Robust gene signatures from microarray data using genetic algorithms enriched with biological pathway keywords.

Genetic algorithms are widely used in the estimation of expression profiles from microarrays data. However, these techniques are unable to produce stable and robust solutions suitable to use in clinical and biomedical studies. This paper presents a novel two-stage evolutionary strategy for gene feature selection combining the genetic algorithm with biological information extracted from the KEGG database. A comparative study is carried out over public data from three different types of cancer (leukemia, lung cancer and prostate cancer). Even though the analyses only use features having KEGG information, the results demonstrate that this two-stage evolutionary strategy increased the consistency, robustness and accuracy of a blind discrimination among relapsed and healthy individuals. Therefore, this approach could facilitate the definition of gene signatures for the clinical prognosis and diagnostic of cancer diseases in a near future. Additionally, it could also be used for biological knowledge discovery about the studied disease.

Effects of metabolic control on vitamin E nutritional status in children with type 1 diabetes mellitus.

OBJECTIVE: To evaluate the effects of the metabolic control of the insulin-dependent diabetes mellitus (IDDM) on the nutritional status of vitamin E. METHODS: A total of 47 children with IDDM and a mean age of 11.91+/-1.60 (mean+/-SD) years were studied, matched for age and sex with 16 healthy children (11.75+/-1.83 years). Following the American and British Associations for IDDM, we used a classification of "good", "moderate" or "poor" control of the illness: (a) good control [glycosilated haemoglobin (HbAlc) < or =7%]; (b) moderate control (7%< HbAlc < or =8%); and (c) poor control (HbAlc>8%). Serum concentrations of total cholesterol (CHOL), triglycerides (TG), high-density lipoproteins-cholesterol (HDLc), very low- and low-density lipoproteins cholesterol (VLDLc and LDLc), plasma and erythrocyte vitamin E (Vit Ep and Vit Ee) and plasma vitamin A (Vit Ap) were measured in all children. RESULTS: The children with "poor" metabolic control of the illness presented significantly higher plasma concentrations of CHOL, LDLc, VLDLc, LDLc/HDLc, (VLDL+LDL)c/HDLc, TG and Vit Ep; higher indices Vit Ep/Vit Ee and Vit Ep/Vit Ap relative to those with a "good" control of the illness. Direct-linear correlations were found between Vit Ep and the percentage of HbAlc and with the markers of atherogenic risk in the IDDM children. CONCLUSION: There is a significant rise in Vit Ep concentrations as metabolic control of the illness worsens, whereas Vit Ee remained unchanged. These results suggest that vitamin E maintains its nutritional status despite a poor control of the IDDM during childhood.

Vitamin A, retinol binding protein and lipids in type 1 diabetes mellitus.

OBJECTIVE: A case-control study was conducted to evaluate the effects of type 1 diabetes mellitus (IDDM) on plasma levels of vitamin A (retinol) and serum levels of retinol-binding protein (RBP) and their relationship with the atherogenic indicators. SUBJECTS: A total of 47 randomised IDDM children were recruited from those treated at the Endocrinology Unit of the University Hospital of Granada (Spain). They were matched for age and sex with 16 healthy children. METHODS: The following parameters were measured in all patients: serum concentrations of total cholesterol, triglycerides, high (HDL, spectrophotometry), very low (VLDL) and low (LDL) density lipoprotein cholesterol (Friedewald's formula); serum levels of RBP (kinetic nephelometry); plasma vitamin A and glycosilated haemoglobin (HbA1c; high performance chromatography). RESULTS: Higher RBP concentrations in IDDM children (P=0.05), lower retinol levels (P=0.05) and lower vitamin A/cholesterol ratio (P=0.02) than in the control group were found; no differences in the atherogenic indicators were observed. There was a correlation between RBP and vitamin A (P=0.0001). Relationships between retinol, RBP and atherogenic indicators were demonstrated in the IDDM group (A-LDLc/HDLc (P=0.01); A-(VLDL+LDL)c/HDLc (P=0.007); RBP-LDLc/HDLc (P=0.05); RBP-(VLDL+LDL)c/HDLc (P=0.02)), and an inverse relationship was found between the vitamin A/TG ratio and HbA1c (P=0.004). The children with HbA1c>8% showed increased atherogenic indicators and lower vitamin A/CHOL and vitamin A/TG ratios than those with good control of the illness. CONCLUSIONS: The IDDM children with poor metabolic control face a higher atherogenic risk and vitamin A 'relative deficiency' risk than those with good metabolic control of their illness. Relationships between retinol and RBP with atherogenic indicators were found. The results suggest that vitamin A therapeutic supplements in IDDM children may reduce or prevent atherogenic risk.

Role of intrapartum hypoxia in carnitine nutritional status during the early neonatal period.

We analyze markers of carnitine insufficiency and deficiency, lysine (LYS) and methionine (MET), in 39 neonates with intrapartum hypoxia (selection criteria: umbilical artery pH <7.20, lactate >1.8 mmol/l and PaO2 <25 mm Hg), and in 35 healthy newborn infants (control group) in the early neonatal period (1-7 days of life). Free (FC), total (TC) carnitine and acylcarnitines (AC=short-chain+long-chain acylcarnitines) were measured using a radioisotopic micromethod; LYS and MET were determined by high-pressure liquid chromatography. AC and TC plasma concentrations and AC/FC ratio were higher while FC/TC ratio was lower in the hypoxic neonates than in the control group. Hypoxic newborn infants (59%) presented "carnitine deficiency" (FC/TC <0.7) and 60% of them "carnitine insufficiency" (AC/FC ratio >0.4) vs. 31% and 28%, respectively, for the neonates of the control group (p<0.05). In the healthy neonates group, MET correlated with FC/TC and the AC/FC ratio. FC, TC, AC, AC/FC and umbilical artery pH (pHua) were inversely correlated. FC/TC and MET correlated with pHua. We conclude that: (1) an important percentage of newborn infants with intrapartum hypoxia suffer carnitine deficiency and carnitine insufficiency in the early neonatal period, related to MET plasma levels; (2) the carnitine deficiency or insufficiency in the neonate is determined by the degree of intrapartum acidosis.