• Korean Journal of Psychosomatic Medicine
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• v.27 no.1
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• pp.60-68
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• 2019

Objectives : The association between thyroid-related hormones and cognitive function has been controversial. The purpose of this study is to compare the levels of thyroid-related hormones in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Furthermore, we investigated the relationship between thyroid-related hormones and cognitive function. Methods : From January 2011 to December 2018, we retrospectively reviewed 105 patients who were diagnosed with AD and MCI by visiting a dementia clinic at Ilsan Paik Hospital. Thyroid-related hormones [triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH)] was measured using chemiluminescent immunoassay. An independent sample t-test was performed to analyze the mean value of thyroid-related hormones in patients of AD and MCI. To investigate whether thyroid-related hormones correlate significantly with Global deterioration scale (GDS), Clinical dementia rating (CDR) and scores of each The Korean version of the consortium to establish a registry for Alzheimer's disease items, we conducted a partial correlation analysis with geriatric depression scale-Korean version (GDS-K) scores as covariates. Results : There was no significant difference in the mean serum T3, T4 and TSH levels between patients of the AD and the MCI, but the Construction Praxis Test (CPT) showed a significant positive correlation with the serum TSH concentration (p-value=0.004). Conclusions : In our study, the positive correlation between serum TSH level and the CPT associated with executive function was found to be helpful in understanding the association between thyroid-related hormones and the pathophysiology of dementia. Prospective studies in regard of the pathophysiology of thyroid-related hormones on cognitive function will be necessary in the future.

• The Journal of Internal Korean Medicine
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• v.39 no.1
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• pp.84-96
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• 2018

Objective: This is aprospective clinical case study that includes the administration of Ahnjeonbaekho-tang (AJBHT) to patients who have suffered from Graves' disease for the 8 weeks of the clinical research. Methods: Without administration of an antithyroid drug, AJBHT was administered 3 times a day for 8 weeks. In Case 1, AJBHT without modification was administered and in Case 2, in accordance with the patients' symptoms, a dose of Gypsum Fibrosum was increased by 4g from the beginning of week 2, and further increased by 16 g, for a total of 20 g between week 6 and week 8. Body mass index (BMI), thyroid function test (TFT), thyroid autoantibody test, complete blood cell count (CBC), and blood chemistry (BC) tests were conducted at an interval of 4 weeks, for a total of 3 times during the study. The clinical manifestations, a spectrum of symptoms of the patients, was observed by Wayne's Index, Euro-QOL-5 Dimension (EQ-5D), and Perceived Stress Scale (PSS). Results: In both cases, an acceptable significance of reduction of value in T3, fT4, Thyroid stimulating antibody (TSAb) and Thyroid stimulating hormone receptor antibody (TSH-R-Ab) was observed. After treatment, in TFT, T3 decreased by 31.66%, fT4 decreased by 32.82% in Case 1, and T3 decreased by 43.42%, and fT4 decreased by 37.32% in Case 2. In the thyroid autoantibody test, TSAb decreased by 7.59%, and TSH-R-Ab decreased by 53.19% in Case 1, and TSAb decreased by 33.45%, TSH-R-Ab decreased by at least 7.75% in Case 2. Besides this, there was a decreasing trend of Wayne's index, and a loss of typical symptoms of hyperthyroidism also declared the efficacy. Conclusion: From these results, AJBHT is very effective in the regulation of TFT and improving the symptoms of hyperthyroidism, and is also expected to be an effective alternative to antithyroid drugs for patients who have side effects or drug intolerance.

• Journal of Sasang Constitutional Medicine
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• v.28 no.2
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• pp.132-146
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• 2016

Objectives This study's object was to observe the comparative effects of Yangkyuksanhwa-tang, Palmulgunja-tang and Cheongpyesagan-tang on the chronic LT4(levothyroxine) induced hyperthyroidism in rats.Methods Six groups, each of 8 rats in group, were used in this study. Saline and distilled water treated rats are intact control group. Hyperthyroidism was induced by daily subcutaneous LT4 300 μg/kg treatment for 27 days(LT4 control). Since 12th LT4 treatment PTU(propylthiouracil) 10 mg/kg was intraperitoneal injected(PTU group) and aqueous extracts of Yangkyuksanhwa-tang, Palmulgunja-tang and Cheongpyesagan-tang(YS, PG and CS) 500 mg/kg were orally administrated(YS, PG, CS group), once a day for 15 days. The differences in the body, thyroid gland and epididymal fat pad weights, serum T3(tri-iodothyronine), T4(thyroxine), TSH(thyroid-stimulating hormone), thyroid gland and epididymal fat pad histopathology, liver weight, AST(asparte aminotransferase), ALT(alanine aminotransferase) concentrations, hepatic lipid peroxidation, GSH(glutathione), SOD(superoxide dismutase), CAT(catalase) activities, liver histopathology were observed to evaluate effects on hyperthyroidism, liver damages and antioxidant effects.Results As results of LT4 treatment, hyperthyroidism and related liver damages such as lower body, thyroid weights, higher serum T3, T4, AST, ALT levels, thinner follicular lining epithelium in thyroid glands were observed. However, these symptoms were inhibited by oral treatment of YS, PG and CS. As compared with PTU treatment, these herbal prescriptions showed lower overall efficacy on the hyperthyroidism, but YS showed more favorable effects on the hepatic antioxidant defense systems.Conclusions This results suggest that YS, PG and CS favorably control the LT4 induced hyperthyroidism and related liver damages in rats through modulation of the hepatic antioxidative defense systems.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.1
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• pp.41-64
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• 2014

Objectives: This study was to evaluate the effect of Jaeumkanghwa-tang (JEKHT) on the propylthiouracil (PTU)-induced rat hypothyroidism. Methods: Six groups, each of 8 rats per group were used in the present study - intact vehicle control, PTU control, Levothyroxine ($LT_4$), JEKHT 500, 250 and 125 mg/kg treated groups. JEKHT were administered once a day for 42 days as an oral dose of 500, 250 and 125 mg/kg, and hypothyroidism was induced by daily subcutaneous treatment of PTU 10 mg/kg for 28 days. The changes on the body and organ weight, serum hormone and lipid profiles, liver and testis antioxidant defense factors were observed with histopathology of organs. Results were compared with $LT_4$ 0.5 mg/kg intraperitoneally treated rats in this experiment. Results: PTU treatment, marked decrease of body weight, increases of thyroid weight, decreases of liver, testis, epididymis and prostate weights, decreases of serum Tri-iodothyronine ($T_3$), and Thyroxine ($T_4$) level with increase of serum Thyroid-stimulating hormone (TSH) level, decreases of serum testosterone and dihydrotestosterone (DHT) level with increases of serum Follicular stimulating hormone (FSH) level, increases of serum High density lipoprotein (HDL), decrease of triglyceride content, increase of serum Aspartate aminotransferase (AST) level, decreases of liver and testis antioxidant defense factors were observed. In addition, marked hyperplasia of follicular cells with decreases of follicular colloid contents and diameters was additionally demonstrated with the decrease of hepatocyte numbers per unit area due to hypertrophy of hepatocytes related to lipid droplet depositions, increase of a/oligospermatic epididymal tubules with epididymal atrophic changes, seminiferous tubular atrophy with decrease of stage I~II seminiferous tubules in testis, prostate tubular atrophic changes at histopathological inspections. However, these PTU induced hypothyroidism and related hepatic and male reproductive organ damages were favorably and dose-dependently inhibited by treatment of JEKHT 500, 250 and 125 mg/kg, and JEKHT also effectively regulated the PTU-induced abnormal antioxidant defense factor changes in the both liver and testis. Conclusions: JEKHT 500, 250 and 125 mg/kg dose-dependently inhibited PTU-induced hypothyroidism and related liver and male reproductive organ damages in rats.

• Clinical and Experimental Pediatrics
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• v.57 no.6
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• pp.287-291
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• 2014

Moyamoya disease is a cerebrovascular condition that results in the narrowing of the vessels of the circle of Willis and collateral vessel formation at the base of the brain. Although relationships between Graves' disease and cerebrovascular accidents in Moyamoya disease are obscure, the coexistence of the two diseases is noteworthy. Moyamoya disease has been rarely reported in adolescent patients with thyrotoxicosis. Recently, we encountered two adolescent Korean patients with Moyamoya disease associated with Graves' disease who presented with episodic right-sided hemiparesis and syncope. These two girls who had Graves' disease had no history of other diseases or head trauma. A thyroid function test revealed a euthyroid state and a high thyroid-stimulating hormone (TSH) receptor antibody titer at that time. The patients were diagnosed with Moyamoya disease based on brain magnetic resonance angiography and cerebral four-vessel angiography. The patients underwent cranial revascularization by encephalo-duroarterio-synangiosis as soon as a diagnosis was made, which resulted in successful symptom resolution. They fared well and had no additional neurological symptoms as of their last follow-up visits. Here, we report these two cases of confirmed Moyamoya disease complicated by Graves' disease with a review of the literature, and discuss the possible association between the two diseases. To our knowledge, this is the first report in South Korea on Moyamoya disease associated with Graves' disease in adolescents with a euthyroid.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.5
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• pp.679-686
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• 2012

This study was to elucidate the effects of Ukgan-san on the hyperthyroidism induced by sodium levothyroxine. Hyperthyroidisms were induced by continuous subcutaneous treatment of LT4, 0.3 mg/kg, once a day for 27days, and 1,500, 1,000 and 500 mg/kg of Ulkansan extracts were orally administered, once a day for 15 days from 12th LT4 treatment, and the changes on the body, thyroid gland, liver and epididymal fat pad weights, serum triiodothyronine(T3), thyroxine(T4), thyroid-stimulating hormone(TSH), asparte aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, hepatic lipid peroxidation(LPO), glutathione(GSH), superoxide dismutase(SOD) and catalase(CAT) activities were investigated with throid gland, liver and epididymal fat pad histopathological changes. The effects of Ukan-san extracts were compared with that of propyl thiouracil(PTU), a standard antithyroidic drug 10 mg/kg(intraperitoneally). 1,500 and 1,000 mg/kg of Ukan-san extracts reversed all LT4-induced hyperthyroidisms and these effects indicating their potential in the regulation of hyperthyroidism. Further, the Ukan-san extract normalized LT4-induced liver oxidative stresses, and also reduced liver damages and epididymal fat pad reducements suggesting its antioxidative and relative organ protective nature. However, nor favorable effects on LT4-induced hyperthyroidisms were detected in Ulkansan 500 mg/kg treated rats as compared with LT4 control rats in the present study. These effects of Ukan-san may help improvement of hyperthyroidisms and accompanied various organ damages.

• Genomics & Informatics
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• v.19 no.3
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• pp.29.1-29.10
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• 2021

In our previous studies, we have demonstrated the association of certain variants of the thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (TG) genes with congenital hypothyroidism. Herein, we explored the mechanistic basis for this association using different in silico tools. The mRNA 3'-untranslated region (3'-UTR) plays key roles in gene expression at the post-transcriptional level. In TSHR variants (rs2268477, rs7144481, and rs17630128), the binding affinity of microRNAs (miRs) (hsa-miR-154-5p, hsa-miR-376a-2-5p, hsa-miR-3935, hsa-miR-4280, and hsa-miR-6858-3p) to the 3'-UTR is disrupted, affecting post-transcriptional gene regulation. TPO and TG are the two key proteins necessary for the biosynthesis of thyroid hormones in the presence of iodide and H₂O₂. Reduced stability of these proteins leads to aberrant biosynthesis of thyroid hormones. Compared to the wild-type TPO protein, the p.S398T variant was found to exhibit less stability and significant rearrangements of intra-atomic bonds affecting the stoichiometry and substrate binding (binding energies, ΔG of wild-type vs. mutant: -15 vs. -13.8 kcal/mol; and dissociation constant, K_d of wild-type vs. mutant: 7.2E^-12 vs. 7.0E^-11 M). The missense mutations p.G653D and p.R1999W on the TG protein showed altered ΔG(0.24 kcal/mol and 0.79 kcal/mol, respectively). In conclusion, an in silico analysis of TSHR genetic variants in the 3'-UTR showed that they alter the binding affinities of different miRs. The TPO protein structure and mutant protein complex (p.S398T) are less stable, with potentially deleterious effects. A structural and energy analysis showed that TG mutations (p.G653D and p.R1999W) reduce the stability of the TG protein and affect its structure-functional relationship.

• The Journal of Korean Medicine
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• v.29 no.4
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• pp.180-193
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• 2008

Objectives: We intended to identify factors related to the severity of hot flush of climacteric women from an East-West medical point of view. Methods: We surveyed 446 climacteric women who had received Korean oriental medical questionnaires about clinical symptom patterns and health medical examinations at Kyung-Hee University Medical Center over 1 year, from June 2007 to May 2008. Then, we compared hot flush with clinical symptom pattern and health medical examination result. Results: As the severity of hot flush increased, hypnagogic disorder in sleep pattern, abdominal gaseous distention in digestion pattern, tenesmus in evacuation pattern, yellow or reddish urine in voiding pattern, spontaneous sweating in sweating pattern, chest oppression in psychologic pattern, not-pulling-bedclothes in cold-heat pattern and mouth dryness in craniocervical symptom increased (p<0.05). In relation to digestion pattern, the severity of hot flush showed statistical significance according to prevalence of gastritis diagnosed by gastroscopy and upper GI series(p<0.01). In relation to voiding pattern, the severity of hot flush showed statistical significance according to prevalence of urine protein diagnosed by urinalysis (p<0.05). In relation to sweating, psychologic & cold-heat pattern, triiodothyronine (T3) increase and thyroid stimulating hormone (TSH) decrease were significantly correlated as the severity of hot flush increased (p<0.01). Conclusions: The result showed that hot flush of climacteric women had to be considered in respect of digestion disorder related to gastritis and sweating psychologic cold-heat disorder related to thyroid hormone.

• Korean Journal of Veterinary Research
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• v.36 no.3
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• pp.699-707
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• 1996

This study was designed to examine the involvement of lead in function of target organ, and the protective effect of selenium in lead-treated guinea pigs for 8 weeks. The effects of exposure to 0.5% lead acetate(lead) and/or 4ppm sodium selenite(selenium) in feed on serveral aspects were evaluated by measuring thyroid stimulating hormone(TSH), triiodothyronine($T_3$), thyroxine($T_4$), serum biochemical activities, organ weights, and serum and organ lead concentrations in growing animals. The many indicators of endocrine function(TSH, $T_3$, and $T_4$ in serum), enzyme and biochemical activities(${\alpha}$-glutamyltranspeptidase, alkaline phosphatase, lactate dehydrogenase, triglyceride, creatinine, $Ca^{2+}$ in serum), and organ weights(kidney, spleen and testis) were correlated with lead exposure or showed significantly different mean values between the exposed and controls. These changes on some aspects were reversed by combination-fed of selenium, but did not statistically significant. The organ(kidney, liver, spleen, testis and brain) and serum lead concentrations of lead-fed group were clearly higher than that of controls. Selenium supplementation resulted in a significant protection against lead accumulation in liver and testis. These results suggest that lead can cause a toxic effect on several organ and that selenium seems to has a protective effect on specific reaction by lead-induced organic function toxicity.

• Biomedical Science Letters
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• v.13 no.2
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• pp.157-160
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• 2007

Endoplasmic reticulum (ER) plays formation of disulfide bonds and proper folding of secretory proteins. Cellular responses to ER stress enhances the stress-activated kinase pathway and the induces a lot of immediate-early genes. Among of them, the early growth response-1 (Egr-1), a transcription factor, which plays an important role in cell growth, development, differentiation, apoptosis and various types of injury. For that reason, we have tested the expression of Egr-1 against ER stress inducible drugs (tunicamycin, DTT, A23187 and BFA) to understand what kind of aspect occurred by ER stresses.