ratios, and thus reduce the risk of coronary heart disease.


Assuntos
Apoproteínas/metabolismo , Metabolismo dos Lipídeos , Lipoproteínas HDL/sangue , Fígado/metabolismo , Microssomos Hepáticos/enzimologia , Adulto , Idoso , Colesterol/metabolismo , HDL-Colesterol , Sistema Enzimático do Citocromo P-450/biossíntese , Indução Enzimática , Feminino , Humanos , Lipoproteínas HDL/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Fosfolipídeos/metabolismo , Triglicerídeos/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA