OB-63 : Positive effects of Teratogenic risk counseling in pregnant women inadvertently exposed to medications

( Hyo Yeon Gwak ),( Jung Eun Lee ),( Ju Young Choi ),( So Yeon Kim ),( Song Mi Park ),( June Seek Choi1,),( Hyun Kyong Ahn ),( Min Hyung Kim ),( Jin Hoon Chung ),( Moon Young Kim ),( Hyun Mee Ryu ),( 대한산부인과학회 2014 대한산부인과학회 학술대회 Vol.100 No.-

목적: To evaluate the positive effects of teratogenic risk counseling in pregnant women inadvertently exposed to medication in early pregnancy. 방법: In a prospective cohort study, 250 pregnant women exposed to medications in early pregnancy were recruited after teratogenic risk counseling at Korean MotherSafe Counsling Center, which has given information about teratogenic risk of medication to pregnant women. Positive effects are evaluated by visual analogue scale(VAS) for perception on teratogenic risk and percent prefering termination of pregnancy after medication exposures in pregnancy. 결과: Mean age of participants is 31.8±5.3years old. Mean gravidity is 2.4±2.1. Medications exposed in early pregnancy include antibiotics, analgesics, anti-inflammatory drugs, antacid and so on. Mean perceptive teratogen risk before and after the counseling is 33.9±1.6% and 15.8±1.6%, respectively. And mean percent prefering termination of pregnancy (≥5) before and after the counseling is 31.1±1.9% and 13.5±1.7%, respectively. 결론: Our data suggest that information on teratogenic risk for pregnant women inadvertently exposed to medication may have positive effects for reassuring pregnant women and preventing termination of pregnancy.

Enrofloxacin과 colistin의 복합제(Enroco)의 아급성 독성시험

윤효인,김민규,박승춘,장범수,이내경,최양웅 충남대학교 수의과대학 동물의과학연구소 1997 動物醫科學硏究誌 Vol.5 No.-

The study was carried out to evaluate toxicity of enrofloxacin and colistin complex (Enroco) with a dose of 10 ㎎/㎏/day, 20 ㎎/㎏/day and 40 ㎎/㎏/day via oral administration for 3 weeks in ICR mice. All procedures of the test were performed by the established regulation of Korean National Institute of Safety Research (1994. 4. 14). Appearance, behavior, mortality and food consumption of treated groups were not affected during the experimental periods. No significant does-related changes of the combined antibacterials were found in urinalysis, eye examination, hematology, serum chemistry, and organ weight. No histopathological lesions were observed in both control and treatment groups. Our results strongly suggested that no toxic changes were found in mice treated orally with enrofloxacin-colistin complex for 3 weeks.

Recommendation for the use of newly introduced Tdap vaccine in Korea

Choi, Kyong-Min,Kim, Kyung-Hyo,Kim, Yae-Jean,Kim, Jong-Hyun,Park, Su-Eun,Lee, Hoan-Jong,Eun, Byung-Wook,Jo, Dae-Sun,Choi, Eun-Hwa,Hong, Young-Jin The Korean Pediatric Society 2011 Clinical and Experimental Pediatrics (CEP) Vol.54 No.4

Pertussis is an acute respiratory infection characterized by paroxysmal cough and inspiratory whoop for over 2 weeks. The incidence of pertussis has decreased markedly after the introduction of DTwP/DTaP vaccine, but the incidence of pertussis has increased steadily among young infant and among adolescents and adults in many countries. Td vaccine was used in this age group but the increase in pertussis has lead to the development of a Tdap vaccine. The Tdap vaccine is a Td vaccine with a pertussis vaccine added and is thought to decrease the incidence and transmission of pertussis in the respective age group. In Korea, two products are approved by the KOREA FOOD & DRUG ADMINISTRATION, which are ADACEL$^{TM}$ (Sanofi-Pasteur, Totonto, Ontario, Canada) and BOOSTRIX$^{(R)}$ (GlaxoSmithKline Biologicals, Rixensart, Belgium) for those aged between 11-64. This report summarizes the recommendations approved by the Committee on Infectious Diseases, the Korean Pediatric Society.

K _Ca 3.1 upregulation preserves endothelium‐dependent vasorelaxation during aging and oxidative stress

Choi, Shinkyu,Kim, Ji Aee,Li, Hai‐,yan,Shin, Kyong‐,Oh,Oh, Goo Taeg,Lee, Yong‐,Moon,Oh, Seikwan,Pewzner‐,Jung, Yael,Futerman, Anthony H.,Suh, Suk Hyo BLACKWELL PUBLISHING 2016 AGING CELL Vol.15 No.5

<P><B>Summary</B></P><P>Endothelial oxidative stress develops with aging and reactive oxygen species impair endothelium‐dependent relaxation (EDR) by decreasing nitric oxide (NO) availability. Endothelial K<SUB>Ca</SUB>3.1, which contributes to EDR, is upregulated by H<SUB>2</SUB>O<SUB>2</SUB>. We investigated whether K<SUB>Ca</SUB>3.1 upregulation compensates for diminished EDR to NO during aging‐related oxidative stress. Previous studies identified that the levels of ceramide synthase 5 (CerS5), sphingosine, and sphingosine 1‐phosphate were increased in aged wild‐type and CerS2 mice. In primary mouse aortic endothelial cells (MAECs) from aged wild‐type and CerS2 null mice, superoxide dismutase (SOD) was upregulated, and catalase and glutathione peroxidase 1 (GPX1) were downregulated, when compared to MAECs from young and age‐matched wild‐type mice. Increased H<SUB>2</SUB>O<SUB>2</SUB> levels induced Fyn and extracellular signal‐regulated kinases (ERKs) phosphorylation and K<SUB>Ca</SUB>3.1 upregulation. Catalase/GPX1 double knockout (catalase<SUP>−/−</SUP>/GPX1<SUP>−/−</SUP>) upregulated K<SUB>Ca</SUB>3.1 in MAECs. NO production was decreased in aged wild‐type, CerS2 null, and catalase<SUP>−/−</SUP>/GPX1<SUP>−/−</SUP>MAECs. However, K<SUB>Ca</SUB>3.1 activation‐induced, NG‐nitro‐<SMALL>L</SMALL>‐arginine‐, and indomethacin‐resistant EDR was increased without a change in acetylcholine‐induced EDR in aortic rings from aged wild‐type, CerS2 null, and catalase<SUP>−/−</SUP>/GPX1<SUP>−/−</SUP> mice. CerS5 transfection or exogenous application of sphingosine or sphingosine 1‐phosphate induced similar changes in levels of the antioxidant enzymes and upregulated K<SUB>Ca</SUB>3.1. Our findings suggest that, during aging‐related oxidative stress, SOD upregulation and downregulation of catalase and GPX1, which occur upon altering the sphingolipid composition or acyl chain length, generate H<SUB>2</SUB>O<SUB>2</SUB> and thereby upregulate K<SUB>Ca</SUB>3.1 expression and function via a H<SUB>2</SUB>O<SUB>2</SUB>/Fyn‐mediated pathway. Altogether, enhanced K<SUB>Ca</SUB>3.1 activity may compensate for decreased NO signaling during vascular aging.</P>

Modification of ginsenoside saponin composition via the CRISPR/Cas9-mediated knockout of protopanaxadiol 6-hydroxylase gene in Panax ginseng

Choi Han Suk,Koo Hyo Bin,Jeon Sung Won,Han Jung Yeon,Kim Joung Sug,Jun Kyong Mi,최용의 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.4

Background: The roots of Panax ginseng contain two types of tetracyclic triterpenoid saponins, namely, protopanaxadiol (PPD)-type saponins and protopanaxatiol (PPT)-type saponins. In P. ginseng, the protopanaxadiol 6-hydroxylase (PPT synthase) enzyme catalyses protopanaxatriol (PPT) production from protopanaxadiol (PPD). In this study, we constructed homozygous mutant lines of ginseng by CRISPR/ Cas9-mediated mutagenesis of the PPT synthase gene and obtained the mutant ginseng root lines having complete depletion of the PPT-type ginsenosides. Methods: Two sgRNAs (single guide RNAs) were designed for target mutations in the exon sequences of the two PPT synthase genes (both PPTa and PPTg sequences) with the CRISPR/Cas9 system. Transgenic ginseng roots were generated through Agrobacterium-mediated transformation. The mutant lines were screened by ginsenoside analysis and DNA sequencing. Result: Ginsenoside analysis revealed the complete depletion of PPT-type ginsenosides in three putative mutant lines (Cr4, Cr7, and Cr14). The reduction of PPT-type ginsenosides in mutant lines led to increased accumulation of PPD-type ginsenosides. The gene editing in the selected mutant lines was confirmed by targeted deep sequencing. Conclusion: We have established the genome editing protocol by CRISPR/Cas9 system in P. ginseng and demonstrated the mutated roots producing only PPD-type ginsenosides by depleting PPT-type ginsenosides. Because the pharmacological activity of PPD-group ginsenosides is significantly different from that of PPT-group ginsenosides, the new type of ginseng mutant producing only PPD-group ginsenosides may have new pharmacological characteristics compared to wild-type ginseng. This is the first report to generate target-induced mutations for the modification of saponin biosynthesis in Panax species using CRISPReCas9 system.

Optimal Sampling Times of Once Daily Gentamicin in Korean Patients with Urinary Tract Infections

( Hyo Jung Park ),( Kie Ho Sohn ),( Kyung Eob Choi ),( Sang Yup Shin ),( Sook In Jung ),( Won Sup Oh ),( Kyong Ran Peck ),( Jae Hoon Song ),( Suk Hyang Lee ) 한국응용약물학회 2003 Biomolecules & Therapeutics(구 응용약물학회지) Vol.11 No.3

Altering sphingolipid composition with aging induces contractile dysfunction of gastric smooth muscle via KC _a 1.1 upregulation

Choi, Shinkyu,Kim, Ji Aee,Kim, Tae Hun,Li, Hai‐,yan,Shin, Kyong‐,Oh,Lee, Yong‐,Moon,Oh, Seikwan,Pewzner‐,Jung, Yael,Futerman, Anthony H.,Suh, Suk Hyo BLACKWELL PUBLISHING 2015 AGING CELL Vol.14 No.6

<P><B>Summary</B></P><P>KC<SUB>a</SUB>1.1 regulates smooth muscle contractility by modulating membrane potential, and age‐associated changes in KC<SUB>a</SUB>1.1 expression may contribute to the development of motility disorders of the gastrointestinal tract. Sphingolipids (SLs) are important structural components of cellular membranes whose altered composition may affect KC<SUB>a</SUB>1.1 expression. Thus, in this study, we examined whether altered SL composition due to aging may affect the contractility of gastric smooth muscle (GSM). We studied changes in ceramide synthases (CerS) and SL levels in the GSM of mice of varying ages and compared them with those in young CerS2‐null mice. The levels of C16‐ and C18‐ceramides, sphinganine, sphingosine, and sphingosine 1‐phosphate were increased, and levels of C22, C24:1 and C24 ceramides were decreased in the GSM of both aged wild‐type and young CerS2‐null mice. The altered SL composition upregulated KC<SUB>a</SUB>1.1 and increased KC<SUB>a</SUB>1.1 currents, while no change was observed in KC<SUB>a</SUB>1.1 channel activity. The upregulation of KC<SUB>a</SUB>1.1 impaired intracellular Ca2+ mobilization and decreased phosphorylated myosin light chain levels, causing GSM contractile dysfunction. Additionally, phosphoinositide 3‐kinase, protein kinase C<SUB>ζ</SUB>, c‐Jun N‐terminal kinases, and nuclear factor kappa‐B were found to be involved in KC<SUB>a</SUB>1.1 upregulation. Our findings suggest that age‐associated changes in SL composition or CerS2 ablation upregulate KC<SUB>a</SUB>1.1 via the phosphoinositide 3‐kinase/protein kinase C<SUB>ζ</SUB>/c‐Jun N‐terminal kinases/nuclear factor kappa‐B‐mediated pathway and impair Ca2+ mobilization, which thereby induces the contractile dysfunction of GSM. CerS2‐null mice exhibited similar effects to aged wild‐type mice; therefore, CerS2‐null mouse models may be utilized for investigating the pathogenesis of aging‐associated motility disorders.</P>

ORIGINAL PAPER : Inhibitory effects of juglanin on cellular senescence in human dermal fibroblasts

( Hyo Hyun Yang ),( Kyong Hwangbo ),( Ming Shan Zhang ),( Jong Keun Son ),( Hwa Young Kim ),( Suk Hwan Baek ),( Hyung Chul Choi ),( So Young Park ),( Jae Ryong Kim ) 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0

Cellular senescence contributes to tissue and organismal aging, tumor suppression and progress, tissue repair and regeneration, and age-related diseases. Thus, aging intervention might be a promising target for treatment and prevention of diverse age-related diseases. In the present study, we investigated whether juglanin purified from the crude extract of Polygonum aviculare exerted inhibitory activity against cellular senescence in human dermal fibroblasts (HDFs). Juglanin decreased senescence-associated β-galactosidase activity (SA-β-gal) and the level of reactive oxygen species in senescent cells induced by adriamycin treatment. Juglanin also repressed SA-β-gal activity in HDFs under replicative senescence. These results suggest that juglanin represses cellular senescence in HDFs and might be useful for the development of dietary supplements or cosmetics that alleviate tissue aging or age-related diseases.

Recommendation for use of the newly introduced pneumococcal protein conjugate vaccines in Korea

Choi, Eun-Hwa,Kim, Kyung-Hyo,Kim, Yae-Jean,Kim, Jong-Hyun,Park, Su-Eun,Lee, Hoan-Jong,Eun, Byung-Wook,Jo, Dae-Sun,Choi, Kyong-Min,Hong, Young-Jin The Korean Pediatric Society 2011 Clinical and Experimental Pediatrics (CEP) Vol.54 No.4

Streptococcus pneumoniae remains a leading cause of invasive infections including bacteremia and meningitis, as well as mucosal infections such as otitis media and pneumonia among children and adults. The 7-valent pneumococcal conjugate vaccine (PCV7) was licensed for use among infants and young children in many countries including Korea. The routine use of PCV7 has resulted in a decreased incidence of invasive pneumococcal disease (IPD) by the vaccine serotypes among the vaccinees and substantial declines in IPD among unvaccinated populations such as older children and adults as well. In addition, there are increasing evidences to suggest that routine immunization with PCV7 is changing the epidemiology of pneumococcal diseases such as serotype distribution of IPD, nasopharyngeal colonization, and antibiotic resistance patterns. In contrast, there is an increase in the number of IPDs caused by nonvaccine serotypes, though it is much smaller than overall declines of vaccine serotype diseases. Several vaccines containing additional serotypes have been developed and tested clinically in order to expand the range of serotypes of Streptococcus pneumoniae. Recently two new pneumococcal protein conjugate vaccines, 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13), have been approved for use in several countries including Korea. This report summarizes the recommendations approved by the Committee on Infectious Diseases, the Korean Pediatric Society.

Single-nucleotide polymorphisms in the promoter of the CDK5 gene and lung cancer risk in a Korean population.

Choi, Hyo Seon,Lee, Youngin,Park, Kyong Hwa,Sung, Jae Sook,Lee, Jong-Eun,Shin, Eun-Soon,Ryu, Jeong-Seon,Kim, Yeul Hong Springer-Verlag 2009 Journal of human genetics Vol.54 No.5

<P>Cyclin-dependent kinase 5 (CDK5), a proline-directed serine/threonine kinase, which was originally known for its regulatory role in neuronal activities, has recently been suggested to play a role in extraneuronal activities. For example, a recent study detected overexpression of the CDK5 gene in non-small-cell lung cancer. Therefore, in order to explore the association of the CDK5 gene with lung cancer risk in a Korean population, the genotypes of the CDK5 promoter region were determined in 407 lung cancer patients and 402 normal participants. The result showed that the -904 G>A genotype affected susceptibility to lung cancer risk (odd ratios (OR)=1.53, 95% confidence interval (CI)=1.02-2.32). Furthermore, subsequent haplotype analysis of three single-nucleotide polymorphism (SNP) regions suggested that the A-G-C haplotype was associated with a higher overall risk of lung cancer (OR=1.59, 95% CI=1.16-2.18). These results suggest that CDK5 promoter polymorphisms contribute to the genetic susceptibility to lung cancer in the Korean population.</P>