RESUMO
The development of contact sensitivity to poison ivy urushiol in guinea pigs was prevented by intravenous injection of 3-n-pentadecylcatechol (I) coupled to autologous blood cells. Hartley, line-bred, guinea pigs were treated with pentadecylcatechol-"modified" blood cells or sham-treated blood cells 2 weeks prior to attempted topical sensitization with I. Skin testing of all guinea pigs with 3-, 1-, and 0.3-microgram doses of I applied in 5 microliter of acetone to abdominal skin sites was begun 2 weeks after attempted sensitization and repeated at 2- or 4-week intervals thereafter for 6 months or until study termination. Profound tolerance to I was observed at all skin testing intervals in the group receiving haptenated red cells and did not weaken with time. Contact sensitivity to I in control animals, however, waned with time; the study was terminated at 6 months because of the low sensitivity level of the control animals at that period. Complete or partial tolerance was induced in approximately 80% of the treated animals. The immune tolerance obtained by the single injection of pentadecylcatechol-associated red blood cells was of long duration and urushiol specific. This treatment also conferred tolerance to three unsaturated congeners of I. The allergenic potencies of the pentadecylcatechols declined with increasing saturation of the alkyl side chain. Binding studies using tritiated pentadecylcatechol showed that 81% of the activity incorporated into the red cell was membrane associated and that 19% was cell sap associated.
Assuntos
Células Sanguíneas/imunologia , Catecóis/imunologia , Dermatite por Toxicodendron/imunologia , Animais , Catecóis/síntese química , Dermatite por Toxicodendron/patologia , Feminino , Cobaias , Tolerância Imunológica , Testes CutâneosRESUMO
The development of contact sensitivity to poison ivy urushiol in Hartley guinea pigs was inhibited by i.v. injection of the diacetate esters of poison ivy and oak urushiols into guinea pigs 2 weeks prior to attempted sensitization with homologous antigen. Immune tolerance to urushiols of poison ivy and oak developed in 80% or more of the treated animals and persisted for the duration of the study, 8 weeks. The tolerance was immunologically specific for urushiols since the tolerant animals were sensitizable to the unrelated sensitizer 2, 4-dinitrochlorobenzene. Guinea pigs already sensitive to urushiol were also desensitized or hyposensitizied by i.v. injection of urushiol acetates in successively increasing doses. After receiving the equivalent of 16 mg of poison ivy and oak urushiols in the acetate form over a period of 12 weeks, 54% of a group of guinea pigs were desensitized to poison ivy. all of the remaining 46% of the guinea pigs still sensitive to poison ivy were substantially hyposensitized (no longer responded to 1.5 or 0.80 microgram test doses of PDC). A control group of guinea pigs was not hyposensitized by injection of vehicle, and remained highly sensitive throughout the 15 week study. The majority of treated animals (less than 80%) were also hyposensitized to poison sumac and cashew nut shell liquid allergens.
Assuntos
Catecóis/imunologia , Dermatite por Toxicodendron/imunologia , Dessensibilização Imunológica , Tolerância Imunológica , Plantas Tóxicas/imunologia , Animais , Esterificação , Feminino , CobaiasAssuntos
Anti-Inflamatórios , Benzopiranos/farmacologia , Canabinoides/farmacologia , Animais , Aspirina/farmacologia , Edema/tratamento farmacológico , Membrana Eritrocítica/efeitos dos fármacos , Feminino , Hemólise/efeitos dos fármacos , Temperatura Alta , Masculino , Fenilbutazona/farmacologia , RatosRESUMO
Of 30 antineoplastic agents studied for their primary irritation potential in rabbits, 9 showed some potential for irritation. Five of these 9 agents produced a significant dermal irritation. None of the irritation observed was considered to be irreversible skin damage. The study further showed a strong correlation between irritation observed by the Draize method and acute inflammation evaluated histopathologically. There was a tendency toward increased epidermal thickness of irritated skin sites. None of the agents produced gross or microscopically visible lesions in the internal organs observed.
Assuntos
Antineoplásicos/toxicidade , Irritantes , Pele/efeitos dos fármacos , Administração Tópica , Animais , Antineoplásicos/administração & dosagem , Dermatite de Contato/etiologia , Feminino , Masculino , Coelhos , Pele/patologia , Fatores de TempoRESUMO
The synthesis of two N-substituted 5,6-benzo-2-azabicyclo[2.2.2]octane analogs of benzomorphan-type analgesics via benzyne addition to appropriate N-substituted N-alkyl-2-pyridones is described. Neither derivative possessed observable analgesic activity at the doses tested.
Assuntos
Analgésicos/síntese química , Benzomorfanos , Compostos Bicíclicos com Pontes/síntese química , Hidrocarbonetos Aromáticos com Pontes/síntese química , Morfinanos , Animais , Compostos Aza/síntese química , Compostos Aza/farmacologia , Comportamento Animal/efeitos dos fármacos , Benzomorfanos/análogos & derivados , Compostos Bicíclicos com Pontes/farmacologia , Masculino , Camundongos , Morfinanos/análogos & derivadosRESUMO
The effects of procaine and four semi-rigid conformational analogs (compounds 1,2,3 and 4) were tested and compared on isolated rabbit atria. Procaine and the four analogs produced positive inotropic effects at all dose levels tested. The antifibrillatory activity of procaine and its analogs arranged in decreasing order of activity was compound 4 greater than 3 greater than 2 greater than 1 greater than procaine. The antifibrillatory activity of the compounds correlated to the distance between the ring nitrogen and the ester oxygen; that is, as the N-O distance increased the concentration required to reduce the following frequency decreased. However, the compound became more toxic as the N-O distance increased. Our data do not confirm the commonly regarded direct relationship between local anesthetic activity and antifibrillatory activity of procaine. Differences in activity displayed by the isomers of procaine could reflect differences in the ability of these analogs to bind to receptors responsible for the respective actions.