• Title/Summary/Keyword: Adenosine stress

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Effect of Moutan Cortex Radicis on gene expression profile of differentiated PC12 rat cells oxidative-stressed with hydrogen peroxide (모단피의 PC12 cell 산화억제 효과 및 neuronal 유전자 발현 profile 분석에 대한 연구)

  • Kim Hyun Hee;Rho Sam Woong;Na Youn Gin;Bae Hyun Su;Shin Min Kyu;Kim Chung Suk;Hong Moo Chang
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.2
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    • pp.529-541
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    • 2003
  • Yukmijihwang-tang has been widely used as an and-aging herbal medicine for hundred years in Asian countries. Numerous studies show that Yukmijihwangtang has anti-oxidative effect both in vivo and in vitro. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective herb in Yukmijihwang-tang on undifferentiated PC12 cells upon oxidative-stressed with hydrogen peroxide. The purpose of this study is to; 1) evaluate the recovery of neuronal damage by assessing the anti-oxidant effect of MCR on PC12 cells differentiated with nerve growth factor (NGF), 2) identify candidate genes responsible for anti-oxidative effect on differentiated PC12 cells by oligonucleotide chip microarray. PC12 cells, which were differentiated by treating with NGF, were treated without or with hydrogen peroxide in the presence or absence of various concentration of MCR. Cell survival was determined by using MTS assay. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2DCFDA assay The viability of cells treated with MCR was significantly recovered from stressed PC12 cell. In addition, wide rage of concentrations of MCR shows dose-dependent inhibitory effect on ROS production in oxidative-stressed cells. Total RNAs of cells without treatment(Control group), only treated with H₂O₂ (stressed group) and treated with both H₂O₂ and of MCR (MCR group) were isolated, and cDNAs was synthesized using oligoT7(dT) primer. The fragmented cRNAs, synthesized from cDNAs, were applied to Affymetrix GeneChip Rat Neurobiology U34 Array. mRNA of Calcium/calmodulin-dependent protein kinase II delta subunit(CaMKII), neuron glucose transporter (GLUT3) and myelin/oligodendrocyte glycoprotein(MOG) were downregulated in Stressed group comparing to Control group. P2X2-5 receptor (P2X2R-5), P2X2-4 receptor (P2X2R-4), c-fos, 25 kDa synaptosomal attachment protein(SNAP-25a) and GLUT3 were downregulated, whereas A2 adenosine receptor (A2AR), cathechol-O-methyltransferase(COMT), glucose transporter 1 (GLUT1), EST223333, heme oxygenase (HO), VGF, UI-R-CO-ja-a-07-0-Ul.s1 and macrophage migration inhibitory factor (MIF) were upregulated in MCA group comparing to Control group. Expression of Putative potassium channel subunit protein (ACK4), P2X2A-5, P2X2A-4, Interferon-gamma inducing factor isoform alpha precursor (IL-18α), EST199031, P2XR, P2X2 purinoceptor isoform e (P2X2R-e), Precursor interleukin 18 (IL-18) were downregulated, whereas MOO, EST223333, GLUT-1, MIF, Neuronatin alpha, UI-R-C0-ja-a-07-0-Ul.s1, A2. adenosine receptor, COMT, neuron-specific enolase (NSE), HO, VGF, A rat novel protein which is expressed with nerve injury (E12625) were upregulated in MCR group comparing to Stressed group. The results suggest that decreased viability and AOS production of PC12 cell by H₂O₂ may be, at lease, mediated by impaired glucose transporter expression. It is implicated that the MCR treatment protect PC12 cell from oxidative stress via following mechanisms; improving glucose transport into the cell, enhancing expression of anti-oxidative genes and protecting from dopamine cytotoxicity by increment of COMT and MIF expression. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the anti-oxidative effects of herbal extract Moutan Cortex Radicis.

Diagnosis of Coronary Artery Disease using Myocardial Perfusion SPECT in Patients with Diabetes Mellitus: Analysis of Risk Factors (당뇨병 환자에서 심근관류 SPECT을 이용한 관동맥질환의 진단: 위험인자 분석)

  • Seo, Ji-Hyoung;Kang, Seong-Min;Bae, Jin-Ho;Jeong, Shin-Young;Lee, Sang-Woo;Yoo, Jeong-Soo;Ahn, Byeong-Cheol;Lee, Jae-Tae
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.3
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    • pp.155-162
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    • 2006
  • Purpose: Diabetes mellitus (DM) is a critical disease with higher rates of cardiovascular morbidity and mortality due to myocardial ischemia and infarction. There is glowing interest in how to determine high-risk patients who are candidates for screening testing. This study was performed to evaluate the incidence of coronary artery disease (CAD) in diabetic patients detected by Tc-99m MIBI myocardial perfusion SPECT (MPS) and to assess risk factors of CAD and cardiac hard events. Subjects and Methods: 203 diabetic patients (64 male, mean age $64.1{\pm}9.0$ years) who underwent MPS were included between Jan 2000 and July 2004. Cardiac death and nonfatal myocardial infarction (MI) were considered as hard events, and coronary angioplasty and bypass surgery >60 days after testing were considered as soft events. The mean follow-up period was $36{\pm}18$ months. Patients underwent exercise (n=6) or adenosine stress (n=197) myocardial perfusion SPECT. Results: Perfusion defects on MPS were detected in 28.6% (58/203) of the patients. There was no cardiac death but 11 hard events were observed. The annual cardiac hard event rate was 1.1%. In univariate analysis of clinical factors, typical anginal pain, peripheral vascular disease, peripheral polyneuropathy, and resting ECG abnormality were significantly associated with the ocurrence of hard events. Anginal pain, peripheral vascular disease, and resting ECG abnormality remained independent predictors of nonfatal MIs with multivariate analysis. Abnormal SPECT results were significantly associated with high prevalence of hard events but not independent predictors on uni- and multivariate analyses. Conclusion: Patients who were male, had longer diabetes duration (especially over 20 years), peripheral vascular disease, peripheral polyneuropathy, or resting ECG abnormality had higher incidence of CAD. Among clinical factors in diabetic patients, typical angina, peripheral vascular disease, peripheral polyneuropathy, and resting ECG abnormality were strong predictors of hard events.

Comparison Study between Myocardial Velocity obtained from Gated Myocardial SPECT and Myocardial Functional indices with a Focus on Myocardial Perfusion (게이트 심근 관류 SPECT에서 구한 심근 속도와 심근 관류를 중심으로 한 심근 기능 지표와의 비교연구)

  • Ha, Jung-Min;Jeong, Shin-Young;Bom, Hee-Seung;Lee, Byeong-Il
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.5
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    • pp.386-394
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    • 2009
  • Purpose: We aimed to assess the myocardial velocity on gated myocardial perfusion SPECT (gated MPS), to compare myocardial velocity between patients without coronary artery disease (CAD) and CAD patients and to assess the correlation of myocardial velocity and perfusion and wall thickening on CAD group. Materials and Methods: Seventeen patients without CAD (M:F=9:8, mean age $61.8{\pm}11.1$ yrs: group A) and thirty-nine patients with CAD (M:F=18:21, mean age $66.9{\pm}8.1$ yrs : group B) had undergone one-day adenosine stress gated MPS. In twenty segment model, 12 segments (except apical and basal segments) of each patient were included. We obtained systolic and diastolic gate ratio in left ventricular volume curve by eight frames per cardiac cycle on gated MPS. Using the systolic and diastolic gate ratio and R-R time of each patient, we obtained systolic and diastolic time ratio. The myocardial velocity was defined as wall thickening over systolic or diastolic time. Results: We presented normal range of myocardial velocities according segments and territories of coronary artery. The myocardial velocity of group B was significantly lower than group A (p=0.00). There was no significant difference between the myocardial velocity of group B with preserved EF and group A. The stress systolic velocity significantly correlated with regional myocardial perfusion in group B with preserved EF (p=0.00) as well as decreased EF (p=0.01). In group B, stress perfusion of segments which had decreased wall thickening and decreased myocardial velocity was significantly lower than segments which had decreased wall thickening and preserved myocardial velocity (p=0.01). Conclusion: The new functional index of velocity will be used as an useful of gated MPS.

Evaluation of Perfusion and Image Quality Changes by Reconstruction Methods in 13N-Ammonia Myocardial Perfusion PET/CT (13N-암모니아 심근관류 PET/CT 검사 시 영상 재구성 방법에 따른 관류량 변화와 영상 평가)

  • Do, Yong Ho;Lee, Hong Jae;Kim, Jin Eui
    • The Korean Journal of Nuclear Medicine Technology
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    • v.18 no.1
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    • pp.69-75
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    • 2014
  • Purpose: The aim of this study was to evaluate changes of quantitative and semi-quantitative myocardial perfusion indices and image quality by image reconstruction methods in $^{13}N$-ammonia ($^{13}N-NH_3$) myocardial perfusion PET/CT. Materials and Methods: Data of 14 (8 men, 6 women) patients underwent rest and adenosine stress $^{13}N-NH_3$ PET/CT (Biograph TruePoint 40 with TrueV, Siemens) were collected. Listmode scans were acquired for 10 minutes by injecting 370MBq of $^{13}N-NH_3$. Dynamic and static reconstruction was performed by use of FBP, iterative2D (2D), iterative3D (3D) and iterative TrueX (TrueX) algorithm. Coronary flow reserve (CFR) of dynamic reconstruction data, extent(%) and total perfusion deficit (TPD) (%) measured in sum of 4-10 minutes scan were evaluated by comparing with 2D method which was recommended by vendor. The image quality of each reconstructed data was compared and evaluated by five nuclear medicine physicians through a blind test. Results: CFR were lower in TrueX 18.68% (P=0.0002), FBP 4.35% (P=0.1243) and higher in 3D 7.91% (P<0.0001). As semi-quantitative values, extent and TPD of stress were higher in 3D 3.07%p (P=0.001), 2.36%p (P=0.0002), FBP 1.93%p (P=0.4275), 1.57%p (P=0.4595), TrueX 5.43%p (P=0.0003), 3.93%p (P<0.0001). Extent and TPD of rest were lower in FBP 0.86%p (P=0.1953), 0.57%p (P=0.2053) and higher in 3D 3.21%p (P=0.0006), 2.57%p (P=0.0001) and TrueX 5.36%p (P<0.0001), 4.36%p (P<0.0001). Based on the results of the blind test for image resolution and noise from the snapshot, 3D obtained the highest score, followed by 2D, TrueX and FBP. Conclusion: We found that quantitative and semi-quantitative myocardial perfusion values could be under- or over-estimated according to the reconstruction algorithm in $^{13}N-NH_3$ PET/CT. Therefore, proper dynamic and static reconstruction method should be established to provide accurate myocardial perfusion value.

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Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Treatment during Pre-maturation Increases the Maturation of Porcine Oocytes Derived from Small Follicles

  • Park, Kyu-Mi;So, Kyoung-Ha;Hyun, Sang-Hwan
    • Journal of Embryo Transfer
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    • v.33 no.1
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    • pp.1-11
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    • 2018
  • Cellular cyclic adenosine-3' 5'-monophosphate (cAMP) modulator is known as meiotic inhibitor and can delays spontaneous maturation in IVM experiment. Among many cAMP modulators, the role of Pituitary adenylate cyclase activating polypeptide (PACAP) on IVM isn't known. The purpose of this study is to improve the maturation of oocytes derived from follicles ${\leq}3mm$ in diameter through PACAP as meiotic inhibitor during pre-in vitro maturation (pre-IVM). First, we checked PACAP and its receptors in cumulus cells and, to establish the optimal phase and concentration of PACAP for pre-IVM, we conducted chromatin configuration assessments. As a result, the rate of GV (Germinal Vesicle) according to duration of pre-IVM was significantly decreased 12 h and 18 h after IVM (87.1 and 84.1%, respectively) compared to 0 h (99.4%). When COC was cultured for 18 h, the GV rate in the $1{\mu}M$ of PACAP treatment group (82.1%) was significantly higher than any other PACAP treatment groups (60.5, 64.1, 74.4 and 69.9 %, respectively). So, we divided into four groups as follows; MF (the conventional IVM group, obtained from follicle from 3 to 6 mm in diameter), SF (the conventional IVM group, obtained from follicle ${\leq}3mm$ in diameter), Pre-SF(-)PACAP (IVM group including 18 h pre-IVM without $1{\mu}M$ of PACAP, obtained from follicle ${\leq}3mm$ in diameter) and Pre-SF(+)PACAP (IVM group including 18 h pre-IVM with $1{\mu}M$ of PACAP, obtained from follicle ${\leq}3mm$ in diameter). To examine the effect of PACAP during pre-IVM, we investigated analysis of nuclear maturation, intracellular glutathione (GSH) and reactive oxygen species (ROS) levels. In cumulus cells, PACAP receptors, ADCYAP1R1 and VIPR1 were detected but were not detected in oocytes. After IVM, the Pre-SF(+)PACAP had the highest Metaphase II rate (91.7%) among all groups (P<0.05). The GSH levels in the MF and Pre-SF(+)PACAP were significantly higher than in the other groups (P<0.05) and ROS levels was no significant difference among all groups. In conclusion, these results indicated that even though the oocytes were derived from SF, pre-IVM application of PACAP improved meiotic and cytoplasmic maturation by regulating intracellular oxidative stress.

Cannabidiol Inhibits Lipogenesis by Regulating Akt/AMPK-SREBP-1 Pathway in Sebocytes (피지세포에서 Akt/AMPK-SREBP-1 경로를 통한 CBD의 피지 합성 억제 효능)

  • Yoon Gyung Kwon;Ji Young Yoon;Hanon Lee;Dong Hyo Kim;Jun Hyo Lee;Diane M Thiboutot;Dae Hun Suh;Byoung Jun Park
    • Journal of Life Science
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    • v.33 no.4
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    • pp.343-348
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    • 2023
  • Acne is one of the most common skin diseases, mainly occurring in adolescence. The pathophysiology of acne involves not only hormonal, genetic and environmental factors, but also other factors including hyperseborrhea, inflammation, over-keratinization of follicular keratinocytes and overgrowth of Cutibacterium acnes (C. acnes). Cannabidiol (CBD) is known to relieve pain, stress and inflammation. Moreover, cannabis extracts containing CBD have been reported to be effective in treating acne. However, the therapeutic effect of CBD on acne remains unclear. Therefore, this study aimed to investigate the effect and mechanism of CBD on lipogenesis in SEB-1 sebocytes. We treated sebocytes with CBD and found that it not only inhibited lipid synthesis, but also inhibited cell proliferation by inducing apoptosis. We then demonstrated that sterol response element-binding protein-1 (SREBP-1) mediates the inhibitory effect of CBD on lipogenesis. Furthermore, Akt and adenosine monophosphate-activated protein kinase (AMPK), upstream regulators of SREBP-1, were regulated by CBD treatment. Taken together, our studies demonstrate that CBD inhibits adipogenesis by regulating the Akt/AMPK-SREBP-1 signaling pathway, providing potential for use as a therapeutic agent for acne. Further research is needed to confirm the effect of CBD on inflammation caused by hyperkeratosis, which will increase the possibility of using CBD for acne treatment.

Myocardial Tracer Uptake in SPECT Images after Direct Intracoronary Injection Of TI-201: Comparison with Stress-Reinjection Images (관동맥내 주사 TI-201 SPECT에서 심근 분절의 섭취: 부하-재주사 TI-201 영상과의 비교)

  • Seo, Ji-Hyoung;Kang, Seong-Min;Bae, Jin-Ho;Lee, Yong-Jin;Lee, Sang-Woo;Yoo, Jeong-Soo;Ahn, Byeong-Cheol;Cho, Yong-Geun;Lee, Jae-Tae
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.4
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    • pp.291-298
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    • 2007
  • Purpose: To investigate the feasibility of TI-201 SPECT with intra coronary injection (lC-I) in the detection of viable myocardium, we have performed SPECT imaging after direct intracoronary injection of TI-201 and images were compared with those of stress-reinjection (Re-I) SPECT. Methods: Fourteen coronary artery disease patients (male 11, mean age 54 years) who had myocardial infarction or demonstrated left ventricular wall motion abnormality on echocardiography were enrolled. Three mCi of TI-201 was injected into both coronary arteries during angiography and images were acquired between 6- and 24-hour after injection. Reinjection imaging with 1 mCi of TI-201 was performed at 4-hour after adenosine stress imaging with 3 mCi of TI-201. Images were interpreted according to 4-grade visual scoring system (grade 0-3). Segments with mild to moderated uptake (${\leq}$grade 1), and upgraded more than one score with reinjection, and were defined as viable myocardium. Results: Image quality was poor in two cases with IC-I. Numbers of non-viable segments were 60 (23.8%) with IC-I, and 38 (15.1%) with Re-I, respectively. Overall agreement for perfusion grade per myocardial segment in each IC-I and Re-I was 76.5%. Overall agreement for viable segment between IC-I and Re-I was 90.5%. Only one out of 38 segments interpreted as non-viable with Re-I were interpretated as viable with IC-I. And 23 out of 214 segments interpreted as viable with Re-I were interpreted as non-viable with IC-I. Conclusion: Intracoronary TI-201 SPECT seemed to be not advantageous over stress-rest reinjection imaging in the assessment of myocardial viability, mainly due to low count statistics at 6-hour or 24-hour delayed time points. The feasibility of intracoronary TI- 201 SPECT is considered to be limited.

Added Value of 3D Cardiac SPECT/CTA Fusion Imaging in Patients with Reversible Perfusion Defect on Myocardial Perfusion SPECT (심근관류 SPECT에서 가역적인 병변을 보인 환자의 3차원 심장 SPECT/CTA 퓨전영상의 유용성)

  • Kong, Eun-Jung;Cho, Ihn-Ho;Kang, Won-Jun;Kim, Seong-Min;Won, Kyoung-Sook;Lim, Seok-Tae;Hwang, Kyung-Hoon;Lee, Byeong-Il;Bom, Hee-Seung
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.6
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    • pp.513-518
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    • 2009
  • Purpose: Integration of the functional information of myocardial perfusion SPECT (MPS) and the morphoanatomical information of coronary CT angiography (CTA) may provide useful additional diagnostic information of the spatial relationship between perfusion defects and coronary stenosis. We studied to know the added value of three dimensional cardiac SPECT/CTA fusion imaging (fusion image) by comparing between fusion image and MPS. Materials and Methods: Forty-eight patients (M:F=26:22, Age: $63.3{\pm}10.4$ years) with a reversible perfusion defect on MPS (adenosine stress/rest SPECT with Tc-99m sestamibi or tetrofosmin) and CTA were included. Fusion images were molded and compared with the findings from the MPS. Invasive coronary angiography served as a reference standard for fusion image and MPS. Results: Total 144 coronary arteries in 48 patients were analyzed; Fusion image yielded the sensitivity, specificity, negative and positive predictive value for the detection of hemodynamically significant stenosis per coronary artery 82.5%, 79.3%, 76.7% and 84.6%, respectively. Respective values for the MPS were 68.8%, 70.7%, 62.1% and 76.4%. And fusion image also could detect more multi-vessel disease. Conclusion: Fused three dimensional volume-rendered SPECT/CTA imaging provides intuitive convincing information about hemodynamic relevant lesion and could improved diagnostic accuracy.

Effect of Natural Plant Mixtures on Behavioral Profiles and Antioxidants Status in SD Rats (자생식물 혼합 추출물이 SD 흰쥐에서의 행동양상 및 항산화 체계에 미치는 영향)

  • Seo, Bo-Young;Kim, Min-Jung;Kim, Hyun-Su;Park, Hae-Ryong;Lee, Seung-Cheol;Park, Eun-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.9
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    • pp.1208-1214
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    • 2011
  • Caffeine, a psychoactive stimulant, has been implicated in the modulation of learning and memory functions due to its action as a non-selective adenosine receptors antagonist. On the contrary, some side effects of caffeine have been reported, such as an increased energy loss and metabolic rate, decrease DNA synthesis in the spleen, and increased oxidative damage to exerted on LDL particles. Therefore, the aim of this study was to develop a safe stimulant from natural plants mixture (Aralia elata, Acori graminei Rhizoma, Chrysanthemum, Dandleion, Guarana, Shepherd's purse) that can be used as a substitute for caffeine. Thirty SD rats were divided into three groups; control group, caffeine group (15.0 mg/kg, i.p.), and natural plants mixture group (NP, 1 mL/kg, p.o.). The effect of NP extract on stimulant activity was evaluated with open-field test (OFT) and plus maze test for measurement of behavioral profiles. Plasma lipid profiles, lipid peroxidation in LDL (conjugated dienes), total antioxidant capacity (TRAP) and DNA damage in white blood, liver, and brain cells were measured. In the OFT, immobility time was increased significantly by acute (once) and chronic (3 weeks) supplementation of NP and showed a similar effect to caffeine treatment. Three weeks of caffeine treatment caused plasma lipid peroxidation and DNA damage in liver cells, whereas there were no changes in the NP group. NP group showed a higher plasma HDL cholesterol concentration compared to the caffeine group. The results indicate that the natural plants mixture had a stimulant effect without inducing oxidative stress.