• Korean Journal of Clinical Pharmacy
• /
• v.28 no.1
• /
• pp.24-29
• /
• 2018

Background: Cyclosporine is an immunosuppressive agent used to treat and prevent graft versus host reaction (GVHR)-a complication associated with stem cell transplantation. This study aimed to develop a population pharmacokinetic model of cyclosporine and investigate factors affecting cyclosporine clearance in pediatric hematopoietic stem cell transplant patients. Methods: A total of 650 cyclosporine concentrations recorded in 65 patients who underwent hematopoietic stem cell transplantation were used. Data including age, sex, weight, height, body surface area (BSA), type of disease, chemotherapy before stem cell transplantation, type of donor, serum creatinine levels, total bilirubin concentration, hematocrit value, and type of concomitant anti-fungal agents and methylprednisolone used were retrospectively collected. Data related to cyclosporine dosage, administration time, and blood concentration were also collected. All data were analyzed using the non-linear mixed effect model; a two-compartment model with first-order elimination was used. Results: The population pharmacokinetic model of cyclosporine using the NONMEM program was as follows: $CL(L/h)=5.9{\times}(BSA/1.2)^{0.9}$, V2 (L) = 54.5, Q (L/h) = 3.5, V3 (L) = 1080.0, $k_a(h^{-1})=0.000377$. BSA was selected as a covariate of cyclosporine clearance, which increased with an increase in BSA. Conclusion: A population pharmacokinetic model for Korean pediatric hematopoietic stem cell transplant patients was developed, and the important factor affecting cyclosporine clearance was found to be BSA. The model might contribute to the development of the most appropriate dosing regimen for cyclosporine. Further studies on population pharmacokinetics should be carried out, prospectively targeting pediatric patients.

• Journal of Periodontal and Implant Science
• /
• v.46 no.6
• /
• pp.415-425
• /
• 2016

Purpose: The present study investigated the impact of 2 different suture techniques, the conventional crossed mattress suture (X suture) and the novel hidden X suture, for alveolar ridge preservation (ARP) with an open healing approach. Methods: This study was a prospective randomized controlled clinical trial. Fourteen patients requiring extraction of the maxillary or mandibular posterior teeth were enrolled and allocated into 2 groups. After extraction, demineralized bovine bone matrix mixed with 10% collagen (DBBM-C) was grafted and the socket was covered by porcine collagen membrane in a double-layer fashion. No attempt to obtain primary closure was made. The hidden X suture and conventional X suture techniques were performed in the test and control groups, respectively. Cone-beam computed tomographic (CBCT) images were taken immediately after the graft procedure and before implant surgery 4 months later. Additionally, the change in the mucogingival junction (MGJ) position was measured and was compared after extraction, after suturing, and 4 months after the operation. Results: All sites healed without any complications. Clinical evaluations showed that the MGJ line shifted to the lingual side immediately after the application of the X suture by $1.56{\pm}0.90mm$ in the control group, while the application of the hidden X suture rather pushed the MGJ line slightly to the buccal side by $0.25{\pm}0.66mm$. It was demonstrated that the amount of keratinized tissue (KT) preserved on the buccal side was significantly greater in the hidden X suture group 4 months after the procedure (P<0.05). Radiographic analysis showed that the hidden X suture had a significant effect in preserving horizontal width and minimizing vertical reduction in comparison to X suture (P<0.05). Conclusions: Our study provided clinical and radiographic verification of the efficacy of the hidden X suture in preserving the width of KT and the dimensions of the alveolar ridge after ARP.

• Imaging Science in Dentistry
• /
• v.38 no.3
• /
• pp.133-146
• /
• 2008

Purpose : To observe and evaluate the effects of Simvastatin-induced osteogenesis on the wound healing of defective bone. Materials and Methods : 64 defective bones were created in the parietal bone of 32 New Zealand White rabbits. The defects were grafted with collagen matrix carriers mixed with Simvastatin solution in the experimental group of 16 rabbits and with collagen matrix carriers mixed with water in the controlled group. The rabbits were terminated at an interval of 3, 5, 7, and 9 days, 2, 4, 6, and 8 weeks after the formation of defective bone. The wound healing was evaluated by soft X-ray radiography. The tissues within defective bones were evaluated through the analysis of flow cytometry for the manifestation of Runx2 and Osteocalcin, and observed histopathologically by using H-E stain and Masson's trichrome stain. Results : 1. In the experimental group, flow cytometry revealed more manifestation of Runx2 at 5, 7, and 9 days and Osteocalcin at 2 weeks than in the controlled groups, but there was few difference in comparison with the controlled group. 2. In the experimental group, flow cytometry revealed considerably more cells and erythrocytes at 5, 7, and 9 days in comparison with the controlled group. 3. In the experimental group, soft x-ray radiography revealed the extended formation of trabeculation at 2, 4, 6, and 8 weeks. 4. Histopathological features of the experimental group showed more fibroblasts and newly formed vessels at 5 and 7 days, and the formation of osteoid tissues at 9 days, and the newly formed trabeculations at 4 and 6 weeks. Conclusion : As the induced osteogenesis by Simvastatin, there was few contrast of the manifestation between Runx2 and Osteocalcin based on the differentiation of osteoblasts. But it was considered that the more formation of cells and erythrocytes depending on newly formed vessels in the experimental group obviously had an effect on the bone regeneration.

• Membrane Journal
• /
• v.25 no.5
• /
• pp.398-405
• /
• 2015

Facilitated transport is considered to be a possible solution to simultaneously improve permeability and selectivity, which is challenging in normal polymeric membranes based on solution-diffusion transport only. We investigated the effect of adding mesoporous $TiO_2$ ($m-TiO_2$) upon the separation performance of facilitated olefin transport membranes comprising poly(vinyl pyrrolidone), Ag nanoparticles, and 7,7,8,8-tetracyanoquinodimethane as the polymer matrix, olefin carrier, and electron acceptor, respectively. In particular, $m-TiO_2$ was prepared by means of a facile, mass-producible method using poly(vinyl chloride)-g-poly(oxyethylene methacrylate) graft copolymer as the template. The crystal phase of $m-TiO_2$ consisted of an anatase/rutile mixture, of crystallite size approximately 16 nm as determined by X-ray diffraction. The introduction of $m-TiO_2$ increased the membrane diffusivity, thereby increasing the mixed-gas permeance from 1.6 to 16.0 GPU ($1GPU=10^{-6}cm^3$(STP)/($s{\times}cm^2{\times}cmHg$), and slightly decreased the propylene/propane selectivity from 45 to 37. However, both the mixed-gas permeance and selectivity of the membrane containing $m-TiO_2$ rapidly decreased over time, whereas the membrane without $m-TiO_2$ had more stable long-term performance. This difference might be attributed to specific chemical interactions between $TiO_2$ and Ag nanoparticles, causing Ag to lose activity as an olefin carrier.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.31 no.3
• /
• pp.243-248
• /
• 2009

Purpose: Rehabilitation of the edentulous posterior maxilla with dental implants often poses difficulty because of insufficient bone volume caused by pneumatization of the maxillary sinus and by crestal bone resorption. Sinus grafting technique was developed to increase the vertical height to overcome this problem. The present study was designed to evaluate the sinus floor augmentation with anorganic bovine bone (Bio-$cera^{TM}$) using histomorphometric and clinical measures. Patients and methods: Thirteen patients were involved in this study and underwent total 14 sinus lift procedures. Residual bone height was ${\geq}2mm$ and ${\leq}6mm$. Lateral window approach was used, with grafting using Bio-$cera^{TM}$ only(n=1) or mixed with autogenous bone from ramus and/or maxillary tuberosity(n=13). After 6 months of healing, implant sites were created with 3mm diameter trephine and biopsies taken for histomorphometric analysis. The parameters assessed were area fraction of new bone, graft material and connective tissue. Immediate and 6 months after grafting surgery, and 6 months after implantation, computed tomography (CT) was taken and the sinus graft was evaluated morphometric analysis. After implant installation at the grafted area, the clinical outcome was checked. Results: Histomorphometry was done in ten patients.Bio-$cera^{TM}$ particles were surrounded by newly formed bone. The graft particles and newly formed bone were surrounded by connective tissue including small capillaries in some fields. Imaging processing revealed $24.86{\pm}7.59%$ of new bone, $38.20{\pm}13.19%$ connective tissue, and $36.92{\pm}14.51%$ of remaining Bio-$cera^{TM}$ particles. All grafted sites received an implant, and in all cases sufficient bone height was achieved to install implants. The increase in ridge height was about $15.9{\pm}1.8mm$ immediately after operation (from 13mm to 19mm). After 6 months operation, ridge height was reduced about $11.5{\pm}13.5%$. After implant installation, average marginal bone loss after 6 months was $0.3{\pm}0.15mm$. Conclusion: Bio-$cera^{TM}$ showed new bone formation similar with Bio-$Oss^{(R)}$ histomorphometrically and appeared to be an effective bone substitute in maxillary sinus augmentation procedure with the residual bone height from 2 to 6mm.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.32 no.4
• /
• pp.293-298
• /
• 2010

Purpose: The objective of the present study was to determine the capability of electrospun silk fibroin as a biomaterial template for bone formation when mixed with nano-hydoxyapatite in vivo. Materials and Methods: Ten New Zealand white rabbits were used for this study and bilateral round shaped defects were formed in the parietal bone (diameter: 8.0 mm). The electrospun silk fibroin was coated by nano-hydroxyapatite and grafted into the right parietal bone (experimental group). The left side (control group) did not receive a graft. The animals were sacrificed at 6 weeks and 12 weeks, humanly. The microcomputerized tomogram (${\mu}CT$) was taken for each specimen. Subsequently, they were undergone decalcification and stained for the histological analysis. Results: The average value of all measured variables was higher in the experimental group than in the control at 6 weeks after the operation. BMC in the experimental group at 6 weeks after operation was $48.94{\pm}19.25$ and that in the control was $26.17{\pm}16.40$ (P = 0.027). BMD in the experimental group at 6 weeks after operation was $324.59{\pm}165.24$ and that in the control was $173.03{\pm}120.30$ (P = 0.044). TMC in the experimental group at 6 weeks after operation was $19.50{\pm}6.00$ and that in the control was $10.52{\pm}6.20$ (P = 0.011). TMD in the experimental group at 6 weeks after operation was $508.88{\pm}297.57$ and that in the control was $273.54{\pm}175.91$ (P = 0.06). Gross image of both groups showed higher calcification area at 12 weeks than them in 6 weeks. The average value of ${\mu}CT$ analysis was higher at 12 weeks than that in 6 weeks in both groups. BMC in the experimental group at 12 weeks after operation was $51.21{\pm}8.81$ and that in the control was $33.47{\pm}11.13$ (P = 0.010). BMD in the experimental group at 12 weeks after operation was $323.39{\pm}21.54$ and that in the control was $197.75{\pm}76.23$ (P = 0.012). TMC in the experimental group at 12 weeks after operation was $21.44{\pm}5.30$ and that in the control was $13.31{\pm}4.17$ (P = 0.008). TMD in the experimental group at 12 weeks after operation was $524.47{\pm}19.37$ and that in the control was $299.60{\pm}136.20$ (P = 0.016). Conclusion: The rabbit calvarial defect could be successfully repaired by electrospun silk nano-fiber combined with nano-hydroxyapatite.

• Clinical and Experimental Pediatrics
• /
• v.48 no.2
• /
• pp.178-185
• /
• 2005

Purpose : The purpose of this study was to evaluate the outcome of children with juvenile myelomonocytic leukemia(JMML) treated with allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods : Eleven JMML patients aged 8-39 months underwent allo-HSCT. The sources of grafts were unrelated donors(n=7), HLA-matched siblings(n=3) and an HLA 1-antigen mismatched familial donor. All patients had received chemotherapy ${\pm}13$-cis-retinoic acid(CRA) before transplant, and CRA was used, posttransplant, in six patients. Results : Only three patients were in complete remission(CR) at the time of transplantation. Initial chimeric status revealed complete donor chimerism(CC) in five patients, mixed chimerism(MC) in five and autologous recovery(AR) in one. One patient with MC having persistent splenomegaly eventually turned to CC and CR after rapid tapering of cyclosporine, combined with daily use of CRA. An AR case relapsed shortly after transplant but was rescued with second, unrelated cord blood transplantation. Ultimately, six patients are alive, event-free, with a median follow-up of 15.5 months posttransplant. All three deaths occurred in patients who failed to achieve CC, leading to disease progression. Conclusion : We suggest that graft-versus-leukemia effect play an important role and CRA a possible role in posttransplant leukemic involution in JMML. In patients whose leukemic burden is still high with MC after transplant, early tapering of immunosuppressants and introduction of CRA might provide a chance of a cure for some patients.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.35 no.5
• /
• pp.284-293
• /
• 2013

Purpose: For reconstruction of craniomaxillofacial defects caused by tumor, trauma, infection etc, free flap transplantation with microvascular surgery is a very useful method. Thrombus formation at the anastomosis site is the major cause of graft failure. 4-Hexylresorcinol (4-HR) is generally known as an antiseptic and antiparasitic agent. This study was conducted in order to evaluate the effect of 4-HR on blood coagulation in vitro. In addition, we investigated thrombus formation and endothelial repair of an injured vessel in an animal model. Methods: In the in vitro experiment, we compared blood coagulation time between the 4-HR treated group and normal blood. Thirty rats were used for in vivo animal experiments. After exposure of the right femoral vein, a micro vessel clamp was placed and the femoral vein was intentionally cut. Microvascular anastomosis was performed on all rats using 10-0 nylon under microscopy. The animals were divided into two groups. In the experimental group (n=15), 4-HR (250 mg/kg) mixed with olive oil (10 mL/kg) was administered per os daily. Animals in the control group (n=15) were given olive oil only. The animals were sacrificed at three days, seven days, and fourteen days after surgery and rat femoral vein samples were taken. Vascular patency and thrombus formation were investigated just before sacrifice. Histologic analysis was performed under a microscope. Results: Results of an in vitro blood coagulation test showed that coagulation time was delayed in the 4-HR treated group. The results obtained from an in vivo 4-HR administered rat model showed that the patency of all experimental groups was better at thirty minutes, seven days, and fourteen days after microvascular anastomosis than that of the control group at seven and fourteen days after anastomosis, and the amount of thrombus in the experimental groups was much less than that of the control group. Endothelial repair was observed in the histologic analysis. Conclusion: Findings of this study demonstrated that blood coagulation was delayed in the vitro 4-HR treated group. In addition, good vascular patency, anti-thrombotic effect, and repair of venous endothelial cells were observed in the vivo 4-HR administered rat group.

• Journal of Chest Surgery
• /
• v.30 no.7
• /
• pp.733-738
• /
• 1997

Sequential bilateral lung transplantation may result in a variety of perioperative and postoperative complications, showing high perioperative morbidity and mortality rates. This research was performed to investigate the hemodynamic changes in adult mongrel dogs after bilateral reimplantation, two methods preferred for avoiding or minimizing graft rejection. The anterior portion of the pulmonary artery and the left atrium proximal to the superior and the inferior pulmonary veins were resected out and then re-anastomosed one hour later to prevent torsion or stenosis of the anastomotic site and the formation of a thrombosis in the left atrium. An everted suture technique was employed for the left atrium; An hour after the division, however, the main bronchus was tightly anastomose by interrupted sutures of No. 4-0 prolene in a telescope method. A modified I-C solution mixed with PGEI was infused into the cut portion of the pulmonary artery at the rate of 15 mllkglmin and at a pressure of 40 cmH20 for a total dosage of 70 mlfkg in order to preserve the transected lung. Topical cooling using wet gauzes soaked with cold I-C solution was performed for one hour to prevent ischemic lung injury. The above procedures are considered to be beneficial for achieving a satisfactory outcome for bilateral lung reimplantation.

• Archives of Plastic Surgery
• /
• v.33 no.2
• /
• pp.205-212
• /
• 2006

Using adipose derived stem cells(ASCs), neurogenic differentiation was induced in a mono layered culture medium containing neuronal induction agents. Cells differentiated to the neuronal cells were observed with a inverted microscope and immunofluorecent study. We made a 15 mm long defect in the sciatic nerve of 14 rats and connected a silicone tube to the defect. Then, we mixed neuronal progenitor cells differentiated from ASCs with collagen gel and grafted them to a group of rats(experimental group) and grafted only collagen gel into another group(control group). In 4 and 8 weeks after the graft, histological observation was made. According to the result, the number and diameter of myelinated axons were significantly increased in the experimental group. In addition, the nerve conduction velocity was improved more in the experimental group and neovascularity also increased. Moreover, reaction with S100 and p75 was observed in regenerated nerves in the experimental group, suggesting that the grafted cells were differentiated into supportive cells such as Schwann's cells. In conclusion, this research proved that ASCs can multiply and differentiate into neuronal cells. If they are grafted into nerve defects, the grafted cells are differ entiated into supportive cells such as Schwann's cells and thus contribute to nerve regeneration. Accordingly, the use of adipose tissue obtained easily without the limitation of donor site can be greatly helpful in treating peripheral nerve defects.