The paramount importance of a healthy diet in the prevention of type 2 diabetes is now well recognized. Blueberries (BBs) have been described as attractive functional fruits for this purpose. This study aimed to elucidate the cellular and molecular mechanisms pertaining to the protective impact of blueberry juice (BJ) on prediabetes. Using a hypercaloric diet-induced prediabetic rat model, we evaluated the effects of BJ on glucose, insulin, and lipid profiles; gut microbiota composition; intestinal barrier integrity; and metabolic endotoxemia, as well as on hepatic metabolic surrogates, including several related to mitochondria bioenergetics. BJ supplementation for 14 weeks counteracted diet-evoked metabolic deregulation, improving glucose tolerance, insulin sensitivity, and hypertriglyceridemia, along with systemic and hepatic antioxidant properties, without a significant impact on the gut microbiota composition and related mechanisms. In addition, BJ treatment effectively alleviated hepatic steatosis and mitochondrial dysfunction observed in the prediabetic animals, as suggested by the amelioration of bioenergetics parameters and key targets of inflammation, insulin signaling, ketogenesis, and fatty acids oxidation. In conclusion, the beneficial metabolic impact of BJ in prediabetes may be mainly explained by the rescue of hepatic mitochondrial bioenergetics. These findings pave the way to support the use of BJ in prediabetes to prevent diabetes and its complications.

The mechanisms by which guanosine 3',5'-cyclic monophosphate (cGMP) modulates the contraction induced by ATP were investigated in small mesenteric resistance arteries of the rat. The nitric oxide donors 3-morpholinosydnonimine (SIN-1, 10 microM) and sodium nitroprusside (SNP, 10 microM) increased cGMP but not adenosine 3',5'-cyclic monophosphate (cAMP) content of the tissue. SIN-1, SNP, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 100 microM) inhibited the myosin light chain phosphorylation and the contractile response to ATP. Both effects were completely reversed by the selective inhibitor of cGMP protein kinase, Rp-8-bromoguanosine 3',5'-cyclic monophosphorothioate (30 microM). The sensitivity to Ca2+ of arteries permeabilized with Staphylococcus aureus alpha-toxin (4,000 hemolytic units/ml) was not affected by 8-BrcGMP. The two nitric oxide donors and 8-BrcGMP decreased the rise in intracellular Ca2+ induced by ATP. The vasodilator agents abolished the contractile response to the exogenous calcium in vessels that were exposed to 3 mM ATP after depletion of intracellular Ca2+ stores. Thapsigargin (1 microM), an inhibitor of the sarcoplasmic reticulum Ca(2+)-adenosinetriphosphatase, reversed the inhibitory effect of the vasodilator agents when the contraction induced by ATP was elicited in the presence of the Ca2+ entry blocker nitrendipine (1 microM) or in Ca(2+)-free medium. These results show that cGMP inhibits ATP-induced contraction by decreasing intracellular Ca2+ concentration in small resistance arteries. They indicate that this effect results from decreased Ca2+ influx and enhanced Ca2+ sequestration through a thapsigargin-sensitive pump via activation of a cGMP protein kinase.

Background Pulmonary rehabilitation (PR) has demonstrated patients’ physiological and psychosocial improvements, symptoms reduction and health-economic benefits whilst enhances the ability of the whole family to adjust to illness. However, PR remains highly inaccessible due to lack of awareness of its benefits, poor referral and availability mostly in hospitals. Novel models of PR delivery are needed to enhance its implementation while maintaining cost-efficiency. We aim to implement an innovative community-based PR programme and assess its cost-benefit. Methods A 12-week community-based PR will be implemented in primary healthcare centres where programmes are not available. Healthcare professionals will be trained. 73 patients with CRD and their caregivers (dyads patient-caregivers) will compose the experimental group. The control group will include dyads age- and disease-matched willing to collaborate in data collection but not in PR. Patients/family-centred outcomes will be dyspnoea (modified Medical Research Council Questionnaire), fatigue (Checklist of individual strength and Functional assessment of chronic illness therapy – fatigue), cough and sputum (Leicester cough questionnaire and Cough and sputum assessment questionnaire), impact of the disease (COPD Assessment Test), emotional state (The Hospital Anxiety and Depression Scale), number of exacerbations, healthcare utilisation, health-related quality of life and family adaptability/cohesion (Family Adaptation and Cohesion Scale). Other clinical outcomes will be peripheral (biceps and quadriceps-hand held dynamometer, 1 or 10 repetition-maximum) and respiratory (maximal inspiratory and expiratory pressures) muscle strength, muscle thickness and cross sectional area (biceps brachialis, rectus femoris and diaphragm-ultrasound imaging), exercise capacity (six-minute walk test and one-minute sit to stand test), balance (brief-balance evaluation systems test) and physical activity (accelerometer). Data will be collected at baseline, at 12 weeks, at 3- and 6-months post-PR. Changes in the outcome measures will be compared between groups, after multivariate adjustment for possible confounders, and effect sizes will be calculated. A cost-benefit analysis will be conducted. Discussion This study will enhance patients access to PR, by training healthcare professionals in the local primary healthcare centres to conduct such programmes and actively involving caregivers. The cost-benefit analysis of this intervention will provide an evidence-based insight into the economic benefit of community-based PR in chronic respiratory diseases. Trial registration The trial was registered in the ClinicalTrials.gov U.S. National Library of Medicine, on 10th January, 2019 (registration number: NCT03799666 ). Electronic supplementary material The online version of this article (10.1186/s12889-019-7045-1) contai...

Das Alkaloid Reserpin kann heute als das wichtigste Rauwolfia-Alkaloid betrachtet werden, denn es scheint der Haupttriiger der sedativen und hypotensiven Wirkung der rohen Extrakte von R a u w o l f i a s e r p e n t i n a Benth. zu sein. Reserpin ist 1952 erstmals von NueZZer, Schlittler & Bein2) aus R. serpentina isoliert worden, und in zwei weiteren vorliiufigen Publikationenl) 3, haben wir uns mit dem Chemismus dieses pharmakologisch hochinteressanten Alkaloids befasst 4). Unmittelbar nach unseren Publikationen sind dann eine Reihe weiterer unabhiingiger Arbeiten erschienen5), die sich ebenfalls mit dem chemiwhen Bau des von uns entdeckten Alkaloids beschiiftigt haben. Da bis jetzt ausser analytischen Daten von keiner Seite experimentelles Material publiziert worden ist, mochten wir hiemit unsere Ergebnisse ausfuhrlich bekanntgeben. Die UV.-und 1R.-Spektren von Reserpin sind bereits publiziert worden3). Da andere Rauwolfia-Alkaloide einen Indolkern enthalten, konnte mit Recht angenommen werden, dass auch Reserpin zu dieser Gruppe gehort. I m Gegensatz zu dieser Auffassung war das UV.-Spektrum des Reserpins nicht dasjenige einer normalen Indolbase. Die beobachtete Verschiebung der Absorptionskurve liess die Anwesenheit einer auxochromen Gruppe am Benzolkern oder ein zweites konjugiertes System oder beides vermuten. Das 1R.-Spektrum wies auf die Anwesenheit einer NH-(3429 cm-l) und zweier Carbonyl-Gruppen (1732, 1713 cm-l) hin. Starke Banden in der Gegend von 1229 -1275 cm-1 machten es wahrscheinlich, dass die Carbonylabsorption durch Estergruppierungen erzeugt wurde. Die starke Bande 1) 7. Mitt., siehe L. Dorfman, C . per. 9, 331 (1953). 4, Ausserdem wurde am 15. September 1953 im Rahmen des ,,Symposium on Hypertensive Drugs" in Boston, Mass., zum erstenmal ausfuhrlich uber die Konstitution des Reserpins referiert.

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