Correspondence between the CYP2C19 and CYP3A4 genotypes with the inferred metabolizer phenotype by omeprazole administration in Mexican healthy children.

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.

Factors associated with the quality of life of mothers of preterm infants with very low birth weight: a 3-year follow-up study.

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.

Characterization of a gene in the car cluster of Fusarium fujikuroi that codes for a protein of the carotenoid oxygenase family.

The ascomycete Fusarium fujikuroi produces carotenoids by means of the enzymes encoded by three car genes. The enzymes encoded by carRA and carB are responsible of the synthesis of beta-carotene and torulene, respectively, while the product encoded by carT cleaves torulene to produce the acidic xanthophyll neurosporaxanthin. carRA and carB are found in a cluster with a third gene, carO, which codes for an opsin-like protein. However, no information is available on the sequence or chromosomal location of carT, which has been identified only by mutant analysis. Transcription of the three clustered genes is stimulated by light and by mutations in a regulatory gene, leading to overproduction of carotenoids. We have now identified a fourth gene in the car cluster, called carX, which codes for a protein similar to known carotenoid-cleaving oxygenases. carX is transcribed divergently from carRA, and exhibits the same transcriptional pattern as carRA, carB and carO. Targeted deletion of carX resulted in a phenotype characterized by a significant increase in the overall carotenoid content. In the dark, the carX mutants accumulate at least five times more carotenoids than the wild type, and exhibit partial derepression of carRA and carB transcription. The mutants also show more intense pigmentation in the light, but the increase in the carotenoid content relative to the wild type is less than twofold. Under these conditions, the mutants also show a relative increase in the amounts of phytoene and cyclic carotenoids formed, suggesting that CarRA activity is enhanced.

Factores de riesgo cardiovascular en niños con diabetes tipo 1 y su relación con el control de la glucemia / Cardiovascular risk factors in children with type 1 diabetes and their relationship with the glycemic control

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)

Factores de riesgo cardiovascular en niños con diabetes tipo 1 y su relación con el control de la glucemia / Cardiovascular risk factors in children with type 1 diabetes and their relationship with the glycemic control

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.

A carotenoid biosynthesis gene cluster in Fusarium fujikuroi: the genes carB and carRA.

Phytoene synthase, phytoene dehydrogenase and carotene cyclase are three of the four enzyme activities needed to produce the acidic carotenoid neurosporaxanthin from the precursor geranylgeranyl pyrophosphate. In the filamentous fungus Fusarium fujikuroi, these three enzyme activities are encoded by two closely linked genes, carRA and carB, oriented in the same direction in the genome. The two genes are separated by 548 bp and code for two polypeptides of 612 and 541 amino acids, respectively, which are highly similar to the homologous proteins from other filamentous fungi. The ORF of carRA contains a 96-bp insertion that is absent in the other fungal homologues. The 32 additional residues are located in one of the two repeated domains responsible for the cyclase activity in the homologous fungal proteins. We have determined the function of carRA by gene disruption. The resulting mutants were albino and had lost the ability to produce phytoene, as expected from the simultaneous loss of phytoene synthase and carotene cyclase. In the same experiments, we also found transformants in which carB had been deleted. These mutants accumulate phytoene, confirming the function of the gene previously shown by gene-targeted mutagenesis. Expression of carRA and carB is strongly induced by light. Loss of carB or disruption of the carRA ORF led to enhanced expression of the carRA gene, suggesting the existence of a feedback regulatory mechanism.

[Changes in the Declaration of Helsinki: economic fundamentalism, ethical imperialism and social control]. / Mudanças na Declaração de Helsinki: fundamentalismo econômico, imperialismo ético e controle social.

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.

[Lumbar puncture in a pediatric emergency department: something more than a diagnostic technic]. / Punción lumbar en Urgencias de Pediatría: algo más que una técnica diagnóstica.

OBJECTIVE: The aim of this study was to know the incidence of serious bacterial infections (SBI) in children without sepsis or intracranial infection in which spinal puncture (LP) was performed in an Emergency Department. PATIENTS AND METHODS: A retrospective study of all 471 previously healthy children between 1 month and 14 years of age in which a lumbar puncture was performed between July 1995 and March 1997 in the Emergency Department of our hospital was performed. RESULTS: Two hundred and three children (43%) had sepsis, meningitis or encephalitis (aseptic meningitis 149, 31.6%; sepsis-bacterial meningitis 26, 5.5%; nonspecific meningitis 26, 5.5%; encephalitis 2, 0.4%) and 14 (5.2%) had pneumonia. Of the other 254 children, 36 (14.1%) had a SBI: 19 urinary tract infections (E. coli), 11 bacteremia (Streptococcus pneumoniae 8, Salmonella enteritidis 1, Proteus mirabilis 1, E. coli 1, the latter two also having a positive urine culture) and 6 bacterial gastroenteritis (salmonella 5, Campylobacter jejuni 1). The incidence of SBI was significantly higher in the group of children younger than 5 years old (32/175, 18.2%) than in the older group (4/79, 5.0%, p = 0.009). Two patients died (one with pneumococcal meningitis and one with meningococcal sepsis). CONCLUSIONS: Children with fever and a normal result in the LP must be carefully examined and, especially in younger patients, urine, blood and stool (if stool abnormalities) cultures should be collected. These children must be closely observed in the hospital or at home and must be re-evaluated by their pediatrician in the following 24 hours.