93 research outputs found

    The PPARγ2 Pro12Ala variant is protective against progression of nephropathy in people with type 2 diabetes

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    Cross-sectional studies suggest the association between diabetic nephropathy and the PPARγ2 Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 (PPARγ2). Prospective data are limited to microalbuminuria and no information on renal function is available to date. The present study evaluates the association between the Pro12Ala polymorphism of PPARγ2 and the progression of albuminuria and decay in glomerular filtration rate (GFR) in type 2 diabetes

    SAR analysis of new anti-TB drugs currently in pre-clinical and clinical development

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    Despite enormous efforts have been made in the hunt for new drugs, tuberculosis (TB) still remains the first bacterial cause of mortality worldwide, causing an estimated 8.6 million new cases and 1.3 million deaths in 2012. Multi-drug resistant-TB strains no longer respond to first-line drugs and are inexorably spreading with an estimated 650 000 cases as well as extensively-drug resistant-TB strains, which are resistant to any fluoroquinolone and at least one of the second-line drugs, with 60 000 cases. Thus the discovery and development of new medicines is a major keystone for tuberculosis treatment and control. After decades of dormancy in the field of TB drug development, recent efforts from various groups have generated a promising TB drug pipeline. Several new therapeutic agents are concurrently studied in clinical trials together with much activity in the hittolead and lead optimization stages. In this article we will review the recent advances in TB drug discovery with a special focus on structure activity relationship studies of the most advanced compound classe

    A 19 year follow-up of a woman with lipoprotein lipase deficiency treated with biliopancreatic diversion

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    We show the long-term efficacy and safety of modified biliopancreatic diversion for the treatment of LPL-deficiency. How this option compares with gene therapy is difficult to evaluate due to limited experience. Surgery may be the first option in patients in whom medical therapy is ineffective and gene therapy not applicable

    Diaphragmatic motility assessment in COPD exacerbation, early detection of Non-Invasive Mechanical Ventilation failure: a pilot study

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    Background Patients with respiratory failure due to Chronic Obstructive Pulmonary Disease (COPD) have decreased diaphragmatic mobility [1]. Non Invasive Mechanical Ventilation (NIMV) is a cornerstone in COPD exacerbation therapy. The availability of early predictors of NIMV failure may be helpful to guide decision-making. Only pH, respiratory rate and PaO2/FiO2 have been considered predictors of response to NIMV [2]. Ultrasonographic (US) assessment of diaphragmatic kinetic is a fast, reliable and reproducible method [3], but its predictive value on NIMV success is not known.Objective:Primary endpoint was to evaluate if the diaphragmatic excursion measurement was able to predict a longer weaning time. Secondary endpoint was to find out a cut-off value of diaphragmatic excursion and a weaning time interval able to predict worst outcome. Methods: Fifty-two (39 males, aged 71±7 years) Caucasian patients with COPD exacerbation treated with NIMV were enrolled. Diaphragm motility was assessed by ultrasonography before starting ventilation at 6 and 24 hours and at the weaning from NIMV. The diaphragmatic excursion (centimeters); the inspiratory and expiratory times (seconds); the inspiration and expiration velocity (cm/sec), the breathing period (seconds), the diaphragm motion time (seconds) and the diaphragm resting time (seconds) were evaluated. Results: Forty-five patients completed the study. The mean time on NIMV was 4.11 ± 1.07 days, with a total time of ventilation of 32.6 ± 86 hours. All the ultrasound diaphragm motility parameters, except for inspiration and expiration velocity, significantly improved at the weaning. Diaphragm excursion at the baseline was significantly correlated with pH (r=0.458; p=0.002), PaO2/FiO2 (r=0.567; p<0.001), and weaning time (r=0.774; p<0.0001). In a multiple linear regression analysis only diaphragm excursion was significantly associated with longer weaning time (coefficient of estimated model -9.247; Standard Error 3.101; p=0.003). ROC curve with weaning time longer than 36 hours was considered as positive state. The AUC value was 0.912 (Standard Error 0.015, p<0.001). The higher sensitivity rate (100%) was achieved with a specificity rate of 86.7% and a cut-off value of 3.165 cm, therefore patients with an excursion lower than 3.165 cm should be weaned after at least 36 hours, while patients with an excursion higher than 3.165 cm could be weaned within 36 hours. Conclusion: US measurements of diaphragmatic performance may have a role in the early evaluation of exacerbation of COPD and in predicting the response to NIMV therapy, it should be included as a routine test in patients presenting to ED with ECOPD

    The combination of UCP3-55CT and PPARγ2Pro12Ala polymorphisms affects BMI and substrate oxidation in two diabetic populations

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    Background and aim: To evaluate the combined contribution of UCP3-55CT and PPARγ2 Pro12Ala polymorphisms as correlates of BMI, energy expenditure (REE) and substrate oxidation in people with type 2 diabetes. Methods and results: Two independent population with type 2 diabetes were studied: population A, n = 272; population B, n = 269. Based on both UCP3 and PPARγ2 genotypes three groups were created. Carriers of the PPARγ2 Pro12Ala in combination with the CC genotype of UCP3 (ProAla/CC, group 1); carriers of only one of these genotypes (either CC/ProPro or CT-TT/ProAla, group 2); people with neither variants (CT-TT/ProPro, group 3). In both populations BMI (kg/m(2)) was highest in group 1, intermediate in group 2 and lowest in group 3, independent of energy intake (i.e 35.3 ± 6.7 vs 33.4 ± 5.4 vs 31.8 ± 3, p < 0.02, population A; 32.4 ± 4.2 vs 31.7 ± 3.8 vs 30.1 ± 2.7; p < 0.03, population B). People with the ProAla/CC genotype (group 1) showed similar REE, but lower lipid oxidation (10.9 vs 13.9 g/kg fat free mass/day; p = 0.04) and higher carbohydrate oxidation (23.6 vs 15.6 g/kg fat free mass/day; p = 0.02) than carriers of other genotypes. Conclusions: The combination of UCP3-55 CC and PPARγ2 Pro12Ala genotypes is associated with significantly higher BMI than other PPARγ2-UCP3 genotype combinations, partly due to a reduced ability in lipids oxidation. The relative importance of these mechanism(s) may be different in non diabetic people

    San Francesco del Deserto, tra finitezza e transitorietà

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    Il saggio riflette sulle trasformazioni fisiche dell'isola di San Francesco del Deserto, nella laguna di Venezia, utilizzando il progetto come strumento di indagine

    Root Exposure to 5-Aminolevulinic Acid (ALA) Affects Leaf Element Accumulation, Isoprene Emission, Phytohormonal Balance, and Photosynthesis of Salt-Stressed Arundo donax

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    Arundo donax has been recognized as a promising crop for biomass production on marginal lands due to its superior productivity and stress tolerance. However, salt stress negatively impacts A. donax growth and photosynthesis. In this study, we tested whether the tolerance of A. donax to salinity stress can be enhanced by the addition of 5-aminolevulinic acid (ALA), a known promoter of plant growth and abiotic stress tolerance. Our results indicated that root exposure to ALA increased the ALA levels in leaves along the A. donax plant profile. ALA enhanced Na+ accumulation in the roots of salt-stressed plants and, at the same time, lowered Na+ concentration in leaves, while a reduced callose amount was found in the root tissue. ALA also improved the photosynthetic performance of salt-stressed apical leaves by stimulating stomatal opening and preventing an increase in the ratio between abscisic acid (ABA) and indol-3-acetic acid (IAA), without affecting leaf methanol emission and plant growth. Supply of ALA to the roots reduced isoprene fluxes from leaves of non-stressed plants, while it sustained isoprene fluxes along the profile of salt-stressed A. donax. Thus, ALA likely interacted with the methylerythritol 4-phosphate (MEP) pathway and modulate the synthesis of either ABA or isoprene under stressful conditions. Overall, our study highlights the effectiveness of ALA supply through soil fertirrigation in preserving the young apical developing leaves from the detrimental effects of salt stress, thus helping of A. donax to cope with salinity and favoring the recovery of the whole plant once the stress is removed

    Recombinant Human Thyroid Stimulating Hormone Improves Endothelial Coronary Flow Reserve in Thyroidectomized Patients With Differentiated Thyroid Cancer

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    The role of thyroid stimulating hormone (TSH) on the cardiovascular system has been poorly investigated. It is unknown whether the changes in the vasculature associated with thyroid diseases result from altered thyroid hormone production or whether they are the expression of the direct effect of TSH on endothelial cells. The present study was designed to evaluate the endothelial response of coronary flow to thyroid-stimulating hormone in patients with differentiated thyroid cancer (DTC) without cardiovascular risk factors
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