Gaseous Mediators in Gastrointestinal Mucosal Defense and Injury

Of the numerous gaseous substances that can act as signaling molecules, the best characterized are nitric oxide, carbon monoxide and hydrogen sulfide. Contributions of each of these low molecular weight substances, alone or in combination, to maintenance of gastrointestinal mucosal integrity have been established. There is considerable overlap in the actions of these gases in modulating mucosal defense and responses to injury, and in some instances they act in a cooperative manner. Each also play important roles in regulating inflammatory and repair processes throughout the gastrointestinal tract. In recent years, significant progress has been made in the development of novel anti-inflammatory and cytoprotective drugs that exploit the beneficial activities of one or more of these gaseous mediators

Pulmonary fungal infections in patients with acute myeloid leukaemia: is it the time to revise the radiological diagnostic criteria?

The definition of pulmonary fungal infections (PFI) according to the EORTC-MSG criteria may lack diagnostic sensitivity due to the possible presentation of PFI with different radiological pictures. We evaluated the hypothesis to apply less restrictive radiological criteria to define PFI in patients with acute myeloid leukaemia (AML) submitted to chemotherapy. Overall, 73 consecutive episodes of pulmonary infiltrates associated to positive serum galactomannan test or fungal isolation or galactomannan detection from respiratory specimens were considered. CT scans acquired at the onset of symptoms (time-0) and within 4 weeks (time-1) were analysed to identify specific (group A) or aspecific radiological signs (group B). Pulmonary infiltrates fulfilled the EORTC-MSG criteria in 49 patients (group A), whereas in 24 patients (group B) they did not reach the criteria due to aspecific CT findings at time-0. Eleven of 21 (52.4%) patients of the group B evaluable for the evolution of the radiological findings fulfilled EORTC-MSG criteria at time-1. All the analysed clinical and mycological characteristics, response to antifungal therapy and survival were comparable in the two groups. Our study seems to confirm the possibility to extend the radiological suspicion of PFI to less restrictive chest CT findings when supported by microbiological criteria in high-risk haematological patients

Comparative Bioavailability Study of Two 81 mg Coated Tablet Formulations of Acetylsalicylic Acid in Fasting Healthy Volunteers

Introduction: Low-dose acetylsalicylic acid is used as antithrombotic agent and the enteric-coated formulations are widely used to minimize the gastrointestinal side effects. Aim: To compare the bioavailability of two acetylsalicylic acid formulations (Ecasil-81®, 81 mg coated tablet) in fasting healthy volunteers. Methods: Healthy volunteers (n=16) were recruited to a monocentric, open label, randomized, two-way crossover pharmacokinetic study, with seven days washout period between the treatments. They received a single 81 mg oral dose of a test (new formulation) or a standard reference formulation of acetylsalicylic acid (Ecasil-81®) after about 8 h fasting. Blood samples were collected over a period of 36 h. The salicylic acid plasma concentration was evaluated by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Noncompartmental pharmacokinetic analysis was performed using the WinNonlin program. Results: The maximum plasma concentration (Cmax) of salicylic acid was 5433 and 5719 ng/mL reached in 3.66 and 4.02 h (tmax) for the test and the reference formulation, respectively. The 90% confidence interval of the ratios of geometric means of Cmax and area under curve of plasma concentration until the last concentration observed (AUC0- last) were within the interval 80-125%. Conclusion: The new acetylsalicylic acid formulation has a bioavailability equivalent to the reference formulation for the rate and the extent of absorption

Lack of relationship between hypertension and cognitive performance in community dwelling older adults

CONTEXTO: Pesquisas documentam que a hipertensão arterial pode estar envolvida no declínio cognitivo em pacientes idosos. Estima-se que até 60% dos idosos apresentem hipertensão arterial, tornando-os mais suscetíveis ao declínio cognitivo. OBJETIVO: Investigar a relação entre hipertensão arterial e desempenho cognitivo em idosos não portadores de demências ou depressão. MÉTODO: A amostra foi constituída por idosos participantes de pesquisa populacional em andamento sobre envelhecimento no município de Amparo (SP). Seguindo critérios de inclusão e exclusão, foram selecionados 80 homens e mulheres (40 hipertensos e 40 normotensos) com idade igual ou superior a 60 anos, equivalentes quanto às variáveis sociodemográficas e de saúde. Para avaliar sintomas depressivos, foi utilizada a Geriatric Depression Scale (GDS). Os testes cognitivos utilizados foram a bateria neuropsicológica Consortium to Establish a Registry for Alzheimer's Disease (CERAD) e o Teste do Desenho do Relógio e Dígitos ordem direta e inversa. A análise estatística foi realizada por meio de análise de regressão logística com modelo univariado e multivariado e análise de conglomerados (cluster analysis). RESULTADOS: Não foram encontradas diferenças estatisticamente significativas para as variáveis cognitivas entre os dois grupos. A diferença para fluência verbal aproximou-se da significância estatística (p = 0,075). CONCLUSÕES: Os resultados encontrados podem ser explicados pela adesão desta população pertencente à estratégia de saúde da família ao tratamento medicamentoso. Estudos longitudinais serão necessários para investigar a relação entre a hipertensão arterial e o declínio cognitivo na pessoa idosa.BACKGROUND: Studies suggest that hypertension might be involved in cognitive decline among older adults. It is estimated that up to 60% of older adults have hypertension, what makes them more vulnerable to cognitive decline. OBJECTIVE: The objective of this study was to investigate the relationship between hypertension and cognitive performance in non-demented non-depressed older adults. METHOD: The sample was constituted by community dwelling older adults from an on-going epidemiological study which includes all senior citizens residing in Amparo (SP). Following inclusion and exclusion criteria, 80 seniors (40 diagnosed as having hypertension), including men and women over 60, were recruited. Both groups were equivalent as to socio-demographic and other health variables. In order to evaluate depressive symptoms the Geriatric Depression Scale (GDS) was used. The cognitive tests included the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery, the Clock Drawing Test, and Digit Span Forward and Backward. Logistic regression analyses with univariate and multivariate models and cluster analyses were carried out. RESULTS: No significant differences were found between the two groups. The difference for verbal fluency approached statistical significance (p = 0.075). DISCUSSION: Present results may be explained by the high compliance of the studied sample to the antihypertensive drug regimen. Longitudinal studies will be needed to continue to investigate the relationship between hypertension and cognition in aging

Prognostic factors and historical trends in the epidemiology of candidemia in critically ill patients: an analysis of five multicenter studies sequentially conducted over a 9-year period (vol 40, pg 1489, 2014)

Universidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilHosp Serv Publ Estadual São Paulo, São Paulo, BrazilIrmandade Santa Casa de Misericordia Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Ciencias Saude Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Parana, BR-80060000 Curitiba, Parana, BrazilUniv Fed Rio de Janeiro, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilWeb of Scienc

Murine model for Fusarium oxysporum invasive fusariosis reveals organ-specific structures for dissemination and long-term persistence

Peer reviewedPublisher PD

Pain assessment in surgical patients with impaired cognition

Pain is considered the 5th vital sign and its measurement/assessment and records are required and must be systematic. Ineffective pain management involves complications in clinical status of patients, longer hospitalization times and higher costs with health. In the surgical patient with impaired cognition, hetero measurements should be made, based on behavioural and physiological indicators. We used to determine the efficacy and efficiency of the Observer Scale, the Abbey Pain Scale and Pain Assessment in Advanced Dementia (PAINAD). Our study is an applied, non-experimental, quantitative, descriptive and analytical research. The data collection instrument consisted of patients’ sociodemographic and clinical data, the Observer Scale, the Abbey Pain Scale (Rodrigues, 2013) and PAINAD (Batalha et al., 2012). We assessed pain at an early phase and 45 minutes after an intervention for its relief. The sample is non-probabilistic for convenience, consisting of 76 surgical patients with impaired cognition, admitted to the surgery services of a central hospital, aged between 38 and 96 years. There was a positive correlation between the results of the three scales, most evident in the initial evaluation. Pain intensity in the same patient is higher when assessed with PAINAD (OM = 2.16) and lower when assessed with the Observer Scale (OM = 1.78). The most effective and efficient scale is PAINAD. Due to the small sample size, we suggest confirmatory studies so that the results can be generalized

Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice.

Published onlineJournal ArticleThis is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.The recently described 'gasomediator' hydrogen sulfide (H2S) has been involved in pain mechanisms, but its effect on pruritus, a sensory modality that similarly to pain acts as a protective mechanism, is poorly known and controversial. The effects of the slow-releasing (GYY4137) and spontaneous H2S donors (Na2S and Lawesson's reagent, LR) were evaluated in histamine and compound 48/80 (C48/80)-dependent dorsal skin pruritus and inflammation in male BALB/c mice. Animals were intradermally (i.d.) injected with C48/80 (3μg/site) or histamine (1μmol/site) alone or co-injected with Na2S, LR or GYY4137 (within the 0.3-100nmol range). The involvement of endogenous H2S and KATP channel-dependent mechanism were also evaluated. Pruritus was assessed by the number of scratching bouts, whilst skin inflammation was evaluated by the extravascular accumulation of intravenously injected (125)I-albumin (plasma extravasation) and myeloperoxidase (MPO) activity (neutrophil recruitment). Histamine or C48/80 significantly evoked itching behavior paralleled by plasma extravasation and increased MPO activity. Na2S and LR significantly ameliorated histamine or C48/80-induced pruritus and inflammation, although these effects were less pronounced or absent with GYY4137. Inhibition of endogenous H2S synthesis exacerbated C48/80-induced responses, whereas the blockade of KATP channels by glibenclamide did not. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) revealed that Na2S and LR, but not GYY4137, significantly attenuated C48/80-induced histamine release from rat peritoneal mast cell in vitro. We provide first evidences that H2S exerted protective effect against acute pruritus mediated via histaminergic pathways in murine skin, thus making of H2S donors a potential alternative/complementary therapy for treatment of acute pruritus.Sao Paulo Research Foundation (Fapesp grant numbers: 2013/04.151-3, 2014/15.576-8, 2014/24.518-1) and CNPq (grant number: 163278/2012-1). GDN, MNM and SKPC are recipients of fellowships from the National Council for Scientific and Technological Development (CNPq). We thank Irene M Gouvea, Flávia B de Lira and Mauro Sucupira for their techinical support