42 research outputs found

    Apple polyphenol extract improves insulin sensitivity in vitro and in vivo in animal models of insulin resistance

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    Background: Apple polyphenols could represent a novel nutritional approach in the management and control of blood glucose, especially in type 2 diabetics. The aim of this study was to test the therapeutic potential of an apple polyphenol extract (APE) in an insulin-resistant rat model and to determine the molecular basis of insulin sensitivity action in skeletal muscle cells.Methods: Acute effect of APE on the postprandial hyperglycemic response was assayed in 15 week old obese Zucker rats (OZR), by using a meal tolerance test (MTT). The ability of APE to improve whole peripheral insulin sensitivity was also assayed in a chronic study by using the euglycemic-hyperinsulinemic clamp technique. To elucidate the molecular mechanisms, rat L6 myotubes were used. Glucose uptake was measured by using 2-[3H]-Deoxy-Glucose (2-DG) and specific inhibitors, as well as phosphorylation status of key kinases, were used to determine the implicated signaling pathway.Results: In vivo study showed that nutritional intervention with APE induced an increase of insulin sensitivity with an increase of glucose infusion rate (GIR) of 45 %. Additionally, in vitro results showed a synergistic effect between APE and insulin as well as increased glucose uptake through GLUT4 translocation in muscle cells. This translocation was mediated by phosphatydil inositol 3-kinase (PI3K) and peroxisome proliferator-activated receptor-gamma (PPARγ) signaling pathways.Conclusions: As a whole, this study describes the mechanisms involved in the insulin sensitizing effect of APE, which could be considered a promising ingredient for inclusion in nutritional products focused on the management of chronic diseases such as diabetes.This research was supported by funds from Abbott Laboratories S.A

    miR-146a rs2431697 identifies myeloproliferative neoplasm patients with higher secondary myelofibrosis progression risk

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    Myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), and remarkably shortens survival. Although JAK2V617F and CALR allele burden are the main transformation risk factors, inflammation plays a critical role by driving clonal expansion toward end-stage disease. NF-κB is a key mediator of inflammation-induced carcinogenesis. Here, we explored the involvement of miR-146a, a brake in NF-κB signaling, in MPN susceptibility and progression. rs2910164 and rs2431697, that affect miR-146a expression, were analyzed in 967 MPN (320 PV/333 ET/314 MF) patients and 600 controls. We found that rs2431697 TT genotype was associated with MF, particularly with post-PV/ET MF (HR = 1.5; p < 0.05). Among 232 PV/ET patients (follow-up time=8.5 years), 18 (7.8%) progressed to MF, being MF-free-survival shorter for rs2431697 TT than CC + CT patients (p = 0.01). Multivariate analysis identified TT genotype as independent predictor of MF progression. In addition, TT (vs. CC + CT) patients showed increased plasma inflammatory cytokines. Finally, miR-146a−/− mice showed significantly higher Stat3 activity with aging, parallel to the development of the MF-like phenotype. In conclusion, we demonstrated that rs2431697 TT genotype is an early predictor of MF progression independent of the JAK2V617F allele burden. Low levels of miR-146a contribute to the MF phenotype by increasing Stat3 signaling

    ARIA 2016 : Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

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    The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.Peer reviewe

    Randomized, allopurinol-controlled trial of the effects of dietary nucleotides and active hexose correlated compound in the treatment of canine leishmaniosis

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    First-line treatment for canine leishmaniosis (CanL) is N-methylglucamine antimoniate (MGA) combined with allopurinol. However, in some dogs allopurinol may induce hyperxanthinuria leading to urolithiasis. Moreover, allopurinol resistance has recently been described in Leishmania infantum isolates from treated dogs with a relapse of the disease. Alternative treatments are thus needed. Since the type of host immune response strongly influences CanL progression and prognosis, dogs could benefit from treatments targeted at modulating such response, such as nucleotides and active hexose correlated compound (AHCC). The aim of this study was to evaluate the effects of an oral combination of nucleotides and AHCC in dogs with clinical leishmaniosis. Sixty-nine dogs with naturally-occurring clinical leishmaniosis were included in this multicenter, open-label, positively-controlled clinical trial and randomized to receive 10 mg/kg allopurinol PO BID (allopurinol group) or 17 mg/kg AHCC plus 32 mg/kg nucleotides PO SID (supplement group) for 180 days. All dogs were also given 50 mg/kg MGA SC BID during the first 28 days. At the time points 0, 30, and 180 days of the trial, dogs underwent a clinical examination, and blood, urine, and bone marrow samples were submitted for analytical tests. Final data analyses (allopurinol group: n = 29; supplement group: n = 24) revealed a significant improvement in both groups in clinical scores and ELISA-determined antibody titers after treatment. However, the supplement group showed a significantly lower clinical score (P = 0.005) and significantly higher antibody titers (P = 0.032) after 180 days, compared to the allopurinol group. RT-PCR parasite loads were reduced in groups (mean ± SD supplement: 0.38 ± 0.56 vs 5.23 ± 18.9; allopurinol: 0.45 ± 1.47 vs 3.09 ± 8.36 parasites/ng of DNA), but there were no significant differences over time or between groups. During the study, 12 dogs in the allopurinol group developed xanthinuria (41%) compared to no dogs (0%) in the supplement group (P = 0.000). Both treatments led to significantly increased CD4+/CD8+ ratio, and improvements in protein electrophoretic pattern and acute phase response. In conclusion, 6-month oral treatment with nucleotides and AHCC in addition to MGA showed similar efficacy to the current first-line treatment for CanL, without producing xanthinuria. This combination could be a good alternative to MGA-allopurinol combination treatment for CanL, especially for dogs suffering allopurinol-related adverse events

    Emerging needle blight diseases in atlantic pinus ecosystems of Spain

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    Red band needle blight caused by Dothistroma septosporum and D. pini, and brown spot needle blight caused by Lecanosticta acicola provoke severe and premature defoliation in Pinus, and subsequent reduction of photosynthetic surfaces, vitality, and growth in young and adult trees. The recurrent damage results in branch and tree death. Until recently, pine needle blight diseases have had only minor impacts on native and exotic forest trees in the North of Spain, but in the past five years, these pathogen species have spread widely and caused severe defoliation and mortality in exotic and native plantations of Pinus in locations where they were not detected before. In an attempt to understand the main causes of this outbreak and to define the effectiveness of owners' management strategies, four research actions were implemented a survey of the management activities implemented by the owners to reduce disease impact, the evaluation of specific symptoms and damage associated with infection, and the identification of the causative pathogenic species and their reproductive capacity. Morphological characteristics of the fungus and molecular identification were consistent with those of Lecanosticta acicola and Dothistroma spp.;D. septosporum, D. Pini, and both mating types were present for the three identified pathogens. The local silvicultural management performed, mainly pruning and thinning, was not resulting in the expected improvement. The results of this study can be applied to establish guidelines for monitoring and controlling the spread of needle blight pathogens. © 2017 by the authors

    Rapid detection of pork gelatin in ice cream samples by using non-destructive FT-NIR spectroscopy and Partial least squares-discriminant analysis

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    This study aimed at developing a fast and low-cost detection method to discriminate between ice cream samples containing pork or non-pork gelatin by using Fourier Transform Near Infrared (FT-NIR) spectroscopy and Partial Least Squares Discriminant Analysis (PLS-DA). Forty two samples of ice cream were used, among which twenty three samples were adulterated with different levels i.e. 1%, 5%, 10%, and 20 % of pork gelatin (Non-Halal). Whereas, the remaining nineteen samples containing only cow gelatin (Halal) were used as a control. All the ice cream samples were measured with the FT-NIR spectrophotometer in the reflection mode. Spectra were collected in the wavenumber range from 10000 to 4000 cm−1 (1000 to 2500 nm). The results show that the PLS-DA model with Unit Vector Normalization (UVN) spectral transformations for 1% pork gelatin adulteration is the optimal one which was based on a compromise between the lowest value of root mean square error of cross validation (RMSECV) for the calibration set. The lowest value of root mean square error of prediction (RMSEP) for the test set, the least number of factors and the percentage of correctly classified samples, the Halal and Non-Halal, for both calibration and test sets. This newly developed method is fast, involves simple sample preparation and is low cost
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