RESUMO
In a screening for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 1985 unrelated male subjects from the general population (Groups A and B) belonging to four states of the Pacific coast, 21 G-6-PD-deficient subjects were detected. Screening for mutations at the G-6-PD gene by PCR-restriction enzyme in these 21 G-6-PD-deficient subjects as well as in 14 G-6-PD-deficient patients with hemolytic anemia belonging to several states of Mexico showed two common G-6-PD variants: G-6-PD A-(202A/376G) (19 cases) and G-6-PD A-(376G/968C) (9 cases). In 7 individuals the mutations responsible for the enzyme deficiency remain to be determined. Furthermore, four silent polymorphic sites at the G-6-PD gene (PvuII, PstI, 1311, and NlaIII) were investigated in the 28 individuals with G-6-PD A- variants and in 137 G-6-PD normal subjects. As expected, only 10 different haplotypes were observed. To date, in our project aiming to determine the molecular basis of G-6-PD deficiency in Mexico, 60 unrelated G-6-PD-deficient Mexican males-25 in previous studies and 35 in the present work-have been studied. More than 75% of these individuals are from states of the Pacific coast (Sinaloa, Nayarit, Jalisco, Michoacán, Guerrero, Oaxaca, and Chiapas). The results show that although G-6-PD deficiency is heterogeneous at the DNA level in Mexico, only three polymorphic variants have been observed: G-6-PD A-(202A/376G) (36 cases), G-6-PD A-(376G/968C) (13 cases), and G-6-PD Seattle(844C) (2 cases). G-6-PD A- variants are relatively distributed homogeneously and both variants explain 82% of the overall prevalence of G-6-PD deficiency. The variant G-6-PD A-(202A/376G) represents 73% of the G-6-PD A- alleles. Our data also show that the variant G-6-PD A-(376G/968C)-which has been observed in Mexico in the context of two different haplotypes-is more common than previously supposed. The three polymorphic variants that we observed in Mexico are on the same haplotypes as found in subjects from Africa, the Canary Islands, and Spain.
Assuntos
Glucosefosfato Desidrogenase/genética , Haplótipos , Indígenas Norte-Americanos/genética , Mutação , DNA/química , DNA/genética , Análise Mutacional de DNA , Frequência do Gene , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Masculino , México , Polimorfismo GenéticoRESUMO
Several studies carried out between 1965 and 1985 showed that G-6-PD deficiency in Mexico is heterogeneous at the biochemical level and that the G-6-PD A- phenotype is relatively common. We have now investigated the molecular basis of G-6-PD deficiency in Mexico. Up-to-date 60 chromosomes with G6PD mutations have been studied, 16 in previous studies and 44 in the present work. Molecular analysis of DNA from G-6-PD deficient Mexican mestizos and their relatives show that G-6-PD A- genotypes are relatively common but also that in Mexico G-6-PD deficiency is heterogeneous at the DNA level. Thus, five different genotypes have been observed: G-6-PD A-(202A/376G) (41 chromosomes), G-6-PD A-(376G/968C) (14 chromosomes), G-6-PD Seattle844C (3 chromosomes), G-6-PD "Mexico City"680A (1 chromosome) and G-6-PD Guadalajara1159T (1 chromosome). The G-6-PD A-(202A/376G), G-6-PD A-(376G/968C) and G-6-PD Seattle844C mutations in Mexico are on the same Pvu II/ Pst I/ 1311 / Nla III haplotypes as found in individuals from Africa, Spain and the Canary Islands. Consequently, these mutations were probably imported to Mexico through African slaves and/or the Spanish immigrants during and after the colonization.
Assuntos
Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , Mutação , Adulto , Feminino , Genótipo , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Haploidia , Humanos , Indígenas Norte-Americanos/genética , Masculino , México/epidemiologia , População Branca/genéticaRESUMO
We present a case of acute lethal poisoning by oil of "epazote" (oil of chenopodium), in a 2 y 9 m female. The volatile oil was administered according to the advice of a "curandera" (female healer), in a total quantity of 40 ml. Clinical features of the poisoning were: vomiting, deep coma, seizures, mydriasis, apnea, metabolic acidosis, neurogenic shock and death. The EEG suggested a diffuse encephalopathy, the CT scan with an image of severe brain edema and ventricular collapse. Relevant postmortem findings were brain edema and neuronal necrosis, pneumonia, enteritis, pericholangitis, mild pancreatitis and tubular necrosis. The phytochemical analysis of volatile oil identified ascaridol, the main active compound of the chenopodium herbs, in a quantity of 39 mg/ml (1,560 mg in the dose administered), and Chenopodium graveolens as the plant employed to prepare it. According to the age of the patient, 60 mg of ascaridol would be the recommended dose formerly used in the treatment of parasitic disease. Thus 1,560 mg was 26 times higher than the recommended dose, and exceeded by 56% the dose of 1,000 mg reported as lethal in humans.
Assuntos
Óleos de Plantas/intoxicação , Terpenos/intoxicação , Pré-Escolar , Evolução Fatal , Feminino , HumanosRESUMO
Evalua la acción antileishmaniásica que podría tener la mefloquina que normalmente se usa como droga antimalárica con gran efectividad para la curación de todas sus formas. Desde 1994, 120 pacientes con leishmaniasis cutánea han sido tratados y curados con la administración oral de mefloquina, siguiendo un protocolo, con la dosis de 125 mg después del desayuno y merienda durante 10 días para los adultos, y una dosis total de 40-50 mg/kg. para los niños, en tomas de 62,5 mg cada 12 horas, con las comidas. En casos severos se repite el tratamiento después de un período de 7-10 días a partir de la última toma. El porcentaje de cicatrización después del tratamiento fue del 100xciento con un tiempo promedio de 27,1 días para las lesiones pequeñas (hasta 1 cm) y de 35,5 días para las lesiones medianas y grandes (de 1.2 a 2.5 cm y de 2.6 en adelante, respectivamente). El tiempo de seguimiento mínimo de 1 año ha sido alcanzado ya por 40 de los pacientes tratados y curados con mefloquina quienes constituyen en primer grupo que presentamos a manera de informe preliminar. Inicialmente se utilizó un grupo control de 18 pacientes quienes recibieron placebo, sin haber ninguno de ellos cicatrizado sus lesiones durante 6 meses de observación. Con esta referencia no se han utilizado nuevamente grupos de control, ya que usualmente los pacientes vienen de sitios lejanos realizando gastos superfluos sin resultados positivos...
Assuntos
Humanos , Leishmaniose Cutânea , Mefloquina , Placebos , Equador , PacientesRESUMO
DNA samples from seven G-6-PD deficient Mexican mestizo patients were analyzed. Three different G-6-PD genotypes were observed: G-6-PD A-202A/376G (three patients), G-6-PD A-376G/968C (three patients) and G-6-PD Seattle844C. The present results, along with previous reports, suggest not only G-6-PD A-genotypes are relatively common but also G-6-PD deficiency seems to be heterogeneous at DNA level in Mexico.
Assuntos
Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , África/etnologia , Análise Mutacional de DNA , Testes Genéticos , Genótipo , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/etnologia , Humanos , Itália/etnologia , Masculino , México/epidemiologia , Espanha/etnologiaRESUMO
Seven new mutations that produce glucose 6 phosphate dehydrogenase (G6PD) deficiency are described. Three are in variants that were biochemically characterized and described previously, while four were found in samples that had not been characterized biochemically. Several of the mutations affect the amino acids that are mutated in other G6PD variants. As had been noted previously, variants that are associated with nonspherocytic anemia are located either near the glucose 6 phosphate or the NADP binding sites. Variants more distant from these sites are not associated with chronic hemolysis.
Assuntos
Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , Sequência de Aminoácidos , Sequência de Bases , Chile/etnologia , Grécia/etnologia , Humanos , Japão/etnologia , México/etnologia , Mutação , Estados Unidos/etnologiaRESUMO
Aldose reductase catalyzes the NADPH-linked reduction of hexoses to their respective sugar-alcohols, which are involved in the pathogenesis of "sugar-cataracts". In the lenses, the reaction catalyzed by G-6-PD is the source of NADPH supply blocking sugar-alcohol formation and consequently prevents or delays the onset of "sugar-cataracts". We have investigated the effect of G-6-PD deficiency, either experimentally induced or genetically transmitted, on the sorbitol accumulation in whole cells incubated in high glucose media and on the "sugar-cataracts" formation in a galactosemic rat model. We also screened 31 Negro male adults with diabetes mellitus for red cell G-6-PD deficiency. G-6-PD deficiency produced a significant inhibition on sorbitol accumulation in rat lenses and human red cells incubated in 50 mM glucose. In the galactosemic rat model G-6-PD deficiency experimentally induced with acetaminophen delayed the development of cataracts. Finally, two diabetic individuals were G-6-PD deficient and did not show cataracts whereas cataracts were identified in six other diabetic patients.
Assuntos
Aldeído Redutase/metabolismo , Deficiência de Glucosefosfato Desidrogenase/metabolismo , L-Iditol 2-Desidrogenase/metabolismo , Sorbitol/metabolismo , Acetaminofen/farmacologia , Acetaminofen/toxicidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , População Negra/genética , Catarata/etiologia , Catarata/metabolismo , Catarata/prevenção & controle , Criança , Cloranfenicol/farmacologia , Costa Rica/epidemiologia , Desidroepiandrosterona/farmacologia , Complicações do Diabetes , Diabetes Mellitus/metabolismo , Modelos Animais de Doenças , Eritrócitos/metabolismo , Galactosemias/complicações , Galactosemias/metabolismo , Glucosefosfato Desidrogenase/antagonistas & inibidores , Deficiência de Glucosefosfato Desidrogenase/induzido quimicamente , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Incidência , Cristalino/metabolismo , Masculino , Pessoa de Meia-Idade , NADP/metabolismo , Oxirredução , Ratos , Ratos Sprague-DawleyRESUMO
Erythrocyte superoxide dismutase activity was determined in four groups of patients, two with hematologic neoplasms with and without therapy and two others with solid tumors also selected on the basis of therapy. Increased activities were found in the two groups where there was no treatment, whereas those under treatment showed normal levels. In addition, an inverse relationship (r = -0.25 p < 0.02) between superoxide dismutase activities and the time under therapy was observed.