Zwitterionic polymer on silicone implants inhibits the bacteria-driven pathogenic mechanism and progress of breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) occurs in the capsule surrounding breast implants. Malignant transformation of T cells by bacteria-driven chronic inflammation may be underlying BIA-ALCL mechanism. Here, we covalently grafted 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymers on a silicone surface and examined its effects against BIA-ALCL pathogenesis. MPC grafting strongly inhibited the adhesion of bacteria and bacteria-causing inflammation. Additionally, cancer T cell proliferation and capsule-derived fibroblast-cancer cell communication were effectively inhibited by MPC grafting. We further demonstrated the effect of MPC against the immune responses causing BIA-ALCL around human silicone implants in micro-pigs. Finally, we generated a xenograft anaplastic T cell lymphoma mouse model around the silicone implants and demonstrated that MPC grafting could effectively inhibit the lymphoma progression. This study is the first to show that bacteria-driven induction and progression of BIA-ALCL can be effectively inhibited by surface modification of implants. STATEMENT OF SIGNIFICANCE: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a major concern in the field of plastic and reconstructive surgery. In this study, we demonstrate strong inhibitory effect of zwitterionic polymer grafting on BIA-ALCL pathogenesis and progression, induced by bacterial infection and inflammation, both in vitro and in vivo. This study provides a molecular basis for the development of novel breast implants that can prevent various potential complications such as excessive capsular contracture, breast implant illness, and BIA-ALCL incidence, as well as for expanding the biomedical applications of zwitterionic polymers.

A Method for Measuring the Surface Free Energy of Topical Semi-solid Dosage Forms.

Our aim was to determine the surface free energy (SFE) of semi-solid dosage forms (SSDFs) by establishing a reproducible method for measuring the contact angle of liquids to SSDFs. Four SSDFs were used: petrolatum, an oil/water (O/W) and a water/oil (W/O) cream, and an alcohol-based gel. The SSDFs were evenly spread on a glass slide, and the change in contact angle over time was measured by dropping water, glycerol, diiodomethane and n-hexadecane as the test liquids. Depending on the combination of test liquid and SSDF, the contact angle was either constant or decreased in an exponential manner. Contact angles may have decreased in an exponential manner because the reaction between the test liquid and the SSDF altered the interfacial tension between the two phases and changed the surface tension of the test liquid and the SFE of the SSDF. The contact angle of the test liquid to the SSDF could be determined reproducibly using the initial contact angle immediately after dropping the liquid on the SSDF as the contact angle before reaction. Using the obtained contact angles and the Owens-Wendt-Rabel-Kaelble equation, we calculated the SFE and its component for the SSDFs tested and found that the results reflect the physicochemical properties of SSDFs. Furthermore, the work of adhesion (WA) of the SSDF to Yucatan micropig skin was calculated using the SFE for the SSDFs. Interestingly, the WA values for all SSDFs tested were comparable.

Whole-genome resequencing analysis of 20 Micro-pigs.

BACKGROUND: Miniature pigs have been increasingly used as mammalian model animals for biomedical research because of their similarity to human beings in terms of their metabolic features and proportional organ sizes. However, despite their importance, there is a severe lack of genome-wide studies on miniature pigs. OBJECTIVE: In this study, we performed whole-genome sequencing analysis of 20 Micro-pigs obtained from Medi Kinetics to elucidate their genomic characteristics. RESULTS: Approximately 595 gigabase pairs (Gb) of sequence reads were generated to be mapped to the swine reference genome assembly (Sus scrofa 10.2); on average, the sequence reads covered 99.15% of the reference genome at an average of 9.6-fold coverage. We detected a total of 19,518,548 SNPs, of which 8.7% were found to be novel. With further annotation of all of the SNPs, we retrieved 144,507 nonsynonymous SNPs (nsSNPs); of these, 5968 were found in all 20 individuals used in this study. SIFT prediction for these SNPs identified that 812 nsSNPs in 402 genes were deleterious. Among these 402 genes, we identified some genes that could potentially affect traits of interest in Micro-pigs, such as RHEB and FRAS1. Furthermore, we performed runs of homozygosity analysis to locate potential selection signatures in the genome, detecting several loci that might be involved in phenotypic characteristics in Micro-pigs, such as MSTN, GDF5, and GDF11. CONCLUSION: In this study, we identified numerous nsSNPs that could be used as candidate genetic markers with involvement in traits of interest. Furthermore, we detected putative selection footprints that might be associated with recent selection applied to miniature pigs.

Age-related compositional and functional changes in micro-pig gut microbiome.

Age-related changes in human gut microbiota composition have been reported, and such changes might be influenced by the intake of nutrients or diets. To investigate the effects of aging on the gut microbiota independent of nutrient effects, we analyzed the gut microbiomes of 126 micro-pigs at a wide range of ages from newborns to 10 years old. The micro-pigs were reared in a constantly controlled environment. The diversity of the gut microbiome was found to continuously change with age. We also found associations between age and specific members and functions of the gut microbiome. Consistent with previous studies on the human gut microbiome, beneficial microbes including probiotic bacteria and short-chain fatty acid-producers decreased in older pigs, whereas Bacteroides increased with age. Based on the correlation network, Bacteroides seemed to have an important role in determining the relative abundances of other beneficial microbes. Our results suggest that maintaining beneficial gut microbes at a specific ratio corresponding to a certain age might contribute to a younger gut microbiome-age. Furthermore, due to similarities with the human system, micro-pigs are a useful animal model to elucidate the links between aging and the microbiome.

The Comparison of Surface Free Energy of Human, Yucatan Micropig, and Hairless Mouse Skins and Influence of Surfactant on Surface Free Energy of the Skin.

Surface free energy (SFE) is an important factor for evaluation of wettability or adhesion. Thus, the SFE of a Yucatan micropig (YMP) skin and a hairless mouse (HM) skin, which are commonly used in skin permeation studies instead of human skin, were compared with the human skin. Contact angles of water and 1-bromo naphthalene to skin were measured and the SFE was calculated using the Owens-Wendt equation. The SFE of the human abdominal skin was 40 mN/m and its polar component σsp was as low as 2 mN/m, which was similar to that of the low sebum skin reported previously. In the case of the YMP skin, σsp was high on the surface but similar to that obtained after the skin was tape-stripped twice. The HM skin showed similar SFE as that of the human skin. When the surfactant was applied on the skin, wiped, and dried, the remaining surfactant increased the SFE in σsp; however, the original SFE was obtained after rinsing with water. The YMP skin and HM skin is similar to the human abdominal skin with a low sebum level. Thus, they are also good skin models for studying wettability or adhesion of a substance.

Transcutaneous pneumatic injection of glucose solution: a morphometric evaluation of in vivo micropig skin and tissue-mimicking phantom.

BACKGROUND: Needle-free, transcutaneous pneumatic injection systems can be used to deliver therapeutic solutions to targeted layers of skin in a minimally invasive manner. METHODS: To evaluate jet infiltration patterns and tissue reactions, 5% isotonic and 20% hypertonic glucose solutions were pneumatically injected into in vivo micropig skin. Gelatin TM phantom was additionally prepared to analyze penetration and dispersion patterns for different experimental settings. RESULTS: As immediate tissue reactions in the in vivo micropig skin, distinct pneumatic injection injury zones (PIIZs) in the dermis, extending from the papillary dermis deep into the dermo-subcutaneous junction, were generated with the 5% and 20% glucose solutions and with pneumatic pressures of 4.64 and 5.7 bars, respectively. PIIZs markedly decreased in appearance at 1 day after treatment, accompanied by inflammatory cell infiltration, and disappeared at 7 days post-treatment with increased collagen and elastin production. In TM phantom study, the PIIZs created by 20% glucose mainly comprised a single, homogenous, round to oval zone, whereas those created by 5% glucose were irregular and multi-lobular. CONCLUSION: The present study suggests that transcutaneous pneumatic injection therapy may exert mechanical stimulatory effects, immediate tissue shrinkage via hypertonic solutions, and late tissue regeneration effects during wound healing.

Approach to Modeling, Therapy Evaluation, Drug Selection, and Biomarker Assessments for a Multicenter Pre-Clinical Drug Screening Consortium for Acute Therapies in Severe Traumatic Brain Injury: Operation Brain Trauma Therapy.

Traumatic brain injury (TBI) was the signature injury in both the Iraq and Afghan wars and the magnitude of its importance in the civilian setting is finally being recognized. Given the scope of the problem, new therapies are needed across the continuum of care. Few therapies have been shown to be successful. In severe TBI, current guidelines-based acute therapies are focused on the reduction of intracranial hypertension and optimization of cerebral perfusion. One factor considered important to the failure of drug development and translation in TBI relates to the recognition that TBI is extremely heterogeneous and presents with multiple phenotypes even within the category of severe injury. To address this possibility and attempt to bring the most promising therapies to clinical trials, we developed Operation Brain Trauma Therapy (OBTT), a multicenter, pre-clinical drug screening consortium for acute therapies in severe TBI. OBTT was developed to include a spectrum of established TBI models at experienced centers and assess the effect of promising therapies on both conventional outcomes and serum biomarker levels. In this review, we outline the approach to TBI modeling, evaluation of therapies, drug selection, and biomarker assessments for OBTT, and provide a framework for reports in this issue on the first five therapies evaluated by the consortium.

Simvastatin Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

Simvastatin, the fourth drug selected for testing by Operation Brain Trauma Therapy (OBTT), is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor used clinically to reduce serum cholesterol. In addition, simvastatin has demonstrated potent antineuroinflammatory and brain edema reducing effects and has shown promise in promoting functional recovery in pre-clinical models of traumatic brain injury (TBI). The purpose of this study was to assess the potential neuroprotective effects of oral administration of simvastatin on neurobehavioral, biomarker, and histopathological outcome measures compared across three pre-clinical TBI animal models. Adult male Sprague-Dawley rats were exposed to either moderate fluid percussion injury (FPI), controlled cortical impact injury (CCI), or penetrating ballistic-like brain injury (PBBI). Simvastatin (1 or 5 mg/kg) was delivered via oral gavage at 3 h post-injury and continued once daily out to 14 days post-injury. Results indicated an intermediate beneficial effect of simvastatin on motor performance on the gridwalk (FPI), balance beam (CCI), and rotarod tasks (PBBI). No significant therapeutic benefit was detected, however, on cognitive outcome across the OBTT TBI models. In fact, Morris water maze (MWM) performance was actually worsened by treatment in the FPI model and scored full negative points for low dose in the MWM latency and swim distance to locate the hidden platform. A detrimental effect on cortical tissue loss was also seen in the FPI model, and there were no benefits on histology across the other models. Simvastatin also produced negative effects on circulating glial fibrillary acidic protein biomarker outcomes that were evident in the FPI and PBBI models. Overall, the current findings do not support the beneficial effects of simvastatin administration over 2 weeks post-TBI using the oral route of administration and, as such, it will not be further pursued by OBTT.

Synthesis of Findings, Current Investigations, and Future Directions: Operation Brain Trauma Therapy.

Operation Brain Trauma Therapy (OBTT) is a fully operational, rigorous, and productive multicenter, pre-clinical drug and circulating biomarker screening consortium for the field of traumatic brain injury (TBI). In this article, we synthesize the findings from the first five therapies tested by OBTT and discuss both the current work that is ongoing and potential future directions. Based on the results generated from the first five therapies tested within the exacting approach used by OBTT, four (nicotinamide, erythropoietin, cyclosporine A, and simvastatin) performed below or well below what was expected based on the published literature. OBTT has identified, however, the early post-TBI administration of levetiracetam as a promising agent and has advanced it to a gyrencephalic large animal model--fluid percussion injury in micropigs. The sixth and seventh therapies have just completed testing (glibenclamide and Kollidon VA 64), and an eighth drug (AER 271) is in testing. Incorporation of circulating brain injury biomarker assessments into these pre-clinical studies suggests considerable potential for diagnostic and theranostic utility of glial fibrillary acidic protein in pre-clinical studies. Given the failures in clinical translation of therapies in TBI, rigorous multicenter, pre-clinical approaches to therapeutic screening such as OBTT may be important for the ultimate translation of therapies to the human condition.

Characterization and tissue incorporation of cross-linked human acellular dermal matrix.

Here, we describe a novel human acellular dermal matrix (ADM) cross-linked using electron beam irradiation. Structural and biomechanical characteristics of the human ADM were assessed by infrared spectrometry and uni-axial tensile testing. Electron beam irradiation affects collagen secondary structure, which can be detected in the amide I spectral region (1660 cm(-1) and 1690 cm(-1)). At doses exceeding 25 kGy, cross-linking of the collagen matrix results in a denser, more stratified appearance and parallel arrangement, with significantly increased tensile strength and elastic modulus. In a micropig model, the implanted ADM elicits rapid host cell infiltration and extracellular matrix deposition; however, the delayed remodeling resulted in long-term structural integrity. Furthermore, mean densities of collagen and elastin, expression of extracellular matrix proteins, and microvessel formation within the implanted ADM increased significantly, whereas the thickness of the implanted ADM did not decrease during the course of the study. Compared with normal adjacent tissue, type I collagen mRNA levels in the ADM increased 12-fold at 3 months after implantation, and transforming growth factor-ß mRNA levels increased 3.3-fold at 2 months. Matrix metalloproteinase (MMP)-1 and MMP-9 mRNA levels were also elevated. Collectively, these results demonstrate that the structural and biomechanical properties of this novel cross-linked human ADM are adequate for use as a biologic tissue substitute.

Development of osteoporosis animal model using micropigs.

Osteoporosis is a known major health problem and a serious disease of the bone, there has been a great need to develop more and newer animal models for this disease. Among animal models used for testing drug efficacy, the minipig model has become useful and effective due to its close similarity with humans (validity), particularly with the pharmacokinetics of compounds via subcutaneous administration, the structure and function of the organs, the morphology of bone and the overall metabolic nature. Based on these advantages, we sought to develop a new animal model of osteoporosis using micropig, which differs from other miniature pigs in the genetic background. Female micropigs were used for the induction of a moderate osteoporosis model by bilateral ovariectomy (OVX) and compared with shamoperated animals. For osteoporosis evaluation, clinical biomarkers such as blood osteocalcin (OSC) and parathyroid hormone (PTH) levels were measured, as well as bone mineral density (BMD) using micro-computed tomography (micro-CT). Compared to sham, OVX animals have decreased blood OSC level, while the blood PTH level increased in blood sera. In addition, we observed the significantly decreased BMDs of tibia region in OVX animals. Based on these results, we report that the micropig model developed in this study can be used to develop a new and effective medical method for diagnosis and treatment of osteoporosis.

Development of osteoporosis animal model using micropigs / 한국실험동물학회지

Osteoporosis is a known major health problem and a serious disease of the bone, there has been a great need to develop more and newer animal models for this disease. Among animal models used for testing drug efficacy, the minipig model has become useful and effective due to its close similarity with humans (validity), particularly with the pharmacokinetics of compounds via subcutaneous administration, the structure and function of the organs, the morphology of bone and the overall metabolic nature. Based on these advantages, we sought to develop a new animal model of osteoporosis using micropig, which differs from other miniature pigs in the genetic background. Female micropigs were used for the induction of a moderate osteoporosis model by bilateral ovariectomy (OVX) and compared with shamoperated animals. For osteoporosis evaluation, clinical biomarkers such as blood osteocalcin (OSC) and parathyroid hormone (PTH) levels were measured, as well as bone mineral density (BMD) using micro-computed tomography (micro-CT). Compared to sham, OVX animals have decreased blood OSC level, while the blood PTH level increased in blood sera. In addition, we observed the significantly decreased BMDs of tibia region in OVX animals. Based on these results, we report that the micropig model developed in this study can be used to develop a new and effective medical method for diagnosis and treatment of osteoporosis.

Development of a type II diabetic mellitus animal model using Micropig®.

Diabetes, which has shown an explosive increase in terms of its incidence, is regarded as a serious disease that must be overcome for the sake of human life. Among animal models used for testing of drug efficacy, the mini-pig model has shown a rapid upload due to its many similarities with human, particularly concerning the pharmacokinetics of compounds after subcutaneous administration, the structure and function of the gastrointestinal tract, the morphology of the pancreas, and overall metabolic status. Based on these various advantages, we sought to develop an animal model of type II diabetic mellitus using the Micro-pig, which differs from other miniature pigs. We used six male Micro-pigs for induction of a moderate insulin deficient model with nicotinamide (NIA)/streptozotocin (STZ) treatment and three animals for control. For evaluation of incidence of type II diabetes, we measured blood glucose level, and performed oral glucose tolerance test and immunohistochemistry on pancreatic tissue using insulin antibody. Compared to control animals, all animals treated with NIA/STZ showed high levels of glucose and low levels of insulin. In addition, we observed the partially destroyed beta cell population from tissue of the pancreas in treated animals. Based on these results, we report that the Micro-pig model developed in this study can be used for testing of the efficacy of therapeutic agents for treatment of Type 2 diabetic mellitus.

Human leukocytes regulate ganglioside expression in cultured micro-pig aortic endothelial cells.

Gangliosides are ubiquitous components of the membranes of mammalian cells that are thought to play important roles in various cell functions such as cell-cell interaction, cell adhesion, cell differentiation, growth control, and signaling. However, the role that gangliosides play in the immune rejection response after xenotransplantation is not yet clearly understood. In this study, the regulatory effects of human leukocytes on ganglioside expression in primary cultured micro-pig aortic endothelial cells (PAECs) were investigated. To determine the impact of human leukocytes on the expression of gangliosides in PAECs, we performed high-performance thin layer chromatography (HPTLC) in PAECs incubated with FBS, FBS containing human leukocytes, human serum containing human leukocytes, and FBS containing TNF-α. Both HPTLC and immunohistochemistry analyses revealed that PAECs incubated with FBS predominantly express the gangliosides GM3, GM1, and GD3. However, the expression of GM1 significantly decreased in PAECs incubated for 5 h with TNF-α (10 ng/mL), 10% human serum containing human leukocytes, and 10% FBS containing human leukocytes. Taken together, these results suggest that human leukocytes induced changes in the expression profile of ganglioside GM1 similar to those seen upon treatment of PAECs with TNF-α. This finding may be relevant for designing future therapeutic strategies intended to prolong xenograft survival.

Contrast-enhanced ultrasound analysis of renal perfusion in normal micropigs

Contrast-enhanced ultrasound is one of method for evaluating renal perfusion. The purpose of this project was to assess perfusion patterns and dynamics in normal micropig kidney using ultrasonographic contrast media. Eight young healthy micropigs were included in this study. Micropigs were anesthetized with propofol and received an intravenous bolus of microbubble contrast media through an ear vein. Time/mean pixel value (MPV) curves were generated for selected regions in the right renal cortex and medulla. The parenchyma was enhanced in two phases. The cortex was first enhanced followed by a more gradual enhancement of the medulla. A significant difference in perfusion was detected between the cortex and medulla. Following the bolus injection, the average upslope was 0.68 +/- 0.27 MPV/sec, downslope was -0.27 +/- 0.13 MPV/sec, baseline was 73.9 +/- 16.5 MPV, peak was 84.6 +/- 17.2 MPV, and time-to-peak (from injection) was 17.5 +/- 6.6 sec for the cortex. For the medulla, the average upslope was 0.50 +/- 0.24 MPV/sec, downslope was -0.12 +/- 0.06 MPV/sec, baseline was 52.7 +/- 7.0 MPV, peak was 65.2 +/- 9.3 MPV, and time-to-peak (from injection) was 27.5 +/- 5.0 sec. These data can be used as normal reference values for studying young micropigs.

Cerebellar maturation ratio of forebrain and brainstem at magnetic resonance imaging in the micropig / 대한수의학회지

The study of pigs as a human disease model has been conducted in neuroscience. But the morphological development of pig brain by using MRI is rare. The purpose of this study is to determine whether cerebellum maintains consistent proportion to other brain regions in aging. Clinically healthy sixteen micropigs, 1, 2, 4, and 8 months were studied. The micropigs were anesthetized with isoflorane. MRI was acquired using a 0.3T system. To figure out development of ratio that allowed identification of normal cerebellum size, we measured the area of the cerebellum, brainstem, and forebrain from the mid-sagittal brain images on T1W. Mid-sagittal cross-sectional area (CSA) of total brain, forebrain, brainstem, and cerebellum were expressed as absolute values and also as percentages which were compared between the four age groups of micropigs for the purpose to define the effect of age on brain morphometry. It was found that there was not a significant difference in the percentage of the brain occupied by an individual region between groups although the absolute CSA differed significantly among age groups. There was no effect of age on the ratio between the cerebellum and total brain in 4 age groups. The normal size of cerebellum changes during brain development maintained a consistent ratio to other brain regions in normal micropigs. The ratio of CSA quantified on the mid-sagittal MR images offers a suitable method to detect presence of cerebellar anomalies in micropigs.

Human leukocytes regulate ganglioside expression in cultured micro-pig aortic endothelial cells / 한국실험동물학회지

Gangliosides are ubiquitous components of the membranes of mammalian cells that are thought to play important roles in various cell functions such as cell-cell interaction, cell adhesion, cell differentiation, growth control, and signaling. However, the role that gangliosides play in the immune rejection response after xenotransplantation is not yet clearly understood. In this study, the regulatory effects of human leukocytes on ganglioside expression in primary cultured micro-pig aortic endothelial cells (PAECs) were investigated. To determine the impact of human leukocytes on the expression of gangliosides in PAECs, we performed high-performance thin layer chromatography (HPTLC) in PAECs incubated with FBS, FBS containing human leukocytes, human serum containing human leukocytes, and FBS containing TNF-alpha. Both HPTLC and immunohistochemistry analyses revealed that PAECs incubated with FBS predominantly express the gangliosides GM3, GM1, and GD3. However, the expression of GM1 significantly decreased in PAECs incubated for 5 h with TNF-alpha (10 ng/mL), 10% human serum containing human leukocytes, and 10% FBS containing human leukocytes. Taken together, these results suggest that human leukocytes induced changes in the expression profile of ganglioside GM1 similar to those seen upon treatment of PAECs with TNF-alpha. This finding may be relevant for designing future therapeutic strategies intended to prolong xenograft survival.

Development of a type II diabetic mellitus animal model using Micropig(R) / 한국실험동물학회지

Diabetes, which has shown an explosive increase in terms of its incidence, is regarded as a serious disease that must be overcome for the sake of human life. Among animal models used for testing of drug efficacy, the mini-pig model has shown a rapid upload due to its many similarities with human, particularly concerning the pharmacokinetics of compounds after subcutaneous administration, the structure and function of the gastrointestinal tract, the morphology of the pancreas, and overall metabolic status. Based on these various advantages, we sought to develop an animal model of type II diabetic mellitus using the Micro-pig, which differs from other miniature pigs. We used six male Micro-pigs for induction of a moderate insulin deficient model with nicotinamide (NIA)/streptozotocin (STZ) treatment and three animals for control. For evaluation of incidence of type II diabetes, we measured blood glucose level, and performed oral glucose tolerance test and immunohistochemistry on pancreatic tissue using insulin antibody. Compared to control animals, all animals treated with NIA/STZ showed high levels of glucose and low levels of insulin. In addition, we observed the partially destroyed beta cell population from tissue of the pancreas in treated animals. Based on these results, we report that the Micro-pig model developed in this study can be used for testing of the efficacy of therapeutic agents for treatment of Type 2 diabetic mellitus.

Characteristics of Wound Contraction according to the Shape and Antomical Regions of the Wound in Porcine Model

PURPOSE: The shape and location, the amount of the wound and the characteristics of the remaining tissues are known to influence wound contraction. The previous studies using small animals have not been an appropriate model because the wound healing mechanisms and skin structures are different from those of the human. The purpose of this study is to evaluate wound contraction according to the shape and location of the wound using a Micropig(R). METHODS: Four Micropigs(R)(Medikinetics, Pyeongtaek, Korea) that were 10 months of age weighed 25kg were used. Full thickness skin defects were made by clearing all the tissues above the fascial layer in the shape of square, a regular triangle and a circle of 9cm2 each on the back around the spine. Eight wounds were created on the back of each pig, 50mm apart from each other. The randomly chosen wound shapes included 11 squares, 11 regular triangles, and 10 circles. Wound dressing was done every other day with polyurethane foam. The wound size was measured using a Visitrak Digital(R)(Smith & Nephew, Hull, UK) on every other day after surgery from day 2 to day 28. A biopsy was performed on day 3, and 1, 2, 3 and 4 weeks to investigate the degree of acute and chronic inflammation, the number of microvesssel and myofibroblast density using H & E stain and immunohistochemistry. The wound contraction rate was calculated to figure out the differences among each of the shapes and the locations. RESULTS: The ultimate shape of the circle wound was oval, and that of the regular triangle and square were stellate. The maximum contraction rate was obtained on 8 to 10 days for all the shapes, which corresponds with the immunohistochemical finding that myofibroblast increases in the earlier 2 weeks whereas it decreases in the later 2 weeks. Epithelialization was seen in the wound margin on day 7 and afterwards. The final wound contraction rates were highest for the regular triangle shapes; however, there were no statistically significant differences. The wound contraction rates by locations showed statistically significant differences. The wound in the cephalic area presented more contractions than that of the wounds in the caudal area. CONCLUSION: The location of a wound is more important factor than the wound shape in wound contraction.

Multidetector computed tomographic angiography evaluation of micropig major systemic vessels for xenotransplantation

Due primarily to the increasing shortage of allogeneic donor organs, xenotransplantation has become the focus of a growing field of research. Currently, micropigs are the most suitable donor animal for humans. However, no standard method has been developed to evaluate the systemic vascular anatomy of micropigs and standard reference values to aid in the selection of normal healthy animals as potential organ donors are lacking. Using 64-channel multidetector row computed tomographic angiography (MDCTA), we evaluated morphological features of the major systemic vessels in micropigs and compared our results to published human data. The main vasculature of the animals was similar to that of humans, except for the iliac arterial system. However, diameters of the major systemic vessels were significantly different between micropigs and humans. Specifically, the diameter of the aortic arch, abdominal aorta, external iliac artery, and femoral artery, were measured as 1.50 +/- 0.07 cm, 0.85 +/- 0.06 cm, 0.52 +/- 0.05 cm, and 0.48 +/- 0.05 cm, respectively, in the micropigs. This MDCTA data for micropig major systemic vessels can be used as standard reference values for xenotransplantation studies. The use of 64-channel MDCTA enables accurate evaluation of the major systemic vasculature in micropigs.