• Archives of Pharmacal Research
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• v.16 no.1
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• pp.71-74
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• 1993

The protective effect of adenosine triphosphate (ATP) on gastic ulcer induced in rats has been studied. Gastic ulceration was induced by hypothemic restraint stress or dicolofenac sodium. Gastic acid secretion and mucosal injury produced by the hypothemic restraint stress was greater as compared with those produced by diclofenac sodifum. ATP significantly reduced area of injury, however, increased cyclic adenosine monophosphate (cATP) content. Administration of dipyridamole along with ATP did not change the total lesion area in both models when compared to ATP alone. Aminophyline antagonized antagonized the protective effect of ATP on the injured area. Famotidine was found to be effective in reducing gastric acid output as well as the total injured area without any change in cAMP content when given along with ATP.

• Korean Journal of Animal Reproduction
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• v.21 no.4
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• pp.325-333
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• 1997

Recent evidence indicates that growth factors modulate response of mammary epithelial cells to environmental stress. The objective of this study was to examine the cellular and biochemical responses of mammary tissue to environmental stress caused by artificial mastitis. For experimental a, pp.oach, toxins of most mastitis causing organisms(Staph. aureus or Strep. agalactiae) and heat stress(42$^{\circ}C$) were artificially exposed to mammary tissue. Effects of these environmental stresses on cell growth, cell death and heat shock protein synthesis were examined. Lactating mammary tissure were cultured under basal medium(DMEM) su, pp.emented with insulin(10$\mu\textrm{g}$/ml) and aldosterone(1$\mu\textrm{g}$/ml). All treatment groups in heat stress at 42$^{\circ}C$ incubation significantly decreased DNA synthesis rates in comparison with those at 39$^{\circ}C$(P<0.05), however, these decreased DNAa synthesis rates were recovered by addition of adenosine(10$\mu$M) and IGFI(10ng/ml). Similar results were obtained when tissue growth rates were measured by DNA content/tissue. Strep. agalactiae toxin did not significantly decreased DNA content/tissue in comparison with no treatment of bacterial toxin with or without heat stress, however, tended to decrease DNA contents/tissue without heat stress. In the fluorography analysis, heat stress(42$^{\circ}C$ incubation) slightly increased 35S-methoionine labelled 70kd protein synthesis. These results indicate that environmental stress caused by artificial mastitis slightly decreased mammary growth or mammary size, however, these results could be recovered by addition of adenosine and IGF-I.

• Journal of Cardiovascular Imaging
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• v.31 no.1
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• pp.26-38
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• 2023

BACKGROUND: Dobutamine and adenosine stress cardiac magnetic resonance (CMR) imaging is relatively contraindicated in patients with moderate to severe aortic valve stenosis (AS). We aimed to determine the safety of dobutamine and adenosine stress CMR in patients with moderate to severe AS. METHODS: In this retrospective study patients with AS who underwent either dobutamine or adenosine stress CMR for exclusion of obstructive coronary artery disease were enrolled. We recorded clinical data, CMR and echocardiography findings, and complications as well as minor symptoms. Patients with AS were compared to matched individuals without AS. RESULTS: A total of 187 patients with AS were identified and compared to age-, gender- and body mass index-matched 187 patients without AS. No severe complications were reported in the study nor the control group. The reported frequency of non-severe complications and minor symptoms were similar between the study and the control groups. Nineteen patients with AS experienced non-severe complications or minor symptoms during dobutamine stress CMR compared to eighteen patients without AS (p = 0.855). One patient with AS and two patients without AS undergoing adenosine stress CMR experienced minor symptoms (p = 0.562). Four examinations were aborted because of chest pain, paroxysmal atrial fibrillation and third-degree atrioventricular block. Inducible ischaemia, prior coronary artery bypass grafting, prior stroke and age were associated with a higher incidence of complications and minor symptoms. CONCLUSIONS: Moderate to severe AS was not associated with complications during CMR stress test. The incidence of non-severe complications and minor symptoms was greater with dobutamine.

• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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• pp.35-50
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• 1993

심근관류 스캔에서 약제부하 검사에 많이 이용되는 것으로는 adenosine, dipyridamole, dobutamine등이 있다. 이 약제들이 혈역학 및 thallium의 약동학에 미치는 효과를 검사하기 위하여 저자들은 15명의 건강인을 대상으로 이들 약제를 정맥주사한 후에와 그리고 운동부하를 시행한 후에 thallium-201 신근관류 스캔을 시행하여 thallium의 약동학에 미치는 영향에 대하여 서로 비교하였다. 부작용은 adenosine (87%), dipyridamole(80%), dobutamine (73%)을 정맥주사할 시에 흔히 나타났으나 경미하였다. 1예에서는 dobutamine을 주사할때의 부작용으로 인하여 최대용량을 투여하지는 못한바 있었다. 대상들은 dipyridamole (13%)이나 dobutamine (27%)보다 adenosine (60%)을 선호하였다 (P<0.05). Thallium의 절대 적인 심근섭취는 운동부하 검사보다 adenosine (1.3배), dipyridamole(1.2배), dobutamine(1.4배) 부하시에 더 많았고, 이들 약제 사이에는 유의한 차이는 없었다. Thallium의 심근제거율(%/hr)는 운동부하 검사보다 약제부하한 후에가 더 늦었다. 폐, 간, 비장, 및 내장지역에서 thallium의 섭취 및 제거는 운동부하 검사보다 약제부하시에 더 많았으나, 이들 약제 사이에는 유의한 차이가 없었다. Dobutamine 투여시의 thallium의 섭취 및 제거는 adenosine 또는 dipyridamole을 투여시의 결과와 상응하였다. 저자들은 adenosine, dipyridamole 및 dobutamine을 이용한 약제부하 thallium-201 심근관류 검사를 시행하는데 코든 대상들에서 어려움 없이 쉽게 시행할 수 있었다. Thallium의 심근내 섭취 및 제거는 각 약제부하에 따라서 다를 수가 있으므로 심근관류 스캔의 정량적인 분석을 시행할 때는 각각 약제에 대한 특별한 진단기준이 마련되어야 할 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.467-479
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• 2018

The aging process induces a plethora of changes in the body including alterations in hormonal regulation and metabolism in various organs including the heart. Aging is associated with marked increase in the vulnerability of the heart to ischemia-reperfusion injury. Furthermore, it significantly hampers the development of adaptive response to various forms of conditioning stimuli (pre/post/remote conditioning). Aging significantly impairs the activation of signaling pathways that mediate preconditioning-induced cardioprotection. It possibly impairs the uptake and release of adenosine, decreases the number of adenosine transporter sites and down-regulates the transcription of adenosine receptors in the myocardium to attenuate adenosine-mediated cardioprotection. Furthermore, aging decreases the expression of peroxisome proliferator-activated receptor gamma co-activator 1-alpha ($PGC-1{\alpha}$) and subsequent transcription of catalase enzyme which subsequently increases the oxidative stress and decreases the responsiveness to preconditioning stimuli in the senescent diabetic hearts. In addition, in the aged rat hearts, the conditioning stimulus fails to phosphorylate Akt kinase that is required for mediating cardioprotective signaling in the heart. Moreover, aging increases the concentration of $Na^+$ and $K^+$, connexin expression and caveolin abundance in the myocardium and increases the susceptibility to ischemia-reperfusion injury. In addition, aging also reduces the responsiveness to conditioning stimuli possibly due to reduced kinase signaling and reduced STAT-3 phosphorylation. However, aging is associated with an increase in MKP-1 phosphorylation, which dephosphorylates (deactivates) mitogen activated protein kinase that is involved in cardioprotective signaling. The present review describes aging as one of the major confounding factors in attenuating remote ischemic preconditioning-induced cardioprotection along with the possible mechanisms.

• Kidney Research and Clinical Practice
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• v.35 no.2
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• pp.69-77
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• 2016

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and its pathogenesis is complex and has not yet been fully elucidated. Abnormal glucose and lipid metabolism is key to understanding the pathogenesis of DN, which can develop in both type 1 and type 2 diabetes. A hallmark of this disease is the accumulation of glucose and lipids in renal cells, resulting in oxidative and endoplasmic reticulum stress, intracellular hypoxia, and inflammation, eventually leading to glomerulosclerosis and interstitial fibrosis. There is a growing body of evidence demonstrating that dysregulation of 50 adenosine monophosphate-activated protein kinase (AMPK), an enzyme that plays a principal role in cell growth and cellular energy homeostasis, in relevant tissues is a key component of the development of metabolic syndrome and type 2 diabetes mellitus; thus, targeting this enzyme may ameliorate some pathologic features of this disease. AMPK regulates the coordination of anabolic processes, with its activation proven to improve glucose and lipid homeostasis in insulin-resistant animal models, as well as demonstrating mitochondrial biogenesis and antitumor activity. In this review, we discuss new findings regarding the role of AMPK in the pathogenesis of DN and offer suggestions for feasible clinical use and future studies of the role of AMPK activators in this disorder.

• Molecules and Cells
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• v.43 no.1
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• pp.58-65
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• 2020

Fat mass and obesity-associated (FTO) gene helps to regulate energy homeostasis in mammals by controlling energy expenditure. In addition, FTO functions in the regulation of obesity and adipogenic differentiation; however, a role in osteogenic differentiation is unknown. This study investigated the effects of FTO on osteogenic differentiation of C3H10T1/2 cells and the underlying mechanism. Expression of osteogenic and endoplasmic reticulum (ER) stress markers were characterized by reverse-transcriptase polymerase chain reaction and western blotting. Alkaline phosphatase (ALP) staining was performed to assess ALP activity. BMP2 treatment increased mRNA expression of osteogenic genes and FTO. Overexpression of FTO increased expression of the osteogenic genes distal-less homeobox5 (Dlx5) and runt-related transcription factor 2 (Runx2). Activation of adenosine monophosphate-activated protein kinase (AMPK) increased FTO expression, and there was a positive feedback loop between FTO and p-AMPK. p-AMPK and FTO induced mild ER stress; however, tunicamycin-induced severe ER stress suppressed FTO expression and AMPK activation. In summary, FTO induces osteogenic differentiation of C3H10T1/2 cells upon BMP2 treatment by inducing mild ER stress via a positive feedback loop with p-AMPK. FTO expression and AMPK activation induce mild ER stress. By contrast, severe ER stress inhibits osteogenic differentiation by suppressing FTO expression and AMPK activation.

• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.531-539
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• 2024

Sleep is one of the most essential physiological phenomena for maintaining health. Sleep disturbances, such as insomnia, are often accompanied by psychiatric or physical conditions such as impaired attention, anxiety, and stress. Medication used to treat insomnia have concerns about potential side effects with long-term use, so interest in the use of alternative medicine is increasing. In this study, we investigated the hypnotic effects of β-lapachone (β-Lap), a natural naphthoquinone compound, using pentobarbital-induced sleep test, immunohistochemistry, real-time PCR, and western blot in mice. Our results indicated that β-Lap exerts a significant hypnotic effect by showing a decrease in sleep onset latency and an increase in total sleep time in pentobarbital-induced sleep model. The results of c-Fos immunostaining showed that β-Lap decreased neuronal activity in the basal forebrain and lateral hypothalamus, which are wakefulness-promoting brain regions, while increasing in the ventrolateral preoptic nucleus, a sleep-promoting region; all these effects were significantly abolished by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A₁ receptor (A₁R) antagonist. Western blot analysis showed that β-Lap increased extracellular signal-regulated kinase phosphorylation and nuclear factor-kappa B translocation from the cytoplasm to the nucleus; these effects were inhibited by DPCPX. Additionally, β-Lap increased the mRNA levels of A₁R. Taken together, these results suggest that β-Lap exerts hypnotic effects, potentially through A₁R.

• The Korean Journal of Nuclear Medicine
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• v.39 no.6
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• pp.473-480
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• 2005

Purpose: Adenosine myocardial perfusion SPECT has proven to be useful in the detection of coronary artery disease, in the follow up the success of various therapeutic regimens and in assessing the prognosis of coronary artery disease. The purpose of this study is to define the reproducibility of myocardial perfusion SPECT using adenosine stress testing between two consecutive Tc-99m sestaMIBI (MIBI) SPECT studies in the same subjects. Methods: Thirty patients suspected of coronary artery disease in stable condition underwent sequential Tc-99m MIBI SPECT studies using intravenous adenosine. Gamma camera, acquisition and processing protocols used for the two tests were identical and no invasive procedures were performed between two tests. Mean interval between two tests were 4.1 days (range: 2-11 days). The left ventricular wall was divided into na segments and the degree of myocardial tracer uptake was graded with four-point scoring system by visual analysis. Images were interpretated by two independent nuclear medicine physicians and consensus was taken for final decision, if segmental score was not agreeable. Results: Hemodynamic responses to adenosine were not different between two consecutive studies. There were no serious side effects to stop infusion of adenosine and side effects profile was not different. When myocardial uptake was divided into normal and abnormal uptake, 481 of 540 segments were concordant (agreement rate 89%, Kappa index 0.74). With four-grade storing system, exact agreement was 81.3% (439 of 540 segments, tau b=0.73). One and two-grade differences were observed in 97 segments (18%) and 4 segments (0.7%) respectively, but three-grade difference was not observed in any segment. Extent and severity scores were not different between two studios. The extent and severity scores of the perfusion defect revealed excellent positive correlation between two test (r value for percentage extent and severity score is 0.982 and 0.965, p<0.001) Conclusion: Hemodynamic responses and side effects profile were not different between two consecutive adenosine stress tests in the same subjects. Adenosine Tc-99m sestaMIBI SPECT is highly reproducible, and could be used to assess temporal changes in myocardial perfusion in individual patients.

• 대한핵의학회:학술대회논문집
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• 2004.11a
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• pp.389.1-389.1
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• 2004