RESUMO
As síndromes mielodisplásicas (SMD) são um grupo de desordens adquiridas da medula óssea, caracterizadas por citopenias no sangue periférico, e hipercelularidade na medula óssea com alterações displásicas em uma ou mais linhagens celulares hematopoiéticas. O objetivo do presente relato é descrever um caso de SMD uma vez que esta enfermidade é de ocorrência rara e existem poucos relatos na medicina veterinária.
RESUMO
As síndromes mielodisplásicas (SMD) são um grupo de desordens adquiridas da medula óssea, caracterizadas por citopenias no sangue periférico, e hipercelularidade na medula óssea com alterações displásicas em uma ou mais linhagens celulares hematopoiéticas. O objetivo do presente relato é descrever um caso de SMD uma vez que esta enfermidade é de ocorrência rara e existem poucos relatos na medicina veterinária.(AU)
The myelodysplastic syndromes (MDS) are a group of bone marrow acquired disorders, characterized by peripheral blood cytopenias, and hypercellular bone marrow with displastyc changes in one or more hematopoietic cell lines. This papers aim is to report a MDS case since this is a rare disease and there are just a few reports in veterinary medicine.(AU)
Assuntos
Animais , Cães , Síndromes Mielodisplásicas/veterinária , Células da Medula Óssea , Células Sanguíneas , Mielografia/veterináriaRESUMO
As síndromes mielodisplásicas (SMD) são um grupo de desordens adquiridas da medula óssea, caracterizadas por citopenias no sangue periférico, e hipercelularidade na medula óssea com alterações displásicas em uma ou mais linhagens celulares hematopoiéticas. O objetivo do presente relato é descrever um caso de SMD uma vez que esta enfermidade é de ocorrência rara e existem poucos relatos na medicina veterinária.
The myelodysplastic syndromes (MDS) are a group of bone marrow acquired disorders, characterized by peripheral blood cytopenias, and hypercellular bone marrow with displastyc changes in one or more hematopoietic cell lines. This papers aim is to report a MDS case since this is a rare disease and there are just a few reports in veterinary medicine.
Assuntos
Animais , Cães , Células Sanguíneas , Células da Medula Óssea , Síndromes Mielodisplásicas/veterinária , Mielografia/veterináriaRESUMO
Se evaluó la seguridad y la tolerancia de fórmulas pediátricas entérales con altas concentraciones de energía, comparándolas con una fórmula estándar. En este estudio abierto, aleatorio, multicéntrico, de fase III, se evaluaron niños de 1 a 6 años de edad que requerían alimentación por sonda para proporcionar al menos el 75 por ciento de sus requerimientos diarios de energía, durante 21 días. Los sujetos (n = 98) recibieron una fórmula de control, Pediasure (C: 1,0 kcal/ mL) o una fórmula experimental similar en su composición nutricional, pero con mayor densidad calórica (1,5 kcal/mL) con fibra (Ef) o sin fibra (E). Los sujetos regresaron a consultas semanales. En todos los grupos mejoraron los parámetros gastrointestinales (p<0,05). La ingestión de energía fue similar entre los grupos, pero se obtuvo con volúmenes más bajos (p< 0,0001) en EyEF, en comparación con C. El aumento de peso fue mayor (p>0,01) en E vs. C. El informe de efectos adversos fue similar entre los grupos. Las fórmulas hipercalóricas son una opción en los niños con restricción de líquidos o con requerimientos aumentados de energía o de fibra, sin comprometer la seguridad o la tolerancia
Assuntos
Alimentos Formulados , Nutrição Enteral/métodos , Nutrição do LactenteRESUMO
An 8-year-old girl developed ataxia-telangiectasia. Western blotting of lysate revealed absence of the ATM protein, and 2 mutations in the ATM gene were found. Subsequently, the patient developed increased respiratory symptoms. Open lung biopsy revealed lymphocytic interstitial pneumonitis, which is not characteristic of ataxia-telangiectasia. There was a therapeutic response to glucocorticosteroid treatment.
Assuntos
Ataxia Telangiectasia/complicações , Hepatomegalia/etiologia , Imunoglobulina M/sangue , Doenças Pulmonares Intersticiais/etiologia , Esplenomegalia/etiologia , Ataxia Telangiectasia/imunologia , Criança , Feminino , HumanosRESUMO
To characterize changes to the heme and the influence of membrane lipids in the reaction of cytochrome c with peroxides, we studied the reaction of cytochrome c with tert-butyl hydroperoxide (tert-BuOOH) by magnetic circular dichroism (MCD) and direct electron paramagnetic resonance (EPR) in the presence and absence of different liposomes. Direct low-temperature (11 degrees K) EPR analysis of the cytochrome c heme iron on exposure to tert-BuOOH shows a gradual (180 s) conversion of the low-spin form to a high-spin Fe(III) species of rhombic symmetry (g = 4.3), with disappearance of a prior peroxyl radical signal (g(o) = 2.014). The conversion to high spin precedes Soret band bleaching, observable by UV/Vis spectroscopy and by magnetic circular dichroism (MCD) at room temperature, that indicates loss of iron coordination by the porphyrin ring. The presence of cardiolipin-containing liposomes delayed formation of the peroxyl radical and conversion to high-spin iron, while dicetylphosphate (DCP) liposomes accelerated these changes. Correspondingly, bleaching of cytochrome c by tert-BuOOH at room temperature was accelerated by several negatively charged liposome preparations, and inhibited by mitochondrial-mimetic phosphatidylcholinephosphatidylethanolaminecardiolipin (PCPECL) liposomes. Concomitant with bleaching, spin-trapping measurements with 5,5-dimethyl-1-pyroline-N-oxide showed that while the relative production of peroxyl, alkoxyl, and alkyl radicals was unaffected by DCP liposomes, PCPECL liposomes decreased the spin-trapped alkoxyl radical signal by 50%. The EPR results show that the primary initial change on exposure of cytochrome c to tert-BuOOH is a change to a high-spin Fe(III) species, and together with MCD measurements show that unsaturated cardiolipin-containing lipid membranes influence the interaction of tert-BuOOH with cytochrome c heme iron, to alter radical production and decrease damage to the cytochrome.
Assuntos
Grupo dos Citocromos c/química , Grupo dos Citocromos c/metabolismo , Heme/química , Ferro/química , terc-Butil Hidroperóxido/farmacologia , Animais , Dicroísmo Circular , Espectroscopia de Ressonância de Spin Eletrônica , Radicais Livres/metabolismo , Heme/metabolismo , Técnicas In Vitro , Ferro/metabolismo , Lipossomos , Lipídeos de Membrana/metabolismo , Oxirredução , Peróxidos/metabolismoRESUMO
Ataxia telangiectasia (A-T) is an autosomal recessive disorder with a broad range of clinical manifestations and a frequency of 1:40,000-100,000 live births. Epidemiological studies have suggested that A-T heterozygotes are at an elevated risk of breast cancer. ATM mutations occur worldwide over the entire ATM gene, making it difficult to identify heterozygotes in large populations. However, some founder-effect mutations are specific for certain populations. Here, we present four mutations in Costa Rican A-T patients that accounted for 86-93% of 41 patients studied in two batches. We have developed assays for rapid detection of these four mutations which can be used diagnostically. They will also enable the Costa Rican population to be used as a model for analyzing the role of ATM heterozygosity in cancer development and other disorders.
Assuntos
Ataxia Telangiectasia/genética , Efeito Fundador , Triagem de Portadores Genéticos , Testes Genéticos/métodos , Haplótipos , Ataxia Telangiectasia/diagnóstico , Códon de Terminação , Costa Rica , Éxons/genética , Genes Recessivos , Humanos , Mutação Puntual , Mapeamento por Restrição , Deleção de SequênciaRESUMO
Peroxynitrite-mediated one-electron oxidations may be an important event in its cytotoxic mechanisms, and yet, free radical formation in the presence of peroxynitrite is difficult to study by EPR-spin trapping because adducts from most spin traps are destroyed by the oxidant. This led to some controversy with regard to the interpretation of experiments in the presence of 5,5-dimethyl-1-pyrroline N-oxide (DMPO), an adequate spin trap to study most of free radicals. In this report we reexamined peroxynitrite-mediate formation of spin-trap adducts. Kinetic studies and EPR experiments with water labeled with 17O are in agreement with the reaction of DMPO with a highly reactive intermediate derived from peroxynitrite to produce the DMPO-hydroxyl radical adduct by a mechanism not involving the oxidation of DMPO to a cation radical followed by water addition. The results cannot discriminate between two mechanisms of DMPO-hydroxyl radical formation, either spontaneous peroxynitrite homolysis to the hydroxyl radical or DMPO-assisted peroxynitrite homolysis. The formation of DMPO adducts during peroxynitrite-mediated oxidation of dimethyl sulfoxide, ethanol, and formate occurs through free radical mechanisms as confirmed by studies of oxygen consumption and product formation. Accordingly, spin-trapping experiments in the presence of 3,5-dibromo-4-nitrosobenzenesulfonic acid, a spin trap that is more resistant to nitrogen dioxide, led to the detection of the methyl and the beta-hydroxyethyl radical during peroxynitrite-mediated oxidation of dimethyl sulfoxide and ethanol, respectively. Oxidation of these hydroxyl radical scavengers to detectable radicals favors the hypothesis that the hydroxyl radical is produced during peroxynitrite homolysis. Bicarbonate was able to modulate peroxynitrite-mediated one-electron oxidations.
Assuntos
Nitratos/química , Radicais Livres , Detecção de SpinRESUMO
Peroxynitrite mediates the oxidation of the thiol group of both cysteine and glutathione. This process is associated with oxygen consumption. At acidic pH and a cysteine/peroxynitrite molar ratio of < or = 1.2, there was a single fast phase of oxygen consumption, which increased with increasing concentrations of both cysteine and oxygen. At higher molar ratios the profile of oxygen consumption became biphasic, with a fast phase (phase I) that decreased with increasing cysteine concentration, followed by a slow phase (phase II) whose rate of oxygen consumption increased with increasing cysteine concentration. Oxygen consumption in phase I was inhibited by desferrioxamine and 5,5-dimethyl-1-pyrroline N-oxide, but not by mannitol; superoxide dismutase also inhibited oxygen consumption in phase I, while catalase added during phase II decreased the rate of oxygen consumption. For both cysteine and glutathione, oxygen consumption in phase I was maximal at neutral to acidic pH: in contrast, total thiol oxidation was maximal at alkaline pH. EPR spin-trapping studies using N-tert-butyl-alpha-phenylnitrone indicated that the yield of thiyl radical adducts had a pH profile comparable with that found for oxygen consumption. The apparent second-order rate constants for the reactions of peroxynitrite with cysteine and glutathione were 1290 +/- 30 M-1.S-1 and 281 +/- 6 M-1.S-1 respectively at pH 5.75 and 37 degrees C. These results are consistent with two different pathways participating in the reaction of peroxynitrite with low-molecular-mass thiols: (a) the reaction of the peroxynitrite anion with the protonated thiol group, in a second-order process likely to involve a two-electron oxidation, and (b) the reaction of peroxynitrous acid, or a secondary species derived from it, with the thiolate in a one-electron transfer process that yields thiyl radicals capable of initiating an oxygen-dependent radical chain reaction.
Assuntos
Nitratos/metabolismo , Consumo de Oxigênio , Compostos de Sulfidrila/metabolismo , Catalase/farmacologia , Cisteína/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Sequestradores de Radicais Livres/farmacologia , Glutationa/metabolismo , Cinética , Oxirredução , Consumo de Oxigênio/efeitos dos fármacos , Superóxido Dismutase/farmacologiaRESUMO
Nitric oxide reacts with superoxide to form peroxynitrite, a strong oxidizing species. Peroxynitrite can either directly oxidize molecules such as thiols or protonate to peroxynitrous acid, which can yield an oxidant with a reactivity similar to that of hydroxyl radical in a transition metal-independent mechanism. This oxidative chemistry of peroxynitrite, however, is inhibited by the metal chelator desferrioxamine. Indeed, desferrioxamine, was a potent inhibitor of dimethylsulfoxide, hydrogen peroxide, 5,5-dimethyl-1-pyrroline-N-oxide, and luminol oxidation, whereas the metal chelator diethylenetriaminepentaacetic acid, and ferrioxamine, the iron complex of desferioxamine, were not. Two other hydroxamates, acetohydroxamate and salicylhydroxamate, were also effective inhibitors. Stopped-flow experiments showed that there is no direct reaction between peroxynitrite anion or cis-peroxynitrous acid with desferrioxamine. Electron paramagnetic resonance (EPR) studies showed the formation of the desferrioxamine nitroxide radical in incubations containing desferrioxamine, but not ferrioxamine, indicating that the hydroxamic group acts as a one-electron donor to peroxynitrite-derived oxidants. Taken together, our results led us to propose that desferrioxamine can inhibit the oxidative chemistry of peroxynitrite by reaction of the hydroxamic acid moieties with trans-peroxynitrous acid.
Assuntos
Desferroxamina/farmacologia , Ácidos Hidroxâmicos/química , Radical Hidroxila/química , Nitratos/química , Óxidos N-Cíclicos/química , Dimetil Sulfóxido/química , Espectroscopia de Ressonância de Spin Eletrônica , Peróxido de Hidrogênio/química , Medições Luminescentes , Luminol/química , Oxirredução , EspectrofotometriaRESUMO
Nitric oxide reacts with superoxide to produce peroxynitrite which has been reported to be highly microbicidal to Trypanosoma cruzi in phosphate buffer but ineffective against Leishmania major in culture medium. This contradiction and the potential importance of peroxynitrite as a cytotoxic effector molecule of both macrophages and neutrophils led us to re-examine its leishmanicidal effects. Our results demonstrate that peroxynitrite inhibits growth of Leishmania amazonensis promastigotes in a concentration-dependent manner both in phosphate buffer and culture medium (DMEM containing 20% fetal calf serum). In the latter, 43% growth inhibition was observed with 4 mM peroxynitrite whereas in buffer a 70% inhibition was already observed with 0.5 mM peroxynitrite. Treated parasites presented reduced motility and became round in shape further confirming the leishmanicidal activity of peroxynitrite. The latter was attenuated by reduced glutathione supporting the view that peroxynitrite-mediated oxidation of critical thiol groups is a major mechanism accounting for its trypanocidal activity.
RESUMO
Nitric oxide reacts with superoxide to produce peroxynitrite, which may be an important mediator of oxidant-induced cellular injury. Here we report that peroxynitrite is able to oxidize a protein, bovine serum albumin (BSA), to the corresponding protein-thiyl free radical as demonstrated by electron paramagnetic resonance (EPR)-spin-trapping experiments with both alpha-phenyl-N-tert-butyl nitrone (PBN) and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). BSA radical adduct yields increased with pH indicating peroxynitrite anion as its main forming agent. Reaction with peroxynitrite may be another aspect of the antioxidant action of albumin in extracellular fluids.
Assuntos
Nitratos/metabolismo , Soroalbumina Bovina/metabolismo , Óxidos N-Cíclicos , Espectroscopia de Ressonância de Spin Eletrônica , Radicais Livres , Concentração de Íons de Hidrogênio , Óxidos de Nitrogênio , Oxirredução , Soroalbumina Bovina/química , Marcadores de SpinRESUMO
Decomposition of peroxynitrite, the reaction product of superoxide and nitric oxide, was studied by electron paramagnetic resonance (EPR)-spin-trapping experiments with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Proton-catalyzed decomposition of peroxynitrite at pH 7.5 resulted in the formation of the DMPO-hydroxyl radical adduct (DMPO-OH). Yields were low as DMPO-OH decomposes by direct reactions with peroxynitrite anion and nitrogen dioxide. The yield of DMPO-OH greatly increased in the presence of glutathione or cysteine. Both thiols inhibited the DMPO-OH signal decay by scavenging excess peroxynitrite anion and presumably nitrogen dioxide yielded during peroxynitrite decomposition. In turn, the reactions of peroxynitrite with either glutathione or cysteine resulted in the formation of thiyl radicals, detectable as the corresponding DMPO adduct. Systematic spin-trapping studies of peroxynitrite decomposition in the presence of glutathione established that DMPO-hydroxyl radical adduct formation was metal independent, occurring in a metal-free buffer and being unaffected by diethylene-triaminepentaacetic acid. Also, quantitative competition experiments with ethanol and formate demonstrated that the oxidant generated during peroxynitrite decomposition reacts with rate constants similar to those expected for free hydroxyl radical and forming the same free radical intermediates, alpha-ethyl-hydroxy and carbon dioxide radicals, respectively. Similar spin-trapping results were obtained in studies of the autooxidation of 3-morpholinosydnonimine, a sydnonimine which generates a flux of both superoxide and nitric oxide. The obtained results contribute for the understanding of the reactivity of peroxynitrite, a transient intermediate of emerging biological significance.