Drug-Induced Anaphylaxis Survey in Portuguese Allergy Departments

Background and Objective: Drug-induced anaphylaxis is an unpredictable and potentially fatal adverse drug reaction. The aim of this study was to identify the causes of drug-induced anaphylaxis in Portugal. Methods: During a 4-year period a nationwide notification system for anaphylaxis was implemented, with voluntary reporting by allergists. Data on 313 patients with drug anaphylaxis were received and reviewed. Statistical analysis included distribution tests and multiple logistic regression analysis to investigate significance, regression coefficients, and marginal effects. Results: The mean (SD) age of the patients was 43.8 (17.4) years, and 8.3% were younger than 18 years. The female to male ratio was 2:1. The main culprits were nonsteroidal anti-inflammatory drugs (NSAIDs) (47.9% of cases), antibiotics (35.5%), and anesthetic agents (6.1%). There was a predominance of mucocutaneous symptoms (92.2%), followed by respiratory symptoms (80.4%) and cardiovascular symptoms (49.0%). Patients with NSAID-induced anaphylaxis showed a tendency towards respiratory and mucocutaneous manifestations. We found no significant associations between age, sex, or atopy and type of drug. Anaphylaxis recurrence was observed in 25.6% of cases, and the risk was higher when NSAIDs were involved. Conclusions: NSAIDs were the most common cause of anaphylaxis in this study and were also associated with a higher rate of recurrence. We stress the need for better therapeutic management and prevention of recurring episodes of drug-induced anaphylaxis

Drug-Induced Anaphylaxis: National Survey 2007-2010

Introdução: A anafilaxia a fármacos constitui uma situação potencialmente fatal e imprevisível, desconhecendo -se a real prevalência em diferentes grupos populacionais e os factores de risco relacionados. Objectivo: Contribuir para o melhor conhecimento epidemiológico da anafilaxia induzida por fármacos no nosso país. Métodos: Durante um período de 4 anos (Janeiro de 2007 a Dezembro de 2010) foi implementado um sistema de notificação nacional de anafilaxia, focalizado na notificação voluntária por clínicos com diferenciação em patologia imunoalérgica. Foram recebidas e analisadas notificações de anafilaxia a fármacos de 313 doentes. No estudo estatístico foram aplicados testes de distribuição e análise de regressão logística múltipla para obter significância e coeficientes de regressão e efeitos marginais. Resultados: A média de idade foi de 43,8 ±17,4 anos, sendo 8% de idade inferior a 18 anos. A relação género feminino/masculino foi de 2/1. A média de idade do primeiro episódio foi de 39 ±18,2 anos. Nove doentes apresentaram mais que uma causa de anafilaxia, correspondendo a um total de 322 notificações de grupos de fármacos envolvidos. As principais causas da anafilaxia a fármacos foram os anti -inflamatórios não esteróides (AINEs), os antibióticos e os agentes anestésicos, com respectivamente 48%, 36% e 6% dos casos. Outros fármacos implicados foram citostáticos, corticosteróides, inibidores da bomba de protões e meios de contraste iodados, entre outros. Houve predomínio de manifestações mucocutâneas (92%), seguido de respiratórias (81%) e de cardiovasculares (49%). Os doentes com anafilaxia a AINEs apresentaram aumento significativo da associação de manifestações mucocutâneas e respiratórias. Não foram observadas diferenças significativas em idade, género ou antecedentes de atopia entre os diferentes grupos de fármacos envolvidos. As reacções ocorreram em ambiente hospitalar em 45% dos casos. Em 53% nos 15 minutos após a administração do fármaco e 35% motivaram internamento. A recorrência da anafilaxia foi observada em 26% e o risco foi significativamente mais elevado nos casos de anafilaxia a AINEs. Apenas 48% dos doentes receberam tratamento com adrenalina e somente em 9% dos casos foi prescrito dispositivo para auto -administração de adrenalina. Conclusões: Neste estudo os AINEs foram os fármacos mais frequentes e os mais associados a recorrência de anafilaxia. Destaca -se o sub -tratamento com adrenalina e a necessidade de serem tomadas medidas no sentido do tratamento eficaz e da prevenção da recorrência de anafilaxia a fármacos

Action of cholecalciferol and alpha-tocopherol on Staphylococcus aureus efflux pumps

Alpha-tocopherol is one the most abundant and biologically active isoforms of vitamin E. This compound is a potent antioxidant and one of most studied isoforms of vitamin E. Vitamin D3 (cholecalciferol) is an important nutrient for calcium homeostasis and bone health, that has also been recognized as a potent modulator of the immune response. Methicillin-resistant Staphylococcus aureus (MRSA) is the most important causative agent of both nosocomial and community-acquired infections. The aim of this study was to evaluate the inhibitory effect of alpha-tocopherol and cholecalciferol on both S. aureus and multidrug resistant S. aureus efflux pumps. The RN4220 strain has the plasmid pUL5054 that is the carrier of gene that encodes the macrolide resistance protein (an efflux pump) MsrA; the IS-58 strain possesses the TetK tetracycline efflux protein in its genome and the 1199B strain resists to hydrophilic fluoroquinolones via a NorA-mediated mechanism. The antibacterial activity was evaluated by determining the Minimal Inhibitory Concentration (MIC) and a possible inhibition of efflux pumps was associated to a reduction of the MIC. In this work we observed that in the presence of the treatments there was a decrease in the MIC for the RN4220 and IS-58 strains, suggesting that the substances presented an inhibitory effect on the efflux pumps of these strains. Significant efforts have been done to identify efflux pump inhibitors (EPIs) from natural sources and, therefore, the antibacterial properties of cholecalciferol and alphatocopherol might be attributed to a direct effect on the bacterial cell depending on their amphipathic structure

Fern extracts potentiate fluconazole activity and inhibit morphological changes in Candida species

Objective: To investigate the antifungal activity of the fern species Lygodium venustum (L. venustum) and Pityrogramma calomelanos (P. calomelanos) against Candida albicans and Candida tropicalis strains. Methods: The microdilution method was used to evaluate the antifungal activity, as well as the modulating effects of ethanolic extracts of these plants in combination with fluconazole. The minimum inhibitory concentration (MIC), minimum fungicide concentration and morphological changes were also determined. Results: The extract obtained from L. venustum presented a MIC > 8192 μg/mL, while the extract obtained from and P. calomelanos presented a MIC = 8192 μg/mL, indicating that they present weak antifungal activity. However, combination of the extracts with Fluconazole potentiated the antifungal activity of this drug. At different experimental conditions, such as concentration of the extract and type of strain, the extracts inhibited hyphae and pseudohyphae formation, indicating that these fern species can affect the morphology of the fungi. Conclusions: The extracts obtained from the fern species L. venustum and P. calomelanos dose not present significant antifungal activity. However, P. calomelanos potentiates the activity of fluconazole and both extracts inhibits the morphological changes in Candida species, indicating that they have potential pharmacological activity as modulators of fungal biology. Therefore, novel studies are required to characterize the interference of these extracts in the virulence and pathogenicity of Candida species as well as the potential of fern species to treat fungal infections

Action of cholecalciferol and alpha-tocopherol on Staphylococcus aureus efflux pumps

Submitted by Adagilson Silva ([email protected]) on 2017-06-13T19:43:53Z No. of bitstreams: 1 27298617 2016 tin-act.pdf: 373418 bytes, checksum: 5674ad4d8b062cd367d34169f62a13a0 (MD5)Approved for entry into archive by Adagilson Silva ([email protected]) on 2017-06-13T19:44:14Z (GMT) No. of bitstreams: 1 27298617 2016 tin-act.pdf: 373418 bytes, checksum: 5674ad4d8b062cd367d34169f62a13a0 (MD5)Made available in DSpace on 2017-06-13T19:44:14Z (GMT). No. of bitstreams: 1 27298617 2016 tin-act.pdf: 373418 bytes, checksum: 5674ad4d8b062cd367d34169f62a13a0 (MD5) Previous issue date: 2016Universidade Regional do Cariri. Departamento de Química Biológica. Laboratório de Microbiologia e Biologia Molecular. Crato, CE, Brasil.Universidade Regional do Cariri. Departamento de Química Biológica. Laboratório de Microbiologia e Biologia Molecular. Crato, CE, Brasil.Universidade Regional do Cariri. Departamento de Química Biológica. Laboratório de Microbiologia e Biologia Molecular. Crato, CE, Brasil.Universidade Regional do Cariri. Departamento de Química Biológica. Laboratório de Microbiologia e Biologia Molecular. Crato, CE, Brasil.Universidade Regional do Cariri. Departamento de Química Biológica. Laboratório de Microbiologia e Biologia Molecular. Crato, CE, Brasil.Universidade Regional do Cariri. Departamento de Química Biológica. Laboratório de Microbiologia e Biologia Molecular. Crato, CE, Brasil.Universidade Regional do Cariri. Departamento de Química Biológica. Laboratório de Microbiologia e Biologia Molecular. Crato, CE, Brasil.Universidade Regional do Cariri. Departamento de Química Biológica. Laboratório de Microbiologia e Biologia Molecular. Crato, CE, Brasil.Universidade Federal da Paraíba. Laboratório de Microrganismos Genéticos. João Pessoa, PB, Brasil.Universidade Regional do Cariri. Departamento de Química Biológica. Laboratório de Microbiologia e Biologia Molecular. Crato, CE, Brasil.Universidade Federal de Pernambuco. Laboratório de Bioinformática e Biologia Evolucionária. Departamento de Genética. Recife, PE, Brazil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Microbiologia. Recife, PE, Brasil.Centro Universitário UniLeão Sampaio. Juazeiro do Norte, CE, Brasil.Universidade Federal de Sergipe. Aracaju, SE, Brasil.Alpha-tocopherol is one the most abundant and biologically active isoforms of vitamin E. This compound is a potent antioxidant and one of most studied isoforms of vitamin E. Vitamin D3 (cholecalciferol) is an important nutrient for calcium homeostasis and bone health, that has also been recognized as a potent modulator of the immune response. Methicillin-resistant Staphylococcus aureus (MRSA) is the most important causative agent of both nosocomial and community-acquired infections. The aim of this study was to evaluate the inhibitory effect of alpha-tocopherol and cholecalciferol on both S. aureus and multidrug resistant S. aureus efflux pumps. The RN4220 strain has the plasmid pUL5054 that is the carrier of gene that encodes the macrolide resistance protein (an efflux pump) MsrA; the IS-58 strain possesses the TetK tetracycline efflux protein in its genome and the 1199B strain resists to hydrophilic fluoroquinolones via a NorA-mediated mechanism. The antibacterial activity was evaluated by determining the Minimal Inhibitory Concentration (MIC) and a possible inhibition of efflux pumps was associated to a reduction of the MIC. In this work we observed that in the presence of the treatments there was a decrease in the MIC for the RN4220 and IS-58 strains, suggesting that the substances presented an inhibitory effect on the efflux pumps of these strains. Significant efforts have been done to identify efflux pump inhibitors (EPIs) from natural sources and, therefore, the antibacterial properties of cholecalciferol and alpha-tocopherol might be attributed to a direct effect on the bacterial cell depending on their amphipathic structure