Assuntos
Anti-Inflamatórios/administração & dosagem , Budesonida/administração & dosagem , Esofagite Eosinofílica/tratamento farmacológico , Administração Oral , Adolescente , Biópsia , Criança , Pré-Escolar , Esofagite Eosinofílica/patologia , Esôfago/patologia , Frutas , Mel , Humanos , Lactente , Veículos Farmacêuticos/administração & dosagem , Sacarose/administração & dosagem , Sacarose/análogos & derivados , Edulcorantes/administração & dosagemRESUMO
BACKGROUND: We report herein a novel strategy for the preparation of protein-based nanodelivery vehicles for hydrophobic active pharmaceutical ingredients. METHODS: The procedure consisted of three steps, ie, exposure of hydrophobic residues of a protein to a pH-induced partial unfolding: interaction between hydrophobic residues on the protein and the hydrophobic active pharmaceutical ingredient, and a final step where the structure of the protein was reversed to a native-like state by returning to neutral pH. As proof of concept, the interaction of paclitaxel with partially unfolded states of human serum albumin was evaluated as a potential method for the preparation of water-soluble complexes of the taxane with albumin. RESULTS: We found that paclitaxel readily binds to pH-induced partially unfolded albumin, leading to the formation of optically clear water-soluble complexes. The complexes thus formed were more stable in solution when the albumin native state was at least partially restored by neutralization of the solution to a pH around 7. It was also observed that the hydrodynamic radius of human serum albumin was only slightly increased after the cycle of pH changes, remaining in a monomeric state with a size according to paclitaxel binding. Furthermore, paclitaxel binding did not affect the overall exposure of charged groups of human serum albumin, as evaluated by its interaction with an ionic exchange resin. CONCLUSION: The in vitro biological activity of the complexes formed was qualitatively equivalent to that of a Cremophor(®)-based formulation.
Assuntos
Paclitaxel/administração & dosagem , Paclitaxel/química , Albumina Sérica/química , Linhagem Celular Tumoral , Cromatografia por Troca Iônica , Estabilidade de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Nanopartículas/ultraestrutura , Concentração Osmolar , Tamanho da Partícula , Veículos Farmacêuticos/administração & dosagem , Veículos Farmacêuticos/química , Polietilenoglicóis/química , Desdobramento de Proteína , Albumina Sérica/administração & dosagem , Solubilidade , TemperaturaRESUMO
OBJECTIVE: In order to clarify the effect of the prenatal (PN) treatment of the drug 1,4,6-androstatriene-3,17-dione (ATD) which blocks the conversion of testosterone into estradiol on male sexual behavior of the rats offsprings, from the effect of the mild stress induced by the PN administration of the Propylene glycol (PG), the vehicle used to dissolve ATD. METHODS: Pregnant Wistar rats were divided into three groups. The CON group did not receive any kind of treatment. The other two groups (PG and ATD) were injected i.p. during gestation (days 11-22) with 0 and 5 mg of ATD, dissolved in 0.1 ml of PG, respectively, doses reported by other authors. Sexual performance of the male pups was analyzed three months later in four successive tests. RESULTS: In the first sexual test of these naive rats, the percentage of males mounting, intromitting, ejaculating and the ejaculation frequency of the ATD group decreased significantly in comparison with the CON group. Also in the first and 4th tests, mounting, intromission and ejaculation latencies, as in the post-ejaculatory refractory period, ATD group, was significantly longer in comparison with the CON group. PG males showed a male sexual behavior (MSB) similar to that observed in the ATD group, but the differences did not reach statistical significance when they were compared with the CON group. CONCLUSION: We considered that the PN stress induced by the daily administration of PG and ATD, results in a slower execution of the MSB in both groups and avoid distinguish the effect of the ATD. Then chronic PN injections, as a route of administration, could act as mild stressor and may have additive effects on drugs affecting brain sexual differentiation.
Assuntos
Androstatrienos/farmacologia , Inibidores Enzimáticos/farmacologia , Veículos Farmacêuticos/farmacologia , Propilenoglicol/farmacologia , Diferenciação Sexual/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Estresse Psicológico/complicações , Androstatrienos/administração & dosagem , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Inibidores Enzimáticos/administração & dosagem , Feminino , Idade Gestacional , Injeções Intraperitoneais , Masculino , Veículos Farmacêuticos/administração & dosagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Propilenoglicol/administração & dosagem , Ratos , Ratos Wistar , Índice de Gravidade de Doença , Estresse Psicológico/psicologia , Fatores de TempoRESUMO
BACKGROUND: Hydration and integrity of the horny layer is essential to normal skin function. OBJECTIVE: Comparison of the hydrating properties of three moisturizers with pimecrolimus cream vehicle. METHODS: Four test preparations (high-quality skin cream, cold cream emulsion, emollient oil, pimecrolimus cream vehicle) were applied to four different regions of the forearms and legs. Transepidermal water loss (TEWL) was assessed by evaporimetry at baseline, and 3 and 6 hours after arm application, and electrical capacitance was assessed by corneometry at baseline, and 1, 2, 3 and 6 hours after leg application. RESULTS: Corneometry assessment - in terms of efficacy in moisturizing the skin, test preparations were ranked (best to worst): high-quality skin cream (45.9 arbitrary units versus 75.3; p < 0.001) > pimecrolimus vehicle cream (46.6 versus 61.5; p < 0.001) > emollient oil (43.5 versus 54.8; p = 0.006) > cold cream emulsion (44.8 versus 49.9; p = 0.738). Untreated skin (control) had a mean capacitance of 44.8 units at baseline and 48.5 units at endpoint. Evaporimetry (assessment of TEWL) revealed no significant differences between control and any test preparation at any timepoint. CONCLUSIONS: Pimecrolimus cream vehicle has skin hydration properties comparable with highly effective commercially available products. No test preparation had a significant effect on TEWL.
Assuntos
Emolientes/administração & dosagem , Ictiose/terapia , Absorção Cutânea/efeitos dos fármacos , Tacrolimo/análogos & derivados , Água/metabolismo , Administração Cutânea , Adulto , Análise de Variância , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/farmacologia , Método Duplo-Cego , Emolientes/farmacologia , Feminino , Humanos , Ictiose/diagnóstico , Masculino , Pessoa de Meia-Idade , Veículos Farmacêuticos/administração & dosagem , Veículos Farmacêuticos/farmacologia , Probabilidade , Higiene da Pele/métodos , Tacrolimo/administração & dosagem , Tacrolimo/farmacologia , Adulto JovemRESUMO
INTRODUCTION: Patients who undergo cardiac surgery are commonly treated with diuretic therapy for the management of volume overload. The concern of hypokalemia important in the adult population submitted to cardiac surgery has been described. Intravenous potassium (K+) replacement dilution is only recommended with sodium chloride 0.9% solution (SF0.9%), likely due to the putative effects of glucose solution 5% (SG5%) on insulin secretion, which influence K+ replacement quality. However, it is not yet experimentally proved the influence of SF0.9% and SG5% on K+ replacement quality. OBJECTIVES: To evaluate the effects of different vehicles of K+ replacement on blood K+ levels in furosemide hypokalemic rats. METHODS: Male Wistar rats divided into four groups: K++SF, K++SG, SF and SG. Jugular vein was cannulation for K+ replacement and femoral vein was cannulated for blood analysis were performed. Furosemide (50mg/kg) was injected S.C. to induce hypokalemia. It was analyzed potassium plasmatic levels 24 hours before furosemide injection, 24 hours after furosemide injection and 30 minutes after post-replacement. RESULTS: There was no significative difference in blood K+ levels when compared to the basal values (pre-furosemide) in all groups. However, the levels [K+] returned to baseline in both groups receiving K++SF or K++SG, which was not observed in groups receiving only SF and SG. Only K+SF presented increased after K+ replacement (P<0.05). CONCLUSION: K+ replacement diluted both in SF and SG did not affect blood K+ levels in rats.
Assuntos
Furosemida/administração & dosagem , Glucose/administração & dosagem , Hipopotassemia/induzido quimicamente , Veículos Farmacêuticos/administração & dosagem , Potássio/sangue , Cloreto de Sódio/administração & dosagem , Animais , Modelos Animais de Doenças , Hipopotassemia/metabolismo , Masculino , Veículos Farmacêuticos/classificação , Ratos , Ratos Wistar , Fatores de TempoRESUMO
BACKGROUND: To evaluate the effect of injections of benzyl alcohol (BA)-free triamcinolone acetonide (TA) solution (MTA-PF) and the supernatant vehicle of TA (STA) containing BA into the subretinal space of rabbit eyes. METHODS: Sixteen rabbits underwent vitrectomy and subretinal injection of 0.02 ml of either 40 mg/ml MTA-PF, 40 mg/ml STA, or balanced salt solution (BSS). The animals were examined 6, 12, and 24 hours and 14 days after the procedure by fundus examination and fluorescein angiography (FA), as well as histological studies by light and transmission electron microscopy. The histological injury was classified in four stages: (1) stage 1, photoreceptor outer segment injury, (2) stage 2, stage 1 + photoreceptor inner segment injury, (3) stage 3, stage 2 + outer nuclear layer damage, and (4) stage 4, stage 3 + retinal pigment epithelium (RPE) damage. RESULTS: FA showed no window defects in areas where MTA-PF, STA, or BSS have been injected. Histological examination revealed that subretinal BSS-injection resulted in stage 1 damage during entire follow-up. Subretinal injection of MTA-PF resulted in damage stage 2 at 24 h and 14 days after surgery. However, at the STA position, stage 3 damage was noted 24 h and 14 days postoperatively. No RPE or choroidal damage was observed. CONCLUSIONS: The histological lesions induced by subretinal STA were more relevant than the damage induced by MTA-PF. The vehicle BA may be involved in these abnormalities. The data indicate that care must be taken when using TA during internal limiting membrane peeling in macular hole surgery, due to the possibility of unintentional subretinal migration and for retinal pharmacotherapy.
Assuntos
Glucocorticoides/toxicidade , Veículos Farmacêuticos/administração & dosagem , Conservantes Farmacêuticos/toxicidade , Retina/efeitos dos fármacos , Retina/ultraestrutura , Triancinolona Acetonida/toxicidade , Animais , Feminino , Angiofluoresceinografia , Glucocorticoides/administração & dosagem , Injeções , Microscopia Eletrônica de Transmissão , Conservantes Farmacêuticos/administração & dosagem , Coelhos , Triancinolona Acetonida/administração & dosagem , VitrectomiaRESUMO
The use of 5-aminolaevulinic acid (ALA) is gaining increasing attention for photosensitization in photodynamic therapy of superficially localized tumours. The aim of this work was to determine the kinetics of porphyrin generation in tissues after topical application of ALA delivered in different vehicles on the skin overlying the tumour and normal skin of mice. Maximal accumulation was found in tumour 3 h after ALA application in both cream and lotion preparations. Normal and overlying tumour skin tissues showed different kinetic patterns, reflecting histological changes when the latter is invaded by tumour cells. Liver, kidney, spleen and blood porphyrins also raised from basal levels, showing that ALA and/or ALA-induced porphyrins reach all tissues after topical application. During the first 24 h of ALA topical application, precursors and porphyrins are excreted by both urine and faeces. ALA lotion applied on the skin overlying the tumour induced higher accumulation of tumoural porphyrins than cream, and lotion applied on normal skin appeared to be the most efficient upon inducing total body porphyrins. This work has demonstrated the great influence of the formulation of ALA vehicle on penetration through the skin. Knowledge of the kinetics of porphyrin generation after different conditions of ALA application is needed for the optimization of diagnosis and phototherapy in human tumours.
Assuntos
Ácido Aminolevulínico/farmacologia , Veículos Farmacêuticos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/biossíntese , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Administração Tópica , Ácido Aminolevulínico/administração & dosagem , Ácido Aminolevulínico/farmacocinética , Animais , Cinética , Masculino , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Veículos Farmacêuticos/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacocinética , Porfirinas/sangue , Distribuição TecidualRESUMO
La medicación preanestésica es de gran utilidad para los niños sometidos a cirugía electiva ambulatoria, se administra fácilmente y es bien aceptada por vía oral. Se administraron dosis de midazolam y ketamina por vía oral de 0.75 mg/kg y 6 mg/kg respectivamente utilizando como vehículo jugo de manzna, en dos grupos de pacientes de 20 cada uno, en niños de 1-10 años de edad. Se observó el grado de sedación, calidad de la separación familiar y facilidad para la aplicación de venopunción a los 15 y 30 minutos después de su administración, grado de amnesia y tiempo de recuperación. El inicio de acción y calidad de sedación resultaron con p< 0.05 a favor del midazolam, el resto de las observaciones registradas fueron similares en ambos grupos
Assuntos
Humanos , Criança , Pediatria , Veículos Farmacêuticos/administração & dosagem , Bebidas , Midazolam/administração & dosagem , Midazolam/farmacocinética , Anestesia Geral , Ketamina/administração & dosagem , Ketamina/farmacocinética , Administração Oral , Pré-Medicação/métodosRESUMO
Cerebellar morphogenesis as well as somatometric parameters of progenies from mothers exposed to ethyl-ether, chloroform, turpentine or thinner were registered a 24, 48 and 7 hours of age. 1. Mortality rate of 20 and 59% was observed in progenies of thinner or turpentine exposed mothers, correspondingly. 2. Delay of intrauterine growth manifested by body weight, size and cephalic diameter was evident in chloroform exposed groups (P < 0.01). 3. Cerebellar maturation delay was found in thinner or turpentine prenatally exposed litters. 4. The number of Purkinje cells was significantly reduced in ethyl-ether and chloroform exposed groups (P < 0.01). These cells were found less affected by thinner or turpentine exposure (P < 0.01).
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Doenças Cerebelares/induzido quimicamente , Retardo do Crescimento Fetal/induzido quimicamente , Prenhez/efeitos dos fármacos , Solventes/toxicidade , Administração por Inalação , Animais , Animais Recém-Nascidos , Cefalometria , Doenças Cerebelares/embriologia , Doenças Cerebelares/patologia , Clorofórmio/administração & dosagem , Clorofórmio/toxicidade , Éter/administração & dosagem , Éter/toxicidade , Feminino , Masculino , Troca Materno-Fetal , Veículos Farmacêuticos/administração & dosagem , Veículos Farmacêuticos/toxicidade , Gravidez , Células de Purkinje/efeitos dos fármacos , Células de Purkinje/patologia , Ratos , Ratos Sprague-Dawley/embriologia , Solventes/administração & dosagem , Terebintina/administração & dosagem , Terebintina/toxicidadeRESUMO
The behavioral effects of intraventricular 1-microliter injections of adrenaline and noradrenaline (both in a concentration of 30 nmol/microliters) were examined in pigeons bearing cannulae chronically implanted into the lateral ventricles. Injections of either catecholamine evoked immediate and intense bouts of feeding behavior, followed by long-lasting increases in sleep duration (50-90% higher than vehicle-treated subjects) in pigeons given free access to food during the observation period. Pigeons treated with adrenaline or vehicle only, and placed in a cage without the feeder set (food-deprived during the observation period), exhibited late increases in exploratory and preening behaviors, and less sleep than controls (vehicle-treated pigeons with free access to food). These data suggest that post-prandial sleep in this situation may represent a by-product of feeding-related processes evoked by both catecholamines.
Assuntos
Comportamento Animal/efeitos dos fármacos , Epinefrina/farmacologia , Norepinefrina/farmacologia , Sono/efeitos dos fármacos , Animais , Columbidae , Epinefrina/administração & dosagem , Comportamento Exploratório/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Feminino , Asseio Animal/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Norepinefrina/administração & dosagem , Veículos Farmacêuticos/administração & dosagemRESUMO
The behavioral effects of intravrnticular 1-micronl injections of adrenaline and noradrenaline (both in a concentration of 30 nmol/micronl) were wxamined in pigeons bearing cannule chronically implanted into the lateral ventricles. Injections of either catcholoamine evoked immediate and intense bouts of feeding behavior, followed by long-lasting incrases in sleep duration (50-90% higher than vehicle-treated subjects) in pigeons given free access to food during the observation period. Pigeons treated with adrenaline or vehicle only, and placed in a cage without the feeder set (food-deprived durngi the observation period), exhibited late increases in exploratory and preening behaviors, and less sleep than controls (vehicle-treated pigeons with free access to food). These data suggest that post-prandial sleep in this situation may represent a by-product of feeding-related processes evoked by both catecholamines