Syndecan-2 and decorin: proteoglycans with a difference--implications in keloid pathogenesis.

BACKGROUND: Growth factors and cytokines involved in the wound healing process seem to be immobilized at the cell surface and extracellular matrix via binding with proteoglycans, making them important modulators of cell dynamics. Our aim was to investigate the expression of two proteoglycans, namely syndecan-2 and decorin, and to elucidate their role in the pathogenesis of an aberrant wound healing process leading to keloid scar. METHODS: Intrinsic expression of syndecan-2, fibroblast growth factor (FGF)-2, and decorin in keloid tissue was investigated using Western blotting and immunohistochemistry. Normal and keloid fibroblasts were treated with serum to see the effects of serum growth factors on the expression of syndecan-2 and decorin. The role of epithelial-mesenchymal interactions in modulating syndecan-2, FGF-2, and decorin expression was investigated using an established two-chamber serum-free coculture model. Finally, the antifibrotic effect of decorin was investigated by studying its effect on the expression of extracellular matrix components. RESULTS: Syndecan-2 and FGF-2 were upregulated in keloid tissue; decorin was downregulated. Normal and keloid fibroblasts treated with serum led to increase in syndecan-2 and decrease in decorin expression. Under coculture conditions, syndecan-2 was shed in the conditioned media. FGF-2 was also upregulated under coculture conditions and, when added to fibroblast monocultures, increased shedding of syndecan-2. Decorin levels were upregulated under coculture conditions only in normal cocultures. Decorin was also able to decrease extracellular matrix proteins, highlighting its importance as an antifibrotic agent. CONCLUSION: Syndecan-2 and FGF-2 are not only overexpressed in keloid tissues but may interact with each other resulting in the shedding of syndecan-2, which in turn might activate a whole cascade of events responsible for a keloidic phenotype. In addition, decorin had an antifibrotic effect and could well be used as a potential therapeutic agent for keloids.

Polymer-coated microparticles for the sustained release of nitrofurantoin.

Suspensions of nitrofurantoin (NTF) microparticles for controlled release were investigated in this study. The microparticles were enteric coated with various combinations of the two polymers, cellulose acetate phthalate/cellulose acetate butyrate (CAP/CAB) by a modified solvent evaporation method. Ratios of NTF to the two polymers (NTF/CAP/CAB) ranged from 1.0:1.6:0.4,1.0:1.0:1.0,1.0: 0.4:1.6 to 1.0:0.0:2.0. The encapsulation efficiency, percentage yield, determined by comparing the final mass of the microparticles with the initial mass of the ingredients used, distribution of particle size and the in-vitro dissolution profiles of the microparticles were determined. Based on light photographs for the evaluation of the microparticle morphology, the drug crystals appeared to be encapsulated sufficiently by the enteric polymers. In our study, the microparticles enteric coated with CAP/CAB in the ratio of 0.4:1.6 displayed the most satisfactory in-vitro release profile (reduced release in the simulated gastric fluid and sustained release in the simulated intestinal fluid). Thus, microparticles with NTF/CAP/CAB in the ratio of 1.0:0.4:1.6 were formulated into a suspension for further bioavailability and ulcerogenicity studies in Sprague-Dawley rats, with the suspension of NTF crystals as a control. The bioavailability study was carried out in eight rats fed with either the free NTF or the corresponding microparticles in a cross-over design. The ulcerogenicity study was carried out in three groups of six rats each: one group received no drug treatment; the control group was treated with free NTF; and the third group was treated with enteric-coated NTF microparticles. The bioavailability of NTF from the microparticles was comparable with the control. More importantly, there was notably less ulceration of the gastric mucosa observed after dosing with the microparticle suspension compared with that after the administration of the control suspension.

Isobolographic analysis of the analgesic interactions between ketamine and tramadol.

Owing to different mechanisms of analgesia, we hypothesized that the combination of ketamine and tramadol could produce synergistic or additive antinociceptive effects. Swiss albino mice were administered intraperitoneally with ketamine, tramadol, a combination of ketamine and tramadol, or saline, and the resulting antinociceptive effects were tested in the mouse tail-flick and formalin tests. The potencies of the two drugs alone or in combination were obtained by fitting data to the Sigmoid Emax equation. Isobolographic analysis was performed to evaluate the interaction. CNS depression was also monitored. Results showed that tramadol exhibited apparent dose-dependent effects in the tail-flick test, and in phase 1 and phase 2 of the formalin test. Ketamine dose-dependently inhibited the phase 2 responses, but failed to modify the phase 1 and tail-flick responses. Combination of tramadol and ketamine produced significant synergistic interactions only in phase 2 of the formalin test (P < 0.05). The synergistic combinations also displayed less CNS depression than when an equianalgesic dose of ketamine was administered alone. We conclude that in the acute thermal or chemical pain model, ketamine is not effective and the net effect of ketamine and tramadol in combination was simply additive after systemic administration. However, the coadministration produced synergistic antinociception in the chemical-induced persistent pain model.