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1.
Ann Biol Clin (Paris) ; 66(6): 621-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19091660

RESUMO

Cystic fibrosis (CF), is the most common life-shortening autosomal recessive disorder in Caucasians. It is caused by mutations in a single gene on the long arm of chromosome 7 that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CF is characterized by abnormal Na+ and Cl- ion transport in several tissues, including the lungs, pancreas, gastrointestinal tract, liver, sweat glands, and male reproductive system. Progressive pulmonary disease is the dominant clinical feature of CF and accounts for morbidity and mortality. The inflammation characterized by an overabundance of activated neutrophils and macrophages on the respiratory epithelial surface is associated to a high production of reactive oxygen species (ROS) which contribute to the pathogenesis of cystic fibrosis. ROS could have different origins but the role of the NADPH oxidase system is essential. The "NADPH oxidases" (NOX/DUOX) family is an enzymatic complex formed by cytosolic and membrane subunits. Until now several homologues of the phagocytic NADPH oxidase have been identified in different tissues and it has been shown that the lungs preferentially expressed DUOX1-2. Thus, DUOX1-2 could be implicated in the anti-infectious defense system. The role of DUOX enzymes as a source of ROS in cystic fibrosis is examined as they could contribute to a better understanding of molecular mechanisms in CF. Moreover they could be a potential target for a new therapeutic approach.


Assuntos
Fibrose Cística/etiologia , NADPH Oxidases/fisiologia , Espécies Reativas de Oxigênio , Fibrose Cística/enzimologia , Fibrose Cística/genética , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Oxidases Duais , Feminino , Humanos , Masculino , Proteínas de Membrana , NADPH Oxidase 5 , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
2.
Ann Biol Clin (Paris) ; 66(2): 143-50, 2008.
Artigo em Francês | MEDLINE | ID: mdl-18390424

RESUMO

Gliomas represent 50% of primary brain tumors, and their prognosis remains poor despite the advances in diagnosis and therapeutic strategies. Low grade gliomas (LGG) are infiltrative tumors and they constantly undergo malignant transformation. Metabolic exploration of human gliomas in vivo, in animals and by using cell culture models showed important differences between tumor tissues and normal brain tissues, which can provide new markers for diagnosis, prognosis and therapeutic targets. In this study, energetic and oxidant metabolisms were explored in biopsy extracts of LGG obtained from the centre and the periphery of tumors. Metabolic pattern of these tumors was explored and the differences between the centre and the periphery pointed. Our study showed a metabolic heterogeneity between tumors, with hypermetabolic and hypometabolic profiles. Lactate to pyruvate ratio was>1, suggesting that the energy metabolism in LGG is glycolytic in nature, particularly in the centre of the tumors. Peripheral samples of tumors showed increased glucose consumption and cytochrome c oxidase activity. Lipid peroxidation and catalase activity were also increased in the periphery compared to the centre of tumors. A relationship between the main antioxidant and energy metabolism enzymes activities was observed, suggesting that periphery of tumors is more active metabolically and more resistant to free radical injury.


Assuntos
Neoplasias Encefálicas/metabolismo , Metabolismo Energético , Glioma/metabolismo , Estresse Oxidativo , Adulto , Idoso , Biópsia , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/patologia , Catalase/metabolismo , Estudos de Coortes , Interpretação Estatística de Dados , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Feminino , Glioma/diagnóstico , Glioma/enzimologia , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Espectrometria de Fluorescência , Espectrofotometria
3.
Ann Biol Clin (Paris) ; 66(2): 131-41, 2008.
Artigo em Francês | MEDLINE | ID: mdl-18390423

RESUMO

This review reports recent observations concerning specificities of the cellular energy metabolism in cerebral tissues that highlight on characteristics of that of glial tumours, such as the association of metabolic alterations aggressiveness of these tumours. Compared to normal cerebral tissue, glial tissue exhibits both a relative independence towards oxygen and substrate furnitures and thus vascularization, as well as the metabolic co-operation of neurons and glial cells within the tumour. Occurrence of a Warburg effect could explain such metabolic autonomy that might be associated to genetic changes observed in gliomas. Characteristics of the glycolytic metabolism within glioma tissue therefore may be novel land therapeutic approaches for the treatment of these tumours.


Assuntos
Neoplasias Encefálicas/metabolismo , Encéfalo/metabolismo , Metabolismo Energético , Glioma/metabolismo , Adulto , Fatores Etários , Animais , Astrócitos/metabolismo , Astrócitos/fisiologia , Encéfalo/patologia , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/patologia , Criança , Modelos Animais de Doenças , Glioma/epidemiologia , Glioma/genética , Glioma/patologia , Glucose/metabolismo , Glicólise , Humanos , Lactatos/metabolismo , Metabolismo , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Estadiamento de Neoplasias
4.
Pathol Biol (Paris) ; 53(3): 174-82, 2005 Apr.
Artigo em Francês | MEDLINE | ID: mdl-15781380

RESUMO

The existence of the natriuric/iodide symporter (NIS) represents a new view to understand the thyroid metabolism of iodide. Due to its cellular localisation on basolateral membrane, this transporter exerts an essential role in the biological functions of the thyroid, especially the capacity to accumulate iodide into the thyrocytes. Clinical perspectives of NIS activity modulation would ameliorate the diagnosis and the treatment of thyroid diseases by using radioisotopes transported by the NIS (131 iodide, 99m technetium, 188 rhenium). The study of the regulation pathways modulating the expression and the activity of the symporter NIS, would allow to understand pathogeny of benign or malignant diseases of the thyroid gland. The relative facility of the therapy management by 131 iodide and its good efficiency associated to the recent advance of NIS function also give an interesting perspective to the gene therapy treatment of the nonthyroid cancers despite existent methodological problems.


Assuntos
Simportadores/fisiologia , Humanos , Radiografia , Compostos Radiofarmacêuticos , Doenças da Glândula Tireoide/diagnóstico por imagem , Doenças da Glândula Tireoide/fisiopatologia , Glândula Tireoide/fisiologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem
5.
Ann Biol Clin (Paris) ; 62(4): 456-61, 2004.
Artigo em Francês | MEDLINE | ID: mdl-15297242

RESUMO

Iodine is an essential element for thyroid hormone synthesis. Iodine disorders induced biological and/to clinical expression of thyroid dysfunction. Inappropriate iodine intake (by default or by excess) is worrying in terms of public health in France regarding the iodine deficiency and the frequency of iatrogen iodine overloads. Urinary iodine determination which generally implicates the use of a cerimetric method, is an useful tool to evaluate iodine intakes. In this study, we described the analytical aspects of a semiquantitative method of urinary iodine using a redox indicator, ferroin. This method allows the screening of iodine excess or deficiency in a short time (< 3 hours) with a good specificity and sensitivity. Since this assay does not require specific apparatus, it could be easily developed in clinical chemistry laboratories for the detection of inappropriate iodine intakes, and could be useful for prevention programs of iodine deficiency.


Assuntos
Indicadores e Reagentes , Iodo , Programas de Rastreamento/métodos , Fenantrolinas , Urinálise/métodos , Viés , Colorimetria/métodos , Colorimetria/normas , Análise Discriminante , Humanos , Iodo/deficiência , Iodo/intoxicação , Iodo/urina , Programas de Rastreamento/normas , Oxirredução , Valores de Referência , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Temperatura , Tiocianatos/urina , Fatores de Tempo , Urinálise/normas
6.
Rev Mal Respir ; 21(1): 67-73, 2004 Feb.
Artigo em Francês | MEDLINE | ID: mdl-15260040

RESUMO

INTRODUCTION: Advertising information on cigarette package participate to the reduction of health risks from smoking. Impact on smokers has been poorly studied. This study intended to determine the smoker perception of nicotine and tar yields of cigarettes. METHODS: Consulting in an outpatient smoking cessation clinic, 171 smokers answered freely and spontaneously to a questionnaire evaluating their perception of nicotine and tar yields, cigarette consumption (number and brand), nicotine dependence. Simultaneously, biological tobacco markers were measured. RESULTS: The number of cigarettes, nicotine dependence and specific tobacco markers were not significantly different according to the cigarette type: "full savour", "light" or "ultra light". Women smoked less than men and 54% preferred "light" cigarettes versus 37% of men. These smokers were entering a tobacco cessation program, it was assumed they had lead a prior reflection about their smoking habits. Only 8% of them gave the correct values of nicotine and tar yields and 14% gave approximate values. Tar levels were highly underestimated. CONCLUSIONS: This study shows that smokers have actually no interest for nicotine and tar yields. As the new decree which modifies manufacture's obligation concerning the legal mentions, is applicable in January 2004 in France; our conclusion may change in the future.


Assuntos
Comportamento do Consumidor , Fumar/epidemiologia , Adulto , Feminino , Humanos , Masculino , Nicotina , Inquéritos e Questionários , Alcatrões , Nicotiana
7.
Ann Biol Clin (Paris) ; 61(2): 147-58, 2003.
Artigo em Francês | MEDLINE | ID: mdl-12702469

RESUMO

Matrix metalloproteinases (MMPs) play a key role in the physiology of connective tissue development, morphogenesis and wound healing, but their unregulated activity has been implicated in numerous disease processes including arthritis, tumor cell metastasis and atherosclerosis. MMP family consists of at least 20 members; MMPs are produced by the different cell types (vascular smooth muscle cells, monocytes, endothelial cells) involved in the atheromatous plaque formation and participate to extracellular matrix remodelling and cell infiltration or migration. Since excessive tissue remodelling and increased matrix metalloproteinase activity have been demonstrated during atherosclerotic lesion progression (including plaque disruption), MMPs represent a potential target for therapeutic intervention to modify vascular pathology, by restoring the MMP/TIMP physiological equilibrium. This review highlights the structures of MMPs and their physiological inhibitors, the Tissue Inhibitors of MMPs (TIMPs), and describes the current developments in pharmacological MMP inhibition.


Assuntos
Arteriosclerose/tratamento farmacológico , Inibidores de Metaloproteinases de Matriz , Metaloproteinases da Matriz/fisiologia , Compostos Orgânicos , Fenilalanina/análogos & derivados , Inibidores Teciduais de Metaloproteinases/fisiologia , Inibidores Teciduais de Metaloproteinases/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Antineoplásicos/uso terapêutico , Doenças da Aorta/sangue , Doenças da Aorta/tratamento farmacológico , Doenças da Aorta/fisiopatologia , Doenças da Aorta/prevenção & controle , Arteriosclerose/sangue , Arteriosclerose/enzimologia , Arteriosclerose/prevenção & controle , Estudos de Casos e Controles , Ensaios Clínicos como Assunto , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/prevenção & controle , Doxiciclina/uso terapêutico , Humanos , Ácidos Hidroxâmicos/uso terapêutico , Hiperlipidemias/complicações , Hipolipemiantes/uso terapêutico , Metaloproteinases da Matriz/sangue , Metaloproteinases da Matriz/genética , Metaloendopeptidases/antagonistas & inibidores , Fenilalanina/uso terapêutico , Polimorfismo Genético , Estudos Prospectivos , Ratos , Fatores de Risco , Tiofenos/uso terapêutico , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-1/fisiologia , Inibidor Tecidual de Metaloproteinase-2/fisiologia , Inibidor Tecidual de Metaloproteinase-3/sangue , Inibidor Tecidual de Metaloproteinase-3/fisiologia , Inibidores Teciduais de Metaloproteinases/sangue , Inibidores Teciduais de Metaloproteinases/metabolismo
8.
Atherosclerosis ; 154(2): 421-7, 2001 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-11166775

RESUMO

BACKGROUND: Hyperhomocysteinemia is a risk factor for cardiovascular disease. Elevation in homocysteine levels has recently been demonstrated during lipid lowering treatment with fibrates. We compared the effect of a statin and a fibrate (atorvastatin and fenofibrate) on plasma levels of homocysteine and other thiol compounds in hyperlipidemic patients. METHOD AND RESULTS: The study was of open randomized, parallel design with a preliminary screening phase, and a 6 week placebo period. After the placebo period, patients were allocated randomly to atorvastatin or fenofibrate for a 6 month period. Plasma thiols were assayed by high pressure liquid chromatography with fluorescence detection. There were 29 patients in the fenofibrate group and 24 in the atorvastatin group. Fenofibrate induced a significant increase in both homocysteine and cysteine plasma levels (+35.8 and +18%, respectively, P<0.0001); by contrast, cysteinylglycine remained stable. There were no significant changes in any thiol compounds in the atorvastatin group. Both treatments induced a significant decrease in uric acid, although fenofibrate was noticeably more effective than atorvastatin (-22.8 and -6.4%, respectively). Fenofibrate induced a non-significant increase in creatinine (12%) while atorvastatin reduced it (4.7%, NS). CONCLUSION: Our study confirms that the induction of elevations in plasma homocysteine and cysteine levels are a distinct feature of the pleiotropic effects of fibrates. Further studies are needed not only to investigate the potential deleterious effects of this modification, but also to define the specific mechanism which underlies such fibrate-mediated action.


Assuntos
Fenofibrato/uso terapêutico , Ácidos Heptanoicos/uso terapêutico , Homocisteína/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo V/sangue , Hipolipemiantes/uso terapêutico , Pirróis/uso terapêutico , Atorvastatina , Biomarcadores/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Cromatografia Líquida de Alta Pressão , Cisteína/sangue , Dipeptídeos/sangue , Feminino , Humanos , Hiperlipoproteinemia Tipo V/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue
11.
Presse Med ; 29(6): 287-93, 2000 Feb 19.
Artigo em Francês | MEDLINE | ID: mdl-10719442

RESUMO

OBJECTIVE: Previous studies suggest that hyperhomocysteinemia may be a risk factor for arterial and venous thrombosis. We retrospectively analyzed data from 75 patients with thrombosis. PATIENTS AND METHODS: Thirty-four patients had arterial thrombosis, 22 venous thrombosis and 19 venous and arterial thrombosis. Of the 75 patients (49 men and 26 women, mean age 49 +/- 15 years) about two-thirds had recurrent episodes of thrombosis. RESULTS: Hyperhomocysteinemia was defined as serum homocysteine level above 14.1 mumol/l (mean + 2.7 SD in healthy subjects) and was found in 67 patients (89%, CI95% = 80-95). Mean total homocysteine concentration was 21.6 +/- 13.6 mumol/l for the 75 patients. About half of the patients were smokers, 35% had hypertension and 25% high serum cholesterol. There was no significant relationship between serum homocysteine level and smoking status, hypertension or serum cholesterol level. Ten patients (13%, CI95% = 7-23) had low serum cobalamin (< 150 pmol/l). Serum folates were < or = 10 nmol in 41% of the patients in the arterial thrombosis group (CI95% = 25-59), in 27% in the venous thrombosis group (CI95% = 11-50), and in 31% in the arterial and venous thrombosis group (CI95% = 13-57). Thirteen patients received vitamin B supplementation. Hyperhomocysteinemia decreased in 12/13 patients (CI95% = 64-100) and returned to normal values in 9/13 patients (69%, CI95% = 38-91). CONCLUSION: Our data show that hyperhomocysteinemia is frequently found in arterial and venous thrombosis. Further studies are needed to determine the clinical impact of homocysteine lowering therapy.


Assuntos
Hiper-Homocisteinemia/sangue , Trombose/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombose/etiologia , Trombose/prevenção & controle , Vitamina B 12/administração & dosagem
12.
Atherosclerosis ; 146(1): 53-9, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10487486

RESUMO

Several studies have reported that moderate hyperhomocysteinemia is related to an increased risk for atherosclerosis, but few data are available with regard to any other thiol compound having a potential vascular toxicity. Therefore, we measured both total cysteine and homocysteine plasma levels in patients with hyperlipidemia (242 males and 147 females, 41-65 years old). Homocysteine was higher in males than in females, 13.2+/-4.1 versus 11.1+/-3.4 micromol/l (P<0.0001). The mean cysteine level was 243.3+/-45.7 micromol/l in the whole study population. The subjects were split in two groups, symptomatic patients with cardiovascular disease (n = 106) and asymptomatic subjects (n = 283). Blood pressure, smoking status, total cholesterol, LDL-cholesterol and triglycerides did not statistically differ between groups, but the mean HDL-cholesterol level was lower in symptomatic patients (1.24+/-0.38 versus 1.42+/-0.41, P<0.0001). Cysteine levels were higher in patients with cardiovascular disease than in asymptomatic patients, respectively 254.7+/-47.7 versus 239.1+/-44.3 micromol/l (P = 0.003). A similar result was found for homocysteine, respectively 13.1+/-4.3 versus 12.2+/-3.9 micromol/l (P = 0.05). To analyse whether cysteine levels were related to atherosclerosis independently of age, adjusted levels were compared between asymptomatic patients with normal carotid arteries (n = 176), carotid atherosclerosis (n = 107) and symptomatic patients (n = 106). Age adjusted cysteine levels differed significantly between groups (P = 0.027) while the P-value was of borderline significance for homocysteine (P = 0.09). Odds ratios for having symptomatic cardiovascular disease were 1.81 (95% CI, 1.02-3.21) and 2.05 (95% CI, 1.16-3.60) for the mid and highest tertiles of cysteine using the lowest as the reference. After adjustment in a multivariate model including age, sex, and creatinine, the odds ratio for disease remained significant between the highest tertile versus the lowest (OR = 1.89). Adjusted odds ratios were found to be weaker when homocysteine tertiles were compared. Our data suggest that plasma total cysteine is a risk factor for atherosclerosis in hyperlipidemic patients.


Assuntos
Arteriosclerose/sangue , Doenças Cardiovasculares/sangue , Cisteína/sangue , Homocisteína/sangue , Hiperlipidemias/sangue , Adulto , Distribuição por Idade , Idoso , Arteriosclerose/epidemiologia , Arteriosclerose/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Cromatografia Líquida de Alta Pressão , Comorbidade , Intervalos de Confiança , Fatores de Confusão Epidemiológicos , Feminino , Humanos , Hiperlipidemias/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Medição de Risco , Fatores de Risco , Distribuição por Sexo
13.
J Cardiothorac Vasc Anesth ; 13(3): 272-5, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10392676

RESUMO

OBJECTIVE: Cardiac failure and myocardial infarction are complications of thoracic aorta, thoracoabdominal aorta, or aortic arch surgery, especially when surgery is performed using profound hypothermia and circulatory arrest (PHCA). Moreover, the diagnosis of non-Q-wave postoperative myocardial infarction (PMI) is challenging because there is no gold standard. The aims of this study were to determine values for cardiac troponin I (cTnl) in patients undergoing aortic arch or thoracoabdominal aortic surgery with PHCA who were free of cardiac complications in the postoperative period, and to test the validity of cutoff values of cTnl to predict postoperative cardiac complications in such patients. DESIGN: Prospective, nonrandomized study. SETTING: Single university hospital; Departments of Anesthesiology, Biochemistry and Vascular Surgery. PARTICIPANTS: Fifty-two consecutive patients were studied over a 2-year period. None was excluded, even patients who underwent emergency surgery. INTERVENTIONS: Patients undergoing aortic arch or thoracoabdominal aortic surgery with PHCA were studied. Thirty patients undergoing coronary artery bypass grafting (CABG) in the same period constituted a control group. MEASUREMENTS AND MAIN RESULTS: The cTnl concentrations were determined using an immunoenzymofluorometric assay on a Stratus analyzer (Dade, Massy, France) on blood samples obtained at recovery and on day 1 (D1) and D2. Seventeen patients developed a cardiac complication, which was lethal in 10 patients. In patients without cardiac complication, the peak level for cTnl was observed on D1. Cutoff values of cTnl were identical in both the CABG control group (11 .6 microg/mL) and the sternotomy group (12.2 microg/mL), but were significantly greater (20.5 microg/mL) in patients with a thoracotomy approach. Sensitivity and specificity of these cutoff values were high in both groups (control group, sensitivity = 100%, specificity = 100%; sternotomy group, sensitivity = 78%, specificity = 100%; thoracotomy group, sensitivity = 100%, specificity = 94%). CONCLUSION: In patients who underwent surgery using PHCA for aortic arch or descending aorta repair, myocardial damage related to cardiac arrest, vents or fibrillation explains the increased cutoff value (12.2 microg/mL). This value is similar to patients undergoing CABG surgery through a sternotomy approach with cardioplegia administration. In contrast, and probably related to the absence of cardioplegia, patients undergoing surgery through a left thoracotomy approach had a greater cutoff value (20.5 microg/mL). Values of cTnl greater than these respective cutoff values were closely related to cardiac complications during the postoperative period.


Assuntos
Parada Cardíaca Induzida , Infarto do Miocárdio/diagnóstico , Miocárdio/química , Complicações Pós-Operatórias/diagnóstico , Troponina I/sangue , Adulto , Idoso , Aorta/cirurgia , Ponte de Artéria Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade
14.
Pathol Biol (Paris) ; 45(4): 299-304, 1997 Apr.
Artigo em Francês | MEDLINE | ID: mdl-9296078

RESUMO

In order to examine the influence of a low-fat diet on iron status, we carried out a study which involved 410 out-patients with hyperlipidaemia, i.e. 256 men and 154 women. Serum iron was positively correlated with protein intake (p = 0.11; p < 0.05) and transferrin saturation was inversely correlated with fat intake (p = - 0.12; p < 0.05). A positive iron balance (serum iron > 27 mumol/l and transferrin saturation > 45%) was found in 1.6% of the male subjects, a frequency which could be explained by the presence of the hemochromatosis genes. A negative iron balance (serum iron < 10 mumol/l and tranferrin saturation < 15%) was found in 13.7% for women aged 21-49 yr, 3.7% for women aged 50-77 yr and 3.5% for men aged 21-77 yr. We found no association between low-fat diet and iron deficiency. Men with iron deficiency had 12% decrease in total calorie intake compared to the Recommended Dietary Allowance. Our results do not provide evidence that hypolipidemic diet is associated with a high frequency of iron deficiency.


Assuntos
Dieta com Restrição de Gorduras , Hiperlipidemias/sangue , Hiperlipidemias/dietoterapia , Ferro/sangue , Adulto , Idoso , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Transferrina/análise
15.
Gerontology ; 43(6): 326-34, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9386984

RESUMO

Erythropoietin secretion was evaluated in the anaemia of chronic disorders in elderly patients, since it has been shown that this secretion is impaired in adults. We looked for a possible role of inflammatory cytokines: tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) on erythropoietin production. The influence of nutritional status on the anaemia was also investigated. Erythropoietin secretion was significantly increased in elderly patients with anaemia of chronic disorders (ACD) and inversely correlated with haemoglobin concentrations in infectious and inflammatory diseases. Plasma TNF alpha levels were significantly enhanced only in cancerous patients, but no correlation could be established between TNF alpha and erythropoietin or haemoglobin. No noticeable increase of IL-1 beta levels was observed in ACD. These findings suggest that systemic TNF alpha or IL-1 beta are not involved in the erythropoietin response to ACD. Albumin levels were decreased in anaemic patients. Further investigations of the effects of a nutritional supplementation in elderly patients with ACD may be of interest.


Assuntos
Envelhecimento/fisiologia , Anemia/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Eritropoetina/sangue , Eritropoetina/metabolismo , Feminino , Hemoglobinas , Humanos , Interleucina-1/sangue , Masculino , Albumina Sérica , Fator de Necrose Tumoral alfa/metabolismo
16.
Ann Biol Clin (Paris) ; 55(6): 583-91, 1997.
Artigo em Francês | MEDLINE | ID: mdl-9499919

RESUMO

Plasma concentrations of homocysteine, cysteine, cysteinylglycine and glutathione were measured using a HPLC technique with fluorescence detection of the derivatives obtained with 7-fluoro-2,1,3-benzoxadiazole-4-sulfonamide (ABD-F). Blood was drawn into chilled EDTA-evacuated tubes. After centrifugation at 4 degrees C without delay, plasma samples were kept frozen at -20 degrees C until analysis. Reduction of protein bound aminothiols and disulfides standards was achieved with tri-n-butylphosphine. N-acetylcysteine was used as internal standard. After protein precipitation, derivatization was carried out at pH 8.0 and 50 degrees C for 20 min. Stability of ABD-thiols was ensured for at least 5 days by lowering pH to 2. Derivatives were separated by isocratic elution on a Waters mu Bondapak C18 column (10 microns, 3.9 x 300 mm) with 0.1 M phosphate buffer pH 3.2 containing 10% acetonitrile. Excitation and emission wavelengths were 385 and 515 nm. Retention times were 4.9, 5.8, 7.3, 9.9 and 20.1 min respectively for cysteine, cysteinylglycine, homocysteine, glutathione and N-acetylcysteine. Peaks were quantified by comparison to a standard curve prepared by plotting peak height versus the different levels of known standard solutions after normalization with internal standard. Between-run CVs varied from 5 to 8.5%. The detection limit was < 0.5 mumol/l for homocysteine and glutathione. In plasma samples from healthy subjects, concentration of homocysteine was higher in men than in women (11.0 +/- 2.9 versus 9.2 +/- 2.7 mumol/l, p < 0.01). These values are similar to those obtained with other widely used methods.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Homocisteína/sangue , Compostos de Sulfidrila/sangue , Acetilcisteína/sangue , Cisteína/sangue , Dipeptídeos/sangue , Feminino , Fluorescência , Glutationa/sangue , Humanos , Masculino , Reprodutibilidade dos Testes
17.
Rev Med Interne ; 17(8): 627-34, 1996.
Artigo em Francês | MEDLINE | ID: mdl-8881190

RESUMO

From a clinical standpoint, the search for iron deficiency is based upon serum ferritin. However, serumferritin values may be pathologic in other numerous pathological conditions such as inflammation, liver diseases, malignant hematologic disorders, hemolysis, etc. Proteic profile combines the analyze of proteins variations: protein results are converted in percent of normal values referenced for the technique used. It has been suggested that on the protein profile, an increase in serum transferrin level compared to a normal serum albumin level (DAT: difference albumin-transferrin), appears early in the course of iron deficiency. In order to know the value of a pathologic DAT > or = 28% in the diagnosis of iron deficiency, we prospectively studied 156 patients consecutively hospitalized in an internal medicine department. Iron deficiency was defined by a low serum ferritin level. Diagnosis performance (sensitivity, specificity, positive and negative predictive values) of different biologic markers of iron deficiency (serum iron, saturation of total iron-binding capacity, low mean erythrocyte volume) and DAT was compared to the performance of low serum ferritin values. With the exception of low serum ferritin (which have by definition a specificity and a positive predictive value of 100%), pathologic DAT appeared as the best index of iron deficiency with the highest sensitivity (67.4%), specificity (97.3%), positive predictive value (91.2%), negative predicitive value (87.7%) and diagnosis efficacy (sensitivity x specificity = 0.66). A pathologic DAT associated to a low serum ferritin level increased the diagnosis performance of both tests to 0.72. Diagnosis efficacy of DAT was not changed (0.66) in 83 patients with a confounding factor for serum ferritin analysis (inflammation, liver diseases, malignant hematologic disorders, hemolysis) when diagnosis efficacy of all other tests decreased. There was a negative correlation between serum ferritin level and DAT level (r = 0.55; P < 0.0001). In conclusion, an increase of serum transferrin of more than 28% compared to serum albumin on a proteic profile gives a significant benefit for the diagnosis of iron deficiency. This benefit increases when data of both DAT and serum ferritin are associated.


Assuntos
Deficiências de Ferro , Albumina Sérica/análise , Transferrina/análise , Anemia Ferropriva/prevenção & controle , Proteínas Sanguíneas/análise , Feminino , Hemorragia Gastrointestinal/sangue , Humanos , Ferro/sangue , Masculino , Distúrbios Nutricionais/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Fatores Sexuais
18.
Carbohydr Res ; 236: 259-65, 1992 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-1291051

RESUMO

Changes were observed in alpha-L-fucosidase forms in cells from acute myelocytic leukemias (AML). Total alpha-L-fucosidase activity was not significantly different for normal granulocytes and leukemic cells, but enzymic profiles obtained by chromatofocusing are quite different. In granulocyte profile, two main peaks are present (B and more acidic A) which were eluted at pH 5.2 with a shoulder at pH 4.6. In AMLs the B form is present but weakly expressed, whereas the more acidic forms are the major ones. This pattern may be related either to the malignancy character or to the stage at which the differentiation is stopped. Experiments on an HL-60 cell line (promyelocytic cells corresponding to the AML 3 type) showed that differentiation induced by dimethyl sulfoxide leads to the appearance of the B form present in normal mature cells. Thus the repartition of the enzyme forms seems to be related to the stage of differentiation of the myelocytic cells.


Assuntos
Leucemia Mieloide/enzimologia , Leucemia Promielocítica Aguda/enzimologia , alfa-L-Fucosidase/sangue , Doença Aguda , Sequência de Carboidratos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Dimetil Sulfóxido , Granulócitos/efeitos dos fármacos , Granulócitos/patologia , Humanos , Leucemia Mieloide/patologia , Leucemia Promielocítica Aguda/patologia , Dados de Sequência Molecular , Células Tumorais Cultivadas
19.
Bull Acad Natl Med ; 175(2): 205-14; discussion 215, 1991 Feb.
Artigo em Francês | MEDLINE | ID: mdl-1863862

RESUMO

The glycosidases, enzymes which participate in the degradation of glycoproteins and glycolipids inside the lysosomes are themselves glycoproteins and, for one enzyme, several forms may be isolated in tissues and in biological fluids, corresponding to variations in the composition or the structure of their glycanic moiety. We have previously studied the different forms of alpha-L-fucosidase in human serum, kidney and urine. Some modifications of the glycanic fraction of glycoproteins have been described in various forms of tumoral cells; therefore, we have attempted to verify if the alpha-L-fucosidase of blood cells might be a useful marker in the diagnosis of leukemias, using the enzymic pattern obtained by chromatographic or electrofocusing methods. Detergent extracts from normal lymphocytes, submitted to ion-exchange chromatography as well as to chromatofocusing, revealed the presence of two forms of alpha-L-fucosidase, A and B, with respective pIs of 5.7 and 6.2. After treatment by neuraminidase, these two forms remain distinct, showing that the degrees of sialylation is not the only difference. Moreover, after desialylation, the two forms have not the same affinity for concanavalin A, an argument for the heterogeneity of the glycanic structures. The determination of the total activity, and of enzymic patterns of alpha-L-fucosidase from leukemic cells led to the observation of three types of modifications, in comparison with normal lymphocytes: quantitative variations in the total activity; variations in the proportions of the two forms; variations due to the modification of pIs. We have studied the lymphocytes from four patients with a hairy-cell leukemia (HCL), four patients with chronic lymphoid leukemia (CLL) and the MO cell-line, proceeding from a HCL. In all cases, the total fucosidase activity is strongly decreased in comparison with normal lymphocytes activity. The chromatofocusing pattern for CLL cells reveals the presence of the A and B forms, without modification of their eluting pH. A characteristic pattern is obtained with hairy cells, presenting only the B form, eluted in more acidic conditions. The normal lymphocytes in peripheral blood are for 80 per cent of the T phenotype, and the CLL lymphocytes exhibit the phenotypic markers B, as well as the hairy cells, but the MO cell-line acquires in culture the T markers. As these last cells express both the A and B forms of enzyme, the absence of the A form of alpha-L-fucosidase seems to be a marker of the HCL.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Leucemia de Células Pilosas/sangue , Leucemia Linfocítica Crônica de Células B/sangue , Linfócitos/química , alfa-L-Fucosidase/química , Biomarcadores/química , Linhagem Celular Transformada , Cromatografia , Humanos , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/enzimologia , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/enzimologia
20.
Clin Chim Acta ; 187(3): 235-41, 1990 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-2323063

RESUMO

The concentration of alpha 1-acid glycoprotein (AGP) was measured in sera from 23 women, 14 pregnant women, 10 women receiving estrogen-progestogen treatment and 12 men. All sera were further subjected to crossed affino-immunoelectrophoresis with addition of conA in the first dimension and alpha-methylglucopyranoside in the second dimension. The distribution of AGP into three microheterogeneity forms, which were the result of this analysis, was estimated by measuring the area under the precipitation curve. The microheterogeneity patterns of AGP in the five groups were analysed from each other. An augmentation of the non reactive form is seen in women in the first part of the cycle and in women receiving estrogen-progestogen treatment compared with the three others groups. The pattern obtained in this latter group is similar to that observed in pregnant women (34 weeks) by several authors.


Assuntos
Estrogênios/administração & dosagem , Ciclo Menstrual/sangue , Orosomucoide/análise , Gravidez/sangue , Progestinas/administração & dosagem , Feminino , Humanos , Masculino
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