PON1 status and homocysteine levels as potential biomarkers for cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death. The mainly risks factors for CVD are diabetes, hypertension and high levels of homocysteine (Hcys), among others. Paraoxonase 1 (PON1) has been proposed as an antiatherogenic target for its ability to hydrolyzing oxi-Low-Density-Lipoproteins (LDL) and Hcys-thiolactone. Thus, the aim of the present study was to evaluate the association of Hcys levels, and the activities and concentration of PON1, as well as vitamin B from the diet with a risk for CVD. METHODS: A case-control study was carry out in patients with cardiovascular diseases (CVD), Arterial hypertension, but not CVD (AH), and in healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, intake of vitamin B, Hcys, serum amyloid A (SAA), PON1 concentration, and PON1 activities (Arylesterase activity (ARE), Lactonase activity (LAC), and CMPA activity (CMPA)) were evaluated. RESULTS: The CVD group had the highest concentration of Hcys and SAA than in the AH and control groups (p < 0.01). ARE, LAC, and CMPA activities and PON1 concentration were lowest in the CVD group. A positive-independent association between Hcys levels and CVD was found (OR = 2.09; 95% CI: 1.69-2.56) and this increase when it was adjusted by age, BMI, ApoA1, vitamin B intake, SAA, and PON1 (OR = 14.41; 95% CI: 1.75-118.71). LAC and CMPA, as well as PON1 concentration, were inversely associated with CVD. CONCLUSION: LAC activity, PON1 concentration, and Hcys levels might be good biomarkers for CVD and their association could be modified by the intake of vitamin B.

Impact of oxidative stress SNPs and dietary antioxidant quality score on prostate cancer.

Purpose: To analyse the relation between antioxidant genotypes and Dietary Antioxidant Quality score (DAQs) effect on prostate cancer (PCa) risk and aggressiveness in a Spanish population.Methods: Men (N = 155 patients and 152 controls) with PSA values >4 ng/ml were enrolled in the project. DAQs were used considering the daily recommended intake for Spanish people (DRI). Genotyping of 5 SNPs rs662 (PON1), rs10432782 (SOD1), rs4880 (SOD2), rs17650792 (GPX1) and rs1001179 (CAT) were included for the analysis.Results: rs17650792 was statistically significant between case and controls subjects. When comparing D´Amico risk, we found that rs662 (CC), rs10432782 (G allele) and rs17650792 (GG) confer a protection. When testing SNP-antioxidant nutrients interactions, we found an intake of vitamin A and rs100179 (T carriers) and selenium and rs17650792 (G carriers) confers a protection of being in low risk classification.Conclusions: We reported by the first time a correlation between rs662 (PON1) and PCa aggressiveness.

Paraoxonase 1 activities and genetic variation in childhood obesity.

Changes in paraoxonase 1 (PON1) activities have been observed in a variety of diseases involving oxidative stress, such as CVD. However, its role in obesity has not been fully established. In the present study, we aimed (1) to genotype sixteen PON1 SNP, (2) to measure serum PON1 activities and (3) to correlate these findings with the incidence of childhood obesity and related traits. We conducted a case-control study of 189 normal-weight and 179 obese prepubertal children, and we measured four different PON1 activities: lactonase; paraoxonase; arylesterase; diazoxonase. Although none of these activities was significantly different between the obese and normal-weight children, lactonase activity was found to be positively correlated with HDL-cholesterol and ApoA1 levels and negatively correlated with myeloperoxidase and fatty acid-binding protein 4 levels. Among the sixteen genotyped PON1 SNP, only the intronic SNP rs854566 exhibited a significant association with obesity (OR 0·61, 95 % CI 0·41, 0·91; P= 0·016). This genetic variant was also associated with increased diazoxonase, lactonase and arylesterase activities and decreased paraoxonase activity. Other genetic variants exhibited different association patterns with serum activities based on their location within the PON1 gene, and SNP that were located within the promoter were strongly associated with lactonase, arylesterase and diazoxonase activities. The functional variant Q192R exhibited the greatest effect on paraoxonase activity (P= 5·88 × 10(-42)). In conclusion, SNP rs854566 was negatively associated with childhood obesity and with increased serum PON1 activities in prepubertal children. We determined that lactonase is a reliable indicator of PON1 activities and should be included in future studies of PON1 function.

Hair testing for cocaine and metabolites by GC/MS: criteria to quantitatively assess cocaine use.

A simple, rapid and sensitive method has been developed and validated for the determination of cocaine and its main metabolites (benzoylecgonine and cocaethylene) in human hair. The method involved solid-phase extraction with an Oasis HLB extraction cartridge and subsequent analysis by GC/MS. The limit of detection was 0.01 ng mg(-1) for cocaine, 0.04 for benzoylecgonine and 0.03 for cocaethylene. The method validation included linearity (with a correlation coefficient >0.99 over the range 0.2-50 ng mg(-1) ), intra- and inter-day precision (always lower than 12%) and accuracy (mean relative error always below 17%) to meet the bioanalytical acceptance criteria. The procedure was further applied to 40 hair samples from self-reported cocaine users arrested by the police who provided a positive urine-analysis for cocaine, and was demonstrated to be suitable for its application in forensic toxicology. New approaches were raised to detect false-negative results that allow a better interpretation of hair testing results.

Validation of a method to quantify chromium, cadmium, manganese, nickel and lead in human whole blood, urine, saliva and hair samples by electrothermal atomic absorption spectrometry.

For biological monitoring of heavy metal exposure in occupational toxicology, usually whole blood and urine samples are the most widely used and accepted matrix to assess internal xenobiotic exposure. Hair samples and saliva are also of interest in occupational and environmental health surveys but procedures for the determination of metals in saliva and hair are very scarce and to our knowledge there is no validation of a method to quantify Cr, Cd, Mn, Ni and Pb in four different human biological materials (whole blood, urine, saliva and axilary hair) by electrothermal atomization atomic absorption spectrometry (ETAAS). In the present study, quantification methods for the determination of Cr, Cd, Mn, Ni and Pb in whole blood, urine, saliva and axilary hair were validated according to the EU common standards. Pyrolisis and atomization temperatures have been determined. The main parameters evaluated were: detection and quantification limits, linearity range, repeatability, reproducibility, recovery and uncertainty. Accuracy of the methods was tested with the whole blood, urine and hair certified reference materials and recoveries of the spiked samples were acceptable ranged from 96.3 to 107.8%.

[Incidence of the consumption of toxic substances in severe trauma patients]. / Incidencia del consumo de tóxicos en pacientes con traumatismos graves.

OBJECTIVE: To determine the incidence of the detection of abuse drugs in severe trauma patients DESIGN: Prospective observational study conducted from July 2004 to January 2006. SETTING: Neurotrauma intensive care unit of a reference tertiary university hospital. PATIENTS: Trauma patients who require admission to ICU during the study period. INTERVENTIONS: Determination of alcohol in blood and of toxics (cocaine, cannabis, amphetamines and other substances) in urine. RESULTS: Toxicological analysis was performed in 196 of the 288 severe trauma patients admitted during the study period. The most frequently detected cause of the trauma was traffic accident (69%). The most frequently detected substance was cannabis (22.4%), followed by alcohol (17.3%) and cocaine (12.8%). Cannabis was detected in 26.1% of under-45-yr-old patients versus 9.3% of older patients (p < 0.05), and cocaine in 16.3% vs. 0% in over-45-yr-olds (p < 0.001). Some substance of abuse was detected in 45% of under-45-yr-olds versus 23% of older patients (p < 0.05). CONCLUSION: The high proportion of positive results to toxic substances in severely traumatized patients suggests that the epidemiological environment for these patients is of great concern. These data may be of interest for the design of future prevention campaign.

Incidencia del consumo de tóxicos en pacientes con traumatismos graves / Incidence of the consumption of toxic substances in severe trauma patients

Objetivo. Determinar la incidencia de detecciónde drogas de abuso en pacientes con traumatismograve.Diseño. Estudio observacional prospectivo,rea lizado entre julio de 2004 y enero de 2006.Ámbito. Unidad de Cuidados Intensivos (UCI)neurotraumatológica de un hospital de tercer nivel.Pacientes. Pacientes con traumatismos queprecisaron el ingreso en la UCI durante el períodode estudio.Intervenciones. Análisis de alcoholemia y de tóxicos(cocaína, cannabis, anfetaminas y otras) enorina.Resultados. Se obtuvo una muestra para análisisde tóxicos en 196 pacientes de los 288 ingresadospor traumatismo grave. La causa más frecuentedel traumatismo fue el accidente detráfico, con un 69%. El tóxico más frecuentementeencontrado fue el cannabis (22,4%), seguidodel alcohol (17,3%) y la cocaína (12,8%). En menoresde 45 años, el cannabis fue detectado en el26,1% frente al 9,3% en mayores de 45 años (p < 0,05)y la cocaína en un 16,3% frente al 0% (p < 0,001).En menores de 45 años fue detectada la presenciade algún tóxico en el 45% frente al 23% en mayoresde 45 años (p < 0,05).Conclusión. La alta proporción de resultadospositivos a tóxicos en pacientes con traumatismosgraves sugiere que el ambiente epidemiológicoen que se mueven estos pacientes es muy preocupante. Estos datos deberían tener importancia para diseñar futuras campañas de prevención

Objective. To determine the incidence of thedetection of abuse drugs in severe trauma patientsDesign. Prospective observational study conductedfrom July 2004 to January 2006.Setting. Neurotrauma intensive care unit of areference tertiary university hospital.Patients. Trauma patients who require admissionto ICU during the study period.Interventions. Determination of alcohol in bloodand of toxics (cocaine, cannabis, amphetaminesand other substances) in urine.Results. Toxicological analysis was performedin 196 of the 288 severe trauma patients admittedduring the study period. The most frequently detectedcause of the trauma was traffic accident(69%). The most frequently detected substancewas cannabis (22.4%), followed by alcohol(17.3%) and cocaine (12.8%). Cannabis was detectedin 26.1% of under-45-yr-old patients versus9.3% of older patients (p < 0.05), and cocainein 16.3% vs. 0% in over-45-yr-olds (p < 0.001).Some substance of abuse was detected in 45% ofunder-45-yr-olds versus 23% of older patients (p< 0.05).Conclusion. The high proportion of positive resultsto toxic substances in severely traumatizedpatients suggests that the epidemiological environmentfor these patients is of great concern These data may be of interest for the design of future prevention campaign