The Effect of Vanishing Twin on Firstand Second-Trimester Maternal Serum Markers and Nuchal Translucency: A Multicenter Prospective Cohort Study

Background@#The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). @*Methods@#This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. @*Results@#Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment,AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. @*Conclusion@#VT can be considered as an adjustment factor for risk assessment in the secondtrimester serum screening test.

Prenatal Diagnosis of Congenital Heart Diseases and Associations with Serum Biomarkers of Aneuploidy: A Multicenter Prospective Cohort Study

Purpose@#We assessed prenatal detection rates of congenital heart disease (CHD) and associations between maternal serum biomarkers and non-chromosomal CHD in singleton pregnancies. @*Materials and Methods@#This study was conducted as a secondary analysis of data obtained during a multicenter prospective cohort study that investigated the cost-effectiveness of prenatal testing for fetal aneuploidy. We analyzed the prenatal detection rate and accuracy for CHD screening via ultrasound during the second trimester, as well as associations between serum biomarkers and CHDs, in singleton newborns without chromosomal abnormalities. @*Results@#Among 6715 women, 142 (2.1%) newborns were born with CHDs, of which 67 (1.0%) newborns had major CHDs. The prenatal detection rate for all CHDs and major CHDs were 34.5% and 58.2%, respectively. After excluding isolated ventricular septal defects, the detection rate for critical CHDs was 85.9%. Women with low pregnancy-associated plasma protein A (PAPP-A) (<0.4 multiples of the median, MOM) face increased risks of non-chromosomal CHDs [adjusted odds ratio (aOR) 2.76; 95% confidence interval (CI) 1.36–5.13] and major CHDs (aOR 7.30; 95% CI 3.18–15.59), compared to those without CHDs. A higher inhibin A level (≥2.5 MOM; aOR 4.84; 95% CI 1.42–12.46) was associated with non-chromosomal major CHDs. @*Conclusion@#Ultrasonography performed during the second trimester by obstetricians detected over 85% of critical CHDs. Low maternal serum PAPP-A or high inhibin-A was associated with non-chromosomal CHDs. These results may contribute to an improvement in prenatal diagnosis of CHDs.

Validation of a Strict Obesity Definition Proposed for Asians to Predict Adverse Pregnancy Outcomes in Korean Pregnant Women

Background@#People are generally considered overweight and obese if their body mass index (BMI) is above 25 kg/m 2 and 30.0 kg/m 2 , respectively. The World Health Organization proposed stricter criteria for Asians (≥ 23 kg/m2 : overweight, ≥ 25 kg/m2 : obese). We aimed to verify whether this criteria could predict adverse pregnancy outcomes in Korean women. @*Methods@#We included 7,547 Korean women from 12 institutions enrolled between June 2016 and October 2018. Women with no pre-pregnancy BMI data, not Korean, or lost to followup were excluded, leaving 6,331. The subjects were categorized into underweight, normal, overweight, class I obesity, and class II/III obesity based on a pre-pregnancy BMI of < 18.5, 18.5–22.9, 23.0–24.9, 25.0–29.9, and ≥ 30.0 kg/m2 , respectively. @*Results@#Overall, 13.4%, 63.0%, 11.8%, 9.1%, and 2.6% of women were underweight, normal, and overweight and had class I obesity and class II/III obesity, respectively. In the multivariable analysis adjusted for maternal age, a higher BMI significantly increased the risk of preeclampsia, gestational diabetes, preterm delivery caused by maternal-fetal indications, cesarean section, large for gestational age, and neonatal intensive care unit admission. @*Conclusion@#Adverse pregnancy outcomes started to increase in those with a pre-pregnancy BMI ≥ 23.0 kg/m2 after adjusting for maternal age. The modified obesity criteria could help predict adverse pregnancy outcomes in Koreans.

Reliability of society of fetal urology and Onen grading system in fetal hydronephrosis

OBJECTIVE: To evaluate the reliability of the Society for Fetal Urology (SFU) and Onen grading systems for fetal hydronephrosis in prenatal ultrasound according to the level of experience of the examiner. METHODS: We reviewed the prenatal ultrasound images of 146 fetuses (292 kidneys) that were diagnosed as having hydronephrosis between January 2005 and December 2014. One expert and two trainees assessed the prenatal renal ultrasound images using the SFU and Onen grading systems. The three examiners independently assessed each ultrasound image with both grading systems and reassessed the same images after 7 to 14 days. Cohen's kappa statistic was used to estimate intra- and inter-observer reliability in prenatal ultrasound images according to training level. RESULTS: The intra-observer reliability of the SFU grading system (κ 0.873–0.945) showed almost perfect agreement and that of the Onen grading system (κ 0.749–0.913) showed substantial to almost perfect agreement. The overall inter-observer reliability of the SFU grading system (κ 0.620–0.825) showed substantial to almost perfect agreement and that of the Onen grading system (κ 0.618–0.724) showed substantial agreement. The weighted kappa value of inter-observer agreement was 0.223 to 0.400 for SFU grade 1 and 0.064 to 0.346 for SFU grade 3. For Onen grading, the inter-observer agreement was 0.012 to 0.214 for grade 2 and 0.193 to 0.334 for grade 3. CONCLUSION: Both the SFU and Onen grading systems showed good intra-observer agreement in prenatal ultrasonography. The inter-observer agreement was decreased in SFU grades 1 and 3 and Onen grades 2 and 3. Therefore, more focus should be given to SFU grades 1 and 3 and Onen grades 2 and 3 for trainees.

Predictive Value of Preoperative Volume-Based 18F-2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography Parameters in Patients with Resectable Lung Adenocarcinoma / 대한핵의학회잡지

PURPOSE@#This study aimed to investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), which are volume-based PET parameters, using 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in patients with surgically resectable lung adenocarcinoma.@*METHODS@#We retrospectively evaluated 149 patients with lung adenocarcinoma who underwent 18F-FDG PET/CT before surgical resection. Maximum standardized uptake value (SUVmax), MTV, and TLG of the primary tumor with threshold value of SUVmax 30, 40, and 50% were calculated, respectively. To compare the predictive performance of volume-based PET parameters, recurrence-free survival was assessed using the Kaplan-Meier method.@*RESULTS@#The study included 70 males and 79 females with an average age of 65.8 years. The median follow-up time was 45.4 months. Recurrence was observed in 53 patients (35.6%). The mean ± SD SUVmax, MTV30%, and TLG(30%) of the entire cohort were 4.79 ± 2.94, 19.45 ± 24.85, and 56.43 ± 101.88, respectively. The cut-off values of MTV30% and TLG(30%) for recurrence were 11.07 ad 30.56, respectively. The 1-year recurrence-free survival (RFS) rate was 96.5% in low-MTV30% patients compared with 86.2% in high-MTV30% patients (p = 0.018) and 96.0% in low-TLG(30%) patients compared with 88.5% in high-TLG(30%) patients (p < 0.001). On univariate and multivariate analysis, TLG(30%) (HR, 2.828, p < 0.001; HR, 2.738, p < 0.001, respectively) was an independent prognostic factor for predicting recurrence-free survival (RFS).@*CONCLUSION@#TLG(30%) value was observed to be a significant prognostic factor for RFS in patients with lung adenocarcinoma treated by surgical resection.

Clinical significance of sonographic soft markers: A review

Sonographic findings with little or no pathological significance, known as soft markers, are often found in aneuploidy fetuses. After normal screening for the aneuploidy in first trimester, there are no uniform recommendations regarding when to disregard or put on clinical significance in isolated soft markers. Associations between some soft markers and adverse pregnancy outcomes including intrauterine fetal death, preterm birth, fetal growth restriction, and congenital infection have been reported in euploidy fetuses. The present article aims to review recent literatures about the clinical significance of soft markers after normal first trimester combined screening or noninvasive prenatal testing, and propose a simple clinical summary for management of specific soft markers in pregnancies.

Predictive Value of Preoperative Volume-Based 18F-2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography Parameters in Patients with Resectable Lung Adenocarcinoma / 대한핵의학회잡지

PURPOSE: This study aimed to investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), which are volume-based PET parameters, using 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in patients with surgically resectable lung adenocarcinoma.METHODS: We retrospectively evaluated 149 patients with lung adenocarcinoma who underwent 18F-FDG PET/CT before surgical resection. Maximum standardized uptake value (SUVmax), MTV, and TLG of the primary tumor with threshold value of SUVmax 30, 40, and 50% were calculated, respectively. To compare the predictive performance of volume-based PET parameters, recurrence-free survival was assessed using the Kaplan-Meier method.RESULTS: The study included 70 males and 79 females with an average age of 65.8 years. The median follow-up time was 45.4 months. Recurrence was observed in 53 patients (35.6%). The mean ± SD SUVmax, MTV30%, and TLG(30%) of the entire cohort were 4.79 ± 2.94, 19.45 ± 24.85, and 56.43 ± 101.88, respectively. The cut-off values of MTV30% and TLG(30%) for recurrence were 11.07 ad 30.56, respectively. The 1-year recurrence-free survival (RFS) rate was 96.5% in low-MTV30% patients compared with 86.2% in high-MTV30% patients (p = 0.018) and 96.0% in low-TLG(30%) patients compared with 88.5% in high-TLG(30%) patients (p < 0.001). On univariate and multivariate analysis, TLG(30%) (HR, 2.828, p < 0.001; HR, 2.738, p < 0.001, respectively) was an independent prognostic factor for predicting recurrence-free survival (RFS).CONCLUSION: TLG(30%) value was observed to be a significant prognostic factor for RFS in patients with lung adenocarcinoma treated by surgical resection.

The Level of Serum and Urinary Nephrin in Normal Pregnancy and Pregnancy with Subsequent Preeclampsia

PURPOSE: The aim of this study was to evaluate serum and urinary nephrin levels of normal pregnancy to establish a standard reference value and to compare them with patients who subsequently developed preeclampsia (PE). MATERIALS AND METHODS: In this prospective study, 117 healthy singleton pregnancies were enrolled between 6 to 20 weeks of gestation at 2 participating medical centers during October 2010 to March 2012. Urine and serum samples were collected at the time of enrollment, each trimester, and at 4 to 6 weeks postpartum. Enzyme-linked immunosorbent assay for nephrin was performed and samples from patients who subsequently developed PE were compared to the normal patients. RESULTS: Of 117 patients initially enrolled, 99 patients delivered at the study centers and of those patients, 12 (12.1%) developed PE at a median gestational age of 34⁺⁴ weeks (range 29⁺⁵–36⁺⁶). In the normal patients (n=68), serum nephrin level decreased and urinary nephrin level increased during the latter of pregnancy. In 12 patients who subsequently developed PE, a significant rise in the 3rd trimester serum and urinary nephrin levels, compared to the controls, was observed (p<0.001), and this increase occurred 9 days prior to the onset of clinical disease. CONCLUSION: As the onset of PE was preceded by the rise in the serum and urinary nephrin in comparison to normal pregnancy, serum and urinary nephrin may be a useful predictive marker of PE.

Current status of infrastructures of obstetrics and gynecology in South Korea

No abstract available.

Pregnancy Outcomes in Women with Moyamoya Disease: Experiences at a Single Center in Korea

PURPOSE: Moyamoya disease (MMD) occurs predominantly in Korean and Japanese women. The aim of this study was to investigate clinical features and pregnancy outcomes in women with MMD. MATERIALS AND METHODS: We conducted a retrospective chart review of women with MMD who visited our Department of Obstetrics and Gynecology between January 2005 and October 2013. For all study subjects, clinical features, demographic characteristics, and perinatal outcomes were recorded. RESULTS: We identified 28 pregnancies in 22 patients who had been diagnosed with MMD. The mean maternal age at delivery was 31.9+/-3.5 years old. The mean gestational age at delivery was 38.0+/-0.9 weeks. Among the 28 pregnancies, 25 (92.5%) underwent cesarean section; 19 (76.0%) of them were performed under regional anesthesia and six (24.0%) under general anesthesia. The mean newborn weight was 3233.7+/-348.2 g. The 5-minute Apgar score in 85% of the newborns was higher than 8, with no other apparent complications. During the puerperal period, transient ischemic attack symptom or seizure occurred in 4 cases, although patients recovered within a few days. CONCLUSION: For pregnant women with MMD, it is important to control blood pressure and prevent hyperventilation during the intrapartum period, and the best methods of delivery and anesthesia should be considered to avoid unfavorable sequelae. Additionally, a multidisciplinary approach (i.e., neurosurgery) is necessary to constantly manage underlying diseases.

Comparison of the performance of screening test for gestational diabetes in singleton versus twin pregnancies

OBJECTIVE: We compared the performance of the 50-g glucose challenge test (GCT) in singleton versus twin pregnancies and investigated the need for adjusting GCT cutoff values for gestational diabetes mellitus (GDM) in twin pregnancies among Korean women. METHODS: A retrospective chart review was performed in women who underwent GCT at 24 to 28 weeks' gestation and delivered in our department between January 2000 and April 2008. GCT performance was compared between singleton and twin pregnancies for an ideal cutoff value of the GCT for GDM screening. RESULTS: GCT results were available in 3,578 pregnancies (3,435 singleton and 143 twin pregnancies). The mean GCT value was higher in the twin group than in the singleton group. Women in the twin group had a higher mean GCT value (P=0.043) and a higher incidence of GCT > or =130, > or =135, and > or =140 mg/dL (P=0.014, 0.005, and 0.015, respectively). The false positive rate for GCT > or =140 mg/dL was significantly higher in the twin than in the singleton group (P=0.042). The optimal GCT screening cutoff value appears to be > or =145 mg/dL in twin pregnancies. CONCLUSION: Our study demonstrates that the GCT is associated with a higher false positive rate in twin rather than singleton pregnancies. This study suggests we should consider adjusting the GCT cutoff value for GDM in Korean twin pregnancies.

Feasibility of three-dimensional reconstruction and automated measurement of fetal long bones using 5D Long Bone

OBJECTIVE: To evaluate the feasibility of five-dimensional Long Bone (5D LB), a new technique that automatically archives, reconstructs images, and measures lengths of fetal long bones, to assess whether the direction of volume sweep influences fetal long bone measurements in three-dimensional (3D) ultrasound and 5D LB, and to compare measurements of fetal long bone lengths obtained with 5D LB and those obtained with conventional two-dimensional (2D) and manual 3D techniques. METHODS: This prospective study included 39 singleton pregnancies at 26+0 to 32+0 weeks of gestation. Multiple pregnancies, fetuses with multiple congenital anomalies, and mothers with underlying medical diseases were excluded. Fetal long bones of the lower extremities-the femur, tibia, and fibula were measured by 2D and 3D ultrasound, and 5D LB, by an expert and non-expert examiner. First, we analyzed the 3D ultrasound and 5D LB data according to 2 different sweeping angles. We analyzed intra- and inter-observer variability and agreement between ultrasound techniques. Paired t-test, interclass correlation coefficient, and Bland-Altman plot and Passing-Bablok regression were used for statistical analysis. RESULTS: There was no statistical difference between long bone measurements analyzed according to 2 different volume-sweeping angles by 3D ultrasound and 5D LB. Intra- and inter-observer variability were not significantly different among all 3 ultrasound techniques. Comparing 2D ultrasound and 5D LB, the interclass correlation coefficient for femur, tibia, and fibula was 0.91, 0.92, and 0.89, respectively. CONCLUSION: 5D LB is reproducible and comparable with conventional 2D and 3D ultrasound techniques for fetal long bone measurement.

Image Settings Affecting Nuchal Translucency Measurement Using Volume NT(TM) Software

PURPOSE: To evaluate the effects of the deviation from the mid-sagittal plane, fetal image size, tissue harmonic imaging (THI), and speckle reduction filter (SRF) on the measurement of the nuchal translucency (NT) thickness using Volume NT(TM) software. MATERIALS AND METHODS: In 79 pregnant women, NT was measured using Volume NT(TM). Firstly, the three-dimensional volumes were categorized based on the angle of deviation in 10degrees intervals from the mid-sagittal plane. Secondly, the operator downsized the fetal image to less than 50% of the screen (Method A) and by magnifying the image (Method B). Next, the image was magnified until the fetal head and thorax occupied 75% of the screen, and the NT was measured (Method C). Lastly, NT values were acquired with THI and SRF functions on, with each function alternately on, and with both functions off. RESULTS: The mean differences in NT measurements were -0.09 mm (p<0.01) between two-dimensional (2D) and a deviation of 31-40degrees and -0.10 mm (p<0.01) between 2D and 41-50degrees. The intraclass correlation coefficients (ICC) for 2D-NT and NT according to image size were 0.858, 0.923, and 0.928 for methods A, B, and C, respectively. The ICC for 2D-NT and NT with respect to the THI and SRF were 0.786, 0.761, 0.740, and 0.731 with both functions on, THI only, SRF only, and with both functions off, respectively. CONCLUSION: NT measurements made using Volume NT(TM) are affected by angle deviation from the mid-sagittal plane and fetal image size. Additionally, the highest correlation with 2D-NT was achieved when THI and SRF functions were used.

Acute Myeloid Leukemia in Suspected Sepsis after Caesarean Section / 대한구급학회지

The incidence of acute leukemia during pregnancy is extremely rare, and often it is not easy to differentiate it from other diseases associated with pregnancy such as sepsis or hemorrhage. Pregnancy itself is not known to affect the natural course of leukemia; however, complications of leukemia like anemia, infections, and coagulopathy can adversely influence both the fetus and the mother. In this case, a pregnant patient misdiagnosed with septic shock and severe leukocytosis was correctly diagnosed with acute myeloid leukemia after surgical delivery.

Random urine protein/creatinine ratio readily predicts proteinuria in preeclampsia

OBJECTIVE: To assess the diagnostic accuracy of random urine protein-creatinine (P/C) ratio for prediction of significant proteinuria in preeclampsia as an alternative to the time-consuming 24-hour urine protein collection. METHODS: Retrospective record analysis was performed on 140 pregnant women who were admitted with suspicion for preeclampsia from January 2006 to June 2011. Random urine protein and/or 24-hour urine protein levels were assessed and their correlation to random urine P/C ratio and 24-hour urine protein excretion was evaluated. RESULTS: Out of 140 patients, random urine P/C ratio or/and 24-hour urine protein was performed in 79 patients to evaluate significant proteinuria. Of 79 patients, 46 (58%) underwent both tests whereas in 33 women (42%) 24-hour urine collection was not available due to urgent delivery. In 39 cases (85%), significant proteinuria (> or =300 mg/24 hr) was detected with 6 cases (13%) having values over 5,000 mg/24 hr, corresponding to the diagnosis of severe preeclampsia. Random urine P/C ratio highly correlated with 24-hour urine protein excretion (r=0.823, P<0.01). The optimal random urine P/C ratio cutoff points were 0.63 and 4.68 for 300 mg/24 hr and 5,000 mg/24 hr of protein excretion, respectively. with each sensitivity, specificity, and positive and negative predictive values of 87.1%, 100%, 100%, and 58.3%; and 100%, 85%, 50%, and 100%, for significant and severe preeclampsia, respectively. CONCLUSION: Random urine P/C ratio is a reliable indicator of significant proteinuria in preeclampsia and may be better at providing earlier diagnostic information than the 24-hour urine protein excretion with more accuracy than the urinary dipstick test.

Role of IL-15 in Sepsis-Induced Skeletal Muscle Atrophy and Proteolysis / 결핵및호흡기질환

BACKGROUND: Muscle wasting in sepsis is associated with increased proteolysis. Interleukin-15 (IL-15) has been characterized as an anabolic factor for skeletal muscles. Our study aims to investigate the role of IL-15 in sepsis-induced muscle atrophy and proteolysis. METHODS: Mice were rendered septic either by cecal ligation and puncture or by intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg i.p.). Expression of IL-15 mRNA and protein was determined by reverse transcriptase polymerase chain reaction and Western blot analysis in the control and septic limb muscles. C2C12 skeletal muscle cells were stimulated in vitro with either LPS or dexamethasone in the presence and absence of IL-15 and sampled at different time intervals (24, 48, or 72 hours). IL-15 (10microg/kg) was intraperitoneally administered 6 hours before sepsis induction and limb muscles were sampled after 24 hours of sepsis. Cathepsin L activity was determined to measure muscle proteolysis. Atrogin-1 and muscle-specific ring finger protein 1 (MuRF1) expressions in limb muscle protein lysates was analyzed. RESULTS: IL-15 mRNA expression was significantly lower in the limb muscles of septic mice compared to that of controls. Cathepsin L activity in C2C12 cells was significantly lower in presence of IL-15, when compared to that observed with individual treatments of LPS or dexamethasone or tumor necrosis factor alpha. Further, the limb muscles of mice pre-treated with IL-15 prior to sepsis induction showed a lower expression of atrogin-1 and MuRF1 than those not pre-treated. CONCLUSION: IL-15 may play a role in protection against sepsis-induced muscle wasting; thereby, serving as a potential therapeutic target for sepsis-induced skeletal muscle wasting and proteolysis.

COMP-Angiopoietin-1 Stimulates Synovial Proliferation but Suppresses Osteoclast by Enhancing Angiogenesis and Osteoblast Maturation in Collagen-Induced Arthritis

OBJECTIVE: Angiopoietin-1 (Ang1) is a potent angiogenic factor that can increase synovial angiogenesis and also enhance osteoblast maturation and bone formation. However, its role in rheumatoid arthritis (RA) has not been well documented. Thus, we investigated roles of Ang1 in collagen-induced arthritis (CIA). METHODS: A recombinant adenovirus carrying the gene that encodes either cartilage oligomeric matrix protein (AdCOMP)-Ang1 (a modified form of Ang1) or LacZ (AdLacZ) was injected intravenously into CIA mice. Clinical, radiological, histopathological, and immunofluorescent analyses were performed. Serum levels of receptor activators of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) and expression of osteoblast maturation genes were analyzed. RESULTS: AdCOMP-Ang1-injected mice developed more severe inflammation than the AdLacZ-injected mice. However, there were no significant differences in cartilage damage and bone erosion. More PECAM-1-positive blood vessels were seen in the synovium of the AdCOMP-Ang1-injected mice than in those injected with AdLacZ. Interestingly, a lower number of TRAP-positive osteoclasts were observed in AdCOMP-Ang1-injected CIA mice than in the AdLacZ group when comparing sections obtained from joints showing similar synovial proliferation. The serum OPG/RANKL ratio and expression of osteoblast maturation genes, such as runt-related transcription factor 2, bone sialoprotein, type 1 collagen, osteopontin, and osterix, were significantly upregulated in the AdCOMP-Ang1 group. CONCLUSION: COMP-Ang1 facilitates arthritis onset and increases synovial inflammation, but enhances osteoblast maturation, which in turn inhibits osteoclastogenesis by increasing the OPG/RANKL ratio in CIA. Our results suggest that careful investigation is necessary to delineate the possible therapeutic use of COMP-Ang1 as an adjunctive agent, in combination with anti-inflammatory therapies, for the prevention of bone destruction in RA.

Induction of Melanogenesis by Rapamycin in Human MNT-1 Melanoma Cells

BACKGROUND: Melanogenesis is one of the characteristic parameters of differentiation in melanocytes and melanoma cells. Specific inhibitors of phosphatidylinositol 3-kinase (PI3K), such as wortmannin and LY294002, stimulate melanin production in mouse and in human melanoma cells, suggesting that PI3K and mammalian target of rapamycin (mTOR) might be involved in the regulation of melanogenesis. OBJECTIVE: The involvement of the mTOR pathway in regulating melanogenesis was examined using human MNT-1 melanoma cells, and the effects of the potent inhibitor of mTOR, rapamycin, in the presence or absence of alpha-melanocyte-stimulating hormone (alpha-MSH) were evaluated. METHODS: In cells treated with rapamycin, cell viability, melanin content, and tyrosinase (TYR) activity were measured and compared with untreated controls. Protein levels of TYR, tyrosinase-related protein (TYRP)-1, TYRP-2, and microphthalmia-associated transcription factor (MITF) were also analyzed by Western blot. RESULTS: In rapamycin-treated cells, the melanin content increased concomitantly with an elevation in TYR activity, which plays a major role in melanogenesis. There was also an up-regulation of TYR, TYRP-1, and MITF proteins. Combined treatment with rapamycin or wortmannin and alpha-MSH increased melanogenesis more strongly than alpha-MSH alone. CONCLUSION: Rapamycin-induced melanin formation may be mediated through the up-regulation of TYR protein and activity. Furthermore, rapamycin and wortmannin, inhibitors of mTOR and PI3K, respectively, have co-stimulatory effects with alpha-MSH in enhancing melanogenesis in melanocyte cells.

Proliferation and Functional Activity of Human Adipose Tissue-Derived CD146 Positive Endothelial Cells According to Culture Mediums

Use of Human Adipose Tissue as a Source of Endothelial Cells