Dysbiotic microbiota contributes to the extent of acute myocardial infarction in rats.

Increasing evidence suggests that the intestinal microbiota composition could play a role in specific pathologies such as hypertension, obesity and diabetes. This study aims to demonstrate that the intestinal microbiota modulated by a diet creating dysbiosis increased the size of the myocardial infarction and that probiotics could attenuate this effect. To do this, microbiota transplants from rats fed a dysbiotic or non-dysbiotic diet in the presence or absence of probiotics were performed for 10 days on rats whose microbiota had been previously suppressed by antibiotic therapy.

Targeting Uric Acid Prevents Brain Injury and Anxiety in a Rat Model of Hemorrhagic Shock.

Secondary brain injury following hemorrhagic shock (HS) is a frequent complication in patients, even in the absence of direct brain trauma, leading to behavioral changes and more specifically anxiety and depression. Despite preclinical studies showing inflammation and apoptosis in the brain after HS, none have addressed the impact of circulating mediators. Our group demonstrated an increased uric acid (UA) circulation in rats following HS.

Impact of uric acid on liver injury and intestinal permeability following resuscitated hemorrhagic shock in rats.

Background: Multiorgan failure is a consequence of severe ischemia-reperfusion injury after traumatic hemorrhagic shock (HS), a major cause of mortality in trauma patients. Circulating uric acid (UA), released from cell lysis, is known to activate proinflammatory and proapoptotic pathways and has been associated with poor clinical outcomes among critically ill patients. Our group has recently shown a mediator role for UA in kidney and lung injury, but its role in liver and enteric damage after HS remains undefined.

Bifidobacterium longum R0175 attenuates post-myocardial infarction depressive-like behaviour in rats.

Caspase-3 activation in the limbic system and depressive-like symptoms are observed after an acute myocardial infarction (MI) and studies suggest that inflammation may play a significant role. Combined treatment with the probiotic strains Bifidobacterium longum and Lactobacillus helveticus in rats has been shown to attenuate caspase-3 activation and depressive-like behaviour together with a reduction in pro-inflammatory cytokines. The present study was designed to determine the respective contribution of these two strains on caspase-3 activity in the limbic system and on depressive-like behaviour.

Caspase-(8/3) activation and organ inflammation in a rat model of resuscitated hemorrhagic shock: A role for uric acid.

Background: Multiple organ failure can develop after hemorrhagic shock (HS). Uric acid (UA) is released from dying cells and can be proinflammatory. We hypothesized that UA could be an alternative mediator of organ apoptosis and inflammation after HS.

Cognitive Deficits Following a Post-Myocardial Infarct in the Rat Are Blocked by the Serotonin-Norepinephrine Reuptake Inhibitor Desvenlafaxine.

Myocardial infarction (MI) in animal models induces cognitive deficits as well as the activation of caspase in the limbic system; both can be blocked by 2 weeks of treatment following MI using tricyclic antidepressants or selective serotonin uptake blockers. Here we used three different treatment schedules to test the short- and long-term effects of the combined serotonin-norepinephrine reuptake inhibitor desvenlafaxine on post-MI-associated cognitive deficits and caspase activation. MI was induced in 39 young adult rats, and 39 rats served as sham-operated controls.

Fluid sparing and norepinephrine use in a rat model of resuscitated haemorrhagic shock: end-organ impact.

Background: Haemostasis and correction of hypovolemia are the pillars of early haemorrhage shock (HS) management. Vasopressors, which are not recommended as first-line therapy, are an alternative to aggressive fluid resuscitation, but data informing the risks and benefits of vasopressor therapy as fluid-sparing strategy is lacking. We aimed to study its impact on end organs, in the setting of a haemodynamic response to the initial volume resuscitation.

Cardioprotective Effects of Omega-3 Polyunsaturated Fatty Acids: Dichotomy between Experimental and Clinical Studies.

The high-fat diet of North Americans has a major impact on cardiovascular disease occurrence. Notably, fatty acids have been identified as important factors that could modulate such diseases, especially myocardial infarction (MI). Experimentally, omega-3 polyunsaturated fatty acids (PUFA) have demonstrated positive effects on cardiovascular disorders and have also shown cardioprotection by decreasing MI size.

A high omega-3 fatty acid diet rapidly changes the lipid composition of cardiac tissue and results in cardioprotection.

The present study was designed to ascertain the effects of 3 diets with different omega-3/6 fatty acid ratios on infarct size and the modifications that these diets induce in the lipid composition of cardiac tissue. Sprague-Dawley rats were fed omega-3/6 fatty acid diets with 1:1, 1:5, or 1:20 ratios for at least 10 days, followed by occlusion of the left anterior descending artery for 40 min and 24 h of reperfusion. Infarct size was significantly smaller in the 1:1 group than in the other groups.

Comparison of the effects of EPA and DHA alone or in combination in a murine model of myocardial infarction.

The aim of this project was to investigate the impact of two dietary omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), alone or in combination, on infarct size. Adult, male Sprague-Dawley rats were fed for 14 days with different omega-3 diets. The animals were subjected to ischemia for 40min followed by reperfusion.

Linoleic acid attenuates cardioprotection induced by resolvin D1.

We previously observed that resolvin D1 (RvD1), a metabolite of the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid, reduces infarct size by a mechanism involving the PI3-K/Akt pathway. In parallel, the beneficial effect of a high omega-3 PUFA diet on infarct size can be attenuated by increased omega-6 PUFA consumption. The present study was designed to determine if augmented linoleic acid (LA), an omega-6 PUFA administered at the same time, attenuates the cardioprotective action of RvD1.

Caspase-3 Activity in the Rat Amygdala Measured by Spectrofluorometry After Myocardial Infarction.

Myocardial infarction (MI) has dramatic mid- and long-term consequences at the physiological and behavioral levels, but the mechanisms involved are still unclear. Our laboratory has developed a rat model of post-MI syndrome that displays impaired cardiac functions, neuronal loss in the limbic system, cognitive deficits and behavioral signs of depression. At the neuronal level, caspase-3 activation mediates post-MI apoptosis in different limbic regions, such as the amygdala - peaking at 3 days post-MI.

Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin-GUCY2C Paracrine Signaling Axis.

Obesity is a well-known risk factor for colorectal cancer but precisely how it influences risks of malignancy remains unclear. During colon cancer development in humans or animals, attenuation of the colonic cell surface receptor guanylyl cyclase C (GUCY2C) that occurs due to loss of its paracrine hormone ligand guanylin contributes universally to malignant progression. In this study, we explored a link between obesity and GUCY2C silencing in colorectal cancer.

Metabolites derived from omega-3 polyunsaturated fatty acids are important for cardioprotection.

Although controversial, some data suggest that omega-3 polyunsaturated fatty acids (PUFA) are beneficial to cardiovascular diseases, and could reduce infarct size. In parallel, we have reported that the administration of Resolvin D1 (RvD1), a metabolite of docosahexaenoic acid, an omega-3 PUFA, can reduce infarct size. The present study was designed to determine if the inhibition of two important enzymes involved in the formation of RvD1 from omega-3 PUFA could reduce the cardioprotective effect of omega-3 PUFA.

Resolvin D1 Reduces Infarct Size Through a Phosphoinositide 3-Kinase/Protein Kinase B Mechanism.

This study was designed to determine if Resolvin D1 (RvD1), a pro-resolution metabolite of the omega-3 polyunsaturated fatty acid docosahexaenoic acid, could decrease myocardial infarct size with delivered at the onset of ischemia. Male Sprague Dawley rats underwent 40 minutes of myocardial ischemia followed by reperfusion. These animals received 1 intraventricular injection of RvD1 (0.

Desvenlafaxine reduces apoptosis in amygdala after myocardial infarction.

This study was designed to determine if desvenlafaxine (DV), a serotonin-norepinephrine reuptake inhibitor, can attenuate apoptosis observed in the limbic system after myocardial infarction (MI). MI was induced in rats by occlusion of the left descending artery for 40 min followed by reperfusion. Another group of sham (control) rats was similarly manipulated, but without occlusion.

Resolvin D1, a metabolite of omega-3 polyunsaturated fatty acid, decreases post-myocardial infarct depression.

We hypothesized that inflammation induced by myocardial ischemia plays a central role in depression-like behavior after myocardial infarction (MI). Several experimental approaches that reduce inflammation also result in attenuation of depressive symptoms. We have demonstrated that Resolvin D1 (RvD1), a metabolite of omega-3 polyunsaturated fatty acids (PUFA) derived from docosahexaenoic acid, diminishes infarct size and neutrophil accumulation in the ischemic myocardium.

Mechanisms of Weight Regain following Weight Loss.

Obesity is a world-wide pandemic and its incidence is on the rise along with associated comorbidities. Currently, there are few effective therapies to combat obesity. The use of lifestyle modification therapy, namely, improvements in diet and exercise, is preferable over bariatric surgery or pharmacotherapy due to surgical risks and issues with drug efficacy and safety.

Intestinal GUCY2C prevents TGF-β secretion coordinating desmoplasia and hyperproliferation in colorectal cancer.

Tumorigenesis is a multistep process that reflects intimate reciprocal interactions between epithelia and underlying stroma. However, tumor-initiating mechanisms coordinating transformation of both epithelial and stromal components are not defined. In humans and mice, initiation of colorectal cancer is universally associated with loss of guanylin and uroguanylin, the endogenous ligands for the tumor suppressor guanylyl cyclase C (GUCY2C), disrupting a network of homeostatic mechanisms along the crypt-surface axis.

New advances in models and strategies for developing anti-obesity drugs.

Introduction: Obesity is a worldwide pandemic. Obesity-related health and economic costs are staggering. Existing strategies to combat obesity through lifestyle improvements and medical intervention have had limited success.

GUCY2C: at the intersection of obesity and cancer.

Guanylyl cyclase C (GUCY2C) has canonical centrality in defense of key intestinal homeostatic mechanisms, encompassing fluid and electrolyte balance, epithelial dynamics, antitumorigenesis, and intestinal barrier function. Recent discoveries expand the homeostatic role of GUCY2C to reveal a novel gut-brain endocrine axis regulating appetite, anchored by hypothalamic GUCY2C which is responsive to intestine-derived uroguanylin. Thus, GUCY2C may represent a new target for anti-obesity pharmacotherapy.

Obesity pharmacotherapy: what is next?

The increase in obesity in the Unites States and around the world in the last decade is overwhelming. The number of overweight adults in the world surpassed 1 billion in 2008. Health hazards associated with obesity are serious and include heart disease, sleep apnea, diabetes, and cancer.

Attenuation of post-myocardial infarction depression in rats by n-3 fatty acids or probiotics starting after the onset of reperfusion.

Proinflammatory cytokines play a central role in depression-like behaviour and apoptosis in the limbic system after myocardial infarction (MI). A PUFA n-3 diet or the combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 probiotics, when given before the ischaemic period, reduce circulating proinflammatory cytokines as well as apoptosis in the limbic system. The present study was designed to determine if the same nutritional interventions maintain their beneficial effects when started after the onset of the reperfusion period and attenuate depression-like behaviour observed after MI.

Present condition analysis of physician assistant in Korea.

This study intended to identify the need for the legalization and development of a systematic program for physician assistants (PAs) by understanding the actual state of PA operation in hospitals. In 114 hospitals assigned as resident training hospitals for surgery, a survey was conducted on the personnel working as PAs in those hospitals; the survey included general personal information, working conditions, training time, and satisfaction. A total of 192 PAs in surgery at 35 hospitals responded to the survey.