Urinary levels of organophosphate pesticides and predictors of exposure in pre-school and school children living in agricultural and urban communities from south Spain.

BACKGROUND: Despite the widespread use of organophosphate (OP) pesticides, information on predictors of children's exposure to such pesticides is scarce. OBJECTIVE: To assess exposure to OP pesticides in children 3-11 year-old living in agricultural communities and urban areas from Andalusia (Southern Spain), and to identify the main determinants of exposure. METHODS: A longitudinal study was conducted in children 3-11-year-old children living in agricultural communities and urban areas from the provinces of Almeria, Granada and Huelva (Andalusia, Spain) between 2010 and 2011. Urinary levels of six dialkylphosphate (DAP) metabolites were measured by UHPLC-QqQ-MS/MS at the periods of low and high pesticide use in the agriculture (LPU and HPU, respectively). Information on sociodemographic characteristics, parental occupation, residential history, lifestyle and diet, among other relevant factors, was obtained from questionnaires administered to the mothers. RESULTS: A total of 559 and 597 children participated in LPU and HPU periods, respectively. The proportion of urine samples below LOD was 67.4% for ΣDMs (sum of dimethyl metabolites), 77% for ΣDEs (sum of diethyl metabolites) and 58.5% for ΣDAPs (sum of total dialkylphosphate metabolites) in LPU period, and 50.4% for ΣDMs, 65.3% for ΣDEs and 43.9% for ΣDAPs in HPU period. Significantly greater urinary ΣDAP, ΣDM and ΣDE levels were observed in HPU relative to LPU period. Maternal schooling years, proximity of the house to crops or greenhouses, use of insecticides at home, spraying the garden with pesticides, storage of pesticides at home, house cleaning frequency, as well as child's frequency of bath/shower, were found to be the major predictors of urinary levels of ΣDAP. Likewise, not washing fruit and vegetables before consumption and banana consumption were also identified as determinants of the exposure levels. CONCLUSIONS: Urinary levels of metabolites of OP pesticides found in this study were relatively lower compared to similar studies. DAP levels were significantly increased in HPU period. Maternal schooling years and variables related to residential environment and home exposures were identified as the most relevant determinants of DAP metabolites. Regarding diet, banana consumption and not washing fruit before consumption were also identified as determinants of the exposure levels. This study contributes to improve our knowledge on the main sources and determinants of children exposure to OPS, and given that children are more vulnerable than adults this information is essential to reduce children exposure and protect their health.

Comparative Population Plasma and Tissue Pharmacokinetics of Micafungin in Critically Ill Patients with Severe Burn Injuries and Patients with Complicated Intra-Abdominal Infection.

Severely burned patients have altered drug pharmacokinetics (PKs), but it is unclear how different they are from those in other critically ill patient groups. The aim of the present study was to compare the population pharmacokinetics of micafungin in the plasma and burn eschar of severely burned patients with those of micafungin in the plasma and peritoneal fluid of postsurgical critically ill patients with intra-abdominal infection. Fifteen burn patients were compared with 10 patients with intra-abdominal infection; all patients were treated with 100 to 150 mg/day of micafungin. Micafungin concentrations in serial blood, peritoneal fluid, and burn tissue samples were determined and were subjected to a population pharmacokinetic analysis. The probability of target attainment was calculated using area under the concentration-time curve from 0 to 24 h/MIC cutoffs of 285 for Candida parapsilosis and 3,000 for non-parapsilosis Candida spp. by Monte Carlo simulations. Twenty-five patients (18 males; median age, 50 years; age range, 38 to 67 years; median total body surface area burned, 50%; range of total body surface area burned, 35 to 65%) were included. A three-compartment model described the data, and only the rate constant for the drug distribution from the tissue fluid to the central compartment was statistically significantly different between the burn and intra-abdominal infection patients (0.47 ± 0.47 versus 0.15 ± 0.06 h(-1), respectively; P < 0.05). Most patients would achieve plasma PK/pharmacodynamic (PD) targets of 90% for non-parapsilosis Candida spp. and C. parapsilosis with MICs of 0.008 and 0.064 mg/liter, respectively, for doses of 100 mg daily and 150 mg daily. The PKs of micafungin were not significantly different between burn patients and intra-abdominal infection patients. After the first dose, micafungin at 100 mg/day achieved the PK/PD targets in plasma for MIC values of ≤0.008 mg/liter and ≤0.064 mg/liter for non-parapsilosis Candida spp. and Candida parapsilosis species, respectively.

First resuscitation of critical burn patients: progresses and problems.

Currently, the aim of the resuscitation of burn patients is to maintain end-organ perfusion with fluid intake as minimal as possible. To avoid excess intake, we can improve the estimation using computer methods. Parkland and Brooke are the commonly used formulas, and recently, a new, an easy formula is been used, i.e. the 'Rule of TEN'. Fluid resuscitation should be titrated to maintain the urine output of approximately 30-35 mL/h for an average-sized adult. The most commonly used fluids are crystalloid, but the phenomenon of creep flow has renewed interest in albumin. In severely burn patients, monitoring with transpulmonary thermodilution together with lactate, ScvO2 and intraabdominal pressures is a good option. Nurse-driven protocols or computer-based resuscitation algorithms reduce the dependence on clinical decision making and decrease fluid resuscitation intake. High-dose vitamin C, propranolol, the avoidance of excessive use of morphine and mechanical ventilation are other useful resources.

Acute kidney injury in critically burned patients resuscitated with a protocol that includes low doses of Hydroxyethyl Starch.

Acute kidney injury (AKI) is an important complication in burn patients. Recently, it has been recommended that hydroxyethyl starch (HES) be avoided in burn patients because it increases the incidence of AKI. Our purpose was to study incidence of AKI in critically ill burn patients resuscitated with Ringer's solution and supplements of HES. We conducted an observational study of 165 patients admitted to the critical care burn unit (with 30 ± 15% TBSA burned). The main outcome measures were incidence of AKI, contributions of colloids and crystalloids, various severity scores, comorbidities, complications and mortality. According to the RIFLE criteria, 10 (6.1%) patients presented with Risk, 11 (6.7%) presented with Injury and 11 (6.7%) presented with Failure. According to the AKIN criteria, 9.7% presented stage I, 3% stage II and 10.3% stage III. Replacement therapy (RRT) was performed in 15 patients (9.1%), but in 6 of them RRT was employed in the final stages of multi-organ failure. The incidence of AKI in severe burn patients is high according to the RIFLE or AKIN criteria and these patients experience more complications and higher mortality. Our study suggests that the use of HES in low doses in the burn resuscitation phase does not cause more AKI than resuscitation without HES, but further evaluation is required. Further studies should be conducted.

La souffrance rénale aiguë (SRA) est une complication sévère des patients brûlés. Il a récemment été recommandé d'éviter les HydroxyEthylAmidons (HEA) chez les patients brûlés en raison de l'augmentation de l'incidence des SRA. Le but de ce travail est d'évaluer l'incidence de la SRA chez des patients réanimés avec du Ringer Lactate et des HEA. Il s'agit d'une étude observationnelle conduite auprès de 165 patients admis en réanimation pour brûlés (surface 30 +/-15%). Les principaux paramètre recueillis étaient la SRA, les cristalloïdes et colloïdes utilisés, les scores de gravité, les comorbidités, les complications et la mortalité. Selon la classification de Rifle, 10 (6,1%) patients étaient dans le groupe à risque, 11 (6,7%) avaient une souffrance rénale et 11 (6,7%) une insuffisance rénale. Selon les critères AKIN, 9,7% des patients étaient au stade 1, 3% au stade 2 et 10,3% au stade 3. Une épuration extra-rénale a été nécessaire à 15 (9,1%) patients, 6 d'entre eux étant à un stade avancé de défaillance multiviscérale. Basée sur les scores Rifle comme AKIN, l'incidence de souffrance rénale est élevée chez les brûlés et ceux qui en souffrent ont une morbidité et une mortalité plus élevées. Toutefois, notre étude laisse à penser que les patients ayant reçu des HEA n'ont pas plus de souffrance rénale que ceux n'en ayant pas reçu, des études plus poussées restant nécessaires.

Optimal excitation and emission wavelengths to analyze amino acids and optimize neurotransmitters quantification using precolumn OPA-derivatization by HPLC.

We describe an analytical methodology to obtain high sensitivity and better resolution through the study of fluorometric excitation (λex) and emission (λem) spectrum wavelengths of OPA-amino acids. The spectrum emission study revealed a maximum signal peak at 450 nm for aspartate and glutamine. For glycine, taurine, and GABA, the maximum signal peak was at 448 and for glutamate at 452 nm. The remaining amino acids analyzed showed a maximum emission around 450 nm. The best signal obtained within the spectrum excitation experiments was using 229- to 450-nm λex-λem. The drawbacks observed at these wavelengths were a baseline drift and negative peaks occurrence. Thus, the excitation wavelength of 240 nm was chosen (240- to 450-nm λex-λem) as a compromise between a very good signal response and a baseline stability to resolve the 18 amino acids studied. Furthermore, this protocol was properly validated. On the other hand, the elution gradient program used for neuroactive amino acids (aspartate, glutamate, glycine, taurine and GABA) showed separation to the baseline, in a 15-min run in all of them. Other amino acids, up to 18, also exhibited a very good separation in a 25-min run. In conclusion, we propose the use of 240- to 450-nm λex-λem wavelengths, in OPA-amino acids analysis, as the most suitable protocol to obtain the best signal response, maintaining an optimum chromatographic resolution.