1.Nootkatol prevents ultraviolet radiation-induced photoaging via ORAI1 and TRPV1 inhibition in melanocytes and keratinocytes
Joo Han WOO ; Da Yeong NAM ; Hyun Jong KIM ; Phan Thi Lam HONG ; Woo Kyung KIM ; Joo Hyun NAM
The Korean Journal of Physiology and Pharmacology 2021;25(1):87-94
Skin photoaging occurs due to chronic exposure to solar ultraviolet radiation (UV), the main factor contributing to extrinsic skin aging. Clinical signs of photoaging include the formation of deep, coarse skin wrinkles and hyperpigmentation.Although melanogenesis and skin wrinkling occur in different skin cells and have different underlying mechanisms, their initiation involves intracellular calcium signaling via calcium ion channels. The ORAI1 channel initiates melanogenesis in melanocytes, and the TRPV1 channel initiates MMP-1 production in keratinocytes in response to UV stimulation. We aimed to develop a drug that may simultaneously inhibit ORAI1 and TRPV1 activity to help prevent photoaging. We synthesized nootkatol, a chemical derivative of valencene. TRPV1 and ORAI1 activities were measured using the whole-cell patch-clamp technique. Intracellular calcium concentration [Ca2+ ] i was measured using calcium-sensitive fluorescent dye (Fura-2 AM). UV-induced melanin formation and MMP-1 production were quantified in B16F10 melanoma cells and HaCaT cells, respectively. Our results indicate that nootkatol (90 μM) reduced TRPV1 current by 94% ± 2% at –60 mV and ORAI1 current by 97% ± 1% at –120 mV. Intracellular calcium signaling was significantly inhibited by nootkatol in response to ORAI1 activation in human primary melanocytes (51.6% ± 0.98% at 100 μM). Additionally, UV-induced melanin synthesis was reduced by 76.38% ± 5.90% in B16F10 melanoma cells, and UV-induced MMP-1 production was reduced by 59.33% ± 1.49% in HaCaT cells. In conclusion, nootkatol inhibits both TRPV1 and ORAI1 to prevent photoaging, and targeting ion channels may be a promising strategy for preventing photoaging.
2.Nootkatol prevents ultraviolet radiation-induced photoaging via ORAI1 and TRPV1 inhibition in melanocytes and keratinocytes
Joo Han WOO ; Da Yeong NAM ; Hyun Jong KIM ; Phan Thi Lam HONG ; Woo Kyung KIM ; Joo Hyun NAM
The Korean Journal of Physiology and Pharmacology 2021;25(1):87-94
Skin photoaging occurs due to chronic exposure to solar ultraviolet radiation (UV), the main factor contributing to extrinsic skin aging. Clinical signs of photoaging include the formation of deep, coarse skin wrinkles and hyperpigmentation.Although melanogenesis and skin wrinkling occur in different skin cells and have different underlying mechanisms, their initiation involves intracellular calcium signaling via calcium ion channels. The ORAI1 channel initiates melanogenesis in melanocytes, and the TRPV1 channel initiates MMP-1 production in keratinocytes in response to UV stimulation. We aimed to develop a drug that may simultaneously inhibit ORAI1 and TRPV1 activity to help prevent photoaging. We synthesized nootkatol, a chemical derivative of valencene. TRPV1 and ORAI1 activities were measured using the whole-cell patch-clamp technique. Intracellular calcium concentration [Ca2+ ] i was measured using calcium-sensitive fluorescent dye (Fura-2 AM). UV-induced melanin formation and MMP-1 production were quantified in B16F10 melanoma cells and HaCaT cells, respectively. Our results indicate that nootkatol (90 μM) reduced TRPV1 current by 94% ± 2% at –60 mV and ORAI1 current by 97% ± 1% at –120 mV. Intracellular calcium signaling was significantly inhibited by nootkatol in response to ORAI1 activation in human primary melanocytes (51.6% ± 0.98% at 100 μM). Additionally, UV-induced melanin synthesis was reduced by 76.38% ± 5.90% in B16F10 melanoma cells, and UV-induced MMP-1 production was reduced by 59.33% ± 1.49% in HaCaT cells. In conclusion, nootkatol inhibits both TRPV1 and ORAI1 to prevent photoaging, and targeting ion channels may be a promising strategy for preventing photoaging.
3.Treatment of Freiberg’s Disease Using the Shortening Effect of the Modified Weil Osteotomy
Tae-Hoon LEE ; Yeong-Hyeon LEE ; Gil-Yeong AHN ; Il-Hyun NAM ; Kyung-Jin LEE ; Sang-Won WOO
Journal of Korean Foot and Ankle Society 2021;25(4):165-170
Purpose:
This study sought to evaluate the clinical effectiveness of the shortening effect of the modified Weil osteotomy for the treatment of Freiberg’s disease.
Materials and Methods:
We reviewed 21 cases treated with the modified Weil osteotomy for Freiberg’s disease from November 2005 to June 2019. The average follow-up period was 32.5 months and the mean age of the patients was 38.3 years. The clinical results were analyzed using the American Orthopaedic Foot and Ankle Society (AOFAS) lesser metatarsophalangeal-interphalangeal scale, the visual analogue scale (VAS), and the range of motion (ROM) of the metatarsophalangeal joint. In the radiologic evaluation, the length of preoperative and postoperative metatarsal shortening was compared.
Results:
The average AOFAS lesser metatarsophalangeal-interphalangeal scale showed an improvement from 60.5 preoperatively to 90.9 at the latest follow-up. VAS showed a decrease from 5.4 preoperatively to 0.9 at the latest follow-up. ROM of the affected metatarsophalangeal joint increased from 40.2 degrees preoperatively to 58.6 degrees at the latest follow-up. The mean length of metatarsal shortening was 6.7 mm. There was no transfer metatarsalgia, osteonecrosis, and definite joint space narrowing.
Conclusion
Modified Weil osteotomy with second layer cutting is an effective treatment option to restore the joint surface and painless joint motion for patients with Freiberg’s disease.
4.Effect of Growth Hormone Secretion on Serum Concentration of Leptin.
Se Eun KIM ; Jeong Nyeo LEE ; Sang Ook NAM ; Woo Yeong CHUNG
Journal of the Korean Pediatric Society 2000;43(7):959-966
PURPOSE: To investigate the effect of growth hormone(GH) secretion on serum concentration of leptin, we evaluated the differences in serum concentration of leptin between patients with growth hormone deficiency(GHD) and GH normal short stature in prepubertal male children, and the relationship between GH and serum leptin level. Also, we analyzed the correlation between serum concentrations of leptin and insulin-like growth factor-I(IGF-I), insulin-like growth factor binding protein-3(IGFBP-3), total cholesterol(TC), free fatty acid(FFA) and body mass index(BMI). METHODS: Eight cases with GHD and 10 cases with GH normal short stature were included in this study. Patients were all male, prepubertal children with mean age 10.6 years. Blood samples were collected in these patients by L-dopa GH provocation test. Statistical analysis of the comparisons of serum leptin level and correlation of multiple variables were performed using PC-SAS program. Significance was defined as P<0.05. RESULTS: The mean serum concentration of leptin in GHD(12.27+/-10.63ng/mL) was significantly higher than in GH normal short stature(5.39+/-3.21ng/mL)(P=0.0344). Serum concentration of leptin was negatively correlated to GH(y=-7.7x+43.3, r=-0.23, P=0.0109). Serum concentration of leptin was positively correlated to BMI(y=2.5x-33.3, r=0.75, P=0.0003). Serum concentration of leptin was not correlated to IGF-I, IGFBP-3, TC and FFA. CONCLUSION: Serum concentration of leptin was siginificantly increased in patients with GHD compared to GH normal short stature and was negatively correlated to GH.
Child
;
Growth Hormone*
;
Humans
;
Insulin-Like Growth Factor Binding Protein 3
;
Insulin-Like Growth Factor I
;
Leptin*
;
Levodopa
;
Male
5.A Case of Traction Retinal Detachment Accompanied by Ocular Syphilis
Jeong Woo HEO ; Nam Yeong KIM ; Yoon Hyung KWON
Journal of the Korean Ophthalmological Society 2022;63(6):542-546
Purpose:
We report a first case of traction retinal detachment accompanied by ocular syphilis in Korea.Case summary: A 20-year-old male visited with poor left-eye vision. His best-corrected visual acuity was 0.3; no inflammation was evident in the anterior chamber, but many inflammatory cells were found in the vitreous cavity. Fundus examination revealed inferior exudative and tractional retinal detachment. Optical coherence tomography revealed an epiretinal membrane; fluorescein angiography showed that the inferior (detached) retina did not fluoresce. Syphilis was serologically detected; ceftriaxone (2 g daily) was intravenously injected for 14 days. The vitreous cavity inflammation improved, but the tractional membrane proliferation triggered tractional retinal detachment. We performed vitrectomy to remove the tractional membrane and prescribed intravitreal antibiotics. The patient was discharged after intravenous injection of penicillin G (20 MU daily) for 14 days. Three months after surgery, the best-corrected left-eye visual acuity had improved to 0.8, and no recurrence of the retinal detachment was noted.
Conclusions
Patients with ocular syphilis may evidence retinal detachment despite initial prescription of systemic antibiotics. A possible need for surgery should be kept in mind; the prognosis is good if an operation is performed in a timely manner.
6.The Association among the Genetic Polymorphism of Dopamine D4 Receptor, Temperament and Alcohol Drinking Behavior in Young Korean Adults.
Yeong Woo NAM ; Sang Ick LEE ; Chul Jin SHIN ; Jung Woo SON ; Sie Kyeong KIM
Journal of the Korean Society of Biological Psychiatry 2011;18(2):101-108
OBJECTIVES: The aim of this study is to explore the association among DRD4 polymorphism, temperament and alcohol drinking behavior of Koreans in their early adulthood. METHOD: Participants were 172 healthy Korean adults (mean age 28.1 +/- 0.8). Their temperament was assessed with the Temperament and Character Inventory (TCI) and their alcohol drinking behavior were evaluated with a self-reported questionnaire including the CAGE and the Korean version of Alcohol Use Disorder Identification Test (AUDIT-K). DRD4 exon III 48 base pair variable number of tandem repeats (VNTR) was genotyped by PCR. RESULTS: No significant association was found between DRD4 polymorphism and TCI temperament dimension (novelty seeking, harm avoidance, reward dependence, and persistence) as well as alcohol drinking behavior scales. However, novelty seeking was significantly associated with alcohol drinking behavior. The higher level of novelty seeking was associated with the higher severity index of drinking (B = -0.225, p < 0.001) and problematic alcohol use on the CAGE and AUDIT-K [Odds Ratio (OR) = 1.111, 95% Confidence Interval (CI) 1.021-1.209, p = 0.015, OR = 1.087, 95% CI 1.009-1.170, p = 0.028]. CONCLUSION: In our study, while there is no significant association of DRD4 polymorphism with temperament and alcohol drinking behavior, novelty seeking affects problematic alcohol use. Results suggest that novelty seeking may play an important role in problematic alcohol use in young Korean adults.
Adult
;
Alcohol Drinking
;
Base Pairing
;
Dopamine
;
Drinking
;
Exons
;
Humans
;
Minisatellite Repeats
;
Polymerase Chain Reaction
;
Polymorphism, Genetic
;
Receptors, Dopamine D4
;
Reward
;
Temperament
;
Weights and Measures
;
Surveys and Questionnaires
7.Suppressors for Human Epidermal Growth Factor Receptor 2/4 (HER2/4): A New Family of Anti-Toxoplasmic Agents in ARPE-19 Cells.
Yeong Hoon KIM ; Lokraj BHATT ; Hye Jin AHN ; Zhaoshou YANG ; Won Kyu LEE ; Ho Woo NAM
The Korean Journal of Parasitology 2017;55(5):491-503
The effects of tyrosine kinase inhibitors (TKIs) were evaluated on growth inhibition of intracellular Toxoplasma gondii in host ARPE-19 cells. The number of tachyzoites per parasitophorous vacuolar membrane (PVM) was counted after treatment with TKIs. T. gondii protein expression was assessed by western blot. Immunofluorescence assay was performed using Programmed Cell Death 4 (PDCD4) and T. gondii GRA3 antibodies. The TKIs were divided into 3 groups; non-epidermal growth factor receptor (non-EGFR), anti-human EGFR 2 (anti-HER2), and anti-HER2/4 TKIs, respectively. Group I TKIs (nintedanib, AZD9291, and sunitinib) were unable to inhibit proliferation without destroying host cells. Group II TKIs (lapatinib, gefitinib, erlotinib, and AG1478) inhibited proliferation up to 98% equivalent to control pyrimethamine (5 μM) at 20 μM and higher, without affecting host cells. Group III TKIs (neratinib, dacomitinib, afatinib, and pelitinib) inhibited proliferation up to 98% equivalent to pyrimethamine at 1–5 μM, but host cells were destroyed at 10–20 μM. In Group I, TgHSP90 and SAG1 inhibitions were weak, and GRA3 expression was moderately inhibited. In Group II, TgHSP90 and SAG1 expressions seemed to be slightly enhanced, while GRA3 showed none to mild inhibition; however, AG1478 inhibited all proteins moderately. Protein expression was blocked in Group III, comparable to pyrimethamine. PDCD4 and GRA3 were well localized inside the nuclei in Group I, mildly disrupted in Group II, and were completely disrupted in Group III. This study suggests the possibility of a vital T. gondii TK having potential HER2/4 properties, thus anti-HER2/4 TKIs may inhibit intracellular parasite proliferation with minimal adverse effects on host cells.
Antibodies
;
Blotting, Western
;
Cell Death
;
Epidermal Growth Factor*
;
Erlotinib Hydrochloride
;
Fluorescent Antibody Technique
;
Humans*
;
Membranes
;
Parasites
;
Protein-Tyrosine Kinases
;
Pyrimethamine
;
Receptor, Epidermal Growth Factor*
;
Toxoplasma
8.Clinical Manifestations and Characteristics in Patients with Horseshoe Kidney.
Yu Kyong KIM ; Nam Hee KWON ; Dong Il KANG ; Woo Yeong CHUNG
Journal of the Korean Society of Pediatric Nephrology 2013;17(2):73-78
PURPOSE: We aimed to investigate the clinical characteristics and associated diseases in children with a horseshoe kidney and compared these data between children and adults. METHODS: We performed a retrospective analysis of the medical records and radiological findings of 43 patients diagnosed with a horseshoe kidney in the Busan Paik Hospital. The subjects were divided into the children's group (14 cases, age <18 years) and the adult group (29 cases, age > or =18 years). RESULTS: The study group consisted of 17 males and 26 females with a median age of 34 years. In the children's group (14 cases), 5 subjects were male and 9 were female, with a mean age of 6.7+/-6.2 years. Most of the subjects were asymptomatic and were incidentally diagnosed with horseshoe kidney during their evaluation for another disease. Among the associated diseases in the children's group, Turner syndrome was the most common (5 cases), whereas ureteropelvic junction (UPJ) stricture was observed in 2 cases (14.2%). None of the children exhibited abnormal renal function during the follow-up period. In the adult group (29 cases), 12 subjects were male and 17 were female, with a mean age of 48 years. Eighteen patients were incidentally diagnosed with horseshoe kidney during their evaluation for another disease, and 11 patients had hematuria or abdominal pain due to renal stones. Among the associated diseases in the adult group, Turner syndrome was the most common (5 cases), and UPJ stricture was observed in 5 cases; the other accompanying diseases included hydronephrosis and overactive bladder. Six patients exhibited decreased renal function (serum creatinine level >1.5) during the follow-up period. CONCLUSION: Horseshoe kidney is usually diagnosed incidentally in both children and adults. In the present study, we noted that Turner syndrome was the most common associated disease in children. In addition, most children were asymptomatic but had a high risk of urologic complications after the transition to adulthood. Therefore, children with horseshoe kidney require continuous follow-up.
Abdominal Pain
;
Adult
;
Child
;
Constriction, Pathologic
;
Creatinine
;
Female
;
Follow-Up Studies
;
Hematuria
;
Humans
;
Hydronephrosis
;
Kidney*
;
Male
;
Medical Records
;
Retrospective Studies
;
Turner Syndrome
;
Urinary Bladder, Overactive
;
Urinary Calculi
;
Urogenital Abnormalities
9.Cardiac Arrest following Epidural Block for Postoperative Pain Control.
Jeong Ae LIM ; Yeong Joo PARK ; Po Sun KANG ; Gyu Chang LEE ; Nam Sik WOO ; Ye Chal LEE
Korean Journal of Anesthesiology 1995;28(4):590-593
The continuous epidural anesthesia is an effective method for postoperative pain control and improvement of pulmonary function. A 39-year-old man was scheduled for postoperative intestinal obstruction. After adhesiolysis under the general anesthesia, epidural anesthesia was done for postoperative pain control. Because an accidental dural puncture was noticed, the adjacent interspace of epidural anesthesia was tried and catheter was inserted. Respiratory depression, hypotension, loss of consciousness and cardiac arrest were developed about 20 minutes after the first injection of 1% lidocain 10ml. Endotracheal intubation was performed and the respiration was controlled using 100% oxygen. Self respiration and alert mentality returned after 180 minutes. No CSF leakage, delayed onset time, severe hypotension, complete recovery may be the result of subdural anesthesia and postoperative hypoxia. But radiological examination was not performed.
Adult
;
Anesthesia
;
Anesthesia, Epidural
;
Anesthesia, General
;
Anoxia
;
Catheters
;
Heart Arrest*
;
Humans
;
Hypotension
;
Intestinal Obstruction
;
Intubation, Intratracheal
;
Oxygen
;
Pain, Postoperative*
;
Punctures
;
Respiration
;
Respiratory Insufficiency
;
Unconsciousness
10.Spatiotemporal Clusters and Trend of Trichomonas vaginalis Infection in Korea
Yeong Hoon KIM ; Hye-Jin AHN ; Dongjae KIM ; Ho-Woo NAM
The Korean Journal of Parasitology 2022;60(2):97-107
This study was done to provide an overview of the latest trichomoniasis status in Korea by finding disease clusters and analyzing temporal trends during 2012-2020. Data were obtained from the Health Insurance Review & Assessment Service (HIRA) of Korea. SaTScan and Joinpoint programs were used for statistical analyses. Gyeonggi-do had the highest average population and highest number of cases. The high incidence of T. vaginalis infections were observed among women aged 40-49 and 30-39 years (33,830/year and 33,179/year, respectively). Similarly, the 40-49 and 30-39 age group in men showed the highest average cases (1,319/year and 1,282/year, respectively). Jeollabuk-do was the most likely cluster, followed by Busan/Gyeongsangnam-do/Ulsan/Daegu and Jeju-do and Gwangju. Urban and rural differences were prominent. Trichomoniasis has decreased significantly in most clusters, except for Incheon. Trichomoniasis was decreasing in women recently after peaking around 2014. Men showed different trends according to age. Trichomoniasis was increasing in the 10-39 age groups, but decreasing in the 40-59 age groups. This study might provide an analytic basis for future health measures, policy-makers, and health authorities in developing effective system for prevention of trichomoniasis.