• Title/Summary/Keyword: CYP3A1

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Testicular adrenal rest tumors in a patient with untreated congenital adrenal hyperplasia

  • Jin, Hye-Young;Choi, Jin-Ho;Kim, Gu-Hwan;Lee, Chung-Sik;Yoo, Han-Wook
    • Clinical and Experimental Pediatrics
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    • v.54 no.3
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    • pp.137-140
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    • 2011
  • Testicular adrenal rest tumors (TARTs) are considered to be formed from aberrant adrenal tissue that has become hyperplastic because of elevated adrenocorticotropic hormone (ACTH) in male patients with congenital adrenal hyperplasia (CAH). A 6-year-old boy presented with testicular enlargement and pubic hair. He was diagnosed with CAH complicated by precocious puberty. However, he was not followed-up. At the age of 17, he visited the outpatient clinic because of testicular enlargement and short stature. His right and left testicles were $10{\times}6$ cm and $7.5{\times}4.5$ cm, respectively. His height was 155.1 cm (standard deviation score (SDS), -2.90). The diagnosis of CAH due to 21 hydroxylase deficiency was confirmed by mutation analysis of CYP21A2. Histological examination of the testes showed large, polygonal, eosinophilic cells with round nuclei and prominent nucleoli, which were suggestive of TARTs. He was treated with dexamethasone for 3 weeks and tumors regressed. Subsequently, dexamethasone was replaced by prednisolone and $9{\alpha}$-fludrocortisone; thereafter, the reduced testis size has been maintained.

Finding Genes Discriminating Smokers from Non-smokers by Applying a Growing Self-organizing Clustering Method to Large Airway Epithelium Cell Microarray Data

  • Shahdoust, Maryam;Hajizadeh, Ebrahim;Mozdarani, Hossein;Chehrei, Ali
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.111-116
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    • 2013
  • Background: Cigarette smoking is the major risk factor for development of lung cancer. Identification of effects of tobacco on airway gene expression may provide insight into the causes. This research aimed to compare gene expression of large airway epithelium cells in normal smokers (n=13) and non-smokers (n=9) in order to find genes which discriminate the two groups and assess cigarette smoking effects on large airway epithelium cells.Materials and Methods: Genes discriminating smokers from non-smokers were identified by applying a neural network clustering method, growing self-organizing maps (GSOM), to microarray data according to class discrimination scores. An index was computed based on differentiation between each mean of gene expression in the two groups. This clustering approach provided the possibility of comparing thousands of genes simultaneously. Results: The applied approach compared the mean of 7,129 genes in smokers and non-smokers simultaneously and classified the genes of large airway epithelium cells which had differently expressed in smokers comparing with non-smokers. Seven genes were identified which had the highest different expression in smokers compared with the non-smokers group: NQO1, H19, ALDH3A1, AKR1C1, ABHD2, GPX2 and ADH7. Most (NQO1, ALDH3A1, AKR1C1, H19 and GPX2) are known to be clinically notable in lung cancer studies. Furthermore, statistical discriminate analysis showed that these genes could classify samples in smokers and non-smokers correctly with 100% accuracy. With the performed GSOM map, other nodes with high average discriminate scores included genes with alterations strongly related to the lung cancer such as AKR1C3, CYP1B1, UCHL1 and AKR1B10. Conclusions: This clustering by comparing expression of thousands of genes at the same time revealed alteration in normal smokers. Most of the identified genes were strongly relevant to lung cancer in the existing literature. The genes may be utilized to identify smokers with increased risk for lung cancer. A large sample study is now recommended to determine relations between the genes ABHD2 and ADH7 and smoking.

Dosage Adjustment before and after Warfarin - Rifampin Combination Therapy (와파린-리팜핀 병용 시 용량 조절)

  • Kim, Dong-Hyun;Kim, Kyung-Hwan;Choi, Kyung-Hee;Lee, Kwang-Ja;Lee, Hye-Suk;Son, In-Ja;Kim, Ki-Bong;Lee, Jae-Woong;Ahn, Hyuk
    • Journal of Chest Surgery
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    • v.41 no.3
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    • pp.354-359
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    • 2008
  • Background: Warfarin is used as an anticoagulant and it is mainly excreted by the liver metabolism (the R-form is mainly metabolized by cytochrome p450 3A4, and the S form by cytochrome p450 2C9). Rifampin is usually used for tuberculosis or endocarditis, and it is a representative drug that induces the CYP families, including 3A4 and 2C9. The anticoagulation effect of warfarin decreases through the increased metabolism that's due to the induction of enzymes, and this iscaused by rifampin when patients take these two medicines together. No one has suggested appropriate guidelines regarding this drug interaction even though an appropriate adjustment of warfarin's dosage is needed. We examined the drug interaction in patients who received warfarin-rifampin combination therapy according to the time interval, and the factors affecting drug interaction were analyzed. Based on the data, we tried to determine the clinically available warfarin dosage guidelines before and after taking this drug combination. Material and Method: We reviewed the OO University Hospital anticoagulation service team's follow up sheets that were filled out from Jan '1998 to Sep 2006 for the patient who took warfarin - rifampin combination therapy (n=15). Result: The average INR of all the patient before rifampin administration was $2.25{\pm}0.52$ $(mean{\pm}SD)$, and that value for the first 100 days after rifampin administration was $1.98{\pm}0.28$. The p value for these two sets of data showed no correlation (paired t-test, p>0.05). The average INR of all the patient before rifampin cessation was $2.19{\pm}0.34$, and the value after rifampin cessation was $2.49{\pm}0.43$. The p value of these two showed correlation (paired t-test, p<0.05) but the average INR falls between the therapeutic INR range. Conclusion: The warfarin dose adjustment equation of before and after warfarin-rifampin combination therapy was derived based on this study's results because the warfarin dosage adjustment of the anticoagulation service team was considered appropriate.

Kisspeptin-10 Enhanced Egg Production in Quails Associated with the Increase of Triglyceride Synthesis in Liver

  • Wu, J.;Fu, W.;Huang, Y.;Ni, Y.;Zhao, R.
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.8
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    • pp.1080-1088
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    • 2013
  • Our previous results showed that kisspeptin-10 (Kp-10) injections via intraperitoneal (i.p.) once daily for three weeks notably promoted the egg laying rate in quails. In order to investigate the mechanism behind the effects of Kp-10 on enhancing the egg laying rate in birds, this study focused on the alternations of lipids synthesis in liver after Kp-10 injections. 75 female quails (22 d of age) were allocated to three groups randomly, and subjected to 0 (control, Con), 10 nmol (low dosage, L) and 100 nmol (high dosage, H) Kp-10 injections via i.p. once daily for three weeks, respectively. At d 52, quails were sacrificed and sampled for further analyses. Serum $E_2$ concentration was increased by Kp-10 injections, and reached statistical significance in H group. Serum triglyceride (TG) concentrations were increased by 46.7% in L group and 36.8% in H group, respectively, but did not reach statistical significance, and TG contents in liver were significantly elevated by Kp-10 injections in a dose-dependent manner. Serum total cholesterol (Tch) concentrations significantly decreased in H group, while in H group the hepatic Tch content was markedly increased. The level of non-esterified fatty acid (NEFA), apolipoprotein A1 and B (apoA1 and apoB) were not altered by Kp-10 injections. The genes expression of sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FAS), apolipoprotein VLDL-II (apoVLDL-II), cholesterol $7{\alpha}$-hydroxylase (CYP7A1) and vitellogenin II (VTG-II) were significantly up-regulated by high but not low dosage of Kp-10 injection compared to the control group. However, the expression of SREBP-2, acetyl-CoA carboxylase ($ACC_{\alpha}$), malic enzyme (ME), stearoyl-CoA (${\Delta}9$) desaturase 1 (SCD1), apolipoprotein A1 (apoA1), fatty acid binding protein 2 (FABP2), 3-hydroxyl-3-methyl glutaryl-coenzyme A reductases (HMGCR), estrogen receptor ${\alpha}$, ${\beta}$($ER{\alpha}$ and ${\beta}$) mRNA were not affected by Kp-10 treatment. In line with hepatic mRNA abundance, hepatic SREBP1 protein content was significantly higher in H group. Although the mRNA expression was not altered, the content of $ER{\alpha}$ protein in liver was also significantly increased in H group. However, SREBP-2 protein content in liver was not changed by Kp-10 treatment. In conclusion, exogenous Kp-10 consecutive injections during juvenile stage significantly advanced the tempo of egg laying in quails, which was associated with the significant elevation in hepatic lipids synthesis and transport.

A Study on the Permeability Reduction Methods of the Riverbed Ground during Urban Railway Tunnel construction (도시철도터널공사 시 하저통과구간의 지반투수저하 공법에 대한 연구)

  • Kim, Joon-Jeong;Cho, Kook-Hwan;Lee, Jun-Seok
    • Proceedings of the KSR Conference
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    • 2007.11a
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    • pp.551-557
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    • 2007
  • This paper describes a study on the permeability reduction of the riverbed ground during urban railway tunnel construction. The research is mainly concentrated on the study of the grouting or injection methods among permeability reduction methods which can be adapted in the riverbed ground. Firstly, the various grouting methods are theoretically reviewed and compared based on the previous research papers and case study results. It is also evaluated the grouting methods in view of a safe construction of the river crossing railway tunnel. Baced on the literature review and previous construction data, the design technology of grouting methods considering the long term hydro-geological behaviour in the riverbed, is suggested. Two injection methods namely, Natural Durable Stabilizer(N.D.S) and Space-Multi Injaction Grouting(S.M.I) methods, are introduced as new approach methods which can be adopted to modify the riverbed ground. In order to evaluate the ground that grouted and modified by the N.D.S and S.M.I method, the pilot test programmes including the field and laboratory permeability tests, are carried out in the river crossing tunnel construction sites. The results obtained from pilot test programme, are also reviewed. In conclusion, the grouting efficiency of the S.M.I method using the non-alcalimeter silica sol is better than that of NDS method using cement. In addition, it hopes that the research results are contributed to develop the grouting design technology.

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Selection and evaluation of reference genes for gene expression using quantitative real-time PCR in Mythimna separata walker (Lepidoptera: Noctuidae)

  • ZHANG, Bai-Zhong;LIU, Jun-Jie;CHEN, Xi-Ling;YUAN, Guo-Hui
    • Entomological Research
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    • v.48 no.5
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    • pp.390-399
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    • 2018
  • In order to precisely assess gene expression levels, the suitable internal reference genes must be served to quantify real-time reverse transcription polymerase chain reaction (RT-qPCR) data. For armyworm, Mythimna separata, which reference genes are suitable for assessing the level of transcriptional expression of target genes have yet to be explored. In this study, eight common reference genes, including ${\beta}$-actin (${\beta}$-ACT), 18 s ribosomal (18S), 28S ribosomal (28S), glyceraldehyde-3-phosphate (GAPDH), elongation fator-alpha ($EF1{\alpha}$), TATA box binding protein (TBP), ribosomal protein L7 (RPL7), and alpha-tubulin (${\alpha}$-TUB) that in different developmental stages, tissues and insecticide treatments of M. separata were evaluated. To further explore whether these genes were suitable to serve as endogenous controls, three software-based approaches (geNorm, BestKeeper, and NormFinder), the delta Ct method, and one web-based comprehensive tool (RefFinder) were employed to analyze and rank the tested genes. The optimal number of reference genes was determined using the geNorm program, and the suitability of particular reference genes was empirically validated according to normalized HSP70, and MsepCYP321A10 gene expression data. We found that the most suitable reference genes for the different experimental conditions. For developmental stages, 28S/RPL7 were the optimal reference genes, both $RPL7/EF1{\alpha}$ were suitable for experiments of different tissues, whereas for insecticide treatments, $28S/{\alpha}-TUB$ were suitable for normalizations of expression data. In addition, $28S/{\alpha}-TUB$ were the suitable reference genes because they have the most stable expression among different developmental stages, tissues and insecticide treatments. Our work is the first report on reference gene selection in M. separata, and might serve as a precedent for future gene expression studies.

Isotopic Determination of Food Sources of Benthic Invertebrates in Two Different Macroalgal Habitats in the Korean Coasts (동위원소 분석에 의한 동해와 남해 연안의 상이한 해조류 군락에 서식하는 저서무척추동물 먹이원 평가)

  • Kang, Chang-Keun;Choy, Eun-Jung;Song, Haeng-Seop;Park, Hyun-Je;Soe, In-Soo;Jo, Q-Tae;Lee, Kun-Seop
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.12 no.4
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    • pp.380-389
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    • 2007
  • Stable carbon and nitrogen isotopes were analyzed in suspended particulate organic matter, macroalgae and macrobenthic invertebrates in order to determine the importance of primary organic matter sources in supporting food webs of rocky subtidal and intertidal macroalgal beds in the Korean coasts. Investigations were conducted at the inter tidal sites within Gwangyang bay, a semi-enclosed and eutrophicated bay, and the subtidal sites of the east coast, a relatively oligotrophic and open environment, in May and June 2005. Water-column suspension feeders showed more negative $\delta^{13}C$ values than those of the other feeding guilds, indicating trophic linkage with phytoplankton and thereby association with pelagic food chains. In contrast, animals of the other feeding guilds, including interface suspension feeders, herbivores, deposit feeders, omnivores and predators, displayed relatively less negative $\delta^{13}C$ values than those of the water-column suspension feeders and similar with that of macroalgae, indicating exclusive use of macroalgae-derived organic matter and association with benthic food chains. Most the macrobenthic species were considered to form strong trophic links with benthic food chains. In addition, the distribution of higher $\delta^{15}N$ values in macrobenthic consumers and macroalgae at the intertidal sites of Gwangyang Bay than those at the subtidal sites of the east coast suggests that anthropogenic nutrients may enhance the macroalgal production at the intertidal sites and in turn be incorporated into the particular littoral food web in Gwangyag Bay. These results confirm the dominant role of macroalgae in supporting rocky subtidal and intertidal food webs in the Korean coasts.

Distribution of Mast cells and Nerves in the Developing Postnatal Submandibular and Sublingual Glands of Rats (생후 발생중인 흰쥐의 턱밑샘 및 혀밑샘에서의 비만세포와 신경의 분포양상)

  • Kim, Jae-Gon;An, Soo-Hyeon;Lee, Young-Su;Baik, Byeong-Ju;Cho, Eui-Sic
    • Journal of the korean academy of Pediatric Dentistry
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    • v.26 no.2
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    • pp.350-364
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    • 1999
  • The distribution of mast cells and nerves were investigated in the submandibular and sublingual glands of postnatal rats, using morphometric, histochemical and immunohistochemical techniques. Mast cells were observed in the submandibular and sublingual glands of postnatal development. Number of mast cells gradually increased in both glands following development. At birth, mast cells were relatively fewer in submandibular gland than those in sublingual gland, and they were mainly distributed in parenchymal tissues. At $2{\sim}4$ weeks, most of the mast cells were observed in the connective tissues, surrounding neurovascular elements, but some mast cells were closely related with the acini of submandibular gland. PGP 9.5 immunoreactive nerve fibers were found in the submandibular and sublingual glands of all developmental age. The nerve fibers were showed in varicose shape, and mainly located in adjacent area of ducts and vascular components of both glands. The number of nerve fibers were increased rapidly until 8 weeks, but they were not increased any more until 24 weeks. Therefore, it is suggested that mast cells and nerve fibers related with each other, and that their interactions may play roles not only in maturation of secretory units but also growth and differentiation of the tubular structures of the rat submandibular and sublingual glands during postnatal development.

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Drug-Drug Interaction Prediction Using Krill Herd Algorithm Based on Deep Learning Method

  • Al-Marghilani, Abdulsamad
    • International Journal of Computer Science & Network Security
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    • v.21 no.6
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    • pp.319-328
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    • 2021
  • Parallel administration of numerous drugs increases Drug-Drug Interaction (DDI) because one drug might affect the activity of other drugs. DDI causes negative or positive impacts on therapeutic output. So there is a need to discover DDI to enhance the safety of consuming drugs. Though there are several DDI system exist to predict an interaction but nowadays it becomes impossible to maintain with a large number of biomedical texts which is getting increased rapidly. Mostly the existing DDI system address classification issues, and especially rely on handcrafted features, and some features which are based on particular domain tools. The objective of this paper to predict DDI in a way to avoid adverse effects caused by the consumed drugs, to predict similarities among the drug, Drug pair similarity calculation is performed. The best optimal weight is obtained with the support of KHA. LSTM function with weight obtained from KHA and makes bets prediction of DDI. Our methodology depends on (LSTM-KHA) for the detection of DDI. Similarities among the drugs are measured with the help of drug pair similarity calculation. KHA is used to find the best optimal weight which is used by LSTM to predict DDI. The experimental result was conducted on three kinds of dataset DS1 (CYP), DS2 (NCYP), and DS3 taken from the DrugBank database. To evaluate the performance of proposed work in terms of performance metrics like accuracy, recall, precision, F-measures, AUPR, AUC, and AUROC. Experimental results express that the proposed method outperforms other existing methods for predicting DDI. LSTMKHA produces reasonable performance metrics when compared to the existing DDI prediction model.

Up-to-date treatment of acetaminophen poisoning (아세트아미노펜 중독의 치료에 대한 최신지견)

  • Sung Phil Chung;Jeongmi Moon;Byeongjo Chun
    • Journal of The Korean Society of Clinical Toxicology
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    • v.20 no.2
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    • pp.39-44
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    • 2022
  • N-Acetylcysteine (NAC) is the standard antidote treatment for preventing hepatotoxicity caused by acetaminophen (AAP) poisoning. This review summarizes the recent evidence for the treatment of AAP poisoning. Several alternative intravenous regimens of NAC have been suggested to improve patient safety by reducing adverse drug reactions and medication errors. A two-bag NAC infusion regimen (200 mg/kg over 4 h, followed by 100 mg/kg over 16 h) is reported to have similar efficacy with significantly reduced adverse reactions compared to the traditional 3-bag regimen. Massive AAP poisoning due to high concentrations (more than 300-lines in the nomogram) needs to be managed with an increased maintenance dose of NAC. In addition to NAC, the combination therapy of hemodialysis and fomepizole is advocated for severe AAP poisoning cases. In the case of a patient presenting with an altered mental status, metabolic acidosis, elevated lactate, and an AAP concentration greater than 900 mg/L, hemodialysis is recommended even if NAC is used. Fomepizole decreases the generation of toxic metabolites by inhibiting CYP2E1 and may be considered an off-label use by experienced clinicians. Since the nomogram cannot be applied to sustained-release AAP formulations, all potentially toxic sustained-release AAP overdoses should receive a full course of NAC regimen. In case of ingesting less than the toxic dose, the AAP concentration is tested twice at an interval of 4 h or more; NAC should be administered if either value is above the 150-line of the nomogram.