RESUMO
Haiti is one of two remaining malaria-endemic countries in the Caribbean. To decrease malaria transmission in Haiti, primaquine was recently added to the malaria treatment public health policy. One limitation of primaquine is that, at certain doses, primaquine can cause hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd). In this study, we genotyped two mutations (A376G and G202A), which confer the most common G6PDd variant in West African populations, G6PDd A-. We estimated the frequency of G6PDd A- in a sample of febrile patients enrolled in an on-going malaria study who represent a potential target population for a primaquine mass drug administration. We found that 33 of 168 individuals carried the G6PDd A- allele (includes A- hemizygous males, A- homozygous or heterozygous females) and could experience toxicity if treated with primaquine. These data inform discussions on safe and effective primaquine dosing and future malaria elimination strategies for Haiti.
Assuntos
Alelos , Anemia Hemolítica/prevenção & controle , Febre/genética , Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , Malária Falciparum/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Hemolítica/etiologia , Antimaláricos/administração & dosagem , Criança , Pré-Escolar , Contraindicações , Feminino , Febre/complicações , Febre/tratamento farmacológico , Febre/enzimologia , Genótipo , Glucosefosfato Desidrogenase/metabolismo , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/tratamento farmacológico , Deficiência de Glucosefosfato Desidrogenase/enzimologia , Haiti , Heterozigoto , Homozigoto , Humanos , Lactente , Malária Falciparum/complicações , Malária Falciparum/tratamento farmacológico , Malária Falciparum/enzimologia , Masculino , Pessoa de Meia-Idade , Mutação , Primaquina/administração & dosagemRESUMO
Heme oxygenase (HO)-1 has antioxidant and cytoprotective properties if properly expressed, whereas nitric oxide (NO) impairs tissue perfusion when greatly increased in the blood circulation. Here we hypothesized that the NO and HO-1 systems are altered during lipopolysaccharide (LPS) tolerance, and that glucocorticoids are crucial modulators of systemic NO production and hepatic HO-1 expression during this intriguing phenomenon of cellular reprogramming. Adrenalectomized (ADX) rats with or without administration of dexamethasone (DEX) were challenged with LPS for 3 consecutive days. The plasma levels of corticosterone and nitrate (NOx), and expression of HO-1 protein were assessed. During tolerance, corticosterone levels were elevated, NOx reduced, and HO-1 overexpressed. ADX rats challenged with LPS for 3 consecutive days exhibited a ~9-fold increase in NOx and a ~6-fold increase in HO-1, reverted by DEX. Our findings strongly support the fact that glucocorticoids downregulate systemic NO synthesis and counteract hepatic HO-1 overexpression during LPS tolerance.
Assuntos
Dexametasona/administração & dosagem , Endotoxemia/enzimologia , Glucocorticoides/administração & dosagem , Heme Oxigenase (Desciclizante)/metabolismo , Terapia de Reposição Hormonal , Fígado/efeitos dos fármacos , Óxido Nítrico/metabolismo , Adrenalectomia , Animais , Corticosterona/sangue , Modelos Animais de Doenças , Regulação para Baixo , Endotoxemia/sangue , Endotoxemia/induzido quimicamente , Febre/induzido quimicamente , Febre/enzimologia , Injeções Subcutâneas , Lipopolissacarídeos , Fígado/enzimologia , Masculino , Nitratos/sangue , Ratos , Ratos Wistar , Fatores de Tempo , Regulação para CimaRESUMO
This study was aimed at testing the hypothesis that the brain heme oxygenase (HO)-carbon monoxide (CO) pathway plays a role in stress fever. To this end, the effect of the HO inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG), on restraint-induced fever was tested. Intracerebroventricular ZnDPBG (200 nmol) did not affect the body core temperature of unrestrained rats, but markedly attenuated restraint-induced fever. However, at the same dose, intraperitoneal ZnDPBG did not affect the febrile response to restraint. Taken together, these results indicate that the brain HO-CO pathway plays a major role in the genesis of stress fever in rats.
Assuntos
Encéfalo/enzimologia , Monóxido de Carbono/fisiologia , Febre/enzimologia , Heme Oxigenase (Desciclizante)/fisiologia , Estresse Fisiológico/enzimologia , Animais , Encéfalo/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Heme Oxigenase (Desciclizante)/antagonistas & inibidores , Masculino , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
Nitric oxide (NO) has been shown to be an important modulator of the febrile response to pyrogens and to psychological stress. In the present study, we aimed to identify the nitric oxide synthase (NOS) isoform (neuronal or inducible, nNOS and iNOS, respectively) involved in restraint stress fever. Colonic temperature (Tc) was measured in unanesthetized rats before and after treatment with the more selective nNOS inhibitor 7-nitroindazole or with the selective iNOS inhibitor aminoguanidine (AG) under unrestrained or restrained conditions. Intraperitoneal injection of AG (25 or 50 mg/kg) did not affect restraint fever, indicating that iNOS is unlikely to be involved in restraint fever. On the other hand, intraperitoneal injection of 7-nitroindazole (25 mg/kg) significantly attenuated the rise in the Tc caused by restraint stress, whereas it caused no change in Tc of euthermic animals. These data show that NO produced by nNOS plays an important role in the genesis of restraint stress-induced fever.
Assuntos
Febre/enzimologia , Óxido Nítrico Sintase/fisiologia , Estresse Psicológico/enzimologia , Animais , Temperatura Corporal/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Febre/etiologia , Guanidinas/farmacologia , Indazóis/farmacologia , Injeções Intraperitoneais , Masculino , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase Tipo I , Óxido Nítrico Sintase Tipo II , Ratos , Ratos Wistar , Restrição Física , Estresse Psicológico/complicaçõesRESUMO
The contribution of serum adenosine deaminase (ADA) activity to the diagnosis of typhoid fever was assessed in 246 children and in 46 adults, by Giusti's original technique. Children included otherwise healthy patients admitted for elective surgical conditions or under follow up for epilepsy which were considered to be a control group (n: 81), presumptive viral diseases (n: 31), miscellaneous febrile diseases except for typhoid fever (n: 41), different kinds of bacteremia (n: 6), diarrhea due to Salmonella typhimurium (n: 14), viral hepatitis (n: 24), and culture proven typhoid fever (n: 49). Adult's group included 39 healthy controls and 7 patients with culture proven typhoid fever. Among children mean ADA activity was as follows: control group 28 +/- 7.8, viral disease 35.3 +/- 13.1, miscellaneous febrile disease 36.1 +/- 15.6, bacteremia group: 30.3 +/- 10.3, salmonellosis group 51.6 +/- 9, hepatitis group 68.3 +/- 34.5, typhoid fever group 124.4 +/- 40.8 U/I 37 degrees C. Among adults, values were 18.4 +/- 7.5 for controls and 112.8 +/- 19.2 U/I 37 degrees C in typhoid fever patients. In both adults and children ADA activity was significantly higher in the typhoid fever group (p < 0.0001). Untreated typhoid fever patients had their higher ADA activity between 10th and 15th day of illness. When ADA cut point was set at 80 U/I, sensitivity of the test was 91.8% and specificity was 91.4% as a preliminary clue to the recognition of typhoid fever.