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1.
Mech Ageing Dev ; 47(3): 265-79, 1989 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2497284

RESUMO

Diabetes mellitus is associated with premature senescence of cultured dermal fibroblasts. The present study investigated the effect of elevated glucose concentrations on cultured human fibroblasts from normal donors. Mean population doubling times, population doublings until senescence, saturation density at confluence (cells/cm2), tritiated thymidine incorporation, and response to platelet-derived growth factor (PDGF) were inhibited with the increasing glucose concentrations (11.0, 22, 44, or 55 mM glucose) (P less than 0.05). Replicative life span was markedly diminished by multiple passages in high glucose medium (5.5 mM glucose: 62.4 +/- 7.9 population doublings; 22 mM glucose: 22.8 +/- 3.4 population doublings: P less than 0.05). Aldose reductase activity was present in the cultured fibroblasts (3.9 +/- 0.5 nmol/min per mg protein), and inhibitors of aldose reductase, including sorbinil (10(-4) M--10(-6) M) and tolrestat (10(-6) M--10(-8) M), completely prevented glucose-mediated inhibition of fibroblast proliferation, restored the response to PDGF, and allowed a normal replicative life span. Myo-inositol (11 microM--5.5 mM) also reversed the adverse effects of glucose. These in vitro data demonstrate that elevated concentrations of glucose inhibit cell growth and promote premature senescence, effects which can be prevented with inhibitors of aldose reductase or supplemental myo-inositol. These aldose reductase-related effects may explain the impaired growth and premature senescence of cultured connective tissue from diabetic patients.


Assuntos
Aldeído Redutase/antagonistas & inibidores , Epiderme/efeitos dos fármacos , Glucose/farmacologia , Imidazóis/farmacologia , Imidazolidinas , Fator de Crescimento Derivado de Plaquetas/farmacologia , Desidrogenase do Álcool de Açúcar/antagonistas & inibidores , Aldeído Redutase/metabolismo , Células Cultivadas , Células Epidérmicas , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos
2.
J Neurophysiol ; 50(1): 125-35, 1983 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-6875642

RESUMO

Field potentials and units were recorded within the boundaries of the cat medial preoptic area (MPO) following stimulation of the fornix. The position of the recording electrode was marked by pressure injection of alcian blue dye. Stimulation of the medial and lateral aspects of the ipsilateral fornix produced a field consisting of four negative waves and a positive wave. The first and second negative waves had a short latency and duration and appeared to be produced by fornix axons in the MPO. The third negative wave had a longer duration and appeared to be generated by the monosynaptic activation of units in the MPO. The fourth negative wave had a long latency and very long duration and appeared to be generated by polysynaptic activation of neurons in the MPO. The positive wave was associated with inhibition of MPO neurons as a result of fornix excitation of inhibitory interneurons. Responses from nerve fibers in the MPO had latencies corresponding to peaks of the first and second peaks of the evoked potential. Monosynaptically evoked responses to ipsilateral fornix stimulation were recorded all over the dorsal two-thirds of the MPO. Units driven from the medial fornix lay in the periventricular nucleus. Units driven from the lateral fornix lay in the medial preoptic nucleus. Units driven from both medial and lateral fornix lay between units driven by the medial fornix medially and the lateral fornix laterally. Units driven polysynaptically from the ipsilateral fornix lay in the medial preoptic nucleus. About one-quarter of such units were also excited by stimulation of the contralateral fornix. Spontaneously discharging units were recorded all over the MPO. The geometric mean frequency was 2.1 +/- 1.7-2.8 Hz; n = 35. Fornix stimulation inhibited spontaneous units in the medial preoptic nucleus for 50-200 ms. Usually inhibition was evoked by lateral fornix stimulation or by medial or lateral fornix stimulation. Spontaneously discharging units in the periventricular nuclei were not inhibited by fornix stimulation. The position of fornix-excited units suggests they might be temperature sensitive and in female animals, play a role in controlling ovulation.


Assuntos
Córtex Cerebral/fisiologia , Hipocampo/fisiologia , Hipotálamo Posterior/fisiologia , Hipotálamo/fisiologia , Área Pré-Óptica/fisiologia , Núcleos Septais/fisiologia , Animais , Axônios/fisiologia , Gatos , Dominância Cerebral/fisiologia , Estimulação Elétrica , Potenciais Evocados , Vias Neurais/fisiologia , Neurônios/fisiologia , Sinapses/fisiologia
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