• Journal of Genetic Medicine
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• v.16 no.2
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• pp.85-89
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• 2019

Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive urea cycle disorder. HHH is caused by a deficiency of the mitochondrial ornithine transporter protein, which is encoded by the solute carrier family 25, member 15 (SLC25A15) gene. Recently, government supported Korean newborn screening has been expanded to include a tandem mass spectrometry (MS/MS) measurement of ornithine level. We report a case of a neonate with HHH syndrome showing a normal MS/MS measurement of ornithine level. A female newborn was admitted to neonatal intensive unit due to familial history of HHH syndrome. Her parents were consanguineous Parkistani couple. The subject's older sister was diagnosed with HHH syndrome at age of 30 months based on altered mental status and liver dysfunction. Even though the subject displayed normal ammonia and ornithine levels based on MS/MS analysis, a molecular test confirmed the diagnosis of HHH syndrome. At 1 month of age, amino acid analysis of blood and urine showed high levels of ornithine and homocitrulline. After 11 months of follow up, she showed normal growth and development, whereas affected sister showed progressive cognitive impairment despite no further hyperammonemia after protein restriction and standard therapy. Our report is in agreement with a previous Canadian study, which showed that neonatal samples from HHH syndrome patients demonstrate normal ornithine levels despite having known mutations. Considering the delayed rise of ornithine in affected patients, genetic testing, and repetitive metabolic testing is needed to prevent patient loss in high risk patients.

• Journal of Life Science
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• v.28 no.7
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• pp.874-883
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• 2018

Osteoporosis is a disease that increases the risk of fracture by decreasing the mass and strength of bone. It is caused by imbalance of osteoclast bone formation and osteoclast bone resorption. Bone formation by osteoblast is activated via bone morphogenetic proteins and runt-related transcription factor 2. $Wnt/{\beta}-catenin$ signaling and bone resorption by osteoclast are initiated by the binding of receptor activator of nuclear $factor-{\kappa}B$ ligand and receptor activator of nuclear $factor-{\kappa}B$. Menopausal women are at risk for many diseases due to hormonal imbalances, and osteoporosis is the most common metabolic disorder in 30% of postmenopausal women. When estrogen is deficient, bone resorption of osteoclasts is promoted, and the risk of osteoporosis especially increases in postmenopausal women. Hormone replacement therapy has been widely used to relieve or treat the symptoms of menopausal syndrome. However, long-term administration of hormone therapy has been associated with a high risk of side effects, such as breast cancer, ovarian cancer, and uterine cancer. Recently, phytochemicals have been actively studied as a phytoestrogen, which has an estrogen-like activity to cope with symptoms of menopausal syndrome. Therefore, in this review, we investigated the differentiation mechanism of osteoblast and osteoclast and the role of estrogen and phytoestrogen in bone metabolism in relation to previous studies.

• Biomedical Science Letters
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• v.8 no.3
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• pp.127-135
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• 2002

Anterior subcapsular cataract was developed by opacification with transdifferentiation and abnormal proliferation of lens epithelial cells (LECs) and pathological accumulation of extracellular matrix (ECM). After-cataract also be caused by a similar transdifferentiation of LECs remaining after surgery and the accompanying increase of ECM deposits. It is blown that prostaglandin E2 and cytokine, such as TGF-$\beta$, bFGF, and IL-1, were associated with abnormal proliferation and transdifferentiation of LECs. The aim of this study was to detect the expression of transforming growth factor-$\alpha$ (TGF-$\alpha$), transforming growth factor-$\beta_1$(TGF-$\beta_1$) and basic fibroblast growth factor (bFGF) in LECs of senile and diabetic cataract. The expressions of these growth factors in lens epithelial cells were determined. The sample for growth factor determination were collected in senile cataract patients without metabolic disorder, especially diabetes mellitus and diabetic cataract patients. The mRNA expression of growth factors was detected by semi-quantitative reverse transcription - polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Statistics were analysed using Wilcoxon rank sum test. Semi-quantitative RT-PCR/southern analysis of RNA obtained from thirty surgical specimens demonstrated that the level of mRNA expression of TGF-$\alpha$, -$\beta_1$ and bFGF was increased in diabetic cataract lens tissues compared with senile cataract specimens but non-significant, bFGF and TGF-$\beta_1$ mRNA expression were detected in most patients, expression level of TGF-$\beta_1$ was most high on the basis of normal ocular concentration. Detection rate of TGF-$\alpha$ in diabetic cataract was 1.5 fold higher than in senile cataract (P=0.098). TGF-$\alpha$, TGF-$\beta_1$, and bFGF mRNA expression of LECs were detected in senile and diabetic cataract. In both patient groups, expression level of TGF-$\beta_1$, mRNA was high, so We suggest TGF-$\beta_1$ strong influence in development of senile cataract and of diabetic cataract also. TGF-$\alpha$ expression level was similar but more frequently detected in diabetic cataract than in senile cataract. In conclusion, TGF-$\alpha$ may be associated with early development of diabetic cataract.

• Clinical and Experimental Pediatrics
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• v.45 no.3
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• pp.413-417
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• 2002

Gitelman's syndrome is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria that has recently been reported to be linked to thiazide- sensitive Na-Cl cotransporter gene mutation. In this study, we performed renal clearance studies to differentiate Gitelman's from Bartter's syndrome and to confirm the diagnosis in two patients clinically diagnosed with Gitelman's syndrome. Each patient was hydrated by 20 mL/kg body weight of oral water within 30 minutes, which was followed by intravenous half saline. When urinary flow reached 10 mL/min, samples of urine and serum were obtained to calculate the osmolar clearance, free water clearance, chloride clearance, and distal fractional chloride reabsorption. Subsequently, furosemide or hydrochlorothiazide was administered. Samples were collected and the same parameters were calculated. In our patients, chloride clearance was increased more than 10 times after furosemide administration(2.1 : 25.7 and 2.2 : 27.4 mL/min/100 mL GFR), but not increased after hydrochlorothiazide treatment(2.1 : 1.6 and 2.2 : 2.6 mL/min/100 mL GFR). And the distal fractional chloride reabsorption was significantly decreased by furosemide injection (73% : 15% and 75% : 4.6%), whereas hydrochlorothiazide had no effect on it(73% : 63% and 75% : 78%). These findings indicate that our patients have a defect in thiazide-sensitive Na-Cl cotransporter in the distal tubule, which is compatible with the pathophysiology of Gitelman's syndrome.

• Clinical and Experimental Pediatrics
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• v.52 no.2
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• pp.256-260
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• 2009

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease affecting mostly children. This disorder is characterized by recurrent episodes of hemoptysis, bilateral diffuse pulmonary infiltrates, and iron-deficiency anemia. An acute fulminant alveolar hemorrhage can be fatal due to respiratory failure, while chronic hemorrhage leads to hemosiderin-laden macrophages and pulmonary fibrosis. Genetic, autoimmune, allergic, environmental, and metabolic mechanisms of pathogenesis have been suggested, but the etiology of IPH remains unknown. We report on a 9-year-old girl with idiopathic pulmonary hemosiderosis who showed seasonal recurrences without cause.

• International Journal of Oral Biology
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• v.35 no.1
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• pp.27-33
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• 2010

Periodontal disease is a major oral disorder and comprises a group of infections that lead to inflammation of the gingiva and the destruction of periodontal tissues. $PPAR{\gamma}$ plays an important role in the regulation of several metabolic pathways and has recently been implicated in inflammatory response pathways. However, its effects on periodontal inflammation have yet to be clarified. In our current study, we evaluated the anti-inflammatory effects of $PPAR{\gamma}$ on periodontal disease. Human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) showed high levels of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), matrix metalloproteinase-2 (MMP-2), and -9 (MMP-9). Moreover, these cells also showed upregulated activities for extracellular signal regulated kinase (ERK1/2), inducible nitric oxide synthase (iNOS) and cyclooxygnase-2. However, cells treated with Ad/$PPAR{\gamma}$ and rosiglitazone in same culture system showed reduced ICAM-1, VCAM-1, MMP-2, -9 and COX-2. Finally, the anti-inflammatory effects of $PPAR{\gamma}$ appear to be mediated via the suppression of the ERK1/2 pathway and consequent inhibition of NF-kB translocation. Our present findings thus suggest that $PPAR{\gamma}$ indeed has a pivotal role in gingival inflammation and may be a putative molecular target for future therapeutic strategies to control chronic periodontal disease.

• Journal of the korean academy of Pediatric Dentistry
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• v.38 no.3
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• pp.284-289
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• 2011

Lesch-Nyhan syndrome is a disease caused by metabolic disorder of purine. General muscle stiffness and hyposomia are shown from infancy and symptoms can include involuntary or irregular movements of arms and legs, mental retardation, and compulsive self-mutilating behaviors. Self-mutilating behaviors begin at approximately the first year or sometimes at late teens. The patients bite their lips, especially lower lip, tongue, buccal mucosa, hands and fingers. Tongue and lips can be injured or mutilated in severe cases. As the patient gets older, self-mutilating behaviors become more serious and extensive and secondary infection of injured areas is possible. Periodic soft tissue damage due to self-mutilating may evolve to cancer. Medical treatment, appliance treatment, extraction of tooth and surgical operation was attempted to control self-mutilaing behaviors. We hereby report the case of child Lesch-Nyhan syndrome patient who has self-inflicted labial damage as chief complaint. When patient was treated with conservate therapy, such as removable or fixed appliance, the frequency of labial damage could be subdued and yielded favorable results.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.2
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• pp.153-160
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• 2017

Data are limited on biological mechanisms underlying the associations of sleep insufficiency with obesity and dyslipidemia. To explore these mechanisms, we investigated appetite-regulating hormones, stress-related hormones, and cardiometabolic indicators in association with sleep fragmentation, which is a type of sleep disorder. In an experimental study, we randomly allocated 40 Wistar male rats aged 7 weeks into four groups; rats with ad libitum sleep and ad libitum intake (Control), those exposed to sleep fragmentation (SF), those with diet restriction (DR), and those exposed to sleep fragmentation and diet restriction (SF+DR). Amongst them, 13-day chronic sleep fragmentation was applied to the SF and SF+DR groups while 50% reduction in chow intake was applied to the DR and SF+DR groups for 13 days. After these experiments, blood lipid and lipoprotein profiles, leptin, ghrelin, adiponectin, cortisol, epinephrine, and norepinephrine levels were compared among the four groups. In the results, the SF group showed the highest levels of serum ghrelin (P<0.001) and the lowest levels of serum adiponectin (P<0.01). All experimental groups showed higher levels of low density lipoprotein-cholesterol (LDL-C) than the Control (P<0.001). LDL-C levels and the ratio of LDL-C and high density lipoprotein-cholesterol were positively correlated with ghrelin levels (P<0.05) in the SF group, but not in the DR and SF+DR groups. In the SF group, the highest levels of serum free fatty acids were also observed and correlated with lower levels of serum adiponectin, which reflects insulin resistance (P<0.05). Based on these findings, we suggest that chronic sleep fragmentation may induce disturbances in lipid metabolism and appetite-regulating hormones independent of food intake, and these metabolic disturbances may be worse due to insulin resistance related to overeating, which is indicated by elevated ghrelin levels in sleep fragmentation. For persons with sleep insufficiency, anti-atherogenic dietary interventions may be recommended to prevent cardiovascular disease.

• Journal of Life Science
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• v.25 no.11
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• pp.1324-1330
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• 2015

The present study was performed to analyze and review the physical and immune responses to overtraining syndrome in humans. Overreaching refers to the initial phage of overtraining syndrome and has been known as a physical fatigue which is mainly from metabolic imbalance. It has been known that overtraining also results in a loss of adaptability which may lead to an attenuation of exercise performance, sleeping disorder, central fatigue, neurohormonal changes, difficulty recovery to physical stress, and immunological changes. Additionally, overtraining syndrome is characterized by persistent fatigue, poor performance in sport due to the prolonged and strenuous physical training. Also, previous studies reported that endurance athletes experienced a high incidence of URTI during intense training and the post training. And also, high-performance athletes reported that suppression of cell mediated and anti-body mediated immune function. NK cell numbers were also reduced in the period of overtraining syndrome. Major components of prevention and treatment for the overtraining syndrome are screening, education, and detraining. Furthermore, the combination of these prevention and treatment strategies will be much helpful. Therefore, the current review will be helpful for athletes and individuals who are at the risk of overtraining syndrome.

• Clinical and Experimental Reproductive Medicine
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• v.36 no.1
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• pp.71-80
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• 2009

Objective: PCOS is one of the most common endocrine disorder affecting reproductive age women. It shows wide range of reproductive and metabolic manifestations. This study was to determine the differences of clinical and laboratory characteristics between adolescent and adult Korean Daegu Kyungpook PCOS patients. We also compared clinical and laboratory values of Korean PCOS patients to Turkish and American PCOS patients. Methods: 88 cases were diagnosed and enrolled as PCOS patients, based on 2003 Rotterdam criteria, who visited KNUH Reproductive Endocrinology division between Jan. 2000 and Apr. 2008. We retrospectively reviewed clinical characteristics, serum hormone levels, ultrasono-graphic findings. And we divided into 2 groups, adolescent and adult. We analyzed them with Chi-square test and Student's t-test statistically. Results: There were no statistically significant differences between adult and adolescent Korean PCOS patients. The prevalence of hyperandrogenism such as facial acne or hirsutism, obesity, and insulin resistance of Korean PCOS women was significantly lower than Turkish and American PCOS women. Conclusion: From the results of this study, we can suggest that it is sure that there are differences of clinical and laboratory characteristics of PCOS patients between races. Genetic background, dietary habits and life style affect the expression of clinical symptoms of PCOS. But we could not find out the difference between adolescent and adult PCOS patients of same race. It might be due to the limitation of small patient number and narrow range of age distribution. So, there must be large scale and multi-center and multi-regional study.