• Title/Summary/Keyword: Therapeutic time window

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Effects of Posttraumatic MgSO4 Injection and Hypothermia an Animal Model of Traumatic Brain Injury(TBI) (실험적 외상성 뇌손상모델에서 외상 후 저체온과 MgSO4의 효과)

  • Han, Seong Rok;Hyun, Dong Keun;Park, Chong Oon;Ha, Young Soo;Kim, Joon Mee
    • Journal of Korean Neurosurgical Society
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    • v.29 no.10
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    • pp.1296-1302
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    • 2000
  • Objective : Traumatic brain injury including diffuse axonal injury has been shown to result in a decrease in brainfree magnesium concentration, an endogenous inhibitor of calcium entry into neuron, that is associated with the development of neurological motor deficits. The goal of this study is to establish the therapeutic window during which the therapy with $MgSO_4$ and/or hypothermia improve damaged neurons by TUNEL stain. Method : Moderate brain injury was induced in 64 adult Sprague-Dawley rats, weighing 350 to 450gm each, by using a simple weight-drop device(Marmarou model). The animals were randomly assigned to four groups(sixteen rats each, a control group, a group treated with $MgSO_4$, a group treated with hypothermia, and a group treated with $MgSO_4$ and hypothermia) and the rats in each group were sacrificed and studied after 12 hrs, 24 hrs, 1 wk, and 2 wks after insult. In hypothermic group, these rats were subjected to hypothermia after injury, with their rectal temperatures maintained at $32^{\circ}C$ for 1 hour. After 1-hour period of hypothermia, rewarming to normothermic level was accomplished over 30-minute period. In the groups treated $MgSO_4$, hypothermia and $MgSO_4$ were subsequently treated with $MgSO_4$($750{\mu}moles/kg$) infused intra-muscularly at 30 minutes after trauma. Result : In all treated groups, a significant reduction in TUNEL positive cells was found in comparison with the control group each time(p<0.001). Between treatment groups, No differnce was seen 12hrs, 24hrs, and 1wk. However, hypothermic group treated with or without $MgSO_4$ showed more significant reduction in apoptotic cells than group treated with $MgSO_4$ 2 weeks after trauma(p<0.05). However, hypothermic group treated with $MgSO_4$ showed no significant reduction in apoptotic cells compared with hypothermic group(p>0.05). Conclusion : These findings suggest that both hypothermia and $MgSO_4$ significantly improve pathological changes. Otherwise simultaneously $MgSO_4$ and hypothermia treatment groups is failed to provide additional neuroprotection. These results may be relevant to the design of future clinical trials of therapeutic hypothermia and $MgSO_4$ for traumatic brain injury.

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Pharmacokinetic Evaluation of Ketorolac Tromethamine Sustained-Release Pellets after Oral Administration in Rabbits (케토롤락트로메타민 서방성 펠렛의 약물속도론적 평가)

  • Kwak, Son-Hyok;Hwang, Sung-Joo;Jiang, Ge;Nam, Kyung-Wan;Moon, Young-Girl;Lee, Hai-Bang;Cho, Sun-Hang;Yuk, Soon-Hong;Lee, Han-Koo;Jeong, Sang-Young;Lee, Young-Won
    • Journal of Pharmaceutical Investigation
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    • v.30 no.4
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    • pp.241-246
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    • 2000
  • To develop a sustained-release preparation containing ketorolac tromethamine, two sustained-release pellet formulations were evaluated with a pharmacokinetic study as compared with a conventional commercial tablets (10 mg $Tarasyn^{TM}$, Roche Korea Ltd.). Two sustained-release formulations were as follows; formulation A was composed of an inner layer containing 75% of drug coated with $Eudragit^{TM}$ RS 100 membrane and an outer layer containing 25% of drug mixed with $Eudragit^{TM}$ NE30D, and formulation B was composed of only an inner layer containing 100% of drug coated with $Eudragit^{TM}$ RS 100 membrane. The dissolution test was performed for two formulations. In case of conventional tablets, 2.5 mg of drug per a dose was administered orally into male Albino rabbit (2.0-2.3 kg of body weight) 3 times at intervals of 4 hours. In case of two sustained formulations, 7.5 mg of drug was administered once orally. Blood samples were withdrawn periodically after the administration, and the blood concentration was determined by HPLC. The conventional tablets showed very high peak-trough fluctuation between administered doses, but two sustained formulations showed less fluctuation. Formulation A with the loading dose showed the time to reach minimum effective concentration (MEC) i.e. the onset time was less than 20 min, while Formulation B had more than 1 hr of the onset time. Formulation A had the more constant plasma level than formulation B. However, formulation B had a time lag, so the plasma level was less than MEC for an initial period of 1 hr. In formulation A, the plasma level was maintained within the therapeutic window $(0.3-5\;{\mu}g/ml)$ for a long period. Formulation A was thought to be an ideal sustained-release formulation for ketorolac tromethamine oral delivery system.

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Video Assisted Thoracic Surgery(VATS) of Pericardial Window Operation (비디오 흉강경을 이용한 심낭막 개창술)

  • 윤석원;김동관;김정원;박창률;김용희;박기성;박승일
    • Journal of Chest Surgery
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    • v.35 no.11
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    • pp.812-816
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    • 2002
  • Pericardial effusions result from various conditions such as inflammation, malignancies, open heart surgery and uremia. Recently, video assisted thoracic surgery (VATS) has been used for diagnostic and therapeutic purposes in the management of pericardial effusion and intrathoracic lesions due to its ability to provide outstanding visibility of intrathoracic structures with less pain, superior cosmetic effects, and shorter hospital stay Material and Method: From April 1995 to October 2001, 51 patients received pericardial window operation via either thoracoscopic(Group A, n=37, m:f=18:19, mean age=56.4 yrs)or thoracotomy approach(Group B, n=14, m:f=8:6, mean age=58.4 yrs). Result: In group A, the operation time, duration of chest tube insertion, recurrence rate of pericardial effusion, and postoperative hospital stay were 61.2 minutes, 9.3 days, 2.7%, 16.2 days, respectively while in group B these values were 58.4 minutes, 12.2 days, 7.1, and 17.3 days. The number of injections for pain control in group A were 4.2 times, whereas in group B it was 6.3 times. Although there was a tendency for the mean hospital stay and duration of chest tube insertion to be shorter in group A than in group B, these differences did not reach statistical significance. There was also no significant difference in the operation time and recurrence rate between the two groups. Conclusion: The safety and effectiveness of VATS in the management of pericardial effusion is comparable to the open thoracotomy method. It allows for a shorter hospital stay, duration of chest tube insertion, lesser postoperative pain and a smaller skin incision.

Video-assisted Thoracoscopic Surgery for Mediastinal Lesions (종격동 질환의 비디오 흉강경 수술)

  • 김연수;김광택;손호성;김일현;이인성;김형묵;김학제
    • Journal of Chest Surgery
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    • v.31 no.1
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    • pp.40-45
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    • 1998
  • Recently, video-assisted thoracoscopic surgery for mediastinal lesions has been considered a new effective therapeutic method. From March, 1992 to April, 1997, 33 cases of video assisted thoracoscopic surgery for mediastinal lesions were performed. Gender distribution was 16 males and 17 females. Average age was 42 years old(ranged from 14 to 69). The locations of lesions were anterior mediastinum in 14 cases, middle mediastinum in 5 cases, posterior mediastinum in 11 cases, and superior mediastinum in 3 cases. These included 9 neurilemmomas, 5 benign cystic teratoma, 4 pericardial cysts, 2 ganglioneuroma, 2 thymus, 2 thymic cyst, 1 thymoma, 2 esophageal leiomyomas, 1 dermoid cyst, 1 lipoma, 1 malignant lymphoma, 1 bronchogenic cyst, 1 pericardial effusion, and 1 Boerhaave's disease with empyema. Working window was needed in 6 cases. We converted to open thoracotomy in 6 cases. Reasons of convertion to open thoracotomy were large sized mass(1), severe adhesion(3), and difficult location to approach(2). The average operation time was 116min($\pm$56 min). The average chest tube drainage time was 4.7days. The average hospital stay was 8.7 days. Operative complications were atelectasis(2), empyema with mediastinitis(1), recurrent laryngeal nerve palsy(1), and plenic nerve palsy(1). In conclusion, VATS for mediastinal lesions were performed with shorter operation time and hospital stay, and lesser complications and pain than those of conventional thoracotomy.

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Potential Risk of Choline Alfoscerate on Isoflurane-Induced Toxicity in Primary Human Astrocytes

  • Hyun Jung Lee;Hye Rim Cho;Minji Bang;Yeo Song Lee; Youn Jin Kim; Kyuha Chong
    • Journal of Korean Neurosurgical Society
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    • v.67 no.4
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    • pp.418-430
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    • 2024
  • Objective : Isoflurane, a widely used common inhalational anesthetic agent, can induce brain toxicity. The challenge lies in protecting neurologically compromised patients from neurotoxic anesthetics. Choline alfoscerate (L-α-Glycerophosphorylcholine, α-GPC) is recognized for its neuroprotective properties against oxidative stress and inflammation, but its optimal therapeutic window and indications are still under investigation. This study explores the impact of α-GPC on human astrocytes, the most abundant cells in the brain that protect against oxidative stress, under isoflurane exposure. Methods : This study was designed to examine changes in factors related to isoflurane-induced toxicity following α-GPC administration. Primary human astrocytes were pretreated with varying doses of α-GPC (ranging from 0.1 to 10.0 µM) for 24 hours prior to 2.5% isoflurane exposure. In vitro analysis of cell morphology, water-soluble tetrazolium salt-1 assay, quantitative real-time polymerase chain reaction, proteome profiler array, and transcriptome sequencing were conducted. Results : A significant morphological damage to human astrocytes was observed in the group that had been pretreated with 10.0 mM of α-GPC and exposed to 2.5% isoflurane. A decrease in cell viability was identified in the group pretreated with 10.0 µM of α-GPC and exposed to 2.5% isoflurane compared to the group exposed only to 2.5% isoflurane. Quantitative real-time polymerase chain reaction revealed that mRNA expression of heme-oxygenase 1 and hypoxia-inducible factor-1α, which were reduced by isoflurane, was further suppressed by 10.0 µM α-GPC pretreatment. The proteome profiler array demonstrated that α-GPC pretreatment influenced a variety of factors associated with apoptosis induced by oxidative stress. Additionally, transcriptome sequencing identified pathways significantly related to changes in isoflurane-induced toxicity caused by α-GPC pretreatment. Conclusion : The findings suggest that α-GPC pretreatment could potentially enhance the vulnerability of primary human astrocytes to isoflurane-induced toxicity by diminishing the expression of antioxidant factors, potentially leading to amplified cell damage.

Comparison of Play Perception and Play Participation of Parents of Disabled Children and Non-disabled Children in Preschool Age (학령전기 장애 아동 부모와 비장애 아동 부모의 놀이 인식과 놀이 참여 비교 연구)

  • Park, DaSol;Lee, EunYoung;Lee, SunHee;Park, Hae Yean
    • Therapeutic Science for Rehabilitation
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    • v.9 no.1
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    • pp.69-78
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    • 2020
  • Objective : The purpose of this study was to conduct a comprehensive survey of children's play in parents of disabled and non-disabled children prior to commencing school. This study aimed to further understanding play recognition and to present a specific direction of play necessary to each parent. Methods : A questionnaire based on prior studies was sent to 700 people who had previously agreed to the take part. A total of 596 questionnaires were analyzed. Uncollected and insincere surveys, of which 106 were questionnaires for parents of disabled children, were exclused from analysis. The SPSS Window 23 program was used for data analysis and frequency analysis and the independent sample T test were performed. Results : Disabled children's parents perceived playing with their children as more important than that of non-disabled children's parents(p<0.01). There was no statistical difference between disabled children and non-disabled children's parents, but there were some differences(p=0,053). Both disabled and non-disabled children had more time to participate with their mothers than with their fathers. Mothers with disabilities had more time to play however, fathers with no disabilities had more time. Both disabled and non-disabled children's parents had the most "ordinary" frequency of buying toys and there was very littele difference between the 2 groups. Both disabled and non-disabled children's parents primarily used the internet to acquire play information, and consideration when buying fun was followed by interest inducement, development level and safety. Conclusion : Through this study, it was possible to compare the status of play recognition and participation by parents of children with or without disabilities. Based on this study, parents will be able to find out what they really need to play and will be provided as a basis for future play studies for children.

The Role of the Endometrium and Embryo in Human Implantation (인간 착상 과정에 자궁내막과 배아의 역할)

  • Jee, Byung-Chul
    • Development and Reproduction
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    • v.13 no.1
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    • pp.1-11
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    • 2009
  • Implantation itself is governed by an array of endocrine, paracrine and autocrine modulators, of embryonic and maternal origin. Window of implantation is the unique temporal and spatial expression of factors allows the embryo to implant via signaling, appositioning, attachment, and invasion in a specific time frame of $2{\sim}4$ days. When the embryo has arrived in the uterine cavity, a preprogrammed sequence of events occurs, which involves the production and secretion of a multitude of biochemical factors such as cytokines, growth factors, and adhesion molecules by the endometrium and the embryo, thus leading to the formation of a receptive endometrium. Cytokines such as LIF, CSF-1, and IL-1 have all been shown to play important roles in the cascade of events that leads to implantation. Integrin, L-selectin ligands, glycodelin, mucin-1, HB-EGF and pinopodes are involved in appositioning and attachment. The embryo also produces cytokines and growth factors (ILs, VEGF) and receptors for endometrial signals such as LIF, CSF-1, IGF and HB-EGF. The immune system and angiogenesis play an important role. The usefulness of these factors to assess endometrial receptivity and to estimate the prognosis for pregnancy in natural and artificial cycles remains to be proven. Integrins, pinopodes, glycodelin and LIF (from biopsies) are promising candidates; from uterine flushings, glycodelin and LIF are also candidates. The ideal serum marker is not available, but VEGF, glycodelin and CSF have some clinical implications. Further evaluation that includes larger groups of infertile women and fertile controls are needed to elucidate whether their presence in plasma, flushing fluid, or endometrial samples can be used as some kind of a screening tool to assess endometrial function and prognosis for pregnancy before and after artificial reproductive therapy. A better understanding of their function in human implantation may lead to therapeutic intervention, thereby improving the success rate in reproduction treatment. New molecular techniques are becoming available for measuring both embryonic and endometrial changes prior to and during implantation. The use of predictive sets of markers may prove to be more reliable than a single marker. Ultimately, the aim is to use these tools to increase implantation in artificial cycles and consequently improve live-birth rates.

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