• 한국임상약학회지
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• 제30권2호
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• pp.81-86
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• 2020

Background: The number of patients with dementia continues to increase as the age of aging continues to grow. Psychiatric symptoms caused by senile dementia are controlled using antipsychotics. However, these antipsychotics can lead to Parkinson's disease, and abuse of dopamine derivatives such as levodopa among Parkinsonian drugs can lead to psychosis. Therefore, we evaluated the patterns of prescribed antipsychotics and antiparkinsonian drugs in patients with senile dementia. Methods: We used data from the sample of elderly patients from the Health Insurance Review and Assessment Service (HIRA-APS-2016). We analyzed the patterns of prescribing antipsychotics and antiparkinsonian drugs including prescribed daily dosage, period of prescription, and number of patients with both antipsychotics and antiparkinsonian drugs for senile dementia. Results: Among the 159,391 patients with dementia included in this analysis, 4,963 patients (3.1%) and 16,499 patients (10.4%) were prescribed typical and atypical antipsychotic drugs, respectively. The most frequently prescribed typical antipsychotic was haloperidol (4,351 patients with dementia), whereas the atypical agent was quetiapine (12,719 patients). The most frequently prescribed antiparkinsonian drugs were in the order of levodopa/carbidopa, benztropine, and ropinirole. In addition, 1,103 and 3,508 patients prescribed typical and atypical antipsychotics, respectively, were co-prescribed antiparkinsonian drugs. Conclusions: Atypical antipsychotics were the preferred prescription in patients with senile dementia. The prescription dose was relatively low; however, the average treatment duration was mostly long-term. Selection of antipsychotics and/or antiparkinsonian drugs should be made carefully in senile dementia and the causal relationship of adverse drug reactions needs further study.

• BMB Reports
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• 제50권7호
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• pp.345-354
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• 2017

Autophagy, a catabolic process necessary for the maintenance of intracellular homeostasis, has recently been the focus of numerous human diseases and conditions, such as aging, cancer, development, immunity, longevity, and neurodegeneration. However, the continued presence of autophagy is essential for cell survival and dysfunctional autophagy is thought to speed up the progression of neurodegeneration. The actual molecular mechanism behind the progression of dysfunctional autophagy is not yet fully understood. Emerging evidence suggests that basal autophagy is necessary for the removal of misfolded, aggregated proteins and damaged cellular organelles through lysosomal mediated degradation. Physiologically, neurodegenerative disorders are related to the accumulation of amyloid ${\beta}$ peptide and ${\alpha}-synuclein$ protein aggregation, as seen in patients with Alzheimer's disease and Parkinson's disease, respectively. Even though autophagy could impact several facets of human biology and disease, it generally functions as a clearance for toxic proteins in the brain, which contributes novel insight into the pathophysiological understanding of neurodegenerative disorders. In particular, several studies demonstrate that natural compounds or small molecule autophagy enhancer stimuli are essential in the clearance of amyloid ${\beta}$ and ${\alpha}-synuclein$ deposits. Therefore, this review briefly deliberates on the recent implications of autophagy in neurodegenerative disorder control, and emphasizes the opportunities and potential therapeutic application of applied autophagy.

• Journal of Korean Neurosurgical Society
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• 제42권6호
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• pp.455-461
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• 2007

Objective : It was hypothesized that dopamine agonist administration and subthalamic nucleus (STN) lesion in the rat might have a synergistic effect on the neuronal activities of substantia nigra pars reticulata (SNpr) as observed in patients with Parkinson's disease. The effects of SKF38393 (a $D_1$ receptor agonist) and Quinpirole (a $D_2$ receptor agonist) were compared in parkinsonian rat models with 6- hydroxydopamine (6-OHDA) after STN lesion. Methods : SKF38393 and Quinpirole were consecutively injected intrastriatally. SNpr was microrecorded to ascertain the activity of the basal ganglia output structure. The effect of SKF38393 or Quinpirole injection on the firing rate and firing patterns of SNpr was investigated in medial forebrain bundle (MFB) lesioned rats and in MFB+STN lesioned rats. Results : The administration of SKF38393 decreased SNpr neuronal firing rates and the percentage of burst neurons in the MFB lesioned rats, but did not alter them in MFB+STN lesioned rats. The administration of Quinpirole significantly decreased the spontaneous firing rate in the MFB lesioned rats. However, after an additional STN lesion, it increased the percentage of burst neurons. Conclusion : This study demonstrated that dopamine agonists and STN lesion decreased the hyperactive firing rate and the percentage of burst neurons of SNpr neurons in 6-OHDA lesioned rats, respectively. Quinpirole with STN lesion increased a percentage of burst neurons. To clear the exact interactive mechanism of $D_1$ and $D_2$ agonist and the corresponding location, it should be followed a study using a nonselective dopamine agonist and $D_1$, $D_2$ selective antagonist.

• Molecules and Cells
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• 제40권7호
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• pp.450-456
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• 2017

Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm. Specifically, genetic deletion of the circadian nuclear receptor Rev-$erb{\alpha}$ induces mania-like behavior caused by increased midbrain dopaminergic (DAergic) tone at dusk. The association between circadian rhythm and emotion-related behaviors can be applied to pathological conditions, including neurodegenerative diseases. In Parkinson's disease (PD), DAergic neurons in the substantia nigra pars compacta progressively degenerate leading to motor dysfunction. Patients with PD also exhibit non-motor symptoms, including sleep disorder and neuropsychiatric disorders. Thus, it is important to understand the mechanisms that link the molecular circadian clock and brain machinery in the regulation of emotional behaviors and related midbrain DAergic neuronal circuits in healthy and pathological states. This review summarizes the current literature regarding the association between circadian rhythm and mood regulation from a chronobiological perspective, and may provide insight into therapeutic approaches to target psychiatric symptoms in neurodegenerative diseases involving circadian rhythm dysfunction.

• Molecular & Cellular Toxicology
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• 제3권2호
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• pp.77-84
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• 2007

Millions of individuals worldwide are currently afflicted with neurodegenerative disorders such as Parkinson's disease and multiple sclerosis which are caused by the death of specific types of specialized cells in the Central Nervous System (CNS). Recently, Neural Stem Cells (NSCs) are able to replace these dead cells with new functional cells, thereby providing a cure for devastating neural diseases. The clinical use of neural stem cells (NSCs) for the treatment of neurological diseases requires overcoming the scarcity of the initial in vivo NSC population. Thus, we developed a novel 3-dimentional cellular automata model for optimum production of neural stem cells and their derivatives in large scale to treat neurodegenerative disorder patients.

• 생명과학회지
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• 제28권2호
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• pp.170-175
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• 2018

파킨슨병은 두번째로 많이 발병하는 퇴행성 신경질환이며 약 5-10%는 유전된다. Leucine-rich repeat kinase 2(LRRK2)는 그 돌연변이의 일부가 파킨슨병을 일으키는 유전자이다. LRRK2에는 인산화효소와 GTPase 기능이 있는 도메인과 함께 단백질 상호작용에 관여하는 Leucine-rich repeat (LRR), WD40 도메인이 존재하여, LRRK2와 상호작용하는 단백질이 파킨슨병 발병에 중요한 역할을 함을 암시한다. 우리는 이러한 LRRK2와 상호작용하는 단백질을 규명하여 그 단백질의 세포내 기능을 통해 역으로 LRRK2의 기능을 밝히고자 하였다. NIH3T3 세포 용해물을 LRRK2 항체와 IgG로 각각 면역침강하여 LRRK2 항체 침강반응에서만 특이적으로 나타나는 단백질 밴드를 질량 분석한 결과, methionyl-tRNA synthetase (MRS)로 나타났다. LRRK2와 MRS의 상호작용은 면역침강반응과 GST-pull down assay를 통해 확인됐다. 병을 유발하는, LRRK2의 돌연변이인 G2019S가 인산화효소 활성을 증가시키므로 LRRK2가 MRS를 인산화하는 지를 조사한 결과, LRRK2재조합단백질은 MRS 단백질을 인산화 하지 않았다. 또한 이들 두 단백질의 각각의 양 증가가 상대 단백질의 양 증가, 즉 안정성에 영향을 미치는 지를 조사하였으나 안정성의 변화를 관찰하지 못하였다. 결론적으로, MRS는 LRRK2와 상호작용을 하지만 LRRK2 인산화효소의 기질은 아니다.

• 제어로봇시스템학회논문지
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• 제20권6호
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• pp.647-650
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• 2014

Assessment and rehabilitation of patients with unilateral visual neglect has been one of the fields that require assistive technology. Paper-and-pencil tests, including the LBT (Line Bisection Test), have been one of the most commonly used visual neglect assessment methods used in a clinical setting. The key motivation of this study was to establish a computer-based real-time assessment system for the hemi-neglect patients without altering the conventional paper-and-pencil based user tools. A digital penbased assessment and rehabilitation system, the ePen System, could eliminate the manual assessment time while maintaining measurement accuracy. As a result, the proposed system may assist rehabilitation specialists to assess and diagnose patients with unilateral visual neglect. This system can be applied to a range assessment and rehabilitation modalities based on a pen and paper. It can also be applied to various patients such as those with Parkinson's disease, stroke sufferers, or those who have experienced different forms of brain lesions.

• 한국임상약학회지
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• 제32권4호
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• pp.313-320
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• 2022

Background: Serotonin syndrome is a life-threatening disease if not appropriately treated. This study aimed to investigate the prescription status of contraindicated drug combinations that cause serotonin syndrome and identify the related factors. Methods: A cross-sectional study was conducted using nationwide claims data. Adult patients taking serotonergic drugs with Parkinson's disease or mental disorders were selected. Based on international medical databases (MDBs) and the Korean Drug Utilization Review (DUR), the status of prescribing contraindicated drug combinations that induce serotonin syndrome, the related factors, and the difference between international MDBs and the Korean DUR were analyzed. Results: Of the 49,773 study subjects, 163 (0.3%) were prescribed contraindicated serotonergic drug combinations based on international MDBs, and among them, only 105 (64.4%) were contraindicated by the Korean DUR. Positive influencing factors for prescribing contraindicated drug combinations include patient age between 65 and 74 and physician's specialties (neurologists, and orthopedists). Negative influencing factors were physician's specialty (internists) and medical institution (primary institutions). Conclusion: Despite the implementation of DUR, 3 out of 1,000 study subjects received contraindicated drug combinations that caused serotonin syndrome. Hence, it is necessary to comply with the DUR and improve it in accordance with international MDBs.

• 대한핵의학회지
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• 제39권1호
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• pp.9-14
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• 2005

목적 : 좌각차단이나 우심실조율박동과 같은 부정맥을 가진 환자들에서 심근관류는 의미있게 변화한다는 것이 알려져 있다. 비정상적인 심근관류는 심실조기흥분에 의해서도 야기될 수 있다고 알려져 있지만, 그 위치 범위 강도와 부전도로와의 관계는 아직 정립되어 있지 않았다. 이에 WPW 증후군 환자에서 부전도로의 위치와 SPECT상에서 관류양상의 관계에 대해 알아보고자 하였다. 대상 및 방법 : WPW 증후군 환자 11명에 대해 Adenosine 99m-Tc MIBI 또는 Tl-201 심근관류 SPECT를 시행하였다, 관류결손은 Fitzpatrick's algorithm을 기초로 한 심전도 또는 전기생리학적검사 및 전극도자 절제술을 이용한 부전도로의 위치와 비교하였다. 결과: 11명의 환자들의 평균 나이는 $39.9{\pm}8.6$세 였고, 비특이적인 흉통을 호소하거나, 증상이 없었다. 11명 모두 관삳동맥의 위험도에 관한 계산도표를 이용하여 관상동맥질환의 확률을 예측했으나 0.1 이하로 위험도가 낮았고 이중 4명은 관상동맥조영술을 시행한 결과 3명은 정상이었고 1명은 관동맥 협착 (50%) 부위의 심근혈류가 정상이었다. 4명의 환자에서 전기생리학적검사 및 전극도자 절제술을 시행하였다. 9명의 가역적 그리고 1명의 비가역적 관류결손이 관찰되었고. 범위는 소에서 대까지 강도는 경도에서 중등도까지 나왔다. 부전도로의 위치가 우외측인 1명은 관류결손이 없었으나, 그 외의 환자들은 다양한 양상을 보였다. 부전도로의 위치가 좌외측인 환자중 1명에 대해 전극도자 절제술을 시행하였고 6주후에 SPECT를 한 결과 시술 전에 있던 관류결손의 범위가 현저하게 감소하였다. 결론: WPW환자에서 심근관류결손은 다양한 범위, 강도 및 위치를 가진다. 거의 대부분의 환자에서 비정상적인 관류결손이 나타났으나, SPECT 소견으로 부전도로의 위치를 특이적으로 예측하기는 어려웠다. 그러므로 WPW증후군 환자에서 심근관류 SPECT의 결과를 주의 깊게 해석해야 한다.

• 한국임상약학회지
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• 제26권2호
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• pp.172-180
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• 2016

Background: Ischemic heart disease is the most common type of heart disease and an important cause of death in Korea. Among marketed anti-anginal medications, molsidomine, nicorandil, and trimetazidine are approved in Korea with unique mechanism of actions. As these drugs are not approved by the US Food and Drug Administration, the access to the up-to-dated and comprehensive safety-related information has been less than optimal from drug information resources used by Korean pharmacists. Methods: A systematic review was conducted using Embase and Korean manuscripts to compile safety updates for these medications. Out of 418 articles from keyword searches, 52 studies were reviewed in full to compare adverse effects (AEs) with the approved package inserts (PI). Results: Molsidomine related adverse effects were mostly mild or moderate, but anxiety, palpitation, epigastric pain, and sexual potency reduction were additional AEs found from the review not listed in PI. Although PI has included ulceration in oral cavity and gastrointestinal tracts including anus by nicorandil, the Korea FDA recently recommended adding corneal, genital, and skin ulcers to the approved PI. Trimetazidine induced Parkinsonism, worsening of the symptoms for patients diagnosed with Parkinson's disease, gastrointestinal burning, and muscle cramps were additionally identified AEs not listed in PI for trimetazidine. Conclusion: Continuous evaluations of the safety profile of these agents are needed to balance the risks and benefits to provide evidence-based safety counseling to the patients. In addition, more focused efforts on spontaneous reporting are warranted by healthcare professionals to safeguard patients against AEs.