Assuntos
RNA Viral/análise , Saliva/virologia , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Adulto , Animais , Sangue/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Tempo , Zika virus/genéticaRESUMO
OBJECTIVE: To evaluate the impact of the two most common CYP2C9 variant alleles (*2 and *3) on the maintenance dose of warfarin and on the quality of anticoagulation control in Brazilians. METHODS: Patients (n = 103) initiated warfarin therapy with 5 mg/day (or 2.5 mg/day when over 80 years old). The international normalized ratio (INR) was targeted between 2 and 3, monitored every week until four consecutive adequate measures had been obtained, and then monthly. Serious hemorrhagic events were defined by the need for inpatient hospitalization. CYP2C9 genotyping was obtained by PCR-RFLP. RESULTS: The frequencies of CYP2C9*2 and CYP2C9*3 were 0.097 and 0.073, respectively, with genotypic distribution fitting Hardy-Weinberg equilibrium. CYP2C9 genotype was the only clinical feature associated with the risk of severe bleeding (one-sided P = 0.019, Fisher exact method), with an odds ratio of 4.8 (95% confidence interval of 1.4-16.6) for any variant genotype as compared to CYP2C9*1*1. Patients with either CYP2C9*2 or CYP2C9*3 were equally difficult to maintain in the INR target range, showing significantly (one-sided P = 0.038, Mann-Whitney U-test) reduced ratio of adequate INR measures (0.54 +/- 0.2), when compared to CYP2C9*1*1 patients (0.63 +/- 0.2). Patients with CYP2C9*3, but not CYP2C9*2, required significantly (one-sided P = 0.001, Mann-Whitney U-test) lower warfarin maintenance doses (3.1 +/- 1.8 mg) than CYP2C9*1*1 patients (5.3 +/- 2.1 mg). CONCLUSION: Patients with either CYP2C9*2 or CYP2C9*3 show higher risk of over-anticoagulation compared to CYP2C9*1*1 subjects and could benefit from a reduction in the initial warfarin standard dose (e.g., to 2.5 mg/day).
Assuntos
Anticoagulantes/farmacologia , Hidrocarboneto de Aril Hidroxilases/genética , Varfarina/farmacologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Brasil , Criança , Citocromo P-450 CYP2C9 , Relação Dose-Resposta a Droga , Feminino , Frequência do Gene , Genótipo , Hemorragia/induzido quimicamente , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Risco , Varfarina/administração & dosagem , Varfarina/efeitos adversosRESUMO
The hypotheses that iron-deficient hosts are less susceptible to severe malaria and that iron supplementation aggravates infection have been supported by some clinical and experimental evidence. In the present study, the course of Plasmodium berghei infection was monitored in an experimental model of dietary iron deficiency and iron supplementation. Weanling Wistar rats were fed purified diets with different iron concentrations: 20 mg/kg (Group D, n = 24), 50 mg/kg (Group N, n = 24) and 100 mg/kg (Group S, n = 12). After 15 d, rats from Group D were anemic (mean hemoglobin 81 g/l). The next day, 12 rats from Group D (thereafter Group DS) and 12 rats from Group N (thereafter Group NS) were transferred to the same iron-supplemented diet as in Group S, whereas the remaining animals (Groups D, N and S) were maintained on the original diets for further 14 d. At that time, 9 rats from each group were inoculated intraperitoneally with 10(6) erythrocytic parasites (P. berghei ANKA strain), whereas 3 rats from each group remained as noninfected controls. All animals were killed 14 d after inoculation, when significantly lower levels of hemoglobin, serum iron and percent transferrin saturation were found in infected animals from Group D compared with all other groups. However, the time course of parasitemias was similar in all groups. These data indicate that the development of P. berghei was neither suppressed by iron deficiency nor enhanced by iron supplementation in this model. Furthermore, iron repletion during infection did produce a noticeable improvement of hematological variables in previously iron-deficient animals.