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Development of Functional Halogenated Phenylpyrrole Derivatives (기능성 할로겐화 페닐피롤 )

  • Min-Hee Jung;Hee Jeong Kong;Young-Ok Kim;Jin-Ho Lee
    • Journal of Life Science
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    • v.33 no.10
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    • pp.842-850
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    • 2023
  • Pyrrolnitrin, pyrrolomycin, and pyoluteorin are functional halogenated phenylpyrrole derivatives (HPDs) derived from microorganisms with diverse antimicrobial activities. Pyrrolnitrin is a secondary metabolite produced from L-tryptophan through four-step reactions in Pseudomonas fluorescens, Burkholderia cepacia, Serratia plymuthica, etc. It is currently used for the treatment of superficial dermatophytic fungal infections, has high antagonistic activities against soil-borne and foliar fungal infections, and has many industrial applications. Since pyrrolnitrin is easily decomposed by light, it is difficult to widely use it outdoors. As an alternative, fludioxonil, a synthetically produced non-systemic surface fungicide that is structurally similar and has excellent light stability, has been commercialized for seed and foliar treatment of plants. However, due to its high toxicity to aquatic organisms and adverse effects in human cell lines, many countries have established maximum residue levels and strictly control its levels. Pyrrolomycin and pyoluteorin, which have antibiotic/antibiofilm activity against Gram-positive bacteria and high anti-oomycete activity against the plant pathogen Pythium ultimum, respectively, were isolated and identified from microorganisms. This review summarizes the biosynthesis and production of natural pyrrolnitrin derived from bacteria and the characteristics of synthetic fludioxonil and other natural phenylpyrrole derivatives among the HPDs. We expect that a plethora of highly effective, novel HPDs that are safe for humans and environments will be developed through the generation of an HPD library by microbial biosynthesis and chemical synthesis.

The Parathyroid Gland: An Overall Review of the Hidden Organ for Radiologists (부갑상선: 부갑상선 영상에 익숙하지 않은 영상의학과 의사들을 위한 전반적인 검토)

  • Suho Kim;Jung Hee Shin;Soo Yeon Hahn;Haejung Kim;Myoung Kyoung Kim
    • Journal of the Korean Society of Radiology
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    • v.85 no.2
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    • pp.327-344
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    • 2024
  • Parathyroid glands are small endocrine glands that regulate calcium metabolism by producing parathyroid hormone (PTH). These are located at the back of the thyroid gland. Typically, four glands comprise the parathyroid glands, although their numbers may vary among individuals. Parathyroid diseases are related to parathyroid gland dysfunction and can be caused by problems with the parathyroid gland itself or abnormal serum calcium levels arising from renal disease. In recent years, as comprehensive health checkups have become more common, abnormal serum calcium levels are often found incidentally in blood tests, after which several additional tests, including a PTH test, ultrasonography (US), technetium-99m sestamibi parathyroid scan, single-photon-emission CT (SPECT)/CT, four-dimensional CT (4D-CT), and PET/CT, are performed for further evaluation. However, the parathyroid gland remains an organ less familiar to radiologists. Therefore, the normal anatomy, pathophysiology, imaging, and clinical findings of the parathyroid gland and its associated diseases are discussed here.

A Cost-benefit Analysis on Neonatal Screening of Phenylketonuria and Congenital Hypothyroidism in Korea (한국에서의 페닐케톤뇨증과 선천성 갑상샘 저하증에 대한 신생아 집단 선별 검사의 경제성 분석)

  • Yun, Hoe Cheol;Kim, Nyeon Cheon;Lee, Dong Hwan
    • Clinical and Experimental Pediatrics
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    • v.48 no.4
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    • pp.369-375
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    • 2005
  • Purpose : Many inborn errors of metabolism can be completely cured with early detection and early treatment. This is why neonatal screening on inborn errors of metabolism is implemented worldwide. In this study, a cost-benefit analysis was performed on the neonatal screening of phenylketonuria and congenital hypothyroidism in Korea. Methods : This study included 2,908,231 neonates who took the neonatal screening on phenylketonuria and congenital hypothyroidism in Korea from January 1991 to December 2003. From those neonates, the incidence rates of phenylketonuria and congenital hypothyroidism were measured. Furthermore, based on 495,000 babies born in 2002, were calculated and compared the total costs in case when neonatal screening on phenylketonuria and congenital hypothyroidism is implemented, and when not. Results : If the neonatal screening on phenylketonuria and congenital hypothyroidism is implemented, benefits far exceed costs at a ratio of 1.77 : 1 in phenylketonuria, and 11.11 : 1 in congenital hypothyroidism. In terms of wons, the present neonatal screening on phenylketonuria and congenital hypothyroidism will gain us more than 29 billion wons every year. Conclusion : This study only concerns the monetary aspects of the neonatal screening. Therefore, the benefits of the neonatal screening is underestimated by ignoring precious but not measurable values such as quality of life. However, the present neonatal screening on phenylketonuria and congenital hypothyroidism is found to be beneficial and should continue for the good of the nation as well as that of the patients.

Effects of Bisphenol and Octylphenol on TM3 Cell : Expression of Cytochrome P450scc and Estrogen Receptor $\alpha$ mRNA (Bisphenol과 Octylphenol이 TM3 세포에 미치는 영향: Cytochrome P450scc와 Estrogen Receptor $\alpha$ 유전자의 발현)

  • 이호준;김묘경;강희규;김동훈;한성원;고덕성
    • Development and Reproduction
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    • v.4 no.2
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    • pp.215-220
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    • 2000
  • Most of endocrine disrupters (EDs) have been reported to exhibit estrogenic or anti-androgenic activity and thereby may disrupt reproductive development in human or wildlife. This study was performed to investigate the effects of estrogen (E$_2$), bisphenol (BP) and octylphenol (OP) on the mouse Leydig cell line (TM3). TM3 originated from testis of 11~13-daly-old BALB/c nu/+ mice was cultured in DMEM supplemented with 10% FBS alone or medium with estrogen (E$_2$), bisphenol (BP) and octylphenol (OP; 1 pM, 1 nM, 1 $\mu$M, 1 mM, respectively) for 48 hours. After culture, total cell number and viability were assessed by heamocyto-meter and trypan blue stain. Expression of cytochrome P450scc (CYPscc) mRNA whose product is involved in steroid hormone biosynthesis and estrogen receptor $\alpha$(ER $\alpha$) mRNA were detected by RT-PCR. As a result, treatment of TM3 with E$_2$, BP and OP(1 mM, respectively) significantly decreased the viability but not all of groups as high as 1 $\mu$M. Exposure of TM3 to OP significantly reduced the total cell number but not E$_2$ or BP. The expression of CYPscc mRNA was slightly reduced in BP (1 nM, 1 $\mu$M) and significantly decreased in OP (1 nM, 1 $\mu$M) treated TM3, except E$_2$ group. But the expression of ER $\alpha$ mRNA was sightly increased in all treated groups. In conclusion, BP and OP (high concentration) might inhibit steroidogenesis by decreasing the CYPscc mRNA expression in the mouse testis. These results suggest that BP and OP might impair spermatogenesis and subsequently disturb testicular function.

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Effect of Ethane 1,2-Dimethane Sulfonate(EDS) on the Expression of Pituitary Gonadotropin in Male Rats (수컷 흰쥐 뇌하수체의 생식소자극호르몬 발현에 미치는 Ethane 1,2-Dimethane Sulfonate(EDS)의 효과)

  • Son, Hyeok-Joon;Kim, Soo-Woong;Paick, Jae-Seung;Lee, Sung-Ho
    • Development and Reproduction
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    • v.11 no.1
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    • pp.49-54
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    • 2007
  • Ethane 1,2-dimethane sulfonate(EDS), a toxin which specifically kills Leydig cells(LC), has been widely used to prepare the reversible testosterone(T) depletion rat model. In the present study, we monitored the gene expression profiles of pituitary gonadotropins, LH and FSH, up to 7 weeks after EDS injection. Adult male Sprague-Dawley rats($300{\sim}350\;g$ B.W.) were injected with a single dose of EDS(75 mg/kg i.p.) and sacrificed on weeks 0, 1, 2, 3, 4, 5, 6 and 7. Total RNAs were purified from each pituitary, and the message levels of common alpha subunit($C{\alpha}$) of pituitary glycoprotein hormones, LH beta subunit($LH{\beta}$), FSH beta subunit($FSH{\beta}$) and GnRH receptor(GnRH-R) were evaluated by semi-quantitative RT-PCRs. The message levels of $C{\alpha}$ increased sharply during weeks 1-4, then return to the control level on week 5. The mRNA levels of $LH{\beta}$ were elevated after week 2, reached the peak at week 4, then declined to the control level after week 5. The message levels of $FSH{\beta}$ were elevated after week 2, reached the peak at week 3, then declined to the nadir at week 5. Similarly, the mRNA levels of GnRH-R were elevated after week 2, reached the peak at week 3, then gradually declined to the control level after week 5. The present study indicated that EDS treatment could induce reversible alterations in the transcriptional activities of gonadotropin subunits and GnRH-R in the anterior pituitary from male rats. EDS injection model might be useful to understand the mechanism of hormonal regulation of hypothalamus- pituitary neuroendocrine axis in male rats.

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Global DNA Methylation Patterns and Gene Expression Associated with Obesity-Susceptibility in Offspring of Pregnant Sprague-Dawley Rats Exposed to BDE-47 and BDE-209 (임신 중 BDE-47 및 BDE-209에 노출된 어미와 새끼 Sprague-Dawley 랫드의 Global DNA 메틸화 양상과 비만 감수성과 연관된 유전자 발현)

  • Park, Byeong-Min;Yoon, Ok-Jin;Lee, Do-Hoon
    • 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.

Efficacy and Safety during the Combination Therapy of Imipramine and Desmopressin in Primary Monosymptomatic Nocturnal Enuresis (어린이의 일차성 단일 증상성 야뇨증에서 Imipramine과 Desmopressin 복합 약물치료의 효과 및 안전성)

  • Yeo Ji-Hyun;Choi Jung-Youn;Chung Hyo-Seok;Lee Kyung-Soo;Ko Cheol-Woo;Kim Kyo-Sun;Kim Kee-Hyuk;Kim Jung-Soe;NamGoong Mee-Kyung;Park Young-Seo;Pai Ki-Soo;Yoo Kee-Hwan;Park Yong-Hoon
    • Childhood Kidney Diseases
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    • v.8 no.2
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    • pp.129-137
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    • 2004
  • Purpose : Nocternal enuresis is a common disorder. Tricyclic antidepressant and desmopressin have been accepted pharmacological treatment for this disorder We conducted a cooperative study to investigate the efficacy and adverse reactions of imipramine, desmopressin and combination treatment in children with primary monosymptomatic nocturnal enuresis(PMNE). Methods: Data from a large multicenter study were analysed. In the period of 8 months in 2002, the study comprised of 168 children(78 boys and 90 girls, 5 to 15 years old) with PMNE for imipramine, desmopressin or combination treatment. Before treatment a history, physical examination and laboratory tests were performed and the children were observed for 2 weeks. Response rate, adverse reactions and enuresis episodes after stopping drug administration were evaluated after 12-weeks of imipramine, desmopressin or combination of both. Results: After 4 weeks, the frequency of bed wetting in all treated patients decreased during treatment significantly Even though a 30-50%, reduction in the number of wet nights were 68.6%, 74.4% and 86.1% during 12 weeks treatment by imipramine, desmopressin and both of them respectively, there was no significant difference between them. The most common adverse reaction was decreased appetite from imipramine administration. But no serious drug-related adverse events were reported. Conclusion: Efficacy of the combination therapy of imipramine and desmopressin in PMNE appears not to be better than either drug alone. It is necessary to pay attention on account of adverse reactions during imipramine treatment even though imipramine and desmopressin were generally well tolerated.

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Relationships with Alanine Aminotransferase Activity, and Anthropometric and Biochemical Measures in Obese Children (단순 비만아에서 간효소치와 신체 계측 및 생화학 측정치와의 관련성)

  • Yun, Gyoung-Bin;Kim, Jae-Young
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.12 no.1
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    • pp.30-38
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    • 2009
  • Purpose: To investigate the physical and biochemical parameters related with elevated serum alanine aminotransferase (ALT) levels in obese children. Methods: One hundred forty-two obese or overweight children who visited the out-patient clinics of Chungnam National University Hospital between January 2006 and August 2008 were enrolled. Physical measures and biochemical tests were performed in all patients. Liver sonography was performed in 43 patients. They were divided into the following 2 groups based on ALT levels: group I, normal ALT levels (n=65); and group II, elevated ALT levels (n=77). We compared the physical measures, biochemical results, and ultrasonographic findings of the livers in both groups. Other causes of elevated serum ALT levels were ruled out. Results: The male-to-female ratios were 1.6:1 in group I and 7.6:1 in group II. Among physical parameters, the waist circumference-to-height ratio and hip circumference-to-height ratio were significantly higher in group II (p=0.001 and 0.046, respectively). Among biochemical parameters, aspartate aminotransferase (AST), ${\gamma}$-glutamyltransferase (${\gamma}$-GT), and total cholesterol levels were significantly higher in group II (p<0.001, 0.001, and 0.001, respectively). The AST/ALT ratio was <1 (mean, 0.55) and statistically lower in group II. There was a positive correlation between the serum ALT level and ${\gamma}$-GT (p<0.001, r=0.750), and a positive correlation between the serum ALT level and the waist circumference-to-height ratio in group II (p<0.001, r=0.401). Conclusion: The results suggest that the waist circumference-to-height ratio and ${\gamma}$-GT may be associated with elevated alanine aminotransferase activity in obese children.

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A Study on the Incidence of Thyroid Cancer in Gender Ultrasound (초음파검사에서 성별에 따른 갑상샘 암의 빈도에 관한 연구)

  • Kwak, Eun-Suk;Lim, Cheong-Hwan;Yang, Oh-Nam
    • Journal of radiological science and technology
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    • v.38 no.2
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    • pp.145-153
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    • 2015
  • Thyroid nodules are an endocrine disease often found in clinical practice, and patients with thyroid nodules found by chance have rapidly increased alongside development of thyroid ultrasound techniques for health examination purposes. This study analyzes the subjects' general characteristics, thyroid ultrasounds, and fine needle aspiration cytology in order to find out the relationship between male and female thyroid nodules and thyroid cancer frequency. An ultrasound examination of the thyroid was performed for 32,973 individuals who visited the K Hospital of Health Examination. Subjects have no history of thyroid disease and are 20 years old or over. Data of general characteristics, diabetes) was collected by a written survey completed by the subject, and the ultrasound of the thyroid(thyroid nodules existence, size, number) and FNAC was used to find out the malignancy rate. Frequency of patients with thyroid nodule was 4,611(26.1%) in men and 5,341(34.9%) in women between 32,973 individuals. Women's prevalence rate is significantly higher than men, and the prevalence rate significantly increased with age in men and women(p < 0.05). The prevalence of multiple nodules was significantly higher in women(43.5%) than in men(35.6%), and significantly increased with age in men and women(p < 0.05). The fine needle aspiration cytology was performed in 692(men 342, women 350) subjects who showed signs of malignancy through ultrasound. Prevalence of malignancy of the nodules was higher in men(33.3%) than in women(29.4%) although it is not statistically significant. It is known that thyroid nodule prevalence in women is much higher than in men. But this study shows the men's prevalence rate was not too low compared with women, and the men showed a rather higher malignancy rate in nodules than women. It is considered that the role of thyroid ultrasound is both important in men and women.