Effect of methylene blue on the genomic response to reperfusion injury induced by cardiac arrest and cardiopulmonary resuscitation in porcine brain

<p>Abstract</p> <p>Background</p> <p>Cerebral ischemia/reperfusion injury is a common secondary effect of cardiac arrest which is largely responsible for postresuscitative mortality. Therefore development of therapies which restore and protect the brain function after cardiac arrest is essential. Methylene blue (MB) has been experimentally proven neuroprotective in a porcine model of global ischemia-reperfusion in experimental cardiac arrest. However, no comprehensive analyses have been conducted at gene expression level.</p> <p>Methods</p> <p>Pigs underwent either untreated cardiac arrest (CA) or CA with subsequent cardiopulmonary resuscitation (CPR) accompanied with an infusion of saline or an infusion of saline with MB. Genome-wide transcriptional profiling using the Affymetrix porcine microarray was performed to 1) gain understanding of delayed neuronal death initiation in porcine brain during ischemia and after 30, 60 and 180 min following reperfusion, and 2) identify the mechanisms behind the neuroprotective effect of MB after ischemic injury (at 30, 60 and 180 min).</p> <p>Results</p> <p>Our results show that restoration of spontaneous circulation (ROSC) induces major transcriptional changes related to stress response, inflammation, apoptosis and even cytoprotection. In contrast, the untreated ischemic and anoxic insult affected only few genes mainly involved in intra-/extracellular ionic balance. Furthermore, our data show that the neuroprotective role of MB is diverse and fulfilled by regulation of the expression of soluble guanylate cyclase and biological processes accountable for inhibition of apoptosis, modulation of stress response, neurogenesis and neuroprotection.</p> <p>Conclusions</p> <p>Our results support that MB could be a valuable intervention and should be investigated as a therapeutic agent against neural damage associated with I/R injury induced by cardiac arrest.</p

Antihypertensive drugs and vascular health

Hypertension is a growing health burden and contributes to serious cardiovascular complications from target organ damage. The vascular system is particularly important in patients with elevated blood pressure, because vascular dysfunction is both a cause and consequence of hypertension. Hypertension is characterised by a vascular phenotype of endothelial dysfunction, vascular inflammation, arterial remodelling and increased stiffness. Of the many classes of antihypertensive drugs, those that influence vascular health have the greatest efficacy for reducing cardiovascular risk. Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and calcium channel blockers ameliorate vascular remodelling and improve endothelial function. Mineralocorticoid receptor antagonists reduce arterial stiffness, improve endothelial function and are established antihypertensive drugs, particularly in patients with resistant hypertension. Patients prone to salt-sensitivity benefit from diuretics, which influence salt physiology and balance and reduce arterial stiffness. Not all antihypertensive drugs are vasoprotective. Beta blockers, like atenolol, reduce blood pressure, but do not regress remodelling and fail to improve endothelial function. Selecting and refining the optimum drug therapy for the treatment of hypertension remains the key challenge and should prompt thought about the diverse pathophysiological mechanisms involved. This should always be in association with lifestyle modifications, which remains a cornerstone in preventing and improving vascular changes associated with high blood pressure

Dyes Depollution of Water Using Porous TiO2-Based Photocatalysts

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