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.

Optimizing treatment of tauroursodeoxycholic acid to improve embryonic development after in vitro maturation of cumulus-free oocytes in mice.

Cumulus-free in vitro maturation (IVM) provides a powerful tool to manipulate immature oocytes, but IVM oocytes lead to poor development after fertilization. Supplementation of the culture medium with tauroursodeoxycholic acid (TUDCA), a bile acid, has been reported to improve the development of embryos derived from in vivo fertilized (IVF) embryos after in vitro culture (IVC) by attenuating endoplasmic reticulum stress. However, it remains unclear if TUDCA can improve development of IVM-IVF embryos. Here, we examined whether TUDCA treatment could improve embryonic development during or after IVM. Immature GV oocytes collected from ovaries of ICR female mice that were free from cumulus cells were subjected to IVM in αMEM containing 5% FBS for 16 h. TUDCA was added to the media at varying concentrations (0-1000 µM) during IVM and IVC. TUDCA treatment during IVM reduced both MII and pronuclear (PN) rates but did not affect blastocyst rates of fertilized embryos. In contrast, TUDCA treatment during IVC significantly increased blastocyst formation rates in a concentration dependent manner. Finally, embryo transfer after TUDCA treatment revealed a significant improvement in the rates of offspring production (15% with 1000 µM TUDCA vs. 6.0% control). These results show that treatment with 1000 µM of TUDCA significantly can improve poor embryonic development of cumulus-free IVM-IVF embryos.

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.

[Base in four types of lidocaine preparation (formulated in hospital)].

PL cream (combination of lidocaine and procaine) was launched on the market in April 2012 in Japan. We investigated differences in the anesthetic effect by employing two types of base: Carbopol and methylcellulose. Electron microscopy showed a distinct difference in appearance: densely-scattered, fine particles for Carbopol and sparse, large particles for methylcellulose. Accordingly, the extensibility of the cream was significantly greater at 4 and 25 degrees centigrade for methylcellulose, but was greater at 34 degrees centigrade for Carbopol. The steady flow viscosity (1 s(-1)) was greater for the Carbopol than methylcellulose base. The difference in the cutaneous permeability between the two bases increased over time: the methylcellulose base was removed at 90 min after application and, 30 min later, showed a significant difference. These results suggest that the methylcellulose base has a superior anesthetic effect in clinical settings.

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.