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Altogether, these observations strongly suggest an essential role of inhibition of mPTP opening in the prevention of reperfusion injury by morphine, confirming the data obtained with specific inhibitors of mPTP, such as cyclosporine A and sangliferin-A ( Hausenloy et al., 2004 ; Shanmuganathan et al., 2005 ), and its role in pre- and postconditioning cardioprotection ( Javadov et al., 2003 ; Argaud et al., 2005 ).

Because in vivo experiments demonstrating that mPTP opening was influenced by morphine and SB did not allow us to establish definitely a cause-effect relationship between the infarct-limiting effect of these drugs and the prevention of mPTP opening (indeed, any cardioprotective agent could produce the same results), we decided to investigate the effect of morphine in a model of isolated cardiomyocytes mimicking ischemia-reperfusion and measuring mPTP opening directly as a function of time. This model consists of beating adult cardiomyocytes loaded with calcein, a relevant marker to detect mPTP opening, subjected to 30 min of severe hypoxia in the presence of a metabolic blocker. The advantage of this model is to match optimally the conditions encountered during ischemia-reperfusion contrary to other protocols, such as permeabilization of the cellular membrane in the presence of high Ca 2+ concentration or exposure of cells to pro-oxidant agents, such as H 2 O 2 ( Park et al., 2006 ) or generation of ROS generated by laser illumination ( Juhaszova et al., 2004 ; Kadono et al., 2006 ). It should be noted that neither cell death nor mPTP opening could be obtained in the absence of electrical stimulation highlighting its crucial role in this model.

Our data show that reoxygenation induced the release of calcein from mitochondria according to two different kinetic profiles, with a rapid release associated with cell death (as demonstrated by propidium iodide staining), preceded or not by a slow gradual decrease in calcein fluorescence that is not detrimental to cell viability (no propidium iodide staining of the cells occurred). These two phenomena are both delayed by cyclosporine A, indicating that they are due to mPTP opening, and suggest that they correspond to the transient (reversible) and long-lasting openings (irreversible) of the pore as described previously ( UGG Ankle Boots MINI BAILEY BUTTON BLING suede Swarovski crystal b20iUMRXRk
; Sharov et al., 2007 ). Our study reveals for the first time that morphine and SB are as efficient as cyclosporine A in preventing mPTP opening. Although the drugs delayed but did not block the mPTP opening, we might question whether delaying opening is beneficial physiologically inasmuch as the opening of the pore is the injurious event. We have no answer to this question presently; however, our results clearly demonstrate that this effect is associated with a concomitant inhibition of cell death in accordance with the infarct-limiting effect of the drugs observed in vivo.

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1. Avoid commercial fried foods. With very few exceptions, these are cooked in polyunsaturated oils and contain highly damaged fats.

2. Avoid commercial salad dressings, mayonnaise and other fatty condiments. Unless otherwise noted, these are generally made with refined vegetable oils.

3. Avoid commercial baked goods. Riddled with bleached flour, refined sugar and chemical additives, these items should be avoided in general for obvious reasons. But their high PUFA content gives you yet another good reason for leaving these items on the shelf where they belong.

4. Cook and bake with butter, coconut oil , olive oil and other heat stable fats. Frankly, these taste a whole lot better than veggie oils anyway, so making this trade should be easy.

5. Go easy on the nuts. While these may be hailed as a health food by many experts, in excess nuts can easily skew your omega-3 to omega-6 ratio and push your polyunsaturated fat intake over the limit. A few servings a week is more than enough, though I personally choose to eat them even more sparingly than that. Hazelnuts and macadamia nuts are the most forgiving since these contain the lowest PUFA content (and they also taste pretty darn good!).

A Historical Perspective on Vegetable Oils

Traditional cultures simply did not liberally use polyunsaturated oils in their diets. Keep in mind that these cultures often exhibited excellent health and did not suffer from modern diseases such as diabetes, cancer and heart disease. Weston A. Price noted in his book Josef Seibel Womens Theresa SlipOn TbcVh1
< that industrial vegetable oils were one of the modern foods that brought health problems to traditional people when they started using these oils in their diets. We should take a hint from our ancestors and ditch the industrial fats. This post is part of Real Food Wednesday hosted by Kelly the Kitchen Kop.

About Elizabeth W.

Elizabeth is the founder and creative director at The Nourished Life. Her mission is to help people find a more balanced (less stressful!) approach to living a happy, healthy life.
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