Teratoxénese

Titulación: Licenciatura en Farmacia -- Materia: ToxicoloxíaA presente unidade didáctica forma parte da lección 3, que trata de mecanismos de toxicidade. Xunto á mutaxénese e a carcinoxénese constitúe un mecanismo especial de toxicidade. Tamén xunto aos anteriores caracterízase polo longo período de latencia que pasa, moitas veces, entre a exposición a un tóxico e a manifestación dos efectos. Comparte, ademais con eles a característica de que, ás veces, un mecanismo xenotóxico está na base fisiopatolóxica do proceso. A teratoxénese é un problema que preocupou o home desde tempos remotos, pero ata mediados do século pasado pensábase que non tiña relación con exposicións ambientais, xa que se consideraba que a placenta actuaba como unha barreira de protección do feto. Foi a raíz do caso da talidomida, un fármaco empregado para tratar as náuseas do primeiro trimestre do embarazo, alá polos anos 60, cando xurdiu a alarma sobre os posibles riscos da exposición intraútero ás substancias químicas. A partir dese punto estableceuse a necesidade de avaliar o risco dos novos fármacos para o seu uso durante o embarazo, para evitar que o caso da talidomida se repetise. Tamén a partir de entón se estableceron uns principios básicos de teratoxénese, que serven para comprender cando unha determinada exposición pode supor un risco para o embarazo ou non. Debido á frecuencia con que as mulleres embarazadas están expostas a tratamentos farmacolóxicos, é preciso que os farmacéuticos teñan unhas nocións básicas e claras sobre estes principios básicos e sobre os mecanismos de teratoxénese. Deste xeito poderán facer unha interpretación crítica do risco que pode supor o uso dun determinado fármaco nunha determinada etapa da xestación. Tamén é importante que coñezan algún sistema de clasificación de fármacos en base ao seu potencial teratoxénico, e que se acostumen ao seu manexo e interpretación.Universidade de Santiago de Compostela. Servizo de Normalización Lingüístic

Intoxicacións por gases asfixiantes

Titulación: Grao en Medicina -- Materia: Medicina LegalEsta unidade didáctica denominada «Intoxicacións por Gases Asfixiantes» forma parte da materia «Medicina Legal» que se imparte no segundo semestre do 5o curso do Grao en Medicina. Esta materia aborda, entre outros contidos, a aplicación dos coñecementos médicos para a resolución de cuestións xudiciais, e estrutúrase en diferentes módulos temáticos. A materia está adscrita ás Areas de Medicina Legal e de Toxicoloxía. A maior parte dos módulos son impartidos pola primeira, mentres que o correspondente á Toxicoloxía Forense é impartido pola área de Toxicoloxía.Universidade de Santiago de Compostela. Servizo de Normalización Lingüístic

Hiperlaxitud articular y displasia de cadera en pacientes pediátricos atendidos en el servicios de medicina física y rehabilitación. Hospital Carlos Alberto Seguín Escobedo, 2019

La finalidad de este estudio será relacionar la hiperlaxitud articular y la displasia de cadera en pacientes pediátricos atendidos en el Servicio de Medicina Física y Rehabilitación. Hospital Carlos Alberto Seguín Escobedo, 2019, para lo cual se realizará un estudio no experimental, de enfoque cuantitativo, de diseño observacional, correlacional y retrospectivo, cuya población de estudio estará conformada por 4000 pacientes pediátricos que acuden a consulta externa del servicio por causas diversas, de los cuales según estadísticas hospitalarias 40%-50% tendría hiperlaxitud articular, y la muestra la conformarán 352 pacientes pediátricos. Como criterios de exclusión se considerarán aquellos pacientes referidos a otras instituciones de salud, y pacientes con información incompleta e ilegible en sus historias clínicas. La técnica de recolección a emplear será el análisis documental, mientras que el instrumento será la ficha de recolección de datos. Finalmente, el análisis inferencial para determinar a relación entre la hiperlaxitud articular y la displasia de cadera en pacientes pediátricos se realizará la prueba Chi cuadrado, considerando un nivel de significancia del 5%.Proyecto de Investigació

Determination of parathion in biological fluids by means of direct Solid Phase Microextraction.

A new and simple procedure for the determination of parathion in human whole blood and urine using direct immersion (DI) solid-phase microextraction (SPME) and gas chromatography/mass spectrometry (GC/MS) is presented. This technique was developed using only 100 ìL of sample, and ethion was used as internal standard (IS). A 65-ìm Carbowax/divinylbenzene (CW/DVB) SPME fibre was selected for sampling, and the main parameters affecting the SPME process such as extraction temperature, adsorption and desorption time, salt addition, agitation and pH effect were optimized to enhance the sensitivity of the method. This optimization was also performed to allow the qualitative determination of parathion’s main metabolite, paraoxon, in blood. The limits of detection and quantitation for parathion were 3 and 10 ng/mL for urine and 25 and 50 ng/mL for blood, respectively. For paraoxon, the limit of detection was 50 ng/mL in blood. The method showed linearity between the LOQ and 50 ìg/mL for both matrices, with correlation coefficients ranging from 0.9954 to 0.9999. Precision and accuracy were in conformity with the criteria normally accepted in bioanalytical method validation. The mean absolute recoveries were 35.1% for urine and 6.7% for blood. Other parameters such as dilution of sample and stability were also validated. Its simplicity and the fact that only 100 ìL of sample is required to accomplish the analysis make this method useful in forensic toxicology laboratories to determine this compound in intoxications, and it can be considered an alternative to other methods normally used for the determination of this compound in biological media

Simultaneous determination of 137 drugs of abuse, new psychoactive substances, and novel synthetic opioids in meconium by UHPLC-QTOF

New psychoactive substances (NPS) have been introduced into the market in recent years, with new analytes reported every year. The use of these substances in women can occur at any stage of life, even in the childbearing age. Drug use during pregnancy presents significant risks for the mother and the fetus, so it is important to have tools that allow to detect prenatal exposure to these substances of abuse. Therefore, an analytical method for the determination of 137 NPS and other drugs of abuse in meconium by UHPLC-QTOF was developed and validated for semi-quantitative purpose. Linearity range, limit of detection (LOD), precision, matrix effect, selectivity, and specificity were evaluated. For all analytes, the calibration curves were studied in the ranges between 2, 10, or 50 ng/g and 750 or 1000 ng/g, (depending on the analyte) and the LOD ranged between 0.04 and 2.4 ng/g. The method was applied to 30 meconium specimens from cases in which fentanyl had been administered as epidural anesthesia at the time of delivery or cases in which the maternal hair was positive to other drug of abuse. Four meconium samples tested positive for fentanyl (range concentration = 440–750 ng/g) and two samples tested positive to acetylfentanyl (range concentration = 190–1400 ng/g)A. López-Rabuñal would like to thank the Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, for her predoctoral contract (ED481A-2019/071)S

Determination of antidepressants and benzodiazepines in paired hair and nail samples

Hair and nails are keratinized matrices that can be used in Toxicology as matrices for the long-term detection of substances. Whereas hair is an established matrix with decades of use in this field, nails have been less studied, especially including a comparison to hair samples. Specifically in the case of antidepressant and benzodiazepine drugs, very few publications analyzing these drugs in nail samples exist as of yet. For this reason, in the present study a method for the detection of 12 antidepressant and benzodiazepine drugs in hair and nail samples was developed. Samples were decontaminated with 3 washes of dichloromethane, and 25 or 30 mg of hair and nails, respectively, were pulverized. Then, the samples were incubated with 1.5 mL water:ACN (50:50, v/v) with horizontal agitation for 90 min. The supernatant was evaporated and reconstituted in 200 µL of methanol and 2 mL of 2% FA in water, submitted to solid phase extraction (SPE) using Oasis MCX cartridges and analyzed by LC-MS/MS. The method was satisfactorily validated in nail and hair samples for the following parameters: linearity, LOD (0.005–0.02 ng/mg), LOQ (0.01–0.02 ng/mg), selectivity, carryover, accuracy, imprecision, matrix effect, extraction efficiency, process efficiency and autosampler stability. Matched fingernail, toenail and hair samples were obtained from 21 patients under treatment with any of the studied drugs and analyzed with the developed method. The most frequently detected drugs were venlafaxine (n = 11), trazodone (n = 6), zolpidem (n = 5), alprazolam (n = 5) and nordiazepam (n = 5). Concentrations in hair, fingernails and toenails, respectively, were 44.31 ng/mg, 8.05–43.35 ng/mg and 7.02–22.69 ng/mg for venlafaxine; 5.40–19.08 ng/mg, 0.13–1.00 ng/mg and 0.42–1.04 ng/mg for trazodone; 13.86 ng/mg, 5.19 ng/mg and 9.11 ng/mg for fluoxetine; 7.42 ng/mg, 1.85 ng/mg and 0.03–2.81 ng/mg for sertraline; 0.40–1.42 ng/mg, 0.12 ng/mg and 0.16 ng/mg for zolpidem; and 0.02–0.11 ng/mg, 0.07–1.07 ng/mg and 0.05 ng/mg for alprazolam for the patients under active treatment. Hair concentrations were higher than nail concentrations for most drugs in patients under active treatment, with the exception of diazepam (n = 1; 0.12 ng/mg in hair and 0.41 ng/mg in fingernails). Fingernail concentrations were lower than toenail concentrations in patients under active treatment in most compared cases. Comparison of fingernails and toenails of a patient with antifungal treatment did not show an observable effect in concentrationsM. Cobo and E. Lendoiro thank Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, for their predoctoral contract (ED481A-2019/021) and postdoctoral contract (ED481D-2019/025). The authors also wish to thank the Xunta de Galicia (Galicia, Spain) for the Competitive Reference Groups Help (ED431C 2021/35)S

LC–MS-MS determination of cytostatic drugs on surfaces and in urine to assess occupational exposure

The ever-increased usage of cytostatic drugs leads to high risk of exposure among healthcare workers. Moreover, workers are exposed to multiple compounds throughout their lives, leading to cumulative and chronic exposure. Therefore, multianalyte methods are the most suitable for exposure assessment, which minimizes the risks from handling cytostatic drugs and ensures adequate contamination containment. This study describes the development and full validation of two liquid chromatography–tandem mass spectrometry methods for the detection of gemcitabine, dacarbazine, methotrexate, irinotecan, cyclophosphamide, doxorubicinol, doxorubicin, epirubicin, etoposide, vinorelbine, docetaxel and paclitaxel in working surfaces and urine samples. The urine method is the frst to measure vinorelbine and doxorubicinol. For surfaces, limits of detection (LOD) and limits of quantifcation (LOQ) were 5–100 pg/cm2 , and linearity was achieved up to 500 pg/cm2 . Inaccuracy was between −11.0 and 8.4%. Intra-day, inter-day and total imprecision were <20%, except for etoposide and irinotecan (<22.1%). In urine, LOD and LOQ were 5–250 pg/mL, with a linear range up to 1,000–5,000 pg/mL. Inaccuracy was between −3.8 and 14.9%. Imprecision was <12.4%. Matrix effect was from −58.3 to 1,268.9% and from −66.7 to 1,636% in surface and urine samples, respectively, and extraction effciency from 10.8 to 75% and 47.1 to 130.4%, respectively. All the analytes showed autosampler (6°C/72 h), freezer (–22°C/2 months) and freeze/thaw (three cycles) stability. The feasibility of the methods was demonstrated by analyzing real working surfaces and patients’ urine samples. Contamination withemcitabine, irinotecan, cyclophosphamide, epirubicin and paclitaxel (5–4,641.9 pg/cm2) was found on biological safety cabinets and outpatients’bathrooms. Analysis of urine from patients under chemotherapy identifed the infused drugs at concentrations higher than the upper LOQ. These validated methods will allow a comprehensive evaluation of both environmental and biological contamination in hospital settings and healthcareworkersThe authors would like to thank the participants and staff of the University Clinical Hospital of Santiago de Compostela, and E.L., J.A.L.-A and L.P.-G. would like to thank the Consellería de Cultura, Educacion e Ordenación Universitaria, Xunta de Galicia (Spain), for her postdoctoral contract (ED481D-2019/025) and their predoctoral contracts (ED481A-2017/087 and ED481A-2018/059), respectively. We also thank the Xunta de Galicia (Galicia, Spain) for the Consolidation and Structuring of Competitive Research Units Help (2021-PG054)S

Usefulness of hair analysis and psychological tests for identification of alcohol and drugs of abuse consumption in driving license regranting.

Implementation of the points-based driving license has helped to change driver behavior, and can be linked to to a reduction of traffic accidents and fatalities. In Spain, a driving licence is revoked when all points are lost, and the driver must enroll on a Driver Awareness and Re-education (DARE) course. However, offenders are currently not subjected to any tests that would confirm the absence of alcohol or other substances, despite the fact that 9% of Spanish drivers lose their driving license as a result of driving under influence (DUI). This pilot study aimed to compare the usefulness of psychological tests and hair analysis, as methods for identifying which DARE-course attendees had a longterm history of alcohol or drug abuse. Volunteers were submitted to the AUDIT and DAST-10 tests. Hair samples were also collected and analyzed, checking for ethylglucuronide (EtG) (LOQ 5 pg/mg), and thirty-five licit and illicit drugs (LOQ 5-50 pg/mg) by LC-MS/MS. Sixty-one participants - with a mean age of 37.2 (plus or minus 11.6 years) and mainly men (90.2%) - were recruited. All participants undertook both AUDIT and DAST-10 tests. All hair samples were analyzed for EtG and 17 samples were analyzed for licit and illicit drugs. The mean AUDIT score was 9.6 (SD = 7.5), showing a value 30 pg/mg) in twenty-one cases. All positive cases for methadone and cannabis - and half of the positive cases for opioids and cocaine - presented higher concentrations than SoHT cut-offs for chronic consumption. Higher AUDIT score and higher EtG concentration in hair were statistically associated with declaration of alcohol consumption > 4 times/month and with historical fines for DUI of alcohol. In addition, AUDIT scores and EtG concentration in hair had a moderate but significant Spearman correlation (r = 0.331, p < 0.05). The combination of psychological tests and hair analysis seems to be a promising way to identify individuals with alcohol or drug abuse problems. Moreover, applying these methods as part of the process of re-acquiring driving licences could increase the effectiveness of DARE courses, reduce recidivism and improve road safety

Metodos secuenciales en la espectroscopia de derivadas. Su aplicacion al analisis simultaneo de drogas de abuso y adulterantes

Available from Centro de Informacion y Documentacion Cientifica CINDOC. Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai