Flap Blood Glucose as a Sensitive and Specific Indicator for Flap Venous Congestion: A Rodent Model Study.

BACKGROUND: Flap blood glucose decreases when flap congestion occurs. The hypothesis that flap blood glucose works as an indicator for venous congestion was tested experimentally, and flap congestion was reproduced in rodent models. METHODS: Blood glucose levels of a rat abdominal skin flap, with or without its vein pedicle clamped, were checked before and every 10 minutes after flap elevation. In rats whose pedicle vein was shut off, it was further followed up every 5 minutes after declamping. To examine the effect of systemic blood glucose on flap blood glucose, in some rats, glucose solution was administered intraperitoneally before the experiment to artificially produce hyperglycemia. Forty-two rats were divided into four groups, with (n = 24) or without (n = 18) venous blockage and with (n = 20) or without (n = 22) glucose preloading. RESULTS: Flap blood glucose decreased rapidly to off-scale low (<20 mg/dl) within 40 minutes only when the vein pedicle was shut off in normoglycemic (40 ± 8.2 minutes, mean ± SD) and hyperglycemic (40 ± 9.9 minutes) rat groups (p < 0.01). There was no significant difference in the time taken for the flap blood glucose to decrease to off-scale low after venous blockage between both groups (p = 0.379). When the vein was declamped, flap blood glucose again rapidly returned to the systemic level in 15 minutes or earlier in both groups (p = 0.0283). CONCLUSIONS: Flap blood glucose sensitively and specifically reflects the state of vein occlusion, whether the systemic blood glucose is normal or high. The authors' results indicate that flap blood glucose works as a reliable indicator for the venous system.

Evaluation of the In Vivo Kinetics and Biostimulatory Effects of Subcutaneously Injected Hyaluronic Acid Filler.

BACKGROUND: Because subcutaneously injected hyaluronic acid filler is absorbed over 6 months to 1 year after the treatment of facial wrinkles, frequent retreatment may be required. However, persistent long-term effects are often clinically observed when hyaluronic acid filler is injected as a bolus for facial augmentation. Therefore, the authors investigated, over time, the changes in volume and histologic features of subcutaneous bolus injections of hyaluronic acid. METHODS: Hyaluronic acid filler was subcutaneously injected as a bolus into the dorsum of 6-week-old rats. At several time points (immediately after injection and 4, 8, 16, 32, and 64 weeks thereafter), magnetic resonance imaging was introduced to observe morphologic changes and to measure volume. Histologic examination of sectioned tissues was also performed. RESULTS: The average volume increased for up to 4 weeks after injection and then gradually decreased, with 74.8 percent of the injected volume remaining after 64 weeks, with no statistical difference compared to the initial volume. Histologic analysis revealed that lattice structures were created by fibroblasts and collagen fibers, and blood vessels and adipocytes were also generated in the filler. CONCLUSIONS: Although subcutaneous bolus injections of hyaluronic acid filler exhibited flattening, the total volume was maintained even after 64 weeks. Histologically, hyaluronic acid filler acted as a scaffold for autogenous tissue replacement by means of fibroblast migration and proliferation, collagen induction, and angiogenesis, followed by proliferation of adipocytes. This study demonstrates that the total volume is maintained long-term by replacing part of the injected hyaluronic acid filler with autologous tissues.

Novel high-throughput screening system for identifying STAT3-SH2 antagonists.

Constitutive activation of the oncogenic transcription factor STAT3 frequently occurs in various human malignancies. STAT3 activation involves dimerization via intermolecular pTyr-SH2 interaction. Thus, antagonizing this interaction is a feasible approach to inhibit STAT3 activation for cancer therapy. In order to identify selective STAT3 inhibitors, we developed a biochemical HTS system based on AlphaScreen technology, which measures the abilities of test compounds to antagonize pTyr-SH2 interactions. We screened our chemical libraries using this system and identified 5,15-diphenylporphyrin (5,15-DPP) as a selective STAT3-SH2 antagonist. Selective inhibition of STAT3 nuclear translocation and DNA biding activity was observed in cells treated with 5,15-DPP. IL-6-dependent dimerization of STAT3, c-myc promoter binding and c-myc protein expression were all suppressed by 5,15-DPP, whereas no decrement in either expression or phosphorylation level of STAT3 was observed. Thus, the HTS assay system represented herein may be useful for identifying novel STAT3-SH2 antagonists.