RESUMO
We studied the content of aquaporin-5 (AQP5) and epithelial sodium channel (ENaC) in rat lungs during the development of toxic pulmonary edema (TPE) caused by intoxication with phosgene and perfluoroisobutylene (1.5 LC50). The lung body weight index (LBI) was calculated and histological examination of the lung tissues was performed. Localization and expression of AQP5 and ENaC were determined by immunohistochemistry. Intoxication led to a significant (p<0.05) increase in LBI and histological changes typical of TPE 1 and 3 h after the exposure. In 1 and 3 h after phosgene intoxication, the AQP5 and ENaC content significantly (p<0.05) increased in comparison with the control. Similar changes in the AQP5 and ENaC content were observed 1 and 3 h after exposure to perfluoroisobutylene. It was hypothesized that AQP5 plays an important role in the formation of TPE caused by intoxication with acylating pulmonotoxicants. An increase in the content of ENaC can be considered as a compensatory reaction of the body aimed at clearance of the alveolar fluid.
Assuntos
Aquaporina 5 , Canais Epiteliais de Sódio , Fluorocarbonos , Fosgênio , Edema Pulmonar , Animais , Aquaporina 5/metabolismo , Canais Epiteliais de Sódio/metabolismo , Fluorocarbonos/toxicidade , Pulmão/metabolismo , Fosgênio/toxicidade , Alvéolos Pulmonares/metabolismo , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/patologia , RatosRESUMO
We studied the dynamics of respiratory function in rats during intratracheal poisoning with diisopropyl fluorophosphate and pentylenetetrazole in doses corresponding to the LD50 in humans. The maximum of external respiration impairment was recorded in 30 min after poisoning. Administration of diazepam and atropine both separately and in combination during the development of the first signs of poisoning did not significantly affect the respiration parameters, but reduced the incidence of seizures and contributed to a decrease in the rate of animal death. Intratracheal administration of cholinolytic, ß2-adrenomimetic, or glutamate receptors antagonist promoted correction of the respiratory function. It was found that the maximum therapeutic effect in case of diisopropyl fluorophosphates poisoning was achieved after intratracheal administration of ipratropium bromide (0.086 mg/kg), salbutamol (0.086 mg/kg), and MK-801 (0.1 mg/kg), while in case of pentylenetetrazole poisoning, intratracheal administration of ipratropium bromide (0.086 mg/kg) was most effective.
Assuntos
Broncodilatadores/administração & dosagem , Isoflurofato/intoxicação , Pentilenotetrazol/intoxicação , Transtornos Respiratórios/induzido quimicamente , Transtornos Respiratórios/tratamento farmacológico , Convulsões/tratamento farmacológico , Administração por Inalação , Albuterol/administração & dosagem , Animais , Atropina/administração & dosagem , Convulsivantes/intoxicação , Diazepam/administração & dosagem , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Epilepsia/patologia , Ipratrópio/administração & dosagem , Masculino , Ratos , Transtornos Respiratórios/complicações , Transtornos Respiratórios/patologia , Mecânica Respiratória/efeitos dos fármacos , Convulsões/complicações , Convulsões/patologiaRESUMO
We studied the influence of the type and structure of polyethyleneimine on bioavailability and expression of plasmid DNA carrying IGF-1 gene. Polymers with different molecular weights (2.5, 10, 25, and 60 kDa) of linear and branching structure were studied. It was found that the time of polyplex circulation in the blood did not exceed 24 h and the maximum concentration of plasmid DNA was attained with complexes with a molecular weight of 60 kDa. Analysis of liver samples showed that administration of 60-kDa branched polyethyleneimine complex provides DNA protection from degradation for 4 h; in 24 h from the start of the experiment, its concentration was significantly higher than the concentration of other studied polyethyleneimines. The expression of plasmid IGF-1 DNA for this complex attained maximum in 4 h and was equal to 15.50 (7.98; 21.98) arb. units/ml. These results allow us to recommend using polyethyleneimines with branched structure and a molecular weight of 60 kDa for improving plasmid DNA protection and bioavailability.
Assuntos
Portadores de Fármacos/química , Fator de Crescimento Insulin-Like I/farmacocinética , Fígado/química , Plasmídeos/farmacocinética , Polietilenoimina/química , Animais , Animais não Endogâmicos , Disponibilidade Biológica , Expressão Gênica , Injeções Intravenosas , Fator de Crescimento Insulin-Like I/genética , Fígado/metabolismo , Masculino , Estrutura Molecular , Peso Molecular , Plasmídeos/sangue , Ratos , Relação Estrutura-Atividade , Transfecção , TransgenesRESUMO
The efficiency of different reactivators of cholinesterase (toxogonin, dipiroxime, pralidoxime, carboxim, HI-6, and methoxime) at inhibition of butyrylcholinesterase and human acetylcholinesterase by organophosphate insecticide malathion was evaluated in in vitro experiments. Most reactivators increased inhibition of butyrylcholinesterase in comparison with the control, but HI-6 in a concentration of 10-3 mol/liter partially (10%) restored activity of the enzyme. Oxime-induced reactivation of acetylcholinesterase was most pronounced in dipyroxime and toxogonin: parameters of the kinetics of reduction of the phosphorylated enzyme differed by more than 2 times from the values received with the use of other reactivators.
Assuntos
Acetilcolinesterase/metabolismo , Butirilcolinesterase/metabolismo , Inseticidas/farmacologia , Compostos Organofosforados/farmacologia , Oximas/farmacologia , Ativação Enzimática/efeitos dos fármacos , HumanosRESUMO
We compared samples of microencapsulated naloxone prepared by using spray drying technique. 2-Hydroxypropyl-ß-cyclodextrin, sodium alginate, polycaprolactone, and carboxymethyl cellulose were used as the carriers. It was found that the combination of naloxone with sodium alginate was characterized by the highest naloxone content in the matrix and the lowest release rate (100% release time was 60 min). Using the model of respiratory disturbances caused by 10 ED50 fentanyl (anesthetic effect), we studied the effects of naloxone-sodium alginate complex on the dynamics of CO2 concentration in the expired air. It was shown that treatment with the developed microencapsulated naloxone after fentanyl injection allowed reducing the therapeutic dose of the antagonist by more than 2 times and eliminated the necessity of repeated injections.
Assuntos
Portadores de Fármacos , Fentanila/intoxicação , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Entorpecentes/intoxicação , 2-Hidroxipropil-beta-Ciclodextrina/química , Alginatos/química , Animais , Animais não Endogâmicos , Carboximetilcelulose Sódica/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Fentanila/antagonistas & inibidores , Fentanila/toxicidade , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Cinética , Masculino , Naloxona/metabolismo , Antagonistas de Entorpecentes/metabolismo , Entorpecentes/toxicidade , Poliésteres/química , Ratos , Respiração/efeitos dos fármacosRESUMO
Properties of nanoscale carriers recommended by the European Pharmacopeia for use in the creation of drugs and their complexes with physiologically active substances are given. Ihe authors present general descriptions of the methods of creation and especially of carriers identified in the accumulation of experience in their use for creating drugs with desired properties of penetration of biological barriers and length of service of the therapeutic effect.
Assuntos
Sistemas de Liberação de Medicamentos , NanotecnologiaRESUMO
The effects of analgesic substances trimeperidine and dexmedetomidine and their combinations in different proportions (0.75:0.25, 0.5:0.5, 0.25:0.75 of the medium effective doses of each substance) on respiratory function was studied in experiments on rats. Administration of substances in 1 ED50 by analgesic effect (corresponded to medium therapeutic dose of trimeperidine in humans) was characterized by significantly longer suppression of respiration over 90 min in comparison with combined treatment with these substances. Administration of the substances in a dose of 8 ED50 by analgesic effect (corresponded to daily therapeutic dose) over 60 min was followed by more than 3-fold reduction in respiration frequency and respiratory minute volume, more pronounced in animals receiving trimeperidine. Combined administration of these drugs in the specifi ed dose induced less pronounced suppression of respiration and combined administration of trimeperidine and dexmedetomidine in proportion of 0.75:0.25 signifi cantly reduced the period of restoration of respiratory parameters in comparison with animals receiving single substances.
Assuntos
Analgésicos não Narcóticos/farmacologia , Analgésicos Opioides/farmacologia , Dexmedetomidina/farmacologia , Promedol/farmacologia , Respiração/efeitos dos fármacos , Animais , Animais não Endogâmicos , Esquema de Medicação , Combinação de Medicamentos , Cálculos da Dosagem de Medicamento , Masculino , Ratos , Testes de Função RespiratóriaRESUMO
The paper presents an overview of cellular therapy products and medical tissue engineering of the leading countries of the world (including the US) and identifies lines of research in the field of cellular technology application in the interests of national military medicine. The authors gave information concerning practical implementation of the achievements of biomedical research in the field of regenerative cellular products and technologies in Russia as different products, which may be used at the stages of medical evacuation. The authors presented results of research, which was, performed on the model of mine blast injury in accordance with principle possibility of the usage of cellular technologies products (multipotent mesenchymal stromal cells) in medical practice.
Assuntos
Medicina Militar , Pesquisa com Células-Tronco , Transplante de Células-Tronco/tendências , Pesquisa Translacional Biomédica/métodos , Humanos , Medicina Militar/métodos , Medicina Militar/tendências , Federação RussaRESUMO
The kinetics of oxime-induced reactivation of malathion-inhibited cholinesterase has been experimentally studied in vitro. It is shown that oximes do not restore the activity of inhibited butyrylcholinesterase. Acetylcholinesterase reactivation peak (5-mins long) was found to take place upon introduction of dipyroxime (32.5%), pralidoxime (18%), carboxyme (16%) at a concentration of 2.5 x 10(-4) mol/l or toxogonine (26%) at a concentration of 5 x 10(-4) mol/l. Toxogonine demonstrated the maximum affinity to phosphorylated enzyme, while dipyroxime is characterized by a high reactivity with respect to oxime. Significant reactivating ability of these preparations (kR -2300 mol(-1) min(-1) makes them promising solution for the treatment of malathion intoxication.
Assuntos
Acetilcolinesterase/química , Antídotos/química , Butirilcolinesterase/química , Inibidores da Colinesterase/química , Reativadores da Colinesterase/química , Malation/química , Animais , Ativação Enzimática , Eritrócitos/química , Eritrócitos/enzimologia , Cavalos , Cinética , Cloreto de Obidoxima/química , Compostos de Pralidoxima/química , Soluções , Torpedo , Trimedoxima/químicaRESUMO
The tolerance of five central muscarinic receptor antagonists has been studied in experimental animals. According to the effect on orientation-exploratory reaction, drugs were arranged in the following order of increasing toxicity: procyclidine < trihexiphenidyl < benactizine < atropine < scopolamine. For the same therapeutic index, trihexiphenidyl and benactizine were characterized by the maximum tolerance (TD50/ED50 > 10) in mice. Scopolamine and atropine exhibited anticonvulsant activity at doses exceeding the threshold values by a factor of 6.3 and 3.9, respectively. For procyclidine, the average anticonvulsant dose was threefold lower than the threshold value. Benactizine and procyclidine had maximum tolerance levels in rats. The TD50/ED50 ratio for these drugs was greater than 3 (against 0.5 - 0.7 in groups treated with trihexiphenidyl, atropine and scopolamine).