Induction of liver transplant immune tolerance in an outbred rat strain model using tacrolimus / 한국실험동물학회지

Background@#Orthotopic liver transplantation is the only option for patients with end-stage liver disease and hepatocellular carcinoma. Post-transplant immunosuppressive therapy is important to prevent graft failure. We investigated the effectiveness of tacrolimus (FK506) and their mechanisms for liver transplant immune tolerance in an outbred rat LT model. @*Results@#To investigate the therapeutic effect of the FK506 on outbred rat LT model, FK506 and postoperative therapy were administered subcutaneously once or twice daily to transplanted rats. Histopathological and immunohistochemical analyses were conducted for all groups. The regulation of inflammatory cytokine signaling in the spleen was analyzed by flow cytometry. FK506 attenuated allograft rejection and increased survival in rat orthotopic liver transplantation models. The FK506-treated group had reduced serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. Furthermore, FK506 decreased the expression of inflammatory cytokines and the activation of pathogenic Th1 and Th17 cells in the liver. @*Conclusions@#Taken together, we revealed that FK506 ameliorated strong allograft rejection in outbred liver transplantation model by anti-inflammatory effect and inhibitory peroperty of pathogenic T cells.

Acute Impact of the Coronavirus Disease Outbreak on Behavioral Patterns and Emotional States of Pediatric Psychiatric Patients and Caregivers in Daegu, South Korea

Objective@#This study aimed to investigate the changes in interpersonal relationships, behavioral patterns, and emotional states of children and adolescents with psychiatric disorders and their caregivers immediately after the coronavirus disease of 2019 (COVID-19) outbreak in Daegu, South Korea. @*Methods@#A total of 147 patients and 147 caregivers participated in the Survey for Outing and Time Usage for Child, Adolescent, and Parents and the COVID-19 Visual Analog Scale for Emotion. We classified the patients and their caregivers into the internalizing disorder (ID) and externalizing disorder (ED) groups and compared the changes. @*Results@#Parent–child relationships for adolescent patients and caregivers were interrupted, and friend relationships in all participants were disrupted, while sibling relationships improved in adolescent patients. They experienced negative emotional changes. Time spent outdoor decreased and digital screen time increased for all participants. Friend and parent–child relationships were interrupted in the ED group compared to those in the ID group. ED patients experienced negative changes in emotional states, while ID patients showed no significant changes. @*Conclusion@#Results are meaningful as a reference for predicting changes in interpersonal relationships and mental status of pediatric psychiatric patients and for determining healthcare system adaptations to allow mental health support during the COVID-19 outbreak.

Acute Impact of the Coronavirus Disease Outbreak on Behavioral Patterns and Emotional States of Pediatric Psychiatric Patients and Caregivers in Daegu, South Korea

Objective@#This study aimed to investigate the changes in interpersonal relationships, behavioral patterns, and emotional states of children and adolescents with psychiatric disorders and their caregivers immediately after the coronavirus disease of 2019 (COVID-19) outbreak in Daegu, South Korea. @*Methods@#A total of 147 patients and 147 caregivers participated in the Survey for Outing and Time Usage for Child, Adolescent, and Parents and the COVID-19 Visual Analog Scale for Emotion. We classified the patients and their caregivers into the internalizing disorder (ID) and externalizing disorder (ED) groups and compared the changes. @*Results@#Parent–child relationships for adolescent patients and caregivers were interrupted, and friend relationships in all participants were disrupted, while sibling relationships improved in adolescent patients. They experienced negative emotional changes. Time spent outdoor decreased and digital screen time increased for all participants. Friend and parent–child relationships were interrupted in the ED group compared to those in the ID group. ED patients experienced negative changes in emotional states, while ID patients showed no significant changes. @*Conclusion@#Results are meaningful as a reference for predicting changes in interpersonal relationships and mental status of pediatric psychiatric patients and for determining healthcare system adaptations to allow mental health support during the COVID-19 outbreak.

Engineering Human Brain Organoids: From Basic Research to Tissue Regeneration

BACKGROUND@#Brain organoids are self-organized from human pluripotent stem cells and developed into various brain region following the developmental process of brain. Brain organoids provide promising approach for studying brain development process and neurological diseases and for tissue regeneration. @*METHODS@#In this review, we summarized the development of brain organoids technology, potential applications focusing on disease modeling for regeneration medicine, and multidisciplinary approaches to overcome current limitations of the technology. @*RESULTS@#Generations of brain organoids are categorized into two major classes by depending on the patterning method.In order to guide the differentiation into specific brain region, the extrinsic factors such as growth factors, small molecules, and biomaterials are actively studied. For better modelling of diseases with brain organoids and clinical application for tissue regeneration, improvement of the brain organoid maturation is one of the most important steps. @*CONCLUSION@#Brain organoids have potential to develop into an innovative platform for pharmacological studies and tissue engineering. However, they are not identical replicas of their in vivo counterpart and there are still a lot of limitations to move forward to clinical applications.

Engineering Human Brain Organoids: From Basic Research to Tissue Regeneration

BACKGROUND@#Brain organoids are self-organized from human pluripotent stem cells and developed into various brain region following the developmental process of brain. Brain organoids provide promising approach for studying brain development process and neurological diseases and for tissue regeneration. @*METHODS@#In this review, we summarized the development of brain organoids technology, potential applications focusing on disease modeling for regeneration medicine, and multidisciplinary approaches to overcome current limitations of the technology. @*RESULTS@#Generations of brain organoids are categorized into two major classes by depending on the patterning method.In order to guide the differentiation into specific brain region, the extrinsic factors such as growth factors, small molecules, and biomaterials are actively studied. For better modelling of diseases with brain organoids and clinical application for tissue regeneration, improvement of the brain organoid maturation is one of the most important steps. @*CONCLUSION@#Brain organoids have potential to develop into an innovative platform for pharmacological studies and tissue engineering. However, they are not identical replicas of their in vivo counterpart and there are still a lot of limitations to move forward to clinical applications.

The Usefulness of Duplex Ultrasound for Hemodialysis Access Selection

PURPOSE: A native vessel is preferable to an artificial graft for dialysis access. Duplex ultrasound (DUS) is noninvasive, cost-effective modality to evaluate the vessels for dialysis. The purpose of this study was to compare the rates of utilization of native vessels after preoperative imaging with DUS and contrast venography (CV). MATERIALS AND METHODS: A retrospective review was performed on patients who received an arteriovenous fistula (AVF) or arteriovenous graft (AVG) between June 2006 and July 2010. Patients were classified into 3 groups. In group 1, CV was used to evaluate the vessel. Both DUS and CV were used in group 2. In group 3, only DUS was used. The frequency of utilization of a native vessel was analyzed in each group. The chi-square test was used for statistical analysis. RESULTS: During the study period, 173 patients received an AVF or AVG. Eighty-nine patients were male. The mean age was 60.6±14.6 years. A native vessel was used in 56/81 patients (69.1%) and 74/81 patients (91.4%) in groups 1 and 3, respectively (P<0.001). In group 2, all patients underwent access procedures using native vessels. AVG was initially planned for 2 patients in group 2 after vessel evaluation using CV, but a native vessel was successfully used because DUS identified optimal vessels for AVF. The 1-year primary patency rate was similar in 3 groups. CONCLUSION: Preoperative DUS is safe and easy to use for vessel evaluation, and can be used as a primary imaging modality for creation of access.

The efficacy of oral contraceptive pre-treatment in controlled ovarian hyperstimulation using a GnRH antagonist in low responders / 대한산부인과학회지

OBJECTIVE: This study was performed to evaluate the efficacy of GnRH antagonist multidose protocol (GnRH-ant MDP) with or without oral contraceptive (OC) pretreatment in low responders undergoing IVF-ET, compared with standard GnRH agonist (GnRH-a) lowdose long protocol (LP). METHODS: Eighty-two patients, aged 28-42 years who were defined as low responders were recruited for this prospective study and they were randomized to undergo GnRH-ant MDP after OC pretreatment (group 1) or GnRH-ant MDP without OC pretreatment (group 2) or GnRH-a luteal lowdose LP (group 3). All of the subjects were administered recombinant human FSH (rhFSH) for ovarian stimulation. RESULTS: Patients' characteristics were comparable among three groups. Total dose and duration of rhFSH used for COH were significantly higher in group 3 than those in group 1 or 2. The number of mature oocytes, fertilization rate and the number of grade I, II embryos were significantly lower in group 2 than those in other groups. The clinical pregnancy rate seemed to be lower in group 2 but the difference did not achieve statistical significance. There were also no differences in the miscarriage rate and multiple pregnancy rate among three groups. CONCLUSION: This study demonstrates that GnRH-ant MDP with OC pretreatment is as effective as GnRH-a lowdose LP and might be considered more advantageous because of the short-term and small dose application in low responders.

Clinical Characteristics of Habitual Abortion According to the Etiological Classification / 대한산부인과학회지

OBJECTIVE: To determine the frequency of factors associated with habitual abortion in 198 Korean couples. METHODS: A total of 198 cases at the department of Obstetrics and Gynecology, Asan Medical Center, Korea from July 1989 to December 2001 that were diagnosed as habitual abortions were included in this study. The cases were divided into 2 main groups; a primary habitual abortion group and a secondary habitual abortion group. They were classified according to etiology. RESULTS: The number of primary habitual abortion cases was 157 (79.3%) and that of secondary habitual abortion cases was 41 (20.7%). The mean age and number of previous abortions were not different between the two groups. The etiologic factors of the primary habitual abortions were anatomical (31.8%, 42/132), immunologic (24.2%, 32/132), unexplained (23.5%, 31/132), endocrinologic (15.2%, 20/132), genetic (12.9%, 17/132), and infection (1.5%, 2/132). The factors of the secondary habitual abortions were immunologic (36.8%, 14/38), unexplained (28.9%, 11/38), anatomical (21.1%, 8/38) and endocrinologic (13.2%, 5/38). The successful pregnancy rate following secondary habitual abortion was 42.0% (17/38), significantly higher than that following primary habitual abortion which was 34.8% (50/132) (p-value<0.05). CONCLUSION: The differences in etiologic factors between primary and secondary habitual abortions are statistically significant. The prognosis of a later successful pregnancy was significantly better in cases of secondary habitual abortion.

The effect of oral contraceptive pre-treatment in controlled ovarian hyperstimulation using GnRH antagonist on IVF-ET outcome / 대한산부인과학회지

OBJECTIVE: Recent reports have demonstrated that GnRH antagonists can be successfully used in controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). In these antagonist stimulation cycles, oral contraceptive (OC) pretreatment was used to schedule COH. This study was performed to evaluate the effect of OC pretreatment before COH in the antagonist cycles according to the duration of OC administration in infertile patients undergoing IVF-ET. METHODS: Prospective trial was performed on a total 85 IVF cycles carried out on 85 infertile patients with tubal factor only. Eighty-five patients was allocated randomly to the short term OC user (14-21 days), long term OC user (>or=22 days) and Non-user of OC. In all patients, COH was carried out using GnRH antagonist and recombinant FSH (rFSH). RESULTS: No differences among the three groups were found in numbers of oocytes retrieved, mature oocytes, fertilized oocytes, embryos grade I/II, transferred embryos and clinical pregnancy rate. There were also no differences in total dose and duration of rFSH used for COH among three groups. CONCLUSION: Oral contraceptive pretreatment can be used successfully to schedule patients before COH in GnRH antagonist cycles. The OCs can be administered for extended period as necessary for cycle timing. However OC pretreatment in antagonists cycles does not offer any advantage in COH and pregnancy outcome.

Efficacy of controlled ovarian hyperstimulation using GnRH antagonist in women with polycystic ovary syndrome undergoing IVF-ET / 대한산부인과학회지

OBJECTIVE: GnRH antagonist has been recently developed and has provided a new treatment option for controlled ovarian hyperstimulation (COH). However, the use of GnRH antagonist (GnRH-ant) has been hesitated in women with polycystic ovary syndrome (PCOS) due to their high levels of tonic luteinizing hormone (LH). This study was performed to evaluate the efficacy of 2 kinds of GnRH-ant multidose protocols (MDPs) in infertile women with PCOS undergoing IVF-ET, compared with standard GnRH agonist (GnRH-a) luteal long protocol (LP). METHODS: Sixty-five patients with PCOS, aged 24-38 years were recruited for this prospective study and they were randomized to undergo GnRH-ant MDP during early and late follicular phase (GnRH-ant MDPEL) (group 1), GnRH-ant MDP during late follicular phase (GnRH-ant MDPL) (group 2), or GnRH-a luteal LP (group 3). All of the subjects were pretreated with low dose monophasic oral contraceptives (OCs) and they were administered recombinant FSH for ovarian stimulation. RESULTS: There were no differences in serum concentrations of progesterone and endometrial thickness on the day of hCG injection among three groups but serum concentrations of estrogen are higher in group 3 (GnRH-a luteal LP) than other groups. Total dose and duration of rFSH used for COH were significantly higher in group 3 than those in group 1 or 2. Number of retrieved oocytes, grade I/II embryos, fertilized oocytes were significantly higher in group 3 than those in group 2 but there were no differences in any parameters including IVF results between group 1 and 3. No difference in ongoing pregnancy rate was found among 3 groups. CONCLUSION: The use of the GnRH-ant, especially during early and late stimulation period (GnRH-ant MDPEL) is as effective as GnRH-a LP and might be considered more advantageous because of the short-term and small dose application, and therefore GnRH-ant MDPEL could be cheaper alternative in COH for PCOS women undergoing IVF-ET.

Effects of Pioglitazone on Insulin Sensitivity, Ovarian Function and Intraovarian Stromal Blood Flow in Women with Polycystic Ovary Syndrome / 대한불임학회지

OBJECTIVE: This study was performed to investigate the effects of pioglitazone, an insulin sensitizing agent, on insulin resistance, ovarian function and intraovarian stromal blood flow in patients with polycystic ovarian syndrome (PCOS). MATERIAL AND METHODS: Thirty patients with PCOS, aged 18~34 years, were recruited. Criteria for diagnosis of PCOS were as defined in 2003 Rotterdam consensus. They were treated for 6 months with pioglitazone at a dose of 30 mg/day orally. The hormonal blood profile, fasting serum glucose levels, a glycemic response to 75 g oral glucose tolerance test (OGTT), and an ovarian stromal artery (OSA) blood flow were assessed at baseline and after 6 months of treatment. RESULTS: Eighteen (60.0%) of 30 patients treated with pioglitazone demonstrated a spontaneous ovulation After pioglitazone treatment, fasting insulin concentrations, serum glucose levels after 75 g OGTT significantly decreased (p=0.001, p=0.04, respectively), and fasting glucose to insulin (G/I) ratio significantly increased (p<0.001). The pioglitazone treatment induced a significant reduction in serum LH, testosterone (T) and free T levels (p<0.001, p=0.02, p=0.002, respectively). The resistance index (RI) values of OSA significantly increased after treatment (p<0.001). In analyzing pioglitazone-treated patients according to their body mass index (BMI), nonobese group as well as obese group showed a significant improvement in fasting G/I ratio (p<0.01). The pioglitazone treatment induced a significant reduction in serum LH and free T levels in nonobese group (p<0.001, p<0.05, respectively) as well as obese group (p=0.001, p<0.05, respectively). The RI values of OSA significantly increased in both nonobese and obese groups after pioglitazone treatment (p<0.001, p=0.003, respectively). CONCLUSIONS: Pioglitazone could ameliorate the glycoinsulinemic metabolism, and this beneficial effects of this drug could improve the endocrine-reproductive condition associated with the decrease of ovarian stromal artery blood flow, in both nonobese and obese patients with PCOS.

The expression of epidermal growth factor and fibroblast growth factor-2 in the eutopic endometrium of women with endometriosis / 대한산부인과학회지

OBJECTIVE: To compare the expression of epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) in the eutopic endometrium of women with and without endometriosis. METHODS: Thirty-two women with histologically confirmed endometriosis after laparotomy or laparoscopy were recruited. Twenty-eight women with carcinoma in situ of the uterine cervix, uterine myoma and ovarian tumor but no evidence of endometriosis served as control. Following isolation of total RNA from endometrial tissue and reverse transcription, cDNA samples were amplified by real time PCR to quantify the expression of EGF, FGF-2, and GAPDH genes. RESULTS: Including all menstrual phases, the levels of mRNA expressions of EGF and FGF-2 were not different between the eutopic endometrium of women with and without endometriosis. When analyzed separately according to the 6 menstrual phases, no differences were found between the two groups, either. CONCLUSION: This study shows that the levels of mRNA expressions of EGF and FGF-2 in the eutopic endometrium were not different between women with and without endometriosis.

Analysis of C(-634)G polymorphism in the promotor region of the vascular endothelial growth factor gene in Korean women with endometriosis / 대한산부인과학회지

OBJECTIVE: This study was designed to investigate the association between C(-634)G polymorphism in the promotor region of vascualr endothelial growth factor (VEGF) and endometriosis. METHODS: The genomic DNA was extracted from 100 patients with surgically confirmed endometriosis and 100 control group from July 2003 to June 2004. Following extraction of genomic DNA, genotyping of C(-634)G polymorphism of VEGF gene was performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: There was no significant difference in the frequency of CC genotype between the patients with endometriosis (21%) and the control group (19%). No significant difference in the frequency of allele of -634C was noted between the two groups (43.5% vs 44%), either. CONCLUSION: The C(-634)G polymorphism in the promotor region of VEGF gene is not associated with susceptibility to endometriosis in Korean women.

Resonance frequency analysis of impl-ants with anodized surface oxides / 대한치과보철학회지

The present experimental study was designed to address two issues. The first was to investigate whether oxidation voltage of titanium implants influenced bone tissue responses after an in vivo implantation. The second aim was to investigate secondary stability change after 1 to 3months period. Screw-shaped implants with a wide range of oxide properties were prepared by electrochemical oxidation methods, where the oxide thickness varied in the range of 3-15micrometer. The micro structure revealed pore sizes of 1-3micrometer, the crystal structures of the titanium oxide were amorphous, anatase and a mixture of anatase and rutile type. Bone tissue responses were evaluated by resonance frequency measurements that were undertaken 1 to 3months after insertion in the rabbit tibia. It was concluded that no statistical difference of RFA values was found between the groups, RFA gains after 1month and 3months were calculated.

Preliminary Report on Efficacy of Speculoscopy for Increasing the Sensitivity of Cervical Cancer Screening Test / 대한산부인과학회잡지

OBJECTIVE: Since the accuracy of Pap smear for cervical neoplasm has been questioned, a number of adjunctive tests have been developed. The purpose of this study was to evaluate the accuracy of speculoscopy, a magnified chemiluminescent examination, as compared with that of the Pap smear in the screening of cervical neoplasm. METHODS: A total of 41 women were included in the study. We conducted Pap smear, speculoscopy, and punch biopsy to all subjects. Targeted biopsies were obtained from any suspicious lesions that were found with positive speculoscopy. Women with negative speculoscopy underwent random biopsies. The data were analysed using McNemar's test. RESULTS: Thirty-one out of 41 biopsy specimen were found to have cervical lesion that were worse than CIN I, including 8 cases of invasive cancer. The sensitivity and specificity of Pap smear were 74.2% and 70.0%, respectively. Those of speculoscopy were 93.5% and 60.0%, respectively. When these two tests were combined, the sensitivity was raised to 96.8%, but the specificity declined to 50.0%. Among 9 cases of ASCUS on Pap smear, 6 cases were found to have cervical pathology worse than CIN II, and these were positive on speculoscopy. CONCLUSION: Speculoscopy combined with a Pap smear can increase the detection of cervical lesions compared with the Pap smear alone. In the cases of ASCUS on Pap smear, speculoscopy may be more useful to detect significant pathology.

Effects of Bone Density as Injections of Salmon Calcitonin Micropheres in Ovariectomized Rats

OBJECTIVE: This study was evaluated the bone protective effects of the salmon calcitonin microspheres against the cancellous bone loss in the ovariectomized rats. METHOD: The experimented rats were total 50 Sprague-Dawley female rats. They were divided randomly 5 groups. The treatment was initiated on the first day after surgery and continued for a period of 4 weeks. Bone measurements were performed in the distal femoral metaphysis and 5th lumbar vertebrae with dual energy x-ray absorptiometry at the time of 2nd week and 4th week after drug injection in all groups. RESULTS: The cancellous bone density in the ovariectomized rats treated with high dose of the salmon calcitonin microspheres was significantly higher than that of the free salmon calcitonin-treated ovariectomized rats, but less than that of the sham-operated control rats. CONCLUSION: This study shows that the salmon calcitonin microspheres were evaluated for protection against the can cellous bone loss in the ovariectomized rats. The bone protective effect of the salmon calcitonin microspheres was greater than that of the free salmon calcitonin.

Peritoneo-Amniotic Shunting in Isolated Fetal Ascites of Unknown Origin / 대한산부인과학회잡지

Although sporadic cases of transient fetal ascites have been described, pulmonary hypoplasia or hydrops fetalis may occur as potentially lethal complications of isolated fetal ascites. Antenatal fetal paracentesis may be useful in improving neonatal pulmonary function, however rapid accumulation of fluid after paracentesis usually required repetitive invasive procedures. We successfully treated an isolated fetal ascites with peritoneo- amniotic shunt. Under the ultrasonographic guidence, we inserted a Double-Basket Catheter into the left lower quadrant of fetal abdominal wall at the end of second trimester. Shunt remained in place until the fetus was delivered at term. The peritoneo-amniotic shunt can improve fetal outcome and avoid repeated paracentesis before delivery.

Pain Relief Effect of Calcitonin Injection in Ovariectomized Rats

OBJECTIVE: To confirm the effect of calcitonin injection relieving pain in ovariectomized rats. METHOD: Thirty five Sprague-Dawley rats were randomly divided into five groups (high dose calcitonin group (112 U/ Kg), low dose calcitonin group (56 U/Kg), free calcitonin group, ovariectomy group, control group). To assess the pain in ovariectomized rats, the tail of rats were dived in waters of 50+/-1degrees C. Then the tail withdrawal time was measured (tail withdrawal test). The tail withdrawal test was performed in once a week for eight weeks. RESULTS: 1. At seven and eight weeks after injection, the tail withdrawal time of high and low dose calcitonin group compared with that of ovariectomy group were significantly prolonged (p<0.05). 2. At eight weeks after injection, the tail withdrawal time of free calcitonin group compared with that of ovariectomy group was significantly prolonged (p<0.05). CONCLUSION: The effect of calcitonin injection relieving pain in ovariectomized rats was found.