RESUMO
WHAT IS KNOWN AND OBJECTIVE: CYP2C19 genotypes presumably allow the prediction of the metabolizer phenotypes: poor (PMs), extensive (EMs) and ultra-rapid (UMs). However, evidence from previous studies regarding this predictive power is unclear, which is important because the benefits expected by healthcare institutions and patients are based on this premise. Therefore, we aimed to complete a formal evaluation of the diagnostic value of CYP2C19 and CYP3A4 genes for predicting metabolizer phenotypes established by omeprazole (OME) administration in 118 healthy children from Jalisco (western Mexico). METHODS: The genotypes for CYP3A4*1B and CYP2C19*2, *3, *4, *5 and *17 alleles were determined. CYP2C19 and CYP3A4 phenotypes were obtained after 20 mg OME administration and HPLC quantification in plasma to estimate the Hydroxylation Index (HI = OME/HOME) and Sulfonation Index (SI = OME/SOME), respectively. RESULTS AND DISCUSSION: The distribution of genotypes and phenotypes for CYP2C19 and CYP3A4 was similar to previous studies in Mexico and Latin America. We estimated the CYP2C19 UM, EM and PM phenotype frequency in 0.84%, 96.61% and 2.54%, respectively. Although differences in the HI distribution were observed between CYP2C19 genotypes, they showed a poor diagnostic ability to predict the CYP2C19 metabolizer phenotype. Similarly, the number of CYP2C19 and CYP3A4 functional alleles was correlated with the HI distribution, but also their diagnostic ability to predict the CYP2C19 phenotype was poor. WHAT IS NEW AND CONCLUSION: The CYP2C19 phenotype is not predicted by the number of functional alleles of CYP2C19 and CYP3A4 genes. Phenotyping is still the most valuable alternative to dose individualization for CYP2C19 substrate drugs.
Assuntos
Antiulcerosos/uso terapêutico , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP3A/genética , Omeprazol/uso terapêutico , Alelos , Criança , Feminino , Genótipo , Humanos , Hidroxilação/efeitos dos fármacos , Hidroxilação/genética , Masculino , México , Fenótipo , Polimorfismo Genético/genéticaRESUMO
AIM: To analyze possible factors associated with the quality of life (QoL) of mothers of preterm infants with very low birth weight (VLBW) during the first 3 years after delivery. METHODS: The World Health Organization Quality of Life (WHOQOL)-bref scores were compared and correlated with maternal and infant-related sociodemographic and clinical variables at maternal discharge (T0) and at 6 (T1), 12 (T2), 24 (T3), and 36 (T4) months after delivery. Multiple linear regression models were fitted to investigate the effect of these variables on the mothers' QoL. RESULTS: The WHOQOL-BREF physical domain scores were higher at T1 and T2 compared to T0 (p = 0.013). Maternal variables that contributed to maternal QoL scores (p < 0.05) were stable marital union (b = 13.60; T0), family income (b = -12.75; T3), Evangelical religion (b = 8.11; T4), and beck depression inventory (BDI) score (-1.42 ≤ b ≤ -0.36; T0, T1, T2, T3, and T4). Infants' variables that most affected maternal QoL (p < 0.05) were posthemorrhagic hydrocephalus (PHH) (-18.84 ≤ b ≤ -10.05; T1, T2, and T4), bronchopulmonary dysplasia (BPD) (b = -7.41; T2), female gender (b = 8.09; T2), and SNAPPE severity score (b = -0.23; T3). CONCLUSION: Mothers of preterm infants with VLBW exhibited transient improvements in physical well-being during the first year after delivery. The presence of depressive symptoms in mothers and the diagnosis of PHH or BPD were negatively associated with QoL. Social, religious, and economic aspects were also important factors for the QoL of mothers of preterm infants with VLBW.
Assuntos
Recém-Nascido Prematuro/psicologia , Recém-Nascido de muito Baixo Peso/psicologia , Mães/psicologia , Qualidade de Vida/psicologia , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Masculino , Adulto JovemRESUMO
Diabetics have an increased risk of cardiovascular disease (CVD). The objective of this work was to evaluate the cardiovascular risk factors in infant-juvenile type 1 diabetics and their association with the degree of glycemic control. A total of 52 patients, aged 5-15 years, were studied and compared with 37 control subjects. The degree of glycemic control, lipid profile, plasma fibrinogen, microalbuminuria and blood pressure were investigated. The patients were grouped in diabetics with good glycemic control [DGGC, glycosilated hemoglobin (HbA1c) < 8%] and poor glycemic control [DPGC, HA1c > or = 8%]. Diabetic patients presented incremented values of total cholesterol (4.1 +/- 0.9 vs. 3.1 +/- 0.7 mmol/l, p = 0.0008), LDL-cholesterol (2.4 +/- 0.9 vs. 1.7 +/- 0.7 mmol/l, p = 0.0001), HDL-cholesterol (1.2 +/- 0.3 vs. 1.0 +/- 0.2 mmol/l, p = 0.0002), with respect to control group. Eighty three per cent of diabetics showed a poor glycemic control. There were not significant differences in lipid profile between DGGC and DPGC, excepting HDL-cholesterol which was higher in DPGC group (p = 0.007). Plasma fibrinogen levels were similar in diabetics and controls, but they were higher in DPGC than in DGGC (265 +/- 46 vs. 229 +/- 22 mg/dl, p = 0.02). Three patients with microalbuminuria and none with hypertension were detected. In these patients the most pronounced risk factors for CVD were dyslipidemia and hyperglycemia, which justify the need for the early detection of these factors as well as strict metabolic control.(AU)
Assuntos
Criança , Adolescente , Pré-Escolar , Feminino , Humanos , Masculino , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Angiopatias Diabéticas/etiologia , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 1/terapia , Angiopatias Diabéticas/sangue , Fibrinogênio/análise , Hiperglicemia/complicações , Fatores de RiscoRESUMO
Diabetics have an increased risk of cardiovascular disease (CVD). The objective of this work was to evaluate the cardiovascular risk factors in infant-juvenile type 1 diabetics and their association with the degree of glycemic control. A total of 52 patients, aged 5-15 years, were studied and compared with 37 control subjects. The degree of glycemic control, lipid profile, plasma fibrinogen, microalbuminuria and blood pressure were investigated. The patients were grouped in diabetics with good glycemic control [DGGC, glycosilated hemoglobin (HbA1c) < 8%] and poor glycemic control [DPGC, HA1c > or = 8%]. Diabetic patients presented incremented values of total cholesterol (4.1 +/- 0.9 vs. 3.1 +/- 0.7 mmol/l, p = 0.0008), LDL-cholesterol (2.4 +/- 0.9 vs. 1.7 +/- 0.7 mmol/l, p = 0.0001), HDL-cholesterol (1.2 +/- 0.3 vs. 1.0 +/- 0.2 mmol/l, p = 0.0002), with respect to control group. Eighty three per cent of diabetics showed a poor glycemic control. There were not significant differences in lipid profile between DGGC and DPGC, excepting HDL-cholesterol which was higher in DPGC group (p = 0.007). Plasma fibrinogen levels were similar in diabetics and controls, but they were higher in DPGC than in DGGC (265 +/- 46 vs. 229 +/- 22 mg/dl, p = 0.02). Three patients with microalbuminuria and none with hypertension were detected. In these patients the most pronounced risk factors for CVD were dyslipidemia and hyperglycemia, which justify the need for the early detection of these factors as well as strict metabolic control.
Assuntos
Criança , Adolescente , Pré-Escolar , Feminino , Humanos , Masculino , Angiopatias Diabéticas/etiologia , Diabetes Mellitus Tipo 1/sangue , Glicemia/metabolismo , Angiopatias Diabéticas/sangue , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 1/terapia , Fibrinogênio/análise , Hiperglicemia/complicações , Fatores de RiscoAssuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Endotelina-1/sangue , Adulto , Pressão Sanguínea , Índice de Massa Corporal , Colesterol/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Fibrinogênio/análise , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
This study is a critical reflection on attempts to alter the Declaration of Helsinki, a key document of the democratic theses achieved in the latter half of the 20th century and thus a legacy for humanity because of its ethical guidelines for research involving human beings. Therefore, there must be worldwide social control over such a document, and any change in it demands ample debate with international participation to avoid any reversal in its humanitarian thrust. The study analyzes current aspects of research with human subjects in so-called "outlying" or "developing" countries. It also brings a social and political focus to the matter, highlighting that the economic fundamentalism exercised by wealthy countries inevitably leads to an ethical imperialism, exposing communities of poor countries to even greater vulnerability, discrimination, and social exclusion.