64 research outputs found

    Medida de la independencia funcional con escala FIM en los pacientes con evento cerebro vascular del Hospital Central Militar de Bogotá en el periodo octubre 2010 - mayo 2011

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    El evento cerebro vascular es la enfermedad neurológica más prevalente en el adulto. Causa un gran índice de discapacidad en nuestro medio. Se clasifica en isquémico, embolico o hemorrágico de acuerdo con su origen. Con la medición del nivel de discapacidad se puede determinar el impacto que tiene el evento cerebro vascular en nuestros pacientes y de acuerdo a esto se fijan las metas en rehabilitación, individualizando las prioridades que se requieran de acuerdo a los hallazgos en la valoración clínica

    Inhibition of SOC/Ca2+/NFAT pathway is involved in the anti-proliferative effect of sildenafil on pulmonary artery smooth muscle cells

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    <p>Abstract</p> <p>Background</p> <p>Sildenafil, a potent phosphodiesterase type 5 (PDE5) inhibitor, has been proposed as a treatment for pulmonary arterial hypertension (PAH). The mechanism of its anti-proliferative effect on pulmonary artery smooth muscle cells (PASMC) is unclear. Nuclear translocation of nuclear factor of activated T-cells (NFAT) is thought to be involved in PASMC proliferation and PAH. Increase in cytosolic free [Ca<sup>2+</sup>] ([Ca<sup>2+</sup>]<sub>i</sub>) is a prerequisite for NFAT nuclear translocation. Elevated [Ca<sup>2+</sup>]<sub>i </sub>in PASMC of PAH patients has been demonstrated through up-regulation of store-operated Ca<sup>2+ </sup>channels (SOC) which is encoded by the transient receptor potential (TRP) channel protein. Thus we investigated if: 1) up-regulation of TRPC1 channel expression which induces enhancement of SOC-mediated Ca<sup>2+ </sup>influx and increase in [Ca<sup>2+</sup>]<sub>i </sub>is involved in hypoxia-induced PASMC proliferation; 2) hypoxia-induced promotion of [Ca<sup>2+</sup>]<sub>i </sub>leads to nuclear translocation of NFAT and regulates PASMC proliferation and TRPC1 expression; 3) the anti-proliferative effect of sildenafil is mediated by inhibition of this SOC/Ca<sup>2+</sup>/NFAT pathway.</p> <p>Methods</p> <p>Human PASMC were cultured under hypoxia (3% O<sub>2</sub>) with or without sildenafil treatment for 72 h. Cell number and cell viability were determined with a hemocytometer and MTT assay respectively. [Ca<sup>2+</sup>]<sub>i </sub>was measured with a dynamic digital Ca<sup>2+ </sup>imaging system by loading PASMC with fura 2-AM. TRPC1 mRNA and protein level were detected by RT-PCR and Western blotting respectively. Nuclear translocation of NFAT was determined by immunofluoresence microscopy.</p> <p>Results</p> <p>Hypoxia induced PASMC proliferation with increases in basal [Ca<sup>2+</sup>]<sub>i </sub>and Ca<sup>2+ </sup>entry via SOC (SOCE). These were accompanied by up-regulation of TRPC1 gene and protein expression in PASMC. NFAT nuclear translocation was significantly enhanced by hypoxia, which was dependent on SOCE and sensitive to SOC inhibitor SKF96365 (SKF), as well as cGMP analogue, 8-brom-cGMP. Hypoxia-induced PASMC proliferation and TRPC1 up-regulation were inhibited by SKF and NFAT blocker (VIVIT and Cyclosporin A). Sildenafil treatment ameliorated hypoxia-induced PASMC proliferation and attenuated hypoxia-induced enhancement of basal [Ca<sup>2+</sup>]<sub>i</sub>, SOCE, up-regulation of TRPC1 expression, and NFAT nuclear translocation.</p> <p>Conclusion</p> <p>The SOC/Ca<sup>2+</sup>/NFAT pathway is, at least in part, a downstream mediator for the anti-proliferative effect of sildenafil, and may have therapeutic potential for PAH treatment.</p

    Monosynaptic Ia projections from intrinsic hand muscles to forearm motoneurones in humans

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    Heteronymous Ia excitatory projections from intrinsic hand muscles to human forearm motoneurones (MNs) were investigated. Changes in firing probability of single motor units (MUs) in the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), extensor carpi radialis (ECR), extensor carpi ulnaris (ECU) and extensor digitorum communis (EDC) were studied after electrical stimuli were applied to the median and ulnar nerve at wrist level and to the corresponding homonymous nerve at elbow level.Homonymous facilitation, occurring at the same latency as the H reflex, and therefore attributed to monosynaptic Ia EPSPs, was found in all the sampled units. In many MUs an early facilitation was also evoked by heteronymous low-threshold afferents from intrinsic hand muscles. The low threshold (between 0.5 and 0.6 times motor threshold (MT)) and the inability of a pure cutaneous stimulation to reproduce this effect indicate that it is due to stimulation of group I muscle afferents.Evidence for a similar central delay (monosynaptic) in heteronymous as in homonymous pathways was accepted when the difference in latencies of the homonymous and heteronymous peaks did not differ from the estimated supplementary afferent conduction time from wrist to elbow level by more than 0.5 ms (conduction velocity in the fastest Ia afferents between wrist and elbow levels being equal to 69 m s−1).A statistically significant heteronymous monosynaptic Ia excitation from intrinsic hand muscles supplied by both median and ulnar nerves was found in MUs belonging to all forearm motor nuclei tested (although not in ECU MUs after ulnar stimulation). It was, however, more often found in flexors than in extensors, in wrist than in finger muscles and in muscles operating in the radial than in the ulnar side.It is argued that the connections of Ia afferents from intrinsic hand muscles to forearm MNs, which are stronger and more widely distributed than in the cat, might be used to provide a support to the hand during manipulatory movements
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