Background. Alzheimer’s disease (AD) is the most common cause of dementia in elderly patients. Recently, several studies have shown that inflammation and oxidative stress precede the cardinal neuropathological manifestations of AD. In view of the proven antioxidant effects of probiotics, we proposed that continuous dietary supplementation with milk fermented with kefir grains might improve cognitive and metabolic and/or cellular disorders in the AD patients. Methods. This study was designed as an uncontrolled clinical investigation to test the effects of probiotic-fermented milk supplementation (2 mL/kg/daily) for 90 days in AD patients exhibiting cognitive deficit. Cognitive assessment, cytokine expression, systemic oxidative stress levels, and blood cell damage biomarkers were evaluated before (T0) and after (T90) kefir synbiotic supplementation. Results. When the patients were challenged to solve 8 classical tests, the majority exhibit a marked improvement in memory, visual-spatial/abstraction abilities, and executive/language functions. At the end of the treatment, the cytometric analysis showed an absolute/relative decrease in several cytokine markers of inflammation and oxidative stress markers (⋅O2–, H2O2, and ONOO−, ~30%) accompanied by an increase in NO bioavailability (100%). In agreement with the above findings by using the same technique, we observed in a similar magnitude an improvement of serum protein oxidation, mitochondrial dysfunction, DNA damage/repair, and apoptosis. Conclusion. In conclusion, we demonstrated that kefir improves cognitive deficits, which seems to be linked with three important factors of the AD—systemic inflammation, oxidative stress, and blood cell damage—and may be a promising adjuvant therapy against the AD progression.

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1 This study investigated several mechanisms involved in the vasorelaxant effects of (À)-epigallocatechin-3-gallate (EGCG). 2 EGCG (1 mM-1 mM) concentration dependently relaxed, after a transient increase in tension, contractions induced by noradrenaline (NA, 1 mM), high extracellular KCl (60 mM), or phorbol 12-myristate 13-acetate (PMA, 1 mM) in intact rat aortic rings. In a Ca 2 þ -free solution, EGCG (1 mM-1 mM) relaxed 1 mM PMA-induced contractions, without previous transient contraction. However, EGCG (1 mM-1 mM) did not affect the 1 mM okadaic acid-induced contractions. Removal of endothelium and/or pretreatment with glibenclamide (10 mM), tetraethylammonium (2 mM) or charybdotoxin (100 nM) plus apamin (500 nM) did not modify the vasorelaxant effects of EGCG. In addition, EGCG noncompetitively antagonized the contractions induced by NA (in 1.5 mM Ca 2 þ -containing solution) and Ca 2 þ (in depolarizing Ca 2 þ -free high KCl 60 mM solution). 3 In rat aortic smooth muscle cells (RASMC), EGCG (100 mM) reduced increases in cytosolic free Ca 2 þ concentration ([Ca 2 þ ] i ) induced by angiotensin II (ANG II, 100 nM) and KCl (60 mM) in 1.5 mM CaCl 2 -containing solution and by ANG II (100 nM) in the absence of extracellular Ca 2 þ . 4 In RASMC, EGCG (100 mM) did not modify basal generation of cAMP or cGMP, but significantly reversed the inhibitory effects of NA (1 mM) and high KCl (60 mM) on cAMP and cGMP production. 5 EGCG inhibited the enzymatic activity of all the cyclic nucleotide PDE isoenzymes present in vascular tissue, being more effective on PDE2 (IC 50 B17) and on PDE1 (IC 50 B25). 6 Our results suggest that the vasorelaxant effects of EGCG in rat aorta are mediated, at least in part, by an inhibition of PDE activity, and the subsequent increase in cyclic nucleotide levels in RASMC, which, in turn, can reduce agonist-or high KCl concentration-induced increases in [Ca 2 þ ] i .

The gut microbiota, the ecosystem formed by a wide symbiotic community of nonpathogenic microorganisms that are present in the distal part of the human gut, plays a prominent role in the normal physiology of the organism. The gut microbiota’s imbalance, gut dysbiosis, is directly related to the origin of various processes of acute or chronic dysfunction in the host. Therefore, the ability to intervene in the gut microbiota is now emerging as a possible tactic for therapeutic intervention in various diseases. From this perspective, evidence is growing that a functional dietary intervention with probiotics, which maintain or restore beneficial bacteria of the digestive tract, represents a promising therapeutic strategy for interventions in cardiovascular diseases and also reduces the risk of their occurrence. In the present work, we review the importance of maintaining the balance of the intestinal microbiota to prevent or combat such processes as arterial hypertension or endothelial dysfunction, which underlie many cardiovascular disorders. We also review how the consumption of probiotics can improve autonomic control of cardiovascular function and provide beneficial effects in patients with heart failure. Among the known effects of probiotics is their ability to decrease the generation of reactive oxygen species and, therefore, reduce oxidative stress. Therefore, in this review, we specifically focus on this antioxidant capacity and its relationship with the beneficial cardiovascular effects described for probiotics.

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Although the natural polyphenol resveratrol posses a direct vasorelaxant effect, its effects on cytoplasmic Ca 2+ concentration ( ] i that was reduced by preincubation with trans-resveratrol or cis-resveratrol. When the isomers were applied during the plateau phase of the agonist-or the high-K + -induced response, a biphasic change in [Ca 2+ ] i was observed: a transient reduction of the plateau (b 5 min) followed by an increase (N 10 min). Finally, trans-resveratrol and cis-resveratrol inhibited voltage-dependent L-type Ca 2+ currents (I Ca(L) ). In conclusion, resveratrol isomers exert a dual effect on [Ca 2+ ] i handling in A7r5 myocytes: 1) a blockade of I Ca(L) and 2) an increase in [Ca 2+ ] i by depletion of intracellular Ca 2+ stores (which interferes with the agonist-induced release of intracellular Ca 2+ ) and influx of Ca 2+, mainly due to activation of capacitative Ca 2+ entry, although other Ca 2+ -permeable channels are also involved. Taken together, these effects may explain, in part, the endotheliumindependent vasorelaxant effects of resveratrol in rat aorta.

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