• Title/Summary/Keyword: Reperfusion injury

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Sertad1 Induces Neurological Injury after Ischemic Stroke via the CDK4/p-Rb Pathway

  • Li, Jianxiong;Li, Bin;Bu, Yujie;Zhang, Hailin;Guo, Jia;Hu, Jianping;Zhang, Yanfang
    • Molecules and Cells
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    • v.45 no.4
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    • pp.216-230
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    • 2022
  • SERTA domain-containing protein 1 (Sertad1) is upregulated in the models of DNA damage and Alzheimer's disease, contributing to neuronal death. However, the role and mechanism of Sertad1 in ischemic/hypoxic neurological injury remain unclear. In the present study, our results showed that the expression of Sertad1 was upregulated in a mouse middle cerebral artery occlusion and reperfusion model and in HT22 cells after oxygen-glucose deprivation/reoxygenation (OGD/R). Sertad1 knockdown significantly ameliorated ischemia-induced brain infarct volume, neurological deficits and neuronal apoptosis. In addition, it significantly ameliorated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Sertad1 knockdown significantly inhibited the ischemic/hypoxic-induced expression of p-Rb, B-Myb, and Bim in vivo and in vitro. However, Sertad1 overexpression significantly exacerbated the OGD/R-induced inhibition of cell viability and apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. In further studies, we demonstrated that Sertad1 directly binds to CDK4 and the CDK4 inhibitor ON123300 restores the effects of Sertad1 overexpression on OGD/R-induced apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. These results suggested that Sertad1 contributed to ischemic/hypoxic neurological injury by activating the CDK4/p-Rb pathway.

Radiomics of Non-Contrast-Enhanced T1 Mapping: Diagnostic and Predictive Performance for Myocardial Injury in Acute ST-Segment-Elevation Myocardial Infarction

  • Quanmei Ma;Yue Ma;Tongtong Yu;Zhaoqing Sun;Yang Hou
    • Korean Journal of Radiology
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    • v.22 no.4
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    • pp.535-546
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    • 2021
  • Objective: To evaluate the feasibility of texture analysis on non-contrast-enhanced T1 maps of cardiac magnetic resonance (CMR) imaging for the diagnosis of myocardial injury in acute myocardial infarction (MI). Materials and Methods: This study included 68 patients (57 males and 11 females; mean age, 55.7 ± 10.5 years) with acute ST-segment-elevation MI who had undergone 3T CMR after a percutaneous coronary intervention. Forty patients of them also underwent a 6-month follow-up CMR. The CMR protocol included T2-weighted imaging, T1 mapping, rest first-pass perfusion, and late gadolinium enhancement. Radiomics features were extracted from the T1 maps using open-source software. Radiomics signatures were constructed with the selected strongest features to evaluate the myocardial injury severity and predict the recovery of left ventricular (LV) longitudinal systolic myocardial contractility. Results: A total of 1088 segments of the acute CMR images were analyzed; 103 (9.5%) segments showed microvascular obstruction (MVO), and 557 (51.2%) segments showed MI. A total of 640 segments were included in the 6-month follow-up analysis, of which 160 (25.0%) segments showed favorable recovery of LV longitudinal systolic myocardial contractility. Combined radiomics signature and T1 values resulted in a higher diagnostic performance for MVO compared to T1 values alone (area under the curve [AUC] in the training set; 0.88, 0.72, p = 0.031: AUC in the test set; 0.86, 0.71, p = 0.002). Combined radiomics signature and T1 values also provided a higher predictive value for LV longitudinal systolic myocardial contractility recovery compared to T1 values (AUC in the training set; 0.76, 0.55, p < 0.001: AUC in the test set; 0.77, 0.60, p < 0.001). Conclusion: The combination of radiomics of non-contrast-enhanced T1 mapping and T1 values could provide higher diagnostic accuracy for MVO. Radiomics also provides incremental value in the prediction of LV longitudinal systolic myocardial contractility at six months.

Neuroprotective Effects of Hydroxyfullerene in Rats Subjected to Global Cerebral Ischemia

  • Kim, Young-Ock;Kim, Hak-Jae;Kim, Su-Kang;Yoon, Bum-Chul
    • Molecular & Cellular Toxicology
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    • v.4 no.3
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    • pp.218-223
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    • 2008
  • Oxidative stress is believed to contribute to the neuronal damage induced by cerebral ischemia/reperfusion injury. The present study was undertaken to evaluate the possible antioxidant neuroprotective effect of hydroxyfullerene (a radical absorbing cage molecule) against neuronal death in hippocampal CA1 neurons following transient global cerebral ischemia in the rat. Transient global cerebral ischemia was induced in male Wistar rats by four vessel- occlusion (4VO) for 10 min. Lipid peroxidation in brain tissues was determined by measuring the concentrations of thiobarbituric acid-reactive substances (TBARS). Furthermore, the apoptotic effects of ${H_2}{O_2}$ on PC12 cells were also investigated. Cell viabilities were measured using MTT [3-(4,5-dimethylthiazolyl-2)-2,-5-diphenyltetrazolium bromide] assays. Hydroxyfullerene, when administered to rats at 0.3-3 mg/kg i.p. at 0 and 90 minutes after 4-VO was found to significantly reduce CA1 neuron death by 72.4% on hippocampal CA1 neurons. Our findings suggest that hydroxyfullerene protects neurons from transient global cerebral injury in the rat hippocampus by reducing oxidative stress and lipid peroxidation levels, which contribute to apoptotic cell death.

Brain Death and Kidney Transplantation in Dogs (개의 뇌사와 신장이식)

  • 우흥명;권오경
    • Journal of Veterinary Clinics
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    • v.18 no.4
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    • pp.358-362
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    • 2001
  • Brain dead (BD) patients remain the largest source of solid organs for transplantation. BD has shown to decrease graft function and survival in rodent models. The aim of this study was to evaluate how brain death affects graft viability in the donor and kidney tolerance to cold preservation as assessed by survival in a canine transplantation. 13 Beagle dogs were used for the study. Brain death was induced by the sudden inflation of a subdural balloon catheter with continuous monitoring of arterial blood pressure and eletroencephalographic activity (n=3). Sixteen hours after conformation of brain death, kidney graft were retrieved (n=6). Non-BD donors served as controls (n=4). All kidneys were flushed with University of Wisconsin (UW) solution and preserved for 24 hours at 4$^{\circ}C$ before transplantation. Recipient survival rates, serum creatinine level were analyzed. Brain death induced the well-known Cushing reaction with a severe increase in blood pressure and tachycardia. Thereafter, cardiac function returned progressively to baseline within 8 hours and remained stable until the end of the experiment. All of dogs in both group transplanted were survived until 7 days (100%), and the kidneys showed functional early rejection at 8.3$\pm$0.5 days and 8.5$\pm$0.5 days after transplantation, in BD and allograft group, respectively. BD kidneys were functionally similar to control kidneys for 7 days after transplantated. Brain death has no deleterious effect on preservation injury and survival of dog kidney transplantation, although it induces changes in hemodynamic parameters. This study reveals that kidneys from BD donors do not exhibit more ischemia reperfusion injury, and support good early function and survival.

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Effects of Astragali Radix and Polygalae Radix on Cerebral Ischemic and Reperfused Injury (황기와 원지분획의 뇌허혈에 관한 약효연구)

  • Han, Suk-Hee;Park, Jin-Hyuk;Kim, Jin-Sook;Lee, Sun-Mee
    • YAKHAK HOEJI
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    • v.44 no.4
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    • pp.371-377
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    • 2000
  • In order to investigate the pharmacological properties of fractions of Astragali Radix and Polygalae Radix, the effects of the fractions on cerebral ischemia and subsequent reperfusion were studied. Brain ischemia was induced by bilateral common carotid artery occlusion in mongolian gerbil. Brains were recirculated for 30 mins after the 20 min occlusion. Methanol and butanol fractions of Astragali Radix and Polygalae Radix were administered orally 2 hrs before common carotid artery occlusion. Histological observations showed that brain ischemia induced severe brain damage evidenced by the presence of necrotic foci, edema and hemorrhage. This injury was prevented by the methanol fraction and butanol fraction of Polygalae Radix. The level of ATP in brain tissue significantly decreased in ischemic gerbils. This decrease was prevented by the pretreatment with butanol fraction of Polygalae Radix. In contrast, the levels of lactate and lipid peroxide were both elevated in ischemic gerbils. This elevation was inhibited by the pretreatments with methanol fraction and butanol fraction of Polygalae Radix. Our findings suggest that the Polygalae Radix improves ischemia-induced brain damage.

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The Safety Evaluation of a Potent Antioxidant, Fructose 1,6-diphosphate(FDP), for the Skin Application (항산화력이 우수한 Fructose 1,6-diphosphate(FDP)를 피부적용제로 응용하기 위한 안전성 평가)

  • 김배환;이병석;정경미;안수미;안수선;심영철
    • Toxicological Research
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    • v.18 no.3
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    • pp.267-273
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    • 2002
  • Fructose 1,6-diphosphate(FDP), a glycolytic metabolite, is reported to ameliorate inflammation and inhibit the nitric oxide production in murine macrophages stimulated with endotoxin. It is also reported that FDP has cytoprotective effects against hypoxia or ischemia/reperfusion injury in brain and heart, and may play a protective role in ultraviolet B (UVB, 280~320 nm)-injured keratinocyte by attenuating prostaglandin (PG)-E$_2$production and cyclooxygenase (COX)-2 expression, which are possibly through blocking the intracellular reactive oxygen species (ROS) accumulation. Therefore FDP is considered to act as a potent antioxidant especially in the skin. We conducted the several safety tests (single-dose toxicity, primary skin irritation test, eye irritation test, skin sensitization test, phototoxicity test, photosenitization test and human patch test) to see if FDP is safe in case used for the skin application. Our data obtained hitherto suggest that FDP is very safe if applied to the skin.

Experimental Studies on the Cold Storage of the Rabbit Heart for Transplantation (이식을 위한 심장의 장시간 보존에 관한 실험)

  • No, Jung-Gi;Lee, Cheol-Se;Lee, Gil-No
    • Journal of Chest Surgery
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    • v.22 no.6
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    • pp.887-893
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    • 1989
  • Donor availability is a major limiting factor in heart transplantation. Prolonging donor heart preservation would facilitate distant heart procurement. The setup used was the isolated retrograde perfused nonworking rabbit heart model and 4 hours of preservation at 2oC. And the electron microscopic findings of the myocardium were evaluated after reperfusion for 5 minutes. The following three groups [each group, n=4] were prepared: Group I: the heart was arrested with the St. Thomas Hospital solution [STH] and stored in Ringers lactate solution [RLS]; Group II: the heart was arrested with STH and stored in Modified Collins-Sachs solution [MCS]; Group g: the heart was arrested with and stored in MCS. The result was the most severe myocardial injury in the Group III on electron microscopic study.

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Synthesis and Biological Evaluation of 4-Heteroaryl-2-amino-5-methylimidazole Analogs as NHE-1 Inhibitors

  • Lee, Sun-Kyung;Yi, Kyu-Yang;Lee, Byung-Ho;Yoon, Boo-Soon
    • Bulletin of the Korean Chemical Society
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    • v.30 no.11
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    • pp.2621-2625
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    • 2009
  • To identify a non-acylguanidine NHE-1 inhibitor, an acylguanidne group was replaced with an imidazole group in the potent NHE-1 inhibitors with furan or benzothiphene core template, found from our previous studies. We synthesized and biologically evaluated 4-heteroaryl-2-amino-5-methylimidazole derivatives. All those imidazole compounds (16-18) represented the potent NHE-1 inhibitory activities, similar to the corresponding acylguanidine compounds.

Critical Care after Lung Transplantation

  • Kim, Song Yee;Jeong, Su Jin;Lee, Jin Gu;Park, Moo Suk;Paik, Hyo Chae;Na, Sungwon;Kim, Jeongmin
    • Acute and Critical Care
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    • v.33 no.4
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    • pp.206-215
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    • 2018
  • Since the first successful lung transplantation in 1983, there have been many advances in the field. Nevertheless, the latest data from the International Society for Heart and Lung Transplantation revealed that the risk of death from transplantation is 9%. Various aspects of postoperative management, including mechanical ventilation, could affect intensive care unit stay, hospital stay, and immediate postoperative morbidity and mortality. Complications such as reperfusion injury, graft rejection, infection, and dehiscence of anastomosis increase fatal adverse side effects immediately after surgery. In this article, we review the possible immediate complications after lung transplantation and summarize current knowledge on prevention and treatment.