RESUMO
The effect of Padma 28 on selected parameters of humoral and cellular immune reactions in rabbits subjected to experimental atherosclerosis was studied. The drug significantly reduced the size of atherosclerotic plaques in the aorta and restored to a varying extent the immune functions studied. The possible mechanism by which Padma 28 may exert its anti-atherosclerotic action is discussed in the scope of the immunological theory of atherosclerosis.
Assuntos
Arteriosclerose/tratamento farmacológico , Arteriosclerose/imunologia , Extratos Vegetais/farmacologia , Animais , Formação de Anticorpos/efeitos dos fármacos , Arteriosclerose/etiologia , Atividade Bactericida do Sangue/efeitos dos fármacos , Dieta Aterogênica , Hemaglutininas/biossíntese , Ativação Linfocitária/efeitos dos fármacos , Masculino , Fagocitose/efeitos dos fármacos , Precipitinas/biossíntese , CoelhosRESUMO
An observation was made that imuthiol exerts inhibitory effect on hemolysins forming cells (PFC) and on NK cells activity. It also reduces the number of T lymphocytes (in vitro), increases the activity of interleukin-1 and of the lymph node permeability factor. Well recognized is also its protective effect on thymocytes against hydrocortisone. Imuthiol was found to enhance rosette formation and to stimulate stem cells and partly suppressor cells. It reduces the level of cAMP. Its effect on the circulatory system is negligible.
Assuntos
Ditiocarb/farmacologia , Sistema Imunitário/efeitos dos fármacos , Adjuvantes Imunológicos/farmacologia , Animais , Células Produtoras de Anticorpos/efeitos dos fármacos , Citotoxicidade Imunológica/efeitos dos fármacos , Ditiocarb/toxicidade , Cães , Cobaias , Humanos , Técnicas In Vitro , Interleucina-1/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos , Nucleotídeos Cíclicos/metabolismo , Ratos , Ratos EndogâmicosAssuntos
Adjuvantes Imunológicos/imunologia , Imunização , Linfócitos T/imunologia , Animais , Aziridinas/imunologia , Ditiocarb/imunologia , Humanos , Inosina Pranobex/imunologia , Levamisol/imunologia , Camundongos , Mycobacterium bovis/imunologia , Peptídeos/imunologia , Polissacarídeos/imunologia , Propionibacteriaceae/imunologia , Coelhos , Toxoides/imunologia , Vacinas/imunologiaRESUMO
The efficacy of the selected immunosuppressive drugs was studied on the model of iridocyclitis in the rabbit. Intensity of the inflammatory process was evaluated on the basis of biochemical parameters -- protein level and acute phase factors (seromucoid and sialic acid). All preparations used in the experiments indicated a decreasing exacerbation of inflammation as evaluated biochemically. Imuran showed the strongest effect while methotrexate, thiotepa and myleran were less effective.
Assuntos
Hipersensibilidade Imediata/tratamento farmacológico , Imunossupressores/uso terapêutico , Uveíte Anterior/tratamento farmacológico , Animais , Humor Aquoso/metabolismo , Azatioprina/uso terapêutico , Bussulfano/uso terapêutico , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Masculino , Metotrexato/uso terapêutico , Orosomucoide/metabolismo , Coelhos , Ácidos Siálicos/metabolismo , Tiotepa/uso terapêuticoRESUMO
The analysis of immunosuppressive and anti-inflammatory effect of adriamycin in vivo was carried out. Adriamycin restrains blast reaction and decreases the building in of H3 thymidine to the nucleus of lymphocytes. At the same time it decreases the number of B lymphocytes in peripheral blood but it does not influence the level of T lymphocytes. Adriamycin restrains also nonspecific inflammatory reactions reducing the intensity of inflammatory reactions induced by xylene and carrageenin. It also reduces the inflammatory process of granulation. It does not affect histamine and prostaglandin receptors. After discussing the results it was noted that cytostatic effect of adriamycin is accompanied by immunosuppressive and inflammatory components.
Assuntos
Doxorrubicina/imunologia , Aglutininas/biossíntese , Angioedema/induzido quimicamente , Angioedema/tratamento farmacológico , Animais , Anti-Inflamatórios , Linfócitos B/imunologia , Carragenina/efeitos adversos , Dinitroclorobenzeno/efeitos adversos , Doxorrubicina/uso terapêutico , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Cobaias , Imunossupressores , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Ratos , Linfócitos T/imunologia , Xilenos/efeitos adversosRESUMO
The influence of l-nitro-9-/2-dihydroxyethylamino-ethylamino-/-acridine (C-835) and l-nitro-9/3-izopropylaminopropylamino/-acridine (C-846) on the basic functions of animal organism in acute and subchronic experiments was studied. Both compounds displayed distinct all-biologic activity. Their toxicity (LD50) in mice was contained in milligramme interval (i.v.), while LD50 administered into the stomach was several dozen times higher. Even administration in protective phosphate buffer, which provides the most neutral pH, produced quite strong local irritant action. The range between LD50 and LD10 was relatively small, which proved relatively small tolerance factor. Both preparations injected intravenously in the doses starting from several mg/kg had hypotensic influence due to their affinity with the myocardium, the parasymphatetic system and the vascular system. The preparations acted spasmolytically on intestine muscles both in vivo and in vitro in a number of animal species. Central action showed clear stimulating component in a behavioric test. The effect of the compounds in interaction to hypnotic and convulsant drugs was equivocal and dependent on the dose and the reference-preparation. The examined compounds did not influence reproduction processes and did not display the teratogenic action. They impaired only the speed of growth of the newborns. The effect of both examined compounds was qualitatively and quantitatively similar.
Assuntos
Aminacrina/toxicidade , Aminoacridinas/toxicidade , Antineoplásicos/toxicidade , Aminacrina/administração & dosagem , Aminacrina/análogos & derivados , Animais , Comportamento Animal/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Túnica Conjuntiva , Avaliação Pré-Clínica de Medicamentos , Feminino , Fertilidade/efeitos dos fármacos , Cobaias , Técnicas In Vitro , Injeções Intramusculares , Injeções Subcutâneas , Intestino Delgado/efeitos dos fármacos , Masculino , Camundongos , Músculo Liso/efeitos dos fármacos , Soluções Oftálmicas , Coelhos , Ratos , Respiração/efeitos dos fármacos , Fatores de TempoRESUMO
Influence of 1-nitro-9-(2-dihydroxyethylaminoethylamino)-acridines (C-835) and 1-nitro-9-(3-isopropylamino-propylamino)-acridines (C-846) on animal organs and their basic functions was studied in the chronic action. Rabbits responded to the drugs with considerable tolerance which was less manifested in rats. Slight toxic effect was observed only after maximal doses with which the animals survived 3-month exposure. Enzyme studies and creatinine clearance test did not show any clear-cut impairment of hepatic and renal function. Neither did the preparations influence the red and white blood system, nor the blood clotting time. Microscopic examinations showed their slight (initially) morphologic changes which later passed into degenerative changes (liver, kidney, myocardium) as well as typical of oncostatics, changes in intestinal villi, nuclei and lymphatic system. Also desquamation of intestinal epithelium, hypertrophy of their lamina propria, impairment of spermato- and spermiogenesis as well as atrophy of lymphatic germinal centers and decreased number of small lymphocytes in lymph nodes and spleen were noted. Deviation between the results of function and morphologic tests were discussed. Microscopic changes observed after treatment of the tested acridine derivatives were considered too small to damage the particular organs function.
Assuntos
Aminacrina/toxicidade , Aminoacridinas/toxicidade , Antineoplásicos/toxicidade , Aminacrina/administração & dosagem , Aminacrina/análogos & derivados , Animais , Coagulação Sanguínea/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Contagem de Eritrócitos , Intestinos/efeitos dos fármacos , Rim/efeitos dos fármacos , Contagem de Leucócitos , Fígado/efeitos dos fármacos , Linfonodos/efeitos dos fármacos , Masculino , Mesentério , Coelhos , Ratos , Testículo/efeitos dos fármacos , Fatores de TempoRESUMO
The authors investigated the immunological and pharmacological activity of l-cysteine hydrazide. It was found, that the preparation exhibited an interesting immunosuppressive and anti-inflammatory effect, which was evoked by the interference of the drug in nucleic acids and by stabilization of the cell membranes. Moreover it diminished the number of T lymphocytes. L-cysteine hydrazide showed no significant side effects. The authors discussed the possibility of its application in clinical therapy.
Assuntos
Cisteína/análogos & derivados , Imunossupressores , Analgesia , Animais , Anti-Inflamatórios não Esteroides , Artrite Experimental/tratamento farmacológico , Cisteína/imunologia , Cisteína/toxicidade , Cães , Cobaias , Hemodinâmica/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Imunossupressores/farmacologia , Imunossupressores/toxicidade , Camundongos , Músculo Liso/efeitos dos fármacos , Coelhos , Ratos , Respiração/efeitos dos fármacosRESUMO
A number of derivatives of piperidine-2,4,6-trione and oxazine-2,4-dione with cyclohexyl and allyl substituents at their ring were evaluated pharmacologically. Piperidine-2,4,6-trione compounds, regardless of type of substituent, were readily absorbed from the site of their introduction and displayed similar biological activity. Introduction of the N-cyclohexylcarboxamide substituent diminished general toxicity of the derivative and increased anti-inflammatory activity in all tests. The oxazine-4,6-dione derivatives were poorly absorbed. The bis-(1-cyclohexyl-5,5-diallyl-piperidine-2,4,6-trione) derivative, product of condensation of two molecules of a simpler compound, was very well absorbed, strongly toxic, and showed distinct anti-inflammatory activity. Limited correlation between chemical structure and biological activity was noted, supporting the concept that introduction of cyclohexyl and allyl radicals imparts anti-inflammatory and immunosuppressive activity to derivatives of this type.
Assuntos
Anti-Inflamatórios/farmacologia , Piperidinas/farmacologia , Piperidonas/farmacologia , Animais , Células Produtoras de Anticorpos/efeitos dos fármacos , Fenômenos Químicos , Química , Avaliação Pré-Clínica de Medicamentos , Cobaias , Hiperemia/tratamento farmacológico , Imunossupressores/toxicidade , Dose Letal Mediana , Camundongos , Piperidonas/uso terapêutico , Ratos , Teste TuberculínicoRESUMO
Preclinical pharmacologic studies of two further acridine derivatives, 1-nitro-9-(diethylaminopropylamino)-acridine (C-410) and 1-nitro-9-(diethylaminoethylamino)-acridine (C-516) are reported. Both compounds are characterized by high toxicity, especially when injected intravenously, poor absorption from the gastrointestinal tract, and local irritant action. Local irritation can be partly alleviated by using phosphate buffer of pH 7.0 as solvent. Both preparations caused hemodynamic changes (hypotension) due to stimulation of the parasympathetic system (in cats), and higher doses showed direct action on the myocardium. Both preparations acted directly on smooth muscles, predominantly spastically (blood vessels, intestines in vivo and in vitro), and spasmolytically only on the smooth muscle of the urinary bladder in cats. Compound C-410 is deprived of a central component, and compound C-516 in most tests exhibited sedative properties. Despite moderate impairment of spermato- and spermiogenesis, neither of the compounds depressed reproductivity of the animals and no teratogenic action was observed.