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Leoni V.,Laboratory of Clinical Chemistry | Leoni V.,Foundation IRCCS Institute of Neurology Carlo Besta | Caccia C.,Foundation IRCCS Institute of Neurology Carlo Besta
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

Huntington disease (HD), an autosomal dominant neurodegenerative disorder caused by an abnormal expansion of CAG trinucleotide repeat in the Huntingtin (HTT) gene, is characterized by extensive neurodegeneration of striatum and cortex and severe diffuse atrophy at MRI. The expression of genes involved in the cholesterol biosynthetic pathway and the amount of cholesterol, lanosterol, lathosterol and 24S-hydroxycholesterol were reduced in murine models of HD. In case of HD-patients, the decrease of plasma 24OHC follows disease progression proportionally to motor and neuropsychiatric dysfunction and MRI brain atrophy, together with lanosterol and lathosterol (markers of cholesterol synthesis), and 27-hydroxycholesterol. A significant reduction of total plasma cholesterol was observed only in advanced stages. It is likely that mutant HTT decreases the maturation of SREBP and the up-regulation LXR and LXR-targeted genes (SREBP, ABCG1 and ABCG4, HMGCoA reductase, ApoE) resulting into a lower synthesis and transport of cholesterol from astrocytes to neurons via ApoE. In primary oligodendrocytes, mutant HTT inhibited the regulatory effect of PGC1α on cholesterol metabolism and on the expression of MBP. HTT seems to play a regulatory role in lipid metabolism. The impairment of the cholesterol metabolism was found to be proportional to the CAG repeat length and to the load of mutant HTT. A dysregulation on PGC1α and mitochondria dysfunction may be involved in an overall reduction of acetyl-CoA and ATP synthesis, contributing to the cerebral and whole body cholesterol impairment. This article is part of a Special Issue entitled Brain Lipids. © 2015 Elsevier B.V.All rights reserved. Source

Tsiafoulis C.G.,University of Ioannina | Exarchou V.,University of Ioannina | Tziova P.P.,University of Ioannina | Bairaktari E.,Laboratory of Clinical Chemistry | And 2 more authors.
Analytical and Bioanalytical Chemistry

The rapid and accurate determination of specific metabolites present in biofluids is a very demanding task which is essential in both medicine and chemistry. l-carnitine (3-hydroxy-4-N-trimethylammonium butyrate) is an important metabolite which participates in a series of biological paths and therefore its determination is of diagnostic importance. A single quantum coherence filtering 1H NMR methodology was used for the accurate and rapid determination of l-carnitine in human serum samples. The methodology is based on spectral simplification, and specifically on the distinction of the N-methyl proton signal of l-carnitine that is greatly overlapped in the 1H-NMR spectrum of serum. The quantitative results provided by the proposed method are in excellent agreement with those obtained by the enzymatic method, which is widely used. The proposed method is rapid (~20 min of experimental time), selective, sensitive, and has good analytical characteristics (accuracy, reproducibility). Selected protein precipitation methods were also investigated and sample pretreatment with EtOH is suggested. © Springer-Verlag 2011. Source

Balducci S.,University of Rome La Sapienza | Balducci S.,Diabetes Unit | Zanuso S.,University of Greenwich | Cardelli P.,University of Rome La Sapienza | And 11 more authors.
Diabetes Care

OBJECTIVE - Physical fitness is inversely related tomortality in the general population and in subjects with type 2 diabetes.Here,we present data concerning the relationship between changes in physical fitness and modifiable cardiovascular risk factors in subjects with type 2 diabetes from the Italian Diabetes and Exercise Study. RESEARCH DESIGN AND METHODS - Sedentary patients with type 2 diabetes (n = 606) were enrolled in 22 outpatient diabetes clinics and randomized to twice-a-week supervised aerobic and resistance training plus exercise counseling versus counseling alone for 12 months. Baseline to end-of-study changes in cardiorespiratory fitness, strength, and flexibility, as assessed by VO 2max estimation, a 5-8 maximal repetition test, and a hip/trunk flexibility test, respectively, were calculated in the whole cohort, and multiple regression analyses were applied to assess the relationship with cardiovascular risk factors. RESULTS - Changes in VO 2max, upper and lower body strength, and flexibility were significantly associated with the variation in the volume of physical activity, HbA 1c, BMI, waist circumference, high-sensitivity C-reactive protein (hs-CRP), coronary heart disease (CHD) risk score, and inversely, HDL cholesterol. Changes in fitness predicted improvements in HbA 1c, waist circumference, HDL cholesterol, hs-CRP, and CHD risk score, independent of study arm, BMI, and in case of strength, also waist circumference. CONCLUSIONS - Physical activity/exercise-induced increases in fitness, particularly muscular, predict improvements in cardiovascular risk factors in subjects with type 2 diabetes independently of weight loss, thus indicating the need for targeting fitness in these individuals, particularly in subjects who struggle to lose weight. © 2012 by the American Diabetes Association. Source

Cotton F.,Free University of Colombia | Wolff F.,Laboratory of Clinical Chemistry | Gulbis B.,Free University of Colombia
Methods in Molecular Biology

Hemoglobinopathies are genetic disorders of globin chains characterized by the decreased expression of α - or β -globin chains (thalassemias) or by the synthesis of an abnormal protein (hemoglobin variants in, e.g., sickle cell disease). The screening of most hemoglobinopathies relies, together with hematological results and clinical elements, on the separation and quantification of normal and abnormal hemoglobin fractions. Gel electrophoresis, isoelectric focusing, and HPLC have been the methods of choice for many years. For about 20 years, capillary electrophoresis has appeared as a strong alternative method. Since the early 2000s, automated instruments are commercially available for the analysis of Hb fractions in adult patients but also for neonatal screening. © Springer Science+Business Media, LLC 2013. Source

Mare L.,University of Insubria | Caretti A.,University of Milan | Albertini R.,Laboratory of Clinical Chemistry | Trinchera M.,University of Insubria
International Journal of Biochemistry and Cell Biology

CA19.9 antigen is a glycoprotein present in human serum and found elevated in various diseases. It is intensively studied since long time as a potential marker for managing cancers of the gastrointestinal tract, but its reliability is widely accepted only for pancreatic cancers. Here, we focused on the tetrasaccharide epitope (NeuAcα2-3Galβ1-3[Fucα1-4]GlcNAc) sialyl-Lewis a studying the biosynthesis, expression, and secretion in colon cancers and related cancer cell lines. We found that the β1,3 galactosyltransferase β3Gal-T5, responsible for sialyl-Lewis a synthesis, is dramatically reduced in colon adenocarcinomas, in terms of both transcript and enzyme activity levels. Moreover, no or very faint antigen is detectable in colon cancer homogenates, by dot-blot or enzyme immunoassay, while it is commonly evident in sera from different patients. In cancer cell lines synthesizing CA19.9, the amount of antigen secreted is proportional to that expressed on the cell surface, and depends on appreciable levels of β3Gal-T5, which appear much higher than those measured in colon cancer specimens. Since colon cancers appear unable to synthesize relevant amount of CA19.9, we suggest that the antigen circulating in the serum of colon cancer patients may have a different and more complex origin than expected so far. © 2013 Elsevier Ltd. Source

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