• Biomolecules & Therapeutics
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• 제25권2호
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• pp.105-111
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• 2017

It has been known that RA, one of major constituents of Perilla frutescens which has been used as a traditional folk remedy for sedation in oriental countries, shows the anxiolytic-like and sedative effects. This study was performed to know whether RA may enhance pentobarbital-induced sleep through ${\gamma}-aminobutyric$ acid $(GABA)_A-ergic$ systems in rodents. RA (0.5, 1.0 and 2.0 mg/kg, p.o.) reduced the locomotor activity in mice. RA decreased sleep latency and increased the total sleep time in pentobarbital (42 mg/kg, i.p.)-induced sleeping mice. RA also increased sleeping time and number of falling sleep mice after treatment with sub-hypnotic pentobarbital (28 mg/kg, i.p.). In electroencephalogram (EEG) recording, RA (2.0 mg/kg) not only decreased the counts of sleep/wake cycles and REM sleep, but also increased the total and NREM sleep in rats. The power density of NREM sleep showed the increase in ${\delta}-waves$ and the decrease in ${\alpha}-waves$. On the other hand, RA (0.1, 1.0 and $10{\mu}g/ml$) increased intracellular $Cl^-$ influx in the primary cultured hypothalamic cells of rats. RA (p.o.) increased the protein expression of glutamic acid decarboxylase ($GAD_{65/67}$) and $GABA_A$ receptors subunits except ${\beta}1$ subunit. In conclusion, RA augmented pentobarbital-induced sleeping behaviors through $GABA_A-ergic$ transmission. Thus, it is suggested that RA may be useful for the treatment of insomnia.

• Biomolecules & Therapeutics
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• 제25권4호
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• pp.390-395
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• 2017

The present study investigated the sedative effects of Sophora flavescens (SF) and its bioactive compound, matrine through performing locomotor activity test and the electroencephalography (EEG) analysis in the rat. The underlying neural mechanism of their beneficial effects was determined by assessing c-Fos immunoreactivity and serotonin (5-HT) in the brain utilizing immunohistochemical method and enzyme-linked immunosorbent assay. The results showed that SF and matrine administration had an effect on normalization of caffeine-induced hyperactivity and promoting a shift toward non-rapid eye movement (NREM) sleep. c-Fos-immunoreactivity and 5-HT level in the ventrolateral preoptic nucleus (VLPO), a sleep promoting region, were increased in the both SF and matrine-injected groups. In conclusion, SF and its bioactive compound, matrine alleviated caffeine-induced hyperactivity and promoted NREM sleep by activating VLPO neurons and modulating serotonergic transmission. It is suggested that SF might be a useful natural alternatives for hypnotic medicine.

• The Korean Journal of Pain
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• 제27권4호
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• pp.313-320
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• 2014

Dexmedetomidine, an imidazoline compound, is a highly selective ${\alpha}_2$-adrenoceptor agonist with sympatholytic, sedative, amnestic, and analgesic properties. In order to minimize the patients' pain and anxiety during minimally invasive spine surgery (MISS) when compared to conventional surgery under general anesthesia, an adequate conscious sedation (CS) or monitored anesthetic care (MAC) should be provided. Commonly used intravenous sedatives and hypnotics, such as midazolam and propofol, are not suitable for operations in a prone position due to undesired respiratory depression. Dexmedetomidine converges on an endogenous non-rapid eye movement (NREM) sleep-promoting pathway to exert its sedative effects. The great merit of dexmedetomidine for CS or MAC is the ability of the operator to recognize nerve damage during percutaneous endoscopic lumbar discectomy, a representative MISS. However, there are 2 shortcomings for dexmedetomidine in MISS: hypotension/bradycardia and delayed emergence. Its hypotension/bradycardiac effects can be prevented by ketamine intraoperatively. Using atipamezole (an ${\alpha}_2$-adrenoceptor antagonist) might allow doctors to control the rate of recovery from procedural sedation in the future. MAC, with other analgesics such as ketorolac and opioids, creates ideal conditions for MISS. In conclusion, dexmedetomidine provides a favorable surgical condition in patients receiving MISS in a prone position due to its unique properties of conscious sedation followed by unconscious hypnosis with analgesia. However, no respiratory depression occurs based on the dexmedetomidine-related endogenous sleep pathways involves the inhibition of the locus coeruleus in the pons, which facilitates VLPO firing in the anterior hypothalamus.

• Biomolecules & Therapeutics
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• 제27권6호
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• pp.584-590
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• 2019

Luteolin, a widespread flavonoid, has been known to have neuroprotective activity against various neurologic diseases such as epilepsy, and Alzheimer's disease. However, little information is available regarding the hypnotic effect of luteolin. In this study, we evaluated the hypnotic effect of luteolin and its underlying mechanism. In pentobarbital-induced sleeping mice model, luteolin (1, and 3 mg/kg, p.o.) decreased sleep latency and increased the total sleep time. Through electroencephalogram (EEG) and electromyogram (EMG) recording, we demonstrated that luteolin increased non-rapid eye movement (NREM) sleep time and decreased wake time. To evaluate the underlying mechanism, we examined the effects of various pharmacological antagonists on the hypnotic effect of luteolin. The hypnotic effect of 3 mg/kg of luteolin was not affected by flumazenil, a GABAA receptorbenzodiazepine (GABAAR-BDZ) binding site antagonist, and bicuculine, a GABAAR-GABA binding site antagonist. On the other hand, the hypnotic effect of 3 mg/kg of luteolin was almost completely blocked by caffeine, an antagonist for both adenosine A1 and A2A receptor (A1R and A2AR), 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), an A1R antagonist, and SCH-58261, an A2AR antagonist. From the binding affinity assay, we have found that luteolin significantly binds to not only A1R but also A2AR with $IC_{50}$ of 1.19, $0.84{\mu}g/kg$, respectively. However, luteolin did not bind to either BDZ-receptor or GABAAR. From these results, it has been suggested that luteolin has hypnotic efficacy through A1R and A2AR binding.

• Journal of Oral Medicine and Pain
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• 제42권1호
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• pp.1-7
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• 2017

Purpose: The aims of this study were to evaluate the clinical characteristics and polysomnographic results of patients visited the Seoul National University Dental Hospital (SNUDH) and to suggest guidelines for the management of sleep disordered-breathing patients in a dental clinic. Methods: Five hundred sixty-two patients who visited the Snoring and Sleep Apnea Clinic of SNUDH were evaluated for clinical characteristics including associated comorbidities, age, gender, body mass index (BMI), neck circumference, and daytime sleepiness and among them 217 patients were performed nocturnal polysomnography for evaluating respiratory disturbance index, apnea-hypopnea index (AHI), oxygen saturation levels, and sleep stages. The associations among clinical characteristics, sleep parameters, and positional and rapid eye movement (REM) dependencies of the patients were analyzed. Results: The most common co-morbidities of the patients were cardiovascular (30.2%), endocrine (10.8%), and respiratory diseases (7.9%). Age (${\beta}=0.394$), total AHI (${\beta}=0.223$), and lowest $O_2$ saturation levels (${\beta}=0.205$) were significantly associated with the number of co-morbidities in patients with obstructive sleep apnea (OSA). Mean $O_2$ saturation was not significantly associated with number of co-morbidities. Non-positional OSA patients had higher BMI, longer neck circumferences, more severe AHI values, and lower mean and lowest $O_2$ saturation levels compared to positional OSA patients. Not-REM-related patients were older and had more severe AHI values compared to REM-related patients. Not-REM-related patients have longer duration of stage I sleep and shorter stage II, III, and REM sleep than REM-related patients. There were no significant differences in each sleep stage between positional and non-positional patients. Neck circumference, positional dependency, REM dependency, and percentage of supine position were significantly associated with severity of OSA. Conclusions: Age, total AHI, and lowest $O_2$ saturation level were significantly associated with the number of co-morbidities in patients with OSA. Neck circumference, positional dependency, REM dependency, and percentage of supine position were significantly associated with severity of OSA.

• Journal of Yeungnam Medical Science
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• 제24권2호
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• pp.107-118
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• 2007

기질적 뇌병변에 의한 부분 간질환자에서 수면이 간질파의 발생에 미치는 영향을 밝히기 위하여 본 연구를 시행하였다. 기질적 뇌병변에 의한 부분 간질환자 16명과 뇌병변이 없는 34명을 대상으로 50% 수면박탈 후에 통상적인 각성뇌파와 수면뇌파를 동시에 기록하였다. 각성 간질파 지수, 수면 간질파 지수 및 수면에 의한 간질파 지수의 증가율을 구한 후에 기질적 병변의 유무, 발작 및 간질의 종류, 야간 수면 발작의 유무, 이차적 전신성 발작의 유무, 항경련제의 복용 여부, 환자의 나이 및 간질의 발병 연령과 유병 기간에 따른 유의한 차이가 있는지 분석하였다. 1. NREM 수면 기간에 간질파의 발생이 유의하게 증가하였으나 기질적인 뇌병변의 유무에 따른 차이는 없었다(p<0.05). 2. 수면 기간 중 간질파의 증가는 이차적 전신발작의 빈도, 간질 및 발작의 종류, 야간 수면 발작의 빈도, 항경련제 복용에 따른 유의한 차이가 없었다. 3. 전체 50명 가운데 13명(26%) 에서는 수면 상태에서만 간질파가 관찰되었고, 1명(2%) 에서는 각성 상태에서만 간질파가 관찰되었다. 4. 대상 환자 50명 가운데 44명(88%)에서 수면 간질파 지수가 높았고, 5명(10%)에서는 각성 간질파 지수가 높았다(p<0.01). 이상의 결과로 볼 때 기질적 뇌병변을 가진 부분 간질환자에서 통상적인 외래 뇌파검사의 진단율을 높이고 간질파를 활성화시키기 위해서는 수면박탈 후에 각성 상태뿐만 아니라 NREM 수면 상태의 뇌파를 기록하여야 할 것이다.

• 한국감성과학회:학술대회논문집
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• 한국감성과학회 2009년도 춘계학술대회
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• pp.209-210
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• 2009

수면단계는 수면감성을 평가하는데 있어서 중요한 생리지표로서 사용되어왔다. 그러나 수면다원검사를 이용한 전통적 수면단계 분류방법은 뇌전도, 안전도, 심전도, 근전도 등을 종합적으로 측정하므로 수면단계를 비교적 정확히 분류할 수 있지만 피험자에게 심한 구속감을 주는 문제가 있다. 본 연구에서는, 각성상태에서 교감신경계가 지배적인 반면에 수면 중에는 부교감신경계가 더 활동적인 점에 착안하여 수면단계를 간단히 분류할 수 있는 방법을 찾고자 수면단계에 따른 심박동변이도(heart rate variability: HRV)를 분석하였다. 단일채널 심전도를 이용하여 수면단계별로 HRV 의 교감신경계/부교감신경계 활성도의 비율을 분석한 결과, W(wakefulness) 단계가 NREN(non REM) 2 단계, 3 단계, 4 단계에 비하여 높게 나타났으며, NREM 4 단계는 REM(rapid eye movement) 단계와 NREM 1단계에 비하여 낮게 나타났다. 또한 교감신경계/부교감신경계 활성도 비율의 수면단계에 따라 변화하는 양상은 W, REM, NREM 1, 2, 3, 4 단계의 순으로 단조 감소하였다.

• 대한임상검사과학회지
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• 제44권2호
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• pp.52-58
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• 2012

Patients with obstructive sleep apnea (OSA) often have more aggravated symptoms in the supine position. We tried to investigate the clinical characteristics and the predictive factors for positional OSA. Polysomnographic data were reviewed for OSA patients (apnea hypopnea index, $AHI{\geq}5$) from April, 2008 to April, 2011 at the Asan Medical Center. Clinical data, comorbid medical condition data and questionnaires (SF-36, MFI-20, ESS, BDI, STAI) were assessed. All patients were classified into two groups: positional patients (PP) group and non-positional patients (NPP) group. PP was defined as a patient who had the AHI in the supine position was at least twice as high as that in the lateral position. The body position of patients was confirmed by sleep position sensor and video monitor. All patients had at least 30 minutes of positional and 30 minutes of non-positional sleep. We compared clinical, medical, polysomnographic data, and questionnaire results between two (PP and NPP) groups and investigated predictive factors for the PP group using binary logistic regression analysis. In total, 371 patients were investigated. 265 (71.4%) was categorized as PP group and 106 (28.5%) as NPP group. The mean age ($mean{\pm}SD$) was higher in the PP group ($52.4{\pm}9.8$) than in the NPP group ($49.5{\pm}11.9$) (p<0.05). Comparison of sleep parameters between the PP and the NPP group showed that the PP group had significantly lower BMI (PP: $26.1{\pm}3.2kg/m^2$; NPP: $27.8{\pm}4.3kg/m^2$, p<0.001), neck circumference (PP: $39.7{\pm}2.8cm$; NPP: $41.5{\pm}3.7cm$, p<0.001) and hypertension rate (PP: n=89/265 (33.5%); NPP: n=48/106 (45.2%), p=0.0240). In the PP group, the percentage of deep sleep (PP: $8.7{\pm}8.1%$; NPP: $5.6{\pm}7.0%$, P=0.001) and rapid eye movement (REM) (PP: $17.5{\pm}6.1%$; NPP: $14.0{\pm}6.9%$, p<0.001) were significantly higher whereas the percentage of light sleep (stage N1) was significantly lower than the NPP group (PP: $30.4{\pm}12.3$; NPP: $44.5{\pm}20.8%$, p<0.001). During the sleep, the AHI in the supine position (PP: $48.6{\pm}19.5$; NPP: $60.5{\pm}22.6$, p<0.001) and in the non-supine position (PP: $9.4{\pm}8.9$; NPP: $48.4{\pm}24.8$, p=<0.001) were significantly lower and the minimal arterial oxygen saturation in non-REM sleep was significantly higher in the PP group (PP: $80.3{\pm}7.6$; NPP: $75.1{\pm}9.9$, p=<0.001). There were no significant differences in all questionnaires including quality of life. The results of the binary logistic regression analysis showed that age, the amount of REM sleep(%) and AHI were significant predictive factors for positional OSA. The significant predictive factors for positional OSA were older age, higher percentage of REM and lower AHI. The questionnaire results were not significantly different between the two groups.