• 제목/요약/키워드: beta blocker

검색결과 123건 처리시간 0.027초

Enhanced antidiabetic efficacy and safety of compound K/β-cyclodextrin inclusion complex in zebrafish

  • Nam, Youn Hee;Le, Hoa Thi;Rodriguez, Isabel;Kim, Eun Young;Kim, Keonwoo;Jeong, Seo Yule;Woo, Sang Ho;Lee, Yeong Ro;Castaneda, Rodrigo;Hong, Jineui;Ji, Min Gun;Kim, Ung-Jin;Hong, Bin Na;Kim, Tae Woo;Kang, Tong Ho
    • Journal of Ginseng Research
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    • 제41권1호
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    • pp.103-112
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    • 2017
  • Background: 20(S)-Protopanaxadiol 20-O-D-glucopyranoside, also called compound K (CK), exerts antidiabetic effects that are mediated by insulin secretion through adenosine triphosphate (ATP)-sensitive potassium ($K_{ATP}$) channels in pancreatic ${\beta}$-cells. However, the antidiabetic effects of CK may be limited because of its low bioavailability. Methods: In this study, we aimed to enhance the antidiabetic activity and lower the toxicity of CK by including it with ${\beta}$-cyclodextrin (CD) (CD-CK), and to determine whether the CD-CK compound enhanced pancreatic islet recovery, compared to CK alone, in an alloxan-induced diabetic zebrafish model. Furthermore, we confirmed the toxicity of CD-CK relative to CK alone by morphological changes, mitochondrial damage, and TdT-UTP nick end labeling (TUNEL) assays, and determined the ratio between the toxic and therapeutic dose for both compounds to verify the relative safety of CK and CD-CK. Results: The CD-CK conjugate ($EC_{50}=2.158{\mu}M$) enhanced the recovery of pancreatic islets, compared to CK alone ($EC_{50}=7.221{\mu}M$), as assessed in alloxan-induced diabetic zebrafish larvae. In addition, CD-CK ($LC_{50} =20.68{\mu}M$) was less toxic than CK alone ($LC_{50}=14.24{\mu}M$). The therapeutic index of CK and CD-CK was 1.98 and 9.58, respectively. Conclusion: The CD-CK inclusion complex enhanced the recovery of damaged pancreatic islets in diabetic zebrafish. The CD-CK inclusion complex has potential as an effective antidiabetic efficacy with lower toxicity.

생쥐 소장 카할세포에서 발생하는 향도잡이 기능의 올란자핀 효능에 관한 연구 (Effects of Olanzapine on the Pacemaker Potentials of Interstitial Cells of Cajal in Murine Small Intestine)

  • 김병주
    • 생명과학회지
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    • 제29권9호
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    • pp.1010-1015
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    • 2019
  • 카할세포는 위장관에서 향도잡이 역할을 한다. 본연구에서는 생쥐 소장 카할세포에서 발생되는 향도잡이 기능에서 올란자핀의 역할을 연구하였다. 패치클램프 방법을 사용하여 향도잡이 전압을 측정하였다. 올란자핀에 의해서 카할세포 향도잡이 전압이 탈분극 되었으며, 이 탈분극은 무스카린성 3번 수용체 억제제에 의해서 억제 되었다. 세포내 $GDP{\beta}S$을 넣어주니 올란자핀에 의해 향도잡이 전압 탈분극이 억제되었다. 또한, 세포밖 $Na^+$ 농도 감소와 비선택성 양이온 통로 억제제에 의해서 올란자핀에 의한 향도잡이 전압 탈분극이 억제 되었다. 세포내 PLC기전의 억제제인 U-73122에 의해서 올란자핀에 의한 향도잡이 전압 탈분극이 억제 되었다. 이러한 결과로 올란자핀은 무스카린성 3번 수용체를 통해서 세포내 G 단백질과 PLC기전 및 세포밖 $Na^+$이 관여함을 알 수 있었다. 따라서 올란자핀은 카할세포를 통해서 장운동성을 조절 할 수 있을 것으로 생각된다.

Sesquiterpenoids Bioconversion Analysis by Wood Rot Fungi

  • Lee, Su-Yeon;Ryu, Sun-Hwa;Choi, In-Gyu;Kim, Myungkil
    • 한국균학회소식:학술대회논문집
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    • 한국균학회 2016년도 춘계학술대회 및 임시총회
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    • pp.19-20
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    • 2016
  • Sesquiterpenoids are defined as $C_{15}$ compounds derived from farnesyl pyrophosphate (FPP), and their complex structures are found in the tissue of many diverse plants (Degenhardt et al. 2009). FPP's long chain length and additional double bond enables its conversion to a huge range of mono-, di-, and tri-cyclic structures. A number of cyclic sesquiterpenes with alcohol, aldehyde, and ketone derivatives have key biological and medicinal properties (Fraga 1999). Fungi, such as the wood-rotting Polyporus brumalis, are excellent sources of pharmaceutically interesting natural products such as sesquiterpenoids. In this study, we investigated the biosynthesis of P. brumalis sesquiterpenoids on modified medium. Fungal suspensions of 11 white rot species were inoculated in modified medium containing $C_6H_{12}O_6$, $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ for 20 days. Cultivation was stopped by solvent extraction via separation of the mycelium. The metabolites were identified as follows: propionic acid (1), mevalonic acid lactone (2), ${\beta}$-eudesmane (3), and ${\beta}$-eudesmol (4), respectively (Figure 1). The main peaks of ${\beta}$-eudesmane and ${\beta}$-eudesmol, which were indicative of sesquiterpene structures, were consistently detected for 5, 7, 12, and 15 days These results demonstrated the existence of terpene metabolism in the mycelium of P. brumalis. Polyporus spp. are known to generate flavor components such as methyl 2,4-dihydroxy-3,6-dimethyl benzoate; 2-hydroxy-4-methoxy-6-methyl benzoic acid; 3-hydroxy-5-methyl phenol; and 3-methoxy-2,5-dimethyl phenol in submerged cultures (Hoffmann and Esser 1978). Drimanes of sesquiterpenes were reported as metabolites from P. arcularius and shown to exhibit antimicrobial activity against Gram-positive bacteria such as Staphylococcus aureus (Fleck et al. 1996). The main metabolites of P. brumalis, ${\beta}$-Eudesmol and ${\beta}$-eudesmane, were categorized as eudesmane-type sesquiterpene structures. The eudesmane skeleton could be biosynthesized from FPP-derived IPP, and approximately 1,000 structures have been identified in plants as essential oils. The biosynthesis of eudesmol from P. brumalis may thus be an important tool for the production of useful natural compounds as presumed from its identified potent bioactivity in plants. Essential oils comprising eudesmane-type sesquiterpenoids have been previously and extensively researched (Wu et al. 2006). ${\beta}$-Eudesmol is a well-known and important eudesmane alcohol with an anticholinergic effect in the vascular endothelium (Tsuneki et al. 2005). Additionally, recent studies demonstrated that ${\beta}$-eudesmol acts as a channel blocker for nicotinic acetylcholine receptors at the neuromuscular junction, and it can inhibit angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase (MAPK) signaling pathway (Seo et al. 2011). Variation of nutrients was conducted to determine an optimum condition for the biosynthesis of sesquiterpenes by P. brumalis. Genes encoding terpene synthases, which are crucial to the terpene synthesis pathway, generally respond to environmental factors such as pH, temperature, and available nutrients (Hoffmeister and Keller 2007, Yu and Keller 2005). Calvo et al. described the effect of major nutrients, carbon and nitrogen, on the synthesis of secondary metabolites (Calvo et al. 2002). P. brumalis did not prefer to synthesize sesquiterpenes under all growth conditions. Results of differences in metabolites observed in P. brumalis grown in PDB and modified medium highlighted the potential effect inorganic sources such as $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ on sesquiterpene synthesis. ${\beta}$-eudesmol was apparent during cultivation except for when P. brumalis was grown on $MgSO_4$-free medium. These results demonstrated that $MgSO_4$ can specifically control the biosynthesis of ${\beta}$-eudesmol. Magnesium has been reported as a cofactor that binds to sesquiterpene synthase (Agger et al. 2008). Specifically, the $Mg^{2+}$ ions bind to two conserved metal-binding motifs. These metal ions complex to the substrate pyrophosphate, thereby promoting the ionization of the leaving groups of FPP and resulting in the generation of a highly reactive allylic cation. Effect of magnesium source on the sesquiterpene biosynthesis was also identified via analysis of the concentration of total carbohydrates. Our current study offered further insight that fungal sesquiterpene biosynthesis can be controlled by nutrients. To profile the metabolites of P. brumalis, the cultures were extracted based on the growth curve. Despite metabolites produced during mycelia growth, there was difficulty in detecting significant changes in metabolite production, especially those at low concentrations. These compounds may be of interest in understanding their synthetic mechanisms in P. brumalis. The synthesis of terpene compounds began during the growth phase at day 9. Sesquiterpene synthesis occurred after growth was complete. At day 9, drimenol, farnesol, and mevalonic lactone (or mevalonic acid lactone) were identified. Mevalonic acid lactone is the precursor of the mevalonic pathway, and particularly, it is a precursor for a number of biologically important lipids, including cholesterol hormones (Buckley et al. 2002). Farnesol is the precursor of sesquiterpenoids. Drimenol compounds, bi-cyclic-sesquiterpene alcohols, can be synthesized from trans-trans farnesol via cyclization and rearrangement (Polovinka et al. 1994). They have also been identified in the basidiomycota Lentinus lepideus as secondary metabolites. After 12 days in the growth phase, ${\beta}$-elemene caryophyllene, ${\delta}$-cadiene, and eudesmane were detected with ${\beta}$-eudesmol. The data showed the synthesis of sesquiterpene hydrocarbons with bi-cyclic structures. These compounds can be synthesized from FPP by cyclization. Cyclic terpenoids are synthesized through the formation of a carbon skeleton from linear precursors by terpene cyclase, which is followed by chemical modification by oxidation, reduction, methylation, etc. Sesquiterpene cyclase is a key branch-point enzyme that catalyzes the complex intermolecular cyclization of the linear prenyl diphosphate into cyclic hydrocarbons (Toyomasu et al. 2007). After 20 days in stationary phase, the oxygenated structures eudesmol, elemol, and caryophyllene oxide were detected. Thus, after growth, sesquiterpenes were identified. Per these results, we showed that terpene metabolism in wood-rotting fungi occurs in the stationary phase. We also showed that such metabolism can be controlled by magnesium supplementation in the growth medium. In conclusion, we identified P. brumalis as a wood-rotting fungus that can produce sesquiterpenes. To mechanistically understand eudesmane-type sesquiterpene biosynthesis in P. brumalis, further research into the genes regulating the dynamics of such biosynthesis is warranted.

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Calcitonin Gene-related Peptide Suppresses Pacemaker Currents by Nitric Oxide/cGMP-dependent Activation of ATP-sensitive K+ Channels in Cultured Interstitial Cells of Cajal from the Mouse Small Intestine

  • Choi, Seok;Parajuli, Shankar Prasad;Yeum, Cheol Ho;Park, Chan Guk;Kim, Man Yoo;Kim, Young Dae;Cha, Kyoung Hun;Park, Young Bong;Park, Jong Seong;Jeong, Han Seong;Jun, Jae Yeoul
    • Molecules and Cells
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    • 제26권2호
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    • pp.181-185
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    • 2008
  • The effects of calcitonin gene-related peptide (CGRP) on pacemaker currents in cultured interstitial cells of Cajal (ICC) from the mouse small intestine were investigated using the whole-cell patch clamp technique at $30^{\circ}C$. Under voltage clamping at a holding potential of -70 mV, CGRP decreased the amplitude and frequency of pacemaker currents and activated outward resting currents. These effects were blocked by intracellular $GDP{\beta}S$, a G-protein inhibitor and glibenclamide, a specific ATP-sensitive $K^+$ channels blocker. During current clamping, CGRP hyperpolarized the membrane and this effect was antagonized by glibenclamide. Pretreatment with SQ-22536 (an adenylate cyclase inhibitor) or naproxen (a cyclooxygenase inhibitor) did not block the CGRP-induced effects, whereas pretreatment with ODQ (a guanylate cyclase inhibitor) or L-NAME (an inhibitor of nitric oxide synthase) did. In conclusion, CGRP inhibits pacemaker currents in ICC by generating nitric oxide via G-protein activation and so activating ATP-sensitive $K^+$ channels. Nitric oxide- and guanylate cyclase-dependent pathways are involved in these effects.

Carbachol Regulates Pacemaker Activities in Cultured Interstitial Cells of Cajal from the Mouse Small Intestine

  • So, Keum Young;Kim, Sang Hun;Sohn, Hong Moon;Choi, Soo Jin;Parajuli, Shankar Prasad;Choi, Seok;Yeum, Cheol Ho;Yoon, Pyung Jin;Jun, Jae Yeoul
    • Molecules and Cells
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    • 제27권5호
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    • pp.525-531
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    • 2009
  • We studied the effect of carbachol on pacemaker currents in cultured interstitial cells of Cajal (ICC) from the mouse small intestine by muscarinic stimulation using a whole cell patch clamp technique and $Ca^{2+}$-imaging. ICC generated periodic pacemaker potentials in the current-clamp mode and generated spontaneous inward pacemaker currents at a holding potential of -70 mV. Exposure to carbachol depolarized the membrane and produced tonic inward pacemaker currents with a decrease in the frequency and amplitude of the pacemaker currents. The effects of carbachol were blocked by 1-dimethyl-4-diphenylacetoxypiperidinium, a muscarinic $M_3$ receptor antagonist, but not by methotramine, a muscarinic $M_2$ receptor antagonist. Intracellular $GDP-{\beta}-S$ suppressed the carbachol-induced effects. Carbachol-induced effects were blocked by external $Na^+$-free solution and by flufenamic acid, a non-selective cation channel blocker, and in the presence of thapsigargin, a $Ca^{2+}$-ATPase inhibitor in the endoplasmic reticulum. However, carbachol still produced tonic inward pacemaker currents with the removal of external $Ca^{2+}$. In recording of intracellular $Ca^{2+}$ concentrations using fluo 3-AM dye, carbachol increased intracellular $Ca^{2+}$ concentrations with increasing of $Ca^{2+}$ oscillations. These results suggest that carbachol modulates the pacemaker activity of ICC through the activation of non-selective cation channels via muscarinic $M_3$ receptors by a G-protein dependent intracellular $Ca^{2+}$ release mechanism.

Risk Factors of On-Pump Conversion during Off-Pump Coronary Artery Bypass Graft

  • Yoon, Sung Sil;Bang, Jung Hee;Jeong, Sang Seok;Jeong, Jae Hwa;Woo, Jong Soo
    • Journal of Chest Surgery
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    • 제50권5호
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    • pp.355-362
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    • 2017
  • Background: Off-pump coronary artery bypass grafting (OPCABG) procedures can avoid the complications of an on-pump bypass. However, some cases unexpectedly require conversion to cardiopulmonary bypass during OPCABG. The risk factors associated with a sudden need for cardiopulmonary bypass were analyzed. Methods: This retrospective study included 283 subjects scheduled for OPCABG from 2001 to 2010. These were divided into an OPCABG group and an on-pump conversion group. Preoperative, operative, and postoperative variables were compared between the 2 groups. Results: Of the 283 patients scheduled for OPCABG, 47 (16%) were switched to on-pump coronary artery bypass grafting (CABG). The mortality of the both the OPCABG and on-pump conversion groups was not significantly different. The major risk factors for conversion to on-pump CABG were congestive heart failure (CHF) (odds ratio [OR], 3.5; p=0.029), ejection fraction (EF) <35% (OR, 4.4; p=0.012), and preoperative beta-blocker (BB) administration (OR, 0.3; p=0.007). The use of intraoperative (p=0.007) and postoperative (p=0.021) inotropics was significantly higher in the conversion group. The amount of postoperative drainage (p<0.001) and transfusion (p<0.001) also was significantly higher in the conversion group. There were no significant differences in stroke or cardiovascular complications between the groups over the course of short-term and long-term follow-up. Conclusion: Patients who undergo OPCABG and have CHF or a lower EF (<35%) are more likely to undergo on-pump conversion, while preoperative BB administration could help prevent conversions from OPCABG to on-pump CABG.

범뇌하수체저하증의 호르몬 대체요법 중단 후 발생한 스트레스 심근병증 (A patient with stress induced cardiomyopathy that occurred after cessation of hormone replacement therapy for panhypopituitarism)

  • 남승완;이준원;심정한;백현성;임창조;임정수;안성균
    • Journal of Yeungnam Medical Science
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    • 제33권2호
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    • pp.125-129
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    • 2016
  • Stress induced cardiomyopathy (SC) is characterized by transient left ventricular (LV) dysfunction in the absence of coronary artery disease. We report on a patient with panhypopituitarism who developed SC resulting from withdrawal of hormonal replacement therapy (HRT). A 52-year-old male visited our hospital for progressively worsening dyspnea. The patient had discontinued HRT 7 days ago, which had been administered for 18 months after transsphenoidal adenomectomy for pituitary macroadenoma. Initial electrocardiogram showed marked sinus bradycardia. Transthoracic echocardiography showed apical ballooning with an LV ejection fraction of 25%. No significant obstructive lesions were observed on coronary angiography. With a clinical diagnosis of SC associated with panhypopituitarism, HRT was restarted, including glucocorticoid and thyroxine, along with standard heart failure management. His LV function had normalized at 2-month follow-up. He remains asymptomatic and administration of beta-blocker and angiotensin converting enzyme inhibitor were discontinued He currently only requires HRT.

특발성 혈소판 감소성 자반증 및 철 결핍성 빈혈을 동반한 Graves 씨병 1례 (Graves' disease Associated with Idiopathic Thrombocytopenic Purpura and Iron Deficiency Anemia)

  • 김종명;윤성철;최수봉;이현우;김경동;김정숙;남혜주;최원희;이태숙
    • Journal of Yeungnam Medical Science
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    • 제5권1호
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    • pp.173-179
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    • 1988
  • Since 1931, sporadic reports have appeared noting an apparent association between hyperthyroidism and idiopathic thrombocytopenic purpura. Recent various studies suggested that these two diseases may share a similar immunologic background, but the the exact mechanism is still a matter of speculation. This 22-year old female patient visisted this hospital because of general weakness and purpura of legs for 2 months. The laboratory findings were compatible with Graves' disease associated with idiopathic thrombocytopenic purpura. The palatclet count was 16000/$mm^3$, hemoglobulin was 10.9g/dl and MCV was 60.1tL. T3 was 490.53ng/dL, T4 was 24ug/dL and free T4 was 5.66ng/dL. Antiplatelet antibody and anti-microsomal antibody were positive. The bone marrow findings were compatible with tron deficiency anemia and idiopathic thrombocytopenic purpura. The thyroid biopsy showed adenomatous goiter. She was administered with propyl thiouracil, Beta-blocker, iron and prednisolon. On the 10th hospital day, platelet count was 184000/$mm^3$, hemoglobulin was 12.0gm/dL and MCV was 67.5fL. On the 20th hospital day, T4 was 10.35ug/dL and free T4 was 2.30ng/dL. Therefore she was discharged and followed up.

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말티즈견에서 발생한 판막상형 폐동맥판 협착증 증례 (A Case of Supravalvular Pulmonic Stenosis in a Maltese Dog)

  • 김성준;강민희;김수찬;최영철;김승곤;이창민;정다민;박희명
    • 한국임상수의학회지
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    • 제31권4호
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    • pp.325-328
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    • 2014
  • A 8-month-old female Maltese dog was presented with a history of heart murmur. In physical examination, grade 4/6 systolic murmur heard at the left heart base. Electrocardiography showed sinus arrhythmia, right axis deviation, deep S wave and splintered QRS complex. Thoracic radiography revealed enlarged right side heart and bulging of the main pulmonary artery. Echocardiography showed mild hypertrophy of right ventricle, a supravalvular stenosis, marked post-stenotic dilation of the main pulmonary artery and a moderately increased pulmonary arterial velocity through the stenotic area (4.4 m/s, pressure gradient of 78.7 mmHg). The dog was diagnosed with supravalvular pulmonic stenosis based on the diagnostic imaging findings. Medical management using ${\beta}1$-blocker and ACE inhibitor was started in this dog and this is first case report described diagnostic characteristic features of supravalvular pulmonic stenosis in korea.

S-1과 티아지드 상승효과에 의한 항이뇨호르몬과다분비증후군 1예 (SIADH Caused by the Synergistic Effect of S-1 and Thiazide)

  • 하태경;권성준
    • Journal of Gastric Cancer
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    • 제6권3호
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    • pp.198-201
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    • 2006
  • 저나트륨혈증은 항암화학요법 중에 발생하는 전해질 장애 중의 하나이며, 조기에 발견하여 치료하지 않을 경우 급사할 수 있다. 저나트륨혈증을 유발하는 여러 원인중에 항이뇨호르몬과다분비증후군(syndrome of inappropriate antidiuretic hormone, SIADH)이 항암화학요법을 시행받은 환자들에게서 발생하였다고 보고되고 있다. SIADH를 유발하는 항암제는 아직까지 몇 가지 외에는 많이 알려져 있지 않다. 본 예는 위암으로 위전절제술, 비장절제술, 횡행결장구역절제술을 시행 받은 55세 여자로 수술 후 복막전이가 발견되어 S-1 ($80\;mg/m^{2}$)과 cisplatin ($60\;mg/m^{2}$)을 이용한 항암화학요법 중 SIADH가 발생하였다. 환자는 3% 생리식염수를 투여한 후 저나트륨혈증이 정상화되어 퇴원하였다.

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