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Obesity and overweight in children and adolescents is increasing rapidly worldwide; however, scarce data have been reported from South America countries. With the purpose of assessing hyperlipidemia, insulin resistance and chronic inflammation, the evaluation of blood biomarkers such as glucose, lipoproteins and chronic inflammation proteins is required. In the context of the SAYCARE study, in children and adolescents (3 to 18 years) from seven South American cities, our aim was to assess the impact of pre analytical conditions on different biomarkers evaluated in 474 fresh serum samples, in different country centers. We also evaluated the stability according to time and frozen storage within this study across the concordance of the results obtained from the 49 blood samples measured in three different centers. Significant correlations as well as concordance were observed in TG, Total-C, HDL-C and glucose between Buenos Aires and São Paulo. The samples evaluated in Teresina and São Paulo presented similar results, with exception of total cholesterol. We observed acceptable concordance between Buenos Aires vs São Paulo and Teresina vs São Paulo, suggesting that samples could be processed in each of these centers. This concordance is a consequence of the strict pre analytical conditions previously established in the SAYCARE study. Fil: López, Graciela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Assali Serruya, Raphael. Universidade de Sao Paulo; Brasil Fil: Barchuk, Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Gaitan-Charry, Diego. Universidad de Antioquia; Colombia Fil: Torres-Leal, Francisco Leonardo. Universidade Federal Do Piaui.; Brasil Fil: Moreno, Luis Alberto. Universidad de Zaragoza; España Fil: Delgado, Carlos Alberto. Universidad Nacional Mayor de San Marcos; Perú Fil: Barbosa Carvalho, Heráclito. Universidade de Sao Paulo; Brasil Fil: De Moraes, Augusto César Ferreira. Universidade de Sao Paulo; Brasil Fil: Berg, Gabriela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina

In 2016, Venezuela faced a large diphtheria outbreak that extended until 2019. Nasopharyngeal or oropharyngeal samples were prospectively collected from 51 suspected cases and retrospective data from 348 clinical records was retrieved from 14 hospitals between November 2017 and November 2018. Confirmed pathogenic Corynebactrium isolates were biotyped. Multilocus Sequence Typing (MLST) was performed followed by next-generation-based core genome-MLST and minimum spanning trees were generated. Subjects between 10 and 19 years of age were mostly affected (n = 95; 27.3%). Case fatality rates (CFR) were higher in males (19.4%), as compared to females (15.8%). The highest CFR (31.1%) was observed among those under 5, followed by the 40 to 49 age-group (25.0%). Nine samples corresponded to C. diphtheriae and 1 to C. ulcerans. Two Sequencing Types (ST), ST174 and ST697 (the latter not previously described) were identified among the eight C. diphtheriae isolates from Carabobo state. Cg-MLST revealed only one cluster also from Carabobo. The Whole Genome Sequencing analysis revealed that the outbreak seemed to be caused by different strains with C. diphtheriae and C. ulcerans coexisting. The reemergence and length of this outbreak suggest vaccination coverage problems and an inadequate control strategy. Open Access funding enabled and organized by Projekt DEAL. This work was supported by the Bernhard Nocht Institute for Tropical Medicine, Department of Infectious Disease Epidemiology budget not related with any particular grant. Sí

Familial hypercholesterolemia (FH) is a monogenic disease, associated with variants in the LDLR, APOB and PCSK9 genes. The initial diagnosis is based on clinical criteria like the DLCN criteria. A score8 points qualifies the patient as "definite" for FH diagnosis. The detection of the presence of a variant in these genes allows carrying out familial cascade screening and better characterizes the patient in terms of prognosis and treatment.In the context of the FH detection program in Argentina (Da Vinci Study) 246 hypercholesterolemic patients were evaluated, 21 with DLCN score8 (definite diagnosis).These patients were studied with next generation sequencing to detect genetic variants, with an extended panel of 23 genes; also they were adding the large rearrangements analysis and a polygenic score of 10 SNP (single nucleotide polymorphism) related to the increase in LDL-c.Of the 21 patients, 10 had variants in LDLR, 1 in APOB with APOE, 1 in LIPC plus elevated polygenic score, and 2 patients showed one deletion and one duplication in LDLR, the later with a variation in LIPA. It is highlighted that 6 of the 21 patients with a score8 did not show any genetic alteration.We can conclude that 28% of the patients with definite clinical diagnosis of FH did not show genetic alteration. The possible explanations for this result would be the presence of mutations in new genes, confusing effects of the environment over the genes, the gene-gene interactions, and finally the impossibility of detecting variants with the current available methods.La hipercolesterolemia familiar (HF) es una enfermedad monogénica asociada a variantes en los genes RLDL, APOB y PCSK9. El diagnóstico inicial se basa en criterios clínicos, como el de la red de clínica de lípidos holandesa (DLCN). Un puntaje8 puntos califica al paciente como “definitivo” para diagnóstico de HF. La identificación de una variante en estos genes permite realizar el cribado en cascada familiar y caracterizar mejor al paciente en cuanto al pronóstico y el tratamiento.En el marco del Programa de Detección de HF en Argentina (Estudio Da Vinci) se evaluó a 246 pacientes hipercolesterolémicos, 21 con puntaje DLCN8 (diagnóstico definitivo). Se estudió a estos pacientes con secuenciación de próxima generación para reconocer variantes genéticas, con un panel ampliado de 23 genes, sumado al análisis de grandes rearreglos y por último se aplicó un score poligénico de 10 SNP (polimorfismo de nucleótido único) relacionados con aumento del c-LDL.De los 21 pacientes, 10 presentaron variantes en RLDL, uno en APOB junto a APOE, uno en LIPC más puntaje poligénico elevado, dos pacientes con una deleción y una duplicación en RLDL y este último caso con una variante en LIPA. Es destacable que 6 de los 21 pacientes con puntaje DLCN8 no mostraron ninguna alteración genética.El 28% de los pacientes con diagnóstico clínico definitivo de HF no evidenció alteración genética. Las posibles explicaciones de este resultado serían la presencia de mutaciones en nuevos genes, los efectos confundidores del ambiente sobre los genes o la interacción gen-gen y por último la imposibilidad de detectar variantes con la metodología actual disponible.

Familial hypercholesterolemia (FH) is a monogenic disease, associated with variants in the LDLR, APOB and PCSK9 genes. The initial diagnosis is based on clinical criteria like the DLCN criteria. A score8 points qualifies the patient as "definite" for FH diagnosis. The detection of the presence of a variant in these genes allows carrying out familial cascade screening and better characterizes the patient in terms of prognosis and treatment.In the context of the FH detection program in Argentina (Da Vinci Study) 246 hypercholesterolemic patients were evaluated, 21 with DLCN score8 (definite diagnosis).These patients were studied with next generation sequencing to detect genetic variants, with an extended panel of 23 genes; also they were adding the large rearrangements analysis and a polygenic score of 10 SNP (single nucleotide polymorphism) related to the increase in LDL-c.Of the 21 patients, 10 had variants in LDLR, 1 in APOB with APOE, 1 in LIPC plus elevated polygenic score, and 2 patients showed one deletion and one duplication in LDLR, the later with a variation in LIPA. It is highlighted that 6 of the 21 patients with a score8 did not show any genetic alteration.We can conclude that 28% of the patients with definite clinical diagnosis of FH did not show genetic alteration. The possible explanations for this result would be the presence of mutations in new genes, confusing effects of the environment over the genes, the gene-gene interactions, and finally the impossibility of detecting variants with the current available methods.La hipercolesterolemia familiar (HF) es una enfermedad monogénica asociada a variantes en los genes RLDL, APOB y PCSK9. El diagnóstico inicial se basa en criterios clínicos, como el de la red de clínica de lípidos holandesa (DLCN). Un puntaje8 puntos califica al paciente como “definitivo” para diagnóstico de HF. La identificación de una variante en estos genes permite realizar el cribado en cascada familiar y caracterizar mejor al paciente en cuanto al pronóstico y el tratamiento.En el marco del Programa de Detección de HF en Argentina (Estudio Da Vinci) se evaluó a 246 pacientes hipercolesterolémicos, 21 con puntaje DLCN8 (diagnóstico definitivo). Se estudió a estos pacientes con secuenciación de próxima generación para reconocer variantes genéticas, con un panel ampliado de 23 genes, sumado al análisis de grandes rearreglos y por último se aplicó un score poligénico de 10 SNP (polimorfismo de nucleótido único) relacionados con aumento del c-LDL.De los 21 pacientes, 10 presentaron variantes en RLDL, uno en APOB junto a APOE, uno en LIPC más puntaje poligénico elevado, dos pacientes con una deleción y una duplicación en RLDL y este último caso con una variante en LIPA. Es destacable que 6 de los 21 pacientes con puntaje DLCN8 no mostraron ninguna alteración genética.El 28% de los pacientes con diagnóstico clínico definitivo de HF no evidenció alteración genética. Las posibles explicaciones de este resultado serían la presencia de mutaciones en nuevos genes, los efectos confundidores del ambiente sobre los genes o la interacción gen-gen y por último la imposibilidad de detectar variantes con la metodología actual disponible.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Recently, triglyceride rich lipoproteins are proposed to contribute to CAD risk; its concentrations would be partly determined by lipoprotein lipase (LPL) and endothelial lipase (EL). Epicardial adipose tissue (EAT), a visceral AT surrounding myocardium and coronary arteries, emerged as an important actor in CAD; the increase in its volume could be a consequence of LPL and EL. Circulating enzymes levels would be conditioned by local tissue factors. Our aim was to evaluate LPL, EL and their regulators levels in serum and EAT from CAD patients, searching for possible parallelisms and their role in the lipoprotein profile.In serum, EAT and subcutaneous AT (SAT) from patients undergoing coronary artery bypass graft (CABG, n = 25) or valve replacement (No CABG, n = 25), LPL, EL and glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein-1 (GPIHBP1) expression were evaluated. Besides, Apoprotein (Apo)CII, CIII and AV were determined in serum, along with lipoprotein profile.Insulin-resistance markers were higher in CABG (p 0.05). Serum LPL levels were decreased (p = 0.045), while EL levels increased (p 0.001) in CABG, without differences in EAT or SAT. Circulating GPIHBP1 concentrations were decreased in CABG (p = 0.047), while EAT GPIHBP1 expression was increased (p 0.001). ApoCII and ApoAV concentrations were higher in CABG (p = 0.016 and p = 0.047, respectively), without differences in ApoCIII concentrations between groups.In EAT, LPL and EL protein levels were not changed in CAD, although GPIHBP1 protein levels were higher. EAT would be a minor contributor to the circulating levels of the enzymes.

OBJECTIVE:Epicardial adipose tissue (EAT) is an active endocrine organ that could contribute to the pathophysiology of coronary artery disease (CAD) through the paracrine release of proatherogenic mediators. Numerous works have analyzed the inflammatory signature of EAT, but scarce informations on its lipidome are available. Our objective was first to study the differences between EAT and subcutaneous adipose tissue (SAT) lipidomes and second to identify the specific untargeted lipidomic signatures of EAT and SAT in CAD. Approach and Results: Subcutaneous and EAT untargeted lipidomic analysis was performed in 25 patients with CAD and 14 patients without CAD and compared with paired plasma lipidomic analysis of isolated VLDL (very low-density lipoprotein) and HDL (high-density lipoprotein). Lipidomics was performed on a C18 column hyphenated to a Q-Exactive plus mass spectrometer, using both positive and negative ionization mode. EAT and SAT had independent lipidomic profile, with 95 lipid species differentially expressed and phosphatidylethanolamine 18:1p/22:6 twenty-fold more expressed in EAT compared with SAT false discovery rate =3×10-4). Patients with CAD exhibited more ceramides (P=0.01), diglycerides (P=0.004; saturated and nonsaturated), monoglycerides (P=0.013) in their EAT than patients without CAD. Conversely, they had lesser unsaturated TG (triglycerides; P=0.02). No difference was observed in the 295 lipid species found in SAT between patients with and without CAD. Fifty-one lipid species were found in common between EAT and plasma lipoproteins. TG 18:0/18:0/18:1 was found positively correlated (r=0.45, P=0.019) in EAT and HDL and in EAT and VLDL (r=0.46, P=0.02).CONCLUSIONS:CAD is associated with specific lipidomic signature of EAT, unlike SAT. Plasma lipoprotein lipidome only partially reflected EAT lipidome. Fil: Barchuk, Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Dutour, Anne. Aix Marseille Universite; Francia Fil: Ancel, Patricia. Aix Marseille Universite; Francia Fil: Svilar, Ljubica. Aix Marseille Universite; Francia Fil: Miksztowicz, Verónica Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Lopez, Graciela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Rubio Mas, Miguel Angel. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Schreier, Laura Ester. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Nogueira, Juan Patricio. Hospital Central de Formosa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Valéro, René. Aix Marseille Universite; Francia Fil: Béliard, Sophie. Aix Marseille Universite; Francia Fil: Martin, Jean Charles. Aix Marseille Universite; Francia Fil: Berg, Gabriela Alicia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Gaborit, Bénédicte. Aix Marseille Universite; Francia

The chronic inflammation associated with rheumatoid arthritis (RA) leads to focal and systemic bone erosion of the joints resulting in a crippling disability. Recent reports indicate an increase in the incidence of RA in the coming years, placing a significant burden on healthcare resources. The incidence of RA is observed to be increasing with age and a significant proportion of those new cases will be aggressively erosive. The altered physiology, due to immune disturbances, contributes towards RA pathogenesis. The imbalance of inflammatory cytokines and non-cytokine immune modulators such as prostaglandin E2 (PGE2) and IL-23-induced pathogenic IL-17, plays a crucial role in persistent inflammation and bone degradation during RA. However, the molecular mechanism of IL-23, a key cytokine, and PGE2 in the development and perpetuation of IL-17 producing effector Th17 cells is poorly understood. This review focuses on research findings that provide insight into the contribution of PGE2 and IL-23 during the development of pathogenic Th17 cells. We also highlight the key transcriptional factors required for Th17 development and therapeutic strategies to disrupt the interaction between IL-23 and IL-17 to prevent the end-organ damage in RA.

Background First description of a technique for left atrium transseptal puncture (TSP) with minimal radiation exposure by using the nonfluoroscopic MediGuide™ tracking system (MG; St. Jude Medical, St. Paul, MN, USA) without the assistance of intracardiac echocardiography. Methods This study included 31 consecutive patients with atrial fibrillation undergoing an MG-assisted percutaneous catheter ablation procedure. A Brockenbrough transseptal needle (BRK) is connected to a standard pressure transducer through a two-input valve. Then, an MG-enabled guidewire is inserted so that its tip exactly matches the BRK's distal tip. After the acquisition of two short radioscopic cine-loops we are able to trace the needle tip on the MG screen, performing the usual TSP maneuver but without fluoroscopy. Successful left atrium access is confirmed by noticing the change in the pressure curve and by advancing the guidewire into the left pulmonary veins. As a control group, 31 matched patients who underwent atrial fibrillation ablation with fluoroscopically guided, pressure-monitored TSP were included. Results Sixty-two MG-assisted TSP attempts were performed; all but two were successfully accomplished without changing to the conventional technique (96.7%). The mean total fluoroscopy time, until the double transseptal access was performed, was 26.65 ± 37.97 seconds in the MG group and 129.13 ± 37.77 seconds in the conventional-TSP group (P < 0.001). No major complications occurred during any of the procedures. Conclusion This new technique for TSP using MG is feasible and can be performed with minimal radiation exposure without the need for additional imaging techniques, achieving a significant reduction of fluoroscopy time.

Epicardial adipose tissue (EAT) is a visceral AT, surrounding myocardium and coronary arteries. Its volume is higher in Type 2 diabetic (DM2) patients, associated with cardiovascular disease risk. Lipoprotein lipase (LPL) hydrolyses triglycerides (TG) from circulating lipoproteins, supplying fatty acids to AT, contributing to its expansion. We aimed to evaluate LPL expression and activity in EAT from DM2 and no DM2 patients, and its regulators ANGPTL4, GPIHBP1 and PPARγ levels, together with VLDLR expression and EAT LPL association with VLDL characteristics.We studied patients undergoing coronary by-pass graft (CABG) divided into CABG-DM2 (n = 21) and CABG-noDM2 (n = 29), and patients without CABG (No CABG, n = 30). During surgery, EAT and subcutaneous AT (SAT) were obtained, in which LPL activity, gene and protein expression, its regulators and VLDLR protein levels were determined. Isolated circulating VLDLs were characterized.EAT LPL activity was higher in CABG-DM2 compared to CABG-noDM2 and No CABG (p=0.002 and p0.001) and in CABG-noDM2 compared to No CABG (p=0.02), without differences in its expression. ANGPTL4 levels were higher in EAT from No CABG compared to CABG-DM2 and CABG-noDM2 (p0.001). GPIHBP1 levels were higher in EAT from CABG-DM2 and CABG-noDM2 compared to No CABG (p= 0.04). EAT from CABG-DM2 presented higher PPARγ levels than CABG-noDM2 and No CABG (p=0.02 and p=0.03). No differences were observed in VLDL composition between groups, although EAT LPL activity was inversely associated with VLDL-TG and TG/protein index (p0.05).EAT LPL regulation would be mainly post-translational. The higher LPL activity in DM2 could be partly responsible for the increase in EAT volume.

Our aim was to analyze the effect of circulating triglyceride rich lipoprotein (TRL) on endothelial function in metabolic syndrome (MetS). Methods We studied 40 patients with MetS (ATPIII), divided into those presenting normal endothelial function (n = 19) and those with endothelial dysfunction (n = 21) by means of the evaluation of pulse wave velocity, before and after brachial artery ischemia. In fasting serum we measured lipid and lipoprotein profile, insulin and glucose (HOMA-IR). Moreover, isolated TRL (d

ResumenEn Argentina no se han realizado estudios destinados a establecer la prevalencia de disglucemias (glucemia alterada en ayunas [GAA], tolerancia alterada a la glucosa [TAG] y diabetes mellitus [DM]) en pacientes con enfermedad renal. Se decidió realizar un estudio observacional, evaluando la frecuencia con prueba de tolerancia oral a glucosa (PTOG) en pacientes con enfermedad renal crónica (ERC), sin registro de disglucemia en sus historias clínicas.Se realizó PTOG a 254 pacientes (60,62% masculinos), con ERC estadios 3, 4 y 5, en tratamiento conservador, hemodiálisis o trasplante.Los resultados mostraron pacientes con valores de DM: 10 pacientes según ayunas exclusivamente (3,94%; IC 95%: 1,35-6,53%); exclusivamente segunda hora, 11 pacientes (4,33%; IC 95%: 1,63-7,03%); por ambos criterios, 15 pacientes (5,91%; IC 95%: 2,81-9,00%); por al menos un criterio, 36 pacientes (14,17%; IC 95%: 9,69-18,66%). En análisis multivariado, la DM se asoció con valor de cintura (OR=1,033 por cm; IC 95%: 1,005-1,062; p=0,019) y con tratamiento sustitutivo vs. conservador (OR=0,41; IC 95%: 0,19-0,92; p=0,028). La GAA (criterio ADA) fue del 19,75% en tratamiento conservador vs. 9,24% en tratamiento sustitutivo, con diferencia estadísticamente significativa. No fue significativa la diferencia de TAG que evidenció 24,6 y 20,3% en tratamiento conservador y sustitutivo, respectivamente.Se propone la realización de PTOG en todo paciente con ERC, ya que permite la detección de todo el rango de disglucemias desconocidas, evitando el subdiagnóstico y favoreciendo la realización de tratamientos para evitar su progresión, en caso de estar ante la presencia de un grupo de riesgo para DM (GAA o TAG), así como la elección de la medicación más adecuada para el trasplante o el inicio del tratamiento de nuevos casos de DM no diagnosticada, para disminuir la morbimortalidad.AbstractIn Argentina, there have been no studies aimed at establishing the prevalence of dysglycaemia (impaired fasting glucose [IFG], impaired glucose tolerance [IGT] and diabetes mellitus [DM]) in patients with chronic kidney disease (CKD). Our group decided to conduct an observational study to evaluate the frequency with oral glucose tolerance test (OGTT) in CKD patients with no previous data for dysglycaemia in their medical records.OGTT was performed in 254 patients (60.62% male) with stage 3, 4 and 5 CKD under conservative treatment, haemodialysis or transplantation.Results for DM were found in 10 patients according to fasting glucose alone (3.94%; 95% CI: 1.35-6.53%), 11 patients with exclusively the second hour criterion (4.33%; 95% CI: 1.63-7.03%), 15 with both criteria (5.91%; 95% CI: 2.81-9.00%) and 36 patients with at least one criteria (14.17%; 95% CI: 9.69-18.66%). In a multivariate analysis, DM was associated with waist circumference (OR=1.033 per cm; 95% CI, 1.005 to 1.062; P=.019) and with conservative treatment vs. replacement therapy (OR=0.41; 95% CI: 0.19-0.92; P=.028). IGT was evident in 24.6% and 20.3 on conservative vs. replacement therapy, with no statistically significant difference. IFG (ADA criteria) was 19.75 vs. 9.24% in conservative vs. replacement therapy, with a statistically significant difference.OGTT is suggested for all CKD patients since it is able to detect the full range of unknown dysglycaemias, which avoids underdiagnoses and favours performing treatments to prevent progression in DM risk groups (IFG and/or IGT). It also aids in the selection of the most appropriate medication for transplantation or treatment initiation in new cases of undiagnosed DM to decrease morbidity and mortality.

Schizophrenia is a complex mental illness that affects 1% of the world population without differences of gender, race, or social status that requires effective antipsychotic treatments producing minimal adverse effects. Schizophrenia is thought as a disconnection disorder of functional brain networks that produces three essential types of clinical manifestations: psychotic symptoms, negative symptoms, and cognitive impairment. The former include loss of contact with reality, including delusions and hallucinations. Negative symptoms are states of deficit in which the basic behavior is diminished or absent. Cognitive impairment includes disturbance in attention, concentration, learning and memory, and operational functions. Schizophrenia is a neurodevelopmental disorder which is the result of multiple factor interactions such as viral illnesses during pregnancy, environmental agents, immunological dysfunction, or obstetric complications. Like other major psychiatric disorders, schizophrenia is also associated with abnormalities in multiple epigenetic mechanisms, resulting in altered gene expression during development and adulthood.

Lipoprotein lipase (LPL) and endothelial lipase (EL) are involved in lipoprotein metabolism. In insulin-resistance, their behavior is altered. Peroxisome proliferator-activated receptors (PPAR) and apoproteins (apo)CII and CIII could be partly responsible for these alterations. To evaluate this response, we assessed Lpl and Lipg expression, protein levels, and enzyme activity in adipose tissue (AT) and heart in an obesity model. Besides, we assessed the role of PPAR and apoC. Male Wistar rats were fed with standard diet (Control, n = 14) or high-fat diet (HFD, n = 14) for 14 weeks. Glucose and lipoprotein profiles were measured. Histological studies were performed in heart and epididymal AT. Lpl and Lipg were assessed by reverse transcription polymerase chain reaction (RT-qPCR), protein levels by Western Blot, and activities by radiometric assays. Cardiac and AT PPAR expression were measured by Western Blot and hepatic Apoc2 and Apoc3 mRNA by RT-qPCR. In HFD, fat deposits were observed in hearts, whereas AT presented a higher adipocyte size. In heart and AT, no differences were found in Lipg mRNA between groups, while AT Lpl mRNA and LPL protein were decreased in HFD, without differences in heart. In both tissues, EL protein levels and activity were increased and inversely associated with decreased LPL activity, being partially responsible for the atherogenic lipoprotein profile in HFD. PPARγ expression in AT was decreased in HFD, without differences in cardiac PPARδ expression and hepatic apoC mRNA. The increase in EL activity could be an alternative pathway for fatty acid release from lipoproteins and uptake in tissues with decreased LPL activity. In AT, PPARγ could be involved in enzyme regulation. Fil: Barchuk, Magalí. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Miksztowicz, Verónica Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Zago, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Cevey, Ágata Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: López, Graciela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Goren, Nora Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Friedman, Silvia. Universidad de Buenos Aires; Argentina Fil: Gelpi, Ricardo Jorge. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Morales, Maria Celina. Universidad de Buenos Aires; Argentina Fil: Fernandez Tomé, María del Carmen. Universidad de Buenos Aires; Argentina Fil: Schreier, Laura Ester. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Berg, Gabriela Alicia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Background: Standard pediatric in-lab polysomnography (PSG) is relatively unavailable and particularly intrusive for children. In low resource settings, nocturnal oximetry has been proposed as a feasible and potentially reliable screening tool for childhood obstructive sleep apnea-hypopnea syndrome (OSAHS), although additional confirmatory evidence is needed. Aims and objectives: Discrete wavelet transform (DWT) could be a useful tool to characterize fluctuations in nocturnal oximetry. We aimed at designing and assessing a model for detecting childhood OSAHS using anthropometric and DWT features. Methods: A total of 298 children with clinical suspicion of OSAHS underwent in-lab PSG. A cut-off of 5 events/h was stipulated as confirming OSAHS. DWT was used to inspect the spectral content of oximetry in frequency bands linked with apnea pseudo-periodicity: detail levels D9 (0.024-0.049 Hz) and D10 (0.012-0.024 Hz). Mean, variance, minimum, and maximum of DWT coefficients were computed. Stepwise logistic regression was employed to build an OSAHS model from DWT, age, gender, and body mass index (BMI) z score. Training (50%) and test (50%) sets were randomly allocated. Results: Age, gender, D9 mean, and D10 variance were automatically selected. Our model reached 79.1% sensitivity, 81.7% specificity, 4.33 LR+, 0.26 LR-, and 80.5% accuracy in the test set. Conclusions: Features from DWT coefficients and anthropometric variables such as age provide complementary information that enables detection of moderate-to-severe childhood OSAHS in a high pre-test probability cohort. Funding: SEPAR (153/2015), Junta Castilla y Leon (VA037U16), MINECO (IJCI-2014-22664).

Methyl gallate is a gallotannin widely distributed in nature. Previous studies have demonstrated its antioxidant, anti-inflammatory, antimicrobial and anti-tumor activities. In the present study, the activity of methyl gallate on experimental models of inflammatory bowel disease has been investigated. Experimental colitis was induced in Sprague–Dawley rats through the intracolonic instillation of an acetic acid solution (2 mL, 4% v/v). Methyl gallate (100 and 300 mg/kg, p.o.) and the reference drug mesalazine (100 mg/kg, p.o.) were tested. Methyl gallate induced a significant reduction in the colon weight/length ratio and macroscopic lesion score. Besides, the malondialdehyde content and the GSSG/GSH ratio were remarkably decreased. Furthermore, the administration of methyl gallate reduced the expression of COX2, IL-6, TNFα and the severity of microscopic tissue damage induced by acetic acid, while the mean goblet cell density was significantly higher in both the group treated with methyl gallate and the one treated with mesalazine, in comparison with untreated animals. The Na+K+ATPase pump activity was recovered in treated groups (control: 827.2 ± 59.6, colitis: 311.6 ± 54.8, methyl gallate 100 mg/kg: 642.2 ± 175.0, methyl gallate 300 mg/kg: 809.7 ± 100.6, mesalazine: 525.3 ± 81.7). Methyl gallate was also found to induce a significant reduction in the castor oil-induced intestinal motility in Swiss mice, decreasing the peristalsis by 74.5 and 58.82% at 100 and 300 mg/kg p.o., respectively. This compound also antagonized the jejunum contractions induced by Ach and CaCl2. This study demonstrates that methyl gallate exerts beneficial effects in a preclinical model of intestinal disorders. Fil: Anzoise, María Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Rodriguez Basso, Angeles Gloria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: del Mauro, Julieta Sofía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Carranza, Maria Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina Fil: López Ordieres, María Graciela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Gorzalczany, Susana Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina

Highlights: - First description of familial hypercholesterolemia mutations in Argentina; - Identification of 7 patients with severe familial hypercholesterolemia; - Wide genetic heterogeneity with 1 relatively common allele, the Lebanese mutation; Description and deep bioinformatics characterization of 4 novel genetic variants; - Studying the exon 14 in a first step could be a low-cost approach for this population. Background: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol and early cardiovascular disease. As cardiovascular disease is a leading cause of mortality in Argentina, early identification of patients with FH is of great public health importance. Objective: The aim of our study was to identify families with FH and to approximate to the characterization of the genetic spectrum mutations of FH in Argentina. Methods: Thirty-three not related index cases were selected with clinical diagnosis of FH. Genetic analysis was performed by sequencing, multiplex ligation-dependent probe amplification, and bioinformatics tools. Results: Twenty genetic variants were identified among 24 cases (73%), 95% on the low-density lipoprotein receptor gene. The only variant on APOB was the R3527Q. Four were novel variants: c.-135C>A, c.170A>C p.(Asp57Ala), c.684G>C p.(Glu228Asp), and c.1895A>T p.(Asn632Ile); the bioinformatics’ analysis revealed clear destabilizing effects for 2 of them. The exon 14 presented the highest number of variants (32%). Four variants were observed in more than 1 case and the c.2043C>A p.(Cys681*) was carried by 18% of index cases. Two true homozygotes, 3 compound heterozygotes, and 1 double heterozygote were identified. Conclusion: This study characterizes for the first time in Argentina genetic variants associated with FH and suggest that the allelic heterogeneity of the FH in the country could have 1 relative common low-density lipoprotein receptor mutation. This knowledge is important for the genotype–phenotype correlation and for optimizing both cholesterol-lowering therapies and mutational analysis protocols. In addition, these data contribute to the understanding of the molecular basis of FH in Argentina. The authors thank the support from University of Buenos Aires, Argentina, UBACyT-B093 and from the Centro Nacional de Genetica Medica, ANLIS ‘‘Dr. Carlos Malbram,’’ Argentina. info:eu-repo/semantics/publishedVersion

Type 2 diabetes (T2DM) and chronic renal disease constitute important risk factors of atherosclerotic cardiovascular disease, associated with lipid abnormalities, and proinflammatory states. Advances in renal replacement therapy such as hemodialysis (HD) have not reduced morbi-mortality. It has not been elucidated if the concomitant presence of T2DM or metabolic syndrome with end-stage renal disease further impairs the atherogenic profiles.We studied 122 HD patients, among which 44 presented with T2DM (HD-T2DM) and 30 with metabolic syndrome (HD-MS); 48 had neither T2DM nor metabolic syndrome (HD-C). Lipoprotein profile, including atherogenic remnant lipoproteins (RLP), and inflammation markers--high sensitivity C-reactive protein (hsCRP), adiponectin, and interleukin-6 (IL-6)--were measured.In all HD patients, triglycerides, free fatty acids, and RLP showed no differences between HD groups, whereas high-density lipoprotein cholesterol (HDL-C) was decreased, particularly in HD-T2DM and HD-MS, with respect to HD-C (P0.01). Regarding inflammatory parameters, both IL-6 and hsCRP were found to be similar between HD groups. Adiponectin paradoxically shows higher values in relation to those expected for insulin resistance situations showing no differences between HD groups.The presence of T2DM or metabolic syndrome did not worsen atherogenic lipoprotein levels, but did reduce HDL-C. Neither was the proinflammatory profile further altered in HD patients in the presence of insulin resistance conditions.

A balance between cell survival and apoptosis is crucial to avoid neurodegeneration. Here, we analyzed whether the pro-apoptotic protein PKCδ, and the pro-survival PKCα and βII, were dysregulated in the brain of R6/1 mouse model of Huntington's disease (HD). Protein levels of the three PKCs examined were reduced in all the brain regions analyzed being PKCδ the most affected isoform. Interestingly, PKCδ protein levels were also decreased in the striatum and cortex of R6/2 and Hdh(Q111/Q111) mice, and in the putamen of HD patients. Nuclear PKCδ induces apoptosis, but we detected reduced PKCδ in both cytoplasmic and nuclear enriched fractions from R6/1 mouse striatum, cortex and hippocampus. In addition, we show that phosphorylation and ubiquitination of PKCδ are increased in 30-week-old R6/1 mouse brain. All together these results suggest a pro-survival role of reduced PKCδ levels in response to mutant huntingtin-induced toxicity. In fact, we show that over-expression of PKCδ increases mutant huntingtin-induced cell death in vitro, whereas over-expression of a PKCδ dominant negative form or silencing of endogenous PKCδ partially blocks mutant huntingtin-induced cell death. Finally, we show that the analysis of lamin B protein levels could be a good marker of PKCδ activity, but it is not involved in PKCδ-mediated cell death in mutant huntingtin-expressing cells. In conclusion, our results suggest that neurons increase the degradation of PKCδ as a compensatory pro-survival mechanism in response to mutant huntingtin-induced toxicity that can help to understand why cell death appears late in the disease.

Huntington's disease is characterized by the formation of protein aggregates, which can be degraded by macroautophagy. Here, we studied protein levels and intracellular distribution of p62 and NBR1, two macroautophagy cargo receptors, during disease progression. In R6/1 mice, p62 and NBR1 protein levels were decreased in all brain regions analyzed early in the disease, whereas at late stages they accumulated in the striatum and hippocampus, but not in the cortex. The accumulation of p62, but not NBR1, occurred in neuronal nuclei, where it co-localized with mutant huntingtin inclusions, both in R6/1 and Huntington's disease patients. Moreover, exportin-1 was selectively decreased in old R6/1 mice brain, and could worsen p62 nuclear accumulation. In conclusion, p62 interacts with mutant huntingtin and is retained in the nucleus along the progression of the disease, mostly in striatal and hippocampal neurons. Thus, cytoplasmic NBR1 might be important to maintain basal levels of selective macroautophagy in these neurons.

Background: Epicardial adipose tissue (EAT) is a visceral adipose tissue (AT) surrounding and infiltrating myocardium and coronary arteries. Increased EAT may represent a chronic inflammatory injury and a link with coronary artery disease (CAD). Metalloproteinases (MMPs) are involved in expansion of AT. Objective: To evaluate MMP-2 and -9 behaviour in EAT from CAD patients. Methods: In EAT and subcutaneous AT (SAT) from patients undergoing coronary artery bypass graft (CABG, n=26) or valve replacement (No CABG, n=18), MMP-2 and -9 activity and localization, inflammatory cells and vascular endothelial growth factor (VEGF) levels were determined. Results: In EAT from CABG, MMP-2 and -9 activity was increased compared with No CABG (p=0.041 and p=0.027, respectively) and compared with SAT (p=0.005 and p=0.048, respectively). In CABG patients EAT showed higher infiltration of macrophages and T lymphocytes than SAT (p=0.01 and p=0.002, respectively). In No CABG patients no sign of cellular retention was observed in EAT or SAT. Vascular density was higher in EAT from CABG than No CABG (p=0.015) and it was directly correlated with MMP-2 (p=0.006) and MMP-9 (p=0.02). VEGF levels in EAT were directly associated with MMP-2 (p=0.016). Conclusion: In EAT from CABG patients the increase of MMP-2 and -9 activity and the presence of inflammatory cells would be partially responsible for extracellular matrix (ECM) remodeling and major vascular density necessary for EAT expansion. Improved knowledge of EAT behaviour may allow to identify new therapeutic targets for the treatment of CAD. Fil: Miksztowicz, Verónica Julieta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Morales, Celina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina Fil: Barchuk, Magalí. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: López, Graciela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Póveda, Ricardo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Gelpi, Ricardo Jorge. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Schreier, Laura Ester. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina Fil: Rubio, Miguel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Berg, Gabriela Alicia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Resumen En Argentina no se han realizado estudios destinados a establecer la prevalencia de disglucemias (glucemia alterada en ayunas [GAA], tolerancia alterada a la glucosa [TAG] y diabetes mellitus [DM]) en pacientes con enfermedad renal. Se decidió realizar un estudio observacional, evaluando la frecuencia con prueba de tolerancia oral a glucosa (PTOG) en pacientes con enfermedad renal crónica (ERC), sin registro de disglucemia en sus historias clínicas. Se realizó PTOG a 254 pacientes (60,62% masculinos), con ERC estadios 3, 4 y 5, en tratamiento conservador, hemodiálisis o trasplante. Los resultados mostraron pacientes con valores de DM: 10 pacientes según ayunas exclusivamente (3,94%; IC 95%: 1,35-6,53%); exclusivamente segunda hora, 11 pacientes (4,33%; IC 95%: 1,63-7,03%); por ambos criterios, 15 pacientes (5,91%; IC 95%: 2,81-9,00%); por al menos un criterio, 36 pacientes (14,17%; IC 95%: 9,69-18,66%). En análisis multivariado, la DM se asoció con valor de cintura (OR = 1,033 por cm; IC 95%: 1,005-1,062; p = 0,019) y con tratamiento sustitutivo vs. conservador (OR = 0,41; IC 95%: 0,19-0,92; p = 0,028). La GAA (criterio ADA) fue del 19,75% en tratamiento conservador vs. 9,24% en tratamiento sustitutivo, con diferencia estadísticamente significativa. No fue significativa la diferencia de TAG que evidenció 24,6 y 20,3% en tratamiento conservador y sustitutivo, respectivamente. Se propone la realización de PTOG en todo paciente con ERC, ya que permite la detección de todo el rango de disglucemias desconocidas, evitando el subdiagnóstico y favoreciendo la realización de tratamientos para evitar su progresión, en caso de estar ante la presencia de un grupo de riesgo para DM (GAA o TAG), así como la elección de la medicación más adecuada para el trasplante o el inicio del tratamiento de nuevos casos de DM no diagnosticada, para disminuir la morbimortalidad. Abstract In Argentina, there have been no studies aimed at establishing the prevalence of dysglycaemia (impaired fasting glucose [IFG], impaired glucose tolerance [IGT] and diabetes mellitus [DM]) in patients with chronic kidney disease (CKD). Our group decided to conduct an observational study to evaluate the frequency with oral glucose tolerance test (OGTT) in CKD patients with no previous data for dysglycaemia in their medical records. OGTT was performed in 254 patients (60.62% male) with stage 3, 4 and 5 CKD under conservative treatment, haemodialysis or transplantation. Results for DM were found in 10 patients according to fasting glucose alone (3.94%; 95% CI: 1.35-6.53%), 11 patients with exclusively the second hour criterion (4.33%; 95% CI: 1.63-7.03%), 15 with both criteria (5.91%; 95% CI: 2.81-9.00%) and 36 patients with at least one criteria (14.17%; 95% CI: 9.69-18.66%). In a multivariate analysis, DM was associated with waist circumference (OR = 1.033 per cm; 95% CI, 1.005 to 1.062; P = .019) and with conservative treatment vs. replacement therapy (OR = 0.41; 95% CI: 0.19-0.92; P = .028). IGT was evident in 24.6% and 20.3 on conservative vs. replacement therapy, with no statistically significant difference. IFG (ADA criteria) was 19.75 vs. 9.24% in conservative vs. replacement therapy, with a statistically significant difference. OGTT is suggested for all CKD patients since it is able to detect the full range of unknown dysglycaemias, which avoids underdiagnoses and favours performing treatments to prevent progression in DM risk groups (IFG and/or IGT). It also aids in the selection of the most appropriate medication for transplantation or treatment initiation in new cases of undiagnosed DM to decrease morbidity and mortality.

Background and objective Hepatic lipase is a lipolytic enzyme mostly synthesized and localized at the surface of liver sinusoidal capillaries, which hydrolyses triglycerides and phospholipids of intermediate density, large low density (LDL) and high density lipoproteins. Hepatic lipase activity is increased in insulin resistant states. Non-alcoholic fatty liver disease (NAFLD) is characterized by insulin resistance. However, at present, no data are available regarding the behaviour of hepatic lipase with regard to the degree of hepatic steatosis. Our aim was to evaluate hepatic lipase activity in NAFLD patients and its relationship to the severity of hepatic steatosis. Design and patients We studied 48 patients with NAFLD (diagnosed by ultrasonography and confirmed by liver biopsy) and 30 controls. Steatosis was semi-quantitatively assessed and considered as mild or grade 1, moderate or grade 2 and severe or grade 3. Measurements: hepatic lipase activity, lipid and lipoprotein profile (including intermediate density lipoproteins and dense LDL), adiponectin, insulin, glucose and high sensitivity C-reactive protein were measured. Homeostasis model assessment for insulin resistance (HOMA) index was calculated. Results Patients with hepatic steatosis presented with higher hepatic lipase activity, HOMA and dense LDL and lower levels of adiponectin, high density lipoproteins, cholesterol and apoA-I. Hepatic lipase activity positively correlated significantly with the severity of hepatic steatosis. Hepatic lipase correlated with a more atherogenic profile and persisted higher in patients even after corrected for age, gender, body mass index, HOMA and adiponectin. Conclusion The higher hepatic lipase activity in NAFLD patients contributes to a more atherogenic profile linked to increased cardiovascular risk, beyond the insulin resistance and the reduction in adiponectin. Copyright © 2012 John Wiley & Sons, Ltd.

Background It is not elucidated if liver fat deposits associated to metabolic syndrome (MS) aggravate the atherogenic state. We evaluated, in MS patients, if the presence of non-alcoholic hepatic steatosis (HS) determines differences in inflammatory markers and VLDL characteristics. Methods Seventy-five patients with MS were divided into 2 groups depending on the presence or absence of HS, assessed by ultrasound. Lipid profile, free fatty acids (FFA), VLDL composition, adiponectin, tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), and soluble adhesion molecules (sVCAM-1 and sICAM-1) were measured. Results HS patients presented increased triglycerides levels, HOMA-IR and FFA. Patients with HS showed a reduction in adiponectin (p = 0.04) and increase in hs-CRP (p = 0.02), independently of insulin-resistance (IR). FFA correlated positively with TNF-α (p = 0.04) and inversely with adiponectin (p = 0.01). hs-CRP correlated with all inflammatory markers, independently of IR: TNF-α (r = 0.34, p = 0.02), sVCAM-1 (r = 0.29 p = 0.03), sICAM-1 (r = 0.56, p = 0.01), adiponectin (r = −0.34, p = 0.04). HS patients presented higher VLDL mass and number of particles. Adiponectin correlated with VLDL cholesterol content (r = −0.47, p = 0.04), independently of IR. VLDL, once secreted, would suffer from changes, becoming more atherogenic. Conclusions Simple HS would play an important role increasing cardiovascular risk, independently of IR. hs-CRP may represent a useful biomarker of this condition.

Both renal failure and type 2 diabetes may contribute synergistically to the dyslipemia of diabetic renal failure with the development of atherosclerosis as the possible consequence. It has not yet been conclusively evaluated whether diabetic patients with end-stage renal failure under maintenance hemodialysis (HD) show accentuated alterations in plasma lipids and lipoproteins in comparison to nondiabetics under HD. These abnormalities would involve hepatic lipase activity and the regulation of triglyceride-rich lipoprotein metabolism. The purpose of the present study was to evaluate whether type 2 diabetic patients undergoing HD exhibited a lipid-lipoprotein profile different from that of nondiabetic hemodialyzed patients. We compared plasma lipids, apoprotein (apo) A-I and B, and lipoprotein parameters among 3 groups: 25 type 2 diabetics, 25 nondiabetics, both undergoing HD, and 20 healthy control subjects. Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) were isolated by sequential ultracentrifugation. Hepatic lipase activity was measured in postheparin plasma. Both groups of HD patients showed higher triglyceride and IDL cholesterol (P.001), and lower high-density lipoprotein (HDL) cholesterol (P.01) and apo A-I (P.001) levels compared to the control group, even after adjustment for age and body mass index (BMI). However, no differences were found in lipid, lipoprotein, and apoprotein concentrations between diabetic and nondiabetic HD patients, except for high LDL triglyceride content of diabetic HD patients (P.01). Nondiabetics undergoing HD also presented higher LDL triglyceride levels than controls (P.05). LDL triglyceride correlated with plasma triglycerides (r = 0.51, P.001). A lower LDL cholesterol/apo B ratio was found in each group of HD patients in comparison to controls (P.02). Comparing the diabetic and nondiabetic patients, hepatic lipase activity remained unchanged, but significantly lower than control subjects (P.001). Hepatic lipase correlated with log-triglyceride (r = -0.31, P.01), IDL cholesterol (r = -0.41, P.001), and LDL triglyceride (r = -0.32, P.01). In conclusion, both diabetic and nondiabetic HD patients shared unfavorable alterations in lipid-lipoprotein profile not different between them but different from a healthy control group. The only difference between the groups of HD patients was a significant LDL triglyceride enrichment, which correlated negatively with hepatic lipase activity. Lipoprotein abnormalities in HD patients would enhance their risk for the development of atherosclerosis.

Background: Metabolic syndrome (MetS) is associated with changes in HDL levels, composition and sub-fraction profile. Whether these alterations affect HDL anti-atherogenic function, specifically measured as its capacity to perform cholesterol efflux, is not yet clearly known. Objective: To evaluate the relation between serum cholesterol efflux capacity and the changes in HDL composition and sub-fraction profile in MetS. Methods: In 35 non-treated MetS patients and 15 healthy controls, HDL mediated cholesterol efflux was measured as the ability of apoB-depleted serum to accept cholesterol from cholesterol-loaded BHK cells expressing either ABCA1 or ABCG1. Additionally we determined: lipid profile, HDL sub-fractions (NMR) and LCAT mass (ELISA). Isolated HDL (δ:1.063-1.210 g/mL) was chemically characterized. Pre-β1-HDL was determined by 2D-electrophoresis in a sub-group of MetS and controls (n = 6 each). Results: Surprisingly, MetS patients presented higher ABCA1 mediated cholesterol efflux (10.4 ± 1.8 vs. 8.7 ± 0.3%; p = 0.0001), without differences in ABCG1 efflux. In MetS, HDL showed reduction in particle size and number (p < 0.02) and lower large/small HDL ratio (p = 0.05), as well as triglyceride enrichment (p = 0.0001). Pre-β1-HDL was increased in MetS (p = 0.048) and correlated with ABCA1-cholesterol efflux (r = 0.64; p = 0.042). LCAT mass showed a tendency to reduction in MetS (p = 0.08), and inversely correlated with ABCA1-cholesterol efflux (r = -0.51; p = 0.001), independently of obesity and insulin-resistance (β = -0.40, p = 0.034). Conclusion: This is the first description of ABCA1 mediated cholesterol efflux in MetS. Regardless the reduced HDL-cholesterol, in vitro cholesterol efflux capacity by ABCA1 was enhanced, linked to increased pre-β1-HDL and slightly reduced in LCAT mass that would probably reflect a delay in reverse cholesterol transport occurring in MetS. Fil: Lucero, Diego Martín. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Fisiopatología y Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Svidirov, Denis. National Institutes of Health; Estados Unidos Fil: Freeman, Lita. National Institutes of Health; Estados Unidos Fil: López, Graciela I.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Fisiopatología y Bioquímica Clínica; Argentina Fil: Fassio, Eduardo. Hospital Nacional Profesor Alejandro Posadas; Argentina Fil: Remaley, Alan T.. National Institutes of Health; Estados Unidos Fil: Schreier, Laura Ester. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Fisiopatología y Bioquímica Clínica; Argentina

SUMMARY Plasma lipid profile and abdominal obesity have been associated with breast cancer risk, however published resuits'have been inconsistent. To clarify these associations we studied lipid and lipoprotein alterations, obesity degree and body fat distribution, in 30 newly diagnosed breast cancer patients without treatment and 30 controls matched by age and menopausal status. Both pre and postmenopausal breast cancer patients presented higher body mass index, waist/hip ratio and insulin levels than their matched controls. An increase in triglycerides and a decrease in HDL-cholesterol, especially in the HDLz subfraction, were observed in patients with breast cancer. Besides, HDL particle from these patients showed increased apo AJHDL-cholesterol ratio. These alterations were correlated with waist/hip ratio. The association between lipoprotein alterations and abdominal obesity independent of menopausal status, in untreated newly diagnosed breast cancer patients is reported for the first time in this study.

Objective: To study size heterogeneity of triglyceride rich lipoproteins (TRL) in metabolic syndrome (MS). Design and methods: Thirty MS patients and 14 healthy subjects were included. In fasting serum we measured: lipid profile, free fatty acids (FFA) and adiponectin; TRL were isolated (d < 1.006 g/mL) and analysis by size exclusion HPLC followed by UV detection was performed; each subfraction was expressed as percentage of total TRL. Results: MS patients, even those with normal triglycerides, presented higher proportion of very large VLDL (90. nm diameter) and large VLDL (60. nm) and slightly lower of typical VLDL (37 nm) (p < 0.04); increased FFA (p. =0.04) and lower adiponectin (p=0.001). FFA correlated with large VLDL% (r. =0.58; p. =0.003), independently of insulin-resistance and waist. Furthermore, the lower the adiponectin, the greater the predominance of large VLDL (r. = - 0.40; p. =0.04). Conclusion: MS was associated with large VLDL, described as more atherogenic beyond triglyceride levels. Size exclusion HPLC would represent a useful tool for assessing subfractions' lipoprotein profile. © 2012 Elsevier Inc. Fil: Lucero, Diego Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Zago, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: López, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: Cacciagiú, Leonardo D.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Lopez, Graciela Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Wigdorovitz de Wikinski, Regina Luisa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Nakajima, Katsuyuki. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Gunma University; Japón Fil: Schreier, Laura Ester. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina

Background: Hepatic steatosis (HS) is closely associated to metabolic syndrome (MS). Both, VLDL-triglyceride oversecretion and intrahepatic deposits, can take place. We evaluated VLDL characteristics, CETP, hepatic lipase (HL), IDL and small dense LDL (sdLDL), in patients with HS associated to MS. Methods: We studied 3 groups matched by age and sex: 25 MS patients with HS (diagnosed by ultrasonography), 25 MS patients without HS and 25 healthy controls. Main measurements were: lipid profile, free fatty acids, VLDL composition, VLDL size by HPLC, CETP and HL activities, IDL-cholesterol and sdLDL-cholesterol. Results: Patients with HS presented higher triglyceride levels, HOMA-IR and free fatty acids, VLDL mass and VLDL-apoB (p < 0.05). No differences in VLDL composition were observed. MS groups presented higher proportion of large VLDL than controls (p < 0.05). HS group showed higher CETP than controls (p = 0.01) and almost higher than MS without HS (p = 0.06). CETP correlated with VLDL-cholesterol content, r = 0.48, p < 0.005. The increase in sdLDL-cholesterol correlated with CETP (r = 0.47) and HL (r = 0.56), independent of insulin resistance (p < 0.003). Conclusion: Despite intrahepatic fat, patients with HS secreted higher number of VLDL particles. CETP would have a remodeling action on VLDL in circulation, enriching it in cholesterol and also favoring, together with HL, the formation of sdLDL. Fil: Lucero, Diego Martín. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina Fil: Zago, Valeria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina Fil: López, Graciela I.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Graffigna, Mabel Nora. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; Argentina Fil: López, Gustavo. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Biología Molecular; Argentina Fil: Fainboim, Hugo. Hospital Muñiz; Argentina Fil: Miksztowicz, Verónica Julieta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina Fil: Gomez Rosso, Leonardo Adrián. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina Fil: Belli, Susana Haydee. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; Argentina Fil: Levalle, Oscar Alberto. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; Argentina Fil: Berg, Gabriela Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Brites, Fernando Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina Fil: Wigdorovitz de Wikinski, Regina Luisa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Schreier, Laura Ester. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina

Adiponectin is an adipokine highly and specifically expressed by adipose cells with antiatherogenic and antiinflammatory activities. The aim of the present study was to evaluate plasma adiponectin concentration in patients with primary hypertriglyceridemia and its relationship with metabolic parameters.Male patients with primary hypertriglyceridemia and without the metabolic syndrome (n=22) were compared with normotriglyceridemic individuals (n=25). Plasma adiponectin concentration was measured by standardised enzyme-linked immunosorbent assay. Body mass index, waist circumference, glucose, insulin and non-esterified fatty acid levels, lipoprotein profile, and CETP activity were evaluated. Adiponectin levels were significantly decreased in hypertriglyceridemic patients in comparison with normotriglyceridemic subjects (4292+/-1717 vs. 6939+/-3249 ng/ml, p0.005, respectively). Adiponectin was negatively associated with glucose (r=-0.44, p0.01), insulin (r=-0.37, p0.01), HOMA (r=-0.40, p0.01), triglycerides (r=-0.36, p0.01), VLDL-C (r=-0.34, p0.05), and CETP (r=-0.47, p0.001). Positive and significant correlations were observed with QUICKI (r=0.49, p0.001) and HDL-C (r=0.33, p0.05). In the multiple linear regression analysis, considering waist circumference, QUICKI, Log-triglycerides, HDL-C, and CETP as independent variables, Log-adiponectin showed a positive correlation with QUICKI, with an r(2)=0.229 and p0.001. Therefore, the independent variable QUICKI explained the 23% of the variance in Log-adiponectin concentration.We found low adiponectin levels in a population of primary hypertriglyceridemic men without the metabolic syndrome and an independent relationship between adiponectin concentration and insulin resistance. A reduction in insulin sensitivity and its impact on adiponectin concentration could be linked to high non-esterified fatty acid levels, increased triglyceride synthesis in the liver and impaired catabolism of triglyceride-rich lipoproteins.

In postmenopausal women (PMW), an adverse lipoprotein pattern and high risk of coronary artery disease has been described. Studies of the mechanisms promoting the higher atherogenic risk observed in healthy PMW are relevant. We evaluated the interactions among several circulating factors involved in the endothelial injury and inflammation in relation to LDL characteristics, beyond LDL cholesterol.Lipoprotein profile, including apolipoproteins A-I and B, small dense LDL, hepatic lipase, cholesterol transfer protein (CETP), LDL composition and oxidability were assessed in PMW (n=30) in comparison to premenopausal (PreMW, n=28). The following emerging factors were measured: homocysteine, phospholipase A2, ferritin, hs-CRP and fibronectin from extracellular vascular matrix. Insulin-resistance was evaluated by waist circumference, HOMA and TG/HDL cholesterol ratios.The risk index apo B/apo A-I was significantly increased in PMW (p0.0001), PMW showed higher proportion of small dense LDL which correlated with the increase in hepatic lipase activity (p0.005) and with insulin-resistance markers (p0.05), but not with CETP. Phospholipase A2 (p0.05), homocysteine (p0.005), hs-CRP (p0.005), fibronectin (p0.05) and ferritin (p0.0001) were increased in PMW. LDL oxidability positively correlated with waist (p0.02), homocysteine (p0.05), fibronectin (p0.05), hs-CRP (p0.04), phospholipase A2 (p0.05), and small dense LDL (p0.01). After adjusting by menopausal condition, age and waist, LDL oxidability remained associated with waist (beta: 0.35, p=0.047), homocysteine (beta: 0,36 p0,038), fibronectin (beta: 0,41 p=0.05), and small dense LDL (beta: 0.36, p=0.027).Evaluation of classic and non-traditional circulating risk factors in hypoestrogenism reflected endothelial and subendothelial inflammation and subclinical atherogenic processes.

Objective Recently, the American Diabetes Association (ADA) proposed a new diagnostic entity for diabetes mellitus that has not been applied in renal failure patients so far. Our goal was to apply the new impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) criteria in a group of hemodialyzed patients to provide data on glucose alterations in chronic renal failure. Design and Patients We evaluated 74 hemodialyzed patients, (38 women, 36 men) without diagnosed diabetes. Blood was collected at fasting and at 120 minutes after a 75-g glucose intake, and insulin levels were determined. The weight, height, waist circumference, and hip circumference of each patient were measured, and the body mass index (BMI) and waist–hip ratio were calculated. Results and Conclusion Values of fasting plasma glycemia and 120-minute oral glucose tolerance test were (mean ± SD) 78 ± 9.4 mg/dL and 121 ± 39 mg/dL, respectively. Among the 74 subjects studied, 5 patients had IFG, none of them showing a glucose level above 110 mg/dL. If the ADA 1997 criteria were applied, these patients would be classified as normal. On the other hand, 15 of the 74 patients showed IGT, this prevalence being higher compared with that of the general population. Finally, in 5 of the 74 patients the presence of type 2 diabetes was shown by the second test. According to sex, no differences were observed in the prevalence of IFG, IGT, or diabetes. Glucose alterations are characteristics that need to be identified in chronic renal failure patients. Our results suggests that the glucose tolerance test might be evaluated during hemodialysis treatment to define its prevalence.