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1.
Journal of the Korean Society of Biological Therapies in Psychiatry ; (3): 35-42, 2023.
Article in English | WPRIM | ID: wpr-1001836

ABSTRACT

Objectives@#This study aimed to develop a machine learning model for diagnosing schizophrenia (SZ) and bipolar disorder (BD) based on diffusion tensor imaging (DTI) data. @*Methods@#We used 3T-magnetic resonance imaging to examine SZ, BD, healthy control (HC) subjects (aged 20-50 years, n=65 in each group). Applying Support Vector Machine (SVM) to fractional anisotropy (FA) values, we built classification models of SZ and HC, BD and HC, and SZ and BD. Features of white matter (WM) tracts were selected through recursive feature elimination, and 5-fold cross validation was performed. @*Results@#The SVM models classified SZ and BD from HC with a mean accuracy of 83.5% and 75.4%, respectively. The SZ-BD classification model archived 75.0% accuracy. These classification models used FA values in 15-18 WM tracts as features, including the retrolenticular part of the internal capsule, superior corona radiata, cingulum, and superior fronto-occipital fasciculus. @*Conclusions@#This study presented a preliminary machine learning model to diagnose SZ and BD based on DTI data. Our findings also suggest that there might be a specific pattern of abnormalities in WM integrity that can differentiate the two psychotic disorders.

2.
Journal of Korean Academy of Pediatric Dentistry ; (4): 35-44, 2022.
Article in Korean | WPRIM | ID: wpr-926214

ABSTRACT

The aim of this study is to evaluate the development of the left mandibular third-molar development with modified Demirjian method and its relation to chronological age.A total of 1653 digital panoramic radiographs of healthy individuals aged between 7 and 23 years who visited Yonsei University Dental hospital were selected. The developmental status of the left mandibular third molars was assessed using dental maturity scoring proposed by Demirjian et al. The mean age of the first appearance of mineralization, complete crown formation, and complete root formation were around 9, 14, 21 years respectively. Statistically significant differences between males and females in the development stage of D and G were revealed that crown formation and root length completion were attained earlier in males than in females. There was significant positive relationship between age and third molar development in both sexes, and new formula was presented to estimate age of children and adolescents based on their developmental stages of third molars.In this study, the use of left mandibular third molar as a developmental marker is appropriate, and age estimation can be attained with dental maturity stage.

3.
Journal of Korean Academy of Pediatric Dentistry ; (4): 255-268, 2021.
Article in Korean | WPRIM | ID: wpr-919868

ABSTRACT

The aim of this study was to investigate the relationships between the stages of calcification of various teeth and skeletal maturity stages among Korean subjects. The samples were derived from hand-wrist, panoramic radiographs, and lateral cephalograms of 743 subjects (359 males and 384 females) with ages ranging from 6 to 14 years. Calcification of seven permanent mandibular teeth on the left side were rated according to the system of Demirjian. To evaluate the stage of skeletal maturation, hand-wrist radiographs were analyzed by skeletal maturity indicators (SMI) system of Fishman and lateral cephalograms by cervical vertebral maturation (CVM) method of Baccetti. Statistically significant relationships were found between dental calcification and skeletal maturity stages according to Spearman rank-order correlation coefficients (r = 0.40-0.84, p < 0.001). The second molar showed the highest correlation and central incisor showed the lowest correlation for female and male subjects. For both sexes, canine stage G and second molar stage F were related to SMI 6 and CS 3. Because of the high correlation coefficients, this study suggests that tooth calcification stages from panoramic radiographs might be clinically useful as a maturity indicator of the pubertal growth period in Korean patients.

4.
Journal of the Korean Ophthalmological Society ; : 266-272, 2021.
Article in Korean | WPRIM | ID: wpr-875049

ABSTRACT

Purpose@#To evaluate the findings and frequencies of retinal microvascular abnormalities observed in patients with type 1 neurofibromatosis. @*Methods@#Fundus photographs of 61 patients with type 1 neurofibromatosis and 61 controls without systemic disease or ophthalmic abnormalities were retrospectively compared and analyzed. The presence or absence of retinal microvascular abnormalities in the form of simple vascular tortuosity, corkscrew retinal vessels, and moyamoya-like patterns was confirmed, and the diagnostic sensitivity, diagnostic specificity, positive predictive value, negative predictive value, and diagnostic accuracy for type 1 neurofibromatosis were analyzed. @*Results@#Retinal microvascular abnormalities were found in 19.7% (12 patients) of the patient group, There was no cases in the control group, thus. The difference between the patient group and the control group was significant (p = 0.0003). Of the 12 patients with abnormalities, 10 exhibited simple vascular tortuosity, one had corkscrew retinal vessels, and one exhibited both findings. The diagnostic sensitivity of retinal microvascular abnormalities for type 1 neurofibromatosis was 23.53%, the diagnostic specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 61%. The diagnostic accuracy was 65.18%, which was slightly lower than the 79.5% diagnostic accuracy for the Lisch nodule, but the diagnostic accuracy was comparable to that of neurofibroma (68.03%). @*Conclusion@#Retinal microvascular abnormalities were observed in 19.7% of type 1 neurofibromatosis patients, of which simple vascular tortuosity was the most common. Considering that retinal microvascular abnormalities were not observed at all in the control group, and the diagnostic accuracy was 65.18%, this type of abnormality could be included as a new ophthalmic clinical feature of type 1 neurofibromatosis.

5.
Journal of the Korean Ophthalmological Society ; : 950-954, 2020.
Article | WPRIM | ID: wpr-833222

ABSTRACT

Purpose@#To report a case of primary conjunctival and tarsal amyloidosis with blepharoptosis.Case summary: A 73-year-old woman presented with left blepharoptosis and foreign body sensation that worsened over a1-year period prior. She presented with severe blepharoptosis on the left upper lid, with slightly reduced levator function. Duringthe operation, a fragile yellowish-pink mass-lesion was observed, widely involving palpebral conjunctiva and the space betweenthe levator aponeurosis and tarsal plate. While levator resection was withheld, the mass was excised as much as possible andblepharoplasty was performed. After surgery, the blepharoptosis improved slightly, and histopathologic examination revealedamyloid deposits. Because there were no abnormal findings in systemic examinations including blood tests, chest X-rays, andabdominal ultrasonography, the patient was diagnosed as primary conjunctival and tarsal amyloidosis. @*Conclusions@#Although local amyloidosis of the conjunctiva and tarsal plate is rare, it should be considered in differential diagnosisof patients with involutional blepharoptosis.

6.
Journal of Korean Academy of Pediatric Dentistry ; (4): 389-396, 2020.
Article in Korean | WPRIM | ID: wpr-919854

ABSTRACT

A pyramidal molar is which has completely fused roots with a solitary enlarged canal. The purpose of this retrospective study was to assess the prevalence and characteristics of pyramidal molars among adolescent.A total of 1,612 patients’ panoramic radiographs were screened. A total of 12,896 first and second molars were evaluated. The relative incidence and the correlations regarding the location of pyramidal molar (maxillary versus mandibular) and gender were analyzed using the chi-square test.The overall incidence of patients with pyramidal molars was 1.49%. 24 patients were found to have a pyramidal molar and it was more prevalent in women (18 women and 6 men). The prevalence of pyramidal molars from all first and second molars examined was 0.31%. 88 percent of pyramidal molars occurred in maxilla. All pyramidal molars were second molar.Pyramidal molar has a relatively poor periodontal prognosis compared with common multi-rooted teeth and it is important to understand the structural characteristics of root canal during pulp treatment. Clinicians should be able to understand the anatomical properties of pyramidal molar and apply it to treatment and prognostic evaluation.

7.
Journal of Korean Academy of Pediatric Dentistry ; (4): 36-43, 2020.
Article in Korean | WPRIM | ID: wpr-919826

ABSTRACT

The aim of this study was to assess the occlusal relationships of primary dentition of Korean preschool children in Hwaseong city.Total 444 children of age group between 2 and 5 years were selected. One pediatric dentist took intraoral photos of children. Evaluation and categorization of the primary molar relationships were done by single examiner. Statistical analysis was performed with Pearson chi-squared test.Total 389 samples, which is consisted of 185 boys, 204 girls were satisfied with inclusion criteria. Bilateral mesial step was seen in 61.7%. Bilateral flush terminal plane was seen in 15.4%. When the primary molar relations of the right and left sides were not the same, the combination of the mesial step and flush terminal plane was 14.7%.The present study provides insight into occlusal relationships in the primary dentition of 2 - 5 years old of Korean children in Hwaseong city. Pediatric dentists should understand occlusal relationships of primary dentition for establishment of appropriate treatment strategies and occlusal guidance.

8.
Journal of Korean Academy of Pediatric Dentistry ; (4): 62-69, 2020.
Article in Korean | WPRIM | ID: wpr-919823

ABSTRACT

This study intended to evaluate noise level of dental handpieces and the effects of noise cancelling devices. An ear model was designed to measure the level of the noise delivered to the inner ear during dental handpiece operation. The level of noise was measured in various conditions using the ear model and the portable noise meter. Noise level was measured again after applying of 4 different noise cancelling devices to the model ear.The noise level of dental handpieces was 82.5 - 84.4 dB. When 4 types of noise canceling devices were applied, the noise level reduced to 67.4 - 73.8 dB. All 4 devices had statistically significant effect in reducing the noise of the handpiece.Considering the intensity and exposure time, noise in dental clinics can cause hearing damage to dentists. For protection from the risk of occupational hearing damages, noise canceling devices can be recommended.

9.
Journal of Korean Academy of Pediatric Dentistry ; (4): 277-292, 2020.
Article in Korean | WPRIM | ID: wpr-919814

ABSTRACT

The pulp treatment of primary and immature teeth in the children and adolescents is affected by the environment of the patients, clinical careers and dentists performing the techniques, as well as clinical modalities and pulpal diagnosis. The purpose of this study was to investigate the current status of pulp treatment performed in real clinical practice, as well as the reasons behind the choice of treatment methods. The study was conducted on a total of 153 members of the Korean Academy of Pediatric Dentistry, and statistical data from the Health Insurance Review and Assessment Service (HIRA) from 2010 to 2018 were analyzed ogether. Both the survey results and the statistics from the HIRA showed that 1-visit pulpectomies of primary teeth were most common, and the frequency of the use of the Ni-Ti file was increased in children with primary or mixed-dentition. In the treatment of immature permanent teeth, regenerative endodontic treatment by individual dentists was found to be less frequent than in university hospitals.

10.
Journal of the Korean Society of Biological Psychiatry ; : 27-35, 2020.
Article in Korean | WPRIM | ID: wpr-901751

ABSTRACT

Objectives@#ZZKetamine has been reported to have antidepressant effects or psychotomimetic effects. The aim of this study was to investigatethe behavioral effects of ketamine treatment at various sub-anesthetic doses in adolescent and adult naïve mice. @*Methods@#ZZIn each experiment for adolescent and adult mice, a total of 60 male Institute of Cancer Research mice were randomly dividedinto 6 groups, which were intraperitoneally treated with physiological saline, 10, 20, 30, 40, and 50 mg/kg ketamine for consecutive3 days. At 1 day after last injection, the locomotor and depressive-like behaviors were evaluated in mice, using open field test (OFT)and forced swim test (FST), respectively. @*Results@#ZZIn case of adolescent mice, ketamine dose was negatively correlated with total distance traveled in the OFT (Spearman’srho = -0.27, p = 0.039). In case of adult mice, we found significant positive correlation between ketamine dose and duration of immobilityin the FST (Spearman’s rho = 0.45, p < 0.001). Immobility time in the 50 mg/kg ketamine-treated mice was significantly higher comparedto the saline-treated mice (Dunnett’s post-hoc test, p = 0.012). @*Conclusions@#ZZWe found that the repeated treatment with ketamine could decrease the locomotor or prolong the duration of immobilityin mice as the dose of ketamine increased. Our findings suggest that sub-anesthetic doses of ketamine might induce schizophrenia-like negative symptoms but not antidepressant effects in naïve laboratory animals.

11.
Journal of the Korean Society of Biological Psychiatry ; : 27-35, 2020.
Article in Korean | WPRIM | ID: wpr-894047

ABSTRACT

Objectives@#ZZKetamine has been reported to have antidepressant effects or psychotomimetic effects. The aim of this study was to investigatethe behavioral effects of ketamine treatment at various sub-anesthetic doses in adolescent and adult naïve mice. @*Methods@#ZZIn each experiment for adolescent and adult mice, a total of 60 male Institute of Cancer Research mice were randomly dividedinto 6 groups, which were intraperitoneally treated with physiological saline, 10, 20, 30, 40, and 50 mg/kg ketamine for consecutive3 days. At 1 day after last injection, the locomotor and depressive-like behaviors were evaluated in mice, using open field test (OFT)and forced swim test (FST), respectively. @*Results@#ZZIn case of adolescent mice, ketamine dose was negatively correlated with total distance traveled in the OFT (Spearman’srho = -0.27, p = 0.039). In case of adult mice, we found significant positive correlation between ketamine dose and duration of immobilityin the FST (Spearman’s rho = 0.45, p < 0.001). Immobility time in the 50 mg/kg ketamine-treated mice was significantly higher comparedto the saline-treated mice (Dunnett’s post-hoc test, p = 0.012). @*Conclusions@#ZZWe found that the repeated treatment with ketamine could decrease the locomotor or prolong the duration of immobilityin mice as the dose of ketamine increased. Our findings suggest that sub-anesthetic doses of ketamine might induce schizophrenia-like negative symptoms but not antidepressant effects in naïve laboratory animals.

12.
Clinical Psychopharmacology and Neuroscience ; : 400-408, 2019.
Article | WPRIM | ID: wpr-763553

ABSTRACT

OBJECTIVE: This study aimed to investigate the long-term effects of aripiprazole treatment during adolescence on behavior, cognitive function, and dopamine D2 receptor (D2R) expression in adult rats. METHODS: Adolescent male Sprague-Dawley rats were injected intraperitoneally with aripiprazole, risperidone, or vehicle control for 3 weeks (postnatal day 36–56). After a 2-week washout period, locomotion, anxiety, and spatial working memory were evaluated in adulthood (postnatal day 71–84), using an open field test, elevated plus maze, and Y-maze, respectively. In addition, we assessed D2R levels in the dorsolateral and medial prefrontal cortex (PFC), dorsal and ventral striatum, and hippocampus using western blot analysis. RESULTS: Spontaneous alternation performance (SAP) in the Y-maze, a measure of spatial working memory, differed significantly among the 3 groups (F = 3.89, p = 0.033). A post-hoc test confirmed that SAP in the aripiprazole group was significantly higher than that in the risperidone group (post-hoc test p = 0.013). D2R levels in the medial PFC (F = 8.72, p = 0.001) and hippocampus (F = 13.54, p < 0.001) were different among the 3 groups. D2R levels in the medial PFC and hippocampus were significantly lower in the aripiprazole-treated rats than that in the risperidone-treated rats (post-hoc test p = 0.025 and p < 0.001, respectively) and controls (post-hoc test p < 0.001, all). CONCLUSION: This study showed that aripiprazole treatment in adolescence could influence cognitive function and dopaminergic neurotransmission into early adulthood.


Subject(s)
Adolescent , Adult , Animals , Humans , Male , Rats , Anxiety , Aripiprazole , Blotting, Western , Cognition , Dopamine , Hippocampus , Locomotion , Memory, Short-Term , Models, Animal , Prefrontal Cortex , Rats, Sprague-Dawley , Receptors, Dopamine D2 , Risperidone , Synaptic Transmission , Ventral Striatum
13.
Journal of Korean Academy of Pediatric Dentistry ; (4): 173-182, 2019.
Article in Korean | WPRIM | ID: wpr-787367

ABSTRACT

Vertical facial growth triggers the rotation of mandible to move the chin point to the downward and backward direction, which showed remarkably effective result making the less prominent chin. Recently, the intraoral removable appliance utilizing class III elastic demonstrated the vertical growth trigger mechanism. The treatment change was very fast and wearing was quite easy, compared to extraoral appliances.The purpose of this study was to verify the duration of the treatment on class III malocclusion using intraoral removable appliances, which designed to accelerate vertical facial growth.56 patients were selected with the complaint of the protruded mandible and class III malocclusion (overjet : −3 – 0 mm, overbite : 0 – 4 mm). Information like; age at start, duration of the treatment events, type of the treatment, overjet, overbite etc. was collected and calculated.The average age of the patients delivering the initial brace was 8.75 ± 1.10 year. Most of the anterior crossbite was resolved within 6 months. The total treatment period was 21.79 ± 10.73 months with the additional procedures like the alignment of anterior teeth and torque control using additional removable and fixed orthodontic appliances. The correlation study showed that patient's cooperation (p = 0.000) and the use of fixed appliance (p = 0.032) were significantly influenced on treatment duration.


Subject(s)
Humans , Braces , Chin , Malocclusion , Mandible , Orthodontic Appliances , Overbite , Statistics as Topic , Tooth , Torque
14.
Journal of Korean Academy of Pediatric Dentistry ; (4): 200-208, 2019.
Article in Korean | WPRIM | ID: wpr-787364

ABSTRACT

The purpose of this study was to analyze the dental consultation of pediatric inpatients to the department of pediatric dentistry in Yonsei University Severance Hospital, and to investigate the change in patterns. In 2017, 268 pediatric patients (384 cases) admitted to the Severance Hospital were referred to the department of pediatric dentistry. The mean age was 6.6 years, and most of the patients were referred from the Department of Pediatric Hematology Oncology and Rehabilitation Medicine. The chief complaints were as follows: oral examination (31%), dental caries (20%), oral pain (10%), tooth mobility (10%), pre-operative evaluation (9%) and others (20%). 41% of the patients received only oral examination without treatment. Dental caries were the most frequent dental diagnosis of the patients. 28% (111 cases) of patients received operative treatments, 22 cases were treated under general anesthesia. Oral health is closely related to systemic diseases, especially for hospitalized patients. Dental consultations should be encouraged for prevention and early appropriate treatments. For this purpose, it is necessary to establish a referral system and perform dental treatment under general anesthesia.


Subject(s)
Humans , Anesthesia, General , Dental Caries , Diagnosis , Diagnosis, Oral , Hematology , Inpatients , Oral Health , Pediatric Dentistry , Referral and Consultation , Rehabilitation , Tooth Mobility
15.
Journal of Korean Academy of Pediatric Dentistry ; (4): 154-161, 2018.
Article in Korean | WPRIM | ID: wpr-787315

ABSTRACT

Sedation is a useful behavior management technique for dental patients who may be uncontrollable or have medical problems. The aim of this study is to investigate the changes in patterns of sedative treatments in pediatric dentistry by analyzing the distribution of patients and used sedative agents.Patients and sedative agents were reviewed based on the electronic medical records (EMR) of the department of pediatric dentistry in Yonsei University Dental Hospital from 2011 to 2016.The number of patients who were treated under sedation generally increased. Male received more sedation treatment than female by 2014, and they became similar from 2015. The treatment percentage of patients with systemic disease decreased in 2013, remained constantly afterwards. The ratio of sedative treatment for the age 4 – 5 and age 6 – 10 generally increased, while that of the age 0 – 2 and older than age 11 decreased. The ratio of the age 3 remained steady. Nitrous oxide was the most frequently used sedative agent. The use of benzodiazepine increased while the use of chloral hydrate decreased.Although the use of sedation has expanded, multidimensional approaches for ensuring safety have been less focused. Therefore, it is necessary to explore further studies for the safety and efficacy of the use of sedation.


Subject(s)
Female , Humans , Male , Behavior Control , Benzodiazepines , Chloral Hydrate , Conscious Sedation , Electronic Health Records , Nitrous Oxide , Pediatric Dentistry
16.
Journal of Korean Academy of Pediatric Dentistry ; (4): 162-169, 2018.
Article in Korean | WPRIM | ID: wpr-787314

ABSTRACT

The purpose of this study was to compare the validity of Cariview®, a new colorimetric caries activity test, with CRT® bacteria, a conventional bacterial culture method. In addition, this study assesses the correlation between the dental caries experience and activity between mothers and their children.34 pairs of mothers and their children under the age of 6 years participated in this study with informed consent. After filling out a questionnaire and oral examination, the two caries activity tests above were performed on each subject.In the results, Cariview® scores were statistically significant with children's caries experience (r = 0.598, p <0.01) and showed higher correlation than CRT® bacteria scores. Cariview® scores showed statistically significant correlation with the number of decayed teeth in both mothers and children (p <0.05). In both Cariview® and CRT® bacteria tests, there was no statistically significant correlation between caries experience and caries activity (p > 0.05).Cariview® colorimetric test will be clinically useful for predicting future caries risk and establishing a preventative strategy in pediatric dentistry.


Subject(s)
Child , Humans , Bacteria , Dental Caries , Diagnosis, Oral , Informed Consent , Methods , Mothers , Pediatric Dentistry , Tooth
17.
The Korean Journal of Physiology and Pharmacology ; : 65-71, 2013.
Article in English | WPRIM | ID: wpr-727487

ABSTRACT

The transient receptor potential melastatin type 7 (TRPM7) channel is a widely expressed non-selective cation channel with fusion to the C-terminal alpha kinase domain and regarded as a key regulator of whole body Mg2+ homeostasis in mammals. However, the roles of TRPM7 during osteoclastogenesis in RAW264.7 cells and bone marrow-derived monocyte/macrophage precursor cells (BMMs) are not clear. In the present study, we investigate the roles of TRPM7 in osteoclastogenesis using methods of small interfering RNA (siRNA), RT-PCR, patch-clamp, and calcium imaging. RANKL (receptor activator of NF-kappaB ligand) stimulation did not affect the TRPM7 expression and TRPM7-mediated current was activated in HEK293, RAW264.7, and BMM cells by the regulation of Mg2+. Knock-down of TRPM7 by siTRPM7 reduced intracellular Ca2+ concentration ([Ca2+]i) increases by 0 mM [Mg2+]e in HEK293 cells and inhibited the generation of RANKL-induced Ca2+ oscillations in RAW264.7 cells. Finally, knock-down of TRPM7 suppressed RANKL-mediated osteoclastogenesis such as activation and translocation of NFATc1, formation of multinucleated cells, and the bone resorptive activity, sequentially. These results suggest that TRPM7 plays an essential role in the RANKL-induced [Ca2+]i oscillations that triggers the late stages of osteoclastogenesis.


Subject(s)
Calcium , Calcium Signaling , HEK293 Cells , Homeostasis , Mammals , NF-kappa B , Phosphotransferases , RNA, Small Interfering
18.
Journal of Korean Medical Science ; : 482-491, 2011.
Article in English | WPRIM | ID: wpr-173916

ABSTRACT

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.


Subject(s)
Animals , Humans , Male , Rats , Adipose Tissue/cytology , Biocompatible Materials/therapeutic use , Bone Diseases/pathology , Bone Regeneration/physiology , Calcium Phosphates/therapeutic use , Diaphyses/diagnostic imaging , Disease Models, Animal , Durapatite/therapeutic use , Femur/pathology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Rats, Nude , Tissue Engineering , Tomography, X-Ray Computed , Transplantation, Heterologous
19.
Laboratory Animal Research ; : 181-196, 2010.
Article in Korean | WPRIM | ID: wpr-108460

ABSTRACT

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.


Subject(s)
Animals , Humans , Mice , Biochemistry , Body Weight , Carcinogenicity Tests , Cicatrix , Dermis , Fibroblasts , Fluorescence , Hematology , Mice, Nude , No-Observed-Adverse-Effect Level , Retention, Psychology , Cell- and Tissue-Based Therapy , Transplants
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