RESUMEN

Intravascular EDRF-NO production is known to be impaired in some diseases, e.g., diabetes. This phenomenon may also contribute to the development of diabetic vascular disease. More recently the presence of NO synthase (ecNOS, iNOS) have been recognized in human platelets. Platelets produce NO only during activation, even though in minute amounts. This platelet derived NO seems to play an important physiological role, as it inhibits further platelet recruitment quite substantially. In the present report washed platelets isolated from healthy persons and patients with chronic myeloproliferative diseases (CMPD) were exposed to common and physiologically relevant activators (i.e., thrombin, collagen, epinephrine etc.). These tests were carried out in 20 healthy volunteers and 15 patients suffering from myeloproliferative disorders associated with thrombocytosis. As a consequence of pathological platelet function observed in CMPD, the in vitro platelet NO response is impaired in the patient group. One may assume, that reduced platelet NO response, at least in part, may contribute to platelet hyperfunction, angiopathy and thrombotic complications in some cases of CMPD.

Asunto(s)

Plaquetas/metabolismo , Trastornos Mieloproliferativos/sangre , Óxido Nítrico/biosíntesis , Óxido Nítrico/fisiología , Activación Plaquetaria , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Enfermedad Crónica , Electroquímica/métodos , Femenino , Humanos , Cinética , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/metabolismo , Óxido Nítrico/análisis , Recuento de Plaquetas , Trombocitosis/sangre , Trombocitosis/metabolismo

RESUMEN

BACKGROUND/AIMS: We examined changes in hemostasis, in levels of total antioxidant capacity, and pancreatic enzymes (amylase, lipase) in patients with pancreatitis 1, 3 and 7 days after admission to the clinic, in order to evaluate the inflammatory processes in acute and chronic pancreatitis and to identify new prognostic markers. METHODOLOGY: The rate of CD62 expression--a marker of platelet hyperactivity--and the rate of platelet-leukocyte aggregates were measured by flow cytometry. The connection between the parameters measured and the severity of pancreatitis and also the differences of the parameters in acute and chronic pancreatitis were investigated. RESULTS: On the basis of previous studies it was assumed, that there is a connection between the level of parameters measured and the inflammatory process in the pancreas, and also between the defending processes of the body against free radicals. CONCLUSIONS: Based on our results, we suggest to extend the laboratory measurements to the investigation of hemostatic parameters. The measurement of plasma level of fibrinogen, von Willebrand factor and the rate of platelet activation is especially important.

Asunto(s)

Antioxidantes/análisis , Pancreatitis/sangre , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Fibrinógeno/análisis , Hemostasis , Humanos , Persona de Mediana Edad , Pancreatitis/fisiopatología , Activación Plaquetaria , Complejo GPIb-IX de Glicoproteína Plaquetaria , Factor de von Willebrand/análisis

RESUMEN

Limited information seems to be available about the role of reduced endothelial production of endotheliumderived relaxing factor (EDRF)-nitrate/nitrite (NO) in the pathogenesis of diabetic angiopathy in insulindependent diabetes. A report of urinary and serum nitrate/nitrite, glucometabolic parameters, endothelial and in vivo platelet activation markers of 22 insulin dependent diabetics (IDDM) patients are given. Urinary and serum nitrate/nitrite concentrations were reduced in IDDM. This was independent of disease duration, presence of angiopathy and the glucometabolic parameters. A significant and inverse correlation of nitrate/nitrite excretion with endothelial markers (von Willebrand factor, soluble thrombomodulin) was documented. Moreover, reduced nitrate/nitrite excretion was strongly associated with elevated plasmatic beta -thromboglobulin levels. EDRF-NO production is reduced in IDDM and this reduction correlates with endothelial damage. Decreased nitrate/nitrite excretion may also influence in vivo platelet function, which results in increased in vivo platelet activation and suggests that the reduced intravascular production of EDRF-NO might play a role in the pathogenesis of angiopathy in IDDM.

RESUMEN

This review is concerning with the endothel derived relaxing factor (EDRF) discovered in 1980 and identified as NO in 1987 in the function and activities of the gastrointestinal tract and the liver. It is of importance, that NO seems to basic mediator of the so called nonadrenerg-noncholinerg inhibitory innervation of the bowel, and also takes part in the regulation of mucosal blood supply and secretory function. In portal hypertension elevated cGMP is found in the urine, as evidence of increased nitrogen oxide synthase (NOS) activity. NO may act both as hepatoprotective and cytotoxic factor in the free radical reactions of several liver disease.

Asunto(s)

Sistema Digestivo/metabolismo , Hígado/metabolismo , Óxido Nítrico/metabolismo , Fenómenos Fisiológicos del Sistema Digestivo , Motilidad Gastrointestinal , Humanos , Hígado/fisiología , Óxido Nítrico Sintasa/metabolismo

RESUMEN

The role of reduced endothelial production of EDRF-NO in the pathogenesis of diabetic angiopathy has received much attention, however, most of the rather conflicting data were gained from animal experiments. Limited human experience seems to be available in insulin dependent diabetes, calling attention to decreased EDRF-NO production. Hereby the clinical, as well as laboratory investigation (urinary and serum nitrate/nitrite, lipid peroxidation, glucometabolic parameters, endothelial and in vivo platelet activation markers, etc.) of 35 non-insulin dependent (NIDDM) and 15 insulin dependent diabetics (IDDM) patients are given. Urinary and serum nitrate/nitrite concentrations were proven to be reduced in both patients groups. This change was independent of diabetes duration, presence of macroangiopathy, coronary heart disease and the glucometabolic parameters, however, correlation was registered with lipid peroxidation (total antioxidant status). An inverse correlation of nitrate/nitrite excretion with endothelial markers (von Willebrand factor, soluble thrombomodulin) was documented in NIDDM, this correlation was much stronger in IDDM. Moreover, in IDDM patients reduced nitrate/nitrite excretion was strongly associated with elevated plasmatic beta-thromboglobulin levels. The data presented here support to the hypothesis, that EDRF-NO production is reduced in diabetes and this reduction seems to correlate with endothelial damage. In IDDM the decreased nitrate/nitrite excretion may also lead to increased in vivo platelet activation, which suggests that the reduced amount of EDRF-NO might play a role in the pathogenesis of angiopathy in IDDM.

Asunto(s)

Diabetes Mellitus/metabolismo , Endotelio Vascular/lesiones , Óxido Nítrico/biosíntesis , Activación Plaquetaria/fisiología , Adulto , Glucemia/metabolismo , Complicaciones de la Diabetes , Diabetes Mellitus/sangre , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Angiopatías Diabéticas/etiología , Endotelio Vascular/metabolismo , Femenino , Humanos , Peroxidación de Lípido , Masculino , Persona de Mediana Edad , Nitratos/sangre , Nitratos/orina , Nitritos/sangre , Nitritos/orina

RESUMEN

Prenatal diagnosis was performed in 92 pregnancies high-risk for cystic fibrosis during six years. Amniotic fluid samples obtained by amniocentesis were examined with regard to their microvillar membrane enzyme activity. Though trehalase, alkaline phosphatase isoenzymes and L-gamma-glutamyltransferase in the amniotic fluid are not specific markers of cystic fibrosis, their activity is significantly lower than in normal pregnancies. By measuring the three enzymes simultaneously, sensitivity, specificity and reliability of the method were found to be over 92%. It is concluded that mid-trimester amniotic fluid diagnosis is indispensable for some heterozygotic couples for cystic fibrosis even in the possession of DNA (desoxyrobonucleic acid) methods.

Asunto(s)

Líquido Amniótico/enzimología , Pruebas Enzimáticas Clínicas , Fibrosis Quística/diagnóstico , Membranas Intracelulares/enzimología , Diagnóstico Prenatal/métodos , Femenino , Humanos , Microvellosidades/enzimología , Embarazo , Estudios Retrospectivos , Factores de Riesgo

RESUMEN

We have analysed the sensitivity, specificity, and reliability of biochemical diagnosis based on microvillar membrane enzyme assay and using discriminant analysis in amniotic fluid samples obtained from 54 pregnancies at high risk for cystic fibrosis and 125 normal pregnancies. Our results show that amniotic fluid trehalase, alkaline phosphatase, alkaline phosphatase isoenzymes and gamma-glutamyltransferase enzyme activities measured during 16-20 gestational weeks, in spite of their non-specificity for cystic fibrosis, have a very good predictive value for fetal cystic fibrosis or exclude the possibility of the disease. Overall enzyme activity analysis provided over 90 per cent reliability of the method.

Asunto(s)

Fosfatasa Alcalina/análisis , Amniocentesis , Líquido Amniótico/enzimología , Fibrosis Quística/diagnóstico , Isoenzimas/análisis , Microvellosidades/enzimología , Trehalasa/análisis , gamma-Glutamiltransferasa/análisis , Biomarcadores , Pruebas Enzimáticas Clínicas , Fibrosis Quística/enzimología , Análisis Discriminante , Femenino , Humanos , Edad Materna , Embarazo , Valores de Referencia , Factores de Riesgo , Ultrasonografía Prenatal , alfa-Fetoproteínas/análisis

RESUMEN

Prenatal diagnosis of cystic fibrosis based on amniotic fluid microvillar enzyme activity assay has become routine practice in the past few years. Normal (median) values of these enzymes were determined in 177 normal healthy pregnancies between 15-20 gestational weeks and were related to enzyme values measured in 50 pregnancies complicated with congenital malformations, 6 monogenic inherited diseases and 4 chromosomal aberrations. It is concluded that increased trehalase activity has diagnostic importance in detecting fetal kidney diseases, and radial-renal syndrome (with elevated GGT activity), while low enzyme activities may indicate chromosomal aberrations (with no signs of intestinal obstruction). With the collection of further data, the analysis of these enzymes might provide an opportunity to set up diagnostic procedures for the detection of other, non-CF-related cases.

Asunto(s)

Líquido Amniótico/enzimología , Aberraciones Cromosómicas/diagnóstico , Anomalías Congénitas/diagnóstico , Fibrosis Quística/diagnóstico , Enzimas/análisis , Enfermedades Genéticas Congénitas/diagnóstico , Diagnóstico Prenatal , Fosfatasa Alcalina/análisis , Fosfatasa Alcalina/genética , Aberraciones Cromosómicas/enzimología , Aberraciones Cromosómicas/genética , Trastornos de los Cromosomas , Anomalías Congénitas/enzimología , Anomalías Congénitas/genética , Fibrosis Quística/enzimología , Fibrosis Quística/genética , Enzimas/genética , Femenino , Enfermedades Genéticas Congénitas/enzimología , Enfermedades Genéticas Congénitas/genética , Humanos , Recién Nacido , Lactasa , Microvellosidades/enzimología , Embarazo , Trehalasa/análisis , Trehalasa/genética , beta-Galactosidasa/análisis , beta-Galactosidasa/genética , gamma-Glutamiltransferasa/análisis , gamma-Glutamiltransferasa/genética

RESUMEN

Prenatal diagnosis was performed in 92 pregnancies high-risk for cystic fibrosis during six years. Amniotic fluid samples obtained by amniocentesis were examined with regard to their microvillar membrane enzyme activity. However, trehalase, alkaline phosphatase isoenzymes and L-gamma-glutamyl-transferase in the amniotic fluid are not specific markers of the cystic fibrosis, their activity is significantly lower than in normal pregnancies. By measuring the three enzymes simultaneously, sensitivity, specificity and reliability of the method were found to be over 92%. It is concluded that the mid-trimester amniotic fluid diagnosis is useful for some heterozygotic couples for cystic fibrosis even in the possession of the DNA methods.

Asunto(s)

Líquido Amniótico/enzimología , Fibrosis Quística/diagnóstico , Amniocentesis , Vellosidades Coriónicas/enzimología , Femenino , Humanos , Embarazo , Diagnóstico Prenatal

RESUMEN

Amniotic fluid intestinal alkaline phosphatase, gammaglutamyltransferase and trehalase activity were quantitated to assess their reliability for the prenatal diagnosis of cystic fibrosis. To obtain optimal diagnostic discrimination, the three enzyme values obtained for each sample were combined into a single linear discriminant function that proved to be a more accurate indicator of the outcome of the pregnancy. From the cases studied here, it appears that this method can be expected to give a correct prediction in 92.0% of all high risk pregnancies.

Asunto(s)

Fibrosis Quística/genética , Líquido Amniótico/enzimología , Fibrosis Quística/diagnóstico , Fibrosis Quística/enzimología , Sondas de ADN , Femenino , Asesoramiento Genético , Humanos , Microvellosidades/enzimología , Embarazo , Diagnóstico Prenatal