The Mechanism of the Late Preconditioning Effect of 3-Nitropropionic Acid

Basgut, Bilgen,Aypar, Eda,Basgut, Ertug,Akin, K. Okhan,Kilic, Nedret,Cakici, Idal 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.10

The aim of the present study was to investigate the mechanism of effect of 3-nitropropionic acid- (3-NP) induced late preconditioning in rat heart. For this purpose 20-30 min before 3-NP (20 mg/kg, i.p.) injection, the rats were treated intraperitoneally with 5-hydroxydecanoate (40 mg/kg, 5-HD, mitochondrial $K_{ATP}$-channel blocker), L-NAME (100 mg/kg, NOS inhibitor), N-2-mercaptopropionylglycine (100 mg/kg, MPG, free radical scavenger), or superoxide dismutase+catalase (10000+10000 IU/kg, SOD+CAT). Control rats received saline only without 3-NP pretreatment. After two days, hearts were isolated and perfused at a constant pressure in a Langendorff apparatus. 15-min global ischemia followed by 30-min reperfusion was applied to all hearts. Pretreatment of 3-NP significantly reduced infarct size, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) levels, and incidence of ventricular tachycardia (VT) compared with the control group receiving saline only. 5-HD, L-NAME, MPG, or SOD+CAT treatment statistically reversed 3-NP-induced reduction in infarct size. Although CK-MB, LDH levels, and incidence of VT were also reduced by L-NAME, MPG, or SOD+CAT treatment, only 5-HD significantly inhibited beneficial effects of 3-NP on all of the parameters above. These results showed that mito-$K_{ATP}$ channels play a pivotal role in late preconditioning effect of 3-NP in the isolated rat heart. However, other mediators such as reactive oxygen species and NO may be, at least in part, involved in mechanisms of this effect.

The Mechanism of the Late Preconditioning Effect of 3-Nitropropionic Acid

Bilgen Basgut,Eda Aypar,Ertug Basgut,K. Okhan Akln,Nedret Klllc,And Iclal Caklcl 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.10

The aim of the present study was to investigate the mechanism of effect of 3-nitropropionic acid- (3-NP) induced late preconditioning in rat heart. For this purpose 20-30 min before 3-NP (20 mg/kg, i.p.) injection, the rats were treated intraperitoneally with 5-hydroxydecanoate (40 mg/kg, 5-HD, mitochondrial KATP-channel blocker), L-NAME (100 mg/kg, NOS inhibitor), N-2-mercaptopropionylglycine (100 mg/ kg , MPG, free radical scavenger), or superoxide dismutase+catalase (10000+10000 IU/kg , SOD+CAT). Control rats received saline only without 3-NP pretreatment. After two days, hearts were isolated and perfused at a constant pressure in a Langendorff apparatus. 15- min global ischemia followed by 30-min reperfusion was applied to all hearts. Pretreatment of 3-NP significantly reduced infarct size, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) levels, and incidence of ventricular tachycardia (VT) compared with the control group receiving saline only. 5-HD, L-NAME, MPG, or SOD+CAT treatment statistically reversed 3-NP-induced reduction in infarct size. Although CK-MB, LDH levels, and incidence of VT were also reduced by L-NAME, MPG, or SOD+CAT treatment, only 5-HD significantly inhibited beneficial effects of 3-NP on all of the parameters above. These results showed that mito-KATP channels play a pivotal role in late preconditioning effect of 3-NP in the isolated rat heart. However, other mediators such as reactive oxygen species and NO may be, at least in part, involved in mechanisms of this effect.

Chronic ouabain treatment induces Rho kinase activation

Aysun Ozdemir,Gürkan Şahan,Ayşegül Demirtas,Eda Aypar,Gürkan Gözübüyük,Nilüfer Nermin Turan,Mustafa Ark 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.10

Ouabain is an endogenous Na?/K?-ATPaseinhibitor whose chronic administration induces hypertension. Endogenous ouabain levels increase in humanessential hypertension. On the other hand, Rho/Rho kinase(ROCK) pathway has been implicated in various animalmodels of hypertension. In the current work, we evaluatedthe possible involvement of Rho kinase in ouabain-inducedhypertension. Ouabain was administered daily (20 lg/kg,i.p.) to Wistar rats for 6 weeks. After the ouabain treatment,we evaluated the possible changes in vascular responsesto KCl and phenylephrine alone and in thepresence of Rho kinase inhibitor Y27632. We also determinedthe expressions of ROCKs, Rho A and phosphorylationof myosin binding subunit of myosin light chainphosphatase (pMYPT) and activation of Rho A. Agonistinducedcontractions in the presence of Y27632 are significantlydecreased and Y27632-induced relaxations inaortas precontracted with phenylephrine are significantlyenhanced with the chronic treatment of ouabain. Althoughthe expressions of ROCK I and ROCK II remained unchanged,pMYPT expression was significantly increased inouabain-treated group. Moreover, Rho A expression andactivation were decreased after treatment with ouabain. Although Rho kinase expression did not change in aortas,increased basal Rho kinase activation may contribute to thedevelopment of ouabain-induced hypertension. Our currentdata present the first evidence that Rho kinase is involvedin the development of ouabain-induced hypertension inrats.

Automated 3D scoring of fluorescence in situ hybridization (FISH) using a confocal whole slide imaging scanner

Frankenstein Ziv,Naohiro Uraoka,Umut Aypar,Ruth Aryeequaye,Mamta Rao,Meera Hameed,Yanming Zhang,Yukako Yagi 한국현미경학회 2021 Applied microscopy Vol.51 No.1

Fluorescence in situ hybridization (FISH) is a technique to visualize specific DNA/RNA sequences within the cell nuclei and provide the presence, location and structural integrity of genes on chromosomes. A confocal Whole Slide Imaging (WSI) scanner technology has superior depth resolution compared to wide-field fluorescence imaging. Confocal WSI has the ability to perform serial optical sections with specimen imaging, which is critical for 3D tissue reconstruction for volumetric spatial analysis. The standard clinical manual scoring for FISH is labor-intensive, time-consuming and subjective. Application of multi-gene FISH analysis alongside 3D imaging, significantly increase the level of complexity required for an accurate 3D analysis. Therefore, the purpose of this study is to establish automated 3D FISH scoring for z-stack images from confocal WSI scanner. The algorithm and the application we developed, SHIMARIS PAFQ, successfully employs 3D calculations for clear individual cell nuclei segmentation, gene signals detection and distribution of break-apart probes signal patterns, including standard break-apart, and variant patterns due to truncation, and deletion, etc. The analysis was accurate and precise when compared with ground truth clinical manual counting and scoring reported in ten lymphoma and solid tumors cases. The algorithm and the application we developed, SHIMARIS PAFQ, is objective and more efficient than the conventional procedure. It enables the automated counting of more nuclei, precisely detecting additional abnormal signal variations in nuclei patterns and analyzes gigabyte multi-layer stacking imaging data of tissue samples from patients. Currently, we are developing a deep learning algorithm for automated tumor area detection to be integrated with SHIMARIS PAFQ.

Do Pregnant Women’s Information Sources Affect their Attitudes toward the Oral Glucose Tolerance Test? A Descriptive Cross-Sectional Study

Hande Ya?can,Elif Uluda?,Nuran Nur Aypar Akba?,Hulya Ozberk 숙명여자대학교 아시아여성연구원 2021 Asian Women Vol.37 No.2

The occurrence of gestational diabetes has increased recently. This condition, which can have extremely negative consequences for both mother and baby, can be detected by using an oral glucose tolerance test, and remedial action can be taken to prevent or reduce complications based on the results of the test. However, information about the oral glucose tolerance test (the OGTT) from different sources can negatively affect pregnant women and their families, resulting in their not taking the test. The aim of this study is to determine the knowledge and attitudes of women in the third trimester of pregnancy in relation to the OGTT. This descriptive cross-sectional study was conducted at two university hospitals between October 2017 and June 2018. The voluntary participants comprised 303 pregnant women in the third trimester of pregnancy. The research data were collected using “Demographic Data Collection Form and Determination Form for the OGTT Screening Status of Pregnant Women.” The relationship between categorical variables was analyzed using chi-square tests. The percentage of pregnant women who did not have the OGTT monitoring was 32.7%. The main reasons for this were media exposure (28.6%), lack of knowledge (19.4%), and doctor’s recommendation (19.4%). Forty-three percent of the pregnant women who did not have the OGTT were not aware of why the test done and 73.3% thought that the OGTT was dangerous for the baby. Of these, 58.8% of pregnant women received the information about the OGTT from doctors and 41.2% from midwives and nurses. A significant difference was found between the OGTT status of women according to their place of residence, number of pregnancies, knowledge about why the OGTT is performed, information sources, and the belief that the test is dangerous to the health of mother and baby (p < 0.05). Not having OGTT screening during pregnancy can lead to irremediable negative complications for the health of both mother and baby.