RESUMO
The fine structure of the triple line for water droplets deposited on porous polymer substrates was investigated. Substrates were obtained with the breath-figures self-assembly. Water droplets demonstrated the pronounced Cassie-Baxter wetting regime. The triple line was imaged with environmental scanning electron microscopy. The roughness of a triple line was characterized with its averaged root-mean-square (rms) width w(L), and its scaling experimental dependence upon the length L of the triple line w(L) is proportional to L(ζ) was analyzed. The values of exponents in the range of 0.60-063 were established. The deduced values of ζ evidence the local nature of the triple-line elasticity and support the idea that the elastic potential of the triple line includes only even powers of the displacement.
Assuntos
Reologia , Água/química , Análise de Fourier , Movimento (Física) , Cimento de Policarboxilato/química , Porosidade , MolhabilidadeRESUMO
Physical mechanisms of Cassie-Wenzel wetting transitions are discussed. The origin of the potential barrier separating the Cassie and Wenzel wetting states is clarified. It may contain contributions originating from the filling of hydrophobic pores and displacement of the triple line along the smooth portions of the relief. One- and two-dimensional scenarios of wetting transitions are considered. We demonstrate that the contribution to the potential barrier because of the displacement of the triple line is not negligible in both cases.
RESUMO
The administration of 13-cis-retinoic acid (13-cisRA), following myeloablative therapy improves 3-year event-free survival rates in children with high-risk neuroblastoma. This study aimed to determine the degree of inter-patient pharmacokinetic variation and extent of metabolism in children treated with 13-cisRA. 13-cis-retinoic acid (80 mg m(-2) b.d.) was administered orally and plasma concentrations of parent drug and metabolites determined on days 1 and 14 of courses 2, 4 and 6 of treatment. Twenty-eight children were studied. The pharmacokinetics of 13-cisRA were best described by a modified one-compartment, zero-order absorption model combined with lag time. Mean population pharmacokinetic parameters included an apparent clearance of 15.9 l h(-1), apparent volume of distribution of 85 l and absorption lag time of 40 min with a large inter-individual variability associated with all parameters (coefficients of variation greater than 50%). Day 1 peak 13-cisRA levels and exposure (AUC) were correlated with method of administration (P<0.02), with 2.44- and 1.95-fold higher parameter values respectively, when 13-cisRA capsules were swallowed as opposed to being opened and the contents mixed with food before administration. Extensive accumulation of 4-oxo-13-cisRA occurred during each course of treatment with plasma concentrations (mean+/-s.d. 4.67+/-3.17 microM) higher than those of 13-cisRA (2.83+/-1.44 microM) in 16 out of 23 patients on day 14 of course 2. Extensive metabolism to 4-oxo-13-cisRA may influence pharmacological activity of 13-cisRA.
Assuntos
Isotretinoína/farmacocinética , Neuroblastoma/tratamento farmacológico , Absorção , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Isotretinoína/efeitos adversos , Isotretinoína/uso terapêutico , Masculino , OxirreduçãoRESUMO
Male Wistar rats were fed a semi-purified diet (MID - minimal inducing diet) with or without addition of 50 ppm of beta-naphthoflavone (BNF) for 1 week. After 1 week the rats were dosed with 20 mg/kg of 1,2-dimethylhydrazine (DMH) subcutaneously and killed at various time intervals from the injection. Enzyme levels were determined in microsomal and cytosolic fractions prepared from the liver and the intestinal mucosa. Feeding of BNF for 1 week caused a 6.5-fold increase of 7-ethoxyresorufin (7-ERR) deethylase in the colon as compared to the controls, but did not alter glutathione (GSH) content nor glutathione-S-transferase (GSHST) activity. Hepatic cytochrome P-450 and 7-ERR deethylation were not significantly altered by feeding of BNF at this concentration, whereas GSH and GSHST were increased by a factor of 1.6 and 2, respectively. In the DMH-dosed rats, O6-methylguanine was formed to a greater extent in the BNF-treated colon than in the controls at 1, 12 and 24 h, whilst N7-methylguanine levels were essentially the same in the induced and uninduced rats. No significant difference was found in the degree of hepatic DNA alkylation at any time points. As shown by our results, the nature of the diet would appear to be able to modulate the rate of metabolic activation of DMH and its binding to DNA in the target organ.
Assuntos
Benzoflavonas/farmacologia , Colo/efeitos dos fármacos , DNA/efeitos dos fármacos , Dimetilidrazinas/toxicidade , Flavonoides/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Metilidrazinas/toxicidade , Microssomos Hepáticos/efeitos dos fármacos , 1,2-Dimetilidrazina , Administração Oral , Alquilação , Animais , Radioisótopos de Carbono , Colo/enzimologia , Citocromo P-450 CYP1A1 , Sistema Enzimático do Citocromo P-450/biossíntese , Dieta , Interações Medicamentosas , Indução Enzimática/efeitos dos fármacos , Glutationa Transferase/biossíntese , Mucosa Intestinal/enzimologia , Masculino , Microssomos Hepáticos/enzimologia , Oxirredutases/biossíntese , Ratos , Ratos Endogâmicos , beta-NaftoflavonaRESUMO
The role of glutathione (GSH) as a determinant of cellular sensitivity to the cytotoxic and DNA-damaging effects of cyclophosphamide (CP) was studied in a dual culture system of rat hepatocytes and K562 human chronic myeloid leukemia cells, which have elevated aldehyde dehydrogenase activity with a corresponding insensitivity to activated CP. Exposure of K562 cells to 50 microM DL-buthionine-S,R-sulfoximine for 24 h resulted in a depletion of cellular GSH content to 10% of control values without toxicity. Subsequent 1-h exposure of GSH-depleted cells to activated cyclophosphamide, obtained by incubation of CP with suspension cultures of rat hepatocytes, resulted in a 5-fold potentiation of the cytotoxicity of CP. Alkaline elution analysis of cellular DNA demonstrated that the level of apparent interstrand cross-linking was 3 to 4 times higher in GSH-depleted cells than in nondepleted cells. GSH-depleted cells were, in addition, more sensitive to induction of DNA single strand breaks than nondepleted cells. Depletion of GSH content did not increase cellular sensitivity to the cytotoxicity of phosphoramide mustard. Preincubation of K562 cells with 1 mM cysteine for 4 h resulted in an approximately 60% increase in cellular GSH content, which was accompanied by decreased sensitivity to the cytotoxicity of hepatocyte-activated CP. Exposure of nondepleted cells to clinically relevant concentrations of hepatocyte-activated CP resulted in depletion of cellular GSH content. Replenishment of GSH content in these cells was relatively slow following CP exposure. Acrolein was highly effective at depleting cellular GSH content, whereas phosphoramide mustard had no effect on cellular GSH content. The depletion of GSH by intracellularly released acrolein may be important in the mechanism of cytotoxicity of CP.