• 제목/요약/키워드: Drug dependency

검색결과 51건 처리시간 0.027초

Emerging paradigms in cancer cell plasticity

  • Hyunbin D. Huh;Hyun Woo Park
    • BMB Reports
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    • 제57권6호
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    • pp.273-280
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    • 2024
  • Cancer cells metastasize to distant organs by altering their characteristics within the tumor microenvironment (TME) to effectively overcome challenges during the multistep tumorigenesis. Plasticity endows cancer cell with the capacity to shift between different morphological states to invade, disseminate, and seed metastasis. The epithelial-to-mesenchymal transition (EMT) is a theory derived from tissue biopsy, which explains the acquisition of EMT transcription factors (TFs) that convey mesenchymal features during cancer migration and invasion. On the other hand, adherent-to-suspension transition (AST) is an emerging theory derived from liquid biopsy, which describes the acquisition of hematopoietic features by AST-TFs that reprograms anchorage dependency during the dissemination of circulating tumor cells (CTCs). The induction and plasticity of EMT and AST dynamically reprogram cell-cell interaction and cell-matrix interaction during cancer dissemination and colonization. Here, we review the mechanisms governing cellular plasticity of AST and EMT during the metastatic cascade and discuss therapeutic challenges posed by these two morphological adaptations to provide insights for establishing new therapeutic interventions.

경련 질환 환아의 정신병리와 신경학적 요인과의 관계에 대한 연구 (THE STUDY ON RELATIONSHIP BETWEEN PSYCHOPATHOLOGY AND NEUROLOGICAL FACTORS IN CHRONIC EPILEPTIC CHILDREN)

  • 김붕년;조수철;황용승
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • 제7권1호
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    • pp.92-109
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    • 1996
  • 본 연구에서는 정상 지능 범위의 만성 특발성 경련 질환으로 치료중인 40명의 환아군과, 나이, 성별, 학업 성적, 지능 지수를 일치시킨 30명의 대조군을 대상으로, 국내외를 통해 신뢰도 및 타당도가 확인된 평가 도구들인, 부모용 아동 행동 조사표(Child Behavior Checklist)의 한국판, DSM-III-R에 따른 파탄적 행동 장애 척도(Disruptive behavior disorders scale according to DBM-III-R)의 한국판, 예일 아동 평가표(Yale children's inventory)의 한국판, 소아 우울 척도(Children's Depression Inventory)의 한국촌, 소아용 상태 및 특성불안 척도(State-Trait Anxiety Inventory for children)의 한국판, 피어스-해리스 자기 개념 척도(Piers-Harris self-concept questionnaire)의 한국판. 가정 환경 척도(Family environment Scale)의 한국판, 간이 정신진단 검사(Symptom check-list-90)의 한국판, 경련질환에 대한 부모태도 척도(Parent's attitude to epilepsy questionnaire)의 한국판, 아동 의존척도(self-administered dependency questionnaire)의 한국판을 사용하였고, 이들 결과로 부터 얻은 자료의 일부인 환아의 정신병리 부분과 경련 질환의 신경과적인 변수들인 환아의 성별 및 나이, 경련 질환 발병시 나이와 유병기간, 경련질환의 임상적 유형, 뇌파의 유형 최근 6개월간의 경련 빈도, 항경련 약물 치료력과 그 반응등과의 관련성을 평가하였다. 위에서 얻은 자료들을 토대로 분석하여 다음과 같은 연구 결과를 얻었다. 환아의 우울과 관계된 위험 요인은, 조기 발병(early onset), 복합성 부분 간질(complex partial seizure), 뇌파상 편측성 측두엽 이상(lateralized temporal focal abnormality in EEG), 약물 병합 투여(drug polypharmacy), 고 빈도 경련(high seizure frequency)임을 알 수 있었고, 이들 위험요인들은 상호 연관되어 있었다. 불안에 영향을 미치는 요인은 높은 연령. 뇌파상 편측성 측두엽 이상, 고 빈도 경련이었고, 학습 및 언어적 문제와 관련이 있는 위험 요인은 환아의 어린나이, 조기 발병, 복합성 부분 간질, 고빈도 경련 등이었다. 주의력 결핍 과잉행동 장애와 반항 및 품행장애에 영향을 미치는 위험 요인은 남성, 어린 나이, 조기 발병, 뇌파상 편측성 측두엽 이상, 고 빈도 경련등이었다. 위의 결과를 종합하면, 우울, 불안, 품행장애 및 주의력 결핍 과잉 행동장애에 공통적으로 관계되는 위험요인은, 뇌파상 편측성 측두엽 이상, 고 빈도 경련이라는 겻을 알 수 있었다. 향후 연구를 통해서는 신경학적 요인이외에 가족 및 사회-인구학적 위험 요인을 찾는 연구가 지속되어야 하며, 이를 통해 종합적 위험 요인 평가 작업과 치료적 대안을 제시하는 후속 작업이 지속 되어야 할 것 이다.

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유리선량계의 선량 특성에 관한 연구 (Study on Dosimetric Properties of Radiophotoluminescent Glass Rod Detector)

  • 라정은;신동오;홍주영;김희선;임천일;정희교;서태석
    • Journal of Radiation Protection and Research
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    • 제31권4호
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    • pp.181-186
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    • 2006
  • 본 연구에서는 최근 들어 새롭게 소개되고 있는 유리선량계의 재현성 및 선량의 선형성 그리고 에너지 의존성을 조사하였다. 50개의 유리선량계를 5번 판독한 결과, 재현성은 모두 ${\pm}1.2%$(1SD)이내에서 잘 일치하는 것을 알 수 있었으며 $^{60}Co$ 감마선에서 선량 0.5 Gy부터 50 Gy까지 유리선량계의 반응도를 평가해 본 결과는 0.9998의 선형계수를 확인할 수 있었다. 또한 유리선량계의 에너지의존성은 원통형의 전리함으로 측정한 선량과 비교했을 때 광자선에너지 6, 15 MV 각각에 대해 $^{60}Co$ 감마선의 반응도로 일반화시킨 결과 모두 ${\pm}1.5%$(1SD)이내에서 일치하였다. 이는 고에너지 광자선에 대해 열형광선량계와는 비슷한 결과이며 다이오드 선량계와 비교해서 했을 때는 낮은 에너지 의존성을 가지는 것이다. 따라서 유리선량계는 기존의 다른 선량계에 비해 사용 가능한 선량범위가 넓고 고에너지 광자선에서 에너지의존성이 낮으며 유효크기가 작은 장점 등으로 인해 소조사면의 고선량을 사용하는 방사선 수술분야의 선량측정에 적합한 선량계라는 것을 확인할 수 있었다.

Functional Implications of Transporters Under Nitrosative Stress Conditions

  • Yu, Kyung-Ha;Maeng, Han-Joo;Chung, Suk-Jae
    • Journal of Pharmaceutical Investigation
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    • 제40권3호
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    • pp.139-153
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    • 2010
  • Nitrosative stress is defined as pathophysiological conditions that are related to covalent modifications of proteins by nitration/nitrosylation by forms of nitrogen oxide ($NO_x$), leading to DNA damage, ultimately, cell death. This type of stress condition appears to be associated with a number of disease states, including diabetes, inflammation and neurodegenerative diseases. Since these pathological conditions are frequently chronic in nature and, thus, require long-term treatment, changes in pharmacokinetics are likely to affect the therapy. Transporters are membrane proteins that facilitate the movement of substrates, including drugs, across plasma membranes of epithelial / endothelial cells. Since it is now increasingly evident that transporters are pharmacokinetically significant, functional alteration of transporters by this stress condition may have therapeutic relevance. In this review, experimental techniques that are used to study both in vivo and in vitro nitrosative stress are summarized and discussed, along with available literature information on the functional implication of transporters under conditions of nitrosative stress conditions. In the literature, both functional induction and impa irment were apparently present for both drug transporter families [i.e., ATP-binding cassette (ABC) and solute carrier families (SLC)]. Furthermore, a change in the function of a certain transporter appears to have temporal dependency by impairment in the early phase of nitrosative stress and induction thereafter, suggesting that the role of nitrosative stress is complex in terms of functional implications of the transporters. Although the underlying mechanisms for these alterations are not fully understood, protein nitration/nitrosylation appears to be involved in the functional impairment whereas transcript factor(s) activated by nitrosative stress may play a role, at least in part, in functional induction. Interestingly, functional induction under conditions of nitrosative stress has not been observed for SLC transporters while such impairment has been documented for both ABC and SLC transporters. Further investigations appear to be necessary to fully delineate the underlying reasons for these differences on the impact and importance of nitrosative stress conditions.

여성건강과 남녀평등 문화 (Women's Health and Equality of Men and Women)

  • 이경혜
    • 여성건강간호학회지
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    • 제5권2호
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    • pp.278-287
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    • 1999
  • Women's health is directly related to economic and developmental level of their nations, and it is very much effected by socio-cultural factors which are related to gender discrimination. women's health needs have been oppressed and neglected in male-dominated society. For maintenance and promotion in women's health and improve of quality of life, the common idea of gender discrimination in our society and preference of having son rather than daughter from its certain from must be banished. Though the common idea of gender discrimination was a basic ideology in liberation of women, recently the aspect of difference rather than discrimination is an important matter and unique characteristics of women are strongly pointed and additionally harmonic living with men is getting to be a man idea in women's health. The social idea in gender discrimination was from christian culture in the western society and confucianism related the social norms of "Namzonyobe" (means men are honorable and women are low), "Samzongzido" (means women ought to obey certain three rules for the family), "Chilgeziak" (means seven wickedness of housewife) in this country, korea. Those ideas deprived women's ability in health management and in the decision making process for their health. Because of those cultural influences, still many pregnant women are experiencing artificial abortion when they know the fetus is a girl through ultrasound and amniocentesis. Nowadays there are many health problems of women in korea. The reasons are that Korea culture has complicatedly mixing with confucianism and western culture. Under the these cultural influences, change in value of beauty and trend of liberation in sexuality have brought out health problems, alcohol, smoking, and drug abuse in young women. In order to solve the women's health problem, first of all women have to come out of the passive manner of dependency on man. Also they should have the insight and the management and/or intervention ability of caring their health. It can be obtained through the family-society-nation wide approach as well as the approach for women themselves.

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인후두역류질환 (Laryngopharyngeal Reflux Disease, LPRD)에서 Rabeprazole Sodium($Pariet^{\circledR}$)의 임상효과 (The clinical effects of rabeprazole sodium($Pariet^{\circledR}$) in the treatment of Layngopharyngeal Reflux)

  • 최홍식;최현승;김한수
    • 대한기관식도과학회지
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    • 제9권1호
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    • pp.60-66
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    • 2003
  • Although there is a wide range of diseases caused by gastric acid reflux and the number of cases is on the rise, it is difficult for the laryngologist to make the correct diagnosis. The treatment for laryngopharyngeal reflux can be grouped into 3 categories - changes in lifestyle, medication, and surgery. The medication used to treat laryngopharyngeal reflux are prokinetic agents and acid supressive agents such as antacids, H2 blockers, and PPIs(Proton pump inhibitor). Rabeprazole sodium($Pariet^{\circledR}$) is a newly developed agent belonging to the PPI group, but in contrast with the existing drugs such as omeprazole, lansoprazole, pantoprazole, has a low dependency on CYP2C19 during the metabolic cycle. Thus, it is known to have a quick but fixed antiacid effect and less individual differences. We analyzed 2166 patients from 32 hospitals who were prescribed $Pariet^{\circledR}$ from May, 2001 to April, 2002. The patients were divided into 4 groups according to the duration of treatment - Group 1: 1-14 days, Group 2: 15-28 days, group 3: 29-56 days, Group 4: more than 56 days. The cases were then analyzed for improvement of 8 symptoms(heart bum, regurgitation, chronic cough, hoarseness, globus sensation, chronic throat clearing, sore throat, and dysphagia), improvement on laryngoscope, usefulness to the doctor, and complication development. Of the total of 2116 patients, 1627(75.1%) cases showed at least 50% improvement of symptoms and the amount of improvement increased according to the duration of medical treatment. Most of the patients showed objective improvement on the laryngoscope, with 32.9% showing significant improvement and 38.7% showing moderate improvement. 37.6% of the doctors questioned replied that $Pariet^{\circledR}$ was very useful and 50.3% said it was useful, showing that most were satisfied with the treatment results. The complications known to develop after taking PPI are headache, nausea, diarrhea, abdominal pain, constipation, dizziness, fatigue, and of these, only a small percentage of the patients complained of mild headache. $Pariet^{\circledR}$ has shown to be a relatively safe and effective drug for the treatment of laryngopharyngeal reflux.

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골다공성 척추체 골절에서 척추 후만변형 복원술의 치료효과 (Therapeutic Effects of Kyphoplasty on Osteoporotic Vertebral Fractures)

  • 박춘근;김동현;류경식;손병철
    • Journal of Korean Neurosurgical Society
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    • 제37권2호
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    • pp.116-123
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    • 2005
  • Objective: Percutaneous kyphoplasty using a balloon-catheter is an widely accepted method which achieves the restoration of vertebral height and the correction of kyphotic deformity with little complication in osteoporotic vertebral compression fractures. The authors assess the results of 59 patients who underwent kyphoplasty, and analyze the factors that could affect the prognosis. Methods: From December 2001 to May 2003, fifty-nine patients underwent kyphoplasty. The patients included 49 women and 10 men aged 52-85 years. Average t-score on bone marrow density was -3.58. About 7cc of polymethylmethacrylate(PMMA) was injected into the fractured vertebral body using $Kyphon^{(R)}$ under local anesthesia. The vertical height of all fractured vertebrae was measured both before and after surgery. Outcome data were obtained by comparing pre- and post-operative VAS score and by assessing postoperative satisfaction, drug dependency and activity. Various clinical factors were analyzed to assess the relationship with the outcome. Results: The VAS score improved significantly, and the mean percentage of restored vertebral height was 53%. The mean improvement in kyphosis was $3.6^{\circ}$. Eighty-nine percent of the patients gained excellent or good results. Any of the clinical factors including the interval between fracture and operation, the degree of height loss, the degree of the vertebral height restoration or the correction rate of kyphosis did not affect the clinical results. Conclusion: Kyphoplasty is associated with a statistically significant improvement in pain and function with little complication. The clinical results are not affected by any clinical parameters. Further follow-up study is needed to determine whether the restoration affects the long-term clinical results.

Comparison of the anesthetic effects of 2,2,2-tribromoethanol on ICR mice derived from three different sources

  • Lee, Mi Ree;Suh, Hye Rin;Kim, Myeong Whan;Cho, Joon Young;Song, Hyun Keun;Jung, Young Suk;Hwang, Dae Youn;Kim, Kil Soo
    • Laboraroty Animal Research
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    • 제34권4호
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    • pp.270-278
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    • 2018
  • This study was conducted to compare the anesthetic effects of 2,2,2-tribromoethanol (TBE, $Avertin^{(R)}$) in ICR mice obtained from three different sources. TBE (2.5%) was intraperitoneally injected at three doses: high-dose group (500 mg/kg), intermediate-dose group (250 mg/kg), and low-dose group (125 mg/kg). Anesthesia time, recovery time, end-tidal peak $CO_2$ ($ETCO_2$), mean arterial blood pressure, heart rate, oxygen saturation ($SpO_2$), body temperature, pH, $PCO_2$, and $PO_2$ of the arterial blood were measured. Stable anesthesia was induced by all doses of TBE and the anesthesia time was maintained exhibited dose dependency. No significant differences in anesthetic duration were found among the three different strains. However, the anesthesia time was longer in female than in male mice, and the duration of anesthesia was significantly longer in female than in male mice in the high-dose group. The recovery time was significantly longer for female than male mice in the intermediate- and high-dose groups. In the ICR strains tested, there were no significant differences in the mean arterial blood pressure, $SPO_2$, arterial blood $PCO_2$, and $PO_2$, which decreased after TBE anesthesia, or in heart rate and $ETCO_2$, which increased after TBE anesthesia. In addition, body temperature, blood biochemical markers, and histopathological changes of the liver, kidney, and lung were not significantly changed by TBE anesthesia. These results suggested that ICR mice from different sources exhibited similar overall responses to a single exposure to TBE anesthesia. In conclusion, TBE is a useful drug that can induce similar anesthetic effects in three different strains of ICR mice.

Comparative Phenotypic Analysis of Anabaena sp. PCC 7120 Mutants of Porin-like Genes

  • Schatzle, Hannah;Brouwer, Eva-Maria;Liebhart, Elisa;Stevanovic, Mara;Schleiff, Enrico
    • Journal of Microbiology and Biotechnology
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    • 제31권5호
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    • pp.645-658
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    • 2021
  • Porins are essential for the viability of Gram-negative bacteria. They ensure the uptake of nutrients, can be involved in the maintenance of outer membrane integrity and define the antibiotic or drug resistance of organisms. The function and structure of porins in proteobacteria is well described, while their function in photoautotrophic cyanobacteria has not been systematically explored. We compared the domain architecture of nine putative porins in the filamentous cyanobacterium Anabaena sp. PCC 7120 and analyzed the seven candidates with predicted OprB-domain. Single recombinant mutants of the seven genes were created and their growth capacity under different conditions was analyzed. Most of the putative porins seem to be involved in the transport of salt and copper, as respective mutants were resistant to elevated concentrations of these substances. In turn, only the mutant of alr2231 was less sensitive to elevated zinc concentrations, while mutants of alr0834, alr4741 and all4499 were resistant to high manganese concentrations. Notably the mutant of alr4550 shows a high sensitivity against harmful compounds, which is indicative for a function related to the maintenance of outer membrane integrity. Moreover, the mutant of all5191 exhibited a phenotype which suggests either a higher nitrate demand or an inefficient nitrogen fixation. The dependency of porin membrane insertion on Omp85 proteins was tested exemplarily for Alr4550, and an enhanced aggregation of Alr4550 was observed in two omp85 mutants. The comparative analysis of porin mutants suggests that the proteins in parts perform distinct functions related to envelope integrity and solute uptake.

Thelephoric acid의 CYP2J2 효소 활성 저해제 평가 (Inhibitory Potential of Thelephoric Acid on CYP2J2 Activities in Human Liver Microsomes)

  • 오철학;이보람;송경식;류광현
    • 생명과학회지
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    • 제23권9호
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    • pp.1126-1132
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    • 2013
  • CYP2J2 효소는 간외의 조직에 존재 하는 효소로써, 주로 심혈관계에 발현되어 있다. CYP2J2는 내인성 대사체 및 여러 치료 약물들의 대사에 중요한 작용을 하고 있다. 또한 CYP2J2는 인체의 종양조직이나 종양 세포주에서 과발현되어 있어, 종양 치료를 위한 새로운 표적이 되고 있다. 본 연구에서는 천연물 10종을 대상으로 시토크롬 2J2 동효소에 저해능을 가지는 화합물을 발굴하고자 하였다. 10종의 천연물 중 thelephoric acid는 CYP2J2에 의해 매개되는 에바스틴($IC_{50}=5.32{\mu}M$), 아스테미졸($IC_{50}3.23{\mu}M$) 및 터페나딘($IC_{50}=3.27{\mu}M$) 대사를 강력하게 저해하였다. 향후, 이 약물을 대상으로 한 항암 활성 평가가 필요할 것으로 판단된다.