RESUMO
Five different types of muscarine-sensitive receptors were identified until now. In routine practice, the nonselective antagonist of cholinoreceptors are replaced by ipratropium bromide that is selectively blocking M1, M2, and M3 subtypes with the same affinity to each of them. However, the blockage of M2 subtype leads to bronchoconstriction and is accompanied by inhibition of M3 receptors in bronchial smooth muscles. The new drug tiotropium bromide selectively inhibits only the M1 and M3 types of receptors and does not affect the M2 subtype. This drug is administered only once a day, which is very important in clinical practice. Thus tiotropium bromide is the drug of choice for basic therapy of COPD.
Assuntos
Broncodilatadores/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Derivados da Escopolamina/uso terapêutico , Animais , Brônquios/metabolismo , Brônquios/fisiopatologia , Broncoconstrição/efeitos dos fármacos , Humanos , Antagonistas Muscarínicos/uso terapêutico , Músculo Liso/metabolismo , Músculo Liso/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Receptores Muscarínicos , Brometo de TiotrópioRESUMO
Data on the therapeutic effectiveness of intravenous injections of immunoglobulins in high doses in patients with bronchial asthma are analyzed. Some possible mechanisms of this therapeutic effect are considered, which are related to of immunoglobulin fragments capable of interacting with cytochrome P-450 and NO-synthase systems of the liver.
Assuntos
Asma/tratamento farmacológico , Sistema Enzimático do Citocromo P-450/metabolismo , Imunoglobulinas/uso terapêutico , Fígado/enzimologia , Óxido Nítrico Sintase/metabolismo , Asma/enzimologia , HumanosRESUMO
The original pseudopeptide drug ingamine (4-[N-[2-(imidazol-4-yl)ethyl]-carbamoyl] butyric acid) was studied on the traditional model of antigen-induced bronchospasm in actively sensitized guinea pigs. The drug was introduced using various methods (by inhalation, via intragastric tube, and by intraperitoneal injections) in a range of doses (20, 50, 150, or 500 mg/kg). The new drug exhibited a pronounced dose-dependent protector action for all ways of introduction, but the most significant effect was observed upon inhalation, whereby the degree of bronchospasm inhibition exceeded 80%. In comparison to the reference drug sodium cromoglycate, ingamine (in equimolar doses) showed a higher activity with respect to the antigen-dependent bronchospasmic reactions. It can be expected that ingamine will provide for the effective treatment of bronchial obstruction under clinical conditions.
Assuntos
Espasmo Brônquico/tratamento farmacológico , Broncoconstrição/efeitos dos fármacos , Histamina/análogos & derivados , Histamina/administração & dosagem , Animais , Hiper-Reatividade Brônquica/tratamento farmacológico , Hiper-Reatividade Brônquica/fisiopatologia , Espasmo Brônquico/fisiopatologia , Relação Dose-Resposta a Droga , Feminino , Cobaias , MasculinoRESUMO
The potential drug ingamine (glutarylhistamine) showed pronounced anti-inflammatory activity on a model of acute noninfectious pneumonia and in the stage of chronic inflammation induced by singe instillation of Sephadex (5 mg/kg) in Wistar rats. A 6-day treatment with ingamine (50-500 microg/kg) by inhalation, intragastric, and intraperitoneal administration produced an anti-inflammatory effect (expressed to various degrees), which was manifested by a decrease in alveolitis, bronchitis, obstructive emphysema, lymphocyte-neutrophile infiltration of interalveolar septa, cytosis, and neutrophile component of bronchoalveolar lavage and by normalization of the cytogram. The most pronounced effect was observed upon inhalation in a dose of 500 microg/kg. In the stage of chronic inflammation, the inhalation of ingamine in a dose of 500 microg/kg produced a significant antiinflammatory action for both 10- and 20-day treatment. The effect was comparable with that of the inhaled glucocorticoid budesonide.
Assuntos
Anti-Inflamatórios/uso terapêutico , Histamina/análogos & derivados , Histamina/uso terapêutico , Pneumonia/tratamento farmacológico , Doença Aguda , Administração por Inalação , Animais , Anti-Inflamatórios/administração & dosagem , Doença Crônica , Histamina/administração & dosagem , Masculino , Pneumonia/induzido quimicamente , Ratos , Ratos WistarRESUMO
Affinity-purified antibodies to morphine (mixture of homeopathic dilutions C30+C200) produced an antitussive effect on male and female guinea pigs with cough induced by citric acid and capsaicin.
Assuntos
Anticorpos/farmacologia , Antitussígenos/farmacologia , Pulmão/efeitos dos fármacos , Morfina/imunologia , Animais , Antitussígenos/imunologia , Capsaicina/farmacologia , Ácido Cítrico/farmacologia , Tosse/induzido quimicamente , Tosse/tratamento farmacológico , Feminino , Cobaias , MasculinoRESUMO
We studied antitussive activity of antibodies to inflammatory mediators (bradykinin, histamine, and serotonin) in ultralow doses. Experiments were performed on guinea pigs with cough induced by citric acid and capsaicin. Test preparations suppressed cough produced by citric acid. Antibodies to bradykinin in ultralow doses were most potent in relieving capsaicin-induced cough (up to 85%); antibodies to serotonin and, particularly, to histamine produced a smaller effect. Potentiated histamine and serotonin possessed polymodal properties.
Assuntos
Anticorpos/farmacologia , Antitussígenos/farmacologia , Bradicinina/imunologia , Histamina/imunologia , Serotonina/imunologia , Animais , Capsaicina/efeitos adversos , Ácido Cítrico/efeitos adversos , Tosse/induzido quimicamente , Tosse/tratamento farmacológico , Relação Dose-Resposta a Droga , Cobaias , Humanos , MasculinoRESUMO
We studied the antiinflammatory effect of a Russian-made glucocorticoid budesonide administered by inhalation and intraperitoneal injection to rats with experimental noninfectious pulmonary granulomatosis. The antiinflammatory effects of budesonide at both administration routes were similar. Intraperitoneal injection, in contrast to inhalation, produced a systemic effect manifested in suppression of hyperplasia of non-encapsulated lymphoid formations in the mucosa.
Assuntos
Anti-Inflamatórios/uso terapêutico , Budesonida/uso terapêutico , Granulomatose Linfomatoide/tratamento farmacológico , Administração por Inalação , Animais , Líquido da Lavagem Broncoalveolar , Hiperplasia/tratamento farmacológico , Infusões Parenterais , Pulmão/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
The influence of gamma-L-glutamylhistamine analogues on the hexenal-induced sleeping, glucocorticoid hormone content in blood plasma and severity of experimental anaphylactic reaction was studied. It was observed that gamma-L-glutamylhistamine analogues caused decrease in the sleeping time and severity of experimental anaphylactic reaction, the elevation of glucocorticoids content in blood plasma. The present results indicate that substances have the wide spectrum of biological activity which depends on the length of the N-acyl radical.
Assuntos
Anafilaxia/tratamento farmacológico , Sistema Enzimático do Citocromo P-450/metabolismo , Glucocorticoides/sangue , Histamina/análogos & derivados , Histamina/farmacologia , Fígado/enzimologia , Anafilaxia/metabolismo , Anafilaxia/fisiopatologia , Animais , Hexobarbital/farmacologia , Histamina/química , Histamina/uso terapêutico , Hipnóticos e Sedativos/farmacologia , Masculino , Camundongos , Sono/efeitos dos fármacosRESUMO
We performed an analysis of the biological activity of dyes possessing certain redox potential. This provided a theoretical basis for the development of a new trend in pharmacology. We demonstrate the wide potential associated with the use of this group of substances to regulate various biochemical processes in the immunity system.
Assuntos
Adjuvantes Imunológicos/farmacologia , Antioxidantes/farmacologia , Corantes/farmacologia , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/uso terapêutico , Animais , Antioxidantes/química , Antioxidantes/uso terapêutico , Asma/tratamento farmacológico , Corantes/química , Corantes/uso terapêutico , Desenho de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Linfócitos/efeitos dos fármacos , Azul de Metileno/uso terapêutico , OxirreduçãoRESUMO
A-25 sephadex-induced granulomatous inflammation of the lungs in rats was treated with beta-carotene and intal in inhalations. Both drugs showed antiinflammatory activity reducing the area of alveolitis and emphysema in the lungs, number of neutrophils and lymphocytes in the bronchoalveolar fluid. The experimental data allow to recommend further trial of intal and beta-carotene in granulomatous pulmonary diseases.
Assuntos
Anti-Inflamatórios/uso terapêutico , Cromolina Sódica/uso terapêutico , Modelos Animais de Doenças , Granuloma de Células Plasmáticas Pulmonar/tratamento farmacológico , beta Caroteno/uso terapêutico , Animais , Líquido da Lavagem Broncoalveolar/citologia , Dextranos , Avaliação Pré-Clínica de Medicamentos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Granuloma de Células Plasmáticas Pulmonar/induzido quimicamente , Granuloma de Células Plasmáticas Pulmonar/patologia , Ratos , Ratos Wistar , Fatores de TempoRESUMO
The authors studied the effect of some antiasthmatic drugs (theophylline, budesonide, sodium cromalyne) and beta-carotene in vitro on spontaneous and PHA-induced proliferation of human peripheral blood mononuclears (PBMN). It was found that the drugs had no effect on spontaneous cell proliferation. But budesonide caused a 4-fold and beta-carotene a 6-fold decrease of the index of PHA-stimulated PBMN proliferation. It is concluded that beta-carotene may be used in clinical practice as an anti-inflammatory agent for bronchial asthma treatment.
Assuntos
Antiasmáticos/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Fito-Hemaglutininas/farmacologia , Timidina/metabolismo , TrítioRESUMO
gamma-L-Glutamyl-histamine (gamma-GluHA) was synthesized at Department of the chemistry and technology of fine organic compounds M. V. Lomonosov Moscow state academy of fine chemical technology. It was investigated the influence of gamma-L-glutamyl-histamine on the severity of experimental anaphylactic reaction, hormonal content in blood plasma and liver cytochrome P-450. The induction of liver cytochrome P-450, the elevation of hormonal content (thyroxine and glucocorticoids) in blood plasma and decrease of the severity of experimental anaphylactic reaction are observed.
Assuntos
Anafilaxia/tratamento farmacológico , Anafilaxia/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Histamina/análogos & derivados , Hormônios/sangue , Fígado/enzimologia , Animais , Cobaias , Histamina/química , Histamina/farmacologia , Histamina/uso terapêutico , Fígado/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The modification of analysis of the hair trace elements involves hair dissolution in nitric acid and analysis of the iron, manganese, and copper by flameless atomic-absorption spectrometry and of zinc by the flame technique. Trace element content has been measured in the hair of 26 normal subjects aged 20-50 and of 20 children. In adults iron, manganese, zinc, and copper concentrations were 12.2 +/- 0.6, 0.55 +/- 0.11, 172 +/- 8, and 12.8 +/- 0.6 micrograms/g, respectively. Higher concentrations of manganese have been observed in females, as well as a tendency to an increase of zinc levels in adults. Analysis of copper in the hair of 44 patients with disseminated sclerosis, carried out by the suggested technique and by direct analysis of the solid sample in a graphite cuvette, has revealed a trend to an elevation of copper content vs. the norm. No significant differences between the hair manganese levels of females and males have been revealed in the patients, such differences being typical of normal subjects. Fluctuations in copper concentrations at different sites of a single hair and a strand have been analyzed in the patients and in normal subjects.
Assuntos
Cabelo/análise , Esclerose Múltipla/metabolismo , Oligoelementos/análise , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
Acetylation phenotype distribution (activity of N-acetyltransferase enzyme) was studied in 29 patients with periodical disease (PD), 73 healthy persons (Armenians), and 20 patients (also Armenians) suffering from epithelial coccygeal cysts. The results obtained indicated the prevalence of slow acetylation phenotype (67%) in the entire Armenian population. PD was characterized by slow acetylation type (28 of 29 patients had slow acetylation with a high frequency of very slow inactivators). The other hereditary pathology, also specific for Armenians (epithelial coccygeal cysts), was characterized by another type of acetylation--a rapid one. The role of slow acetylation as a genetic marker of PD was discussed.