The protective effect of cilostazol on isolated rabbit femoral arteries under conditions of ischemia and reperfusion: the role of the nitric oxide pathway

OBJECTIVES: The clinical significance of ischemia/reperfusion of the lower extremities demands further investigation to enable the development of more effective therapeutic alternatives. This study investigated the changes in the vascular reactivity of the rabbit femoral artery and nitric oxide metabolites under partial ischemia/ reperfusion conditions following cilostazol administration. METHODS: Ischemia was induced using infrarenal aortic clamping. The animals were randomly divided into seven groups: Control 90 minutes, Ischemia/Reperfusion 90/60 minutes, Control 120 minutes, Ischemia/Reperfusion 120/90 minutes, Cilostazol, Cilostazol before Ischemia/Reperfusion 120/90 minutes, and Ischemia 120 minutes/Cilostazol/ Reperfusion 90 minutes. Dose-response curves for sodium nitroprusside, acetylcholine, and the calcium ionophore A23187 were obtained in isolated femoral arteries. The levels of nitrites and nitrates in the plasma and skeletal muscle were determined using chemiluminescence. RESULTS: Acetylcholine-and A23187-induced relaxation was reduced in the Ischemia/Reperfusion 120/90 group, and treatment with cilostazol partially prevented this ischemia/reperfusion-induced endothelium impairment. Only cilostazol treatment increased plasma levels of nitrites and nitrates. An elevation in the levels of nitrites and nitrates was observed in muscle tissues in the Ischemia/Reperfusion 120/90, Cilostazol/Ischemia/Reperfusion, and Ischemia/ Cilostazol/Reperfusion groups. CONCLUSION: Hind limb ischemia/reperfusion yielded an impaired endothelium-dependent relaxation of the femoral artery. Furthermore, cilostazol administration prior to ischemia exerted a protective effect on endotheliumdependent vascular reactivity under ischemia/reperfusion conditions

Development of the MESH modelling system for hydrological ensemble forecasting of the Laurentian Great Lakes at the regional scale

International audienceEnvironment Canada has been developing a community environmental modelling system (Modélisation Environmentale Communautaire ? MEC), which is designed to facilitate coupling between models focusing on different components of the earth system. The ultimate objective of MEC is to use the coupled models to produce operational forecasts. MESH (MEC ? Surface and Hydrology), a configuration of MEC currently under development, is specialized for coupled land-surface and hydrological models. To determine the specific requirements for MESH, its different components were implemented on the Laurentian Great Lakes watershed, situated on the Canada-US border. This experiment showed that MESH can help us better understand the behaviour of different land-surface models, test different schemes for producing ensemble streamflow forecasts, and provide a means of sharing the data, the models and the results with collaborators and end-users. This modelling framework is at the heart of a testbed proposal for the Hydrologic Ensemble Prediction Experiment (HEPEX) which should allow us to make use of the North American Ensemble Forecasting System (NAEFS) to improve streamflow forecasts of the Great Lakes tributaries, and demonstrate how MESH can contribute to a Community Hydrologic Prediction System (CHPS)

Using the MESH modelling system for hydrological ensemble forecasting of the Laurentian Great Lakes at the regional scale

International audienceEnvironment Canada has been developing a community environmental modelling system (Modélisation Environmentale Communautaire ? MEC), which is designed to facilitate coupling between models focusing on different components of the earth system. The ultimate objective of MEC is to use the coupled models to produce operational forecasts. MESH (MEC ? Surface and Hydrology), a configuration of MEC currently under development, is specialized for coupled land-surface and hydrological models. To determine the specific requirements for MESH, its different components were implemented on the Laurentian Great Lakes watershed, situated on the Canada?U.S. border. This experiment showed that MESH can help us better understand the behaviour of different land-surface models, test different schemes for producing ensemble streamflow forecasts, and provide a means of sharing the data, the models and the results with collaborators and end-users. This modelling framework is at the heart of a testbed proposal for the Hydrologic Ensemble Prediction Experiment (HEPEX) which should allow us to make use of the North American Ensemble Forecasting System (NAEFS) to improve streamflow forecasts of the Great Lakes tributaries, and demonstrate how MESH can contribute to a Community Hydrologic Prediction System (CHPS)

Comparação do uso da pressão positiva com a fisioterapia convencional e incentivadores respiratórios após cirurgia cardíaca: revisão de literatura

Introduction: Postoperative pulmonary complications in patients undergoing cardiac surgeries are usually a clinical challenge, which can be prevented and treated with specific physical therapy techniques.However, it is not known which technique is the most effective. Objective: Literature review with theobjective of assessing the effectiveness of positive pressure (CPAP, IPPB, NIV-2P) compared to standardphysioterapy therapy and incentive spirometry on improving pulmonary function in postoperative cardiacsurgery patients. Methods: English and Portuguese studies were used as references, searching forspecific descriptors on the following data sources: BIREME, SciELO Brazil, LILACS, PUBMED, from 1985to 2010. Only randomized clinical trials were included. Results: Ten randomized control trials wereincluded in this review. About the most effective technique, two studies showed that CPAP and NIV-2Pwere more effective than standard physioterapy and incentive spirometry. In other two studies, NIV-2Pwere more effective than nasal oxygen catheter and standard physioterapy. Conclusion: There is noevidence in the literature about the most effective physiotherapy technique. Also, it is not known if theassociation of positive pressure, standard physioterapy and incentive spirometry can be more effective.It is important to emphasize that no selected study compared the three modalities of positive pressure.Introdução: No pós-operatório de cirurgia cardíaca frequentemente ocorrem complicações pulmonares, as quais podem ser prevenidas e tratadas com técnicas específicas de fisioterapia respiratória.Porém não se sabe qual a técnica mais efetiva. Objetivo: Revisão de literatura com o objetivo de verificara efetividade da pressão positiva (CPAP, VNI-2P, RPPI) comparada às técnicas de fisioterapia convencional e incentivador respiratório (IR) na recuperação da função pulmonar em pacientes no pós-operató-rio de cirurgia cardíaca. Métodos: Seleção de referências em inglês e português com descritores específicos ao tema nas seguintes fontes de dados: BIREME, SciELO Brazil, LILACS, PUBMED, de 1985 até2010. Foram incluídos apenas ensaios clínicos randomizados. Resultados: Dez ensaios clínicos randomizados foram incluídos para revisão. Em relação à superioridade de uma técnica sobre a outra, doisestudos verificaram que a modalidade CPAP e VNI-2P mostrou-se mais efetiva do que a fisioterapiaconvencional e o IR, enquanto que em dois outros estudos, demonstrou-se a superioridade da VNI-2P,em relação ao uso de cateter de oxigênio e à fisioterapia convencional. Apenas um estudo demonstroudiferença significativa ao comparar duas modalidades de pressão positiva, sendo a RPPI mais efetivaque a CPAP. Conclusão: Não há evidências acerca da melhor técnica a ser utilizada. Também não estáesclarecido se a associação da pressão positiva, fisioterapia convencional e IR poderia ser maisefetiva. Ressalta-se que nenhum dos estudos comparou simultaneamente as três modalidades depressão positiva

Mechanism of phage sensing and restriction by toxin-antitoxin-chaperone systems

\ua9 2024 The Author(s). Toxin-antitoxins (TAs) are prokaryotic two-gene systems composed of a toxin neutralized by an antitoxin. Toxin-antitoxin-chaperone (TAC) systems additionally include a SecB-like chaperone that stabilizes the antitoxin by recognizing its chaperone addiction (ChAD) element. TACs mediate antiphage defense, but the mechanisms of viral sensing and restriction are unexplored. We identify two Escherichia coli antiphage TAC systems containing host inhibition of growth (HigBA) and CmdTA TA modules, HigBAC and CmdTAC. HigBAC is triggered through recognition of the gpV major tail protein of phage λ. Chaperone HigC recognizes gpV and ChAD via analogous aromatic molecular patterns, with gpV outcompeting ChAD to trigger toxicity. For CmdTAC, the CmdT ADP-ribosyltransferase toxin modifies mRNA to halt protein synthesis and limit phage propagation. Finally, we establish the modularity of TACs by creating a hybrid broad-spectrum antiphage system combining the CmdTA TA warhead with a HigC chaperone phage sensor. Collectively, these findings reveal the potential of TAC systems in broad-spectrum antiphage defense

Vascular relaxation of canine visceral arteries after ischemia by means of supraceliac aortic cross-clamping followed by reperfusion

<p>Abstract</p> <p>Background</p> <p>The supraceliac aortic cross-clamping can be an option to save patients with hipovolemic shock due to abdominal trauma. However, this maneuver is associated with ischemia/reperfusion (I/R) injury strongly related to oxidative stress and reduction of nitric oxide bioavailability. Moreover, several studies demonstrated impairment in relaxation after I/R, but the time course of I/R necessary to induce vascular dysfunction is still controversial. We investigated whether 60 minutes of ischemia followed by 30 minutes of reperfusion do not change the relaxation of visceral arteries nor the plasma and renal levels of malondialdehyde (MDA) and nitrite plus nitrate (NOx).</p> <p>Methods</p> <p>Male mongrel dogs (n = 27) were randomly allocated in one of the three groups: sham (no clamping, n = 9), ischemia (supraceliac aortic cross-clamping for 60 minutes, n = 9), and I/R (60 minutes of ischemia followed by reperfusion for 30 minutes, n = 9). Relaxation of visceral arteries (celiac trunk, renal and superior mesenteric arteries) was studied in organ chambers. MDA and NOx concentrations were determined using a commercially available kit and an ozone-based chemiluminescence assay, respectively.</p> <p>Results</p> <p>Both acetylcholine and calcium ionophore caused relaxation in endothelium-intact rings and no statistical differences were observed among the three groups. Sodium nitroprusside promoted relaxation in endothelium-denuded rings, and there were no inter-group statistical differences. Both plasma and renal concentrations of MDA and NOx showed no significant difference among the groups.</p> <p>Conclusion</p> <p>Supraceliac aortic cross-clamping for 60 minutes alone and followed by 30 minutes of reperfusion did not impair relaxation of canine visceral arteries nor evoke biochemical alterations in plasma or renal tissue.</p

Cardiovascular Agents Affect the Tone of Pulmonary Arteries and Veins in Precision-Cut Lung Slices

Cardiovascular agents are pivotal in the therapy of heart failure. Apart from their action on ventricular contractility and systemic afterload, they affect pulmonary arteries and veins. Although these effects are crucial in heart failure with coexisting pulmonary hypertension or lung oedema, they are poorly defined, especially in pulmonary veins. Therefore, we investigated the pulmonary vascular effects of adrenoceptor agonists, vasopressin and angiotensin II in the model of precision-cut lung slices that allows simultaneous studies of pulmonary arteries and veins.Precision-cut lung slices were prepared from guinea pigs and imaged by videomicroscopy. Concentration-response curves of cardiovascular drugs were analysed in pulmonary arteries and veins.Pulmonary veins responded stronger than arteries to α(1)-agonists (contraction) and β(2)-agonists (relaxation). Notably, inhibition of β(2)-adrenoceptors unmasked the α(1)-mimetic effect of norepinephrine and epinephrine in pulmonary veins. Vasopressin and angiotensin II contracted pulmonary veins via V(1a) and AT(1) receptors, respectively, without affecting pulmonary arteries.Vasopressin and (nor)epinephrine in combination with β(2)-inhibition caused pulmonary venoconstriction. If applicable in humans, these treatments would enhance capillary hydrostatic pressures and lung oedema, suggesting their cautious use in left heart failure. Vice versa, the prevention of pulmonary venoconstriction by AT(1) receptor antagonists might contribute to their beneficial effects seen in left heart failure. Further, α(1)-mimetic agents might exacerbate pulmonary hypertension and right ventricular failure by contracting pulmonary arteries, whereas vasopressin might not