This study investigated the effects of 5-fluorouracil in a slow-release biodegradable gelatin system on tendon healing. Gelatin blocks prepared in a size of 10 × 20 × 1 mm were loaded with 10, 20, and 30 mg of 5-fluorouracil, and 30 adult white Leghorn chickens were used. The tendons to the third and fourth toes were severed and repaired. The extremities were casted for three weeks. After sacrifice, the tendons were examined histologically and biomechanically for adhesion formation. The 10 mg-loaded gelatin group showed a decrease in adhesion formation when compared with the operative control group; the 20 and 30 mg groups showed signs of severe inflammation. Low doses of 5-fluorouracil applied via a slow-release gelatin system reduced adhesion formation in flexor tendon healing.
Bone grafts, used for providing structural integrity of cranial vault remodeling, could not always integrate with the remaining bone structures. All efforts are focused on increasing incorporation of the applied bone grafts. Allografts were covered by chitosan so that slow release of bone morphogenetic protein-2 (BMP-2) and Transforming growth factor-beta-2 (TGF-beta-2) was achieved. Two hundred forty Wistar-Albino rats were distributed equally in 8 study groups. Study groups were designed as; defect group, autograft group, allograft group, chitosan group, allograft + chitosan, TGF-beta-2 group, BMP-2 group, and TGF-Beta-2 +BMP-2 group. Bone biopsies were obtained at second, eight, and 14th weeks. Bone regeneration was evaluated by morphologic studies detecting histologic bone healing and radiologic studies detecting bone density. Histologic findings were evaluated in 2 categories; tissue response to the implant and defect healing. Additionally, scanning electron microscopy for detailed morphologic evaluation was done. Bone density of the applied scaffold and the parietal bone at the same computed tomography section were measured in Hounsfield scale and this ratio was used for densitometry evaluations. Kruskal-Wallis test was used to analyze difference among groups according to the histologic and radiologic data. Pairwise comparisons were done using Mann-Whitney U test with Bonferroni correction. P < 0.05 was considered significant. In the morphologic studies, bone regeneration in BMP-2 group was found to be compatible with bone regeneration in gold standard autograft group and even better than it within 15 days. Chitosan is a biocompatible material. TGF-Beta-2 alone is not effective enough in bone regeneration; BMP-2 alone has a positive effect in every step of bone regeneration. Combining TGF-Beta-2 with BMP-2 does not lead to a better bone regeneration than using BMP-2 alone. A synergistic effect is not obtained by using these 2 factors together.
Lorazepam is normally administered as a solution in organic solvents such as propylene glycol. This type of formulation is undesirable. This study describes the development of a parenteral emulsion formulation for lorazepam. The stability of lorazepam in the emulsion was examined. Ten per cent corn oil emulsions stabilized with egg lecithin, Pluronic F68 and Pluronic F88 were used. The incorporation of lorazepam does not appear to destabilize the emulsion, and lorazepam itself appears to be stable for at least 1 year in this liquid formulation. Haemolysis caused by emulsion formulations containing lorazepam and different emulsifiers was evaluated using human and rabbit blood to assess their safety as parenteral drug carriers. The results show that the emulsions did not have any significant haemolytic activity whereas organic solvents and solutions of lorazepam in organic solvents caused substantial haemolysis.
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