El laboratorio bioquímico en los desórdenes óseos esclerosantes: creatinquinasa y osteopetrosis

Introducción: la osteopetrosis (enfermedad de huesos de mármol) es un raro tipo de displasia ósea esclerosante caracterizada por una alteración en el funcionamiento / morfología del osteoclasto, lo que conduce a un defecto en la resorción ósea. El diagnóstico está basado principalmente en los hallazgos radiográficos. La isoenzima BB de la creatinquinasa(CK-BB) es sintetizada por los osteoclastos y se encuentra casi siempre aumentada en esta patología. Su determinación sérica podría ser útil para el estudio e identificación de la osteopetrosis. Objetivos: alertar frente a resultados discordantes de Creatinquinasa-MB (inmunoinhibición), por la interferencia producida por CKBB osteoclástica en osteopetrosis e incorporar técnicas de mediana complejidad, que permiten reconocer a CKBB, en el estudio de esta rara patología. Materiales y Métodos: suero de cuatro pacientes adultos, con diagnóstico de osteopetrosis, en el que se determinó: actividad de Creatinquinasa y Aspartatoaminotransferasa (IFCC), Lactato-deshidrogenasa(DGKC) y Creatinquinasa-MB (inmunoinhibición), en autoanalizado COBAS6000-Roche; e isoenzimas de Creatinquinasa (electroforesis). Resultados: Se obtuvieron actividades en relación al rango de referencia, superiores de Creatinquinasa (3/4 pacientes) y Aspartato-aminotransferasa (1/4 pacientes); Lactato-deshidrogenasa normales (todos los pacientes); Creatinquinasa-MB (inmunoinhibición) superiores a Creatinquinasa-total (3/4 pacientes). Se constató la presencia de Creatinquinasa-BB (electroforesis), en los mismos pacientes con resultados discordantes de Creatinquinasa-MB. Conclusiones: En los pacientes con clínica e imágenes radiografías que orientan al diagnóstico de osteopetrosis, los resultados aberrantes obtenidos de CKMB, se deben a la Creatinquinasa-BB de aporte óseo, considerada una limitación metodológica. La presencia Creatinquinasa-BB en la electroforesis apoya el diagnóstico, excluyendo a otras enfermedades esclerosantes óseas, brindando una herramienta bioquímica de fácil implementación para el estudio de osteopetrosis.Introduction: Osteopetrosis (marble bone disease) is a rare type of sclerosing bone disorder, characterized by an altered functionality / morphology of the osteoclasts, which generates a defective bone resorption. The diagnosis is based mainly on radiographic findings. In most cases of osteopetrosis, the BB isoenzyme of creatine kinase (CK-BB), which is synthesized by osteoclasts, is increased. Thus, its serum determination may be useful for the study and identification of osteopetrosis. Objectives: To alert against discordant results of Creatine kinase-MB (immunoinhibition), due to the interference produced by osteoclastic CK-BB in osteopetrosis, and to incorporate techniques of medium complexity, which allow recognizing CK-BB, in the study of this rare pathology. Materials and Methods: Sera from four adult patients with diagnosis of osteopetrosis were used to determine: activity of: Creatine kinase and Aspartate-aminotrasferase (AST) (IFCC), Lactate-dehydrogenase (DGKC) and Creatine kinase-MB (immunoinhibition), in an autoanalyzer (COBAS 6000-Roche); and CK isoenzymes (electrophoresis). Results: CK activities (three out of four patients) and AST (one out of four patients) were obtained in relation to the reference range; normal LDH (all patients); CK-MB (immunoinhibition) higher than total CK (three out of four patients). The presence of CK-BB (electrophoresis) was verified in the patients with discordant results of CK-MB. Conclusion: In patients with clinical and radiographic images that guide the diagnosis of osteopetrosis, the aberrant results obtained from CK-MB are due to the CK-BB contributed by the bones, which interferes as a methodological limitation. The presence of CK-BB in electrophoresis supports the diagnosis, excluding other sclerosing osseous diseases, providing a biochemical tool of easy implementation for the study of osteopetrosisFil: Mauro, Florencia Luciana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Pugliese, Lucas Jose. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Brance, María Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Ósea; ArgentinaFil: Guelman, Rodolfo. Hospital Italiano. Instituto Universitario. Escuela de Medicina; ArgentinaFil: Plantalech, Luisa. Hospital Italiano. Instituto Universitario. Escuela de Medicina; ArgentinaFil: Di Carlo, Maria Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentin

Evidence of Helicobacter sp. in dental plaque of captive dolphins (Tursiops gephyreus)

Gastrointestinal lesions have been extensively reported in wild and captive marine mammals. However, their etiology remains unclear. In humans and other animals, chronic gastritis and peptic ulcers have been associated with Helicobacter sp. Therefore, the aim of our study was to investigate the presence of Helicobacter sp. in the gastric juice, dental plaque, and saliva of marine mammals living in a controlled environment. Five dolphins (Tursiops gephyreus), one killer whale (Orcinus orca), one false killer whale (Pseudorca crassidens), three sea lions (Otaria flavescens), two elephant seals (Mirounga leonina), and two fur seals (Arctocephalus australis) were studied. Saliva, dental plaque, and gastric juice samples were examined for Helicobacter sp. using polymerase chain reaction. None of the gastric juice or saliva samples were positive for Helicobacter sp. However, Helicobacter sp. DNA was detected in dental plaque from two dolphins, suggesting the oral cavity might be a reservoir of this bacterium.Fil: Goldman, Cinthia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Loureiro, Julio D.. Fundación Mundo Marino; ArgentinaFil: Quse, Viviana. Fundación Mundo Marino; ArgentinaFil: Corach, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Calderon, Enrique. Fundación Mundo Marino; ArgentinaFil: Caro, Ricardo A.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Boccio, José. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Heredia, Sergio Rodríguez. Fundación Mundo Marino; ArgentinaFil: Di Carlo, Maria Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Zubillaga, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Increased Na+ /Ca2+ exchanger expression/activity constitutes a point of inflection in the progression to heart failure of hypertensive rats

Spontaneously hypertensive rat (SHR) constitutes a genetic model widely used to study the natural evolution of hypertensive heart disease. Ca2+ -handling alterations are known to occur in SHR. However, the putative modifications of Ca2+ -handling proteins during the progression to heart failure (HF) are not well established. Moreover, the role of apoptosis in SHR is controversial. We investigated intracellular Ca2+ , Ca2+ -handling proteins and apoptosis in SHR vs. control Wistar rats (W) from 3 to 15 months (mo). Changes associated with the transition to HF (i.e. lung edema and decrease in midwall fractional shortening), occurred at 15 mo in 38% of SHR (SHRF). In SHRF, twitch and caffeine-induced Ca2+ transients, significantly decreased relative to 6/9 mo and 15 mo without HF signs. This decrease occurred in association with a decrease in the time constant of caffeine-Ca2+ transient decay and an increase in Na+ /Ca2+ exchanger (NCX) abundance (p, 0.05) with no changes in SERCA2a expression/activity. An increased Ca2+ -calmodulin-kinase II activity, associated with an enhancement of apoptosis (TUNEL and Bax/Bcl2) was observed in SHR relative to W from 3 to 15 mo. Conclusions: 1. Apoptosis is an early and persistent event that may contribute to hypertrophic remodeling but would not participate in the contractile impairment of SHRF. 2. The increase in NCX expression/activity, associated with an increase in Ca2+ efflux from the cell, constitutes a primary alteration of Ca2+ -handling proteins in the evolution to HF. 3. No changes in SERCA2a expression/activity are observed when HF signs become evident.Fil: Rodriguez, Jesica S.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Velez Rueda, Jorge Omar. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Salas, Margarita. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Becerra, Romina Valeria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; ArgentinaFil: Di Carlo, Mariano Nahuel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Said, Maria Matilde. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Vittone, Leticia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Rinaldi, Gustavo Juan. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Portiansky, Enrique Leo. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Mundiña, Cecilia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Palomeque, Julieta. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Mattiazzi, Ramona Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentin

Core-rod myopathy due to a novel mutation in BTB/POZ domain of KBTBD13 manifesting as late onset LGMD

Few genes (RYR1, NEB, ACTA1, CFL2, KBTBD13) have been associated with core-rod congenital myopathies [7]. KBTBD13 belongs to the Kelch-repeat super-family of proteins and is implicated in the ubiquitination pathway. Dominant mutations in KBTBD13 have been associated with a peculiar form of core-rod myopathy (NEM6) so far [10]. Childhood onset, slowly progressive proximal muscle weakness with characteristic slowness of movements and combination of nemaline rods, irregular shaped cores and unusual type2 fibres hypotrophy at muscle biopsy, were the main characteristics shared in all the affected members of the four KBTBD13 families reported in the literature [12]. We report on a 65 years old patient, of Sardinian origin, with atypical clinical and morphological presentation of NEM6 due to a novel mutation in KBTBD13 gene

Core-rod myopathy due to a novel mutation in BTB/POZ domain of KBTBD13 manifesting as late onset LGMD

Few genes (RYR1, NEB, ACTA1, CFL2, KBTBD13) have been associated with core-rod congenital myopathies [7]. KBTBD13 belongs to the Kelch-repeat super-family of proteins and is implicated in the ubiquitination pathway. Dominant mutations in KBTBD13 have been associated with a peculiar form of core-rod myopathy (NEM6) so far [10]. Childhood onset, slowly progressive proximal muscle weakness with characteristic slowness of movements and combination of nemaline rods, irregular shaped cores and unusual type2 fibres hypotrophy at muscle biopsy, were the main characteristics shared in all the affected members of the four KBTBD13 families reported in the literature [12]. We report on a 65 years old patient, of Sardinian origin, with atypical clinical and morphological presentation of NEM6 due to a novel mutation in KBTBD13 gene

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Functional network resilience to pathology in presymptomatic genetic frontotemporal dementia

© 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)The presymptomatic phase of neurodegenerative diseases are characterized by structural brain changes without significant clinical features. We set out to investigate the contribution of functional network resilience to preserved cognition in presymptomatic genetic frontotemporal dementia. We studied 172 people from families carrying genetic abnormalities in C9orf72, MAPT, or PGRN. Networks were extracted from functional MRI data and assessed using graph theoretical analysis. We found that despite loss of both brain volume and functional connections, there is maintenance of an efficient topological organization of the brain's functional network in the years leading up to the estimated age of frontotemporal dementia symptom onset. After this point, functional network efficiency declines markedly. Reduction in connectedness was most marked in highly connected hub regions. Measures of topological efficiency of the brain's functional network and organization predicted cognitive dysfunction in domains related to symptomatic frontotemporal dementia and connectivity correlated with brain volume loss in frontotemporal dementia. We propose that maintaining the efficient organization of the brain's functional network supports cognitive health even as atrophy and connectivity decline presymptomatically.This work was funded by the UK Medical Research Council, the Italian Ministry of Health, and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant [grant number CoEN015]. JBR was supported by the Wellcome Trust [grant number 103838]. JBR, RB, TR, and SJ were supported by the NIHR Cambridge Biomedical Research Centre and Medical Research Council [grant number G1100464]. The Dementia Research Centre at UCL is supported by Alzheimer's Research UK, Brain Research Trust, and The Wolfson Foundation, NIHR Queen Square Dementia Biomedical Research Unit, NIHR UCL/H Biomedical Research Centre and Dementia Platforms UK. JDR is supported by an MRC Clinician Scientist Fellowship [grant number MR/M008525/1] and has received funding from the NIHR Rare Disease Translational Research Collaboration [grant number BRC149/NS/MH]. MM is supported by the Canadian Institutes of Health Research, Department of Medicine at Sunnybrook Health Sciences Centre and the University of Toronto, and the Sunnybrook Research Institute. RL is supported by Réseau de médecine génétique appliquée, Fonds de recherche du Québec—Santé [grant number FRQS]. FT is supported by the Italian Ministry of Health. DG is supported by the Fondazione Monzino and Italian Ministry of Health, Ricerca Corrente. SS is supported by Cassa di Risparmio di Firenze [grant number CRF 2013/0199] and the Ministry of Health [grant number RF-2010-2319722]. JvS is supported by The Netherlands Organisation for Health Research and Development Memorable grant [grant number 733050103] and Netherlands Alzheimer Foundation Memorable grant [grant number 733050103].info:eu-repo/semantics/publishedVersio