Extravasamiento de doxorubicina em punto de mano y tratamiento – Relato de caso

Breast cancer is one of the main causes of mortality in the Brazilian female population and doxorubicin is one of the drugs used to prevent the replication of tumor cells. Our report describes a patient with malignant neoplasm of breast that suffered the extravasation of this drug during the infusion procedure. The evolution of the lesion in the patient’s hand, the treatment and prognosis were evaluated in this caseEl cáncer de mama es una de las principales causas de mortalidad en la población femenina brasileña y la doxorubicina es uno de los medicamentos utilizados para evitar la replicación de células tumorales. Nuestro relato describe una paciente con neoplasia maligna de mama que sufrió el extravase de este fármaco durante el procedimiento de infusión. La evolución de la lesión en la mano de la paciente, el tratamiento y el pronóstico se evaluaron en este caso

Evaluation of the influence of fluoroquinolone chemical structure on stability: forced degradation and in silico studies

Fluoroquinolones are a known antibacterial class commonly used around the world. These compounds present relative stability and they may show some adverse effects according their distinct chemical structures. The chemical hydrolysis of five fluoroquinolones was studied using alkaline and photolytic degradation aiming to observe the differences in molecular reactivity. DFT/B3LYP-6.31G* was used to assist with understanding the chemical structure degradation. Gemifloxacin underwent degradation in alkaline medium. Gemifloxacin and danofloxacin showed more degradation perceptual indices in comparison with ciprofloxacin, enrofloxacin and norfloxacin in photolytic conditions. Some structural features were observed which may influence degradation, such as the presence of five member rings attached to the quinolone ring and the electrostatic positive charges, showed in maps of potential electrostatic charges. These measurements may be used in the design of effective and more stable fluoroquinolones as well as the investigation of degradation products from stress stability assays

Developing analytical methods for identification of drug-facilitated crime in urine samples

As drogas facilitadoras de crime (DFC) são uma série de substâncias químicas que permitem o ato sexual e/ou roubo com pouca ou nenhuma resistência da vítima. Benzodiazepínicos, gama-hidroxibutirato (GHB), cetamina e etanol são clássicas DFC, porém outras substâncias também têm sido utilizadas. Devido às diferentes classes de DFC e a necessidade de métodos sensíveis, a determinação dessas substâncias é um desafio aos toxicologistas forenses. A proposta do estudo foi desenvolver métodos analíticos para determinação principais analitos alvos de DFC para benzodiazepínicos, cetamina e GHB em amostras de urina. Esta matriz biológica é considerada uma amostra não-invasiva e apresenta um período de detecção maior que o sangue. A preparação das amostras foi avaliada através de microextração em fase líquida (LPME) e extração líquido-líquido (LLE). A LPME é uma técnica de extração de drogas que utiliza menor quantidade de solventes orgânicos, maior praticidade e possibilidade de obtenção de altos valores de recuperação. Os analitos foram determinados por cromatografia gasosa acoplada à espectrometria de massas (GC-MS). A LPME validada para benzodiazepínicos e seus produtos de biotransformação exigiu uma combinação de solventes e dupla derivatização para atingir a sensibilidade exigida, enquanto o método para determinação de cetamina, norcetamina e deidronorcetamina utilizou óleo essencial de eucalipto como meio extrator, caracterizando-se um procedimento ecologicamente correto com alta sensibilidade. A extração de GHB foi efetiva por LLE com redução da quantidade de solvente e tempo de análise sem o prejuízo na sensibilidade. Em geral, os métodos desenvolvidos neste trabalho são sensíveis e confiáveis para todos os analitos relatados e conclui-se que a LPME é uma técnica de preparo de amostra eficiente, versátil de baixo custo. Estas condições permitem que sua implementação em qualquer laboratório de análises toxicológicas, podendo ser aplicada em situações de DFC ou de qualquer outra natureza.Drug-facilitated crime (DFC) are a series of chemicals that allow the sexual act and/or theft with little or no resistance from the victim. Benzodiazepines, gamma-hydroxybutyrate (GHB) and ketamine and ethanol are considered classic DFC, however other substances were also used as the DFC. Due to the different classes of DFC and the need for sensitive methods, the determination of these substances is a challenge to forensic toxicologists. The purpose of this study was to develop analytical methods for determination of the main target analytes of DFC for benzodiazepines, ketamine and GHB in urine samples. This biological matrix is considered a non-invasive sample and shows a larger window of detection than blood. Sample preparation was assessed using liquid phase microextraction (LPME) and liquid-liquid extraction (LLE). The LPME is a drug extraction technique that uses less organic solvents, greater practicality and possibility of obtaining high recovery values. The analytes were determined by gas chromatography - mass spectrometry (GC-MS). The validated LPME technique for benzodiazepines and their metabolites required a combination of solvents and double derivatization to achieve the required sensitivity, while the ketamine, norketamine and dehydronorketamine method used essential oil of eucalyptus as solvent, characterizing a green chemistry approach with high sensitivity. The extraction of GHB was effective by LLE with a reduced amount of solvent and the analysis time without loss in sensitivity. In general, the methods developed in this work using GC-MS are sensitive and reliable for all analytes reported and LPME technique showed to be an efficient sample preparation, versatile and low cost. These conditions allow LPME implementation in any laboratory of toxicological analysis and it can be applied in situations of DFC or any other kind of analysis

Perspectivas teóricas na interação entre varfarina e compostos de alho com um estudo in silico de cyp3a4

Garlic (Allium sativum L.) is one of the most consumed food supplements in the world and has multiple biological properties. Among all molecules obtained from garlic, S-allyl-L-cysteine (SAC), S-methyl-L-cysteine (SMC) and S-allylmercaptocysteine (SAMC) are highlighted. There are in vitro and in vivo studies which correlate the interactions of these molecules with medicinal drugs such as warfarin by competition site in the cytochrome P450 isoenzymes (CYP). Warfarin is an oral anticoagulant belong to vitamin K antagonist class and metabolized by CYP 3A4, 2C9 and 2C19. This article consists in a review showing studies with extracts and/or isolated garlic compounds, metabolic pathways and biological consequences considering drug interactions. The results revealed that garlic extracts express an inhibitory activity in CYP 3A4, 2C9 and 2C19. Inhibition of CYP3A4 were greater than 50% for SAC and SAMC. In silico experiment was performed for SAC, SMC and SAMC in the CYP3A4 isoenzyme which SAMC showed lower energy of interaction (-85.9 Kcal mole-1). (R)-warfarin was docked in same molecular cavity from this active site and showed lower value of energy interaction (-101.1 Kcal mole-1) in comparison with three compounds, which may suggest the warfarin showed better affinity with CYP3A4. Consequently, SAMC interacts better with CYP3A4, followed by SAC and SMC (-80.4 and -70.2 Kcal mole-1, respectively). These results indicate the mercaptocysteine shows better fit with the active site of human CYP3A4. So, these interactions may potentiate the risk of bleeding in patients during warfarin therapy, because some of the garlic compounds inhibit the CYP enzymes responsible for the biotransformation of (R)-warfarin. These findings suggest the consume of garlic should be monitored in patients receiving warfarin therapy and health professionals must be aware of this interaction.Alho (Allium sativum L.) é um dos suplementos alimentares mais consumidos no mundo e tem mpultiplas pripriedades biológicas. Entre todas as moléculas obtidas de alo, S-alil-Lcisteína (SAC), S-metil-L-cisteína (SMC) e S-alilmercaptocisteína (SAMC) são destacadas. Existem estudos in vitro e in vivo que correlacionam as interações destas mléculas com drogas medicinais como varfarina pela competição no sítio de ligação das isenzimas do citocromo P450 (CYP). Varfarina é um anticoagulando oral pertencente à classe dos antagonistas da vitamina K e meraboliza por CYP3A4, 2C9 e 2C19. Este artigo consiste em uma revisão mostrando estudos com extrados e/ou compostos isolados do alho, vias metabólicas e consequências biológicas considerando interações armacológicas. Os resultados revelaram que os extratos de alho expressam uma atividade inibitória em CYP3A4, 2C9 e 2C19. A inibiçã de CYP3A4 foi maior que 50% para SAC e SAMC. O experimento in silico foi realizado para SAC, SMC e SAMC na isoenzima CP3A4 em que SAMC mostrou menor energia de interação (-85, 9Kcal mol-1). (R)-varfarina foi estudada na mesma cavidade molecular deste sítio ativo e mostrou menor valor de energia de interação (-101, 1Kcal mol-1) en comparação com três compostos,  que pode suregir que varfarina mostrou melhor afinidade com CYP3a4. Consequentemente, SAMC interage melhor co CYP3A4, seguida de SAC e SMC (-80,4 e 70,2 Kcal mol-1, respectivamente). Estes resultados indicam que mercaptocisteína mostra melhor encaixe com o sítio ativo da CYP3A4 humana. Então, estas interações podem potencializar o risco de sangramento em pacientes durante terapia com varfaria, pois em alguns dos compostos de alho inibem a CYP responsával pela biotransformaço de (R)-varfarina. Estes achados sugerem que o consume de alho deveria ser monitorado em pacientes que recebem terapia anticoagulante com varfarina e os profissionais da saúde devem esta conscientes deste potencial de interação.

Doping genético e possíveis metodologias de detecção

O doping genético caracteriza-se pelo uso não terapêutico de células, genes e elementos gênicos, ou a modulação da expressão gênica com objetivo de aumentar o desempenho esportivo. Isto somente pode ser realizado através de manipulação gênica. Esta prática dopante caracteriza-se como virtualmente "indetectável", o que representa novos desafios analíticos para sua detecção. Esta revisão apresenta o doping genético e possíveis métodos de detecção para evitar futuras fraudes desportivas

Serum quantification of vitamin c by hplc-uv and stability study

Vitamin C, an exogenous antioxidant, is essential to human health. In this study, a method was validated to serum vitamin C quantification by HPLC-UV. Its stability with and without the use of tris [2-carboxy-ethyl] phosphine hydrochloride (TCEP), at-20 and -80 ºC, in serum and supernatant were also evaluated. Analysis showed r2 > 0.99, precision CV% < 15% and % bias < 15%, being linear, precise and accurate. The stability test revealed that using TCEP in serum storage at-20 and -80 ºC or in supernatant at -80 ºC the vitamin C levels remain stable for 30 and 12 days, respectively

Evaluation of the influence of fluoroquinolone chemical structure on stability: forced degradation and in silico studies

<div><p>ABSTRACT Fluoroquinolones are a known antibacterial class commonly used around the world. These compounds present relative stability and they may show some adverse effects according their distinct chemical structures. The chemical hydrolysis of five fluoroquinolones was studied using alkaline and photolytic degradation aiming to observe the differences in molecular reactivity. DFT/B3LYP-6.31G* was used to assist with understanding the chemical structure degradation. Gemifloxacin underwent degradation in alkaline medium. Gemifloxacin and danofloxacin showed more degradation perceptual indices in comparison with ciprofloxacin, enrofloxacin and norfloxacin in photolytic conditions. Some structural features were observed which may influence degradation, such as the presence of five member rings attached to the quinolone ring and the electrostatic positive charges, showed in maps of potential electrostatic charges. These measurements may be used in the design of effective and more stable fluoroquinolones as well as the investigation of degradation products from stress stability assays.</p></div