RESUMEN
Copper toxicity is thought to be a rare condition in horses. However, the number of cases diagnosed in Brazil is growing. This article aims to describe cases of copper toxicity involving horses from different geographic locations and discuss findings of physical examinations, differential diagnoses and potential causes. Five cases referred from 4 different properties where at least 15 other horses were affected were described. Hemolytic anemia and hemoglobinuria, presence of Heinz bodies and elevated aspartate aminotransferase and gamaglutamil transferase levels were detected in all cases. The diagnosis was based on clinical history and signs, laboratory tests results, copper level determination in feed and/or soil and histopathological findings. Two horses progressed to acute death; remaining horses responded to clinical management with or without blood transfusion, depending on disease severity. However, one of these horses, after several returns to the veterinary hospital, was euthanized due to complications. One horse was treated with ammonium tetrathiomolybdate. Two horses had several recurring episodes over the course of several months, an uncommon presentation in ruminants suffering from copper toxicity. Excess copper was associated with soil fertilization with poultry litter or treatment of previous or neighbor crops with copper-containing products. It can be concluded that copper toxicity does occur in horses and may arise from several sources and/or be associated with predisposing dietary factors. Given the growing number of cases, the condition should be included in the differential diagnosis list and proper preventive dietary and pasture fertilization measures adopted.
Asunto(s)
Anemia Hemolítica , Enfermedades de los Caballos , Anemia Hemolítica/inducido químicamente , Anemia Hemolítica/veterinaria , Animales , Cobre/toxicidad , Cuerpos de Heinz , Hemoglobinuria/veterinaria , Enfermedades de los Caballos/inducido químicamente , CaballosRESUMEN
Las variantes estructurales de hemoglobina son, en su mayoría, el resultado de sustituciones puntuales de aminoácidos en una de las cadenas de globina. En muchos casos, estas hemoglobinopatías son inocuas, mientras que en otros determinan alteraciones en la estabilidad y función de la hemoglobina, ocasionando manifestaciones clínicas de severidad variable. En las hemoglobinas inestables, las alteraciones disminuyen la solubilidad, y así facilitan la formación de complejos de hemoglobina precipitada y desnaturalizada (Cuerpos de Heinz) que ocasionan el daño de la membrana y finalmente la destrucción prematura de los eritrocitos. Representan una rara etiología de anemia hemolítica congénita. Hasta la actualidad se han descrito alrededor de 150 hemoglobinas inestables diferentes, la mayoría de las cuales ocasionan hemólisis crónica, exacerbada por infecciones o la ingesta de medicamentos. Su diagnóstico puede ser difícil, sobre todo en pacientes no esplenectomizados. Su identificación requiere inicialmente de la sospecha clínica, pero dado que las pruebas básicas de laboratorio pueden no ser concluyentes e inducir un diagnóstico erróneo, el estudio molecular será necesario para la confirmación.
The structural hemoglobin variants mostly result from single amino-acid substitutions in globin chains. In many cases these are innocuous, but in others they may alter the stability or functional properties of hemoglobin, leading to clinical manifestations of variable severity. They represent a rare cause of congenital hemolytic anemia. Unstable hemoglobins cause alterations that reduce solubility, with increased tendency to Heinz Body formation, damaging red blood cell membrane and finally the premature destruction of red blood cells. Up to 150 unstable hemoglobins have been described; most of them cause chronic hemolytic anemia, aggravated by infections and or drugs. Diagnosis can be difficult, especially in non-splenectomized patients. Initially, identification requires a high degree of clinical suspicion, but due to the fact that basic laboratory tests might be inconclusive, molecular analysis is necessary for final confirmation.
As variantes estruturais de hemoglobina são, em sua maioria, o resultado de substituições pontuais de aminoácidos numa das cadeias de globina. Em muitos casos, estas hemoglobinopatias são inócuas, ao passo que em outros determinam alterações na estabilidade e função da hemoglobina, produzindo manifestações clínicas de severidade variável. Nas hemoglobinas instáveis, as alterações diminuem a solubilidade, facilitando a formação de complexos de hemoglobina precipitada e desnaturalizada (Corpos de Heinz) que ocasionam o dano da membrana e finalmente a destruição prematura dos eritrócitos. Representam uma rara etiologia de anemia hemolítica congênita. Até a atualidade foram descritas aproximadamente 150 hemoglobinas instáveis diferentes, a maioria das quais produzem hemólise crônica, exacerbada por infecções ou pela ingestão de medicamentos. Seu diagnóstico pode ser difícil, principalmente em pacientes não esplenectomizados. Sua identificação requer inicialmente da suspeita clínica, mas devido a que as provas básicas de laboratório podem não ser concluintes e induzir um diagnóstico errado, o estudo molecular será necessário para a confirmação.
Asunto(s)
Humanos , Hemoglobinopatías/diagnóstico , Hemoglobinopatías/terapia , Anemia Hemolítica/diagnóstico , Hemoglobinas , Hemoglobinas/análisis , Cuerpos de HeinzRESUMEN
This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 µg/mL) and paucibacillary (0.662±0.123 µg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDT-supervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software.
Asunto(s)
Clofazimina/uso terapéutico , Dapsona/uso terapéutico , Lepra/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Rifampin/uso terapéutico , Adulto , Análisis de Varianza , Catalasa/sangre , Citocromo P-450 CYP2C19/metabolismo , Dapsona/sangre , Dapsona/metabolismo , Quimioterapia Combinada , Femenino , Glutatión/sangre , Cuerpos de Heinz/efectos de los fármacos , Cuerpos de Heinz/metabolismo , Humanos , Leprostáticos/uso terapéutico , Lepra/sangre , Masculino , Metahemoglobina/metabolismo , Persona de Mediana Edad , Oxidación-Reducción , Unión Proteica , Especies Reactivas de Oxígeno/sangre , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Dogs and cats are the animals that owners most frequently seek assistance for potential poisonings, and these species are frequently involved with toxicoses due to ingestion of poisonous food. Feeding human foodstuff to pets may prove itself dangerous for their health, similarly to what is observed in Allium species toxicosis. Allium species toxicosis is reported worldwide in several animal species, and the toxic principles present in them causes the transformation of hemoglobin into methemoglobin, consequently resulting in hemolytic anemia with Heinz body formation. The aim of this review is to analyze the clinicopathologic aspects and therapeutic approach of this serious toxicosis of dogs and cats in order to give knowledge to veterinarians about Allium species toxicosis, and subsequently allow them to correctly diagnose this disease when facing it; and to educate pet owners to not feed their animals with Allium-containg food in order to better control this particular life-threatening toxicosis.
Asunto(s)
Animales , Gatos , Allium/toxicidad , Anemia Hemolítica/tratamiento farmacológico , Gatos , Perros , Preparaciones de Plantas/farmacología , Cuerpos de HeinzRESUMEN
The mature human erythrocyte, when submitted to oxidative stress, can demonstrate depletion of reduced glutathione, oxidation of the hemoglobin molecule and aggregation of complexes of iron close to the membrane. These can produce abnormalities in the erythrocyte membrane and hemolysis. The aim of this work was to study the antioxidative action of vitamin C (vit. C), deferroxamine (DFO) and the flavonoids quercetin and rutin in normal human erythrocytes, submitted to in vitro oxidative stress induced by tert-butylhydroperoxide ((t)BHP). Venous blood was collected in citrate-phosphate-dextrose (CPD) solution, as anticoagulant, from healthy adult individuals after informed consent. The erythrocytes were resuspended in PBS to obtain 35% globular volume, and then submitted to the oxidative action of (t)BHP for up to 30 min, with or without previous incubation for 60 min with vit. C, DFO, quercetin and rutin. Decrease in the GSH concentration, G6-PD and GR activities, and increase in the methemoglobin and Heinz bodies (HB) formation, occurred with the increase in (t)BHP concentration. (t)BHP did not effect on the membrane proteins detected by SDS-PAGE. Quercetin, partially prevented the GSH decrease and the formation of HB, but did not prevent MetHb formation from oxidative damage by (t)BHP. Rutin, after (t)BHP induction, prevented the GSH decrease and the formation of HB. Vit. C, had no influence on the depletion of GSH, inhibited partially the metHb formation, and it protected GR, but not G6-PD from oxidative damage by (t)BHP. DFO partially inhibited the metHb formation and GSH decrease, but it did not protect GR and G6-PD from oxidative damage by (t)BHP. The results obtained suggest that vit. C, DFO and the flavonoids quercetin and rutin contribute to the decrease in the oxidative stress caused by (t)BHP.
Asunto(s)
Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Deferoxamina/farmacología , Eritrocitos/efectos de los fármacos , Quercetina/farmacología , Rutina/farmacología , terc-Butilhidroperóxido/efectos adversos , Adulto , Eritrocitos/metabolismo , Femenino , Glucosafosfato Deshidrogenasa/metabolismo , Glutatión/metabolismo , Cuerpos de Heinz/efectos de los fármacos , Cuerpos de Heinz/metabolismo , Humanos , Masculino , Metahemoglobina/metabolismo , Persona de Mediana Edad , Estrés Oxidativo/efectos de los fármacos , Adulto JovenRESUMEN
Este trabalho tem como objetivo descrever um caso de intoxicação por fenazopiridina, rotineiramente utilizado como anti-sépticos de vias urinárias em humanos, em um felino. O animal apresentou sinais de metemoglobinemia, que incluíam taquipinéia, cianose das mucosas e depressão quatro dias após o início da terapia com o medicamento em questão. O diagnóstico foi confirmado através da análise hematológica, que evidenciou a coloração amarronzada e presença de corpúsculos de Heinz no sangue do animal
Drugs commonly used as urinary analgesic and antiseptics in human patients are not indicated in cats with lower urinary tract diseases. They mat cause erythrocyes oxidative injury, methemoglobinemia and Heinz body anemia. The reported case describes clinical signs and treatment in a female Siamese vat presented with anemia, cyanosis and tachypnea after five days of phenazopyridine therapy
Asunto(s)
Animales , Gatos , Cuerpos de Heinz , Fenazopiridina , Gatos , Metahemoglobinemia , Patología VeterinariaRESUMEN
Este trabalho tem como objetivo descrever um caso de intoxicação por fenazopiridina, rotineiramente utilizado como anti-sépticos de vias urinárias em humanos, em um felino. O animal apresentou sinais de metemoglobinemia, que incluíam taquipinéia, cianose das mucosas e depressão quatro dias após o início da terapia com o medicamento em questão. O diagnóstico foi confirmado através da análise hematológica, que evidenciou a coloração amarronzada e presença de corpúsculos de Heinz no sangue do animal(AU)
Drugs commonly used as urinary analgesic and antiseptics in human patients are not indicated in cats with lower urinary tract diseases. They mat cause erythrocyes oxidative injury, methemoglobinemia and Heinz body anemia. The reported case describes clinical signs and treatment in a female Siamese vat presented with anemia, cyanosis and tachypnea after five days of phenazopyridine therapy(AU)
Asunto(s)
Animales , Gatos , Gatos , Fenazopiridina , Cuerpos de Heinz , Metahemoglobinemia , Patología VeterinariaRESUMEN
The understanding of the oxidative stress mechanisms helps to explain many of the processes of cellular lesion and death, especially those related to the hemolytic diseases. Sickle cell anemia, thalassemias and G6-PD deficiency are among the more frequent genetic anomalies accompanied by oxidative stress. In the sickle cells, one of the factors that predisposes to the hemolytic process is the oxidative degradation of the hemoglobin S due to its deoxigenation leading to hemichrome formation and precipitation as Heinz bodies. The oxidative stress contributes to the sickle process and shortening of the erythrocyte survival. Here we analyzed the oxidative process in erythrocytes of patients with two different genotypes for HbS (AS and SS). Units of blood from donors of the Center of Hematology and Hemotherapy of Paraná (HEMEPAR), from normal individuals (AA) and from heterozygote individuals (AS), and venous blood collected from patients with sickle cell anemia (SS) were analyzed. In order to evaluate the protective action of the vitamins C and E in oxidative stress, erythrocytes were treated with antioxidant substances, vitamin C and vitamin E, and then treated with the oxidant tert-butilhydroperoxide (TBHP). The oxidative action induced by TBHP was observed in erythrocytes AAAsunto(s)
Anemia de Células Falciformes/metabolismo
, Eritrocitos/metabolismo
, Hemoglobina Falciforme/metabolismo
, Estrés Oxidativo
, Anemia de Células Falciformes/tratamiento farmacológico
, Ácido Ascórbico/uso terapéutico
, Donantes de Sangre
, Eritrocitos/efectos de los fármacos
, Glutatión/sangre
, Cuerpos de Heinz/metabolismo
, Hemoglobina Falciforme/efectos de los fármacos
, Humanos
, Oxidación-Reducción
, Valores de Referencia
, Vitamina E/uso terapéutico
Asunto(s)
Anemia Hemolítica Congénita/complicaciones , Anemia Hemolítica Congénita/genética , Cuerpos de Heinz/patología , Hemoglobinas Anormales/análisis , Hemoglobinas Anormales/genética , Anemia Hemolítica Congénita/patología , Brasil , Preescolar , Femenino , Pruebas Genéticas , Globinas/genética , Humanos , Mutación Puntual , Reacción en Cadena de la Polimerasa/métodos , Sensibilidad y Especificidad , Análisis de Secuencia de ADNRESUMEN
A intoxicação por cebola é relatada em várias espécies animais em muitas partes do mundo. O princípio tóxico (n-propil dissulfito) presente na cebola causa a transformação da hemoglobina em metemoglobina. Para estudar os achados laboratoriais, de necropsia e histopatológicos da intoxicação por cebola em gatos, cinco gatos de quatro meses de idade receberam cada um uma dose única de 10g/kg de cebola desidratada por via oral. Um outro gato de mesma idade não recebeu a refeição com cebola e serviu como controle. Todos os cinco gatos desenvolveram sinais clínicos da toxicose; um deles morreu dentro de 24 horas após a ingestão da cebola. Os sinais clínicos incluíram apatia, taquicardia, taquipnéia e cianose. Os achados laboratoriais se caracterizavam por anemia hemolítica associada a corpúsculos de Heinz e metemoglobinemia. Os principais achados de necropsia foram esplenomegalia e sangue de cor marrom. Os achados histopatológicos foram hemossiderose e hematopoese extramedular no baço e fígado (AU)
Asunto(s)
Animales , Intoxicación por Plantas , Cebollas , Liliaceae/envenenamiento , Anemia Hemolítica , Metahemoglobinemia , Cuerpos de HeinzRESUMEN
A intoxicaçäo por cebola é relatada em várias espécies animais em muitas partes do mundo. O princípio tóxico (n-propil dissulfito) presente na cebola causa a transformaçäo da hemoglobina em metemoglobina. Para estudar os achados laboratoriais, de necropsia e histopatológicos da intoxicaçäo por cebola em gatos, cinco gatos de quatro meses de idade receberam cada um uma dose única de 10g/kg de cebola desidratada por via oral. Um outro gato de mesma idade näo recebeu a refeiçäo com cebola e serviu como controle. Todos os cinco gatos desenvolveram sinais clínicos da toxicose; um deles morreu dentro de 24 horas após a ingestäo da cebola. Os sinais clínicos incluíram apatia, taquicardia, taquipnéia e cianose. Os achados laboratoriais se caracterizavam por anemia hemolítica associada a corpúsculos de Heinz e metemoglobinemia. Os principais achados de necropsia foram esplenomegalia e sangue de cor marrom. Os achados histopatológicos foram hemossiderose e hematopoese extramedular no baço e fígado
Asunto(s)
Animales , Masculino , Femenino , Gatos , Anemia Hemolítica , Cuerpos de Heinz , Liliaceae , Metahemoglobinemia , Cebollas , Intoxicación por PlantasRESUMEN
Haemoglobin, either in the intact red blood cells or in their haemolysate, readily reacts with mono- and di-nitrobenzoates. For all the nitroaromatics considered, the rate of the process is faster in the haemolysate than in the whole red blood cell. At low (< 8 mM) concentrations, almost quantitative production of methaemoglobin is observed and the process follows second order kinetics. At higher concentrations, the kinetics become complex and other haemoglobin derivatives are produced. The bimolecular rate constants obtained at low substrate concentrations show little relationship to the nitroaromatic reduction potential. The data indicate that mono-nitrobenzoate derivatives are very active in oxidizing haemoglobin in in vitro erythrocyte suspensions, the activities being similar to that of 3,5-dinitrobenzoate. The measured reactivity follows the order m-nitrobenzoate > 3,5-dinitrobenzoate > p-nitrobenzoate > o-nitrobenzoate and the reactivity of all the compounds is considerably larger than that of nitrobenzene. The present results constitute the first kinetic data bearing on the reactivity of nitroaromatics with haemoglobin, both free and incorporated in the intact red cell. Furthermore, they indicate that the interaction of the nitroaromatics with haemoglobin, leading to total oxidation and transformation, in spite of the total disruption of the membrane, does not produce significant lipid-peroxidation, as measured by chemiluminescence emission, production of TBA reactive material and oxygen consumption.
Asunto(s)
Eritrocitos/efectos de los fármacos , Hemoglobinas/efectos de los fármacos , Nitrobenzoatos/toxicidad , Animales , Cuerpos de Heinz/efectos de los fármacos , Hemólisis/efectos de los fármacos , Masculino , Nitrobenzoatos/química , Oxidación-Reducción/efectos de los fármacos , Consumo de Oxígeno , Ratas , Ratas Sprague-DawleyRESUMEN
This study was undertaken after the observation in a premature infant of a hemolytic anemia with Heinz bodies that appeared to result from administration of a multivitamin preparation. In vitro incubation of erythrocytes of premature infants with sodium ascorbate (0.1 mg/ml) for 3 hours significantly raised the number of Heinz body-containing cells from 17.6 +/- 5.7% to 27.2 +/- 8.2% (mean +/- SE). Erythrocytes of term infants and those of adults developed Heinz bodies after exposure to higher sodium ascorbate concentrations (1.0 mg/ml). Erythrocytes of adult and newborn guinea pigs were similarly affected by sodium ascorbate. Daily intraperitoneal injections of 500 mg of sodium ascorbate, given for 7 days to four adult guinea pigs, caused significant Heinz body formation. These studies indicate that the erythrocytes of premature infants are uniquely sensitive to the development of Heinz bodies after exposure to sodium ascorbate. The levels required to produce Heinz bodies in vitro are in the range of those found in vivo after routine administration of vitamin C to premature infants. The significance of these observations in the development of hyperbilirubinemia in premature infants and in the safety of vitamin C remains to be determined.
Asunto(s)
Anemia Hemolítica/inducido químicamente , Ácido Ascórbico/efectos adversos , Eritrocitos/efectos de los fármacos , Enfermedades del Prematuro/sangre , Adulto , Anemia Hemolítica/patología , Animales , Eritrocitos Anormales/patología , Femenino , Cobayas , Cuerpos de Heinz/efectos de los fármacos , Humanos , Recién Nacido de Bajo Peso/sangre , Recién Nacido , Enfermedades del Prematuro/inducido químicamenteAsunto(s)
Contaminación Ambiental/efectos adversos , Enfermedades Hematológicas/inducido químicamente , Adolescente , Adulto , Anciano , Brasil , Niño , Eritrocitos/ultraestructura , Femenino , Cuerpos de Heinz/ultraestructura , Humanos , Plomo/sangre , Masculino , Persona de Mediana Edad , Óxidos de Nitrógeno/envenenamiento , Óxidos de Azufre/envenenamientoAsunto(s)
Anemia Hemolítica/inducido químicamente , Cuerpos de Heinz , Enfermedades del Prematuro/inducido químicamente , Azul de Metileno/efectos adversos , Anemia Hemolítica/sangre , Nutrición Enteral , Eritrocitos/análisis , Cuerpos de Heinz/análisis , Humanos , Recién Nacido , Intubación GastrointestinalAsunto(s)
Anemia Hemolítica Congénita/diagnóstico , Eritrocitos/enzimología , Enfermedades del Recién Nacido/enzimología , Anemia Hemolítica Congénita/terapia , Transfusión Sanguínea , Enfermedad Crónica , Diagnóstico Diferencial , Hipersensibilidad a las Drogas/etiología , Edema/etiología , Eritroblastosis Fetal/diagnóstico , Eritroblastosis Fetal/terapia , Eritrocitos/inmunología , Recambio Total de Sangre , Femenino , Edad Gestacional , Deficiencia de Glucosafosfato Deshidrogenasa/complicaciones , Deficiencia de Glucosafosfato Deshidrogenasa/diagnóstico , Glucólisis , Cuerpos de Heinz , Humanos , Hiperbilirrubinemia/enzimología , Recién Nacido , Kernicterus , Errores Innatos del Metabolismo , EmbarazoRESUMEN
Some aspects of red-cell matabolism were studied in blood samples taken from patients on long-term dapsone therapy. Glucose consumption by the Embden-Meyerhof pathway (EMP) was not abnormal and adenosine-triphosphate (ATP) levels lay within the normal range and were well maintained during incubation. Hexose monophosphate patchway (HMP) activity was increased above that which would be expected from the age of the red-cell population. Red-cell reduced glutathione (GSH) levels tended to be lower than normal, proportional to the dose od dapsone and GSH levels were unstable on incubation. Red-cell fractionation studies showed that the older cell fraction had lower GSH levels and more Heinz bodies but proportionally greater HMP activity than the younger cell fraction. It is suggested that the low GSH levels are probably due to the binding of GSH to sulphydryl groups in haemoglobin and possibly the red-cell membrane. The increased HMP activity in the older cells many, in part, be a compensatory mechanism.