RESUMO
BACKGROUND: The Population Council studied a pre-coital contraceptive microbicide vaginal product containing levonorgestrel (LNG) as active component and Carraguard gel as a vehicle (Carra/LNG gel) for couples who engage in occasional unplanned intercourse. The objective of this study was to evaluate the effect of sexual intercourse after vaginal application of Carra/LNG gel on serum levels of LNG in women and to assess LNG absorption by the male partner. STUDY DESIGN: This was a randomized, cross-over, pharmacokinetic study including an abstinence arm and an arm in which couples engaged in sexual intercourse between 2 and 4 h after gel application. In each study arm, each woman received a single application of Carra/LNG gel (0.75 mg in 4 mL gel) followed by serial blood samples taken at 0, 1, 2, 4, 8, 24 and 48 h after gel application for LNG measurements. In the intercourse arm, LNG was measured in blood samples taken from the male partner before intercourse and at 4, 8 and 24 h after gel application in the female partner. RESULTS: Time concentration curves for serum LNG levels showed a mean C(max) of 7.8+/-5.5 and 8.3+/-5.7 nmol/L, a mean T(max) of 6.2+/-5.9 and 7.5+/-5.7, and comparable area under the curve for the intercourse and abstinence arm, respectively. Pharmacokinetic parameters presented large variability between subjects, but excellent reproducibility within each subject. LNG was undetectable in 10 out of 12 male partners. CONCLUSION: Sexual intercourse does not appear to interfere with vaginal absorption of LNG after application of a Carra/LNG gel. A vaginal pre-coital contraceptive gel is feasible.
Assuntos
Carragenina/farmacocinética , Coito/fisiologia , Anticoncepcionais Femininos/farmacocinética , Levanogestrel/farmacocinética , Cremes, Espumas e Géis Vaginais/farmacocinética , Absorção , Administração Intravaginal , Adulto , Carragenina/administração & dosagem , Carragenina/sangue , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/sangue , Estudos Cross-Over , Feminino , Humanos , Levanogestrel/administração & dosagem , Levanogestrel/sangue , Masculino , Pessoa de Meia-Idade , Cremes, Espumas e Géis Vaginais/administração & dosagemRESUMO
The partially cyclized mu/nu-carrageenan 1C3, isolated from the red seaweed Gigartina skottsbergii, was previously shown to be a potent inhibitor of the in vitro replication of Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Here the protective effect of 1C3 in a murine model of intraperitoneal ( i. p.) HSV-1 infection was evaluated. OF1 mice were i. p. infected with 5 x 10 (5) PFU of HSV-1 KOS strain, and the effects of different treatments with 1C3 were studied. When 30 mg/kg of body weight of 1C3 was administered by the i. p. route immediately after HSV-1 infection, 87.5 % survival of the animals was achieved (p < 0.005), associated with a delay in the mean day of death in 1C3-treated non-surviving mice. Animal survival was not improved when multiple doses of 1C3 were also given in the period 1 - 48 h post-infection, and no protection was afforded when treatment was started after 24 h of infection. When virus and compound were injected by different routes, i. p. and intravenous ( i. v.), respectively, a still significant protection was achieved (40 % survival, p < 0.05). No toxicity of 1C3 for the animals was recorded. The pharmacokinetic properties were analyzed after injection of 1C3 into the tail vein by monitoring of [ (3)H]-1C3 in plasma and organs and by a bioassay of the anti-HSV-1 activity remaining in serum after non-radioactive 1C3 inoculation. A very rapid disappearance of the compound from the blood was observed since only 5.9 - 0.9 % of the radioactivity of the initially administered [ (3)H]-1C3 appeared in the plasma between 5-300 minutes after administration. A transient peak of radioactivity was detected in the kidney 15 minutes after inoculation. The bioassay confirms the presence of the compound circulating in a biologically active form up to 1 hour after injection.
Assuntos
Antivirais/uso terapêutico , Carragenina/uso terapêutico , Herpes Simples/tratamento farmacológico , Fitoterapia , Rodófitas/química , Animais , Antivirais/isolamento & purificação , Carragenina/isolamento & purificação , Carragenina/farmacocinética , Modelos Animais de Doenças , Injeções Intraperitoneais , Masculino , Camundongos , Preparações de Plantas/uso terapêutico , Distribuição TecidualRESUMO
A cavidade natural da bexiga natatória de Oreochromis niloticus (Tilápia-do-Nilo), pesando entre 100 e 150g, foi utilizada para o estudo da cinética celular inflamatória induzida pela carragenina (n=42). A injeçäo de 0,1ml do irritante (0,5 por cento) na luz da bexiga natatória determinou um processo inflamatório caracterizado por congestäo e edema de sua parede e migraçäo de células, predominantemente mononucleares, para a cavidade. Este fenômeno teve início 3 horas após a injeçäo do irritante, atingindo um máximo às 24 horas. Para caracterizar as células inflamatórias que migraram para a cavidade do órgäo, foi realizada uma análise das células sangüíneas desses animais em nível de microscopia de luz comum e eletrônica. Pode-se demonstrar que as células que migraram para a luz da bexiga natatória após diferentes tempos da injeçäo do irritante eram predominantemente trombócitos. Poucos macrófagos, linfócitos, granulócitos e outras células näo caracterizadas morfofuncionalmente também faziam parte do exsudato
Assuntos
Animais , Carragenina/farmacocinética , Peixes/fisiologiaRESUMO
In order to understand the neuronal mechanisms involved in acute and chronic pain, we studied the thalamic and cortical control action, which allows the suppression of the neuronal responses to noxious stimulation. As an experimental pain model we used carrageenin injected in the paw of male Wistar rats. The tonic facilitatory cortical control on centralis lateralis thalamic nuclei (CL) activity is described at different times after carrgeenin-produced inflammation. Simultaneous extracellular unit recordings were carried out at CL and medial prefrontal cortex (PCx) cells in anesthetized male Wistar rats. The PCx control was tested by blocking in a transient and reversible manner, using the cortical spreading depression (CSD). Carrageenin injection (1 percent; 0.2 ml) into the plantar surface of the right hind paw, and the influence of Lidocaine (2 percent; 0.2 ml) applied in the inflamed paw, was tested on unit activity in PCx and CL cells. Thalamic cells recorded in acute and subacute stages (24-72 h aftercarrageenin administration) were activated by tactile, light pressure and joint movement stimulation yielded before the injection. After carrageenin, the thalamic cells displayed spontaneous high frequency burst discharges, also presenting a progressive and significant increase (p < 0.001, ANOVA test) of their spontaneous firing when rate when compared with control cell activity. Lidocaine reduced the enhanced activity induced by carrageenin in thalamic neurones (p < 0.001, Student t test). In PCx neurones were also recorded in acute and subacute stages. Cortical cells from acute and subacute group were activated by nociceptive and non-nociceptives stimulation. In acute stage, cortical cells increased their firing rate after carrageenin and we could not observe modifications upon their firing rate due to Lidocaine. The CSD blocked all cortical activity in acute subacute stages. During the CSDs, overall thalamic activity was suppressed in neurones from acute (91 percent) and subacute (87 percent) stages. The blockage was observed when the propagated weve produced by CSD arrived into the medial prefrontal cortex. the CSD also suppressed the PCx and the CL noxious responses evoked by pressure in the receptive field. This study show the tonic facilitatory control of the PCx upon intralaminar thalamic noxious responses, during acute and subsacute stages of carrageenin produced inflammation. In the literature, it has been proposed that the CL thalamic...
Assuntos
Ratos , Animais , Carragenina/farmacocinética , Eletrofisiologia/métodos , Dor/fisiopatologia , Ratos Wistar/fisiologia , Tálamo/fisiologia , UretanaRESUMO
Este trabalho descreve o padräo de resposta de edema, aumento de permeabilidade vascular e exsudaçäo celular induzidos pela injeçäo de diferentes suspensöes de carragenina nos coxins plantares de 80 pintos machos, de três a quatro semanas de idade. As suspensöes de carragenina 0,5 por cento foram preparadas em: soluçäo de Ringer-Locke (RL), soluçäo aquosa de Glicose (G), água desmineralizada (W) ou tampäo fosfato salino (PBS). Antes, e às 0:15, 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 e 4:00 horas após a injúria, o volume da pata e a permeabilidade vascular foram avaliados através de pletismografia e extravasamento de Azul de Evans respectivamente. A exsudaçäo celular foi observada em cortes finos de tecido corado, 0:30, 1:30, 2:30 e 4:00 horas após a injeçäo de carragenina ou somente do veículo. A resposta inflamatória variou de acordo com a suspensäo de carragenina utilizada. A suspensäo C/PBS induziu uma resposta inflamatória menos intensa nos coxins plantares do que as suspensöes de C/W, C/G e C/RL
Assuntos
Animais , Masculino , Carragenina/farmacocinética , Galinhas/imunologia , Inflamação/metabolismoRESUMO
Se revisan las evidencias de la localización anatómica y el papel de los péptidos opioides en el procesamiento de la información sensorial nociceptiva y no nociceptiva en la médula espinal. En particular se analizan algunos de los mecanismos que se constituyen per se, en generadores de estados complejos de nocicepción , como la alodinia, es decir estímulos sensoriales no nociceptivos que producen dolor. se propone un modelo experimental con el cual se obtienen resultados prolongados (más de 2 h.) de actividad unicelular, de neuronas registradas en el asta dorsal de la médula espinal de la rata íntegra y anestesiada (uretano, 1500mg/kg). La preparación permite la indentificación de las neuronas registradas, por medio de la activación directa de su campo sensorial. Los cambios en la codificación sensorial se inducen mediante la infiltración subcutánea de carragenina (200 µl, al 1 por ciento) en el mismo campo. Los resultados muestran un incremento de la frecuencia de disparo de las neuronas, que en situación control responden sólo a estimulación táctil suave o al movimiento del pelo. Este incremento es lo que consideramos dolor, dado que se revirtió con la administración de naloxona (1 mg/kg iv) incrementó la frecuencia, después de 80 min. de infiltrada la carragenina. Se puede concluir que con el abordaje experimental presentado se han obtenido datos que reproducen el fenómeno de la alodinia y que éste se encuentra mediado por el sistema opioide