Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Más filtros












Base de datos
Intervalo de año de publicación
1.
Leukemia ; 29(12): 2307-16, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26104660

RESUMEN

P38α/ß has been described as a tumor-suppressor controlling cell cycle checkpoints and senescence in epithelial malignancies. However, p38α/ß also regulates other cellular processes. Here, we describe a role of p38α/ß as a regulator of acute lymphoblastic leukemia (ALL) proliferation and survival in experimental ALL models. We also report first evidence that p38α/ß phosphorylation is associated with the occurrence of relapses in TEL-AML1-positive leukemia. First, in vitro experiments show that p38α/ß signaling is induced in a cyclical manner upon initiation of proliferation and remains activated during log-phase of cell growth. Next, we provide evidence that growth-permissive signals in the bone marrow activate p38α/ß in a novel avian ALL model, in which therapeutic targeting can be tested. We further demonstrate that p38α/ß inhibition by small molecules can suppress leukemic expansion and prolong survival of mice bearing ALL cell lines and primary cells. Knockdown of p38α strongly delays leukemogenesis in mice xenografted with cell lines. Finally, we show that in xenografted TEL-AML1 patients, ex vivo p38α/ß phosphorylation is associated with an inferior long-term relapse-free survival. We propose p38α/ß as a mediator of proliferation and survival in ALL and show first preclinical evidence for p38α/ß inhibition as an adjunct approach to conventional therapies.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Proteínas Quinasas p38 Activadas por Mitógenos/fisiología , Adolescente , Animales , Proliferación Celular , Niño , Preescolar , Femenino , Humanos , Masculino , Ratones , Fosforilación , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
2.
J Cardiovasc Pharmacol ; 35(5): 708-15, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10813371

RESUMEN

In vitro experiments suggest that beta blockade and angiotensin-converting enzyme (ACE) inhibition may protect the failing heart by reduction of myocardial oxidative stress. To test this hypothesis in an in vivo model, the beta blocker metoprolol (350 mg) and the ACE inhibitor ramipril (1 mg) were given either alone or in combination to rats (per kilogram body weight per day) for 6 weeks after myocardial infarction. Left ventricular end-diastolic pressure (LVEDP), contractile function of papillary muscles, enzymatic antioxidative defense (indicated by the activities of the superoxide dismutase isoenzymes and glutathione peroxidase), and the extent of lipid peroxidation were studied. Placebo-treated rats showed cardiac hypertrophy, increased LVEDP, lower rates of contraction and relaxation, as well as a deficit in the myocardial antioxidative defense associated with increased lipid peroxide levels, when compared with sham-operated animals. Combined beta blockade and ACE inhibition improved the antioxidative defense, reduced hypertrophy and LVEDP, and enhanced rates of contraction. Thus prolonged beta blockade and ACE inhibition after infarction may decrease myocardial oxidative stress and thereby could be beneficial in heart failure.


Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Infarto del Miocardio/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Interacciones Farmacológicas , Glutatión Peroxidasa/metabolismo , Isoenzimas/metabolismo , Peróxidos Lipídicos/metabolismo , Masculino , Contracción Muscular/efectos de los fármacos , Infarto del Miocardio/tratamiento farmacológico , Músculos Papilares/efectos de los fármacos , Músculos Papilares/fisiología , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Función Ventricular Izquierda/efectos de los fármacos
3.
Cardiovasc Drugs Ther ; 14(6): 597-606, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11300360

RESUMEN

Beneficial effects of monotherapy with ACE inhibitors or beta-blockers on hemodynamic function after myocardial infarction are well known. Until now, the effects of combined treatment on cardiac function and energy metabolism have been poorly described. This study examines the effects of combined ramipril and metoprolol treatment on the creatine kinase (CK) system and hemodynamic function in rats after infarction. Wistar rats with experimental infarction were randomized for treatment with ramipril (R), metoprolol (M), combined treatment (MR), or placebo (P). Sham-operated (SO) animals served as controls. After 6 weeks, we assayed for CK isoenzymes and performed hemodynamic measurements. In P versus SO, left ventricular systolic pressures (dp/dt(max) and dp/dt(min)) diminished, whereas left ventricular end-diastolic pressure (LVEDP) increased. Decreased total CK activity and mitochondrial CK isoenzyme, increased CK-MB, and increased CK-BB isoenzymes were measured in P versus SO. With infarct size < or =45%, mitochondrial CK increased in M and R versus P. Combined treatment had an additional enhancing effect on mitochondrial CK isoenzyme level versus M and R, decreased LVEDP versus P, as well as increased dp/dt(max) and dp/dt(min) versus R. These results provide evidence of an interaction between normalization of energy metabolism and improvement in cardiac function due to a combination of ACE inhibition and beta blockade after myocardial infarction.


Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Creatina Quinasa/metabolismo , Hemodinámica/efectos de los fármacos , Metoprolol/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Ramipril/uso terapéutico , Animales , Cardiomegalia/patología , Quimioterapia Combinada , L-Lactato Deshidrogenasa/metabolismo , Masculino , Infarto del Miocardio/enzimología , Infarto del Miocardio/fisiopatología , Ratas , Ratas Wistar , Función Ventricular Izquierda/fisiología
4.
J Mol Cell Cardiol ; 29(11): 2941-51, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9405169

RESUMEN

We tested whether ACE-inhibition with ramipril (A), beta-adrenergic blockade with metoprolol (beta) or combined treatment (beta A) for 6 weeks after inducing myocardial infarction in rats by left coronary artery ligation modifies contractile function of hypertrophied papillary muscle from left ventricles with different infarct size (IS) compared to a placebo group (P). At IS<40% of left ventricle, contraction and relaxation were less impaired than at IS>40% compared to sham operated rats (SO). Isometrically developed peak force and calcium sensitivity of myofilaments, measured in skinned fibres, were significantly higher in beta. Treatment with ramipril or metoprolol improved contraction rate and force development, respectively, mainly at IS<40%, but deteriorated relaxation rate. ACE-inhibition and beta-adrenergic blockade had no significant improving effect on the relaxation rate and further characteristics of the contractile function at IS>40%, although combined treatment reduced the infarct size and ramipril treatment suppressed the development of hypertrophy. Post-extrastimulatory potentiation was increased in beta and beta A at IS>40%. Post-rest potentiations were influenced hardly at IS<40% and were significantly smaller in A at IS>40%. The twitch-to-twitch decay of the potentiations was faster at IS>40%. Increase in the degree of post-extrastimulatory potentiation, steeper twitch-dependent decay of the potentiations and loss of rest-dependent potentiation at IS>40% indicate relatively increased trans-sarcolemmal Ca2+ transports via Ca2+ channels and Na+/Ca2+ exchange, partly modified by ramipril and metoprolol. The results demonstrate that ACE-inhibition and beta-adrenergic blockade induce a dissociation between trophic effects and phenotypic effects on contractile function after chronic infarction.


Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Contracción Miocárdica/efectos de los fármacos , Infarto del Miocardio/tratamiento farmacológico , Músculos Papilares/efectos de los fármacos , Animales , Calcio/farmacología , Quimioterapia Combinada , Técnicas In Vitro , Contracción Isométrica/efectos de los fármacos , Masculino , Fibras Musculares Esqueléticas/efectos de los fármacos , Ratas , Ratas Wistar
5.
Z Gesamte Hyg ; 36(6): 323-5, 1990 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-2392850

RESUMEN

An ELISA for the detection of IgM rheumatoid factors was developed. Additionally agglutination tests on the basis of polystyrene latex particles were developed. The results of these tests were compared with one another and with those of Latex-Schnelltest from SSW. A good agreement between ELISA and latex agglutination tests was found.


Asunto(s)
Artritis Reumatoide/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina M/análisis , Pruebas de Fijación de Látex , Factor Reumatoide/análisis , Adulto , Humanos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...