• Animal Bioscience
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• v.37 no.3
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• pp.522-535
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• 2024

Objective: Transition period is considered from 3 weeks prepartum to 3 weeks postpartum, characterized with dramatic events (endocrine, metabolic, and physiological) leading to occurrence of production diseases (negative energy balance/ketosis, milk fever etc). The objectives of our study were to analyze the periodic concentration of serum beta-hydroxy butyric acid (BHBA), glucose and oxidative markers along with identification, and validation of the putative markers of negative energy balance in buffaloes using in-silico and quantitative real time-polymerase chain reaction (qRT-PCR) assay. Methods: Out of 20 potential markers of ketosis identified by in-silico analysis, two were selected and analyzed by qRT-PCR technique (upregulated; acetyl serotonin o-methyl transferase like and down regulated; guanylate cyclase activator 1B). Additional two sets of genes (carnitine palmotyl transferase A; upregulated and Insulin growth factor; downregulated) that have a role of hepatic fatty acid oxidation to maintain energy demands via gluconeogenesis were also validated. Extracted cDNA (complementary deoxyribonucleic acid) from the blood of the buffaloes were used for validation of selected genes via qRTPCR. Concentrations of BHBA, glucose and oxidative stress markers were identified with their respective optimized protocols. Results: The analysis of qRT-PCR gave similar trends as shown by in-silico analysis throughout the transition period. Significant changes (p<0.05) in the levels of BHBA, glucose and oxidative stress markers throughout this period were observed. This study provides validation from in-silico and qRT-PCR assays for potential markers to be used for earliest diagnosis of negative energy balance in buffaloes. Conclusion: Apart from conventional diagnostic methods, this study improves the understanding of putative biomarkers at the molecular level which helps to unfold their role in normal immune function, fat synthesis/metabolism and oxidative stress pathways. Therefore, provides an opportunity to discover more accurate and sensitive diagnostic aids.

• Clinical and Experimental Pediatrics
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• v.45 no.5
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• pp.654-658
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• 2002

Purpose : Endocrine and immune systems are connected and interdependent. Adrenal glands play an important role in this network and control the balance between serum levels of dehydroepiandrosterone sulfate(DHEAS) and cortisol. These steroids have an antagonistic effect on the T cell progression into Th1 and Th2 cells and on the induction of correlated interleukins. Therefore we evaluated the role of adrenal androgen and cortisol as immune modulators in Kawasaki disease( KD) with changes of T cell immunity. Methods : From April to August in 2001, we examined serum DHEAS and 24 hour urine free cortisol(F) before administration of immunoglobulin and steroids by radioimmunoassay in 14 KD patients. It's clinical severity was determined by Harada score and coronary lesion. Results : The age of the patient group ranged from 4 months to 4 years; its average age was 2.3 years. Three patients(21.4%) were below 1 year, 2(14.3%) between 1 and 2 years, 5(35.7%) between 2 and 3 years, 4(28.6%) between 3 and 4 years of age. Male to female ratio was 1:1.3. DHEAS was significantly decreased in patients($11.1{\pm}6.0{\mu}g/dL$) more than controls($81.6{\pm}13.3{\mu}g/dL$)(P<0.05). Twenty-four hour urine free cortisol was significantly increased in patients($36.9{\pm}21.9{\mu}g/dL$) more than controls($13.6{\pm}5.5{\mu}g/dL$)(P<0.05). Ratio of DHEAS/F was decreased remarkably in patients($0.33{\pm}0.20$) more than controls($6.65{\pm}2.56$)(P=0.016). There was no difference between ratio of DHEAS/F and Harada score, but its ratio was very low in patients with coronary aneurysm. Conclusion : These data demonstrate that there are changes of DHEAS and cortisol in acute stage of KD and the dis-equilibrium between two steroids may be relevant in the T cell immune response induction of Kawasaki disease. These changes support the use of DHEAS/F ratio as one of the predictive factors of coronary arteries complication.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.1
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• pp.28-39
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• 2017

Persistent organic pollutants (POPs) can affect epigenetic mechanisms and obesity development. Polybrominated diphenyl ethers (PBDEs)-widely used to make flames-are one of the important POPs. Prenatal exposure to endocrine disrupting chemicals (EDCs), such as POPs, may affect global DNA methylation in long interspersed nuclear elements (LINE-1), increasing the risk of obesity later in life. Therefore, pregnant Sprague-Dawley (SD) rats were used to elucidate whether BDE-47 and BDE-209 transferred through placenta and breast milk cause epigenetic changes in LINE-1 and increase genetic susceptibility to obesity as obesogen during the developmental periods. Global DNA methylation in LINE-1 and gene expression related to obesity were measured in dams and offspring, using a methylation-sensitive high resolution melting analysis (MS-HRM) and direct bisulfite sequencing and quantitative real time polymerase chain reaction (qPCR), respectively. The results of MS-HRM showed global DNA hypomethylation patterns in LINE-1 of exposed offspring (2 of total 4) at PND 4, but bisulfite sequencing showed no difference in both the exposed and non-exposed groups. Gene expression in dams related to ${\beta}$-oxidation pathway and those related to adipokines showed different patterns between the two groups. On the contrary, gene expressions of offspring showed a similar pattern. Gene expressions related to ${\beta}$-oxidation pathway and obesity were significantly increased when compared with 'at birth', but not $PPAR-{\alpha}$. In conclusion, this study demonstrated the possibility that co-exposure to BDE-47 and BDE-209-via the placenta and breast milk-may affect epigenetic changes and modulate gene expression levels related to obesity.

• The Journal of Internal Korean Medicine
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• v.21 no.1
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• pp.74-86
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• 2000

Objectives : This is the experimental paper to study the curative and preventive effects of Dansambohyultang, Methods : Oriental herb medicine for gastro-intestinal disease caused by stress, on the rats put under the stress through starvation, heating and immoblization, the author used four different group; the normal group, which was not put under stress and well fed, and the control group, to which the drug was not administered and put under the stress through starvation, heating and immoblization, the Sample I, to which the drug was administered before they were put under stress, the Sample lI, to which the drug was administered after they were put under stress. Results : When a Masson's trichrome stain method was applied to the control group, a small size of ulcer was found in the fundus and the pylorus, and atrophy was observed in the neck region of mucous membrane. When the drug was administered to the Sample I and the Sample II, the former recovered from the ulcer and atrophy to almost normal and showed better results than the latter. When a Masson's trichrome stain method was applied to the control group, atrophy of mucous membrane was found all over the intestines. When the drug was administered to the Sample I and the Sample ll, the curative and recovered effects was seen in both, but the former showed better results than the latter. After application of Mayer's hematoxylin stain method, the observation of numerical changes of goblet cells in the small intestines showed the most significant decrease in the control group. In the Sample I, the number of the cells in the duodenum, the jejunum and the ileum returned to an almost normal level. In the Sample II, a slight increase was observed only in the ileum. After application of Mayer's hematoxylin stain method, the observation of numerical changes of goblet cell in the large intestines showed a significant decreased in the control group. Both the Sample I and the Sample II showed an increase in the number of goblet cells in comparison with the control group. When a serotonin-immunoreaction test was applied, the control group showed a general decrease in the number of gastro-entero-endocrine cells, The Sample I showed the effect in all over gastro.intestinal tract as compared with control group and the Sample II showed the effect in all over gastro-intestinal tract except the duodenum and the former showed better results than the latter. Conclusion : According to the above results, the regions which are most sensitive to stress were observed to the ileum and the colon. It was concluded that Dansambohyultang has a remedical value particularly on the abnormalities caused by stress in all over gastro-intestinal tract and it was found to be more effective in the Sample I than in the Sample ll. Judging from the fact that the Sample I showed better results than the Sample ll, Dansambohyultang can be said to have a preventive effect more than a curative effect on gastro-intestinal tract disease.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.185-195
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• 1991

Seventy four patients with pituitary adenoma received radiation therapy (RT) on the pituitary area using 6 MV linear accelerator during the past 7 years at the Division of Radiation Therapy, Kangnam St. Mary's Hospital, Catholic University Medical College. Thirty nine were men and 35 were women. The age ranged from 7 to 65 years with the mean being 37 years. Sixty five ($88\%$) patients were treated postoperatively and 9 ($12\%$) primary RT, To evaluate the effects of RT, we analyzed the series of endocrinologic studies with prolactin (PRL), growth hormone (GH), adrenocorticotrophic hormone (ACTH), leuteinizing hormone (LH), follicular stimulating hormone (FSH) and thyroid stimulating hormone (TSH) etc after RT. All but one with Nelson's syndrome showed abnormal neuroradiologic changes in the sella turcica with invasive tumor mass around supra- and/or parasella area. The patients were classified as 23 ($29\%$) prolactinomas and 20 ($26\%$) growth hormone (GH) secreting tumors, and 6 ($8\%$ ACTH secreting ones consisting of 4 Cushing's disease and 2 Nelson's syndrome. Twentynine ($37\%$) had nonfunctioning tumor and four ($5\%$) of those secreting pituitary tumors were mixed PRL-GH secreting tumors. The hormonal level in 15 ($65\%$) of 23 PRL and 3 ($15\%$) of 20 GH secreting tumors returned to normal by 2 to 3 years after RT, but five PRL and five GH secreting tumors showed high hormonal level requiring bromocriptine medication. Endocrinologic insufficiency developed by 3 years after RT in 5 of 7 panhypopituitarisms, 4 of seven hypothyroidisms and one of two hypogonadisms, respectively. Fifteen ($20\%$) patients were lost to follow up after RT.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.19 no.10
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• pp.243-253
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• 2018

This study aimed to investigate the effects of DCI on glucose control, quality of life(SF-36 Version 2.0, Korean) and SDSCA(Summary of Diabetes Self-Care Activities) in patients with type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled study was performed on 46 patients with HbA1c 7.0% taking triple anti-diabetic drug regimen who visited the department of Endocrinology and Metabolism in Chungnam National University Hospital between March 2015 and May 2016. As a result, DCI treatment in the intervention group resulted in significantly reduced HbA1c levels $8.75{\pm}0.79%$(baseline), $8.36{\pm}1.03%$(after 12weeks), and $8.65{\pm}0.81%$(after 24weeks). However, patients in the control group did not show any significant change. Interestingly, both DCI treatment group and the control group significantly showed improvements in SDSCA. Participants in the intervention group showed a small yet significant improvement in their only fasting blood glucose test in SDSCA and revealed significant increase in the quantitative levels of quality of life, from $73.05{\pm}16.85$ to $82.74{\pm}10.68$. By using pathway analysis, improvement of SDSCA scores(${\beta}=-0.505$, t=-2.743) was the most influential factor to the fasting blood glucose. The quality of life of patients with type 2 diabetes mellitus was affected by changes of SDSCA scores(${\beta}=0.411$, t=2.024) and fasting c-peptide(${\beta}=-0.445$, t=-2.668) in DCI treatment group. In conclusion, treatment of DCI effectively improved glucose control in patients with type 2 DM(HbA1c level>7.0%) after 12 weeks of treatment, although it had no impact on glucose control after 24 weeks of treatment. Improved glucose control may encourage diabetic patients to conduct self-care activities and improve the quality of life. Based on the present study, we suggest that diabetes self-management, as well as consideration of comprehensive laboratory findings, may be important factor in regulating the quality of life in type 2 DM patients.

• Proceedings of the Korean Nutrition Society Conference
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• 1995.11b
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• pp.11-34
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• 1995

Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.

• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.225-235
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• 1993

Pituitary LH release has been known to be regulated by the hypothalamic gonadotropin releasing hormone (GnRH) and the gonadal steroid hormones. In addition, neurotransmitters and neuropeptides are actively involved in the control of LH secretion. The alteration in LH release might reflect changes in biosynthesis and/or posttranslational processing of LH. However, little is known about the mechanism by which biosynthesis of LH subunits is regulated, especially at the level of transcription. In order to investigate if ovarian steroid hormones regulate the LH subunit gene expression, ${\alpha}\;and\;LH{\beta}$ steady state mRNA levels were determined in anterior pituitaries of ovariectomized rats. Serum LH concentrations and pituitary LH concentrations were increased markedly with time after ovariectomy. ${\alpha}\;and\;LH{\beta}$ subunit mRNA levels after ovariectomy were increased in a parallel manner with serum LH concentrations and pituitary LH contents, the rise in $LH{\beta}$ subunit mRNA levels being more prominent than the rise in ${\alpha}\;subunit$ mRNA. ${\alpha}\;and\;LH{\beta}$ subunit mRNA levels in ovariectomized rats were negatively regulated by the continuous treatment of ovarian steriod hormones for $1{\sim}4\;days$ and $LH{\beta}\;subunit$ mRNA seemed to be more sensitive to negative feedback of estradiol than progesterone. Treatment of estrogen antagonist, LY117018 or progesterone antagonist, RU486 significantly restroed LH subunit mRNA levels as well as LH release which were suppressed by estradiol or progesterone treatment. These results suggest that ovarian steroids negatively regulate the LH synthesis at the pretranslational level by modulating the steady state levels of ${\alpha}\;and\;LH{\beta}\;subunit$ mRNA and $LH{\beta}\;subunit$ mRNA seemed to be more sensitive to negative feedback action of estradiol than progesterone.

• Development and Reproduction
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• v.5 no.2
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• pp.175-180
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• 2001

The ectopic expression of gonadotropin releasing hormone(GnRH and luteinizing hormone(LH) in several tissues is a quite intriguing phenomenon. Recently, the presence of GnRH and its receptor has been clearly demonstrated in rodents and human mammary gland. In this context, one can postulate that the presence of local circuit composed of GnRH and LH in the gland. The present study was undertaken to elucidate whether there is a correlation between the LH expression in rat mammary gland and physiological status during the process of mammary differentiation. LH contents in mammary gland from cycling to weaning rats were measured by radioimmunoassay(RIA). In cycling rats, changes of the LH level in both serum and mammary gland showed similar pattern as the highest level in proestrus and the lowest level in diestrus II stage. While the serum LH levels were fluctuated from pregnant through involution stage, a sharp decline of mammary LH contents was observed in the lactating rats. This decrement was recovered in involuting rats to the level of proestrus stage. Reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analyses demonstrated that the transcriptional activities of the mammary LH and GnRH were increased from diestrus I stage to estrus stage, and the increased levels were maintained in pregnant, lactation and involution stages. To test the hypothesis that the alteration in mammary LH expression might be steroid-dependant, ovariectomy(OVX) and steroid supplement model was employed. As expected, supplement of estradiol(E$_2$) after OVX remarkably decreased serum LH level compared to that in serum from vehicle-only treated rats. Likewise, administration of E$_2$ significantly reduced the mammary LH content. The present study demonstrated that (i) the LH expression in mammary gland could be altered by some physiological parameters such as estrous cycle, pregnancy, lactation and involution, and (ii) ovarian steroid especially estrogen seems to be one of major endocrine factors which are responsible for regulation of mammary LH expression.

• Childhood Kidney Diseases
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• v.6 no.2
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• pp.209-217
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• 2002

Purpose : Corticosteroid has been used as the mainstay therapy of childhood NS. But SIO is one of the serious complications of long-term steroid therapy, especially in growing children. Recently calcium, calcitonin, PTH, vitamin D and bisphosphonate has been used to treat or prevent SIO in adult, which is rare in children with NS. We studied the effect of $1{\alpha}-(OH)D_3$ and Pamidronate on SIO using dual energy X-ray absorptiometry (DEXA). Patients and methods : We studied thirty patients who admitted in the Dept. of Pediatrics of Kyung Hee Medical Hospital with NS. All patients was received longterm steroid therapy. There was no history of bone, liver, or endocrine disease. The samples, serum protein, albumin, BUN, creatinine, calcium, phosphorus, and BMD were obtained before and the six months after the dose of $1{\alpha}-(OH)D_3$ and Pamidronate, respectively Results : The mean age was $6.9{\pm}3.3\;and\;6.5{\pm}2.5$ years old. The mean duration of steroid therapy was $28.8{\pm}1.8\;and\;27.6{\pm}1.0$ months. The changes of serum protein, albumin, BUN, creatinine, calcium and phosphorus level between pre-treatment and post-treatment did not show statistical significance in both $1{\alpha}-(OH)D_3$ and Pamidronate treatment group. However, BMD was increased in both from $0.472{\pm}0.12\;and\;0.457{\pm}0.10\;g/cm^2\;to\;0.533{\pm}0.12$ and $0.529{\pm}0.09\;g/cm^2$ after treatment. (P<0.05) Conclusion : Both $1{\alpha}-(OH)D_3$ and Pamidronate appears to be effective in treating and preventing SIO in children with nephrotic syndrome requiring long-term steroid therapy.