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Conducting biomedical research is essential in both the clinical and research areas;. It entails a series of dangers for people involved in these activities. These risks, could be biological, chemical or radiological. These risks can be mitigated or controlled with appropriate protocols and recommendations. This guide shows in a simple way, the main measures and considerations that a researcher who carries out a protocol must know and apply, in order to make a correct assessment of the risk that the activities involved in the protocol. Thus, is essential to implement measures to ensure health and safety of involved people, whether they directly participate or not in the protocol. [ABSTRACT FROM AUTHOR]

Introduction: The CYP450 complex participates in the metabolism of ifosfamide, an antineoplastic drug used to treat solid tumors. CYP450 genes contain several single nucleotide polymorphisms (SNPs) that confer different activity towards the enzyme. The aim of our study was to analyze gene frequencies of allelic variants and their association with ifosfamide blood levels and patient prognosis.Material and Methods: 148 DNA samples from children were analyzed. Genotyping was performed by real-time PCR with TaqMan probes and ifosfamide levels were determined in dried blood drop by UPLCMS/MS.Results: Ifosfamide levels increased according to the genotype, and patients with the variant rs1799853 in CYP2C9 genotype CC had lower levels of ifosfamide (median = 1.8 μmol/l, Q25 0.9-Q75 4.6) compared with patients with genotype TT + CT (median = 2.8 μmol/l, Q25 1.9-Q75 5.1), p < 0.001. In the case of the rs2740574 variant in the CYP3A4 gene, patients with normal genotype (TT) presented median = 1.4 μmol/l, (Q25 0.7-Q75 2.7), while patients with the CC + TC genotype had higher levels of ifosfamide (median = 2.0 μmol/l, Q25 1.0-Q75 4.3), p = 0.024. In addition, patients with CC + CT genotype of this variant had a higher risk of non-response to treatment compared to patients with TT genotype (RR = 1.3, 95% CI: 1.07-1.59, p = 0.03).Conclusions: Polymorphisms in CYP2C9 and CYP3A4 genes are associated with high levels of ifosfamide. In addition, the polymorphism rs2740574 in CYP3A4 was associated with a worse therapeutic response. [ABSTRACT FROM AUTHOR]

Context: Ifosfamide (IFA) is an effective antineoplastic for solid tumours in children, although it is associated with high levels of systemic toxicity and causes death in some cases. Objective: The aim of this study was to determine whether the presence of certain allelic variants of genes CYP2B6, CYP2C9, CYP3A4 and CYP3A5 increases the risk of toxicity in children with solid tumours treated with ifosfamide. Materials and methods: A total of 131 DNA samples were genotyped by real-time polymerase chain reaction (RT-PCR) using TaqMan probes. Toxicity was assessed using WHO criteria, and survival analysis was performed using Kaplan–Meier curves. Results: The rs3745274 allelic variant in CYP2B6 was associated with haematological toxicity, affecting neutrophils; CYP3A4 variant rs2740574 was also associated with toxicity, affecting both leukocytes and neutrophils. Additionally, the CYP3A5 gene variant rs776746 was found to affect haemoglobin. Conclusions: Our results show that allelic variants rs3745274 (CYP2B6), rs2740574 (CYP34) and rs776746 (CYP3A5) increase the risk for high haematological toxicity. Clinical trial registration: 068/2013 [ABSTRACT FROM AUTHOR]

Copyright of Acta Pediatrica de Mexico is the property of Instituto Nacional de Pediatria (INP) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Pediatrica de Mexico is the property of Instituto Nacional de Pediatria (INP) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The recent use of antidiabetic drugs such as metformin and glyburide for the treatment and control of childhood obesity, insulin resistance and type II diabetes mellitus in children and adolescents, has encouraged physicians to determine plasma levels of these drugs for the right dose adjustment. Objective: To implement and validate a UPLC-UV method to quantify metformin and glyburide in blood samples. Materials and methods: Only a 0.1 mL-volume blood sample was used. Both drugs are removed by precipitation with methanol. Quantitation was carried out with mobile phase of 4.6 mM potassium phosphate monobasic (KH2PO4) 0.1 M pH = 6.5, sodium dodecyl sulphate (SDS) and acetonitrile (63:7:30), at 0.8 mL/min through a VARIAN Pursuit® C8 150 x 3.9 mm column at 40°C, 236 nm. Results: The method allows the measurement of 20 to 600 nanograms of metformin and from 100 to 2000 nanograms of glyburide per milliliter of blood. Both drugs are physicochemically stable in blood samples for up to 30 days at 4°C. Conclusion: Our method allows quantification of metformin and glyburide in paediatric blood samples, to support the clinicians to monitor treatment compliance, bioavailability and pharmacokinetic profiles. [ABSTRACT FROM AUTHOR]

Pharmacological management of insulin resistance and dyslipidaemias in children and adolescents is required to prevent the development of metabolic syndrome (MS) and type II diabetes mellitus (DM2). Material and method: we developed extemporaneous formulations from 500 mg-tablets from three generic brands, commercially available in Mexican drugstores: Medimart™, Farmacias del Ahorro™ and Primer NivelTM, dissolved in water sweetened with Splenda, which made them palatable and allowed customised dose adjustment. Solutions were stored at four environmental conditions: 25°C exposed to light, 25°C protected from light, 4°C and 40°C, and their physicochemical stability was assayed. The stability of the drug was determined by ultra performance liquid chromatography and ultraviolet detection (UPLC-UV) and by measuring the pH of the stock solution. The mobile phase consisted of (KH2PO4) 0.1 M, pH = 6.5, 4.6 mM sodium dodecyl sulphate (SDS) and acetonitrile (63:7:30) at 0.8 mL/min, column VARIAN Pursuit C8 150 x 3.9 mm tempered at 40°C, with detection at 236 nm. Results: Metformin from all trademarks was stable at all storage conditions for up to 30 days, retaining more than 90% of the initial amount of active drug, with a pH of 7.4 ± 0.3. Conclusion: Metformin extemporaneous formulations may be developed from either the innovator or generic brands, having the advantage of saving money and conserving the stability of its physicochemical properties. [ABSTRACT FROM AUTHOR]

The aim of the present study was to develop a simple, selective and reliable method to quantify acetaminophen and its toxic metabolite N-acetyl- p-benzoquinoneimine (NAPQI) for pediatric studies using 100 µL plasma samples, by reverse-phase HPLC and UV detection. The assay was performed using a C column and an isocratic elution with water-methanol-formic acid (70:30:0.15; v/v/v) as mobile phase. Linearity of the method was assayed in the range of 1-30 µg/mL for acetaminophen and 10-200 µg/mL for NAPQI, with a correlation coefficient r = 0.999 for both compounds, and inter- and intra-day coefficients of variation of less than 13%. Several commonly co-administered drugs were analyzed for selectivity and no interference with the determinations was observed. The detection and quantification limits for acetaminophen and NAPQI were 0.1 and 1 µg/mL, and 0.1 and 10 µg/mL respectively. The present method can be used to monitor acetaminophen levels using 100 µL plasma samples, which may be helpful when very small samples need to be analyzed, as in pharmacokinetics determination or drug monitoring in plasma in children. This assay is also able to detect the NAPQI for drug monitoring in patients diagnosed with acetaminophen intoxication. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Buprenorphine (BPN) is a widely used analgesic in the pediatric population, although there are few studies on the pharmacokinetics and pharmacodynamics of this drug. Objective: The objective was to characterize the pharmacokinetics of BPN after intravenous administration and analyze the effect of age, gender, weight, height, body mass index (BMI), and drug-drug interactions as covariates. Methods: Ninety-nine children (2-10 years), who underwent orthopedic surgery under regional, general, or combined anesthesia were included. Patients evaluated according to the American Society of Anesthesiologists Physical Status Classification, who received intravenous BPN 2 μg/kg were enrolled. Blood was collected from 1-240 min. Drug plasma concentrations were determined by LC-MS/MS. Population pharmacokinetic parameters were obtained with Monolix 2021R1 software. Pearson's correlation and/or ANOVA were used for statistical analysis. Results: Age was associated with changes in clearance and central compartment volume and the female gender was associated with lower intercompartmental clearance, while BMI modified clearance, central and peripheral compartment volume. Concomitant administration of BPN with fentanyl and dexamethasone produced decreases in clearance. Conclusions: The covariates of sex, age, and BMI are directly related to the increase or decrease in BPN pharmacokinetic parameters. [ABSTRACT FROM AUTHOR]

Levetiracetam (LEV) is an anticonvulsant drug with a unique mechanism of action that is not completely understood. However, its activity profile may involve effects on excitatory and/or inhibitory neurotransmission since the primary target of LEV, synaptic vesicle protein 2A, is ubiquitously expressed in all types of synaptic vesicles. Therefore, the objective of the present study was to explore the effect of LEV (300 mg/kg/day for one week, administered via osmotic mini-pumps) on neurotransmitter release and its probable selective effect on extracellular gamma-amino butyric acid (GABA), glutamate (Glu), aspartate (Asp), glutamine (Gln), taurine (Tau) and glycine (Gly) concentrations (using in vivo microdialysis under basal and high-K + conditions) in the dorsal hippocampus (DH), a region that undergoes major synaptic changes during epilepsy. Epileptic rats developed clear signs of hyperexcitability, i.e., an elevated Glu/GABA ratio in the DH. The LEV concentration in blood after 7 days of treatment was within the therapeutic range. In contrast, LEV was not detected four days after mini-pump removal (washout period). Furthermore, LEV restored the Glu/GABA ratio to approximately the control level and significantly increased the GABA concentration after the initiation of high-K + conditions. Based on these data, LEV treatment restored the lost balance between the excitatory and inhibitory systems under basal conditions. Moreover, LEV showed a selective effect by preferentially increasing vesicular release of GABA, a mechanism by which LEV could reduce epileptic seizures., (Copyright © 2018 Elsevier B.V. All rights reserved.)