462 research outputs found
Metabolic interactions between vitamin A and conjugated linoleic acid
Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA) is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol) and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4). However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR- and RXR heterodimer. We also present preliminary data that may position PPAR- at the crossroads between the metabolism of lipids and vitamin
(1)H-NMR analysis provides a metabolomic profile of patients with multiple sclerosis
OBJECTIVE: To investigate the metabolomic profiles of patients with multiple sclerosis (MS) and to define the metabolic pathways potentially related to MS pathogenesis.
METHODS: Plasma samples from 73 patients with MS (therapy-free for at least 90 days) and 88 healthy controls (HC) were analyzed by (1)H-NMR spectroscopy. Data analysis was conducted with principal components analysis followed by a supervised analysis (orthogonal partial least squares discriminant analysis [OPLS-DA]). The metabolites were identified and quantified using Chenomx software, and the receiver operating characteristic (ROC) curves were calculated.
RESULTS: The model obtained with the OPLS-DA identified predictive metabolic differences between the patients with MS and HC (R2X = 0.615, R2Y = 0.619, Q2 = 0.476; p < 0.001). The differential metabolites included glucose, 5-OH-tryptophan, and tryptophan, which were lower in the MS group, and 3-OH-butyrate, acetoacetate, acetone, alanine, and choline, which were higher in the MS group. The suitability of the model was evaluated using an external set of samples. The values returned by the model were used to build the corresponding ROC curve (area under the curve of 0.98).
CONCLUSION: NMR metabolomic analysis was able to discriminate different metabolic profiles in patients with MS compared with HC. With the exception of choline, the main metabolic changes could be connected to 2 different metabolic pathways: tryptophan metabolism and energy metabolism. Metabolomics appears to represent a promising noninvasive approach for the study of M
Deletion of the Williams Beuren syndrome critical region unmasks facioscapulohumeral muscular dystrophy
Among 1339 unrelated cases accrued by the Italian National Registry for facioscapulohumeral muscular dystrophy (FSHD), we found three unrelated cases who presented signs of Williams-Beuren Syndrome (WBS) in early childhood and later developed FSHD. All three cases carry the molecular defects associated with the two disorders. The rarity of WBS and FSHD, 1 in 7500 and 1 in 20,000 respectively, makes a random association of the two diseases unlikely. These cases open novel and unexpected interpretation of genetic findings. The nonrandom association of both FSHD and WBS points at a gene co-expression network providing hints for the identification of modules and functionally enriched pathways in the two conditions
Unilateral leg swelling in a newborn
A female neonate was born with asymmetric lower limbs, the right leg appearing enlarged, with thickened, reddish-purple skin and ectasic superficial reticulum (figure 1A,B). Limb pulses were present and symmetrical. The girl's family history and prenatal scans were unremarkable. Laboratory findings were within the normal range, except for a mild thrombocytopenia (90 000/μL), which spontaneously resolved during the next few days. A leg X-ray and the Doppler analysis ruled out the presence of calcifications and venous varices, respectively. Ultrasound showed significant skin thickening, with marked dermal hypertrophy and hyperechogenicity. Magnetic resonance showed circumferential thickening of the derma, with mild hypertrophy of some perforating vessels (figure 2). A biopsy of the right thigh showed capillary malformations on histology. edpract;archdischild-2020-320450v1/BLKF1F1BLK_F1Figure 1(A, B) Hypertrophy of the right lower limb, with large capillary malformation extending to the gluteus and the external genitalia. edpract;archdischild-2020-320450v1/BLKF2F2BLK_F2Figure 2Axial THRIVE magnetic resonance scan of the thighs' proximal third, showing circumferential dermal thickening and inhomogeneity of the right leg's subcutaneous tissue. QUESTIONS: Based on the clinical picture and investigations results, which is the most likely diagnosis?Beckwith-WiedemannCLOVES syndromeKlippel-Trenaunay syndromeKaposiform hemangioendotheliomaHow can the diagnosis be confirmed?CT with PETLymphoscintigraphyGenetic testingNone of the above, the diagnosis is clinicalWhat is the mainstay of management?Conservative with follow-upPharmacotherapySclerotherapySurgeryWhich of the following complications can occur?ScoliosisGlaucomaUrinary and gastrointestinal bleedingAll of the above Answers can be found on page 02
Spring diet of the pine marten in Sardinia, Italy
Alimentación primaveral de la marta en Cerdeña, ItaliaEl conocimiento del comportamiento de alimentación de un carnívoro es esencial para entender su ecología. La marta Martes martes se define comúnmente como un depredador generalista oportunista, porque su dieta en Europa incluye mamíferos, frutas, aves y invertebrados. A partir del análisis de las heces, hemos descrito los hábitos alimenticios en primavera y la amplitud del nicho trófico de la marta en ambiente mediterráneo en Cerdeña (Italia central). Los pequeños mamíferos (sobre todo Apodemus sylvaticus, Mus musculus y Eliomys quercinus) representan la fuente más importante de alimentación de la marta, ya que constituyen aproximadamente el 52% del volumen medio. Otra fuente importante de alimentos secundarios la constituyen los invertebrados (especialmente escarabajos y larvas de insectos) y las aves (paseriformes casi exclusivamente), mientras que los grandes mamíferos, los lagomorfos, los reptiles y las frutas están poco representados en la dieta. La composición de la dieta y el valor del índice de Levins indican que la marta en Cerdeña es un depredador especialista facultativo, con una especialización en la depredación de los micromamíferos.Knowledge of a carnivore’s foraging behaviour is essential to understand its ecology. The pine marten Martes martes is commonly defined as an opportunistic generalist predator since its diet in Europe includes mammals, fruits, birds and invertebrates. Based on faecal analyses, we evaluated spring feeding habits and trophic niche breadth of the pine marten in a Mediterranean landscape on the island of Sardinia (Central Italy). The most important source of food for the pine marten was small mammals (mainly Apodemus sylvaticus, Mus musculus and Eliomys quercinus), accounting for 52% of the percent mean volume. Important secondary foods were invertebrates (mainly beetles and insect larvae) and birds (almost exclusively passerines), whereas large mammals, lagomorphs, reptiles and fruits made little contribution to the diet. The diet composition and the Levins’ index value suggest that the pine marten in Sardinia behaves as a facultative specialist predator, with a specialization towards small mammals.Alimentación primaveral de la marta en Cerdeña, ItaliaEl conocimiento del comportamiento de alimentación de un carnívoro es esencial para entender su ecología. La marta Martes martes se define comúnmente como un depredador generalista oportunista, porque su dieta en Europa incluye mamíferos, frutas, aves y invertebrados. A partir del análisis de las heces, hemos descrito los hábitos alimenticios en primavera y la amplitud del nicho trófico de la marta en ambiente mediterráneo en Cerdeña (Italia central). Los pequeños mamíferos (sobre todo Apodemus sylvaticus, Mus musculus y Eliomys quercinus) representan la fuente más importante de alimentación de la marta, ya que constituyen aproximadamente el 52% del volumen medio. Otra fuente importante de alimentos secundarios la constituyen los invertebrados (especialmente escarabajos y larvas de insectos) y las aves (paseriformes casi exclusivamente), mientras que los grandes mamíferos, los lagomorfos, los reptiles y las frutas están poco representados en la dieta. La composición de la dieta y el valor del índice de Levins indican que la marta en Cerdeña es un depredador especialista facultativo, con una especialización en la depredación de los micromamíferos
Clinical course and features of persistent polyclonal B-cell lymphocytosis with BCL-6 amplification during pregnancy
Background: Persistent polyclonal B-cell lymphocytosis is a rare nonmalignant disorder characterized by mild persistent lymphocyte proliferation with possible evolution to aggressive lymphoma. Its biology is not well known, but it is characterized by a specific immunophenotype with rearrangement of the BCL-2/IGH gene, whereas amplification of the BCL-6 gene has rarely been reported. Given the paucity of reports, it has been hypothesized that this disorder is associated with poor pregnancy outcomes. Case report: To our knowledge, only two successful pregnancies have been described in women with this condition. We report the third successful pregnancy in a patient with PPBL and the first with amplification of the BCL-6 gene. Conclusions: PPBL is still a poorly understood clinical condition with insufficient data to demonstrate an adverse effect on pregnancy. The role of BCL-6 dysregulation in the pathogenesis of PPBL and its prognostic significance are still unknown. Evolution into aggressive clonal lymphoproliferative disorders is possible and prolonged hematologic follow-up is warranted in patients with this rare clinical disorder
Dietary triacylglycerols with palmitic acid in the sn-2 position modulate levels of N-acylethanolamides in rat tissues
BACKGROUND:
Several evidences suggest that the position of palmitic acid (PA) in dietary triacylglycerol (TAG) influences different biological functions. We aimed at evaluating whether dietary fat with highly enriched (87%) PA in sn-2 position (Hsn-2 PA), by increasing PA incorporation into tissue phospholipids (PL), modifies fatty acid profile and biosynthesis of fatty acid-derived bioactive lipids, such as endocannabinoids and their congeners.
STUDY DESIGN:
Rats were fed for 5 weeks diets containing Hsn-2 PA or fat with PA randomly distributed in TAG with 18.8% PA in sn-2 position (Lsn-2 PA), and similar total PA concentration. Fatty acid profile in different lipid fractions, endocannabinoids and congeners were measured in intestine, liver, visceral adipose tissue, muscle and brain.
RESULTS:
Rats on Hsn-2 PA diet had lower levels of anandamide with concomitant increase of its congener palmitoylethanolamide and its precursor PA into visceral adipose tissue phospholipids. In addition, we found an increase of oleoylethanolamide, an avid PPAR alpha ligand, in liver, muscle and brain, associated to higher levels of its precursor oleic acid in liver and muscle, probably derived by elongation and further delta 9 desaturation of PA. Changes in endocannabinoids and congeners were associated to a decrease of circulating TNF alpha after LPS challenge, and to an improved feed efficiency.
CONCLUSIONS:
Dietary Hsn-2 PA, by modifying endocannabinoids and congeners biosynthesis in different tissues may potentially concur in the physiological regulation of energy metabolism, brain function and body fat distribution
Vitamin D responsive elements within the HLA-DRB1 promoter region in Sardinian multiple sclerosis associated alleles
Vitamin D response elements (VDREs) have been found in the promoter region of the MS-associated allele HLA-DRB1*15:01, suggesting that with low vitamin D availability VDREs are incapable of inducing *15:01 expression allowing in early life autoreactive T-cells to escape central thymic deletion. The Italian island of Sardinia exhibits a very high frequency of MS and high solar radiation exposure. We test the contribution of VDREs analysing the promoter region of the MS-associated DRB1 *04:05, *03:01, *13:01 and *15:01 and non-MS-associated *16:01, *01, *11, *07:01 alleles in a cohort of Sardinians (44 MS patients and 112 healthy subjects). Sequencing of the DRB1 promoter region revealed a homozygous canonical VDRE in all *15:01, *16:01, *11 and in 45/73 *03:01 and in heterozygous state in 28/73 *03:01 and all *01 alleles. A new mutated homozygous VDRE was found in all *13:03, *04:05 and *07:01 alleles. Functionality of mutated and canonical VDREs was assessed for its potential to modulate levels of DRB1 gene expression using an in vitro transactivation assay after stimulation with active vitamin D metabolite. Vitamin D failed to increase promoter activity of the *04:05 and *03:01 alleles carrying the new mutated VDRE, while the *16:01 and *03:01 alleles carrying the canonical VDRE sequence showed significantly increased transcriptional activity. The ability of VDR to bind the mutant VDRE in the DRB1 promoter was evaluated by EMSA. Efficient binding of VDR to the VDRE sequence found in the *16:01 and in the *15:01 allele reduced electrophoretic mobility when either an anti-VDR or an anti-RXR monoclonal antibody was added. Conversely, the Sardinian mutated VDRE sample showed very low affinity for the RXR/VDR heterodimer. These data seem to exclude a role of VDREs in the promoter region of the DRB1 gene in susceptibility to MS carried by DRB1* alleles in Sardinian patients
Different Dietary n-3 Polyunsaturated Fatty Acid Formulations Distinctively Modify Fatty Acid and N-Acylethanolamine Profiles in Rat Brain
Application of a Novel Method for a Simulation of Conductivity of a Building Material in a Climatic Chamber
This work proposes the application of a new simulation method based on fractal geometry for the calculation of the thermal conductivity for building materials. The results obtained are compared with the measurement, in a climatic chamber, of the heat flow through a material chosen as the sample. The test sample is made with “pietracantone”, a stone widely used as a building material and as an ornamental stone in the areas of Cagliari and Sassari in Sardinia. This material is characterized by a limestone matrix and a porosity which significantly influences the value of thermal conductivity. It is not known to the authors that this material had already been studied for its thermal propertie
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