Suppression of Lipid Accumulation in the Differentiation of 3T3-L1 Preadipocytes and Human Adipose Stem Cells into Adipocytes by TAK-715, a Specific Inhibitor of p38 MAPK.

Excessive preadipocyte differentiation is linked with obesity. Although previous studies have shown that p38 MAPK is associated with adipogenesis, the regulation of preadipocyte differentiation by TAK-715, an inhibitor of p38 mitogen-activated protein kinase (MAPK), remains unclear. Interestingly, TAK-715 at 10 µM vastly suppressed the accumulation of lipid and intracellular triglyceride (TG) content with no cytotoxicity during 3T3-L1 preadipocyte differentiation. On mechanistic levels, TAK-715 significantly decreased the expressions of the CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor gamma (PPAR-γ), fatty acid synthase (FAS), and perilipin A. Similarly, the phosphorylation of the signal transducer and activator of transcription-3 (STAT-3) in differentiating 3T3-L1 cells was also reduced with TAK-715 treatment. Moreover, TAK-715 significantly blocked the phosphorylation of activating transcription factor-2 (ATF-2), a p38 MAPK downstream molecule, during 3T3-L1 preadipocyte differentiation. Of importance, TAK-715 also markedly impeded the phosphorylation of p38 MAPK and suppressed lipid accumulation during the adipocyte differentiation of human adipose stem cells (hASCs). Concisely, this is the first report that TAK-715 (10 µM) has potent anti-adipogenic effects on the adipogenesis process of 3T3-L1 cells and hASCs through the regulation of the expression and phosphorylation of p38 MAPK, C/EBP-α, PPAR-γ, STAT-3, FAS, and perilipin A.

An anatomical study of the saphenous nerve, artery, and artery perforators within the thigh using cadaveric dissection.

Although the saphenous flap has been used in reconstruction as a free flap, there has not yet been an anatomic study about the perforators of the saphenous artery. The aim of this study is to investigate the anatomy of the saphenous artery and the number and locations of its perforators. We dissected parts of 10 legs from 5 cadavers. Measurements of the positions of the dissected saphenous arteries and their perforators were taken from the medial epicondyle of the femur. We observed the origin, end point, and the diameter of each of the arteries, and we investigated the numbers and locations of both septocutaneous and musculocutaneous perforators. The average length of saphenous artery was 14.8 cm, and it was located 12.0 cm above the medial epicondyle of the femur. The average diameter was 1.63 mm. A median average of 4 perforators branched out from a single saphenous artery. There was a median average of 2 septocutaneous perforators and 2 musculocutaneous perforators from the saphenous artery. The perforators were mainly located at 7 cm proximal to the medial epicondyle of the femur. The saphenous artery has many perforators and is therefore useful as the pedicle of the perforator flap. The saphenous artery perforator flap can be designed within 7 cm proximal to the medial epicondyle of the femur. Our results may be helpful in the applications of the neurocutaneous flap using the saphenous artery or the perforator flap based on septocutaneous perforators.

The evaluation of relevant factors influencing skin graft changes in color over time.

BACKGROUND: Objective studies evaluating the relevant factors that affect skin graft changes in color over time have yet to be published. OBJECTIVE: Therefore, the patterns of the grafted skin's color changes and the presence of relevant factors were analyzed statistically. MATERIALS AND METHODS: The study included 107 skin grafts in 107 subjects. Using a chromameter, the colors of skin graft, the area adjacent to the recipient site, and the donor site were measured. The grafted skin's color changes and the color difference were analyzed with respect to several factors. RESULTS: Over time, the grafted skin became lighter, redness decreased, yellowness increased, and the color difference decreased. As the donor site was lighter, the grafted skin was lighter and less red. The grafted skin was lighter in females than in males. The skin graft type was not related to the lightness and the redness. The grafted skin was lightest in the upper arm and darkest in the lower leg. The grafted skin was lighter in Fitzpatrick Skin Type III, followed by Type IV and then Type V. CONCLUSION: The factors that affected the skin graft's lightness were time, the lightness of the donor, sex, the hand, the foot, and Fitzpatrick skin type.

An anatomic study of the superficial peroneal nerve accessory artery and its perforators, and clinical application of superficial peroneal nerve accessory artery perforator flaps.

In the 1990s, skin island flaps supplied by the vascular axis of sensitive superficial nerves, like the sural and saphenous nerves, were introduced. Flaps supplied by the superficial peroneal nerve accessory artery (SPNAA), however, are still not commonly used. The aim of this study is to understand the anatomic structure of the SPNAA and its perforators in the anterior intermuscular septum and to use SPNAA perforator flaps in the clinic. We dissected 16 cadavers and assessed the location and number of the SPNAA, its perforators, and the septocutaneous perforators originating from the anterior tibial artery. A SPNAA perforator flap was applied to 12 patients, the free flap was applied to 11 patients, and the pedicled flap was applied to 1 patient. SPNAA varied from 7 to 16 cm in length, with an average of 4.5 perforators to supply the lateral aspect. An average of 3.13 septocutaneous perforators originated from the anterior tibial artery. The mean size of the SPNAA perforator flaps was 65.5 cm. The complete follow-up period was 3-20 months. Although 1 flap was lost as a result of arterial thrombosis, the procedure was successful in the remaining 11 patients. In addition, reduced flap thickness made them more esthetically appealing. SPNAA perforator flaps could be an excellent alternative to perforator flaps that use the lower leg as a donor site.

Flow-through arterialised venous free flap using the long saphenous vein for salvage of the upper extremity.

We used two flow-through arterialised venous free flap transfers with the long saphenous vein to reconstruct major arteries and injured skin and soft tissues in the upper extremity. Operating time was reduced, only one donor site was used, and reconstruction of a long arterial defect (24-25 cm) was possible.

Glucagon-like peptide-1 enhances glucokinase activity in pancreatic ß-cells through the association of Epac2 with Rim2 and Rab3A.

Glucokinase (GK), which phosphorylates D-glucose, is a major glucose sensor in ß-cells for glucose-stimulated insulin secretion (GSIS) and is a promising new drug target for type 2 diabetes (T2D). In T2D, pancreatic ß-cells exhibit defective glucose sensitivity, which leads to impaired GSIS. Although glucagon-like peptide-1-(7-36)-amide (GLP-1) is known to enhance ß-cell glucose sensitivity, the effect of GLP-1 on GK activity is still unknown. The present study demonstrated that GLP-1 pretreatment for 30 min significantly enhanced GK activity in a glucose-dependent manner, with a lower Michaelis-Menten constant (K(m)) but unchanged maximal velocity (V(max)). Thus, GLP-1 acutely enhanced cellular glucose uptake, mitochondrial membrane potential, and cellular ATP levels in response to glucose in rat INS-1 and native ß-cells. This effect of GLP-1 occurred via its G protein-coupled receptor pathway in a cAMP-dependent but protein kinase A-independent manner with evidence of exchange protein activated by cAMP (Epac) involvement. Silencing Epac2, interacting molecule of the small G protein Rab3 (Rim2), or Ras-associated protein Rab3A (Rab3A) significantly blocked the effect of GLP-1. These results suggested that GLP-1 can further potentiate GSIS by enhancing GK activity through the signaling of Epac2 to Rim2 and Rab3A, which is the similar pathway for GLP-1 to potentiate Ca(2+)-dependent insulin granule exocytosis. The present finding may also be an important mechanism of GLP-1 for recovery of GSIS in T2D.

Aesthetic reconstruction of lower leg defects using a new anterolateral lower leg perforator flap.

Our objective in this study was to report on the successful clinical use of a new perforator flap obtained from the proximal quarter of the anterolateral lower leg. Eight patients had the procedure either as a result of trauma (seven patients) or to treat Marjolin's ulcer (one patient). During the procedure, a line was drawn from the anterior fibular head to the anterior lateral malleolus. Then, using Doppler, a septocutaneous perforator from the fibular head to the proximal quarter point of the line was identified. The subfascial dissection was continued to the detected perforator. Along the perforator in the anterior intermuscular (peroneal) septum, a deep dissection was performed. The perforator was then separated and the flap harvested. The septocutaneous perforator was the perforator of the superficial peroneal nerve accessory artery in three cases, the perforator of the superior lateral peroneal artery in one case, and the perforator originating directly from the anterior tibial artery in four cases. Seven of eight cases were treated successfully. The results obtained were satisfactory, both aesthetically and functionally. This flap is a valuable alternative to the various perforator flaps from the lower leg. This flap has the advantage of being very thin, which makes it suitable for reconstruction of defects in the foot, ankle, pretibial area, and knee. However, one limitation of this procedure is that the diameter of the perforator was approximately 0.6-1.2 mm.

Correction of the nasal tip and columella in Koreans by a complete septal extension graft using an extensive harvesting technique.

The nose of most Koreans is characterised by a low nasal dorsum, retracted columella, and an acute columella-labial angle. For the surgical correction of the tip and columella, a complete septal extension graft, along with augmentation rhinoplasty has been developed. However, the use of this type of graft is frequently problematic because the septal cartilage is not large enough. In a study involving 10 cadavers, a complete septal extension graft was achieved in two of them by using septal cartilage harvested according to standard techniques. Therefore, the septal cartilage was harvested, leaving a 5-mm L-shaped strut, and a complete septal extension graft was implanted. The present report describes the results obtained in 34 patients and offers an analysis of the results as judged by the columella-labial angle and three proportional indices (nose height index, nasal bridge length index, and nasal tip projection index), measured by photogrammetry. The postoperative values obtained in these four categories increased significantly compared to the preoperative ones, thus confirming that the projection of tip was augmented, the nose was lengthened, and the columella was advanced caudally. Moreover, these positive outcomes were maintained during long-term follow-up, and no side effects, such as saddle nose deformity, were reported.

The replantation of an amputated tongue by supermicrosurgery.

The tongue has important roles in deglutition, speech, airway protection, taste, and sexual function, and its amputation is very serious. Using supermicrosurgical techniques, we replanted successfully a patient's tongue, the distal part of which had been amputated by the bite of another person, through the anastomosis of a blood vessel that was only 0.7-0.8mm. The result was that the state of the replanted tongue was relatively good both functionally and aesthetically, and the patient was very satisfied.

Analysis of loss of heterozygosity in Korean patients with keratoacanthoma.

Loss of heterozygosity (LOH) has been established as an important genetic mechanism giving rise to malignant neoplasia. The mechanism of LOH has been shown to cause basal cell carcinoma and malignant melanoma as well as other types of skin cancer. A few studies on LOH in sporadic keratoacanthomas have been reported. The purpose of this study was to investigate the significance of LOH in the pathogenesis of sporadic keratoacanthomas developed in 10 Korean patients. The presents of LOH at 7 microsatellite markers (D2S286, D3S1317, D5S346, D9S160, D9S171, D10S185, and D17S261) were evaluated in sporadic keratoacanthomas. LOH was found in only 1 of 10 cases at D10S185. The low frequency of LOH detected in this study suggests that LOH may not be significant in the induction of sporadic keratoacanthomas.