Acetonitrile adducts of tranexamic acid as sensitive ions for quantification at residue levels in human plasma by UHPLC-MS/MS

The quantitative analysis of pharmaceuticals in biomatrices by liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) is often hampered by adduct formation. The use of the molecular ion resulting from solvent adducts for quantification is uncommon, even if formed in high abundance. In this work, we propose the use of a protonated acetonitrile adduct for the quantitative analysis of tranexamic acid (TXA) by LC-MS/MS. The high abundance of the protonated acetonitrile adduct [M + ACN + H]+ was found to be independent of source-dependent parameters and mobile phase composition. The results obtained for TXA analysis in clinical samples were comparable for both [M + ACN + H]+ and [M + H]+ , and no statistically significant differences were observed. The relative stability and structure of the [M + ACN + H]+ ions were also studied by analyzing probable structures from an energetic point of view and by quantum chemical calculations. These findings, and the studied fragmentation pathways, allowed the definition of an acetimidium structure as the best ion to describe the observed acetonitrile protonated adduct of TXA.info:eu-repo/semantics/publishedVersio

Requisitos de sustentabilidade em meios de hospedagem no Brasil/Sustainability requirements for lodging facilities in Brazil

Quais requisitos de sustentabilidade constam no Sistema Brasileiro de Classificação de Meios de Hospedagem (SBClass)? As medidas de sustentabilidade adotadas pelos meios de hospedagem cinco estrelas estão disponibilizadas em seus sites? O objetivo do estudo é analisar as informações que são disponibilizadas na forma on-line sobre os requisitos de sustentabilidade dos meios de hospedagem cinco estrelas classificados no Brasil. A pesquisa foi conduzida em 2015 e caracteriza-se como de caráter exploratório e descritivo, identificando 59 meios de hospedagem classificados no Brasil, sendo 15 com cinco estrelas. Desses empreendimentos, apenas dez meios de hospedagem disponibilizam informações sobre as medidas de sustentabilidade implantadas nos mesmos. Conclui-se sobre a importância da divulgação dessas informações nos sites dos empreendimentos, motivando os clientes a escolher o meio de hospedagem por critérios sustentáveis

ALERGIA A FÁRMACOS COM MANIFESTAÇÕES CUTÂNEAS - ABORDAGEM DIAGNÓSTICA

Adverse drug reactions constitute a major health problem in clinical practice. Drug allergy is defined as an immunologically mediated hypersensitivity reaction and represents 6-10% of all adverse drug reactions. Cli- nically, drug-induced allergic reactions can be classified as immediate (type I) and non-immediate (heterogeneous clinical manifestations, mostly related to type IV reactions). Several issues are considered in this revision, particularly immunopathologic mechanisms, cross-reactivity and the most relevant cutaneous reactions (maculopapular exanthe- ma, fixed drug eruption, acute generalized exanthematic pustulosis, drug hypersensitivity syndrome, also referred as drug rash with eosinophilia and systemic symptoms – DRESS, Stevens-Johnson syndrome and toxic epidermal necrolysis). The role of skin tests (epicutaneous or intradermal with late reading) in the diagnostic approach of non- -immediate reactions is also analysed. The most important causes of hypersensitivity reactions are antibiotics, parti- cularly beta-lactams. This group poses significant diagnostic and management difficulties and deserves, therefore, a more thorough attention, with particular attention to cross-reactivity patterns. Induction of drug tolerance should be considered in selected cases, especially when no safe or effective drug alternatives are available.KEYWORDS – Drug hypersensitivity; Beta-Lactams; Cross reactions; Skin Tests.As reacções adversas a fármacos (RAF) representam um problema frequente na prática clínica. A alergia a fármacos resulta de mecanismos de hipersensibilidade imunológica e representa 6-10% do total de RAF. Clinica- mente, as reacções alérgicas a fármacos podem ser classificadas como imediatas (tipo I) ou não-imediatas (com manifestações clínicas diversas e associadas sobretudo a reacções de tipo IV). Neste artigo são abordados aspectos gerais, nomeadamente os mecanismos imunopatogénicos implicados na alergia a fármacos e reactividade cruzada mas também as manifestações cutâneas mais relevantes, nomeadamente exantemas máculo-papulares, eritema fixo a fármacos (EFF), pustulose exantemática aguda generalizada (PEAG), síndrome de hipersensibilidade a fármacos (DRESS – drug rash with eosinophilia and systemic symptoms), síndrome de Stevens-Johnson/necrólise epidérmica tóxica (SSJ/NET). O papel dos testes cutâneos (epicutâneos ou intradérmicos de leitura tardia) na abordagem de reacções não-imediatas é também revisto. Os beta-lactâmicos (BL) são o grupo farmacológico mais frequentemente envolvido em reacções de hipersensibilidade imunológica e que mais dificuldades coloca na prática clínica diária, nomeadamente devido aos riscos de reactividade cruzada, pelo que é analisado em maior detalhe ao longo da revisão. A indução de tolerância a fármacos poderá ser considerada em casos selecionados, sobretudo quando na ausência de alternativas terapêuticas igualmente eficazes ou seguras.PALAVRAS-CHAVE – Hipersensibilidade a fármacos; Beta-Lactâmicos; Reactividade cruzada; Testes cutâneos

Avocado (Persea americana) pulp improves cardiovascular and autonomic recovery following submaximal running: a crossover, randomized, double-blind and placebo-controlled trial

Previous studies have demonstrated that regular avocado consumption presents advantageous effects on cardiovascular system. However, little attention has been paid to the use of avocado as a dietary supplement, in particular, for individuals involved in physical exercise training. Therefore, this study aims to evaluate the effect of acute avocado pulp intake on cardiovascular and autonomic recovery subsequent to moderate exercise. Using a crossover, randomized, double-blind and placebo-controlled trial design, 16 healthy female adults underwent two protocols: Avocado pulp (600 mg in capsule) and placebo (600 mg starch in capsule). After the ingestion of Avocado pulp or placebo, the subjects were seated for 60 min at rest, followed by running on a treadmill at a submaximal level and then remained seated for 60 min during recovery from the exercise. Heart rate (HR), heart rate variability (HRV) [rMSSD, SD1, HF (ms2)] and skin conductance were evaluated before and during exercise, as well as during recovery. HR, systolic blood pressure, HRV and skin conductance recovered faster when subjects were given avocado pulp prior to exercise. In conclusion, avocado pulp improved cardiovascular and autonomic recovery after exercise, suggesting a reduced risk of cardiovascular events after exertion. The current results support the beneficial effects of ingestion of avocado prior to submaximal treadmill running

Oral health self-perception for transgender people: a controlled cross-sectional study

This article aims to verify the use of dental services, oral health self-perception, and the impacts of oral health on the daily lives of transgender people. A controlled cross-sectional study was conducted in which transvestites, transsexuals, and transgender people were compared to cisgender people. For data collection, the oral health self-perception questionnaire was applied to 90 people, from which 45 were cisgender and 45 were transgender. There were no differences regarding access to dental services. The data analysis revealed that transgender people perceive their teeth to cause nervousness (p=0.002) and shame (p=0.033), respectively 3.8 and 5.0 times higher than that observed for cisgender people. Although differences in access were not observed, there was a difference in the perception of the need for treatment and the impacts of oral health. Therefore, it is important to consider that comprehensive care for the transgender population should go beyond the treatment of oral diseases and include aesthetic expectations as well

Capacidade funcional e suporte familiar em idosos longevos residentes em domicílio

Objective: to evaluate the functional capacity and family support of long-lived elderly people living at home. Methods: This is a descriptive research, with a cross-sectional and observational design carried out in the municipality of Jequié with 117 long-lived elderly people registered in five family health units. The data collection instrument consisted of sociodemographic characterization, health conditions, Barthel Index, Lawton Scale and Perception Inventory of Family Support, with a descriptive analysis of the study variables. Result: There was a higher frequency of elderly females (59.0%), aged between 80 and 84 years (57.3%) illiterate (51.3%), independent in basic activities of daily living ( 59.0%), dependent on instrumental activities of daily living (80.3%), with high score (62.4%) in the Affectivity-Consistency domain, high score (53.0%) in the Family Adaptation domain and high score (60.7%) in the Autonomy domain. It was found in relation to functional capacity that there was a predominance of independence to perform BADLs, while for performing IADLs a dependency was observed. Conclusion: Regarding family support, it was evidenced that the elderly in the study have impairment in the domains Affectivity-Consistency and Autonomy. In the assessment of ABVD, it was found that the majority of the elderly were classified as independent and as dependents in IADL.Objetivo: avaliar a capacidade funcional e o suporte familiar de idosos longevos residentes em domicílio. Métodos: Trata-se de uma pesquisa do tipo descritiva, com delineamento transversal e observacional realizada no município de Jequié com 117 idosos longevos cadastrados em cinco unidades de saúde da família. O instrumento de coleta de dados foi constituído de caracterização sociodemográfica, condições de saúde, Índice de Barthel, Escala de Lawton e Inventário de Percepção de Suporte Familiar, sendo realizada análise descritiva das variáveis de estudo. Resultado: Constatou-se uma maior frequência de idosos do sexo feminino (59,0%), faixa etária de 80 a 84 anos (57,3%) não alfabetizados (51,3%), independentes nas atividades básicas de vida diária (59,0%), dependentes nas atividades instrumentais de vida diária (80,3%), com pontuação alta (62,4%) no domínio Afetividade-Consistência, pontuação alta (53,0%) no domínio Adaptação Familiar e pontuação alta (60,7%) no domínio Autonomia. Constatou-se em relação a capacidade funcional que houve uma predominância de independência para realização das ABVD, enquanto para realização das AIVD foi observada uma dependência. Conclusão: Quanto ao suporte familiar ficou evidenciado que os idosos do estudo possuem comprometimento nos domínios Afetividade-Consistência e Autonomia. Na avaliação das ABVD, verificou- se que a maioria dos idosos foram classificados como independentes e como dependentes nas AIVD

Docetaxel-loaded liposomes: The effect of lipid composition and purification on drug encapsulation and in vitro toxicity

Docetaxel (DTX)-loaded liposomes have been formulated to overcome DTX solubility issue, improve its efficacy and reduce its toxicity. This study investigated the effect of steric stabilisation, varying liposome composition, and lipid:drug molar ratio on drug loading and on the physicochemical properties of the DTX-loaded liposomes. Size exclusion chromatography (SEC) was used to remove free DTX from the liposomal formulation, and its impact on drug loading and in vitro cytotoxicity was also evaluated. Liposomes composed of fluid, unsaturated lipid (DOPC:Chol:DSPE-PEG2000) showed the highest DTX loading compared to rigid, saturated lipids (DPPC:Chol:DSPE-PEG2000 and DSPC:Chol:DSPE-PEG2000). The inclusion of PEG showed a minimum effect on DTX encapsulation. Decreasing lipid:drug molar ratio from 40:1 to 5:1 led to an improvement in the loading capacities of DOPC-based liposomes only. Up to 3.6-fold decrease in drug loading was observed after liposome purification, likely due to the loss of adsorbed and loosely entrapped DTX in the SEC column. Our in vitro toxicity results in PC3 monolayer showed that non-purified, DTX-loaded DOPC:Chol liposomes were initially (24h) more potent than the purified ones, due to the fast action of the surface- adsorbed drug. However, we hypothesize that over time (48 and 72h) the purified, DTX-loaded DOPC:Chol liposomes became more toxic due to high intracellular release of encapsulated DTX. Finally, our cytotoxicity results in PC3 spheroids showed the superior activity of DTX-loaded liposomes compared to free DTX, which could overcome the DTX poor tissue penetration, drug resistance, and improve its therapeutic efficacy following systemic administration

Chronic Urticaria in the Real-Life Clinical Practice Setting in Portugal: Baseline Results from the Non-Interventional Multicentre AWARE Study

Introduction: There is a paucity of information regarding chronic urticaria patients’ care in a real-world setting. The objective of this study was to report and evaluate the baseline characteristics of Portuguese chronic urticaria patients refractory to H1-antihistamines included in the AWARE study. Material and Methods: This is a non-interventional cohort study. Adult patients with a diagnosis of chronic urticaria with symptoms for at least two months, refractory to H1-antihistamines, consulting one of the 10 participating urticaria centers throughout Portugal have been included in the study. Baseline sociodemographic data, medical history, clinical parameters, medication, weekly urticaria activity score, and dermatology quality of life index have been collected. Results: Seventy six patients were included, of which 76.3% were women. The majority of patients had a diagnosis of chronic spontaneous urticaria (88.2%) and 39.5% had angioedema. Around 91.0% of patients were medicated with non-sedative H1-antihistamines and 35.4% with a third line therapy. Median dermatology quality of life index was 5.0 and median weekly urticaria activity score was 13.0. Discussion: The baseline results suggest that patients with chronic urticaria refractory to H1-antihistamines are being under-treated in the real-world setting. Conclusion: The AWARE study demonstrates the real impact of chronic urticaria on Portuguese patients refractory to H1-antihistamines treatment, and 30% report a very large or extremely large deleterious effect on their quality of life. The follow-up of these patients will allow evaluating strategies aimed at optimizing disease control