RESUMO
A recently observed developmental instability of the ano-genital distance (AGD) in female mice indicates that natural prenatal androgens do not have such a robust effect on female genital morphology as has been generally assumed. Part of this instability might be caused by oestrous cyclicity. To check this assumption, we examined the effect of the stage of the oestrous cycle on the AGD in adult (61-75 days old) female mice. Consistent with our assumption, the female AGD (1) varied during the oestrous cycle (p < 0.05), indicating thus rapid changes in morphology of female external genitalia, and (2) showed good repeatability (>0.66) in each stage of the oestrous cycle, suggesting that female genital morphology systematically varied within the oestrous cycle. Therefore, the stage of the oestrous cycle should be considered when assessing prenatal masculinization in adult female mice.
Assuntos
Ciclo Estral/fisiologia , Camundongos/anatomia & histologia , Camundongos/fisiologia , Períneo/anatomia & histologia , Animais , Pesos e Medidas Corporais , Feminino , Camundongos Endogâmicos ICR , Períneo/fisiologia , Reprodutibilidade dos TestesRESUMO
T-20 is a novel antiretroviral agent that inhibits the fusion of human immunodeficiency virus (HIV) with target cell membranes. It is delivered by self-administered, twice-daily, subcutaneous injections. The impact of this mode of administration on patients' ability to conduct normal activities of daily living (ADL) and comply with a T-20 treatment regimen was assessed as part of a 48-week, phase 2 trial (T20-205). Patients' opinions on the impact of T-20 on ADL, ease of use of T-20, and choice to continue with T-20 were assessed by two questionnaires completed at baseline and week 48 (or study withdrawal). ADL were measured using a Likert-type scale based on established instruments with questions added to assess HIV-specific issues. Seventy previously treated patients received T-20 in combination with an average of five oral antiretroviral agents. Relative to other HIV/AIDS drugs, T-20 had little impact on ADL, with the majority of patients (54%-96%) agreeing (somewhat or strongly) that subcutaneous injections had not limited ADL. Patients found the injections relatively easy to perform with more than 47% of patients stating that each aspect of the injections (ease of injection, storage, reconstitution, and disposal of sharps) were very easy or easy. If medically indicated, 98% of patients stated that they would choose to continue with T-20. The most common reasons for this were the perceived effectiveness of T-20 and lack of side effects. In conclusion, the need to deliver T-20 via twice-daily subcutaneous injections was not considered an important barrier by HIV-positive patients seeking improvement or stabilization of their condition.
Assuntos
Atividades Cotidianas , Fármacos Anti-HIV/uso terapêutico , Proteína gp41 do Envelope de HIV/uso terapêutico , Inibidores da Fusão de HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Satisfação do Paciente , Fragmentos de Peptídeos/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Enfuvirtida , Feminino , Proteína gp41 do Envelope de HIV/administração & dosagem , Inibidores da Fusão de HIV/administração & dosagem , Humanos , Injeções Subcutâneas , Masculino , Fragmentos de Peptídeos/administração & dosagem , Autoadministração , Inquéritos e QuestionáriosAssuntos
Fármacos Anti-HIV/farmacocinética , Inibidores da Protease de HIV/farmacocinética , Nelfinavir/farmacocinética , Nevirapina/farmacocinética , Inibidores da Transcriptase Reversa/farmacocinética , Fármacos Anti-HIV/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Interações Medicamentosas , Inibidores da Protease de HIV/farmacologia , Humanos , Nelfinavir/farmacologia , Nevirapina/farmacologia , Inibidores da Transcriptase Reversa/farmacologiaAssuntos
Fármacos Anti-HIV/uso terapêutico , Proteína gp41 do Envelope de HIV/química , Infecções por HIV/tratamento farmacológico , Peptídeos/química , Peptídeos/uso terapêutico , Administração Oral , Quimioterapia Combinada , Inibidores da Protease de HIV , Humanos , Masculino , Pessoa de Meia-Idade , Nelfinavir , Nevirapina , Inibidores da Transcriptase Reversa , SaquinavirRESUMO
Nevirapine and indinavir have the potential of affecting the pharmacokinetics of each other. In a prospective trial, 24 human immunodeficiency virus (HIV)-infected subjects on stable nucleoside or no therapy were treated with 800 mg of indinavir every 8 h. After 7 days, 200 mg of nevirapine a day was added for 14 days and then increased to 200 mg twice a day. At day 7 (before nevirapine), there was a sevenfold difference among the subjects in indinavir area under the curve (AUC), and there was a significant correlation between indinavir AUC (r2=0.378, P=.019), minimum plasma concentration (Cmin; r2=0.359, P=.023), maximum plasma concentration (Cmax; r2=0.340, P=.028), and plasma HIV RNA decline. Nevirapine significantly reduced median indinavir Cmin (47.5%) and AUC (27.4%) and, to a lesser extent, Cmax (11%). Plasma HIV RNA values were =20 copies/mL in 10 of 17 (58.8%) subjects at 58 weeks or last visit. These data suggest that indinavir dosing should be dependent on drug exposure and not on cotherapy with nevirapine.