Multisystemic inflammatory syndrome related to COVID-19, with latent tuberculosis in bone marrow, and satisfactory response to tocilizumab, in a 7-year-old boy.

Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C) is a new acute-onset systemic inflammatory disease, which mainly affects children. Latent tuberculosis infection (LTBI) is characterized by the presence of immune sensitization to Mycobacterium tuberculosis (MTB) in the absence of any clinical or radiological evidence of active disease. We present a child with MIS-C related to COVID-19, with latent TB in the bone marrow, and satisfactory response to tocilizumab. It is important to pay attention in the investigation of TB cases in countries with a high prevalence of tuberculosis, especially when opting for immunusuppression.

Osteoblastic protein tyrosine phosphatases inhibition and connexin 43 phosphorylation by alendronate.

Bisphosphonates (BPs), potent inhibitors of bone resorption which inhibit osteoclasts, have also been shown to act on osteocytes and osteoblasts preventing apoptosis via connexin (Cx) 43 hemichannels and activating the extracellular signal regulated kinases ERKs. We previously demonstrated the presence of a saturable, specific and high affinity binding site for alendronate (ALN) in osteoblastic cells which express Cx43. However, cells lacking Cx43 also bound BPs. Herein we show that bound [(3)H]-alendronate is displaced by phosphatase substrates. Moreover, similar to Na3VO4, ALN inhibited the activity of transmembrane and cytoplasmic PTPs, pointing out the catalytic domain of phosphatases as a putative BP target. In addition, anti-phospho-tyrosine immunoblot analysis revealed that ALN stimulates tyrosine phosphorylation of several proteins of whole cell lysates, among which the major targets of the BP could be immunochemically identified as Cx43. Additionally, the transmembrane receptor-like PTPs, RPTPµ and RPTPα, as well as the cytoplasmic PTP1B, are highly expressed in ROS 17/2.8 cells. Furthermore, we evidenced that Cx43 interacts with RPTPµ in ROS 17/2.8 and ALN decreases their association. These results support the hypothesis that BPs bind and inhibit PTPs associated to Cx43 or not, which would lead to the activation of signaling pathways in osteoblasts.

Role of connexin 43 in the mechanism of action of alendronate: dissociation of anti-apoptotic and proliferative signaling pathways.

Bisphosphonates (BPs) inhibit osteocyte and osteoblast apoptosis via opening of connexin (Cx) 43 hemichannels and activating the extracellular signal regulated kinases ERKs. Previously, we hypothesized that intracellular survival signaling is initiated by interaction of BPs with Cx43. However, using whole cell binding assays with [(3)H]-alendronate, herein we demonstrated the presence of saturable, specific and high affinity binding sites in the Cx43-expressing ROS 17/2.8 osteoblastic cells, authentic osteoblasts and MLO-Y4 cells expressing Cx43 or not, as well as in HeLa cells lacking Cx43 expression and ROS 17/2.8 cells pretreated with agents that disassemble Cx channels. In addition, both BPs and the PTP inhibitor Na(3)VO(4) increased proliferation of cells expressing Cx43 or not. Furthermore, although BPs are internalized and inhibit intracellular enzymes in osteoclasts, whether the drugs penetrate non-resorptive bone cells is not known. To clarify this, we evaluated the osteoblastic uptake of AF-ALN, a fluorescently labeled analog of alendronate. AF-ALN was rapidly internalized in cells expressing Cx43 or not indicating that this process is not mediated via Cx43 hemichannels. Altogether, these findings suggest that although required for triggering intracellular survival signaling by BPs, Cx43 is dispensable for cellular BP binding, its uptake, as well as the proliferative effects of these agents.

[The pedunculopontine nucleus. A structure involved in motor and emotional processing]. / Núcleo pedunculopontino. Una estructura involucrada en el procesamiento motor y emocional.

INTRODUCTION: There is currently a growing interest for conducting studies into the electrical and neurochemical activity of the pedunculopontine nucleus (PPN) due to the privileged position occupied by this structure in the flow of information to and from the cortex. This nucleus acts as a relay, not only for the motor information that is processed in the basal ganglia but also for information of an emotional type, whose main centre is the nucleus accumbens. It is also strongly linked with the aspects that determine the mechanisms governing addiction to certain drugs. DEVELOPMENT: We conduct a detailed analysis of the main findings from studies of the role played by the PPN in the physiopathology of Parkinsonism, namely the study of metabolic activity, immunohistochemical studies with different tracers, electrophysiological studies that have confirmed the immunohistochemical observations, as well as deep electrical stimulation carried out in non human primates. Furthermore, we also examine the part played by this structure in the processing of emotional information associated with different learning tasks. CONCLUSIONS: Overall, the authors grant the PPN a privileged position in the physiopathology of the axial disorders related to Parkinson s disease; its most important afference, stemming from the subthalamic nucleus, appears to play a key role in the understanding of the part played by the PPN in Parkinsonism.

Núcleo pedunculopontino. Una estructura involucrada en el procesamiento motor y emocional / The pedunculopontine nucleus. A structure involved in motor and emotional processiong

Introducción. Existe en la actualidad un interés creciente por abordar el estudio de la actividad eléctrica y neuroquímica del núcleo pedunculopontino (NPP), debido a la posición privilegiada de esta estructura en el flujo de información que procede de la corteza y regresa a ella. Este núcleo sirve de relevo no sólo a la información motora que se procesa en los ganglios basales, sino también a la información de tipo emocional cuyo principal centro es el núcleo accumbens y está estrechamente relacionado con los mecanismos de adicción a determinados fármacos. Desarrollo. Se realiza un análisis detallado de los principales resultados sobre la función que desempeña el NPP en la fisiopatología del parkinsonismo, a saber: estudio de su actividad metabólica, estudios inmunohistoquímicos con diferentes trazadores, estudios electrofisiológicos-que han confirmado las observaciones inmunohistoquímicas-, así como estimulación eléctrica profunda practicada en primates. Igualmente, se aborda la participación de esta estructura en el procesamiento de información emocional asociada a distintas tareas de aprendizaje. Conclusiones. En general, los autores confieren al NPP una función privilegiada en la fisiopatología de los trastornos axiales relacionados con la enfermedad de Parkinson; su aferencia más importante, procedente del núcleo subtalámico, parece ser una pieza clave para entender la participación del NPP en el parkinsonismo (AU)

[Microdialysis cerebral. Main application of this technique]. / Microdiálisis cerebral. Principales aplicaciones de la técnica.

INTRODUCTION: Microdialysis cerebral technique has been widely employed in order to study the neurotransmitter release. DEVELOPMENT: This technique present numerous advantages such as: allow to work with sample in vivo from animals freely moving, by means of microdialysis can be infused simultaneously different drugs in different points implanted probes in several coordinates; also allow carry out pharmacokinetics studies that show correlation with behavior patter as well as to study metabolic changes, which is not possible when this determination are carry out in tissue, in post mortem stadio. CONCLUSIONS: In the present work is carry out a review about the main results obtaining in the sensitization and abstinence to several drug study and approach to biochemical characteristics to Parkinson s disease (PD) by means of microdialysis technique. In relation to sensibilization studies, the temporal changes in different behavior pattern that modify after amphetamine administration have been studied. Microdialysis study allowed correlationate dopamine concentration with behavior pattern above mentioned. In relation with PD, dopamine concentration after systemic and central (intracerebral) administration of levodopa and another dopaminergic drugs have been studied in different nucleus of basal ganglia as well as its respectively behavior correlates.

Microdiálisis cerebral. Principales aplicaciones de la técnica / Microdialysis cerebral. Main application of this technique

Introducción. La microdiálisis cerebral se ha utilizado ampliamente para estudiar la liberación de neurotransmisores.Desarrollo. Esta técnica presenta numerosas ventajas: permite trabajar con animales vivos en libre movimiento, infunde simultáneamente diferentes fármacos en diferentes puntos, implantando cánulas en distintas coordenadas; permite asimismo llevar a cabo estudios farmacocinéticos que exploren correlaciones con patrones conductuales y estudiar los cambios metabólicos, lo cual no es posible cuando se realizan determinaciones en tejido en un estadio post mortem. Conclusiones. En el presente trabajo se hace un compendio de los principales resultados obtenidos en los estudios de sensibilización y abstinencia a distintos fármacos, y del abordaje que se ha hecho del estudio de la enfermedad de Parkinson (EP) mediante el uso de esta técnica. En relación con los estudios de sensibilización, se han estudiado los cambios temporales en diferentes patrones conductuales que se modifican tras la administración de anfetamina. La microdiálisis también ha permitido correlacionar las concentraciones de dopamina con dichos patrones conductuales. En relación con la EP, se ha estudiado la administración sistémica y central de levodopa y otros fármacos dopaminérgicos en diferentes núcleos de los ganglios basales, junto a sus correlatos conductuales (AU)