Renal macro- and microcirculation autoregulatory capacity during early sepsis and norepinephrine infusion in rats

INTRODUCTION: The relationships between systemic hemodynamics and renal blood flow and renal microcirculation are poorly known in sepsis. Norepinephrine (NE) infusion may add another level of complexity. METHODS: Ventilated and anesthetized rats were submitted to various mean arterial pressure (MAP) steps by blood removal, in presence and absence of sepsis and/or NE. Renal blood flow (RBF) and blood velocity (Vm) in renal cortical capillaries (using Sidestream Dark Field Imaging) were measured. Data were analyzed using linear mixed models enabling us to display the effects of both the considered explanatory variables and their interactions. RESULTS: Positive correlations were found between MAP and RBF. Sepsis had no independent impact on RBF whereas norepinephrine decreased RBF, regardless of the presence of sepsis. The relationship between MAP and RBF was weaker above a MAP of 100 mmHg as opposed to below 100 mmHg, with RBF displaying a relative "plateau" above this threshold. Sepsis and NE impacted carotid blood flow (CBF) differently compared to RBF, demonstrating organ specificity. A positive relationship was observed between MAP and Vm. Sepsis increased Vm while nNE decreased Vm irrespective of MAP. Sepsis was associated with an increase in serum creatinine determined at the end of the experiments, which was prevented by NE infusion. CONCLUSION: In our model, sepsis at an early phase did not impact RBF over a large range of MAP. NE elicited a renal vasoconstrictive effect. Autoregulation of RBF appeared conserved in sepsis. Conversely, sepsis was associated with "hypervelocity" of blood flow in cortical peritubular capillaries reversed by NE infusion

Redox-Sensitive Induction of Src/PI3-kinase/Akt and MAPKs Pathways Activate eNOS in Response to EPA:DHA 6:1

AIMS: Omega-3 fatty acid products containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have vasoprotective effects, in part, by stimulating the endothelial formation of nitric oxide (NO). This study determined the role of the EPA:DHA ratio and amount, and characterized the mechanism leading to endothelial NO synthase (eNOS) activation. METHODS AND RESULTS: EPA:DHA 6ratio1 and 9ratio1 caused significantly greater endothelium-dependent relaxations in porcine coronary artery rings than EPA:DHA 3ratio1, 1ratio1, 1ratio3, 1ratio6, 1ratio9, EPA and DHA alone, and EPA:DHA 6ratio1 with a reduced EPA + DHA amount, which were inhibited by an eNOS inhibitor. Relaxations to EPA:DHA 6ratio1 were insensitive to cyclooxygenase inhibition, and reduced by inhibitors of either oxidative stress, Src kinase, PI3-kinase, p38 MAPK, MEK, or JNK. EPA:DHA 6ratio1 induced phosphorylation of Src, Akt, p38 MAPK, ERK, JNK and eNOS; these effects were inhibited by MnTMPyP. EPA:DHA 6ratio1 induced the endothelial formation of ROS in coronary artery sections as assessed by dihydroethidium, and of superoxide anions and hydrogen peroxide in cultured endothelial cells as assessed by electron spin resonance with the spin probe CMH, and the Amplex Red based assay, respectively. CONCLUSION: Omega-3 fatty acids cause endothelium-dependent NO-mediated relaxations in coronary artery rings, which are dependent on the EPA:DHA ratio and amount, and involve an intracellular activation of the redox-sensitive PI3-kinase/Akt and MAPKs pathways to activate eNOS

Effects of hydrogen sulfide on hemodynamics, inflammatory response and oxidative stress during resuscitated hemorrhagic shock in rats

Introduction Hydrogen sulfide (H2S) has been shown to improve survival in rodent models of lethal hemorrhage. Conversely, other authors have reported that inhibition of endogenous H2S production improves hemodynamics and reduces organ injury after hemorrhagic shock. Since all of these data originate from unresuscitated models and/or the use of a pre-treatment design, we therefore tested the hypothesis that the H2S donor, sodium hydrosulfide (NaHS), may improve hemodynamics in resuscitated hemorrhagic shock and attenuate oxidative and nitrosative stresses. Methods Thirty-two rats were mechanically ventilated and instrumented to measure mean arterial pressure (MAP) and carotid blood flow (CBF). Animals were bled during 60 minutes in order to maintain MAP at 40 ± 2 mm Hg. Ten minutes prior to retransfusion of shed blood, rats randomly received either an intravenous bolus of NaHS (0.2 mg/kg) or vehicle (0.9% NaCl). At the end of the experiment (T = 300 minutes), blood, aorta and heart were harvested for Western blot (inductible Nitric Oxyde Synthase (iNOS), Nuclear factor-κB (NF-κB), phosphorylated Inhibitor κB (P-IκB), Inter-Cellular Adhesion Molecule (I-CAM), Heme oxygenase 1(HO-1), Heme oxygenase 2(HO-2), as well as nuclear respiratory factor 2 (Nrf2)). Nitric oxide (NO) and superoxide anion (O2 -) were also measured by electron paramagnetic resonance. Results At the end of the experiment, control rats exhibited a decrease in MAP which was attenuated by NaHS (65 ± 32 versus 101 ± 17 mmHg, P < 0.05). CBF was better maintained in NaHS-treated rats (1.9 ± 1.6 versus 4.4 ± 1.9 ml/minute P < 0.05). NaHS significantly limited shock-induced metabolic acidosis. NaHS also prevented iNOS expression and NO production in the heart and aorta while significantly reducing NF-kB, P-IκB and I-CAM in the aorta. Compared to the control group, NaHS significantly increased Nrf2, HO-1 and HO-2 and limited O2 - release in both aorta and heart (P < 0.05). Conclusions NaHS is protective against the effects of ischemia reperfusion induced by controlled hemorrhage in rats. NaHS also improves hemodynamics in the early resuscitation phase after hemorrhagic shock, most likely as a result of attenuated oxidative stress. The use of NaHS hence appears promising in limiting the consequences of ischemia reperfusion (IR)

Aurore Koechlin, La norme gynécologique. Ce que la médecine fait au corps des femmes

À la fois spécifique à un genre et indépendant de tout symptôme pour se perpétuer, le suivi gynécologique paraît évident tant il est fréquent. En effet, l’étude Fecond 2010 montre que « 90 % des femmes interrogées déclarent avoir un·e “gynécologue habituel·le” » ou un·e médecin qui les « suit habituellement pour la contraception ou d’autres raisons gynécologiques » ». C’est à partir de ce constat qu’Aurore Koechlin débute sa réflexion autour de la prétendue naturalité de ce suivi. Afin de ré..

Etude des mécanismes d'ischémie/reperfusion et des états de choc (conséquences hémodynamiques, inflammatoires et métaboliques dans des modèles expérimentaux de choc induisant une ischémie/reperfusionévaluation et réduction des risques)

L objectif de ce travailest l étude des mécanismes d ischémie/reperfusion et des états de choc ainsi que les conséquences sur les effets hémodynamiques in vivo et ex vivo, les réponses inflammatoires, la production de radicaux libres, la fonction rénale et la modulation de la respiration mitochondrialedans des modèles expérimentaux de choc induisant une ischémie/reperfusion. Ce travail s inscrit dans la suite des études réalisées dans le laboratoire et vise plus particulièrement à préciser les mécanismes mis en jeu tant sur le plan hémodynamique que sur le plan métabolique. Deux modèles expérimentaux (choc hémorragique et choc septique) ont été mis au point dans le laboratoire pour étudier cette approche thérapeutique et mécanistique. L exploration de la réactivité vasculaire in vivo repose sur les techniques hémodynamiques standards (pression artérielle moyenne, fréquence cardiaque, débits régionaux) alors que l évolution microcirculatoire est évaluée par vidéomicroscopie par lumière polarisée (technique SDF - Sidestream Dark Field). L exploration de la réponse inflammatoire est réalisée par technique de western-blot, la fonction mitochondriale par oxygraphie et la production de radicaux libres par résonance paramagnétique électronique. Suite à un choc hémorragique retransfusé et contrôlé chez le rat, le NaHS, donneur d hydrogène sulfuré (H2S) limite la diminution de la pression artérielle moyenne après la reperfusion. Il se comporte comme un modulateur de l inflammation et du stress oxydant dans les lésions d ischémie/reperfusion. Il présente une action protectrice à long terme qui est probablement liée à sa capacité à moduler la fonction mitochondriale et la respiration cellulaire. Cependant, l'inflammation et le stress oxydant semblent jouer un rôle majeur dans l'insuffisance rénale aiguë survenant au cours des états de choc. Les effets bénéfiques sur la fonction rénale sont indépendants des effets hémodynamiques macro et microcirculatoires et passent probablement par une modulation de la réponse inflammatoire post ischémie/reperfusion. Lorsque le rein est agressé, après un choc hémorragique ou en cas de sepsis, une modification de la réponse rénale aux stimuli vasoconstricteurs et vasodilatateurs, une altération de l autorégulation rénale avec perte du maintien du débit sanguin rénal lors des variations de pression artérielle ont été observées. Notre modèle montre que lors de la phase précoce, le sepsis n a pas d impact particulier sur le rein alors que le débit rénal varie en réponse aux variations de pression artérielle, incluant le phénomène d autorégulation . D un point de vue microcirculatoire, le sepsis est associé très rapidement à une augmentation du flux sanguin dans les capillaires corticaux péritubulaires et une dysfonction rénale limitée par la perfusion de noradrénaline.The objective of this work is to study the mechanisms of ischemia/reperfusion and shock and the consequences of the hemodynamic effects in vivo and ex vivo inflammatory responses, the production of free radicals, renal function and the regulation of mitochondrial respiration in experimental models of shock. Following hemorragic shock and reinfused controlled rats, NaHS, donor of hydrogen sulfide (H2S) limit the decrease in mean arterial pressure after reperfusion. It presents a long-term protective effect wich is probably linked to its ability to modulate mitochondrial function and cellular respiration. It acts as a modulator of inflammation and oxidative stress in the ischemia/reperfusion. Inflammation and oxidative stress appears to play a major role in acute renal failure occuring during shock. Beneficial effects on renal function are independent of macro and microvascular hemodynamic effects and probably spend a modulation of the inflammatory response post ischemia/reperfusion. When the kidney is attacked after hemorrhagic shock or sepsis, changes in the renal response to vasoconstrictor and vasodilator stimuli, impaired renal autoregulation with the loss of maintenance of renal blood blood flow during variations in blood were been observed. Our model shows that sepsis is associated with a very rapid increase in blood flow in cortical peritubular capillaries and renal dysfunction limited by infusion of noradrenaline.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

The Network of Innovation in Biodiversity Medications-RedesFito: the look of popular education: Case study of Local Ecoproductive Arrangements in the medicinal plants production chain

Made available in DSpace on 2020-02-17T11:44:31Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) melanie_et_all.pdf: 288949 bytes, checksum: a66b2baa392cded484148c1c3c76fe4c (MD5) Previous issue date: 2019Universidade Paris 8. Departamento de Ciências da Educação. Saint-Denis, França.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Centro de Inovação em Biodiversidade e Saúde. Rio de Janeiro, RJ, Brasil.O desempenho das RedesFito quanto à inclusão social destaca os indicadores de Educação Popular e a análise do diálogo entre o conhecimento popular e o conhecimento acadêmico. Neste contexto, este trabalho teve por objetivo analisar as RedesFito sob o olhar da Educação Popular em Arranjos Ecoprodutivos Locais/AELs na Cadeia Produtiva de Plantas Medicinais nos AEL/Itapeva-Itaberá/SP e AEL/Prado/BA. Discutiu-se  as RedesFito no olhar da emancipação e poder de agir dos agricultores locais, que participaram da pesquisa de campo, durante a aplicação da Metodologia da Pesquisa-Ação-participante, com coleta de dados através de entrevistas não diretivas aplicadas aos agricultores, pesquisadores, atores sociais, gestores e representantes de instituições, organizações sociais e empresas. Concluiu-se que a construção dialógica dos saberes, a emancipação, o poder de agir dos agricultores e a cooperação representam os três pilares para a Educação Popular na rede pesquisada. Entretanto, o desafio é a integração dos agricultores produtores de plantas medicinais, como parceiros completos das RedesFito, bem como da Fiocruz, das instituições e empresas públicas/privadas, de governos locais, entre outros. O uso da ferramenta "Observatório Socianalítico" permitiu avaliar os avanços para o conhecimento dos AELs e a criação de parcerias.The performance of RedesFito regarding social inclusion highlights the indicators of Popular Education and the analysis of the dialogue between popular knowledge and academic knowledge. In this context, this work aimed to analyze the RedesFito under the perspective of Popular Education in Local Ecoproductive Arrangements/AELs in the Production Chain of Medicinal Plants in AEL/Itapeva-Itaberá/SP and AEL/Prado/BA. RedesFito was discussed in terms of the emancipation and power of action of local farmers, who participated in the field research, during the application of the Action- Participant Research Methodology, with data collection through non-directive interviews applied to farmers, researchers, social actors, managers and representatives of institutions, social organizations and companies. It was concluded that the dialogic construction of knowledge, emancipation, the power of action of farmers and cooperation represent the three pillars for Popular Education in the researched network. However, the challenge is the integration of farmers producing medicinal plants as complete partners of RedesFito, as well as Fiocruz, public / private institutions and companies, local governments, among others. The use of the "Socianalitic Observatory" tool made it possible to evaluate advances in the knowledge of AELs and the creation of partnerships

Docosahexaenoic acid, but not eicosapentaenoic acid, improves septic shock-induced arterial dysfunction in rats

International audienc

EPA:DHA 6∶1 induces the phosphorylation of Src, Akt and eNOS in porcine coronary artery endothelial cells in a time- and EPA:DHA ratio-dependent manner.

<p>(A) Cultured endothelial cells were exposed to EPA:DHA 6∶1 (0.4% v/v) for the indicated times at 37°C. (B) Cultured endothelial cells were exposed to products with either an EPA:DHA ratio of 6∶1 or 1∶1 at the concentration of 0.4% (v/v) for 30 min at 37°C. Representative immunoblots of p-Src, p-Akt and p-eNOS proteins as assessed by Western blot analysis (top), and corresponding cumulative data (bottom). Results are shown as means ± SEM of 3 different experiments. *<i>P</i><0.05 versus control,^#<i>P</i><0.05 versus EPA:DHA 6∶1 treatment.</p

EPA:DHA 6∶1 induces the formation of ROS involving superoxide anions and hydrogen peroxide in endothelial cells.

<p>A) The EPA:DHA 6∶1-induced oxidative stress was assessed in coronary artery sections with endothelium using the redox-sensitive probe dihydroethidium (2.5 µM for 30 min). The EPA:DHA 6∶1-induced formation of B) superoxide anions in cultured endothelial cells was assessed using electron spin resonance and the cell permeable spin probe CMH, and C) of hydrogen peroxide using the Amplex Red assay. B) Top: Representative original traces showing the three signals used for quantification (vertical bars). Bottom: Corresponding cumulative data. Means of the amplitude (height) of the three signals was measured for each spectrum. Results are shown as means ± SEM of 3-5 different experiments. *<i>P</i><0.05 versus control,^#<i>P</i><0.05 versus EPA: DHA 6∶1 treatment.</p