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Increases in Plasma Tryptophan Are Inversely Associated with Incident Cardiovascular Disease in the Prevención con Dieta Mediterránea (PREDIMED) Stud…
2017
Background: During development of cardiovascular disease (CVD), interferon-γ-mediated inflammation accelerates degradation of tryptophan into downstream metabolites. A Mediterranean diet (MedDiet) consisting of a high intake of extra-virgin olive oil (EVOO), nuts, fruits, vegetables, and cereals has been demonstrated to lower the risk of CVD. The longitudinal relation between tryptophan and its downstream metabolites and CVD in the context of a MedDiet is unstudied.Objective: We sought to investigate the relation between metabolites in the tryptophan-kynurenine pathway and CVD in the context of a MedDiet pattern.Methods: We used a case-cohort design nested in the Prevención con Dieta Medite…
Association of Tryptophan Metabolites with Incident Type 2 Diabetes in the PREDIMED Trial: A Case–Cohort Study
2018
Abstract BACKGROUND Metabolites of the tryptophan–kynurenine pathway (i.e., tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxyanthranilic) may be associated with diabetes development. Using a case–cohort design nested in the Prevención con Dieta Mediterránea (PREDIMED) study, we studied the associations of baseline and 1-year changes of these metabolites with incident type 2 diabetes (T2D). METHODS Plasma metabolite concentrations were quantified via LC-MS for n = 641 in a randomly selected subcohort and 251 incident cases diagnosed during 3.8 years of median follow-up. Weighted Cox models adjusted for age, sex, body mass index, and other T2D risk factors were used. RESULTS …
Bainbridge-Ropers syndrome caused by loss-of-function variants in ASXL3: a recognizable condition
2016
International audience; Truncating ASXL3 mutations were first identified in 2013 by Bainbridge et al. as a cause of syndromic intellectual disability in four children with similar phenotypes using whole-exome sequencing. The clinical features - postulated by Bainbridge et al. to be overlapping with Bohring-Opitz syndrome - were developmental delay, severe feeding difficulties, failure to thrive and neurological abnormalities. This condition was included in OMIM as 'Bainbridge-Ropers syndrome' (BRPS, #615485). To date, a total of nine individuals with BRPS have been published in the literature in four reports (Bainbridge et al., Dinwiddie et al, Srivastava et al. and Hori et al.). In this re…
Nandrolone decanoate interferes with testosterone biosynthesis altering blood-testis barrier components
2017
Abstract The aim of this study was to investigate whether nandrolone decanoate (ND) use affects testosterone production and testicular morphology in a model of trained and sedentary mice. A group of mice underwent endurance training while another set led a sedentary lifestyle and were freely mobile within cages. All experimental groups were treated with either ND or peanut oil at different doses for 6 weeks. Testosterone serum levels were measured via liquid chromatography–mass spectrometry. Western blot analysis and quantitative real‐time PCR were utilized to determine gene and protein expression levels of the primary enzymes implicated in testosterone biosynthesis and gene expression leve…
Association Between Atrophy of the Caudate Nuclei, Global Brain Atrophy, Cerebral Small Vessel Disease and Mild Parkinsonian Signs in Neurologically …
2017
Background: Mild Parkinsonian signs (MPS) are commonly seen in aging, and have been related to cerebral Small Vessel Diseases (SVD) with no univocal results. Objective: The aim of this study was to investigate the cross-sectional relation between MPS and White Matter Hyperintensities (WMH), lacunes, caudate atrophy, and global cerebral atrophy in a large cohort of Neurologically and Cognitively Healthy (NCH) aging individuals. Method: 1,219 NCH individuals were included in the analysis, and underwent standard brain MRI. The items of the motor section of the Unified Parkinson’s Disease Rating Scale were used to evaluate tremor, rigidity, bradykinesia, and gait/balance/axial dysfunction. Cau…
Mild cognitive impairment in Parkinson’s disease: the Parkinson’s disease cognitive study (PACOS)
2018
Approximately 30% of Parkinson's disease (PD) patients show impaired cognitive performance, which is suggestive of Mild Cognitive Impairment (MCI), representing a predictor of dementia, especially when present at diagnosis. The objective of the study was to evaluate the frequency and clinical predictors of MCI in a large hospital-based cohort of PD patients. We collected cross-sectional data from the Parkinson's disease cognitive impairment study (PACOS), a multicenter study involving two Movement Disorder centers, which are located in south Italy. The PD subjects were diagnosed according to the UK Brain Bank criteria and they underwent an extensive neuropsychological assessment. PD-MCI was…
Brain BDNF levels are dependent on cerebrovascular endothelium-derived nitric oxide
2016
International audience; Scientific evidence continues to demonstrate a link between endothelial function and cognition. Besides, several studies have identified a complex interplay between nitric oxide (NO) and brain-derived neurotrophic factor (BDNF), a neurotrophin largely involved in cognition. Therefore, this study investigated the link between cerebral endothelium-derived NO and BDNF signaling. For this purpose, levels of BDNF and the phosphorylated form of endothelial NO synthase at serine 1177 (p-eNOS) were simultaneously measured in the cortex and hippocampus of rats subjected to either bilateral common carotid occlusion (n=6), physical exercise (n=6) or a combination of both (n=6) …
Retinal arteriole reactivity in mice lacking the endothelial nitric oxide synthase (eNOS) gene
2018
Dysfunctional vascular endothelial nitric oxide synthase (eNOS) has been proposed to play a main pathophysiological role in various ocular diseases. The aim of the present study was to test the hypothesis that the chronic lack of eNOS impairs endothelium-dependent vasodilation in retinal arterioles. The relevance of eNOS for mediating vascular responses was studied in retinal vascular preparations from eNOS-deficient mice (eNOS-/-) and wild-type controls in vitro. Changes in luminal diameter in response to vasoactive agents were measured by videomicroscopy. The thromboxane mimetic, U46619, induced similar concentration-dependent constriction of retinal arterioles in eNOS-/- and wild-type mi…
Uncoupling of Endothelial Nitric Oxide Synthase in Perivascular Adipose Tissue of Diet-Induced Obese Mice
2015
Objective— The present study was conducted to investigate the contribution of perivascular adipose tissue (PVAT) to vascular dysfunction in a mouse model of diet-induced obesity. Approach and Results— Obesity was induced in male C57BL/6J mice with a high-fat diet for 20 weeks, and vascular function was studied with myograph. In PVAT-free aortas isolated from obese mice, the endothelium-dependent, nitric oxide–mediated vasodilator response to acetylcholine remained normal. In contrast, a clear reduction in the vasodilator response to acetylcholine was observed in aortas from obese mice when PVAT was left in place. Adipocytes in PVAT were clearly positive in endothelial nitric oxide synthase…
Reversing behavioural abnormalities in mice exposed to maternal inflammation
2016
Viral infection during pregnancy is correlated with increased frequency of neurodevelopmental disorders, and this is studied in mice prenatally subjected to maternal immune activation (MIA). We previously showed that maternal T helper 17 cells promote the development of cortical and behavioural abnormalities in MIA-affected offspring. Here we show that cortical abnormalities are preferentially localized to a region encompassing the dysgranular zone of the primary somatosensory cortex (S1DZ). Moreover, activation of pyramidal neurons in this cortical region was sufficient to induce MIA-associated behavioural phenotypes in wild-type animals, whereas reduction in neural activity rescued the be…