• Reproductive and Developmental Biology
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• 제35권2호
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• pp.167-174
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• 2011

Acute ischemic stroke results from sudden decrease or loss of blood supply to an area of the brain, resulting in a coinciding loss of neurological function. The antioxidant action of melatonin is an important mechanism among its known effects to protective activity during ischemic/reperfusion injury. The focus of this research, therapeutic efficacy of melatonin on recovery of neurological function following long term treatment in ischemic brain injured rats. Male Sprague-Dawley rats (n=40; 8 weeks old) were divided into the control group, and MCAo groups (Vehicle, MT7 : MCAo+ melatonin injection at 7:00, MT19 : MCAo+melatonin injection at 19:00, and MT7,19 : MCAo+melatonin injection at 7:00 and 19:00). Rat body weight and neurological function were measured every week for 8 weeks. After 8 weeks, the rats were anesthetized with a mixture of zoletil (40 mg/kg) and xylazine (10 mg/kg) and sacrificed for further analysis. Tissues were then collected for RNA isolation from brain tissue. Also, brain tissues were analyzed by histological procedures. We elucidated that melatonin was not toxic in vital organs. MT7,19 was the most rapidly got back to mild symptom on test of neurological parameter. Also, exogenous melatonin induces both the down-regulation of detrimental genes, such as NOSs and the up-regulation of beneficial gene, including BDNF during long term administration after focal cerebral ischemia. Melatonin treatment reduced the loss of primary motor cortex. Therefore, we suggest that melatonin could be act as prophylactic as well as therapeutic agent for neurorehabilitative intervention.

• Journal of Chest Surgery
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• 제29권9호
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• pp.931-939
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• 1996

폐이식의 임상적용에 있어 공여폐의 기능보존 여부가 술후 경과에 결정적인 영향을 미치므로, 이식폐의 채취에서부터 이식까지의 기간동안의 적절한 보존 방법의 개발이 선행되어야되므로, 폐기능 보존에 적절한 용액의 조성을 알아보기위하여 이 실험을 시행하였다. 실험은 세포외액 조성인 Hartmann's solution에 보존한 군을 대조군(1군)으로 하고, 세포내액 조성 인 modified University of Wisconsin solution에 보존한 군(2군), 세포내액과 세포외액 중간형에 여러가지 substrates가 함유된 Kosin solution에 보존한 군(3군)으로 나누어 가토의 적출폐를 대상으로 시행하였다. 폐기능 보존효과를 비교하기 위하여 heart-lung blocs의 중량의 변화, 기도내압, 관류액내의 이산화탄소 분압의 변화를, 폐조직내의 lactate 및 adenosine deaminase의 수치를 측정하였고, 폐조직의 미세구조 변화를 관찰하여 다음과 같은 결과를 얻었다. 1. 재관류후 heart-lung bloc의 중량변화는 3군에서 가장 낮았다(P< .05). 2. 기도내압은 1군에서는 재관류후 증가되 었으나, 2, 3군에서는 감소되 었고, 특히 2군에서는 보존전의 기 도내압보다 더 낮았다. 3.재관류동안의 \ulcorner동맥압은 3군에서 가장 낮았고, 2군은 1군보다 더 높았다(P>0.1). 4. 폐조직내에서의 lactate와 ADA치는 3군이 1,2군보다 높았다(P< .05). 5. 관류액내의 이산화탄소 분압의 변화률은 3군이 1,2군보다 약간 높았다. 6.폐조직 미세구조의 변화는전반적얀 폐부종, 간질조직의 확장, 출혈 및 기저막의 이상소견을 보였으나 각 군간의 저명한 차이는 없었다. 결론적으로 modified University of Wisconsin solution과 Kosin solution의 폐기능 보존 효과는 Hartmann's solution 에 비하여 다소 우수한 것으로 생각된다.

• Clinical and Experimental Pediatrics
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• 제49권3호
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• pp.317-325
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• 2006

목 적 : 주산기 저산소성 허혈성 뇌손상의 병태 생리에서 nitric oxide(NO)가 급성 저산소성 허혈(hypoxia-ischemia, HI) 후 재산소-재관류기(reoxygenation-reperfusion, RR)에 대뇌의 혈역학 및 에너지 대사에 미치는 영향을 규명하기 위하여, NO 합성 억제제인 NG-monomethyl-L-arginine(L-NMMA)와 NO 합성 촉진제인 L-arginine(L-Arg) 투여를 통하여 뇌신경 세포에 어떠한 영향을 주는지 알아보고자 하였다. 방 법 : 생후 3일 이내의 신생자돈 28마리를 대상으로 무작위로 나누어, Sham 처치만 받은 정상 대조군(n=9), HI와 RR만 유발한 실험 대조군(n=7), HI 이후 RR 직전에 L-NMMA 투여군(n=6)과 L-arginine 투여군(n=6) 등 4군으로 구분하였다. 실험은 ether을 흡입 시킨 후 thiopental을 정주하고, 기관 삽관 후 인공호흡기 등의 처지를 끝낸 후, HI를 유발하기 위하여 실험군에서 수술 겸자로 양측 경동맥을 폐쇄한 후 8% 산소로 30분간 흡입하였고, RR을 시행하기 위하여 경동맥 폐색을 풀고 흡입 산소농도를 60%로 올려 1시간까지 투여하면서 관찰하였다. 생리적 변수로 혈압과 동맥혈 가스 소견을 관찰하였고, 뇌의 혈역학적 변화와 에너지 상태는 near infrared spectroscopy(NIRS)를 이용하여 대뇌의 산화 헤모글로빈($HbO_2$), 환원헤모글로빈(Hb), 환산 헤모글로빈(HbD), 싸이토크롬 $aa_3$(Cyt $aa_3$) 등을 지속적으로 관찰하여 비교하였다. 또한 실험 종료 시 얻은 뇌조직에서 $Na^+$, $K^+$-ATPase의 활성도 및 지질 대사산물인 conjugated dienes, 고에너지 인분자인 ATP(adeninetriphosphate)와 phosphocreatine(PCr)을 비교하였다. 결 과 : 생리적 변수의 변화에서는 실험군 모두에서 정상 대조군에 비하여 혈압, 동맥혈 산소 분압, pH, base excess 등이 유의하게 감소하였고(P<0.05), 젖산은 유의하게 증가하였다(P<0.05). L-NMMA와 L-Arg군에서 실험 대조군과 유의한 차이는 없었다. 실험군에서 RR 1시간 후 pH를 제외한 혈압, 동맥혈 산소 분압, base excess 등의 이상소견은 모두 기저치로 회복되었고, 실험군간에 유의한 차이가 없었다. NIRS 소견에서 $HbO_2$와 HbD는 HI 동안 정상 대조군에 비하여 실험군 모두에서 유의하게 감소하였으나(P<0.05), RR 직후 기저치로 회복되었으며, $HbO_2$는 RR 40분 이후 정상 대조군에 비해 유의하게 감소하였다(P<0.05). Hb은 정상 대조군을 제외한 모든 실험군에서 HI 동안 유의하게 증가하였다가(P<0.05), RR 직후 기저치로 회복되었다. 산화 Cyt $aa_3$는 HI 동안 실험군 모두에서 감소하는 경향을 보였고, RR 이후 다시 증가하였다. 정상 대조군과 각 실험군간에 유의한 차이는 없었다. 뇌의 $Na^+$, $K^+$-ATPase 활성도와 conjugated dienes은 실험군 모두에서 정상 대조군(제1군)에 비하여 유의하게 감소하였다(P<0.05). 뇌의 ATP, phosphocreatine은 실험군 모두에서 정상 대조군과 차이가 없었고, 또한 실험군간에도 유의한 차이가 없었다. 결 론 : 신생 자돈에서 급성 저산소성 허혈 이후 재산소-재관류기 동안 NO 합성 억제제인 L-NMMA나 NO 생성 촉진제인 L-arginine이 뇌 혈역학이나 뇌의 에너지 대사에는 특별한 변화를 일으키지 않았다. 따라서 급성 저산소성 허혈성 뇌손상에서 재산소화 재관류기 초기에는 NO가 뇌손상의 주요한 기전으로 작용하지 않을 것으로 사료된다. 또한 뇌혈역학 및 생화학적 검사 결과 등에서 급성기에는 에너지 부전 상태가 주요한 세포손상 기전이 아니고, 이온 농도의 변화에 의한 뇌부종, 산소유리기에 의한 뇌세포 손상이 저산소성 허혈성 뇌손상의 급성기에 주로 작용하는 뇌세포 손상의 주요 기전임을 시사한다. 따라서 NO 생성 억제제 혹은 생성 전구물질인 L-Arg은 뇌신경 세포 보호 효과를 보이지 않아 급성 주산기 가사의 치료제로서 제한이 됨을 알 수 있었다. 그러나 좀 더 명확한 효과를 보기 위하여 선택적 억제제의 사용, 제제의 용량 및 투여시기, 손상 후 좀더 긴 시간 이후의 변화에 대한 연구가 필요하다.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVII)
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• pp.205-205
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• 2005

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.82.2-83
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• 2003

Beta-amyloid peptide (A${\beta}$) is considered to be responsible for the pathogenesis of the Alzheimer's disease. Several lines of evidence support that A${\beta}$-amyloid-induced cytotoxicity is mediated through the generation of reactive oxygen species (ROS). Agents that are able to scavenge excess ROS may be useful as protecting or reducing agents for development or progress of AD. Green tea extract has been known to have antioxidant property. Our previous studies also demonstrate that green tea extract protected ischemia/reperfusion-induced brain injury by reduction of cell death through scavenging of oxidative damages of macromolecules. (omitted)

• 한국임상수의학회지
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• 제18권4호
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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.

• BMB Reports
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• 제48권4호
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• pp.200-208
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• 2015

The field of redox proteomics focuses to a large extent on analyzing cysteine oxidation in proteins under different experimental conditions and states of diseases. The identification and localization of oxidized cysteines within the cellular milieu is critical for understanding the redox regulation of proteins under physiological and pathophysiological conditions, and it will in turn provide important information that are potentially useful for the development of novel strategies in the treatment and prevention of diseases associated with oxidative stress. Antioxidant enzymes that catalyze oxidation/reduction processes are able to serve as redox biomarkers in various human diseases, and they are key regulators controlling the redox state of functional proteins. Redox regulators with antioxidant properties related to active mediators, cellular organelles, and the surrounding environments are all connected within a network and are involved in diseases related to redox imbalance including cancer, ischemia/reperfusion injury, neurodegenerative diseases, as well as normal aging. In this review, we will briefly look at the selected aspects of oxidative thiol modification in antioxidant enzymes and thiol oxidation in proteins affected by redox control of antioxidant enzymes and their relation to disease. [BMB Reports 2015; 48(4): 200-208]

• 동의생리병리학회지
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• 제18권4호
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• pp.1014-1020
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• 2004

The study was designed to investigate the effects of Palmul-Tang(PMT) on the change of cerebral hemodynamics [regional cerebral blood flow(rCBF), pial arterial diameter(PAD) and mean arterial blood pressure(MABP)] in normal and cerebral ischemic rats. The change of rCBF and MABP were determinated by laser-doppler flowmetry(LDF), and the change of PAD was determinated by video-microscopy. The results in normal rats were as follows ; PMT significantly increased rCBF and PAD in a dose-dependent, and PMT increased MABP in a dose-dependent. This results were suggested that PMT significantly increased rCBF by dilating PAD. The results in cerebral ischemic rats were as follows ; Both rCBF and PAD were significantly and stably increased by PMT(10㎎/㎏, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. The present authors thought that PMT had an anti-ischemic effect through the improvement of cerebral hemodynamics.

• 동의생리병리학회지
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• 제19권6호
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• pp.1546-1551
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• 2005

This Study was designed to investigate the effects of Nelumbinis Rhizomatis Nodus (NRN) on the change of cerebral hemodynamics [regional cerebral blood flow (rCBF), pial arterial diameter (PAD) and mean arterial blood pressure (MABP)] in normal and cerebral ischemic rats. And, this study was designed to investigate the inhibition of lactate dehydrogenase activity in neuronal cells The results were as follows NRN significantly increased rCBF and PAD in a dose-dependent manner, and NRN increased MABP in a dose-dependent manner. This results suggested that NRN significantly increased rCBF by dilating PAD. Both rCBF and PAD were significantly and stably increased by NRN (10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. NRN significantly inhibited lactate dehydrogenase activity in neuronal cells. This results suggested that NRN prevented the neuronal death. It is suggested that NRN had an anti-ischemic effect through the improvement of cerebral hemodynamics and inhibitive effect on the brain damage.

• Journal of Yeungnam Medical Science
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• 제38권1호
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• pp.27-33
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• 2021

The gut is a complex organ that has played an important role in digestion, absorption, endocrine functions, and immunity. The gut mucosal barriers consist of the immunologic barrier and nonimmunologic barrier. During critical illnesses, the gut is susceptible to injury due to the induction of intestinal hyperpermeability. Gut hyperpermeability and barrier dysfunction may lead to systemic inflammatory response syndrome. Additionally, gut microbiota are altered during critical illnesses. The etiology of such microbiome alterations in critical illnesses is multifactorial. The interaction or systemic host defense modulation between distant organs and the gut microbiome is increasingly studied in disease research. No treatment modality exists to significantly enhance the gut epithelial integrity, permeability, or mucus layer in critically ill patients. However, multiple helpful approaches including clinical and preclinical strategies exist. Enteral nutrition is associated with an increased mucosal barrier in animal and human studies. The trophic effects of enteral nutrition might help to maintain the intestinal physiology, prevent atrophy of gut villi, reduce intestinal permeability, and protect against ischemia-reperfusion injury. The microbiome approach such as the use of probiotics, fecal microbial transplantation, and selective decontamination of the digestive tract has been suggested. However, its evidence does not have a high quality. To promote rapid hypertrophy of the small bowel, various factors have been reported, including the epidermal growth factor, membrane permeant inhibitor of myosin light chain kinase, mucus surrogate, pharmacologic vagus nerve agonist, immune-enhancing diet, and glucagon-like peptide-2 as preclinical strategies. However, the evidence remains unclear.