OBJECTIVES To evaluate the day-night variation of acute myocardial infarction (MI) in patients with obstructive sleep apnea (OSA). BACKGROUND OSA has a high prevalence and is characterized by acute nocturnal hemodynamic and neurohormonal abnormalities that may increase the risk of MI during the night. METHODS AND RESULTS We prospectively studied 92 patients with MI, for which the time of onset of chest pain was clearly identified. The presence of OSA was determined by overnight polysomnography. For patients with and without OSA we compared the frequency of MI during different intervals of the day based on the onset time of chest pain. The groups had similar prevalence of comorbidities. MI occurred between midnight and 6am in 32% of OSA patients and 7% of non-OSA patients (P=0.01). The odds of having OSA in those patients whose MI occurred between midnight and 6am was six-fold higher than in the remaining 18 hours of the day (95% C.I: 1.3 −27.3, P=0.01). Of all patients having an MI between midnight and 6am, 91% had OSA. CONCLUSIONS The diurnal variation in the onset of MI in OSA patients is strikingly different from the diurnal variation in non-OSA patients. Patients with nocturnal onset of MI have a high likelihood of having OSA. These findings suggest that OSA may be a trigger for MI. Patients having nocturnal onset of MI should be evaluated for OSA, and future research should address the effects of OSA therapy for prevention of nocturnal cardiac events. CONDENSEND ABSTRACT We studied 92 patients with MI, for whom the time of onset of chest pain was clearly identified. MI occurred between midnight and 6am in 32% of OSA patients and 7% of non-OSA patients (P=0.01). The odds of having OSA in those patients whose MI occurred between midnight and 6am was 6 fold higher than in the remaining 18 hours of the day (95% C.I: 1.3 −27.3, P=0.01). The diurnal variation in the onset of MI in patients with OSA is strikingly different; patients with nocturnal onset of MI have a high likelihood of having OSA.

Since the early 1990s, several strains of genetically modified mice have been developed as models for experimental atherosclerosis. Among the available models, the apolipoprotein E-deficient (apoE-/-) mouse is of particular relevance because of its propensity to spontaneously develop hypercholesterolemia and atherosclerotic lesions that are similar to those found in humans, even when the mice are fed a chow diet. The main purpose of this review is to highlight the key achievements that have contributed to elucidating the mechanisms pertaining to vascular dysfunction in the apoE-/- mouse. First, we summarize lipoproteins and atherosclerosis phenotypes in the apoE-/- mouse, and then we briefly discuss controversial evidence relative to the influence of gender on the development of atherosclerosis in this murine model. Second, we discuss the main mechanisms underlying the endothelial dysfunction of conducting vessels and resistance vessels and examine how this vascular defect can be influenced by diet, aging and gender in the apoE-/- mouse.

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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BackgroundThe beverage obtained by fermentation of milk with kefir grains, a complex matrix containing acid bacteria and yeasts, has been shown to have beneficial effects in various diseases. However, its effects on hypertension and endothelial dysfunction are not yet clear. In this study, we evaluated the effects of kefir on endothelial cells and vascular responsiveness in spontaneously hypertensive rats (SHR).MethodsSHR were treated with kefir (0.3 mL/100 g body weight) for 7, 15, 30 and 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Vascular endothelial function was evaluated in aortic rings through the relaxation response to acetylcholine (ACh). The balance between reactive oxygen species (ROS) and nitric oxide (NO) synthase was evaluated through specific blockers in the ACh-induced responses and through flow cytometry in vascular tissue.ResultsSignificant effects of kefir were observed only after treatment for 60 days. The high blood pressure and tachycardia exhibited by the SHR were attenuated by approximately 15 % in the SHR-kefir group. The impaired ACh-induced relaxation of the aortic rings observed in the SHR (37 ± 4 %, compared to the Wistar rats: 74 ± 5 %), was significantly attenuated in the SHR group chronically treated with kefir (52 ± 4 %). The difference in the area under the curve between before and after the NADPH oxidase blockade or NO synthase blockade of aortic rings from SHR were of approximately +90 and −60 %, respectively, when compared with Wistar rats. In the aortic rings from the SHR-kefir group, these values were reduced to +50 and −40 %, respectively. Flow cytometric analysis of aortic endothelial cells revealed increased ROS production and decreased NO bioavailability in the SHR, which were significantly attenuated by the treatment with kefir. Scanning electronic microscopy showed vascular endothelial surface injury in SHR, which was partially protected following administration of kefir for 60 days. In addition, the recruitment of endothelial progenitor cells was decreased in the non-treated SHR and partially restored by kefir treatment.ConclusionsKefir treatment for 60 days was able to improve the endothelial function in SHR by partially restoring the ROS/NO imbalance and the endothelial architecture due to endothelial progenitor cells recruitment.

The present study was designed to investigate the role of the autonomic nervous system in experimental hypertension induced by chronic administration of N-nitro-L-arginine methyl ester (L-NAME) in the drinking water (1 mg/mL) over 6 days. L-NAME ingestion caused a large rise in resting mean arterial pressure (MAP) (175 +/- 5 mm Hg) and heart rate (HR) (440 +/- 17 beats per minute) compared to nontreated control rats (resting MAP: 112 +/- 2 mm Hg and HR: 345 +/- 8 beats per minute). Ganglionic blockade induced by trimethaphan (5 mg/kg, intravenously) caused a significantly (P < .01) greater decrease in MAP (delta -86 +/- 7 mm Hg) compared to control rats MAP (delta -44 +/- 4 mm Hg). This strongly suggests that the level of central sympathetic tone in L-NAME-treated rats is much greater than in nontreated rats. Using atenolol and atropine alone and combined, the level of resting sympathetic drive to the heart was found to be significantly increased in L-NAME-treated rats compared to control rats. However, vagal tone to the heart was found to be virtually abolished in L-NAME-treated rats compared to control rats. These results indicate that an increase in central sympathetic drive plays an important role in the hypertension induced by chronic inhibition of nitric oxide synthesis with L-NAME.

A large body of evidence indicates that the central nervous system plays an essential role in the pathogenesis of hypertension. However, in many cases the specific brain regions involved and the mechanisms by which these regions promote hypertension are not known. In recent years, research in this and other laboratories has attempted to determine the mechanisms by which neural and humoral signals arising in response to pathological conditions (often occurring in the periphery) interact with the central nervous system to produce hypertension. In this article, we illustrate the coupling of peripheral and central factors in the pathogenesis of hypertension by examining the central actions of angiotensin II and mineralocorticoids in the expression of renal hypertension and mineralocorticoid-salt hypertension, respectively. We also review recent data from this laboratory illustrating the involvement of medullary vasomotor centers in the development of neurogenic hypertension after sinoaortic deafferentation and in the maintenance of hypertension in the spontaneously hypertensive rat.

BackgroundDiabetic nephropathy (DN) is one of the major causes of end-stage renal disease in diabetic patients. Increasing evidence from studies in the rodents has suggested that this disease is associated with increased oxidative stress due to hyperglycemia. In the present study, we evaluated the renoprotective, anti-oxidative and anti-apoptotic effects of the flavonoid quercetin in C57BL/6J model of DN.MethodsDN was induced by streptozotocin (STZ, 100 mg/kg/day, for 3 days) in adult C57BL/6J mice. Six weeks later, mice were divided into the following groups: diabetic mice treated with quercetin (DQ, 10 mg/kg/day, 4 weeks), diabetic mice treated with vehicle (DV) or non-treated non-diabetic (ND) mice.ResultsQuercetin treatment caused a reduction in polyuria (~45%) and glycemia (~35%), abolished the hypertriglyceridemia and had significant effects on renal function including, decreased proteinuria and high plasma levels of uric acid, urea and creatinine, which were accompanied by beneficial effects on the structural changes of the kidney including glomerulosclerosis. Flow cytometry showed a decrease in oxidative stress and apoptosis in DN mice.ConclusionTaken together, these data show that quercetin effectively attenuated STZ-induced cytotoxicity in renal tissue. This study provides convincing experimental evidence and perspectives on the renoprotective effects of quercetin in diabetic mice and outlines a novel therapeutic strategy for this flavonoid in the treatment of DN.