Facial dimple creation is a simple surgical procedure. Nonetheless, several complications can occur. Actinomycosis is a rare chronic granulomatous infection caused by Actinomyces species. Some conditions that can cause actinomycosis are trauma, oral surgery, and poor dental hygiene. We report a case of actinomycosis that developed on a created facial dimple. A 51-year-old woman presented with a palpable mass on her left cheek that was approximately 1 cm in size. She had undergone facial dimple-creating surgery on both perioral areas at a local clinic 12 years previously. She had not experienced any problems until she was diagnosed with rheumatoid arthritis and diabetes mellitus about 2 years previously, for which she took leflunomide and methotrexate. The mass was completely excised through an intraoral approach. The specimen was grossly described as a gray-yellow cystic mass containing non-absorbable suture material. The filamentous nature of the Actinomyces organisms was observed in dark-stained foci on a histologic examination, confirming the diagnosis of actinomycosis. Indwelling non-absorbable suture materials may increase the risk for opportunistic infections, such as actinomycosis, in immunocompromised patients. Therefore, plastic surgeons should be aware of a patient's general hygiene, immune condition, and medical history when using these materials.
Actinomyces ; Actinomycosis* ; Arthritis, Rheumatoid ; Cheek ; Diabetes Mellitus ; Diagnosis ; Female ; Humans ; Hygiene ; Immunocompromised Host ; Immunosuppressive Agents ; Methotrexate ; Middle Aged ; Opportunistic Infections ; Oral Hygiene ; Plastics ; Surgeons ; Surgery, Oral ; Sutures

Bowel ischemia is a life-threatening surgical emergency. We report a case of rapidly progressive bowel necrosis in a previously healthy child without proven mechanical small bowel obstruction. The definite diagnosis was established at the time of an exploratory operation. Of note, imaging studies and even a laparotomy did not reveal any evidence of acute appendicitis or mechanical obstruction such as intussusception or Meckel's diverticulum. During hospitalization, since we could not rule out surgical abdomen after inconclusive image findings, we closely followed the patient and repeated physical examinations carefully. Eventually surgical exploration was performed based on changes in clinical condition, which proved to be the right decision for the patient. We propose that in children with suspected strangulation of small bowel obstruction, especially when imaging findings do not provide a conclusive diagnosis, the timely exploratory surgical approach ought to be chosen based on carefully observed clinical findings and other evaluations.
Abdomen ; Appendicitis ; Child ; Diagnosis ; Emergencies ; Hospitalization ; Humans ; Intestine, Small ; Intussusception ; Ischemia ; Laparotomy ; Meckel Diverticulum ; Mesenteric Ischemia ; Necrosis ; Physical Examination

Human adipose tissue-derived mesenchymal stem cell (hATMSC) have emerged as a potentially powerful tool for bone repair, but an appropriate evaluation system has not been established. The purpose of this study was to establish a preclinical assessment system to evaluate the efficacy and safety of cell therapies in a nude rat bone defect model. Segmental defects (5 mm) were created in the femoral diaphyses and transplanted with cell media (control), hydroxyapatite/tricalcium phosphate scaffolds (HA/TCP, Group I), hATMSCs (Group II), or three cell-loading density of hATMSC-loaded HA/TCP (Group III-V). Healing response was evaluated by serial radiography, micro-computed tomography and histology at 16 weeks. To address safety-concerns, we conducted a GLP-compliant toxicity study. Scanning electron microscopy studies showed that hATMSCs filled the pores/surfaces of scaffolds in a cell-loading density-dependent manner. We detected significant increases in bone formation in the hATMSC-loaded HA/TCP groups compared with other groups. The amount of new bone formation increased with increases in loaded cell number. In a toxicity study, no significant hATMSC-related changes were found in body weights, clinical signs, hematological/biochemical values, organ weights, or histopathological findings. In conclusion, hATMSCs loaded on HA/TCP enhance the repair of bone defects and was found to be safe under our preclinical efficacy/safety hybrid assessment system.
Adipose Tissue/*cytology ; Animals ; Biocompatible Materials/therapeutic use ; Bone Diseases/pathology/radiography/*therapy ; Bone Regeneration/physiology ; Calcium Phosphates/therapeutic use ; Diaphyses/radiography/surgery/ultrastructure ; Disease Models, Animal ; Durapatite/therapeutic use ; Femur/*pathology/radiography/surgery ; Humans ; Male ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/*cytology ; Rats ; Rats, Nude ; Tissue Engineering ; Tomography, X-Ray Computed ; Transplantation, Heterologous

Thread-embedding therapy has been widely applied for cosmetic purposes such as wrinkle reduction and skin tightening. Particularly, gold thread was reported to support connective tissue regeneration, but, its role in hair biology remains largely unknown due to lack of investigation. When we implanted gold thread and Happy Lift™ in human patient for facial lifting, we unexpectedly found an increase of hair regrowth in spite of no use of hair growth medications. When embedded into the depilated dorsal skin of mice, gold thread or polyglycolic acid (PGA) thread, similarly to 5% minoxidil, significantly increased the number of hair follicles on day 14 after implantation. And, hair re-growth promotion in the gold threadimplanted mice were significantly higher than that in PGA thread group on day 11 after depilation. In particular, the skin tissue of gold thread-implanted mice showed stronger PCNA staining and higher collagen density compared with control mice. These results indicate that gold thread implantation can be an effective way to promote hair re-growth although further confirmatory study is needed for more information on therapeutic mechanisms and long-term safety.
Animals ; Biology ; Collagen ; Connective Tissue ; Hair Follicle ; Hair Removal ; Hair* ; Humans* ; Lifting ; Mice* ; Minoxidil ; Polyglycolic Acid ; Proliferating Cell Nuclear Antigen ; Regeneration ; Skin

Among three representative species of Angelica found in Asian countries, including Korea, China, and Japan, Angelica acutiloba (AA) has been used as traditional herbal medicine with antitumor, anti-inflammatory, anti-obesity, and anti-diabetes activities. In this study, the potential genotoxicity and mutagenicity of the AA extract were examined in a battery of in vitro and in vivo tests (bacterial reverse mutation assay, in vitro chromosomal aberrations assay, and in vivo micronucleus assay) in accordance with the test guidelines for toxicity testing developed by the Organization for Economic Cooperation and Development. Upon testing in the bacterial mutation assay (Ames test) using five Salmonella typhimurium TA98, TA100, TA102, TA1535 and TA1537, no significant increase the number of revertant colonies in the metabolic activation system and non-activation system was noted in the AA extract groups. Also, in the chromosome aberration test, the AA extract did not cause chromosomal aberration with or without metabolic activation by S9 mix. A bone marrow micronucleus test of mice demonstrated that the incidence of micronucleated polychromatic erythrocytes in the AA extract groups (500, 1000 and 2000 mg/kg BW) was equivalent to that of the negative control group. Based on these results from a standard battery of assays, the AA extract was concluded to have no genotoxic at the proper dose.
Activation, Metabolic ; Angelica* ; Animals ; Asian Continental Ancestry Group ; Bone Marrow ; China ; Chromosome Aberrations ; Erythrocytes ; Herbal Medicine ; Humans ; In Vitro Techniques* ; Incidence ; Japan ; Korea ; Medicine, Traditional ; Mice ; Micronucleus Tests ; Organisation for Economic Co-Operation and Development ; Salmonella typhimurium ; Toxicity Tests

Angelica acutiloba (AA), a Japanese species of Danggui, has been used worldwide as a traditional herbal medicine with several bioactivities including anti-diabetic, anti-allergic, anti-inflammatory, anti-tumor, and anti-obesity. However, there is lack of toxicological data available to evaluate potential long-term toxicity and the no-observed-adverse-effect level (NOAEL) of AA extract in accordance with the test guidelines published by the Organization for Economic Cooperation and Development. In the 14-day repeat-dose toxicity study, no adverse effects on mortality, body weight change, clinical signs, and organ weights was found following repeat oral administration to rats for 14 days (125, 250, 500, 1000, and 2000 mg/kg body weight), leading that 2000 mg/kg is the highest recommended dose of AA extract for the 13-week repeat-dose oral toxicity study. In the 13-week repeat-dose oral toxicity study, the AA extract was orally administered to groups of rats for 13 weeks (125, 250, 500, 1000, and 2000 mg/kg body weight) to compare between control and AA extract groups. The administration of AA extract did not produce mortality or remarkable clinical signs during this 13-week study. And, the data revealed that there were no significant differences in food/water consumption, body weight, hematological parameters, clinical chemistry parameters, gross macroscopic findings, organ weight and histopathology in comparison to the control group. On the basis of these results, the subchronic NOAEL of the AA extract was more than 2000 mg/kg/day when tested in rats. And, the AA extract is considered safe to use orally as a traditional herbal medicine.
Administration, Oral ; Angelica* ; Animals ; Asian Continental Ancestry Group ; Body Weight ; Body Weight Changes ; Chemistry, Clinical ; Herbal Medicine ; Humans ; Medicine, Traditional ; Mortality ; No-Observed-Adverse-Effect Level ; Organ Size ; Organisation for Economic Co-Operation and Development ; Rats*

The risk posed to human health by environmental manganese (Mn) exposure is unknown. The purpose of this study is to establish if subclinical effects related to Mn exposure and examine the factors influencing psychoneurobehaviral outcomes of Mn exposed workers. This study involved 121 male workers of welding, alloy furnace, and manufacturing of welding stick. Study investigations include: a questionnaire covering demographic characteristics, job and exposure history and medical symptoms and conditions, monitoring workplace air for personal exposure to respirable and inhalable manganese, analysis of blood and urine samples. psychoneurobehaviral test(neurobehaviral core test battery (NCTB), signal change on magnetic resonance imaging (MRJ) scans, minimental state and neurological examination). The main results of this study were as follows: 1. Preliminary results showed that, with increasing manganese exposure, neurobehaviral performance was poorer and signal change on MRI scans increased. 2. The results of examination revealed significant relations on psychoneurobehaviral out-comes (neurobehaviral performance, signal change on MRI scans, and neurological features). 3. In multiple regression, age and educational status as demographic variables and exposure level were significantly related to 4neurobehaviral test. Also exposure level and serum Mn concentrations were positively relatel to signal change on MRI scans and neurological features affected by Mn on the brain (signal change). 4. Psychoneurobehaviral outcomes from Mn exposure were related to neurobehaviral performance, signal change on MRJ scans, neurological features and profile of mood states (POMS), and influnced positively with age, alcohol and smoking history, and duration of Mn exposure, negatively with educational status. Serum Mn concentrations in combination with brain MRI scans, and perhaps a battery of neurobehaviral tests, appear to be the best way to monitor excessive exposure to Mn. These results are consistent with our knowledge on Mn action on the brain and are similar to the type of neurobehaviral dysfunction. They suggest that there may be age, educational status, and life style (alcohol and drinking history) differences with chronic environmental exposure. These findings suggest further evaluation, particularly on relationships between Mn exposure, aging, and susceptibility factors.
Aging ; Alloys ; Brain ; Drinking ; Educational Status ; Environmental Exposure ; Humans ; Life Style ; Magnetic Resonance Imaging ; Male ; Manganese* ; Questionnaires ; Risk Factors ; Smoke ; Smoking ; Welding

Human fibroblasts were developed for cellular therapy with the aim of correcting of depressed scars, but the safety of that in vivo is unclear. In this study, we assessed the safety of human fibroblasts by investigating the tumorigenicity, 13-week toxicity and through distribution studies. In the tumorigenicity test, nude mice were divided into three dosage level treatment groups with a negative/positive control group. At 6 months after intradermal transplantation, all of the treatment groups showed no development of a nodule on the injection sites and organs. Toxicity studies were performed using ICR and BALB/c mice for 13 weeks. The mice were divided into three dosage level treatment groups with a control and a syngeneic group. There was no treatment-related effect on clinical signs, mortality, body weight, food/water consumption, hematology, serum biochemistry, urine, necropsy findings and histopathological findings in any groups. These results suggest that the no-observed-effect level (NOEL) of the human fibroblasts was greater than 7.5x10(7) cells/kg for mice. In the distribution study, groups were treated with fibroblasts labeled with a fluorescent dye (CM-DiI) at low and high doses with a control and a syngeneic group. At 24 hours, a large percentage of the labeled fibroblasts were observed at the dermal layer. At 3 months, fluorescence of the labeled fibroblasts continued to be observed. Other tissues were not detected the fluorescence at any time. These studies demonstrate that the safety of human fibroblasts is reasonable with no toxic effect, no tumorigenicity and retention in the dermis. Our studies define preclinical safety testing standards relevant to the development of cellular therapeutics.
Animals ; Biochemistry ; Body Weight ; Carcinogenicity Tests ; Cicatrix ; Dermis ; Fibroblasts ; Fluorescence ; Hematology ; Humans ; Mice ; Mice, Nude ; No-Observed-Adverse-Effect Level ; Retention (Psychology) ; Tissue Therapy ; Transplants

Recombination activating gene-2 (RAG-2) plays a crucial role in the development of lymphocytes by mediating recombination of T cell receptors and immunoglobulins, and loss of RAG-2 causes severe combined immunodeficiency (SCID) in humans. RAG-2 knockout mice created using homologous recombination in ES cells have served as a valuable immunodeficient platform, but concerns have persisted on the specificity of RAG-2-related phenotypes in these animals due to the limitations associated with the genome engineering method used. To precisely investigate the function of RAG-2, we recently established a new RAG-2 knockout FVB mouse line (RAG-2(−/−)) manifesting lymphopenia by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease. In this study, we further characterized their phenotypes focusing on histopathological analysis of lymphoid organs. RAG-2(−/−) mice showed no abnormality in development compared to their WT littermates for 26 weeks. At necropsy, gross examination revealed significantly smaller spleens and thymuses in RAG-2(−/−) mice, while histopathological investigation revealed hypoplastic white pulps with intact red pulps in the spleen, severe atrophy of the thymic cortex and disappearance of follicles in lymph nodes. However, no perceivable change was observed in the bone marrow. Moreover, our analyses showed a specific reduction of lymphocytes with a complete loss of mature T cells and B cells in the lymphoid organs, while natural killer cells and splenic megakaryocytes were increased in RAG-2(−/−) mice. These findings indicate that our RAG-2(−/−) mice show systemic lymphopenia with the relevant histopathological changes in the lymphoid organs, suggesting them as an improved Rag-2-related immunodeficient model.
Animals ; Atrophy ; B-Lymphocytes ; Bone Marrow ; Genome ; Homologous Recombination ; Humans ; Immunoglobulins ; Killer Cells, Natural ; Lymph Nodes ; Lymphocytes ; Lymphopenia* ; Megakaryocytes ; Methods ; Mice* ; Mice, Knockout ; Negotiating ; Phenotype ; Receptors, Antigen, T-Cell ; Recombination, Genetic ; Sensitivity and Specificity ; Severe Combined Immunodeficiency ; Spleen ; T-Lymphocytes ; Thymus Gland

Stem cell technologies are particularly attractive in Parkinson's disease (PD) research although they occasionally need long-term treatment for anti-parkinsonian activity. Unfortunately, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) widely used as a model for PD has several limitations, including the risk of dose-dependent mortality and the difficulty of maintenance of PD symptoms during the whole experiment period. Therefore, we tested if our novel MPTP regimen protocol (2 mg/kg for 2 consecutive days and 1 mg/kg for next 3 consecutive days) can be maintained stable parkinsonism without mortality for long-term stem cell therapy. For this, we used small-bodied common marmoset monkeys (Callithrix jacchus) among several nonhuman primates showing high anatomical, functional, and behavioral similarities to humans. Along with no mortality, the behavioral changes involved in PD symptoms were maintained for 32 weeks. Also, the loss of jumping ability of the MPTP-treated marmosets in the Tower test was not recovered by 32 weeks. Positron emission tomography (PET) analysis revealed that remarkable decreases of bindings of ¹⁸F-FP-CIT were observed at the striatum of the brains of the marmosets received MPTP during the full period of the experiment for 32 weeks. In the substantia nigra of the marmosets, the loss of tyrosine hydroxylase (TH) immunoreactivity was also observed at 32 weeks following the MPTP treatment. In conclusion, our low-dose MPTP regimen protocol was found to be stable parkinsonism without mortality as evidenced by behavior, PET, and TH immunohistochemistry. This result will be useful for evaluation of possible long-term stem cell therapy for anti-parkinsonian activity.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine* ; Brain ; Callithrix* ; Haplorhini ; Humans ; Immunohistochemistry ; Models, Animal ; Mortality ; Parkinson Disease* ; Parkinsonian Disorders ; Positron-Emission Tomography ; Primates ; Stem Cells* ; Substantia Nigra ; Tyrosine 3-Monooxygenase