• Archives of Pharmacal Research
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• 제19권4호
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• pp.280-285
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• 1996

The sustained release dosage form which delivers melatonin (MT) in a circadian fashion over 8 h is of clinical value for those who have disordered circadian rhythms because of its short halflife. The purpose of this study was to evaluate the gelling properties and release characteristics of alginate beads varying multivalent cationic species $(Al^{+++}, \; Ba^{++}, \; Ca^{++}, \; Mg^{++}, \; Fe^{+++}, \; Zn^{++})$. The surface morphologies of Ca- and Ba-alginate beads were also studied using scanning electron microscope (SEM). MT, an indole amide pineal hormone was used as a model drug. The $Ca^{++}, \; Ba^{++}, \; Zn^{++}, \; Al^{++}\; and\; Fe^{+++}\; ions\; except\; Mg^{++}$ induced gelling of sodium alginate. The strength of multivalent cationic alginate beads was as follows: $Al^{+++}\llFe^{+++} the induced hydrogel beads were very fragile and less spherical. Fe-alginate beads were also fragile but stronger compared to Al-alginate beads. Ba-alginate beads had a similar gelling strength but was less spherical when compared to Ca-alginate beads. Zn-alginate beads were weaker than Ca- and Ba-alginate beads. Very crude and rough crystals of Ba- and Ca-alginate beads at higher magnifications were observed. However, the type and shape of rough crystals of Ba- and Ca-alginate beads were quite different. No significant differences in release profiles from MT-loaded multivalent cationic alginate beads were observed in the gastric fluid. Most drugs were continuously released upto 80% for 5 h, mainly governed by the passive diffusion without swelling and disintegrating the alginate beads. In the intestinal fluid, there was a significant difference iq the release profiles of MT-loaded multivalent cationic alginate beads. The release rate of Ca-alginate beads was faster when compared to other multivalent cationic alginate beads and was completed for 3 h. Ba-alginate beads had a very long lag time (7 h) and then rapidly released thereafter. MT was continuously released from Feand Zn-alginate beads with initial burstout release. It is assumed that the different release rofiles of multivalent cationic alginate beads resulted from forces of swelling and disintegration of alginate beads in addition to passive diffusion, depending on types of multivalent ions, gelling strength and drug solubility. It was estimated that 0.2M $CaCl_2$ concentration was optimal in terms of trapping efficiency of MT and gelling strength of Ca-alginate beads. In the gastric fluid, Ca-alginate beads gelled at 0.2 M $CaCl_2$ concentration had higher bead strength, resulting in the most retarded release when compared to other concentrations. In the intestinal fluid, the decreased release of Ca-alginate beads prepared at 0.2 M $CaCl_2$ concentration was also observed. However, release profiles of Ca-alginate beads were quite similar regardless of $CaCl_2$ concentration. Either too low or high $CaCl_2$ concentrations may not be useful for gelling and curing of alginate beads. Optimal $CaCl_2$ concentrations must be decided in terms of trapping efficiency and release and profiles of drug followed by curing time and gelling strength of alginate beads.

• Journal of Pharmaceutical Investigation
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• 제23권3호spc1호
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• pp.9-18
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• 1993

Sugar spheres loaded with melatonin (MT) were coated with $Aquacoat^{\circledR}$ to control the release rate of MT over 8 hours. A zero-order release pattern over 8 hours was obtained with 20% coating on 8-10 mesh beads in USP basket dissolution studies. MT in 20% coated beads was quite stable at room temperature with less than 5% MT degraded during 6 months' storage. Dissolution profiles were also unchanged after 6 months. An oral preparation containing MT-loaded uncoated beads for immediate release and 20% coated beads with $Aquacoat^{\circledR}$ for controlled release over 8 hours was evaluated in six human subjects. When total 0.5 mg MT as low dose (immediate release portion of MT, 0.1 mg) was administered to four subjects, average peak plasma MT concentration was reached at about 600 pg/ml and maintained at about 10 pg/ml over 8 hours. Plasma MT concentration-time profiles were similar in shape to computer-simulated profiles. However, maximal plasma MT concentrations were three times greater compared to computer simulated curve. These results suggest that MT dose, ratio of immediate and controlled release MT, and pharmacokinetic parameters selected are adjusted to mimic endogenous MT concentration-time curve. In another study, 0.2 mg MT having 10% of immediate release portion and 80% controlled release portion produced plasma MT concentration-time curve which is more similar to endogenous profiles. A low bioavailability (<20%) may result from extensive first pass metabolism and remaining amounts of MT from controlled beads. A good correlation between plasma MT concentration and urinary excretion rate of 6-sulphatoxymelatonin (6-STMT), a major metabolite of MT was observed. As plasma MT concentration increased, urinary excretion rate of 6-STMT increased concomitantly. The linear relation between plasma MT and urinary excretion rate of 6-STMT was statistically significant. This result suggests that urinary 6-STMT may be used as an index of circadian rhythms of MT in humans.

• Asian-Australasian Journal of Animal Sciences
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• 제16권12호
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• pp.1701-1704
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• 2003

Melatonin regulates circadian rhythms and reproduction changes in seasonally reproductive mammals through binding to high-affinity, G-protein-coupled receptors. Small Tail Han sheep that has significant characteristics of high prolificacy and nonseasonal ovulatory activity is an excellent local sheep breed in P. R. China. The exon 2 of the ovine melatonin receptor 1a (MTNR1A) gene was amplified and a uniform fragment of 824 bp was obtained in 150 ewes of Small Tail Han sheep. The 824 bp PCR product was digested with restriction endonucleases Mnl I and Rsa I, and genetic polymorphism was detected by PCR-RFLP. Polymorphic Mnl I site was detected at base position 605 of the exon 2 of the MTNR1A gene. There were two kinds of genotypes in Small Tail Han sheep, AB (303 bp, 236 bp/67 bp) and BB (236 bp/67 bp, 236 bp/67 bp). The results indicated that genotype AA (303 bp, 303 bp) at Mnl I-RFLP site did not exist in non-seasonal estrous Small Tail Han sheep, which suggested that there was an association between genotype AA (303 bp, 303 bp) and reproductive seasonality in sheep. Polymorphic Rsa I site was detected at base position 604 of the exon 2 of the MTNR1A gene. Three kinds of genotypes were found in Small Tail Han sheep, AA (290 bp, 290 bp), AB (290 bp, 267 bp/23 bp) and BB (267 bp/23 bp, 267 bp/23 bp). Least squares means of litter size in the first parity and the second parity for genotype AA (290 bp, 290 bp) at Rsa I-RFLP site were 0.43 and 1.06 more than those for genotype AB (290 bp, 267 bp/23 bp) in Small Tail Han sheep.

• Psychiatry investigation
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• 제15권12호
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• pp.1188-1202
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• 2018

Objective This study protocol aims to determine, using a rigorous approach in patients with bipolar disorder (BD) and non-seasonal major depressive episode (MDE), the characteristics of bright light therapy (BLT) administration (duration, escalation, morning and mid-day exposures) depending on the tolerance (hypomanic symptoms). Methods Patients with BD I or II and treated by a mood stabilizer are eligible. After 1 week of placebo, patients are randomized between either morning or mid-day exposure for 10 weeks of active BLT with glasses using a dose escalation at 7.5, 10, 15, 30 and 45 minutes/day. A further follow-up visit is planned 6 months after inclusion. Patients will be included by cohorts of 3, with at least 3 days of delay between them, and 1 week between cohorts. If none meet a dose limiting toxicity (DLT; i.e hypomanic symptoms), the initiation dose of the next cohort will be increased. If one patient meet a DLT, an additionnal cohort will start at the same dose. If 2 or 3 patients meet a DLT, from the same cohort or from two cohorts at the same dose initiation, the maximum tolerated dose is defined. This dose escalation will also take into account DLTs observed during the intra-subject escalation on previous cohorts, with a "Target Ceiling Dose" defined if 2 DLTs occured at a dose. Discussion Using an innovative and more ergonomic device in the form of glasses, this study aims to better codify the use of BLT in BD to ensure a good initiation and tolerance.

• 생물정신의학
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• 제29권2호
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• pp.33-39
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• 2022

Objectives The early growth response 3 (EGR3) gene located in chromosome 8p21.3 is one of the susceptibility loci in many psychiatric disorders. EGR3 gene plays critical roles in signal transduction in the brain, which is involved in neuronal plasticity, neuronal development, learning, memory, and circadian rhythms. Recent studies have suggested EGR3 as a potential susceptibility gene for bipolar disorder (BPD). However, this requires further replication with an independent sample set. Methods To investigate the genetic role of EGR3 in Korean patients, we genotyped six single-nucleotide polymorphisms (SNPs) in the chromosome region of EGR3 in 1076 Korean BPD patients and 773 healthy control subjects. Results Among the six examined SNPs of EGR3 (rs17088531, rs1996147, rs3750192, rs35201266, rs7009708, rs1008949), SNP rs35201266, rs7009708, rs1008949 showed a significant association with BPD (p = 0.0041 for rs35201266 and BPD2, p = 0.0074 for rs1008949 and BPD, p = 0.0052 for rs1008949 and BPD1), which withstand multiple testing correction. In addition, the 'G-C-C-C' and 'G-C-G-C' haplotypes of EGR3 were overrepresented in the patients with BPD (p = 0.0055, < 0.0001, respectively) and the 'G-T-G-C' haplotype of EGR3 was underrepresented in patients with BPD (p = 0.0040). Conclusions In summary, our study supports the association of EGR3 with BPD in Korean population sample, and EGR3 could be suggested as a compelling susceptibility gene in BPD.

• 시큐리티연구
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• 제31호
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• pp.7-24
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• 2012

본 연구에서는 경호경비현장에서 이루어지고 있는 실제적인 경호경비원들의 장시간 경계근무 중 발생하는 하는 생체리듬의 변화를 알아보기 위해 K대학교 경호학과 학생 9명을 대상으로 실제 경계근무와 같은 형태로 180분간 경계근무를 실시하였다. 30분 간격으로 HRV(Heart rate variability)를 통하여 심박동 변이도와 자율신경검사를 실시 한 결과 심박동 변이도 HRT과 SDNN은 유의한 차이가 없어 180분간의 경계근무 시간 동안 안정적으로 유지 하였다. 자율신경계의 전체적인 활성정도를 반영하는 TP는 안정시 보다 90분과 120분에 유의(p<.05)한 차이로 높게 나타났다. 또한 120분 이후에는 유의한 감소하여, 120분 이상의 경계근무에서는 자율신경계의 활성도가 감소하는 것으로 나타났다. VLF, LF, HF 모두 유의한 차이는 아니지만 120분에 감소하는 경향을 보여 TP 변화에 영향을 주었다. 교감신경과 부교감신경의 균형도를 나타내는 LF/HF ratio는 경계근무 30분에 유의하게(p<.05)높은 것으로 나타났다. 따라서 경계근무 120분 이후에는 집중력이 감소하는 것으로 사료되며, 경계근무 시작 30분 까지는 근무시작으로 인한 긴장감과 흥분감이 있는 것으로 나타났다.

• 수산해양교육연구
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• 제26권1호
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• pp.72-80
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• 2014

Oxygen consumption (OC) of male black porgy Acanthopagrus schlegelii reared in freshwater (BFW) and seawater (BSW) during the reproductive period was $165.4{\pm}11.0$, $77.6{\pm}8.0$ mg $O_2/kg/h$ at $15^{\circ}C$, $186.2{\pm}13.1$, $133.4{\pm}6.7$ mg $O_2/kg/h$ at $20^{\circ}C$ and $267.9{\pm}19.1$, $198.6{\pm}8.3$ mg $O_2/kg/h$ at $25^{\circ}C$, respectively. During the non-reproductive period, it was shown as $174.0{\pm}7.0$, $85.6{\pm}5.5$ mg $O_2/kg/h$ at $15^{\circ}C$, $200.6{\pm}11.1$, $119.2{\pm}8.7$ mg $O_2/kg/h$ at $20^{\circ}C$ and $271.1{\pm}7.5$, $194.7{\pm}16.7$ mg $O_2/kg/h$ at $25^{\circ}C$, respectively. Thus, OC of BFW was higher than BSW both for non-reproductive and reproductive period. Also, OC increased in proportion to the rise in water temperature, and there was no difference of OC between BFW and BSW at each water temperature during the reproductive or non-reproductive period. OC of BFW and BSW showed clear circadian rhythms on photic conditions of reproductive and non-reproductive period, and the fish consumed more oxygen during the dark phase than for the light phase. In particular, OC of BFW during the reproductive period increased more sharply compared to non-reproductive period when the increase of water temperature was accompanied by the shift from dark to light phase. This implies that they react to the light more sensitively for reproductive period than for non-reproductive period.

• 수면정신생리
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• 제6권1호
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• pp.61-67
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• 1999

목 적 : 본 연구의 목적은 간호사들의 심인적, 신체적 그리고 사회적 적응에 대한 교대근무의 영향을 조사하는데 있다. 방 법 : 299명(교대근무 179, 비교대근무 120)의 간호사를 대상으로 본 연구의 목적에 알맞게 고안된 56항의 설문지를 이용하여 조사하였다. 결 과 : 교대근무는 간호사들의 심인적, 신체적, 사회적 그리고 수면관련 요소에 부정적인 영향을 미치고 있었다. 교대 근무 간호사들의 심인적, 신체적 건강에 대한 주관적인 인식이 비교대 근무자들에 비하여 유의하게 부정적이었다. 교대근무 간호사들은 비교대근무 간호사들에 비하여 교대근무와 관련된 사회생활의 장애 및 사회활동의 제한을 호소하고 있었고, 수면과 관련된 장애들을 유의하게 더 많이 호소하고 있었다. 결 론 : 본 연구결과는 교대근무가 정신생리적 기능의 일주기 리듬에 장애를 초래할 수 있기 때문에 교대근무자들의 정신적, 신체적 건강에 부정적인 영향을 줄 수 있음을 뒷받침 한다. 또한 교대 근무자들은 가족 및 일반적인 사회관계에서 여러움을 겪고 있음을 알 수 있다. 이상의 결과들은 교대근무의 부작용을 최소화하기 위한 적절한 대응전략이 필요함을 시사한다.

• 대한지역사회작업치료학회지
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• 제8권2호
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• pp.29-37
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• 2018

목적 : 수면장애는 노인에게 있어 다양한 이유로 빈발하고 있다. 이러한 노인의 수면장애에서 운동 강도에 따른 지속적인 운동습관이 수면장애의 치료적 효과를 줄 수 있는지를 밝히기 위해서 뇌파와 멜라토닌의 농도를 이용한 과학적인 방법으로 접근하는 것이 본 연구의 목적이다. 연구방법 : 일부지역의 노인시설에 거주하는 65세 이상의 노인 30명을 대상으로 하였다. 수면장애의 판단은 수면시간 6시간 이하의 경우(Kozier et al, 2004)와 PSQI(Pittsburgh Sleep Quality Index)의 점수를 동시에 만족하는 경우로 정하였다. 운동유형별 적용은 저강도의 걷기운동, 중강도의 유산소 운동, 고강도의 저항성 근력운동을 적용하였으며 측정도구는 뇌파에서 파형을 체크하기 위하여 QEEG 8-System(LAXTHA Inc. KOREA) 기기와 수면의 질을 검사하기 위해서 수면다원검사에 사용하는 Polysomnograpy (Compumedics, Australia) 기기를 사용하였다. 그리고 TTC(triphenyltetrazolium chloride) 염색과 H & E(Hematoxylin & Eosin) 염색을 통해 조직학적 양상을 관찰하였다. 결과 : 중강도의 유산소 운동 후에 멜라토닌의 농도와 뇌파로 측정한 수면지수에는 긍정적인 유의미한 변화가 있었다. 중강도의 유산소 운동에서는 SWS가 저강도, 고강도 운동보다 유의한 효과가 있었고 SWS의 관찰지표인 델타파의 유의한 변화가 있었다. 결론 : 인체의 일주기성 리듬의 생화학적, 행동학적 기능에 변화를 가져오는 노인에게서 수면장애에 대한 지속적인 운동은 운동의 유형에 따라 효과가 다름을 알 수 있었고 특히 유산소 운동이 다른 운동보다 노인 수면장애에 효과가 크다는 것을 멜라토닌의 농도와 뇌파를 통하여 알 수 있었다. 노인에게 맞춤형 운동을 제공하여 노인들의 삶의 질에 유용하고 건강한 말년을 제공할 수 있을 것이다.

• Journal of Preventive Medicine and Public Health
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• 제25권4호
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• pp.374-385
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• 1992

교대근무자들이 호소하는 생체리듬의 부조화로 인한 일련의 증상들은 개인특성, 작업환경, 교대형태의 영향을 많이 받는다. 따라서 본 연구에서는 개인특성과 작업환경의 영향을 고려하여 교대주기에 따른 근로자들의 자각증상의 차이를 보고자, 작업환경이 같고 교대주기에 있어 2일, 7일인 두 회사의 3교대근로자 182명과 86명을 대상으로 개인 특성 및 자각증상을 설문조사하였다. 결과를 요약하면 다음과 같다. 1. 수면장해증상 6문항 중 '근무 중 피로감을 느낀다', '예민하다'의 두 항목에서 7일주기의 교대근무자에서 증상호소의 빈도가 통계적으로 유의하게 높았으며(P<0.05), 점수화하여 두 군간의 평균을 비교한 결과 7일주기인 군에서 증상점수가 높았다(P<0.01). 2. 1일 평균 6시간의 수면을 기준으로 할 때, 수면시간에 있어서는 두 군간에 유의한 차이가 없었으며, 2일주기인 군에서는 수면시간이 증가함에 따라 장해증상에 현저히 줄었으나 (P<0.05), 7일주기인 군에서는 수면시간에 따른 장해증상의 차이가 없었다. 3. 소화기장해증상 10문항에서는, 7일주기인 군에서 '자주 그렇다'고 호소하는 빈도가 높았으나 통계적인 유의성은 없었으며, 점수화하여 두 군간의 평균을 비교한 결과 역시 7일 주기인 군이 평균점수가 높았으나 통계적으로 유의한 차이는 아니었다. 4. 피로자각증상은 육체적, 정신적 피로 호소율이 7일주기의 교대근무자들에게 현저히 높았으며(P<0.01), 신경감각적 피로 역시 유의한 차이가 있었다(P<0.05). 5. 공분산분석 (ANCOVA)을 통해 개인특성의 영향을 고려한 결과, 교대주기에 파라 수면장해 증상, 육체적, 정신적 피로에 통계적으로 유의한 차이를 보였다(P<0.01). 이상의 결과를 종합해 볼때, 2일주기의 교대근무자들보다 7일주기 교대근무자들이 피로와 수면장해증상 호소가 더 많았다. 따라서 향후 자각증상 뿐 아니라 객관적인 검사를 병행하여 현재 가장 많이 시행되고 있는 7일주기의 교대제에 대한 검토가 필요할 것으로 사료된다.