Novel bioequivalent oral disintegrating tablet of aripiprazole prepared by direct compression technique with shortened disintegration time.

Herein, we aimed to formulate a novel oral disintegrating tablet (ODT) of aripiprazole (ARP) capable of rapid disintegration using a direct compression technique. Different ODTs were fabricated with directly compressible excipients, and their disintegration time, wettability (water absorption ratio and wetting time), and mechanical properties (hardness and friability) were evaluated. The optimized ODT comprised F-Melt® type C, Prosolv® SMCC HD90, and Na croscarmellose (10 mg of ARP in a 130 mg tablet). The ODT with 3.1-5.2 kp hardness exhibited rapid disintegration (14.1-17.2 sec), along with appropriate mechanical strength (friability < 0.24%). In a bioequivalent study in Korean healthy subjects (randomized, single-dose, two-period crossover design, n = 37), the novel ODT offered the equivalent pharmacokinetic profile to that of a conventional immediate release tablet (Otsuka, Abilify®, Japan), despite different disintegration and dissolution profiles. The 90% confidence intervals of the geometric mean test to reference ratios considering the area-under-the-curve and maximum plasma drug concentrations were 1.0306-11051 and 0.9448-1.1063, respectively, satisfying FDA regulatory criteria for bioequivalence. The novel ART ODT was physicochemically stable under the accelerated storage condition (40 °C, RH75%) for 24 weeks. Therefore, the novel ARP-loaded ODT is expected to be an alternative to oral ARP therapy, providing improved patient adherence.

Learning curve for minimally invasive transforaminal lumbar interbody fusion: a systematic review.

PURPOSE: Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) is commonly used to treat degenerative lumbar spinal disorders. It facilitates a full-scale spinal decompression and interbody fusion with minimal neural retraction using the tubular retractor system. Despite the benefits of surgical efficiency and minimalism, this technique requires a long learning curve. There is currently no consensus on the learning curve characteristics and proper training methods for MI-TLIF. Thus, this systematic review aimed to discuss the cutoff point at which technical proficiency is achieved and ways to enhance the learning process. METHODS: Major databases, including PubMed, Embase, and Cochrane Library, were searched for learning curve studies that have evaluated the clinical outcome and learning progress of MI-TLIF using quantitative data. The qualities of the selected studies were assessed using the Newcastle‒Ottawa scale. The plateau points in the "learning curve" were analyzed according to various outcome measures. RESULTS: Nine full-text articles, representing 753 cases, were included from 9743 screened studies. The most commonly used outcome measures were the operative time, followed by the complication rate. The mean cutoff point for the operative time was 31.33 ± 11.98 (range 13‒45) cases. CONCLUSION: The plateau point in the learning curve for MI-TLIF may differ according to the outcome measures used. Most studies have demonstrated the learning progress based on simple task efficiency, rather than patient outcomes. Moreover, the learning rate may be affected by the patients' and technical conditions. Therefore, great care is required in interpreting the learning curve and cutoff point for MI-TLIF proficiency.

Do IL-3/GM-CSF effect on the myofibroblastic differentiation of human adipose derived stromal cells?

BACKGROUND: Capsular contracture is an incurable complication after silicone-based implant surgery. Myofibroblast is the predominant cell in the contracted capsule. We hypothesized that human adipose derive stromal cells (hASCs) together with fibroblast may show a similar phenotypic characteristics of myofibroblast after the treatment of inflammatory cytokines in vitro. MATERIALS AND METHODS: Interleukin 3 (IL-3) and granulocyte macrophage colony stimulating factor (GM-CSF) were treated in the culture of hASCs and HDFs. Lyn peptide inhibitor was applied as an inhibitor. The changes of cell surface markers (CD105, CD73, CD34, CD45, CD31, CD325 and CD146) were assessed. The expression of various cytokines related to wound contraction were tested such as TGF-ß, α-SMA, HGF, FGF, ENT-1, and TSP-1. Myo-D, α-SMA, and glial fibrillary acidic protein (GFAP) were evaluated by blotting and immunocytochemical staining. The collagen-gel contraction assay was performed for the functional contraction of myofibroblastic phenotype. RESULTS: The expression of α-SMA, Myo-D and GFAP after the treatment of IL-3/GM-CSF showed similar results in hASCs and HDFs. Enhanced expression of TGF- ß was observed in HDFs and the increase of ENT-1 and TSP-1 was significant in hASCs. Collagen-gel with HDFs contracted significantly within 24h after the treatment of IL-3/GM-CSF, and the contraction was inhibited by Lyn peptide inhibitor. But in hASCs, the gel-contraction was not significant. CONCLUSION: IL-3/ GM-CSF effected on the myofibroblastic differentiation of hASCs as well as it did on HDFs. But hASCs did not show the phenotypic gel-contraction within 24h.

Experiments on laser cleaning of sooted optical windows.

To develop laser-ignition technology, transparent glass plates were artificially sooted and irradiated repetitively by laser from the front (sooted) and back sides separately. Generally, the back-side irradiation was more effective at soot removal. However, the cleaning effect was saturated after thousands of laser shots. Although the saturated soot quantity was a decreasing function of the laser fluence per pulse, its magnitude remained the same for both front-side and back-side irradiations. In examining several soot-removal mechanisms proposed so far, it was found that the aerodynamic force produced by the flow induced by the laser heating of the soot was the most plausible mechanism.

In Vitro Evaluation of Betafoam, a New Polyurethane Foam Dressing.

BACKGROUND: A new polyurethane foam dressing impregnated with 3% povidone-iodine (Betafoam; Genewell, Seoul, Korea) was recently developed based on the hypothesis that its physical properties, including improved moisture-retention capacity and antimicrobial activity, are at least as good as those achieved with the current foam dressings that contain silver, but also associated with reduced cost and cytotoxicity to host cells. The purpose of this in vitro study was to evaluate the efficacy of Betafoam by comparing its physical properties, antimicrobial activity, and cytotoxicity with those of 3 silver foam dressings (Allevyn-Ag [Smith & Nephew, Hull, United Kingdom]; Mepilex-Ag [Mölnlycke Health Care, Gothenburg, Sweden]; and PolyMem-Ag [Ferris MFG Corp, Burr Ridge, Illinois]) used worldwide. METHODS: This study measured each dressing's pore size, fluid absorption time, fluid absorption capacity, fluid retention capacity, antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa, and cytotoxicity to mouse fibroblasts. RESULTS: Betafoam had the smallest pore size, the fastest fluid absorption time, greatest fluid absorption, and best retention capacities among the tested foam dressings. Antimicrobial activity was not significantly different among the dressings. However, Betafoam also demonstrated the lowest cytotoxicity to the fibroblasts. CONCLUSIONS: Betafoam may result not only in desirable rapid regulation of exudation but also antimicrobial activity with minimal cytotoxicity to host cells that are key requirements for wound healing.

Evaluation of the Efficacy of Highly Hydrophilic Polyurethane Foam Dressing in Treating a Diabetic Foot Ulcer.

OBJECTIVE: To demonstrate the efficacy of a highly hydrophilic polyurethane foam dressing in the treatment of diabetic ulcers. BACKGROUND: Diabetic foot ulcers often pose a difficult treatment problem. Polyurethane foam dressings have been used worldwide to accelerate wound healing, but only a few clinical studies demonstrate the effect of foam dressing on the healing of diabetic ulcers. METHODS: Medical records of 1342 patients with diabetic ulcers who were admitted and treated at the authors' institution were reviewed. A total of 208 patients met the study's inclusion criteria. Of these 208 patients, 137 were treated with a highly hydrophilic polyurethane foam dressing, and 71 were treated with saline gauze (control group). Except for the application of polyurethane foam dressing, the treatment method was identical for patients in both groups. The wound healing outcomes of the 2 groups were compared. RESULTS: Complete wound healing occurred in 87 patients (63.5%) in the polyurethane foam dressing group and in 28 patients (39.4%) in the control group within 12 weeks (P < .05, X test). The mean percentage of wound area reduction in both groups was statistically significant (P < .05, Mann-Whitney U test). The mean time required for complete closure in patients who achieved complete healing within 12 weeks was 6.2 (SD, 3.4) weeks and 7.3 (SD, 2.6) weeks in the polyurethane foam dressing and control groups, respectively (P < .05, Mann-Whitney U test). CONCLUSION: These results indicate that the highly hydrophilic polyurethane foam dressing may provide an effective treatment strategy for diabetic foot ulcers.

Influence of Negative-Pressure Wound Therapy on Tissue Oxygenation in Diabetic Feet.

OBJECTIVE: Negative-pressure wound therapy (NPWT) has become a common wound care treatment modality for a variety of wounds. Several previous studies have reported that NPWT increases blood flow in the wound bed. However, NPWT might decrease tissue oxygenation in the wound bed because the foam sponge of NPWT compresses the wound bed under the influence of the applied negative pressure. Adequate tissue oxygenation is an essential consideration during diabetic foot management, and the foot is more sensitive to ischemia than any other region. Furthermore, the issue as to whether NPWT reduces or increases tissue oxygenation in diabetic feet has never been correctly addressed. The aim of this study was to evaluate the influence of NPWT on tissue oxygenation in diabetic feet. PARTICIPANTS: Transcutaneous partial oxygen pressures (TcPO2) were measured to determine tissue oxygenation levels beneath NPWT dressings on 21 feet of 21 diabetic foot ulcer patients. DESIGN: A TcPO2 sensor was fixed at the tarsometatarsal area of contralateral unwounded feet. A suction pressure of -125 mm Hg was applied until TcPO2 reached a steady state. The TcPO2 values for diabetic feet were measured before, during, and after NPWT. MAIN RESULTS: The TcPO2 levels decreased significantly after applying NPWT in all patients. Mean TcPO2 values before, during, and after therapy were 44.6 (SD, 15.2), 6.0 (SD, 7.1), and 40.3 (SD, 16.4) mm Hg (P < .01), respectively. CONCLUSION: These results show that NPWT significantly reduces tissue oxygenation levels in diabetic feet.

Risk factors for major amputation in hospitalised diabetic foot patients.

Diabetic foot ulcers are the main cause of non-traumatic lower extremity amputation. The objective of this study was to evaluate the risk factors for major amputation in diabetic foot patients. Eight hundred and sixty diabetic patients were admitted to the diabetic wound centre of the Korea University Guro Hospital for foot ulcers between January 2010 and December 2013. Among them, 837 patients were successfully monitored until complete healing. Ulcers in 809 patients (96·7%) healed without major amputation and those in 28 patients (3·3%) healed with major amputation. Data of 88 potential risk factors including demographics, ulcer condition, vascularity, bioburden, neurology and serology were collected from patients in the two groups and compared. Among the 88 potential risk factors, statistically significant differences between the two groups were observed in 26 risk factors. In the univariate analysis, which was carried out for these 26 risk factors, statistically significant differences were observed in 22 risk factors. In a stepwise multiple logistic analysis, six of the 22 risk factors remained statistically significant. Multivariate-adjusted odds ratios were 11·673 for ulcers penetrating into the bone, 8·683 for dialysis, 6·740 for gastrointestinal (GI) disorders, 6·158 for hind foot ulcers, 0·641 for haemoglobin levels and 1·007 for fasting blood sugar levels. The risk factors for major amputation in diabetic foot patients were bony invasions, dialysis, GI disorders, hind foot locations, low levels of haemoglobin and elevated fasting blood sugar levels.

Effects of Panax ginseng extract on human dermal fibroblast proliferation and collagen synthesis.

Current studies of Panax ginseng (or Korean ginseng) have demonstrated that it has various biological effects, including angiogenesis, immunostimulation, antimicrobial and anti-inflammatory effects. Therefore, we hypothesised that P. ginseng may also play an important role in wound healing. However, few studies have been conducted on the wound-healing effects of P. ginseng. Thus, the purpose of this in vitro pilot study was to determine the effects of P. ginseng on the activities of fibroblasts, which are key wound-healing cells. Cultured human dermal fibroblasts were treated with one of six concentrations of P. ginseng: 0, 1, 10 and 100 ng/ml and 1 and 10 µg/ml. Cell proliferation was determined 3 days post-treatment using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay, and collagen synthesis was evaluated by the collagen type I carboxy-terminal propeptide method. Cell proliferation levels and collagen synthesis were compared among the groups. The 10 ng/ml to 1 µg/ml P. ginseng treatments significantly increased cell proliferation, and the 1 ng/ml to 1 µg/ml concentrations significantly increased collagen synthesis. The maximum effects for both parameters were observed at 10 ng/ml. P. ginseng stimulated human dermal fibroblast proliferation and collagen synthesis at an optimal concentration of 10 ng/ml.

Wound-healing potential of human umbilical cord blood-derived mesenchymal stromal cells in vitro--a pilot study.

BACKGROUND AIMS: Our previous studies demonstrated that human bone marrow-derived mesenchymal stromal cells have great potential for wound healing. However, it is difficult to clinically utilize cultured stem cells. Recently, human umbilical cord blood-derived mesenchymal stromal cells (hUCB-MSCs) have been commercialized for cartilage repair as a first cell therapy product that uses allogeneic stem cells. Should hUCB-MSCs have a superior effect on wound healing as compared with fibroblasts, which are the main cell source in current cell therapy products for wound healing, they may possibly replace fibroblasts. The purpose of this in vitro study was to compare the wound-healing activity of hUCB-MSCs with that of fibroblasts. METHODS: This study was particularly designed to compare the effect of hUCB-MSCs on diabetic wound healing with those of allogeneic and autologous fibroblasts. Healthy (n = 5) and diabetic (n = 5) fibroblasts were used as the representatives of allogeneic and autologous fibroblasts for diabetic patients in the control group. Human UCB-MSCs (n = 5) were used in the experimental group. Cell proliferation, collagen synthesis and growth factor (basic fibroblast growth factor, vascular endothelial growth factor and transforming growth factor-ß) production were compared among the three cell groups. RESULTS: Human UCB-MSCs produced significantly higher amounts of vascular endothelial growth factor and basic fibroblast growth factor when compared with both fibroblast groups. Human UCB-MSCs were superior to diabetic fibroblasts but not to healthy fibroblasts in collagen synthesis. There were no significant differences in cell proliferation and transforming growth factor-ß production. CONCLUSIONS: Human UCB-MSCs may have greater capacity for diabetic wound healing than allogeneic or autologous fibroblasts, especially in angiogenesis.

Effect of fibroblast-seeded artificial dermis on wound healing.

In covering wounds, efforts should include use of the safest and least invasive methods with a goal of achieving optimal functional and cosmetic outcome. The recent development of advanced technology in wound healing has triggered the use of cells and/or biological dermis to improve wound healing conditions. The purpose of the study was to evaluate the effects of fibroblast-seeded artificial dermis on wound healing efficacy.Ten nude mice were used in this study. Four full-thickness 6-mm punch wounds were created on the dorsal surface of each mouse (total, 40 wounds). The wounds were randomly assigned to one of the following 4 treatments: topical application of Dulbecco phosphate-buffered saline (control), human fibroblasts (FB), artificial dermis (AD), and human fibroblast-seeded artificial dermis (AD with FB). On the 14th day after treatment, wound healing rate and wound contraction, which are the 2 main factors determining wound healing efficacy, were evaluated using a stereoimage optical topometer system, histomorphological analysis, and immunohistochemistry.The results of the stereoimage optical topometer system demonstrated that the FB group did not have significant influence on wound healing rate and wound contraction. The AD group showed reduced wound contraction, but wound healing was delayed. The AD with FB group showed decreased wound contraction without significantly delayed wound healing. Histomorphological analysis exhibited that more normal skin structure was regenerated in the AD with FB group. Immunohistochemistry demonstrated that the AD group and the AD with FB group produced less α-smooth muscle actin than the control group, but this was not shown in the FB group.Fibroblast-seeded artificial dermis may minimize wound contraction without significantly delaying wound healing in the treatment of skin and soft tissue defects.

Comparison of the Matrix Synthesizing Abilities of Human Adipose-Derived Stromal Vascular Fraction Cells and Fibroblasts.

For facial soft tissue augmentation or wound coverage using tissue-engineering technology, cultured fibroblasts have been most commonly used as key cells and their properties have been extensively studied. Clinical strategies based on human cultured fibroblasts, however, require Food and Drug Administration (FDA) approval for the facilities and the procedures used and time-consuming culture. Adipose tissue-derived stromal vascular fraction (SVF) cells may be a reliable alternative to fibroblasts because they are easily harvested by liposuction and do not require culture or FDA approval. No quantitative standard governing their use has, however, been issued. The purpose of this study was to quantitatively compare matrix-forming abilities of SVF cells and fibroblasts. Human dermal fibroblasts were obtained from the dermis of 10 healthy adults and cultured, and SVF cells were obtained from 10 patients who underwent liposuction. Monolayer and suspension cell cultures were performed using both cell types for 3 days. Cell proliferations, collagen synthesis levels, and glycosaminoglycan levels were compared using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, a collagen type I carboxy-terminal propeptide enzyme immunoassay, and the Blyscan Dye method, respectively. Cell proliferation ratios (fibroblasts versus SVF cells) in monolayer and suspension cultures were 1:0.75 and 1:0.99, respectively; collagen synthesis ratios in monolayer and suspension cultures were 1:0.50 and 1:0.52, respectively; and glycosaminoglycan production ratios were 1:0.70 and 1:0.74, respectively. The results of this in vitro study indicate that SVF cells have 50-74% of the matrix-forming ability of fibroblasts.

Optimal Viscosity and Particle Shape of Hyaluronic Acid Filler as a Scaffold for Human Fibroblasts.

The authors previously reported that cultured human fibroblasts suspended in a hyaluronic acid filler can produce human dermal matrices with extended in vivo stability in animal and clinical studies. The present study was undertaken to determine the optimal viscosity and particle shape of hyaluronic acid filler as a scaffold for cultured human dermal fibroblasts to enhance the maximal viability of injected cells. The fibroblasts were suspended in either 1 of 3 hyaluronic acid viscosities at 2 different particle shapes. The viscosities used in this study were low (600,000-800,000 centipoises), moderate (2,000,000-4,000,000 centipoises), and high (8,000,000-12,000,000 centipoises). The particle shape was evaluated by testing round and irregular shapes. The fibroblast mixed bioimplants were injected into the back of individual athymic nude mice. The levels of type I collagen were measured using fluorescent-activated cell sorting (FACS) and immunohistochemical staining at 16 weeks after the injections. Results of FACS demonstrated that the mean cell ratio with human collagens in the moderate viscosity group was greater than those of control, low, and high viscosity groups. An immunohistochemical study showed similar results. The moderate viscosity group demonstrated the highest positive staining of human collagens. However, there were no significant differences between groups of irregular and round shape particles. A hyaluronic acid bioimplant with moderate viscosity is superior to that with low or high viscosity in the viability for human fibroblasts. However, the particle shape does not influence the viability of the fibroblasts.

Effect of antibiotic use and mold exposure in infancy on allergic rhinitis in susceptible adolescents.

BACKGROUND: Antibiotic use in infancy induces alteration in intestinal microbiota and is associated with the development of allergic diseases. Mold exposure is also associated with allergic diseases. Genetic susceptibility may interact with specific environmental factors in allergic disease development. OBJECTIVE: To investigate independent and combined effects of antibiotic use and mold exposure in infancy on the risk of allergic rhinitis (AR) in adolescents. METHODS: Data on AR and environmental factors were collected using the International Study of Asthma and Allergies in Childhood questionnaire from 7,389 adolescents from Seoul, Korea. TaqMan genotyping was performed for interleukin 13 (IL-13) (rs20541) and Toll-like receptor 4 (rs1927911) polymorphisms in 1,395 adolescents. RESULTS: Age, parental history of AR, antibiotic use in infancy, and pet ownership during pregnancy or infancy were associated with an increased risk of current AR (diagnosis of AR and symptoms of AR within the preceding 12 months). Having older siblings was a protective effect. The adjusted odds ratio (aOR) for current AR for combined antibiotic use and mold exposure in infancy was 1.45 (95% confidence interval [CI], 1.01-2.09). For each factor separately, aORs were 1.25 (95% CI, 1.04-1.50) and 0.99 (95% CI, 0.75-1.31), respectively. Antibiotic and mold exposure in infancy, GA or AA genotypes of IL-13 (rs20541) (aOR 4.53; 95% CI, 1.66-12.38; P for interaction = .05), and CT+TT genotype of Toll-like receptor 4 (rs1927911) (aOR, 3.20; 95% CI, 1.24-8.26; P for interaction = .18) increased the risk of current AR. CONCLUSION: Antibiotic use and mold exposure in infancy have additive effects on the risk of current AR in genetically susceptible adolescents. Gene-environment interactions between IL-13 (rs20541) and antibiotics or mold may play a role in AR.

Comparison of tissue-engineered and artificial dermis grafts after removal of basal cell carcinoma on face--a pilot study.

BACKGROUND: Planning reconstruction for facial defects should include the safest and least-invasive methods, with a goal of achieving optimal functional and cosmetic outcomes. OBJECTIVE: To compare tissue-engineered dermis grafts with artificial dermis grafts after removal of basal cell carcinoma (BCC) on the face. MATERIALS AND METHODS: A tissue-engineered dermis composed of autologous cultured dermal fibroblasts seeded on a hyaluronic acid sheet was applied to 16 patients. Grafting of hyaluronic acid sheets that did not contain fibroblasts (artificial dermis group) was performed in 13 patients. Healing time, scar condition, and patient satisfaction were compared. RESULTS: The wounds of the tissue-engineered dermis group reepithelialized after 31.4 ± 5.3 days and those of the artificial dermis group after 34.2 ± 4.9 days. The tissue-engineered dermis graft was superior in scar quality. In particular, statistically significant differences were detected in the height and contracture of scars, although there were no significant differences in terms of scar texture or color match. Patient satisfaction in the tissue-engineered dermis graft group (8.3 ± 1.0) was also statistically superior to that in the artificial dermis group (6.9 ± 1.4). CONCLUSION: The tissue-engineered dermis graft is superior to the artificial dermis graft for covering defects after removal of BCC on the face.

Influence of the pedicle orientation and length on viability of unipedicled venous island flaps.

The use of unipedicled venous flaps has been limited due to their unconventional perfusion patterns and inconsistent survival. Further information regarding the optimal conditions required for unipedicled venous flap coverage is needed to increase flap survival. The purpose of this study was to investigate the effect of the pedicle orientation and length on the viability of unipedicled venous flaps based on a review of our clinical experience. Thirty-one skin and soft tissue hand defects of 29 patients were treated with unipedicled venous flaps. Sixteen defects were treated with proximally pedicled flaps and 15 were treated with distally pedicled flaps. Five of the 16 proximally pedicled flaps and eight of the 15 distally pedicled flaps had pedicle lengths ≥ 5 cm. All proximally pedicled flaps survived, and distally pedicled flaps with pedicle lengths <5 cm (n = 7) also survived. Distally pedicled flaps with pedicle lengths ≥5 cm (n = 8) developed congestion within 1-2 days after surgery, and external bleeding was applied. Four of the eight flaps survived completely, and partial necrosis developed in the other four. The results demonstrate that proximally pedicled venous flaps of the hand can survive regardless of pedicle length. Distally pedicled venous flaps can also survive completely when pedicle length is <5 cm. Distally pedicled venous flaps with pedicle lengths ≥5 cm should be used with caution.

Potential of oncostatin M to accelerate diabetic wound healing.

Oncostatin M (OSM) is a multifunctional cytokine found in a variety of pathologic conditions, which leads to excessive collagen deposition. Current studies demonstrate that OSM is also a mitogen for fibroblasts and has an anti-inflammatory action. It was therefore hypothesised that OSM may play an important role in healing of chronic wounds that usually involve decreased fibroblast function and persist in the inflammatory stage for a long time. In a previous in vitro study, the authors showed that OSM increased wound healing activities of diabetic dermal fibroblasts. However, wound healing in vivo is a complex process involving multiple factors. Thus, the purpose of this study was to evaluate the effect of OSM on diabetic wound healing in vivo. Five diabetic mice were used in this study. Four full-thickness round wounds were created on the back of each mouse (total 20 wounds). OSM was applied on the two left-side wounds (n = 10) and phosphate-buffered saline was applied on the two right-side wounds (n = 10). After 10 days, unhealed wound areas of the OSM and control groups were compared using the stereoimage optical topometer system. Also, epithelialisation, wound contraction and reduction in wound volume in each group were compared. The OSM-treated group showed superior results in all of the tested parameters. In particular, the unhealed wound area and the reduction in wound volume demonstrated statistically significant differences (P < 0·05). The results of this study indicate that topical application of OSM may have the potential to accelerate healing of diabetic wounds.

Effect of paracetamol use on the modification of the development of asthma by reactive oxygen species genes.

BACKGROUND: Recent studies have identified an increase in the prevalence of asthma associated with paracetamol use. OBJECTIVE: To identify the relationship among asthma, biomarkers, genes, and paracetamol use in preschool children. METHODS: We undertook a population-based, cross-sectional survey of 933 preschool children. Asthma status was classified according to medical history and asthmatic symptoms. History of paracetamol use in infancy was recorded. Impulse oscillometry, blood tests for eosinophils and total IgE, and genotyping of NAT2, Nrf2, and GSTP1 polymorphisms by TaqMan assay were conducted. RESULT: Paracetamol use in infancy was associated with an increased risk of treatment for asthma within the previous 12 months. Paracetamol use together with a family history of asthma increased the risk of asthma diagnosis ever, current asthma, and treatment for asthma within the previous 12 months. Gene polymorphisms in NAT2 (rs4271002), Nrf2 (rd6726395), and GSTP1 (rd1695) increased the risk of treatment for asthma within the last 12 months. Eosinophils were significantly elevated in the group with paracetamol use and a family history of asthma; however, the serum total IgE level and IOS did not show any significant difference. CONCLUSION: Paracetamol use in infancy was significantly associated with increased risk of asthma. The association is more significant in genetically susceptible children, related to antioxidant genes, and the effect may be mediated by eosinophilic inflammation.

Reconstruction of extensive abdominal wall defect using an eccentric perforator-based pedicled anterolateral thigh flap: a case report.

Reconstruction of extensive abdominal wall defects is a challenge for reconstructive surgeons. In this report, a case of reconstruction of a large abdominal wall defect using an eccentric perforator-based pedicled anterolateral thigh (ALT) flap is presented. A 30-year-old man presented with recurrent desmoid-type fibromatosis in the abdominal wall. The recurrent tumor was radically excised, and the en bloc excision resulted in a full-thickness, large abdominal wall defect (25 cm × 20 cm). An eccentric perforator-based pedicled ALT flap, including wide fascial extension, was transferred to the abdominal defect; fascial portions were sutured to the remnant abdominal fascia. Plication of the fascia along the sutured portion was performed to relieve the skin tension between the flap and the marginal skin of the abdominal defect. Eight months after surgery, the reconstructed abdomen had an acceptable esthetic appearance without tumor recurrence or hernia. The use of an eccentric perforator-based pedicled ALT flap may be an alternative method for the reconstruction of extensive abdominal wall defects.

What tissue is formed after graft of adipose-derived stromal vascular fraction cells?

Cultured human fibroblasts have been used for soft-tissue augmentation in the face. However, if cultured cells are to be used clinically, the approval of the Food and Drug Administration and time-consuming culturing procedures are required. For this reason, we investigated adipose-derived stromal vascular fraction (SVF) cells, which could be obtained in large quantities without cell culture. However, unlike fibroblasts, SVF cells are a heterogenic cell population. Therefore, it was hypothesized that a SVF cell graft may possibly form various tissues. This study was performed to determine what tissue would form after a graft of SVF cells. Stromal vascular fraction cells were isolated from liposuctioned human adipose tissue. For a test group, SVF cells were suspended in hyaluronic acid filler. For a control group, no cells were included in the filler. These implants were subcutaneously injected into the backs of 4 nude mice. After 16 weeks, the injection areas were excised, and histologic examination was performed including immunohistochemistry to confirm the presence of human collagen. The test group specimens revealed fibrous connective tissues infiltrating into and surrounding the hyaluronic acids. Collagen fibers and fibroblasts were found around newly formed vascular structures. In contrast, the control group did not show cells or hyaluronic acid particles. Immunohistochemistry of the test group displayed strong expression of human collagen. However, the control group exhibited negative staining. This suggests that transplanted uncultured human SVF cells combined with hyaluronic acid filler generate fibrovascular tissue.