• Clinical and Experimental Reproductive Medicine
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• v.47 no.2
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• pp.94-100
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• 2020

The inverse correlation between maternal age and pregnancy rate represents a major challenge for reproductive endocrinology. The high embryo ploidy error rate in failed in vitro fertilization (IVF) cycles reflects genetic misfires accumulated by older oocytes over time. Despite the application of different follicular recruitment protocols during IVF, gonadotropin modifications are generally futile in addressing such damage. Even when additional oocytes are retrieved, quality is frequently poor. Older oocytes with serious cytoplasmic and/or chromosomal errors are often harvested from poorly perfused follicles, and ovarian vascularity and follicular oxygenation impact embryonic chromosomal competency. Because stimulation regimens exert their effects briefly and immediately before ovulation, gonadotropins alone are an ineffective antidote to long-term hypoxic pathology. In contrast, the tissue repair properties (and particularly the angiogenic effects) of platelet-rich plasma (PRP) are well known, with applications in other clinical contexts. Injection of conventional PRP and/or its components (e.g., isolated platelet-derived growth factors as a cell-free substrate) into ovarian tissue prior to IVF has been reported to improve reproductive outcomes. Any derivative neovascularity may modulate oocyte competence by increasing cellular oxygenation and/or lowering concentrations of intraovarian reactive oxygen species. We propose a mechanism to support intrastromal angiogenesis, improved follicular perfusion, and, crucially, embryo ploidy rescue. This last effect may be explained by mRNA upregulation coordinated by PRP-associated molecular signaling, as in other tissue systems. Additionally, we outline an intraovarian injection technique for platelet-derived growth factors and present this method to help minimize reliance on donor oocytes and conventional hormone replacement therapy.

• Natural Product Sciences
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• v.25 no.2
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• pp.136-142
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• 2019

Ischemia/reperfusion-induced myocardial injury is the main cause of acute myocardial infarction. Dendropanax morbifera $L{\acute{e}}veille$ has been used in traditional medicines for the treatment of various diseases such as headache, infectious diseases, and general debility. However, the effect of extract from D. morbifera (EDM) on myocardial ischemic injury is still unknown. In this study, the effects of EDM on neonatal rat cardiomyocytes with hypoxia/reoxygenation (H/R) injury were investigated. The viability of cardiomyocytes with H (30 min)/R (1 h) decreased; however, treatment with EDM significantly inhibited H/R injury-induced cardiomyocyte death. Further, we observed that reactive oxygen species (ROS) generation and intracellular calcium concentration ($Ca^{2+}{_i}$) were significantly reduced in EDM-treated cardiomyocytes compared with that in H/R-injured positive control. In addition, western blotting results showed that EDM attenuated abnormal changes of RyR2 and SERCA2a genes in hypoxic cardiomyocytes. These results suggest that EDM ameliorates ROS generation and $Ca^{2+}{_i}$ homeostasis to prevent dysregulation of calcium regulatory proteins in the heart, thereby exerting cardioprotective effects and reducing hypoxia-induced cardiomyocyte damage, which verifies the potential use of EDM as a new therapeutic agent for the treatment of myocardial ischemic injury.

• Radiation Oncology Journal
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• v.9 no.1
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• pp.7-15
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• 1991

Pentoxifylline (PENTO) has been known to improve RBC fluidity, and thus improve the flux of RBC through narrow capillaries. Additionally, PENTO also decreases the $O_2$ affinity of hemoglobin by increasing 2,3-DPG levels, thereby increasing the $O_2$ release from RBC. Nicotinamide (NA) has been reported to decrease the number of acutely hypoxic cells in tumors by temporarily increasing tumor blood flow. Therefore, the purpose of this study was to examine whether the combination of PENTO and NA (PENTO+NA) would reduce the radioresistance of the Fsall murine fibrosarcoma by oxygenating the hypoxic cells. We obsewed a significantly enhanced radiation-induced growth delay of the FSaII tumors by PENTO+NA. Thus the enhancement ratio was between 2.5 and 2.8 in growth delay assay. The $TCD_{50}$ of control tumors was about 57 Gy, but that of PENTO+NA treated tumors was about 32Gy. Thus $TCD_{50}$ was modified by a factor of 1.8. We also observed that PENTO+NA exerted no effect on the radiation-induced skin damage after the legs without bearing tumors were exposed to X-irradiation. In order to clarify radiosensitizing effects of PENTO+ NA, changes in tumor blood flow and intratumor pOf were measured using laser Doppler flowmetry and $O_2$ microelectrode methods. The tumor blood flow significantly increased at 10 min. after injection of PENTO+ NA. Furthermore, we also found that PENTO+ NA significantly increased intratumor $pO_2$ from 8 to 19 mmHg. We concluded that PENTO+MA was far more effective than NA alone or PENTO alone. The increase in the response of tumors in vivo to X-irradiation appeared to be due mainly to an increase in the tumor oxygenation. Further studies using various concentrations of PENTO alone and in combination with NA to obtain better sequencing and maximal radiosensitization are warranted.

• Clinical and Experimental Pediatrics
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• v.52 no.1
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• pp.105-110
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• 2009

Purpose : Perinatal asphyxia is an important cause of neonatal mortality and subsequent lifelong neurodevelopmental handicaps. Although many treatment strategies have been tested, there is currently no clinically effective treatment to prevent or reduce the harmful effects of hypoxia and ischemia in humans. Erythropoietin (Epo) has been shown to exert neuroprotective effects in various brain injury models although the exact mechanisms through which Epo functions are not completely understood. This study investigates the effect of Epo on hypoxic-ischemic (HI) brain injury and the possibility that its neuroprotective actions may be associated with iron-mediated metabolism. Methods : HI brain injury was produced in 7-day-old rats by unilateral carotid artery ligation followed by hypoxia with 8% oxygen for 2 h. At the end of HI brain injury, the rats received an intraperitoneal injection of 5,000 units/kg erythropoietin. Random premedication with iron, deferoxamine, iron-deferoxamine, or saline were performed 23 d before HI brain injury. The severity of the brain injury was assessed at 7 d after HI. Results : Single Epo treatment post-HI brain injury reduced the gross and histopathological findings of brain injury. Iron premedication did not increase the incidence or severity of the injury as measured by the damage score. Deferoxamine administration before HI brain injury improved the brain injury as compared to no treatment or Epo treatment. Conclusion : These findings indicate that Epo provides neuroprotective benefits after HI in the developing brain. These findings suggest that Epos neuroprotective actions may involve reducing iron in tissues that mediate the formation of free radicals.

• Clinical and Experimental Pediatrics
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• v.51 no.11
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• pp.1205-1210
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• 2008

Purpose : The development of the corpus callosum occupies the entire period of cerebral formation. The myelination pattern on magnetic resonance imaging (MRI) is very useful to evaluate neurologic development and to predict neurologic outcome in high risk infants. The thickness of the corpus callosum is believed to depend on the myelination process. It is possible to calculate the length and thickness of the corpus callosum on MRI. Thus, we can quantitatively evaluate the development of the corpus callosum. We investigated the clinical significance of measuring various portions of the corpus callosum in neonate with neurologic disorders such as hypoxic brain damage and seizure disorder. Methods : Forty-two neonates were evaluated by brain MRI. We measured the size of the genu, body, transitional zone, splenium, and length of the corpus callosum. Each measurement was divided by the total length of the corpus callosum to obtain its corrected size. The ratio of corpus callosal length and the anteroposterior diameter of the brain was also measured. Results : There was no statistical significance in the sample size of each part of the corpus callosum. However, the corrected size or the ratio of body of the corpus callosum correlated with periventricular leukomalacia and hypoxic ischemic encephalopathy. Conclusion : The abnormal size of the corpus callosum showed a good correlation with periventricular leukomalacia and hypoxic ischemic encephalopathy in neonates. We can predict clinical neurological problems by estimation of the corpus callosum in the neonatal period.

• Clinical and Experimental Pediatrics
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• v.60 no.12
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• pp.403-407
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• 2017

Purpose: Quadriplegic children with cerebral palsy are more susceptible to osteoporosis because of various risk factors that interfere with bone metabolism. Pamidronate is effective for pediatric osteoporosis, but there are no guidelines for optimal dosage or duration of treatment in quadriplegic children with osteoporosis. We aimed to evaluate the efficacy of low-dose pamidronate treatment in these patients. Methods: Ten quadriplegic patients on antiepileptic drugs (6 male, 4 female patients; mean age, $10.9{\pm}5.76years$), with osteoporosis and gross motor function classification system level V, were treated with pamidronate (0.5-1.0 mg/kg/day, 2 consecutive days) every 3-4 months in a single institution. The patients received oral supplements of calcium and vitamin D before and during treatment. The lumbar spine bone mineral density (BMD) z score and biochemical markers of bone metabolism were measured regularly during treatment. Results: The main underlying disorder was perinatal hypoxic brain damage (40%, 4 of 10). The mean cumulative dose of pamidronate was $4.49{\pm}2.22mg/kg/yr$, and the mean treatment period was $10.8{\pm}3.32months$. The BMD z score of the lumbar spine showed a significant increase from $-4.22{\pm}1.24$ before treatment to $-2.61{\pm}1.69$ during treatment (P=0.008). Alkaline phosphatase decreased during treatment (P=0.037). Significant adverse drug reactions and new fractures were not reported. Conclusion: Low-dose pamidronate treatment for quadriplegic children with cerebral palsy increased lumbar BMD and reduced the incidence of fracture.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1733-1739
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• 2004

The water extract of Hwangryunhaedog-tang(HRHDT} has been traditionally used for treatment of ischemic heart and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of HRHDT rescues cells from these damages. This study was designed to investigate the protective mechanisms of HRHDT on hypoxia-induced cytotoxicity in H9c2 cardiomyoblast cells. Hypoxia, markedly decreased the viability of H9c2 cells, which was characterized with apparent apoptptic features such as chromatin condensation as well as fragmentation of genomic DNA and nuclei. However, HRHDT significantly reduced hypoxia-induced cell death and apoptotic characteristics. Also, HRHDT prevented the mitochondrial dysfunction including the disruption of mitochondria membrane permeability transition (MPT) and an increase in expression of anti-apoptotic Bcl-2 proteins in hypoxia-H9c2 cells. Taken together, this study suggests that the protective effects of the water extract of HRHDT against hypoxic damages may be mediated by the modulation of Bcl-2 and Bak expression.

• Journal of Chest Surgery
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• v.30 no.7
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• pp.724-728
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• 1997

We experienced a case of thoracic aortic aneurysm combined with coronary artery disease. A 68-year-old man complained of anginal pain in the left anterior chest and nonspecific pain in the posterior chest. The aneurysm was extending from left subclavian artery to the diaphragm and sign of impending rupture was noted in the chest CT. Coronary angiograms r vealed significant obstruction of left circumflex coronary artery(>95%) and left anterior descending artery(>50%). Exposure was obtained through the left posterolateral thoracotomy incision in the 4th intercostal space and then partial femoro-femoral cardiopulmonary bypass was established. After aortic cross clamping, the aneurysmal sac was opened and repaired with interposition of 26 mm Hemashield graft. Under the beating heart with femoro-femoral cardiopulmonary bypass, aorto-left circumflex coronary bypass with autogenous saphenous vein used as conduit was performed. Postoperatively multiple cerebral infarction ensued due to intraoperative hypovolemic shock and hypoxic brain damage during cardiopulmonary bypass. Currently, the patient's mental status is drowsy and in an improving state.

• Journal of Chest Surgery
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• v.43 no.2
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• pp.164-167
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• 2010

Extracorporeal membrane oxygenation (ECMO) during acute respiratory failure due to any cause aids in the recovery of respiratory function. The use of ECMO for acute respiratory failure due to near drowning was reported to be a successful therapeutic option in those patients who do not respond to optimal conventional therapies. We performed veno-venous ECMO for 2 acute respiratory failures due to near-drownings. All cannulations were performed percutaneously via both femoral veins. The 2 patients were successfully weaned off ECMO, but one patient experienced diffuse hypoxic brain damage and a subarachnoid hemorrhage.

• Journal of Trauma and Injury
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• v.31 no.2
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• pp.51-57
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• 2018

Purpose: Patients with diffuse axonal injury experience various disabilities and have a high cost of treatment. Recent researches have revealed the underlying mechanism and pathogenesis of diffuse axonal injury. This study aimed to investigate the correlation between the radiological grading of diffuse axonal injury and the clinical outcomes of patients. Methods: From January 2011 to December 2016, among 294 patients with traumatic brain injury, 44 patients underwent magnetic resonance imaging (MRI). A total of 18 patients were enrolled in this study except for other cerebral injuries, such as cerebral hemorrhage or hypoxic brain damage. Demographic data, clinical data, and radiological findings were retrospectively reviewed. The grading of diffuse axonal injury was analyzed based on patient's MRI findings. Results: For the most severe diffuse axonal injury patients, prolonged intensive care unit (ICU) stay (p=0.035), hospital stay (p=0.012), and prolonged mechanical ventilation (p=0.030) were observed. However, there was no significant difference in healthcare-associated infection rates between MRI grading (p=0.123). Massive transfusion, initial hemoglobin and lactate levels, and MRI gradings were found to be highly significant in predicting the duration of unconsciousness. Conclusions: This study showed that patients with high grade diffuse axonal injury have prolonged ICU stays and significantly longer hospital stays. Deteriorated mental patients with high energy injuries should be evaluated to identify diffuse axonal injuries by using an appropriate imaging tool, such as MRI. It will be important to predict the duration of consciousness recovery using MRI scans.