Sodium alkyl sulfate micelles are predicted to grow as a power law of the total counterion salt concentration, Yaq, in the aqueous phase as follows: NA = K2(Yaq)Y, where NA is the micelle aggregation number and k2 and y are constants which are estimated from the critical micelle concentration and the apparent degree of counterion attachment. For sodium dodecyl sulfate, NA = 162(yaq)1/4 is predicted and is shown to be in good agreement with aggregation numbers measured by a number of techniques over a wide range of yaq whether this quantity is varied by changing the concentrations of the detergent, the added counterion salt, or both. Values of k2 and y are estimated for six members of the sodium alkyl sulfate family.

Binding and localization of the vasodilator and antitumor drug coactivator dipyridamole (DIP) and one of its derivatives, RA25, to phospholipid vesicles of DMPC (dimyristoylphosphatidylcholine) and DPPC (dipalmitoylphosphatidylcholine) was studied using fluorescence spectroscopy as well as quenching of fluorescence. The analysis of fluorescence data indicates that neutral dipyridamole binds to the phospholipids in their liquid crystalline phase with an association constant of 950 M(-1) and 1150 M(-1) to DMPC and DPPC, respectively. Protonation of DIP leads to a 3-fold reduction of the association constant. For the gel phospholipid phase, the binding is smaller (a factor of 2), independently of pH, suggesting that the more flexible lipid packing in the liquid crystalline phase facilitates the binding of the drug. The association constant of RA25 neutral form is considerably lower than for DIP, being around 295 M(-1). Fluorescence quenching with nitroxides TEMPO and stearic acid doxyl derivatives suggests the localization of DIP to be closer to the 5th carbon of alkyl chain. The quenching effect of 5-DSA below the lipid phase transition suggests that a strong static quenching may be operative. The quenching effect of 16-DSA is almost as great as that for 5-DSA below the phase transition, being even higher above the phase transition. This effect is probably due to the trans-gauche isomerization of the stearic acid nitroxide, making the encounter of its paramagnetic fragment with the DIP chromophore possible. Our data are consistent with DIP location close to the bilayer surface in the border of hydrophobic-polar heads interface which is similar to the data in micellar systems. In the case of RA25, the drug is in the outer part of the head group interface being much exposed to the aqueous phase and being significantly less accessible to the membrane nitroxide quenchers.

ABSTRACT:The aim of the present work was to evaluate the effect of a selective cyclooxygenase-2 (COX-2) inhibitor (meloxicam) on the alveolar bone loss progression in experimentally induced periodontitis. Forty (40) Wistar rats were separated into 8 experimental groups (n = 5). Cotton ligatures were placed at the gingival margin level of the lower right first molars of some rats. Four groups were treated for 5 or 15 days with an oral dose of 15 mg/kg of body weight/day of the selective COX-2 inhibitor. The other groups were used as positive control (sham) or negative control in each experimental period. Standardized digital radiographs were taken after sacrifice at 5 and 15 days to measure the amount of bone loss at the mesial root surface of the first molar tooth in each rat. The treatment with meloxicam did not induce weight alteration or other visible systemic manifestations. One way analysis of variance (ANOVA) indicated that groups treated with meloxicam, after 5 days, had significantly less alveolar bone loss (p < 0.05) when compared with control groups. On the other hand, no significant differences in bone loss were observed after 15 days of treatment with meloxicam. These data provide evidence that systemic therapy with meloxicam can modify the progression of experimentally induced periodontitis in rats during the initial experimental period. DESCRIPTORS: Alveolar bone loss; Anti-inflammatory agents, non-steroidal; Cyclooxygenase inhibitors; Periodontitis; Radiography, dental. RESUMO:O objetivo deste trabalho foi avaliar o efeito de um inibidor seletivo da cicloxigenase-2 (COX-2) (meloxicam) na progressão da perda óssea alveolar durante o desenvolvimento da doença periodontal experimental induzida. Quarenta (40) ratos Wistar foram separados em 8 grupos experimentais (n = 5). Ligaduras de fio de algodão foram colocadas na margem gengival do primeiro molar inferior direito de alguns ratos. Quatro grupos foram tratados por 5 ou 15 dias com uma dose oral de 15 mg/kg de peso corporal/dia do inibidor seletivo de COX-2. Os outros grupos foram usados como controle positivo (sham) e controle negativo dentro de cada período experimental. Radiografias digitais padronizadas foram realizadas para medir a perda óssea na região mesial do primeiro molar inferior de cada rato. O efeito do tratamento com meloxicam não induziu alteração de peso ou outras manifestações sistêmicas visíveis. A Análise de Variância (ANOVA) indicou que os grupos tratados com meloxicam após 5 dias apresentaram perda óssea alveolar significativamente menor (p < 0,05). Por outro lado, a perda óssea não foi significativa após 15 dias de tratamento com meloxicam. Os dados apresentados no presente trabalho sugerem que o tratamento sistêmico com meloxicam pode modificar a progressão da periodontite experimental em ratos no período experimental inicial.

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Interaction of the coronary vasodilator dipyridamole (DIP) with vesicles of dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG), and mixtures of them has been studied by fluorescence spectroscopy of the drug. Association constants were determined both below and above the phase transition temperature for the lipids, at different pHs (4.0 and 7.0). These constants at pH 7.0 were 633 M -1 (30 °C) and 1.15 × 10 3 M -1 (50 °C) for pure DPPC and 727 M -1 (30 °C) and 1.48 × 10 3 M -1 (50 °C) for pure DPPG. At pH 4.0 the association constants showed different behavior; Kb values decreased by a factor of 3 for DPPC but increased for DPPG due to the electrostatic interaction of the protonated drug with the phospholipid headgroup. In the mixed system formed by DPPC and DPPG (11% and 20%) the resulting variations in the mixture compositions have a marked effect on drug-vesicle interaction; a decrease of the association constants was observed consistent with a more tightly packed bilayer. Steady-state anisotropy binding data demonstrated the validity of the two-state binding model. Fluorescence quenching experiments with 5-doxylstearic acid (5-DSA) were also performed at pH 4 and pH 7 and with different compositions of lipids. The results support the interfacial location of the drug (close to the fifth carbon of the alkyl chain), suggesting also a strong dependence of binding on lipid packing and the presence of charges at the membrane interface. Fluorescence anisotropy decay experiments were also performed for dipyridamole (DIP) in pure DPPC and DPPG at different pHs and temperatures. The results show clearly that the initial anisotropy r0 of DIP in model systems (glycerol, sucrose) is quite high, above 0.3, attaining values of 0.20-0.24 in DPPG and being smaller in DPPC. These values are consistent with steady-state anisotropy values at saturating lipid concentrations. The anisotropy decays are best described as a single rotational correlation time which varies in the range 1.5-5.0 ns together with a limiting anisotropy value which also varies between 0.03 and 0.08. Data for anisotropy are in agreement with the binding data, also suggesting the location of the drug at the membrane interface.