• Archives of Pharmacal Research
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• v.19 no.4
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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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• v.23 no.3
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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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• v.16 no.12
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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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• v.15 no.12
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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.

• Korean Journal of Biological Psychiatry
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• v.29 no.2
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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.

• Korean Security Journal
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• no.31
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• pp.7-24
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• 2012

In this study a practical guarding work is carried out for 180 minutes as the same as the actual guarding work that is done by nine students of the department of security services in K University in order to investigate changes in circadian rhythms during long hour guarding in bodyguards at practical sites. In the results of the tests of the heart rate variation and autonomic nervous system with the interval of 30 minutes using HRV (Heart rate variability), there are no significant differences in HRV and SDNN and that leads to maintain it stably during the guarding work for 180 minutes. In the case of TP which reflects the overall activity level in the autonomic nervous system, it shows a high significant difference (p<.05) at 90 and 120 minutes compared to that of normal states. Also, it shows a significant decrease in the level after a lapse of 120 minutes and that shows a decrease in the activity of the autonomic nervous system for the guarding work more than 120 minutes. Although differences in VLF, LF, and HF are not significant levels, these are influenced on the change in TP. The LH/HF ratio that represents the balance between the sympathetic nerve and the parasympathetic nerve shows a significant high level (p<.05) after a lapse of 30 minutes. Thus, it is considered that the concentration of the guarding work after a lapse of 120 minutes is decreased and there are some tensions and excitations after a lapse of 30 minutes since the beginning of the guarding work.

• Journal of Fisheries and Marine Sciences Education
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• v.26 no.1
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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.

• Sleep Medicine and Psychophysiology
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• v.6 no.1
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• pp.61-67
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• 1999

Objectives: The aim of this study was to examine the impact of shift work on psychological, physical and social adjustment in nurses. Methods: Two hundred ninety-nine female nurses(179 shift worker, 120 non-shift worker) filled out a questionnaire, which consisted of fifty-six items including demographic characteristics. Subjective ratings of psychological, physical, social and sleeprelated distresses were assessed with a visual analogue scale(100mm). Results: Shift work exerted significantly negative impacts on all psychological, physical, social and sleep-related variables of the shift work nurses. The subjective perception about psychological and physical health of shift work nurses was significantly negative as compared to that of non-shift work nurses. Shift work nurses complained of more shift work related social dysfunction and limited social activity. Shift work nurses were also suffering from significant sleep difficulties as compared to non-shift work nurses. Conclusions: This study suggests that shift work can exert a negative impact on psychological and physical health of nurses as it can cause disturbances of the normal circadian rhythms of the psychophysiological functions, beginning with the sleep-wake cycle. Shift work can also cause difficulties in maintaining the usual relationships both at family and social levels. These results may suggest that we need appropriate coping strategies to overcome adverse effects of shift work.

• The Journal of Korean society of community based occupational therapy
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• v.8 no.2
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• pp.29-37
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• 2018

Objective : Sleep disorder caused by stress or disease to elderly currently. We tried to make clear constant exercise according to exercise intensity would have effect on sleep disorder in elderly using EEG and melatonin. Methods : Thirty subjects were over 65 years old who lived a senior facility in some parts. They were able to communicate and understand the purpose of the study. They also expressed their intension to participate actively in experiment. They should have alert consciousness and orientation about time, place, and people. Sleep disorder was assessed via below 6 hr total sleep time and Pittsburge Sleep Quality Index, which was satisfied with both of criterion at the same time. Exercises composed of low intensity walking, moderate aerobic exercise, and high intensity resistance strength. We used QEEG 8-System (LAXTHA Inc. KOREA) to check wave type and Polysomnograpy (Compumedics, Australia) to test quality of sleep. and Histologic features were observed by TTC (triphenyltetrazolium chloride) staining and H & E (Hematoxylin & Eosin) staining. Results : There was a significant sleep index and change of melatonin after aerobic exercise. There was a significant SOL, S1, S2, and SWS in aerobic exercise, but there was a significant SWS in walking and resistance strength. There was a significant change of delta wave especially in frontal and temporal region between exercises. Conclusion : They had different effects according to type of exercise, when elderly who have chemical, behavioral change of circadian rhythms did exercise consistently. Aerobic exercise had more effect on sleep disorder than other exercise. Therefore, we may supply proper exercise to elderly and high quality of life.

• Journal of Preventive Medicine and Public Health
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• v.25 no.4 s.40
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• pp.374-385
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• 1992

Some circadian rhythms can become disorgnized due to rotating shift work. This lack of organization, termed desynchronization, can produce a group of symptoms such as insomnia, GI disturbance and fatigue among many rotating shift workers. The magnitude of these symptoms are influenced by personal and environmental factors and the patterns of shift work. This study was carried out to investigate the subjective symptoms related to rotational schedules of shift work after personal and environmental factors adjusted. 182 male workers in rapidly rotating shift system and 86 male workers in weekly rotating shift system were conducted the questionnaire on personal factors and subjective sleep, GI and fatigue symptoms. Major findings obtained from this study are as follows: 1. The symptoms of 'feeling tired at work' and 'being irritable' were more frequent in weekly rotating shift workers (P<0.05), and the mean of symptom score was significantly higher in weekly rotating shift workers(P<0.01). 2. According to 6 hours of sleeping which is a definite elevation point of fatigue, there was not a significant difference between two groups in sleeping hours. Among workers in rapidly rotating shift system, the mean of symptom score was significatly higher in workers of less than 6 hours of sleeping(P<0.05), but it was not different among weekly rotating shift workers. 3. The symptoms of GI disturbance were more frequent in weekly rotating shift workers but statistically not significant. 4. The positive rate of mental and physical fatigue symptoms were significantly higher in weekly rotating shift workers(P<0.01) and mental and physical fatigue symptoms were more frequent in them (P<0.01). 5. After the effect of the factors that were significantly different between two groups by $X^2-test$ were controlled, the mean score of sleep disturbance was significantly higher in weekly rotating shift workers (P<0.01) and mental physical fatigue symptoms were more frequent in them (P<0.01). Based on these study results, subjective symptoms were more common in the weekly rotating shift workers. In future, medical examination and laboratory test will be also administered to evaluate a more accurate health outcomes and the review of current shift schedules will be required.