• Reproductive and Developmental Biology
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• 제35권4호
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• pp.449-455
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• 2011

Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by etopic expression of transcription factors. iPS cells are indistinguishable from ES cells in terms of morphology and stem cell marker expression. Moreover, mouse iPS cells give rise to chimeric mice that are competent for germline transmission. However, mice derived from iPS cells often develop tumors. Furthermore, the low efficiency of iPS cell generation is a big disadvantage for mechanistic studies. Nonviral plasmid.based vectors are free of many of the drawbacks that constrain viral vectors. The histone deacetylase inhibitor valproic acid (VPA) has been shown to improve the efficiency of mouse and human iPS cell generation, and vitamin C (Vc) accelerates gene expression changes and establishment of the fully reprogrammed state. The MEK inhibitor PD0325901 (Stemgent) has been shown to increase the efficiency of the reprogramming of human primary fibroblasts into iPS cells. In this report, we described the generation of mouse iPS cells devoid of exogenous DNA by the simple transient transfection of a nonviral vector carrying 2A-peptide-linked reprogramming factors. We used VPA, Vc, and the MEK inhibitor PD0325901 to increase the reprogramming efficiency. The reprogrammed somatic cells expressed pluripotency markers and formed EBs.

• Clinical and Experimental Pediatrics
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• 제50권7호
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• pp.694-697
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• 2007

발작성 운동이상증(Paroxysmal kinesigenic dyskinesia, PKD)은 경련성 발작과 구분해야 하는 드문 신경질환으로써 1940년에 Mount와 Reback에 의해 발작성 무도무위증(paroxysmal dystonic choreoathetosis)란 용어로 처음 보고되었으며 1967년 Kertesz에 의해 처음으로 발작성 운동이상증(Dyskinesia)으로 명명 되어졌다. PKD는 아동기에서 성인기 초에 호발하며 가족성 우성 유전으로도 나타날 수 있고 chromosome 16p11.2-q12.1, 16q13-q22.1, 2q32-36과 관계 있다는 보고가 있다. 증상은 대부분 수 초 이내 멈추나 드물게 5분 이상 지속되는 경우도 있다. 증상 발현 전에 감각 이상 등의 전구 증상이 동반되는 경우가 있으며 의식소실은 동반되지 않는다. 치료는 carbamazepne, phenytoin, valproic acid, clonazepam 등의 항경련제를 투여하는데 일부에서는 oxycarbazepine이나 levodopa를 투여하기도 한다. 저자들은 한 가족의 세명의 형제에서 나타난 발작성 이상운동증을 경험하고 항경련제(Oxcarbamazepine or Carbamazepine)를 통한 좋은 치료성적을 거두었기에 보고하는 바이다.

• 대한임상독성학회지
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• 제7권2호
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• pp.150-155
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• 2009

Purpose: Extracorporeal elimination of drugs is a critical part of managing poisonings, although the indications and optimal method remain a matter of debate. The aim of this study is to report our clinical experiences with continuous renal replacement therapy (CRRT), as performed by emergency room physicians, as method of extracorporeal drug elimination in patients with poisoning. Methods: This study was a retrospective study of the consecutive patients who underwent CRRT, as performed by an emergency room physician, for acute poisoning. The patient characteristics, the kinds of drugs and the method of extracorporeal elimination were analyzed by reviewing the patients' charts. Results: During eleven months, 26 patients with acute poisoning underwent extracorporeal elimination (2 patients; intermittent hemodialysis, 24 patients; CRRT). The mean time from the decision to performing extracorporeal elimination was $206.0{\pm}36.8$ minutes for intermittent hemodialysis, $62.9{\pm}8.5$ minutes for continuous venoveno-hemodiafiltration (CVVHDF) and $56.6{\pm}6.8$ minutes for charcoal hemoperfusion. For the patients with CRRT, CVVHDF was conducted in 10 patients (3 patients; valproic acid, 2 patients; Lithium, 1 patient; salicylates, 1 patient; methanol) and charcoal hemoperfusion by using CRRT was done in 14 patients (13 patients; paraquat, 1 patient; dapsone). For the 12 patients who required hemodialysis due to severe poisoning, 7 patients underwent CRRT because of their unstable vital signs. Conclusion: CRRT was an effective method of extracorporeal drug elimination in patients with acute poisoning, and especially for the cases with unstable vital sign and for those patients who required an early start of extracorporeal elimination according to the characteristics of the drug. (ED note: the writing of the abstract was not clear. Check it carefully.)

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2000년도 The 7th International Symposium
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• pp.116-122
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• 2000

The molecular modification of antiepileptic drugs and direct synthesis of new drugs with the predetermined antiepileptic properties are perspective. New neurochemical attacking to solve the problem including prevention and inhibition of seizures seems to be related to ginsenosides and ginseng polypeptides. The main study based on the severity of febrile convulsions of rat pups has been done from the earlier investigations of antiepileptical action of ginsenosides between KGTRI and MSU (Chepurnov, Park et al., 1995) with different kinds of experimental models of epilepsy. From the cultured cell line DAN25 of ginseng root, the extracts of ginsenosides made in "BIOKHIMMASH" were studied by the project of preclinical anticonvulsant screening (Stables, Kupferberg, 1997). The inhibition of severity of convulsions, decrease of seizures threshold, decrease of audiogenic seizures in rats of different strains and normalization of cerebral blood flow (measured by hydrogen test) were demonstrated in rats after i.c.v., intraperitoneally and orally administration, respectively. The antiepileptical effects by the combination of compounds from ginseng; were compared with the iuluence of Rg1, Rb1, Rc and with the well known antiepileptical drugs such as carbamazepine, valproic acid. The base for the research is obtained by using the WAG/Rij strain (Luijtelaar, Coenen, Kuznetcova), an excellent genetic model for human generalized absence epilepsy. The improving action of gensinosides was effectively demonstrated on the model of electrical kindling of amygdala of WAG/Rij rats with genetically determined absences, and the influences of ginsenosides on the slow wave discharges have also been being investigated. The different characteristics of a kindling process exerted in the sex-different region of the amygdala and demonstrated that the level of sex steroids and content of neurosteroids in amygdaloid tissue can modify the development of seizures. The chemical structures of ginsenosides not only have some principal differences from well-known antiepileptical drugs but the Plant Pharmacology gives us unique possibility to develop new class of antiepileptic drugs and to improve its biological activity.

• Clinical and Experimental Pediatrics
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• 제55권5호
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• pp.171-176
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• 2012

Purpose: The aim of this study was to investigate the natural history of epilepsy and response to anti-epileptic drug treatment in patients with Angelman syndrome (AS) in Korea. Methods: We retrospectively reviewed the clinical records of 14 patients diagnosed with epilepsy out of a total of 17 patients with a genetic diagnosis of AS. These patients were seen at the Department of Pediatric Neurology at Severance Children's Hospital from March 2005 to March 2011. Results: Fourteen (9 males and 5 females) subjects (82.3%) were diagnosed with epilepsy in AS. The most common seizure types were generalized tonic-clonic (n=9, 27%) and myoclonic (n=9, 27%), followed by atonic (n=8, 24%), atypical absence (n=4, 12%) and complex partial seizure (n=3, 9%). The most commonly prescribed antiepileptic drug (AED) was valproic acid (VPA, n=12, 86%), followed by lamotrigine (LTG, n=9, 64%), and topiramate (n=8, 57%). According to questionnaires that determined whether each AED was efficacious or not, VPA had the highest response rate and LTG was associated with the highest rate of seizure exacerbation. Complete control of seizures was achieved in 6 patients. Partial control was achieved in 7 patients, while one patient was not controlled. Conclusion: Epilepsy is observed in the great majority of AS patients. It may have early onset and is often refractory to treatment. There are few reports about epilepsy in AS in Korea. This study will be helpful in understanding epilepsy in AS in Korea.

• KSBB Journal
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• 제30권1호
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• pp.44-51
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• 2015

Chinese hamster ovary (CHO) cells are the most widely used mammalian host for the commercial production of recombinant proteins. However, they show relatively low yields of recombinant proteins in comparison with microbial cells. Various strategies have been tried to overcome this drawback. The acetyl moieties are attached to the N-terminus of histone by histone acetyltransferase (HAT) while histone deacetylase (HDAC) removes histone-bound acetyl groups. HDAC inhibitor (HDACi), such as sodium butyrate, sodium propionate and valproic acid, can enhance specific productivity of CHO cells. Human albumin-erythropoietin (Alb-EPO) is a novel 105 kDa protein comprising recombinant human EPO fused to human albumin. In this study, we examined the effects of HDACi on the production of Alb-EPO in CHO cells with various concentrations in the range of 0-1 mM. The results showed that sodium butyrate was found to be the best HDACi for enhancing productivity. It enhanced not only the production of Alb-EPO but also the apoptosis of recombinant CHO cells.

• Annals of Clinical Neurophysiology
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• 제2권1호
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• pp.27-30
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• 2000

Reflex epilepsies are distinct but not clearly understood clinical entity. Various cerebral activities induced by simple stimulation including visual, auditory, somatosensory stimulation, as well as diverse functional tasks such as reading, calculation, complex thinking are believed to be seizure-inducing factors. We experienced two patients whose seizures were readily precipitated by complex, strenuous thinking. Both patients was teen-aged boy at the onset of seizure(13, and 15 years of age each) with normal physical and mental growth. Although first seizure was precipitated by watching TV and playing puzzles in each patient, initial diagnosis was idiopathic generalized epilepsy, possibly juvenile myoclonic epilepsy( JME). For the first few years, seizures were infrequent but mostly precipitated by the tasks needs concentration such as playing computer games, decision-making, mathematics, reading, or during the examination. EEG revealed various thinking process including reading hard books, drawing complex figure, complex calculation induced epileptic discharges even if it usually needs certain period of concentration. Phenytoin, valproic acid, clonazepam, vigabatrin, and lamotrigine sometimes abated their seizures but none of these made them seizure-free. Complex reflex epilepsy induced by thinking was proposed to be a separate type of epilepsy or a variant of JME. Age, sex, stereotypic seizure-inducing factors, clinical course, and refractory epilepsies in these patients highly suggested this type of epilepsy as a variant of JME but its refractoriness and unique provocation still needs more speculation.

• Clinical Psychopharmacology and Neuroscience
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• 제16권4호
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• pp.505-507
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• 2018

Clozapine may be associated with cardiovascular adverse effects including QTc prolongation and, more rarely, with myocarditis and pericarditis. Although rare, these latter cardiovascular adverse effects may be life-threatening and must be immediately recognized and treated. Several cases of clozapine related-pericarditis have been described and often it has a subtle and insidious onset with symptoms that may be often misdiagnosed with psychiatric manifestations (e.g. anxiety, panic or somatization) leading to a delayed correct diagnosis with potential fatal consequences. In the present report we describe the case of a 27-year-old girl with schizoaffective disorder taking long acting aripiprazole and valproate who developed a sudden onset clozapine-related pericarditis during titration phase that resolved with immediate clozapine discontinuation and indomethacin administration. We underline the importance of an early diagnosis of clozapine-related pericarditis and the need to have monitoring protocols to prevent this potentially fatal adverse effect especially when polypharmacy is administered to patients taking clozapine.

• Clinical and Experimental Pediatrics
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• 제48권5호
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• pp.527-533
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• 2005

목 적 : 소아 간질 환아에서 장기간 항경련제를 투여시 저신장, 저칼슘혈증, 골밀도 저하가 올 수 있는 것으로 알려져 있다. 저자들은 골밀도 및 골표지자의 연구를 통해 항경련제 투여 환아의 골대사 질환의 위험을 조기 발견할 수 있는지 알아보고자 하였다. 방 법 : 간질로 단국대학교병원 소아과에서 12개월 이상 항경련제 치료를 받고 있는 환자들 중 5-16세의 환아 30명을 대상으로 2003년 7월부터 2004년 2월 사이에 본 연구를 시행하였다. 대상 환아들을 carbamazepine과 valproic acid를 단독 투여군과 2가지 이상의 항경련제를 병합투여한 군으로 나누었고, 요추부 골밀도, 체질량지수, 골연령 및 골표지자들을 측정한 후, 남녀별, 연령별로 분류하여 대조군과 비교하였다. 결 과 : 총 30명이었으며, 검사 당시 평균연령은 $10.4{\pm}3.1$세(5-16세)이었다. Carbamazpine 단독 투여군 10명, valproic acid 단독 투여군 6명, 2가지 이상의 약물을 투여 받은 복합 투여군이 14명이었고 복합 투여군 중에는 뇌성마비 2명, 소두증 2명, 뇌연화증 1명, 선천성심장병 1명이 포함되었다. 각 투여군 간에는 요추 골밀도, 칼슘, 인, 알칼리성 인산화효소, $25(OH)D_3$, 오스테오칼신, 부갑상선호르몬, deoxypyridinoline, 골연령 등의 차이는 없었다. 남녀별, 연령별로 나누었을 때 5세 및 15세 여아에서 -2.5 SDS 미만의 의미있는 골밀도의 감소를 보였으며, 체질량지수는 5 percentile 미만의 현저한 감소를 보이고 있었고, 골 연령 및 신장도 감소되어 있었다. 이러한 감소를 보인 두 명의 환아 중 5세 환아는 심방중격결손증 및 소두증을 가지고 있었으며 15세 여아는 뇌성마비 및 뇌연화증이 있었고 좌하지 골절의 기왕력이 있었으며 두 환아 모두 2가지 항경련제를 4년 이상 투약 받았다. 골밀도는 체질량지수 및 골연령과 통계적으로 의미있는 양의 상관관계를 보였다. 결 론 : 장기간 항경련제를 복용하는 소아환자들에 있어 특히, 신체활동이 제한되어 있거나 다른 만성질환을 동반한 경우에는 골대사에 대한 세심한 주의가 필요하며 주기적으로 키, 몸무게를 측정하여 체질량지수 및 신장의 SDS를 산출하는 것이 골대사에 대한 간단하면서도 중요한 검사가 될 수 있을 것으로 생각된다.

• 대한임상검사과학회지
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• 제36권1호
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• pp.13-18
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• 2004

This study was designed to establish working range for reoportable range in own laboratory in order to cover the upper and lower limits of the range in test method. We experimented ten times during 10 days for setting of reportable range with between run for method evaluation. It is generally assumed that the analytical method produces a linear response and that the test results between those upper and lower limits are then reportable. CLIA recommends that laboratories verify the reportable range of all moderate and high complexity tests. The Clinical Laboratory Improvement Amendments(CLIA) and Laboratory Accreditation Program of the Korean Society for Laboratory Medicine states reportable range is only required for "modified" moderately complex tests. Linearity requirements have been eliminated from the CLIA regulations and from others accreditation agencies, many inspectors continue to feel that linearity studies are a part of good lab practice and should be encouraged. It is important to assess the useful reportable range of a laboratory method, i.e., the lowest and highest test results that are reliable and can be reported. Manufacturers make claims for the reportable range of their methods by stating the upper and lower limits of the range. Instrument manufacturers state an operating range and a reportable range. The commercial linearity material can be used to verify this range, if it adequately covers the stated linear interval. CLIA requirements for quality control, must demonstrate that, prior to reporting patient test results, it can obtain the performance specifications for accuracy, precision, and reportable range of patient test results, comparable to those established by the manufacturer. If applicable, the laboratory must also verify the reportable range of patient test results. The reportable range of patient test results is the range of test result values over which the laboratory can establish or verify the accuracy of the instrument, kit or test system measurement response. We need to define the usable reportable range of the method so that the experiments can be properly planned and valid data can be collected. The reportable range is usually defined as the range where the analytical response of the method is linear with respect to the concentration of the analyte being measured. In conclusion, experimental results on reportable range using concentrated control sample and zero calibrators covering from highest to lowest range were salicylate $8.8{\mu}g/dL$, phenytoin $0.67{\mu}g/dL$, phenobarbital $1.53{\mu}g/dL$, primidone $0.16{\mu}g/dL$, theophylline $0.2{\mu}g/dL$, vancomycine $1.3{\mu}g/dL$, valproic acid $3.2{\mu}g/dL$, digitoxin 0.17ng/dL, carbamazepine $0.36{\mu}g/dL$ and acetaminophen $0.7{\mu}g/dL$ at minimum level and salicylate $969.9{\mu}g/dL$, phenytoin $38.1{\mu}g/dL$, phenobarbital $60.4{\mu}g/dL$, primidone $24.57{\mu}g/dL$, theophylline $39.2{\mu}g/dL$, vancomycine $83.65{\mu}g/dL$, valproic acid $147.96{\mu}g/dL$, digitoxin 5.04ng/dL, carbamazepine $19.76{\mu}g/dL$, acetaminophen $300.92{\mu}g/dL$ at maximum level.