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Backgroud Although the scallop sign is considered the most important risk factor for extensor tendon ruptures (ETRs) in patients with osteoarthritis of the distal radioulnar joint (DRUJ), previous reports provide a limited understanding of the changes at DRUJ, as risk factors were examined in plain radiographs of the wrist. The aim of this study was to assess the changes of DRUJ using axial images of computed tomography (CT) in patients with DRUJ osteoarthritis and associated ETRs and to evaluate the relationship between the changes of DRUJ and ETRs. Methods Twelve patients with ETRs due to osteoarthritis of the DRUJ were enrolled. The changes of DRUJ were examined on axial images of CT and the following 8 parameters were measured: width of radius, anteroposterior (AP) length of radius, width of sigmoid notch (SN), AP length of SN, AP length of ulnar head, subluxation length of ulnar head, dorsal inclination of SN, and distance from Lister's tubercle to SN. Radiological parameters of the DRUJ were measured in 60 control wrists without trauma or osteoarthritis, and the patient and control groups were statistically compared. Results Statistically significant differences were observed between the patient and control groups in all the radiological parameters except for the AP length of SN and AP length of ulnar head. The width of radius, AP length of radius, width of SN, subluxation length of ulnar head, and dorsal inclination of SN were greater and the distance from Lister's tubercle to SN was smaller in the patient group than in the control group. The width of SN, dorsal inclination of SN, and distance from Lister's tubercle to SN were statistically significant risk factors among the 8 parameters. Conclusions ETRs due to osteoarthritis of the DRUJ was related to the changes of DRUJ, especially the changes around SN of the distal radius. In addition to the existing risk factors, a decreased distance from Lister's tubercle to SN and increased dorsal inclination of SN were identified as new risk factors. Axial images of CT were effective to evaluate degenerative changes at the DRUJ.

Background: Little is known about capsule endoscopy (CE) findings in patients with intestinal tu berculosis who exhibit small bowel lesions. The aim of the present study was to distinguish be tween Crohn’s disease (CD) and intestinal tuberculosis based on CE findings. Methods: Findings from 55 patients, who underwent CE using PillCam SB CE (Given Imaging, Yo qneam, Israel) between February 2003 and June 2015, were retrospectively analyzed. Results: CE revealed small bowel lesions in 35 of the 55 patients: 19 with CD and 16 with intes tinal tuberculosis. The median age at diagnosis for patients with CD was 26 years and 36 years for those with intestinal tuberculosis. On CE, three parameters, ≥10 ulcers, >3 involved segments and aphthous ulcers, were more common in patients with CD than in those intestinal tuberculo sis. Cobblestoning was observed in five patients with CD and in none with intestinal tuberculosis. The authors hypothesized that a diagnosis of small bowel CD could be made when the number of parameters in CD patients was higher than that for intestinal tuberculosis. The authors calculated that the diagnosis of either CD or intestinal tuberculosis would have been made in 34 of the 35 patients (97%). Conclusion: The number of ulcers and involved segments, and the presence of aphthous ulcers, were significantly higher and more common, respectively, in patients with CD than in those with intestinal tuberculosis. Cobblestoning in the small bowel may highly favor a diagnosis of CD on CE.

We investigated the inhibitory effect of active hexose correlated compound (AHCC) on muscle atrophy in hindlimb-suspended rats. Twenty-four six-week-old male Sprague-Dawley rats were randomly divided into three groups: the control sedentary group (CS, n = 8), the hindlimb-suspended group (HS, n = 8), and the hindlimb-suspended and AHCC-supplemented group (HSA, n = 8). Hindlimb suspension and AHCC supplementation were performed for two weeks. The HSA group was treated with AHCC (1 g/1 kg of body weight (BW)) orally in 0.3 mL of PBS solution, while the HS group received the vehicle (PBS solution) only. After two weeks, the cross-sectional area (CSA) of the HS and HSA groups decreased by approximately 36% (p < 0.05) and 19%, respectively, compared to the CS group. In addition, myonuclear numbers of the HS and HSA groups and the extensor digitorum longus (EDL) muscle weight of the HS group decreased 30% (p < 0.05) and 18%, respectively, compared to the CS group. AHCC supplementation increased the phosphorylation of pAkt/Akt in the HSA group compared to the HS group (p < 0.05). Furthermore, Fbx32 and MuRF1 protein expression in the HSA group recovered to the level of the CS group. Based on these results, AHCC supplementation may have a positive role in the prevention of muscle atrophy via Akt activation in hindlimb-suspended rats.

This study aimed to determine which preoperative factors affect the postoperative change in the joint line convergence angle (JLCA) by preoperatively quantifying soft tissue laxity. Thirty-four patients who underwent medial open-wedge high tibial osteotomy (HTO) with a navigation were analysed. The JLCA change after HTO was calculated using standing long-bone anteroposterior radiographs taken preoperatively and 6 months postoperatively. Latent soft tissue laxity was defined as the amount of soft tissue that can be extended to valgus or varus from the weight-bearing position, and calculated by subtracting the JLCA on weight-bearing standing radiographs from that on stress radiographs. Multiple linear regression was performed to determine the preoperative factors that statistically correlated with the postoperative JLCA change. In multiple linear regression, JLCA change had a statistically significant correlation with latent medial laxity (R = 0.6) and a statistically borderline significant correlation with correction angle (R = 0.2). These imply that the postoperative JLCA change increased by 0.6° per 1° increase in latent medial laxity, and increased by 0.2° per 1° increase in correction angle. Latent medial laxity was the most crucial factor associated with postoperative JLCA changes. The JLCA change could be larger in patients with large latent medial laxity or severe varus deformity requiring a large correction, which could lead to unexpected overcorrection in HTO. Postoperative JLCA change should be considered in preoperative surgical planning. Target point shifting within the hypomochlion point could be a strategy to prevent overcorrection, especially in patients with large latent medial laxity. Level IV.

Extensor tendon rupture of the finger is a very rare complication of Kienböck’s disease. However, advanced Kienböck’s disease can cause an attritional rupture of extensor tendons due to displaced lunate fragment. An extensor tendon of the thumb is frequently damaged in the distal radial fracture, and an extensor tendon of the fifth finger is mainly ruptured in arthritis of distal radio-ulnar joint. On the other hand, the extensor tendons of the 2nd, 3rd and 4th fingers are usually ruptured in advanced Kienböck’s disease. We report two elderly patients diagnosed with advanced Kienböck’s disease after non-traumatic rupture of extensor tendon of the fingers. Since the extensor tendon rupture in Kienböck’s disease present as a loss of active extension of metacarpophalangeal joint in the central fingers, these patients should undergo imaging of the wrist joints to ascertain concomitant Kienböck’s disease.

Cuttlefish bone is a calcium carbonate composite with a homogeneous, interconnected porous structure. The aim of this study was to investigate the potentiality of surface modified unprocessed cuttlefish bone as a bone substitute. For this purpose, the surface of unprocessed cuttlefish bone (CB) was modified with hydroxyapatite (HA) and collagen (COL). The internal lamellar matrix of cuttlefish bone was cut into small uniform blocks and kept submerged into simulated body fluid (SBF) to form a hydroxyapatite layer on the surface (CB-HA scaffold). Then it was coated with collagen using the freeze drying method (CB-HA-COL scaffold). Scaffolds were characterized morphologically. Biocompatibility of the scaffolds was tested using rat bone marrow mesenchymal stem cells (RBMSCs). CB-HA-COL scaffold exhibited higher cell proliferation rate and alkaline phosphatase activity of RBMSCs in vitro conditions. These findings suggest that surface modified unprocessed cuttlefish bone can be beneficial for bone tissue engineering.

Polyvinyl alcohol gelatin hydrogels were fabricated using genipin as a crosslinking agent for bone regeneration application. Optimized formulation of PVA-GE hydrogel was fabricated using genipin as crosslinking agent. Characterizations such as FTIR, morphology, porosity, pore size, degradation and swelling rate were investigated. Bone regeneration potential of optimized genipin cross-linked polyvinyl alcohol-gelatin (PVA20) hydrogels was assessed by implanting in rabbit’s femur defect for 1, 5 and 15 weeks period. Results showed interconnected porosity as observed in scanning electron microscopy and successful crosslinking as confirmed by FTIR analysis. Increased porosity (92% ± 2.46%) and pore size distribution (100 - 200 μm) were also observed as well as decrease in swelling rate (426% ± 10.50%). Bone formation was evident in micro-CT after 5 and 15 days of in vivo implantation period. Micro-CT analysis showed 32.67% increased bone formation of PVA-GE hydrogel defect compared with negative control after 15 weeks of in-vivo implantation. Histological analyses showed no inflammatory reaction post implantation and increase in cell matrix formation after 5 and 15 weeks. The combined physical and chemical method of crosslinking promises improved mechanical properties of PVA-GE hydrogel making it a potential scaffold for bone tissue engineering applications.

A new hydrogel scaffold, containing both osteoconductive and osteoinductive properties, was developed for enhanced bone regeneration. Simvastatin loaded Gelatin-nanofibrillar cellulose-β tricalcium phosphate (GNTS) hydrogel scaffold was prepared by the freeze-drying method. Gelatin and β tricalcium phosphate were added to the scaffold to provide osteoconductivity. As an osteoinductive molecule, simvastatin was entrapped in the scaffold. Nanofibrillar cellulose contributed to the slower degradation rate of the scaffold, which in turn favored the sustainable release of simvastatin. Three different concentrations of simvastatin (S) (0.25, 0.5 and 1 μM), were loaded in these scaffolds to make GNTS.25, GNTS.5 and GNTS1 scaffolds, respectively. Simvastatin was released from the scaffolds gradually and constantly for up to 30 days, with an initial burst release. Cell proliferation on the scaffolds was not perturbed up to 0.5 μM simvastatin. Quantitative analysis (PT-PCR) showed that alkaline phosphatase (ALP), osteopontin (OPN) and osteocalcin (OCN) mRNAs, responsible for the osteoblastic differentiation of rat bone marrow mesenchymal stem cells (RBMSCs), were expressed in higher amounts in GNTS.5 scaffold than in other scaffolds. Scaffolds were implanted in critical-sized rat calvarial defects for 4 and 8 weeks. Micro-CT and histological analysis revealed that greater extent of bone formation, with higher amount of collagen matrix deposition, was observed in GNTS.5 scaffold at both time points. These results suggest that GNTS.5 scaffold, along with its osteoconductive architecture, releases the optimum concentration of simvastatin to enhance osteogenesis.

Bone regeneration is a coordinated process mainly regulated by multiple growth factors. Vascular endothelial growth factor (VEGF) stimulates angiogenesis and bone morphogenetic proteins (BMPs) induce osteogenesis during bone healing process. The aim of this study was to investigate how these growth factors released locally and sustainably from nano-cellulose (NC) simultaneously effect bone formation. A biphasic calcium phosphate (BCP)-NC-BMP2-VEGF (BNBV) scaffold was fabricated for this purpose. The sponge BCP scaffold was prepared by replica method and then loaded with 0.5% NC containing BMP2-VEGF. Growth factors were released from NC in a sustainable manner from 1 to 30 days. BNBV scaffolds showed higher cell attachment and proliferation behavior than the other scaffolds loaded with single growth factors. Bare BCP scaffolds and BNBV scaffolds seeded with rat bone marrow mesenchymal stem cells were implanted ectopically and orthotopically in nude mice for 4 weeks. No typical bone formation was exhibited in BNBV scaffolds in ectopic sites. BMP2 and VEGF showed positive effects on new bone formation in BNBV scaffolds, with and without seeded stem cells, in the orthotopic defects. This study demonstrated that the BNBV scaffold could be beneficial for improved bone regeneration. Stem cell incorporation into this scaffold could further enhance the bone healing process.

A composite scaffold of gelatin (Gel)-pectin (Pec)-biphasic calcium phosphate (BCP) was fabricated for the successful delivery of growth factors. Bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) were coated on the Gel-Pec-BCP surface to investigate of effect of them on bone healing. Surface morphology was investigated by scanning electron microscopy, and BCP dispersion in the hydrogel scaffolds was measured by energy dispersive X-ray spectroscopy. The results obtained from Fourier transform infrared spectroscopy showed that BMP-2 and VEGF were successfully coated on Gel-Pec-BCP hydrogel scaffolds. MC3T3-E1 preosteoblasts were cultivated on the scaffolds to investigate the effect of BMP-2 and VEGF on cell viability and proliferation. VEGF and BMP-2 loaded on Gel-Pec-BCP scaffold facilitated increased cell spreading and proliferation compared to Gel-Pec-BCP scaffolds. In vivo, bone formation was examined using rat models. Bone formation was observed in Gel-Pec-BCP/BMP-2 and Gel-Pec-BCP/VEGF scaffolds within 4 weeks, and was greatest with Gel-Pec-BCP/BMP-2 scaffolds. In vitro and in vivo results suggest that Gel-Pec-BCP/BMP-2 and Gel-Pec-BCP/VEGF scaffolds could enhance bone regeneration.

The increasing interest in chitosan-based biomaterials stems from its desirable physicochemical properties. Although calcium phosphates have been mixed with chitosan to form injectable scaffolds, its application for bone tissue engineering has been limited and is still being explored to improve its clinical translatability. We report a biocomposite comprised of preformed chitosan cryogel with dispersed biphasic calcium phosphate that can flow under moderate pressure allowing passage through a small gauge needle, while maintaining sufficient integrity and strength during injection for gel recovery. The formed samples were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction analysis and protein adsorption measurements. Composite with 1% w/v biphasic calcium phosphate (CSG1) resulted in a homogeneous and rigid final structure. Injectable composite cryogel CSG1 (2.5 ± 0.2 N, 23G needle) exhibited good protein adsorption and biocompatibility. Results of subcutaneous implantation in rats reveal relatively high presence of polymorphonuclear cells but with no fibrous encapsulation with the composites, allowing further infiltration of cells within the sample implants. The biocomposite system presents a less-invasive delivery of bone filling material for stabilizing pathologic fractures.

Blood serum contains various kinds of proteins which are necessary for tissue repair and regeneration process. Defect healing of fractured bone is initiated by the influx of blood and then clot formation. Thus, proteins in serum may have the ability to stimulate the bone regeneration process. In this work, we investigated the fabrication of serum-loaded oxidized alginate–gelatin–biphasic calcium phosphate hydrogels with various contents of blood serum (0%, 5%, 10%, and 15% in % v/v) to evaluate the stimulatory effect of serum proteins on bone regeneration. This system was also evaluated for rat bone marrow–derived stem cell delivery to get faster bone healing. The serum-loaded oxidized alginate–gelatin–biphasic calcium phosphate hydrogel samples were characterized by scanning electron microscopy, porosity meter, X-ray diffraction, and Fourier transform infrared for morphology and phase characterization together with their mechanical behavior. Protein release behavior, degradation, and swelling of the samples were studied. In vitro study was performed using bone marrow–derived stem cells to study cell attachment, viability, and proliferation. These studies revealed the best cell attachment and highest proliferation for 5% serum-loaded oxidized alginate–gelatin–biphasic calcium phosphate hydrogel scaffold. This composition also showed the ability to deliver stem cell in the defect zone which significantly improved the bone regeneration extent found in the in vivo animal model. In vivo study revealed that for the critical 5-mm calvarial defect into nude mouse skull, the 5% serum-loaded sample with bone marrow–derived stem cells shows the best bone regeneration potential.

This study aims to demonstrate the morphology and in vitro biocompatibility of neat and surface-modified hydroxyapatite sponge scaffold (SM-HASS) which was fabricated using a sponge replica method, and compared with the commercially available demineralized freeze-dried bone allograft (DFDBA). Surface-modifications were done by coating the surface area of the neat hydroxyapatite sponge scaffold (HASS) with either gelatin alone (HASS/G) or gelatin and BMP-2 growth factor (HASS/G+B). Scanning electron microscope (SEM), Fourier transform infrared (FTIR), porosity, pore size distribution, and compressive strength analyses showed that the addition of gelatin in HASS/G produced a morphologically and structurally similar scaffold to that of the allograft. The addition of BMP-2 improved the biocompatibility of the HASS/G+B in vitro using MC3T3-E1 cells which showed better cell viability, proliferation, and cell adhesion than on the allograft. Therefore, hydroxyapatite scaffold coated with gelatin polymer and gelatin with BMP-2 growth factor showed comparable performance against commercially available DFDBA from cadaver with regards to structure and in vitro biocompatibility.

In this study, the optimized formulations of polycaprolactone (PCL) combined with poly(lactic-co-glycolic acid) (PLGA), gelatin (GEL), and biphasic calcium phosphate (BCP) were analyzed in terms of cytocompatibility with bone-related cells, hemocompatibility, and in vivo bone-regenerating capacity to determine their potentials for bone tissue regeneration. Fiber morphology of PCL/GEL and PCL/BCP electrospun mats considerably differs from that of the PCL membrane. Based on the contact angle analyses, the addition of GEL and PLGA was shown to reduce the hydrophobicity of these membranes. The assessment of in vitro cytocompatibility using MC3T3-E1 cells indicated that all of the membranes were suitable for pre-osteoblast proliferation and adhesion, with PCL/BCP having a significantly higher reading after seven days of incubation. The results of the in vitro hemocompatibility of the different fibrous scaffolds suggest that coagulation and platelet adhesion were higher for hydrophobic membranes (PCL and PCL/PLGA), while hemolysis can be associated with fiber morphology. The potential of the membranes for bone regeneration was determined by analyzing the microCT data and tissue sections of samples implanted in 5 mm sized defects (one and two months). Although all of the membranes were suitable for pre-osteoblast proliferation, in vivo bone regeneration after two months was found to be significantly higher in PCL/BCP (p

A common and prevailing complication for patients with abdominal surgery is the peritoneal adhesion that follows during the post-operative recovery period. Biodegradable polymers have been suggested as a barrier to prevent the peritoneal adhesion. In this work, as a preventive method, PVA/Gelatin hydrogel-based membrane was investigated with various combinations of PVA and gelatin (50/50, 30/70/, and 10/90). Membranes were made by casting method using hot PVA-gelatin solution and the gelatin was cross-linked by exposing UV irradiation for 5 days to render stability of the produced sheathed form in the physiological environment. Physical crosslinking was chosen to avoid the problems of potential cytotoxic effect of chemical crosslinking. Their materials characterization and mechanical properties were evaluated by SEM surface characterization, hydrophilicity, biodegradation rate, and so forth. Cytocompatibility was observed by in vitro experiments with cell proliferation using confocal laser scanning microscopy and the MTT assay by L-929 mouse fibroblast cells. The fabricated PVA/Gel membranes were implanted between artificially defected cecum and peritoneal wall in rats and were sacrificed after 1 and 2 weeks post-operative to compare their tissue adhesion extents with that of control group where the defected surface was not separated by PVA/Gel membrane. The PVA/Gel membrane (10/90) significantly reduced the adhesion extent and showed to be a potential candidate for the anti-adhesion application.

The main objective of this study was to determine the central mechanisms involved in suppression of thermal sweating after seasonal acclimatization (SA) during passive heating (immersing the legs in 43 °C hot water for 30 min). Testing was performed in July (before-SA) and August (after-SA) [25.2±2.2 °C, 73.9±10.3% relative humidity (RH), Cheonan (Chungnam,126° 52′N, 33.38′E), in the Republic of Korea. All experiments were carried out in an automated climatic chamber (25.0±0.5 °C and RH 60.0±3.00%). Twelve healthy men (height, 174.6±5.40 cm; weight, 65.4±5.71 kg; age, 22.7±2.90 yr) participated. The local sweat onset time was delayed in the after-SA compared to that in the before-SA (p

A biodegradable fibrous tube was fabricated by electrospinning method using a combination of Poly(lactic-co-glycolic acid) (PLGA) and gelatin dissolved in trifluoroethanol (TFE). Different ratios of the two polymers (PLGA/Gelatin: 1/9, 3/7, 5/5) were used for electrospinning to determine the optimum condition appropriate for intestinal stent application. Fiber morphology was visualized and analyzed using a scanning electron microscope (SEM). Characterizations of physical properties were done according to its tensile strength, surface hydrophilicity, swelling ability, and biodegradability. Biocompatibility of the scaffolds was investigated in vitro using IEC-18 (Rat intestinal epithelial cell). Cell proliferation was quantified using MTT assay and cell adhesion behavior was visualized by SEM and confocal laser scanning microscope. PLGA/Gelatin (5/5) was determined to have adequate material properties and sufficient in vitro biocompatibility. This was then implanted in a male Sprague-Dawley rat for 14 days to determine in vivo behavior of the sample. Histological examination on the intestinal tissue surrounding the graft showed normal morphology comparable to non-implanted intestine. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

In this work, we fabricated injectable bone substitutes modified with the addition of bioactive glass powders synthesized via ultrasonic energy-assisted hydrothermal method to the calcium phosphate-based bone cement to improve its biocompatibility. The injectable bone substitutes was initially composed of a powder component (tetracalcium phosphate, dicalcium phosphate dihydrate and calcium sulfate dehydrate) and a liquid component (citric acid, chitosan and hydroxyl-propyl-methyl-cellulose) upon which various concentrations of bioactive glass were added: 0%, 10%, 20% and 30%. Setting time and compressive strength of the injectable bone substitutes were evaluated and observed to improve with the increase of bioactive glass content. Surface morphologies were observed via scanning electron microscope before and after submersion of the samples to simulated body fluid and increase in apatite formation was detected using x-ray diffraction machine. In vitro biocompatibility of the injectable bone substitutes was observed to improve with the addition of bioactive glass as the proliferation/adhesion behavior of cells on the material increased. Human gene markers were successfully expressed using real time-polymerase chain reaction and the samples were found to promote cell viability and be more biocompatible as the concentration of bioactive glass increases. In vivo biocompatibility of the samples containing 0% and 30% bioactive glass were evaluated using Micro-CT and histological staining after 3 months of implantation in male rabbits’ femurs. No inflammatory reaction was observed and significant bone formation was promoted by the addition of bioactive glass to the injectable bone substitute system.

In this study, hyaluronic acid–gelatin (HyA–Gel) scaffolds were prepared with HyA:Gel ratios of 15:85, 50:50, and 85:15 with the goal of obtaining a porous biocompatible scaffold for bone tissue engineering applications. Scanning electron microscopy and Fourier-transform infrared spectroscopy were done to characterize the morphological orientations of the scaffolds. The biocomposite structure was highly porous and the pores in the scaffolds were interconnected. The compressive strength of the scaffold was 7.39 ± 0.2 MPa for the HyA–Gel when fabricated at a ratio of 15:85. To assess the biocompatibility and cell behavior on the HyA–Gel biocomposite, the proliferation of MG-63 osteoblast cell on the scaffolds was examined using the MTT assay, optical microscopy, and confocal microscopy. Collagen type I and osteopontin expression of cells cultured on the scaffolds were examined using immunoblotting. The scaffolds fabricated with a 15:85—HyA:Gel ratio showed excellent biocompatibility, good mechanical properties, and high porosity, which suggest that the highly porous scaffold holds great promise for use in bone tissue engineering applications.

Microparticles formulated from poly (D,L-lactic-co-glycolide) (PLGA), a biodegradable polymer, have been investigated extensively as a drug delivery system. In this study, solid tiny PLGA microspheres were fabricated using the electrospraying method. PLGA polymer was dissolved in dichloromethane (DCM), and the solution was electrosprayed. The electrospraying conditions were adjusted so that the stream ejected from the needle was divided into spheres instead of continuous fibers or irregular-shaped particles. Several experiments were carried out using the PLGA-DCM source solution with different amounts of simvastatin (SIM), a drug that enhances bone regeneration, to understand this drug delivery system. The surface morphology and microstructure of the microspheres formed were characterized by scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and differential scanning calorimetry. The in vitro experiments on drug loading and drug release behavior of the microspheres suggested a drug encapsulation efficacy >90%. The drug was continuously released from the microspheres for >3 weeks. Other experiments, such as MTT, cell attachment and proliferation and reverse transcription-polymerase chain reaction showed good biocompatibility of the electrosprayed PLGA microspheres, which increased in the presence of SIM. Thus, electrosprayed PLGA microspheres have potential as a drug delivery system and application in bone tissue engineering.

We developed a continuously porous scaffold with laminated matrix and bone-like microstructure by a multi-pass extrusion process. In this scaffold, tetragonal ZrO2, biphasic calcium phosphate and poly-caprolactone layers were arranged in a co-axially laminated unit cell with a channel in the center. The entire matrix phase had a laminated microstructure of alternate lamina of tetragonal ZrO2, biphasic calcium phosphate and poly-caprolactone—biphasic calcium phosphate with optimized designed thickness and channeled porosity. Each of the continuous pores was coaxially encircled by the poly-caprolactone—biphasic calcium phosphate layer, biphasic calcium phosphate layer and finally tetragonal ZrO2 layer, one after the other. Before extrusion, 5 vol% graphite powder was mixed with tetragonal ZrO2 to ensure pores in the outer layer and connectivity among the lamellas. The design strategy is aimed to incorporate a lamellar microstructure like the natural bone in the macro-scaled ceramic body to investigate the strengthening phenomenon and pave the way for fabricating complex microstructure of natural bone could be applied for whole bone replacement. The final fabricated scaffold had a compressive strength of 12.7 MPa and porosity of 78 vol% with excellent cell viability, cell attachment and osteocalcin and collagen expression from cultured MG63 cells on scaffold.

We assessed the effect of caffeine on sudomotor activity and sweating sensitivity during physical loading. Both physiological responses could occur due to energy expenditure. Subjects were 13 athletically trained males (22.1 ± 3.7 years old, 174.2 ± 5.4 cm tall, and weighing 70.9 ± 4.6 kg, with maximal oxygen consumption [VO(2)max] of 53.6 ± 4.4 mL/kg/minute). The study involved a within-subject, random, crossover design. Tests were performed following the ingestion of 3 mg/kg caffeine. The physical loading involved running for 30 minutes at 60% VO(2)max (24.0 ± 0.5°C, 40 ± 3.0% relative humidity). Tympanic temperature (TYMP) was significantly higher in the caffeine-consuming group (Caffe-I) at pre-exercise (40 minutes after caffeine intake and immediately before running) (P

To improve the naval ship acquisition process, systems engineering, modeling and simulation, etc. have been introduced, and there has been ongoing research on acquisition systems for effective support of it. However, due to characteristics of the naval ship acquisition process, development process mainly carried out at a shipyard such as basic design, detailed design, construction and test is difficult to integrate with the acquisition systems of IPT(Integrated Project Team). In addition, research aimed to improve this is rather lacking. In this paper, the naval ship product structure concept proposed in previous research was applied to the basic design system at shipyard, and basic research for expanding the coverage of naval ship acquisition systems to the basic design phase is performed. A data structure of modeling system appropriate to the basic design phase was proposed through research findings and the prototype system based on it was implemented.

This study investigated the effects of oligonol intake on cortisol, interleukin (IL)-1β, and IL-6 concentrations in the serum as well as body temperature after leg immersion into hot water. Thirteen healthy male volunteers participated in this study. Each subject received oligonol (100 mg) before leg immersion into hot water. Skin and tympanic temperatures were measured and mean body temperatures were calculated. Serum concentrations of cortisol, IL-1β, and IL-6 were measured during and after leg immersion. Individuals who received oligonol had significantly decreased cortisol concentrations and serum levels of IL-1β and IL-6 compared to ones who did not receive oligonol. In addition, skin, tympanic, and mean body temperatures of oligonol group were maintained at lower degree overall recovery period compared with placebo group. These results suggest that oral oligonol intake before hot water immersion had a significant effect on inhibition of pyrogenic cytokine response and thermal suppression in healthy young men.

Epidermal growth factor receptor (EGFR) is one of the most promising targets for cancer therapy. Here, we show the in vitro and in vivo anticancer effects and associated mechanisms of KO-202125, one of the synthesized aristolactam analogs, as a novel EGFR inhibitor, in EGFR-overexpressing cancer cell lines. KO-202125 showed more effective growth inhibition and apoptosis induction than gefitinib, a representative EGFR inhibitor, in various EGFR-overexpressing human cancers including estrogen receptor (ER)-negative MDA-MB-231 human breast cancer cells. Epidermal growth factor receptor phosphorylation at Tyr1068 was reduced and, consequently, the association of EGFR with p85 was decreased by KO-202125 treatment in MDA-MB-231 cell lines. This led to inactivation of the PI3K/Akt pathway, and consequently suppression of activation of the Wnt pathway and enhancement of the nuclear import of p27Kip1. KO-202125 treatment in nude mice injected with MDA-MB-231 cells showed inhibition of tumor growth without toxicity. Collectively, our results showed the possibility of KO-202125 as an effective therapy agent of EGFR-overexpressing cancer cells through reduced EGFR activity and downregulation of the Akt pathway.

The weakness of bone plate made up from metal alloys and almost ceramics as well as thermosetting polymers is non biodegradable or very slow biodegradable. Thermoplastic and elastomeric polymers are degradable with various rates. A composite consisted of these polymers could be adjusted for required biodegradable rate. Beside, the composites would overcome mechanical behavior requirements to become promising device in tissue engineering. To support this point, fine hydroxyapatite (HAp) particles were penetrated in the composite. A hybrid composite with polymer mixture with HAp was fabricated by electrospinning method. Poly methyl methacrylate (PMMA) is a thermoplastic polymer, it was demon- strated good biocompatibility. However, PMMA inhibited inappropriate degradable rate in prosthetic treatment. Polyvinyl alcohol (PVA) is an elastomeric polymer; it has good biocompatibility, and rapidly bioabsorbable. These polymers were sprayed by electrospinning machine to form mats. HAp, was synthesized by microwave assisted process, and the contents in the composites were 0%, 2%, 4% and 6% by weight. Warm-pressing process was applied to form bone plate from mats. In MTT assay, the composites were non-toxic and showed good biocompatibility.

Bioceramics based on calcium phosphate have been widely used due to their excellent biocompatibility and bioactivity as well as chemical composition. Sponge replica method has been developed because of its interconnected pores which are similar to cancellous bone. Porous Biphasic Calcium Phosphate (BCP) scaffold was fabricated with the synthesized powder by the replica method. BCP slurry was coated 3 times and then PU was burnt out at 800 °C. The scaffolds were prepared infiltrated with PCL slurry and sintering at 1200 °C for 3 hours to improve the compressive strength. Bending strength and relative density were measured. Microstructures of the composites were observed using SEM. The biocompatibility and one cell morphology of the fabricated porous body were investigated by MTT assay and SEM observation.

In this study, the bioactivity and biocompatibility of new calcium phosphate bone cements (CPC) using Hydroxy-propyl-methyl-Cellulose (HPMC) was evaluated to understand the effect of HPMC on bone-bonding apatite formation and biocompatibility. In vitro bioactivity was investigated by incubating the CPC samples containing different ratios of HPMC (0%, 2% and 4% HPMC) in simulated body fluid (SBF) for 2, 7, 14 and 28 days. The formation of bone like apatite was confirmed on CPC surfaces by SEM and XRD analysis. Higher HPMC content of CPC showed faster apatite deposition in SBF. A high Ca ion dissolution profile was also reported with an increase of pH in all samples in SBF. The apatite formation ability of these CPC samples was found to be dependent on both surface chemistry and immersion time in SBF. The In vitro cytotoxicity test showed that the CPC samples with 4% HPMC were fairly cytocompatible for fibroblast L-929 cells. SEM images showed that MG-63 cells were successfully attached to the CPC samples and well proliferated.

Electrospinning of polyvinyl alcohol (PVA), gelatin (GE), and a PVA/GE blend was conducted with the aim of fabricating biodegradable scaffolds for tissue engineering. The process parameters including the concentration of GE in PVA/GE blends, electrical field, and tip-to-collector distance (TCD) were investigated. Electrospinning processes were conducted at three different GE concentrations (PVA/GE = 2/8, 6/4, and 8/2), and the voltage and TCD were varied from 18 to 24 kV and 7 to 20 cm, respectively. The average diameter of the electrospun PVA, GE, and PVA/GE blend fibers ranged from 50 to 150 nm. The TCD had significant effects on the average diameter of the PVA/GE nanofiber, while changes in the voltage did not significantly affect the diameter of the PVA/GE nanofiber. The miscibility of the PVA/GE blend fibers was examined by differential scanning calorimetry, and X-ray diffraction was used to determine the crystallinity of the membrane. Tensile strength was measured to evaluate the physical properties of the membrane. Based on the combined results of this study, the PVA/GE membrane holds great promise for use in tissue engineering applications, especially in bone or drug delivery systems.

This study measured caffeine-induced changes in activated sweat gland density (ASGD) and fat oxidation using a randomized crossover design with 10 healthy volunteers given caffeine (Caffe-I, 3 mg/kg ingested 30 min before experiment) and non-caffeine (No-Caff). Subjects were 173.0±3.2 cm in height, 72.5±4.3 kg in weight, and 21.5±2.5 years in age. All experiments were performed in an automated climate chamber (24.0±0.5°C, relative humidity 50±3%, air velocity less than 1 m/sec) between 2–5 p.m. The ASGD on the chest, upper arm, upper back, and lower back were measured (after 30 min running at 60% VO2max), and blood samples were taken (at 40 min before, immediately before and after 30 min running). Activated sweat gland density levels were higher in Caffe-I (Chest p

This study investigated the effects of Oligonol intake on cortisol, interleukin (IL)-1beta, and IL-6 concentrations in the serum at rest and after physical exercise loading. Nineteen healthy sedentary male volunteers participated in this study. The physical characteristics of the subjects were: a mean height of 174.2 +/- 2.7 cm, a mean weight of 74.8 +/- 3.6 kg and a mean age of 22.8 +/- 1.3 years. Each subject received 0.5 L water with Oligonol (100 mg/day) (n = 10) or a placebo (n = 9) daily for four weeks. The body composition, the white blood cell (WBC) and differential counts as well as the serum cortisol, IL-1beta, and IL-6 concentrations were measured before and after Oligonol intake. The cortisol concentration and serum levels of IL-1beta and IL-6 after Oligonol intake were significantly decreased compared to before treatment (P0.01, respectively). In addition, the rate of increase of these factors after exercise was decreased compared to the placebo group. There was no change in the WBC and differential cell counts. These results suggest that oral Oligonol intake for four weeks had a significant effect on inhibition of inflammatory markers in healthy young men.

This study investigated the anti-inflammatory effects of Pellinus linteus (PL) extract supplementation in healthy young men. The subjects were 18 healthy young males 20 years of age that were given 1.5 L of 0.12% PL extract orally (n=8) or a placebo (control group, n=10) daily for 4 weeks. The body composition, the white blood cell (WBC) count and differential as well as the serum cortisol, interleukin (IL)-1β, and IL-6 concentrations were measured before and after the supplementation. Serum concentrations of cortisol and IL-1β at rest after oral supplementation were significantly decreased compared to before treatment (p

Calcium phosphate bone substitutes are widely used for providing support for the in-growth of hard tissue in various medical applications (e.g., dental, orthopedic). Recently, research involving bone substitutes with interconnected open pore structures has focused on improving the mechanical properties of the substitutes and modifying their surfaces with proteins (e.g., collagen, bone morphogenetic protein) to induce early bone formation. In particular, it is highly desirable to develop a functional gradient-structured bone substitute that has the potential to control the bioresoption rate. A porous BCP scaffold was fabricated by the sponge replica method using a PU sponge. The sponge was dip coated three times followed by oven drying, burning out, and microwave sintering. Several approaches were used to fabricate a functional gradient scaffold. TCP was synthesized using the sol-gel process, and it infiltrated into the pore channel that formed after the burning out of the PU sponge. X-ray diffraction analysis characterized the phase identification of the BCP scaffold. Microstructures of the composites were observed using scanning electron microscopy.

Granular shape biphasic calcium phosphate (BCP) bone grafts with and without doping of silicon cations were evaluated in regards to biocompatibility and MG-63 cellular response. To do this we studied Cellular cytotoxicity, cellular adhesion and spreading behavior and cellular differentiation with alizarin red S staining. Gene expression in MG-63 cells on the implanted bone substitutes was also examined at different time points using RT-PCR. In comparison, the Si-doped BCP granule showed more cellular viability than the BCP granule without doping in MTT assay. Moreover, cell proliferation was much higher when Si doping was employed. The cells grown on the silicon-doped BCP substitutes had more active filopodial growth with cytoplasmic webbing that proceeded to the flattening stage, which was indicative of well cellular adhesion. When these cells were exposed to Si-doped BCP granules for 14 days, well differentiated MG-63 cells were observed. Osteonectin and osteopontin genes were highly expressed in the late stage of differentiation (14 days), whereas collagen type I mRNA were found to be highly expressed during the early stage (day 3). These combined results of this study demonstrate that silicon-doped BCP enhanced osteoblast attachment/spreading, proliferation, differentiation and gene expression.

Background The sagittal alignment of the spine and pelvis is not only closely related to the overall posture of the body but also to the evaluation and treatment of spine disease. In the last few years, the EOS imaging system, a new low-dose radiation X-ray device, became available for sagittal alignment assessment. However, there has been little research on the reliability of EOS. The purpose of this study was to evaluate the intrarater and interrater reliability of EOS for the sagittal alignment assessment of the spine and pelvis. Methods Records of 46 patients were selected from the EOS recording system between November 2016 and April 2017. The exclusion criteria were congenital spinal anomaly and deformity, and previous history of spine and pelvis operation. Sagittal parameters of the spine and pelvis were measured by three examiners three times each using both manual and EOS methods. Means comparison t-test, Pearson bivariate correlation analysis, and reliability analysis by intraclass correlation coefficients (ICCs) for intrarater and interrater reliability were performed using R package "irr." Results We found excellent intrarater and interrater reliability of EOS measurements. For intrarater reliability, the ICC ranged from 0.898 to 0.982. For interrater reliability, the ICC ranged from 0.794 to 0.837. We used a paired t-test to compare the values measured by manual and EOS methods: there was no statistically significant difference between the two methods. Correlation analysis also showed a statistically significant positive correlation. Conclusions EOS showed excellent reliability for assessment of the sagittal alignment of the spine and pelvis.

Natives of the tropics are able to tolerate high ambient temperatures. This results from their long-term residence in hot and often humid tropical climates. This study was designed to compare the peripheral mechanisms of thermal sweating in tropical natives with that of their temperate counterparts. Fifty-five healthy male subjects including 20 native Koreans who live in the temperate Korean climate (Temperate-N) and 35 native tropical Malaysian men that have lived all of their lives in Malaysia (Tropical-N) were enrolled in this study after providing written informed consent to participate. Quantitative sudomotor axon reflex testing after iontophoresis (2 mA for 5 min) with 10% acetylcholine (ACh) was used to determine directly activated (DIR) and axon reflex-mediated (AXR) sweating during ACh iontophoresis. The sweat rate, activated sweat gland density, sweat gland output per single gland activated, and oral and skin temperature changes were measured. The sweat onset time of AXR (nicotinic-receptor-mediated) was 56 s shorter in the Temperate-N than in the Tropical-N subjects (P0.0001). The nicotinic-receptor-mediated sweating activity AXR (1), and the muscarinic-receptor-mediated sweating activity DIR, in terms of sweat volume, were 103% and 59% higher in the Temperate-N compared to the Tropical-N subjects (P0.0001). The Temperate-N group also had a 17.8% (P0.0001) higher active sweat gland density, 35.4% higher sweat output per gland, 0.24 degrees C higher resting oral temperature, and 0.62 degrees C higher resting forearm skin temperature compared to the Tropical-N subjects (P0.01). ACh iontophoresis did not influence oral temperature, but increased skin temperature near where the ACh was administered, in both groups. These results suggest that suppressed thermal sweating in the Tropical-N subjects was, at least in part, due to suppressed sweat gland sensitivity to ACh through both recruitment of active sweat glands and the sweat gland output per each gland. This physiological trait guarantees a more economical use of body fluids, thus ensuring more efficient protection against heat stress.

Various calcium phosphate bioceramics are distinguished by their excellent biocompatibility and osteoconductivity. Especially, the exceptional biodegradability of β-TCP makes it a bone graft substitute of choice in many clinical applications. The activation of osteoclasts, differentiated from macrophage precursor cells, trigger a cell-mediated resorption mechanism that renders β-TCP biodegradable. Based on this evidence, we studied the biodegradation process of granular-type β-TCP bone graft substitute through in vitro and in vivo studies. Raw 264.7 cells treated with RANKL and M-CSF differentiated into osteoclasts with macrophage-like properties, as observed with TRAP stain. These osteoclasts were cultured with β-TCP nano powders synthesized by microwaveassisted process. We confirmed the phagocytosis of osteoclasts by observing β-TCP particles in their phagosomes via electron microscopy. No damage to the osteoclasts during phagocytosis was observed, nor did the β-TCP powders show any sign of cytotoxicity. We also observed the histological changes in subcutaneous tissues of rats implanted with granule-type β-TCP synthesized by fibrous monolithic process. The β-TCP bone graft substitute was well surrounded with fibrous tissue, and 4 months after implantation, 60% of its mass had been biodegraded. Also, histological findings via H&E stain showed a higher level of infiltration of lymphocytes as well as macrophages around the granule-type β-TCP. From the results, we have concluded that macrophages play an important role in the biodegradation process of β-TCP bone graft substitutes.

Using poly-methyl methacrylate as a pore-forming agent, porous β-tricalcium phosphate (β-TCP)/t-ZrO2 composites were fabricated depending on the volume percentages (vol.%) of t-ZrO2 powder. In the porous sintered bodies, hybrid pores, about 20 and 200 μm in diameter, were homogenously dispersed in the β-TCP/t-ZrO2 matrix and showed good interconnection. On the other hand, β-TCP-(t-ZrO2)/polycaprolactone (PCL) composites were fabricated by the melt infiltration process using porous β-TCP/t-ZrO2 bodies. The relative density of the β-TCP-(t-ZrO2)/PCL composites increased as the vol.% of t-ZrO2 increased and its maximum value was about 98.6%. However, the hardness, bending strength and elastic modulus of β-TCP-(t-ZrO2)/PCL composites decreased due to the low densification of porous β-TCP/t-ZrO2 bodies as the volume percentages of t-ZrO2 content increased. The values (using 20 vol.% of t-ZrO2) were 11.4 Hv, 25.5 MPa and 17.2 GPa, respectively.

Recent studies showed that tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), as well as high-sensitive C-reactive protein (hsCRP) levels are predictive factors of cardiovascular risk. However, the effect of cardiac rehabilitation (CR) intervention in coronary artery disease (CAD) patients on these factors is not known. The aim of this study was to evaluate the effects of CR and exercise on hsCRP and inflammatory cytokine levels in patients with CAD after percutaneous coronary intervention (PCI). CAD patients who underwent PCI were divided into a CR and exercise group (CRE, n = 29) or a control group (CON, n = 10). CR and exercise consisted of 6 weeks supervised exercise training and 8 weeks home-based, self-managed exercise. Compared to pre-experimental levels, TNF-alpha (by 20.4%; p = 0.006) and IL-6 (by 49.0%; p < 0.0001), as well as hsCRP (by 59.4%; p < 0.0001), were markedly decreased after CR and exercise in CAD patients but not in control group, except for IL-6 (by 41.6%; p = 0.001). However, there was no significant alteration of adiposity-related variables such as BMI, percent body fat, and waist circumferences, in both groups. We suggest that CR and exercise in CAD patients after PCI induce significant reduction in hsCRP and inflammatory cytokines (TNF-alpha and IL-6), and marked increase in exercise tolerance and capacity.

Serological anlysis of recombinant cDNA expression libraries (SEREX) has led to identification of several categories of new antigens recognized by the immune system of cancer patients, which are referred to as the cancer immunome. We analyzed normal testis cDNA expression libraries with serumobtained from non-small lung cancer patient and isolated 40 distinct antigen designated KP-LuT-1 through KP-LuT-40. Among these antigens 20 antigens were previously identified by SEREX analysis of other tumor types, and 20 out of 40 antigens (50%) did not match entries in Cancer Immunome Database and were considered newly identified antigens. Sequencing analysis showed that the antigens comprised 26 functional known proteins and 14 noble/uncharacterized gene products. Of these, the hypothetical protein KP-LuT-6 was shown tissue-restricted. RT-PCR showed it to be expressed strongly only in normal testis. In addition to normal tissues-restricted expression, KP-LuT-6 mRNA was detected in lung tumor samples(3/10), stomach tumor samples(3/10), and breast tumor samples(1/5), whereas not detected in colon tumor samples(0/12). These data suggest that KP-LuT-6 is a cancer/testis (CT)-like antigen as a potential target for cancer immunotherapies.

Bone repair in the critical size defect zone using 3D hydrogel scaffold is still a challenge in tissue engineering field. A novel type of hydrogel scaffold combining ceramic and polymer materials, therefore, was fabricated to meet this challenge. In this study, oxidized alginate-gelatin-biphasic calcium phosphate (OxAlg-Gel-BCP) and spherical hydroxyapatite (HAp) granules encapsulated OxAlg-Gel-BCP hydrogel complex were fabricated using freeze-drying method. Detailed morphological and material characterizations of OxAlg-Gel-BCP hydrogel (OGB00), 25wt% and 35wt% granules encapsulated hydrogel (OGB25 and OGB35) were carried out for micro-structure, porosity, chemical constituents, and compressive stress analysis. Cell viability, cell attachment, proliferation and differentiation behavior of rat bone marrow-derived stem cell (BMSC) on OGB00, OGB25 and OGB35 scaffolds were confirmed by MTT assay, Live-Dead assay, and confocal imaging in vitro experiments. Finally, OGB00 and OGB25 hydrogel scaffolds were implanted in the critical size defect of rabbit femoral chondyle for 4 and 8 weeks. The micro-CT analysis and histological studies conducted by H&E and Masson's trichrome demonstrated that a significantly higher (***p

Tropical natives possess heat tolerance due to the ability to off-load endogenous and exogenous heat efficiently using a minimum amount of sweat. On the other hand, exposure of temperate natives to heat results in exaggerated production of sweat, of which part is lost by dripping and, thus, not available for evaporation. How sweating is modified in natives of temperate climate zones by prolonged residence in the tropics is not well-understood. The aim of this study was to investigate possible changes in the peripheral sweating mechanisms. Sweating responses to iontophoretically applied acetylcholine (ACh) were compared between Japanese subjects having either permanently resided in Japan (Japan resident Japanese, JRJ) or having stayed in the tropics for 2 years or longer (Tropics resident Japanese, TRJ). Quantitative sudomotor axon reflex tests by iontophoresis of ACh (10%, 2 mA for 5 min) were applied to determine directly activated (DIR) and axon reflex-mediated sweating during [AXR(1)] and after [AXR(2)] ACh iontophoresis. The sweat onset time of AXR(1) was 0.6 min shorter in JRJ than in TRJ (P