ABSTRACT
Group I of metabotropic glutamate receptors (ImGluRs) are a family of G-protein-coupled receptors which activate a multitude of signaling pathways important for modulating neuronal excitability and synaptic plasticity as well as anti- and prosurvival pathways initiated by hypoxia. However these functions are still not complete and sometimes controversial. The present work is a review of data concerning involvement of ImGluRs in mechanisms of cell response to hypoxia. We also present original data demonstrating their participation in forming pathogenic and adaptogenic intracellular events, appearing in rat neocortex during a day after severe or moderate hypobaric hypoxia, respectively. Ca2+ responses to ImGluRs stimulation in survival cortical slices and expression of ImGluRs, IP3Rs and PLCbeta1 in immunolabelled cortical preparations were estimated for these two different hypoxic models.
Subject(s)
Brain/metabolism , Hypoxia, Brain/metabolism , Receptors, Metabotropic Glutamate/metabolism , Signal Transduction , Adaptation, Physiological , Animals , Brain/enzymology , Brain/pathology , Brain/physiopathology , Calcium Signaling , Humans , Hypoxia, Brain/enzymology , Hypoxia, Brain/pathology , Hypoxia, Brain/physiopathology , Immunohistochemistry , Inositol Phosphates/metabolism , Neurons/enzymology , Neurons/metabolism , Neurons/pathology , Phospholipases/metabolism , Protein Kinase C/metabolismABSTRACT
Hypoxia modifies glutamatergic signaling in the brain producing an increase of intracellular Ca2+ level. Depending on the power of survived hypoxia, degres and spatial-temporal profile of posthypoxic Ca2+ accumulation induce different Ca2+-dependent processes leading cells either to death or to hypoxia tolerance. To elucidate the specificity of different glutamate receptors involvement in these alternative processes the patterns of Ca2+ responses to stimulation of different subtype of ionotropic and metabolotropic glutamate receptors by their agonists were determined in perfused slices of piriform cortex obtained from the rats surviving either severe (pathogenic) or moderate (preconditioning) hypobaric hypoxia. It was shown that hypoxia of different modality modified Ca2+ responses of all tested receptor subtypes in different manner. The greatest difference was found for Ca2+ responses to stimulation of group I metabolotropic glutamate receptors.
Subject(s)
Calcium Signaling , Calcium/metabolism , Cerebellar Cortex/metabolism , Hypoxia/metabolism , Receptors, Glutamate/metabolism , Animals , Male , Rats , Rats, WistarABSTRACT
Low-energy laser irradiation was used in treatment of 77 patients with surgical diseases of the lung and pleura. Laser therapy was performed by means of transcutaneous irradiation of the patients with the use of a semiconductor arsenide-gallium laser and influencing with helium-neon laser on the biologically active points. The use of laser therapy contributed to decrease in incidence of postoperative complications, shortening the duration of treatment of the patients at a hospital.
Subject(s)
Empyema, Pleural/surgery , Laser Therapy , Lung Diseases/surgery , Lung Neoplasms/surgery , Postoperative Complications/radiotherapy , Adult , Aged , Female , Humans , Male , Middle Aged , Postoperative Complications/prevention & controlSubject(s)
Blood Circulation , Pericarditis, Constrictive/physiopathology , Pericardium/surgery , Adolescent , Adult , Aged , Child , Child, Preschool , Hemodynamics , Humans , Infant , Middle Aged , Pericarditis, Constrictive/surgery , Plethysmography, Impedance , Postoperative Period , Time FactorsABSTRACT
To study the possible mechanisms of the formation of secondary therapeutic resistance, the author carried out a chronic experiment on animals which were administered different doses of a neuroleptic (haloperidol) for 20 days. The neuroleptic effect of the drug was shown to significantly decrease following prolonged administration. It was found that upon the first administration of haloperidol mice developed marked catalepsy 2 hours after administration. In conditions of a prolonged administration of the drug its cataleptogenic action was observed to diminish by the 20th day. Diminution of catalepsy was explained by a decrease of the blocking effect of the neuroleptic on the dopamine system. Change in the function of dopamine receptors (zigzag administration of haloperidol or administration of the drug simultaneously with apomorphine) was found to restore the cataleptogenic properties of the neuroleptic. The data obtained were used in the treatment of 47 patients with paranoid schizophrenia who developed resistance to pharmacotherapy.
Subject(s)
Haloperidol/therapeutic use , Schizophrenia, Paranoid/drug therapy , Trifluoperazine/therapeutic use , Animals , Apomorphine/administration & dosage , Catalepsy/chemically induced , Drug Therapy, Combination , Drug Tolerance , Haloperidol/administration & dosage , Haloperidol/pharmacology , Male , MiceABSTRACT
Clinical and experimental studies into the phenomenon of adaptation to neuroleptic agents and into the methods of its overcoming were carried out. An experimental study of the long-term administrations of haloperidol revealed the formation of adaptation to the drug which can be overcome by a zigzag-like sharp elevation of the dosage followed by rapid reduction to the baseline level. The trial of this method under clinical conditions showed that it was expedient to use on a large scale the experimental findings on the specific features of the formation and prevention of the secondary therapeutic resistance.
Subject(s)
Haloperidol/therapeutic use , Schizophrenia, Paranoid/drug therapy , Adult , Animals , Catalepsy/chemically induced , Corpus Striatum/metabolism , Disease Models, Animal , Drug Therapy, Combination , Drug Tolerance , Haloperidol/administration & dosage , Humans , Male , Mice , Receptors, Dopamine/metabolism , Spiperone/metabolism , Trifluoperazine/therapeutic useABSTRACT
It has been shown in experiments on male mice that prolonged administration (for 20 days) of haloperidol in doses of 0.1, 1.0, 5.0 and 10.00 mg/kg produced an increase in the tolerance to thecataleptogenic effect at the end of administration and a rise in 3H-spiroperidole binding with striatum membranes on the 5th day after discontinuation of the neuroleptic, which attests to an increase in the sensitivity of dopamine receptors. Variation of haloperidol dose every other three days during 20 days of drug administration (1.0--0.1 ... 1.0 mg/kg and 1.0--10.00 ... 1.0 mg/kg) eliminated the manifestations of tolerance and hypersensitivity of dopamine receptors. It is assumed that variation of the neuroleptic dose during prolonged administration prevents the development of extrapyramidal disorders of the hyperkinetic type.