The prevalence of obesity is rapidly growing throughout the developing and developed world. Given the seriousness of obesity, it critically needs to develop new therapeutic ways to defend against its growth. Persistent increase in food intake is a primary cause of the energy imbalance. The arcuate nucleus of the hypothalamus is a key region to integrate signals originating from various regions in periphery and leptin resistance in the central nervous system (CNS) contributes to the impaired regulation of food intake. It has been endeavor to treat obesity by understanding the mechanisms of CNS regulation of food intake. Adipose tissue has been regarded as a tumor because of its reversible expansibility and dependency on vasculature. There has been a challenge to starve adipose tissue by inhibiting adipose tissue vasculature. A peptide to cause apoptosis of endothelium only in white adipose tissue greatly loses body weight by reducing food intake independent of the action of leptin. This study provides convincing evidence for a previously unknown relationship between the status of adipose tissue vasculature and the regulation of food intake that may provide a novel way for decreasing body fat. However, the mechanism by which the inhibition of angiogenesis in white adipose tissue decreases food intake and body weight remains unclear. In this review, we describe the potential mechanisms of regulation of food intake induced by inhibition of angiogenesis in white adipose tissue.
Adipose Tissue ; Adipose Tissue, White ; Apoptosis ; Arcuate Nucleus ; Body Weight ; Central Nervous System ; Dependency (Psychology) ; Eating ; Endothelium ; Hypothalamus ; Leptin ; Obesity ; Prevalence

Bone age is important to evaluate growth status and remaining growth. The Greulich and Pyle atlas is widely used and is so far the most common assessment method of bone age. However, this technique has some limitations, especially during puberty : (1) 11.5 and 12.5 years of bone age in girls and 14.5 years of bone age in boys are not represented in the atlas ; (2) Hand and wrist radiographs are difficult to assess between 11 and 13 years of bone age in girls and between 13 and 15 years of bone age in boys. Sauvegrain et al. developed a method to assess bone age by using elbow radiographs(AP& lateral projections) during pubertal age. Between 11 and 13 years of bone age in girls and between 13 and 15 years of bone age in boys, the olecranon apophysis is characterized by clear morphological development. This method is a reliable tool to assess bone age during puberty because significant morphological changes in the elbow happened every six months.
Elbow ; Hand ; Olecranon Process ; Puberty ; Wrist

PURPOSE: The aim of this study was to evaluate growth status using the insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) concentrations in children with subclinical hypothyroidism (SCH). METHODS: The study included 93 SCH patients (33 males and 60 females, age 8.1+/-1.9 years) and 94 healthy control subjects (31 males and 63 females, age 8.0+/-0.7 years). Patients' height and weight were measured, and their body mass index (BMI) and Z-scores were calculated. The relationship between growth parameters, including IGF-I and IGFBP-3 concentrations and thyroid functions (thyroid-stimulating hormone (TSH) and free thyroxine 4 (fT4) was explored. RESULTS: Although weight and BMI were greater in SCH patients, the Z-score of height, weight and BMI, and serum IGF-I and IGFBP-3 levels in SCH children were not significantly different compared to the control. In SCH patients, TSH showed a negative correlation with weight Z-scores (r=-0.23, P=0.028) and BMI Z-scores (r=-0.21, P=0.048). FT4 showed a positive correlation with IGFBP-3. CONCLUSION: The positive correlation of fT4 and IGFBP-3 and the negative relationship between TSH and weight and BMI Z-scores in SCH children suggest that subnormal thyroid functions could be related to growth impairment.
Body Mass Index ; Child ; Female ; Humans ; Hypothyroidism ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Male ; Thyroid Gland ; Thyroxine

PURPOSE: IGFBP-3 leads to the induction of insulin resistance in 3T3-L1 adipocytes. We carried out a series of experiments to elucidate the effects of IGFBP-3 on adipokines and gene expressions. METHODS: We treated fully-differentiated 3T3-L1 adipocytes with IGFBP-3 (0.5, 1, and 2 microg/mL) for one day and measured the mRNA levels of adiponectin, leptin, resistin, and TNF-alpha by RT-PCR, and adiponectin, leptin, resistin, and IL-6 protein levels in the culture supernatant were measured using multiplex adipokine assay ELISA Kits (Linco Research, St. Charles, Missouri). Gene expression in 3T3-L1 adipocyte cells using a microarray method was performed. RESULTS: IGFBP-3 inhibited the expression of adiponectin, leptin, resistin, and TNF-alpha mRNA. IGFBP-3 at 0.5 and 1 micro/mL decreased adiponectin release, but IL-6 release was increased at 2 micro/mL IGFBP-3. A dose-dependent inhibition of leptin was released by IGFBP-3 at 50%. Resistin release was decreased by 40%. The effect of IGFBP-3 on the gene expression in 3T3-L1 adipocyte cells using a microarray assay related to an increase of agouti-realted proteins (Agrp) and Janus kinase 2 (JAK2), and a decrease of the ras homolog gene family (Rhoq), acyl-CoA synthetase long-chain family member 6 (Acsl6), and the interleukin-1 receptor-associated kinase 1 (Irak1). CONCLUSION: IGFBP-3 regulates several adipokines gene expressions that are known to modulate insulin sensitivity, and this regulation may be attributable to the insulin resistance effect of IGFBP-3 on adipocytes.
Adipocytes ; Adipokines ; Adiponectin ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Humans ; Insulin Resistance ; Insulin-Like Growth Factor Binding Protein 3 ; Interleukin-1 Receptor-Associated Kinases ; Interleukin-6 ; Janus Kinase 2 ; Leptin ; Ligases ; Proteins ; Resistin ; RNA, Messenger ; Tumor Necrosis Factor-alpha

PURPOSE: The purpose of this test was to investigate the changes of serum IGF-1 and IGFBP-3 levels during a one-year gonadotropin releasing hormone agonist (GnRHa) treatment in central precocious puberty (CPP) girls. METHODS: From 2007 to 2009, 26 girls were enrolled in this study. They were diagnosed as having central precocious puberty and were treated with GnRHa (leuprolide actete) for one year. Their height, bone age, and serum IGF-1 and IGFBP-3 levels were evaluated every six months. RESULTS: At the time of diagnosis, their mean serum IGF-1 and IGFBP-3 levels were 302.90+/-102.54 ng/mL and 3,103.58+/-705.08 ng/mL, respectively. At six month after treatment, the serum IGF-1 and IGFBP-3 levels were slightly decreased. One year later, IGF-1 concentrations were higher than before treatment and IGFBP-3 levels were lower (P=NS). This result, however, was not statistically significant. CONCLUSION: Gonadal suppression with gonadotropin releasing hormones inversely influenced circulating IGF-1 and IGFBP-3 levels. However, the serum IGF-1 and IGFBP-3 levels were maintained at relatively steady levels, preserving a normal height velocity.
Gonadotropin-Releasing Hormone ; Gonadotropins ; Gonads ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Puberty, Precocious

PURPOSE: Diverse cytokines influence the pathogenesis of type 1 diabetes mellitus (T1DM) in different ways. We studied the profile of cytokines in sera from type 1 diabetic patients at diagnosis. METHODS: Serum levels of 11 cytokines (IL-1alpha, IL-1beta, IL-1Ra, IL-2, IL-4, IL-6, IL-10, IL-12 (p70), INF-gamma, and TNF-alpha) from 38 newly-diagnosed T1DM patents and 39 healthy controls were measured, using multiplex immunoanalytic xMAP. RESULTS: Patients showed significantly higher levels of IL-1beta (P < 0.01), IL-10 (P < 0.01), and TNF-alpha (P = 0.019), than the healthy controls. In 12 of 35 patients, the insulin autoantibody (IAA) was positive (34%) and the level of IAA was correlated with IL-10 (r = 0.454, P = 0.006), and TNF-alpha (r = 0.368, P = 0.030). CONCLUSION: These results suggest that IL-1beta, TNF-alpha, and IL-10 play a role in the pathogenesis of T1DM, and the level of the IAA is correlated with IL-10 and TNF-alpha.
Autoantibodies ; Cytokines ; Diabetes Mellitus, Type 1 ; Humans ; Insulin ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-10 ; Interleukin-12 ; Interleukin-1beta ; Interleukin-2 ; Interleukin-4 ; Interleukin-6 ; Tumor Necrosis Factor-alpha

As a result of recent advances in life science and technology, various therapeutic drugs have been developed and active research in the fields of medicine for the development of novel drugs are under progress. Among these researches, the Drug Delivery System (DDS) is an advanced technology that effectively delivers therapeutic drugs to desired targets and thereby reduces adverse effects and increases efficacy. The application of this technology in the industry is technology-intensive and high value-added and therefore suitable for Korea's condition which is poor of material resources while abundant of human resources. Therefore there are many efforts in developing DDS as a major fundamental industry in Korea. Therefore this technology has emerged as a new technology that has a substantial impact in the development and growth of biotechnology related industries in Korea. In this review, we introduce the basic concepts and principles of DDS, so that pediatric endocrinologists may obtain a more comprehensive understanding and may benefit in treating patients with this advanced technology.
Biological Science Disciplines ; Biotechnology ; Drug Delivery Systems ; Endocrinology ; Growth and Development ; Humans ; Korea

Adult growth hormone deficiency (GHD) is associated with increased morbidity and mortality and reduced quality of life. GH status should be reevaluated in the transitional age for continued treatment to complete somatic development. All children diagnosed with GHD should be retested by insulin provocative tests upon completion of skeletal growth. A low insulin-like growth factor (IGF)-I is a reliable diagnostic indicator of GHD in the presence of hypopituitarism, however, a normal IGF-I does not rule out GHD. When the diagnosis of adult GHD is established, continuation of GH therapy is strongly recommended. Continued GH treatment from adolescence into early adulthood may contribute to the attainment of a normal bone and muscle mass and contribute to a decrease of the cardiovascular risk of GHD adults. There is ongoing debate about nearly every aspect of GH therapy.
Adolescent ; Adult ; Child ; Growth Hormone ; Humans ; Hypopituitarism ; Insulin ; Insulin-Like Growth Factor I ; Muscles ; Quality of Life

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism characterized by recurrent paralysis of skeletal muscle and hypokalemia caused by a massive intracellular shift of potassium. TPP mainly affects young male patients of Asian descent. We describe a case of TPP in a 14-year-old girl who presented with palpitation and intermittent weakness of the lower extremities especially after physical exercises. The patient showed sinus tachycardia, proximal weakness of both legs and a severe hypokalemia. Thyroid function tests showed hyperthyroidism, and thyroid scan revealed diffusely enlarged goiter consistent with Graves' disease. After the management with antithyroid drug, beta-adrenergic blocker and potassium supplementation for TPP, she has remained euthyroid state and symptom free on the follow-up. TPP should be considered in children with acute paralysis of skeletal muscle and hypokalemia, also thyroid function should be evaluated.
Adolescent ; Asian Continental Ancestry Group ; Child ; Exercise ; Follow-Up Studies ; Goiter ; Graves Disease ; Humans ; Hyperthyroidism ; Hypokalemia ; Hypokalemic Periodic Paralysis ; Leg ; Lower Extremity ; Male ; Muscle, Skeletal ; Paralysis ; Potassium ; Tachycardia, Sinus ; Thyroid Function Tests ; Thyroid Gland

Hypomagnesemia may arise from various disorders such as renal magnesium wasting, familial hypomagnesemia, inadequate intake and increased gastrointestinal loss. Hypomagnesemia and hypocalcemia were found in a month-old female patient with generalized tonic-clonic seizure. Twenty-four hour urine collection samples were used to assess renal magnesium wasting; fractional excretion of 24-hr urine magnesium was less than 1.45%, i.e., within the normal limits. The patient had no history of chronic diarrhea or failure to thrive, which supports the conclusion that intake was adequate. She had no family history of hypocalcemia, hypomagnesemia, or seizures. Here, we report a case of idiopathic hypomagnesemia.
Diarrhea ; Failure to Thrive ; Female ; Humans ; Hypocalcemia ; Magnesium ; Seizures ; Urine Specimen Collection