Since the publication of the Framingham Heart Study, which suggested that uric acid should no longer be associated with coronary heart disease after additional adjustment for cardiovascular disease ...risk factors, the number of publications challenging this statement has dramatically increased. The aim of this paper was to review and discuss the most recent studies addressing the possible relation between sustained elevated serum uric acid levels and the onset or worsening of cardiovascular and renal diseases. Original studies involving American teenagers clearly showed that serum uric acid levels were directly correlated with systolic and diastolic pressures, which has been confirmed in adult cohorts revealing a 2.21-fold increased risk of hypertension. Several studies involving patients with coronary artery disease support a role for serum uric acid level as a marker and/or predictor for future cardiovascular mortality and long-term adverse events in patients with coronary artery disease. Retrospective analyses have shown an inverse relationship between serum uric acid levels and renal function, and even a mild hyperuricemia has been shown to be associated with chronic kidney disease in patients with type 2 diabetes. Interventional studies, although of small size, showed that uric acid (UA)-lowering therapies induced a reduction of blood pressure in teenagers and a protective effect on renal function. Taken together, these studies support a role for high serum uric acid levels (>6 mg/dL or 60 mg/L) in hypertension-associated morbidities and should bring awareness to physicians with regards to patients with chronic hyperuricemia.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Adenosine is an endogenous nucleoside which strongly impacts the cardiovascular system. Adenosine is released mostly by endothelial cells and myocytes during ischemia or hypoxia and greatly regulates ...the cardiovascular system via four specific G-protein-coupled receptors named A
R, A
R, A
R, and A
R. Among them, A
subtypes are strongly expressed in coronary tissues, and their activation increases coronary blood flow via the production of cAMP in smooth muscle cells. A
receptor modulators are an opportunity for intense research by the pharmaceutical industry to develop new cardiovascular therapies. Most innovative therapies are mediated by the modulation of adenosine release and/or the activation of the A
receptor subtypes. This review aims to focus on the specific exploration of the adenosine plasma level and its relationship with the A
receptor, which seems a promising biomarker for a diagnostic and/or a therapeutic tool for the screening and management of coronary artery disease. Finally, a recent class of selective adenosine receptor ligands has emerged, and A
receptor agonists/antagonists are useful tools to improve the management of patients suffering from coronary artery disease.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In the absence of a well-established therapeutic approach, patients with irritable bowel syndrome seek alternative strategies such as probiotics.
The current trial named LAPIBSS aimed to demonstrate ...the efficacy of a 2-strain mixture of Lactobacillus acidophilus to improve irritable bowel syndrome symptoms.
Eighty patients diagnosed for irritable bowel syndrome were recruited to a multicentre, double-blinded, in parallel groups, placebo-controlled, randomized clinical trial. Patients were provided with a daily dose of two capsules containing either probiotics (5 × 109 cfu/capsule) or placebo for 8 weeks. The primary outcome was abdominal pain score assessed with a 100-mm visual analogue scale. Secondary outcomes included scores of bloating, flatus and rumbling assessed with a 100-mm visual analogue scale, a composite score and bowel habits.
Abdominal pain score was significantly improved in both groups at weeks 4 and 8 (P < 0.0001), but no significant differences were found between groups at week 8 (19.0 ± 2.5 vs 25.1 ± 2.6, respectively; LS Means differences = 6.0 ± 3.2; P = 0.06). Significant differences between groups were observed for flatus score at week 4 (P = 0.04) and week 8 (P = 0.03) and composite score (P = 0.04) at week 8.
The consumption of the 2-strain mixture of L. acidophilus over 8 weeks is safe and decreases significantly flatus and composite scores.
EudraCT No 2008 A00844-51.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We investigated the effects of long-term anti-ischemic therapy with trimetazidine on Na,K-ATPase (NKA) activity and protein expression in cardiomyopathy. NKA isoforms in membrane fractions from ...cardiomyopathic hamsters of the BIO 14.6 strain were studied and compared with those from healthy Syrian golden hamsters (F1B). Trimetazidine was orally administered to a subset of cardiomyopathic hamsters in the early stage of active disease (30 days) until the congestive stage (350 days). In the congestive stage of cardiac failure, the cardiomyopathic hamsters displayed altered NKA activity (-55 % vs. F1B; p<0.01), which was related to a specific decrease in abundance of the membrane NKA ?1 isoform (-27 % vs. F1B). Trimetazidine partially prevented the cardiomyopathy-induced changes in NKA activity (+38 %) and ?1 membrane expression (+ 66 %) without inducing changes in the expression of the ?2 isoform or 1 isoform of NKA. Cardiac hypertrophy and remodeling were reduced after trimetazidine treatment. Additionally, the abundance of NKA ?1 in membranes was negatively correlated with the ventricular weight/body weight ratio (an index of cardiac hypertrophy) (r2 = 0.99; p<0.0015). These findings suggest that some of the cardioprotective effect of trimetazidine during long-term cardiomyopathy may be achieved via regulation of cardiac remodeling and selective modulation cardiac NKA isoforms.
Une allégation de santé dans l’UE nécessite des preuves cliniques de l’efficacité et de la sécuritéd’une supplémentation nutrititionnelle. Les probiotiques, en particulier les bactéries ...lactiques,rentrent dans ce cadre règlementaire dans lequel l’EFSA indique que les preuves obtenues chez despatients avec des troubles fonctionnels intestinaux sont transposables chez une population de sujetssains. Le protocole LAPIBSS est un essai clinique de haute qualité méthodologique évaluantl’efficacité de 2 souches de Lactobacillus acidophilus à diminuer la sévérité des symptômes dusyndrome de l’intestin irritable. Les résultats confirment la sécurité d’emploi des souches utiliséesmais ne montrent pas une diminution significative des symptômes comparée au placebo après 8semaines. L’effet global du traitement est statistiquement significatif sur le score de flatulence. Uneffet placebo et l’hétérogénéité importante de la sévérité des symptômes à l’inclusion pourraientexpliquer nos résultats. Une meilleure compréhension des effets physiologiques des probiotiqueschez l’homme pourrait améliorer le rationnel de leur utilisation en recherche clinique.
A health claim across the EU requires clinical evidence about the efficacy and safety of a nutritionalsupplementation. Probiotics, especially lactic acid bacteria, fall within this regulatory framework inwhich EFSA indicates that the evidence from patients with functional gastrointestinal disorder aretransferable in a population of healthy subjects. The LAPIBSS protocol is a high-quality clinicaltrial assessing the efficacy of 2 strains of Lactobacillus acidophilus to reduce the irritable bowelsyndrome symptoms severity. Results confirm the safety of strains used but do not show asignificant decrease of symptoms compared with placebo after 8 weeks. The overall treatment effectis statistically significant on the flatus score. A placebo effect and the considerable heterogeneity ofsymptoms severity at baseline would explain our results. A better understanding of physiologicaleffects of probiotics in human would be needed to upgrade the rationale for their use in clinicalresearch.
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