Effects of long-term anti-ischemic drug treatment on Na,K-ATPase isoforms in cardiomyopathic hamsters.

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.

Adenosine and Its Receptors: An Expected Tool for the Diagnosis and Treatment of Coronary Artery and Ischemic Heart Diseases.

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 A1R, A2AR, A2BR, and A3R. Among them, A2 subtypes are strongly expressed in coronary tissues, and their activation increases coronary blood flow via the production of cAMP in smooth muscle cells. A2A 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 A2A receptor subtypes. This review aims to focus on the specific exploration of the adenosine plasma level and its relationship with the A2A 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 A2A receptor agonists/antagonists are useful tools to improve the management of patients suffering from coronary artery disease.

Clinical effects of Lactobacillus strains as probiotics in the treatment of irritable bowel syndrome. Results from the LAPIBSS trial: Future objectives.

The objective of this communication is to present and analyze the recent results from the LAPIBSS study in order to improve future clinical trials on the effects of Lactobacillus strains in the treatment of irritable bowel syndrome (IBS). Using a tightly-controlled clinical trial protocol with the highest Jadad score of 5/5, the current trial aimed to demonstrate the efficacy of a 2-strain mixture of Lactobacillus acidophilus (L. acidophilus) to improve IBS symptoms. Eighty patients diagnosed with IBS according to Rome III criteria were recruited to a multicentric, double-blind, in parallel groups, placebo-controlled, randomized clinical trial. Patients were provided with a daily dose of two capsules containing either two probiotic strains (5 x 109 cfu/capsule) or placebo for 8 weeks. The primary endpoint was abdominal pain score assessed with a 100-mm visual analogue scale (VAS). Secondary endpoints included scores of bloating, flatus and rumbling assessed with a 100-mm VAS, a composite score that consisted of the sum of the 4 VAS scores, and the stool frequency and consistency assessed with the Bristol Stool Form Scale. Our study has failed to demonstrate a significant improvement of the primary endpoint of abdominal pain. Significant differences between groups were observed for flatus score at week 4 (P=0.04) and week 8 (P=0.03) and for composite score at week 8 (P=0.04). The consumption of the 2-strain mixture of L. acidophilus over 8 weeks is safe, significantly decreases flatus and composite scores. The significant effect on flatus could result from the species-specific homofermentative properties of L. acidophilus strains. The negative results on abdominal pain and the gained experience are discussed for the future clinical trials in IBS.

A 2-strain mixture of Lactobacillus acidophilus in the treatment of irritable bowel syndrome: A placebo-controlled randomized clinical trial.

BACKGROUND: In the absence of a well-established therapeutic approach, patients with irritable bowel syndrome seek alternative strategies such as probiotics. AIMS: The current trial named LAPIBSS aimed to demonstrate the efficacy of a 2-strain mixture of Lactobacillus acidophilus to improve irritable bowel syndrome symptoms. METHODS: 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. RESULTS: 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 ±â€¯2.5 vs 25.1 ±â€¯2.6, respectively; LS Means differences = 6.0 ±â€¯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. CONCLUSIONS: The consumption of the 2-strain mixture of L. acidophilus over 8 weeks is safe and decreases significantly flatus and composite scores. TRIAL REGISTRATION NUMBER: EudraCT No 2008 A00844-51.

Hyperuricemia and Hypertension, Coronary Artery Disease, Kidney Disease: From Concept to Practice.

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.