Activation profile of pro-inflammatory cytokines in acute cardiac overload

INTRODUCTION:Pro-inflammatory cytokines have been implicated in ventricular remodeling during heart failure progression. In the present study, we investigated the effects of acute volume and RV pressure overload on biventricular hemodynamics and myocardial gene expression of IL-6 and TNF-alpha.METHODS:Male Wistar rats (n = 45) instrumented with RV and LV tip micromanometers were randomly assigned to one of three protocols: i) acute RV pressure overload (PrOv) induced by pulmonary trunk banding in order to double RV peak systolic pressure, for 120 or 360 min; ii) acute volume overload (VolOv) induced by dextran40 infusion (5 ml/h), for 120 or 360 min; iii) Sham. Free wall samples from the RV and LV were collected for mRNA quantification.RESULTS:In the RV, acute overload induced IL-6 and TNF-alpha gene expression, higher in VolOv (IL-6: + 669.7 +/- 263.4%; TNF-alpha: + 5149.9 +/- 1099.0%; 360 min) than in PrOv (IL-6: + 64.9 +/- 44.2%; TNF-alpha: + 628.1 +/- 229.3%; 360 min). In PrOv, TNF-alpha mRNA levels in the LV were increased, in the absence of ventricular overload. IL-6 and TNF-alpha mRNA levels did not correlate in the LV, while in the RV a positive correlation was found (r = 0.574; p < 0.001).CONCLUSIONS:Acute cardiac overload induces overexpression of pro-inflammatory cytokines. This gene activation is not uniform, being higher in volume overload and involving both load-dependent and load-independent mechanisms

Extracellular environment contribution to astrogliosis-lessons learned from a tissue engineered 3D model of the glial scar

Glial scars are widely seen as a (bio)mechanical barrier to central nervous system regeneration. Due to the lack of a screening platform, which could allow in-vitro testing of several variables simultaneously, up to now no comprehensive study has addressed and clarified how different lesion microenvironment properties affect astrogliosis. Using astrocytes cultured in alginate gels and meningeal fibroblast conditioned medium, we have built a simple and reproducible 3D culture system of astrogliosis mimicking many features of the glial scar. Cells in this 3D culture model behave similarly to scar astrocytes, showing changes in gene expression (e.g., GFAP) and increased extra-cellular matrix production (chondroitin 4 sulfate and collagen), inhibiting neuronal outgrowth. This behavior being influenced by the hydrogel network properties. Astrocytic reactivity was found to be dependent on RhoA activity, and targeting RhoA using shRNA-mediated lentivirus reduced astrocytic reactivity. Further, we have shown that chemical inhibition of RhoA with ibuprofen or indirectly targeting RhoA by the induction of extracellular matrix composition modification with chondroitinase ABC, can diminish astrogliosis. Besides presenting the extracellular matrix as a key modulator of astrogliosis, this simple, controlled and reproducible 3D culture system constitutes a good scar-like system and offers great potential in future neurodegenerative mechanism studies, as well as in drug screenings envisaging the development of new therapeutic approaches to minimize the effects of the glial scar in the context of central nervous system disease.This work had the financial support of the Portuguese Fundação para a Ciência e Tecnologia (FCT) / Ministério da Educação e Ciência (MEC) through National Funds and, when applicable, co-financed by the FEDER via the PT2020 Partnership Agreement under the 4293 Unit I&D. DR acknowledges FCT for her PhD scholarship /SFRH/BD/64079/2009). Authors thank Dr. Michiyuki Matsuda (Kyoto University, Japan) for the RhoA FRET probe with enhanced sensitivity and Dr. Yingxiao Wang (University of California, USA) for the Src FRET probe

Social moral judgment among students that consume alcohol beverages: acceptability, categories of justification and authority jurisdiction

O conhecimento sobre o uso de álcool e outras drogas entre adolescentes e jovens está bem descrito na literatura científica, mas pouco se sabe sobre o julgamento desta conduta em termos sócio-morais. Partindo desta perspectiva, este trabalho avalia como 46 estudantes de ensino médio de uma cidade do interior do estado de São Paulo, Brasil, julgam as condutas de uso de bebidas alcoólicas (incluindo o beber e dirigir), furto, agressão e uso de capacete em motocicletas. Resultados mostram que beber e dirigir, agressão e furto são os eventos considerados menos aceitáveis e que o uso de bebidas alcoólicas é classificado nos domínios convencional e de prudência.El conocimiento acerca del uso de alcohol y otras drogas entre adolescentes y jóvenes está bien relatado en la literatura científica, pero poco se sabe a respecto de cómo es juzgado en términos sociomorales este comportamiento. En esta perspectiva la presente investigación evalúa como 46 estudiantes de la enseñanza media de una ciudad del interior del estado de São Paulo, Brasil, juzgan las conductas de uso de bebidas alcohólicas (incluso beber y conducir), hurto, agresión y uso de cascos. Resultados señalan que beber y conducir, agresión y hurto son los eventos considerados menos aceptables y el uso de bebidas alcohólicas es clasificado en los dominios convencional y de prudencia.The knowledge about the use of alcohol and other drugs among adolescents and young people is well described in scientific literature, however, little is known about how this behavior is judged in socio moral terms. This research aims to assess how 46 high-school students in a city in the interior of the state of São Paulo, Brazil, judge the behavior of consumption of alcohol beverages (including drinking and driving), theft, aggression and crash helmet use. Results show that drinking and driving, aggression and theft are considered the least acceptable behaviors, and the use of alcohol beverages is classified in the conventional and prudence domains

Sentinel Node Total Tumour Load As a Predictive Factor for Non-Sentinel Node Status in Early Breast Cancer Patients – The porttle study

OSNA is a molecular assay for the detection of sentinel node metastasis. TTL emerged as a concept that seems to accurately predict the status of the NSN. Authors tried to confirm this motion. This is a retrospective and multicentric study that analyzed 2164 patients, 579 of whom had positive SN and completion AD. Logistic regression models were performed in order to identify a suitable cutoff to identify patients who benefit from AD. Univariate and multivariate regression analysis showed a relationship between TTL>30000 and the presence of NSN metastasis (OR 2.84, CI 1.99-4.08, p < 0.001). Logistic regression indicated that the cutoff of 30000 copies/μL better discriminates patients with NSN positivity and allows wide use of these criteria. This cutoff value may safely assist clinicians and patients to decide to proceed or not with an AD.info:eu-repo/semantics/publishedVersio

Endogenous production of ghrelin and beneficial effects of its exogenous administration in monocrotaline-induced pulmonary hypertension

We investigated the endogenous production of ghrelin as well as cardiac and pulmonary vascular effects of its administration in a rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH). Adult Wistar rats randomly received a subcutaneous injection of MCT (60 mg/kg) or an equal volume of vehicle. One week later, animals were randomly assigned to receive a subcutaneous injection of ghrelin (100 mug/kg bid for 2 wk) or saline. Four groups were analyzed: normal rats treated with ghrelin (n = 7), normal rats injected with saline (n = 7), MCT rats treated with ghrelin (n = 9), and MCT rats injected with saline (n = 9). At 22-25 days, right ( RV) and left ventricular (LV) pressures were measured, heart and lungs were weighted, and samples were collected for histological and molecular analysis. Endogenous production of ghrelin was almost abolished in normal rats treated with ghrelin. In MCT-treated animals, pulmonary expression of ghrelin was preserved, and RV myocardial expression was increased more than 20 times. In these animals, exogenous administration of ghrelin attenuated PH, RV hypertrophy, wall thickening of peripheral pulmonary arteries, and RV diastolic disturbances and ameliorated LV dysfunction, without affecting its endogenous production. In conclusion, decreased tissular expression of ghrelin in healthy animals but not in PH animals suggests a negative feedback in the former that is lost in the latter. A selective increase of ghrelin mRNA levels in the RV of animals with PH might indicate distinct regulation of its cardiac expression. Finally, ghrelin administration attenuated MCT-induced PH, pulmonary vascular remodeling, and RV hypertrophy, indicating that it may modulate PH

Contraceção e risco de tromboembolismo venoso: um estudo caso-controlo

Objetivos: Comparar o risco de tromboembolismo venoso (TEV) entre a 4ª geração e as gerações anteriores de contracetivos orais combinados (COC); analisar a correlação existente entre a idade, índice de massa corporal (IMC) e duração da toma do COC e o risco de TEV. Tipo de estudo: Estudo caso-controlo. Local: Centro Hospitalar doAlto-Ave, Hospital de Braga e Unidade Local de Saúde doAlto Minho. População: Foram estudadas no total 257 mulheres, das quais 122 tinham diagnóstico prévio de TEV e 135 não tinham história de TEV. Métodos: Reviram-se os registos clínicos de mulheres em seguimento por TEV, ocorrido entre 2010 e 2013. As mulheres a tomar COC aquando do evento tromboembólico eram os casos.Os controlosforam as mulheresseguidas em consulta de planeamento familiar,a tomar COC e sem antecedentes de TEV. Resultados: Os COC de 4ª geração não aumentam o risco de TEV comparativamente com as gerações anteriores (OR = 1,77; IC95 0,93-3,38; p = 0,083). Não se observou correlação entre o IMC e o risco de TEV (OR = 1,53; IC95 0,76-3,06; p = 0,234). Por outro lado, a idade (OR = 1,5; IC95 1,02-1,09; p = 0,001) e a duração da toma do COC (OR = 2,41; IC95 1,19-4,87; p = 0,014) estiveram associados a risco de TEV. Conclusões: O risco de TEV depende da idade e duração do uso do COC.Tendo em consideração as limitações do estudo, a interpretação dos resultados deve ser cautelosa, quanto à segurança dos COC de 4ª geraçã

Health promoting potential of herbal teas and tinctures from Artemisia campestris subsp maritima: from traditional remedies to prospective products

This work explored the biotechnological potential of the medicinal halophyte Artemisia campestris subsp. maritima (dune wormwood) as a source of health promoting commodities. For that purpose, infusions, decoctions and tinctures were prepared from roots and aerial-organs and evaluated for in vitro antioxidant, anti-diabetic and tyrosinase-inhibitory potential, and also for polyphenolic and mineral contents and toxicity. The dune wormwood extracts had high polyphenolic content and several phenolics were identified by ultra-high performance liquid chromatography-photodiode array-mass-spectrometry (UHPLC-PDA-MS). The main compounds were quinic, chlorogenic and caffeic acids, coumarin sulfates and dicaffeoylquinic acids; several of the identified phytoconstituents are here firstly reported in this A. campestris subspecies. Results obtained with this plant's extracts point to nutritional applications as mineral supplementary source, safe for human consumption, as suggested by the moderate to low toxicity of the extracts towards mammalian cell lines. The dune wormwood extracts had in general high antioxidant activity and also the capacity to inhibit a-glucosidase and tyrosinase. In summary, dune wormwood extracts are a significant source of polyphenolic and mineral constituents, antioxidants and a-glucosidase and tyrosinase inhibitors, and thus, relevant for different commercial segments like the pharmaceutical, cosmetic and/or food industries.FCT - Foundation for Science and Technology [CCMAR/Multi/04326/2013]; Portuguese National Budget; FCT [IF/00049/2012, SFRH/BD/94407/2013]; Research Foundation - Flanders (FWO) [12M8315N]info:eu-repo/semantics/publishedVersio

Acute changes of biventricular gene expression in volume and right ventricular pressure overload

Objective: We investigated the effects of acute volume and RV pressure overload on biventricular function and gene expression of BNP, proinflammatory cytokines (IL-6 and TNF-alpha), iNOS, growth factors (IGF-1, ppET-1), ACE and Ca2+-handling proteins (SERCA2a, phospholamban and calsequestrin). Methods: Male Wistar rats (n =45) instrumented with pressure tip micromanorneters in right (RV) and left ventricular (LV) cavities were assigned to one of three protocols: i) Acute RV pressure overload induced by pulmonary trunk banding in order to double RV peak systolic pressure, during 120 or 360 min; ii) acute volume overload induced by dextran40 infusion (5 ml/h), during 120 or 360 min; iii) Sham. RV and LV samples were collected for mRNA quantification. Results: BNP upregulation was restricted to the overloaded ventricles. TNF-alpha, IL-6, ppET-1, SERCA2a and phospholamban gene activation was higher in volume than in pressure overload. IGF-1 overexpression was similar in both types of overload, but was limited to the RV. TNF-alpha and CSQ mRNA levels were increased in the non-overloaded LV after pulmonary trunk banding. No significant changes were detected in ACE or iNOS expression. RV end-diastolic pressures positively correlated with local expression of BNP, TNF-alpha, IL-6, IGF- 1, ppET-1 and SERCA2a, while RV peak systolic pressures correlated only with local expression of IL-6, IGF-1 and ppET-1. Conclusions: Acute cardiac overload alters myocardial gene expression profile, distinctly in volume and pressure overload. These changes correlate more closely with diastolic than with systolic load. Nonetheless, gene activation is also present in the non-overloaded LV of selectively RV overloaded hearts