• Archives of Pharmacal Research
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• v.20 no.6
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• pp.555-559
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• 1997

The three different batches of an oral sustained release melatonin (MT) delivery system were prepared by aqueous-based fluid-bed coating of the sugar spheres for the evaluation of in vitro release characteristics and plasma concentration profiles in human subjects. The MT contents in 20% coated sugar spheres of three batches (B1, B2 and B3) were $3.3{\pm}0.08$, $2.4{\pm}0.1$ and $2.5{\pm}0.13$ mg per gram of coated sugar spheres, respectively. The release profiles of three different batches had a very similar fashion. However, the release profiles of three different batches had a very similar fashion. However, the release half-lives $(T_{50%})$ of MT from B1, B2 and B3 was $3.70{\pm}0.2$, $5.2{\pm}0.2$ and $4.9{\pm}0.07h$, respectively. Plasma concentration profiles of sustained release 0.2mg melatonin-loaded sugar spheres containing 10% immediate release melatonin in gelatin capsules (B1 and B2) were then evaluated in human subjects. The in vivo plasma concentration profies of the two batches (B1 and B2) were very similar each other and located between the physiological endogenous ranges. The time to reach the peak concentration $(T_max)$ was more advanced in case of B1 when compared to B2. However, there was no statistically significant difference in the maximum concentration $(C_max)$ and the area under the curve (AUC) between B1 and B2. The AUC of melatonin-loaded sugar spheres containing 10% and 20% immediate release MT in human subjects had a good linearity between dose and AUC, regardless of the fraction of immediate release MT, indicating the first order elimination process of MT within these doses. The current oral sustained release MT delivery system may be utilized to treat circadian rhythm disorders if it is proven to be more clinically useful when compared to immediate release MT.

• 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 Life Science
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• v.23 no.6
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• pp.804-811
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• 2013

Melanopsin is an opsin-like photopigment found in the small proportion of photosensitive ganglion cells of the retina. It is involved in the regulation of the synchronization of the circadian cycle as well as in the control of pupillary light reflex. The purpose of the present study is to investigate whether melanopsin is also expressed in the other areas of the central visual system outside the retina. We have studied the distribution and morphology of neurons containing melanopsin in the mouse visual cortex with antibody immunocytochemistry. Melanopsin immunoreactivity was mostly present in neuronal soma, but not in nuclei. We found that melanopsin was present in a large subset of neurons within the adult mouse visual cortex with the highest density in layer II/III. In layer I of the visual cortex, melanopsin-immunoreactive (IR) neurons were rarely encountered. In the mouse visual cortex, the majority of the melanopsin-IR neurons consisted of round/oval cells, but was varied in morphology. Vertical fusiform and pyramidal cells were also rarely labeled with the anti-melanopsin antibody. The labeled cells did not show any distinctive distributional pattern. Some melanopsin-IR neurons in mouse visual cortex co-localized with nitricoxide synthase, calbindin and parvalbumin. Our data indicate that melanopsin is located in specific neurons and surprisingly widespread in visual cortex. This finding raises the need of the functional study of melanopsin in central visual areas outside the retina.

• Korean Journal of Biological Psychiatry
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• v.24 no.2
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• pp.59-67
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• 2017

Shift workers experience a disruption in the circadian sleep-wake rhythm, which brings upon adverse health effects such as fatigue, insomnia and decreased sleep quality. Moreover, shift work has deleterious effects on both work productivity and safety. In this review, we present a brief overview of the current literature on the consequences of shift work, especially focusing on attention-associated cognitive decline and related behavioral changes. We searched two electronic databases, PubMed and RISS, using key search terms related to cognitive domains, deleterious effects, and shift work. Twenty studies were eligible for the final review. The consequences of shift work can be classified into the following three categories extracted from the literature review : 1) work accidents ; 2) commuting accidents such as car accidents that occur on the way to and from work ; and 3) attendance management at work (i.e., absenteeism, tardiness, and unscheduled early departure). These cognitive and behavioral consequences of shift work were also found to be associated with sleep disorders in shift workers. Thus, improvements in the shift work system are necessary in order to enhance workers' health conditions, work productivity, and safety.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7169-7174
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• 2014

Background: NPAS2 is a product of the circadian clock gene. It acts as a putative tumor suppressor by playing an important role in DNA damage responses, cell cycle control and apoptosis. Chronic lymphocytic leukemia (CLL) appears to be an apoptosis related disorder and alteration in the NPAS2 gene might therefore be directly involved in the etiology of CLL. Here, the Ala394Thr polymorphism (rs2305160:G>A) in the NPAS2 gene was genotyped and melatonin concentrations were measured in a total of seventy-four individuals, including thirty-seven CLL cases and an equal number of age- and sex-matched healthy controls in order to examine the effect of NPAS2 polymorphism and melatonin concentrations on CLL risk in a Pakistani population. Materials and Methods: Genotyping of rs2305160:G>A polymorphism at NPAS2 locus was carried out by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Melatonin concentrations were determined by enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed using Statistical Package for Social Sciences software. Results: Our results demonstrated no association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with risk of CLL. Similarly, no association of rs2305160 with CLL was observed in either females or males after stratification of study population on a gender basis. Moreover, when the subjects with CLL were further stratified into shift-workers and non-shift-workers, no association of rs2305160 with CLL was seen in either case. However, significantly low serum melatonin levels were observed in CLL patients as compared to healthy subjects (p<0.05). Also, lower melatonin levels were seen in shift-workers as compared to non-shift-workers (p<0.05). There was no significant difference (p>0.05) in the melatonin levels across NPAS2 genotypes in all subjects, subjects with CLL who were either shift workers or non-shift-workers. General Linear Model (GLM) univariate analysis revealed no significant association (p>0.05) of the rs2305160 polymorphism of the NPAS2 gene with melatonin levels in any of the groups. Conclusions: While low melatonin levels and shift-work can be considered as one of the risk factors for CLL, the NPAS2 rs2305160 polymorphism does not appear to have any association with risk of CLL in our Pakistani population.

• Journal of Preventive Medicine and Public Health
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• v.42 no.4
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• pp.231-236
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• 2009

Objectives : This study was conducted to determine the appropriate sampling time of the salivary stress markers, chromogranin A (CgA) and cortisol as objective indices of job stress assessment in adult females. Methods : The subjects were 20${\sim}$39-year-old women (13 office workers, 11 sales-service workers, and 11 college students) who were eligible for the study and free of acute and chronic medical conditions. Salivary CgA and cortisol levels were determined by enzyme-linked immunosorbent assay (ELISA). Saliva samples were collected (2 $m{\ell}$ each) at 7:00, 8:00, 10:30, 12:00, 17:30, and 22:30 on a typical day. Salivary CgA and cortisol levels, according to sampling time, were compared among the three groups using general linear model. The full version of the Korean Occupational Stress Scale (KOSS), which includes socioeconomic characteristics, health behavior, workrelated characteristics, and BMI, was used to access the subjects' job stress. Multiple regression analysis of the job stressors identified by the KOSS was performed on salivary CgA and cortisol levels. Results : The salivary CgA level peaked at 7:00 (time of awakening), then decreased and were maintained at a low level throughout the day, and increased slightly at 17:30. The salivary cortisol level increased steeply within the 1st hour after awakening, followed by a gradual decrease by 12:00, and was then maintained at a low level throughout the day. The salivary cortisol levels of subjects who worked ${\leq}$5 days per week and graduated from the university were significantly lower at 8:00 (p=0.006). The salivary cortisol levels of non-smokers were significantly lower at 7:00 p=0.040) and 8:00 (p=0.003) compared to smokers. There were no significant differences in salivary CgA and cortisol levels at 10:30 and 12:00 in general characteristics. The regression coefficients on salivary CgA level were significant with interpersonal conflict at 17:30 and job insecurity at 22:30. Regression coefficients on salivary cortisol level were significant with organizational system and total job stressors at 17:30. Conclusions : We suggest that the appropriate sampling times for the salivary stress markers, CgA and cortisol, are at 7:00 (time of awakening), 8:00 (1 hour after awakening), 17:30 (early evening), and 22:30 (before sleep).

• Sleep Medicine and Psychophysiology
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• v.8 no.2
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• pp.129-137
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• 2001

Objectives: The purpose of this study is to investigate the effects of 38-hour sleep deprivation on fine motor performance. The Motor Performance Series (MPS) in the Vienna Test System (computerized neurocognitive function tests) was used in this study. Methods: Twenty four subjects participated in this study. Subjects had no past history of psychiatric disorders and physical illness. Subjects had normal sleep-waking cycle without current sleep disturbances and were all right-handed (Annett's Hand Preference Questionnaire: above +9 points). To minimize the learning effects, familiarization with the Vienna Test System was performed one day before the study. Subjects were to get up at 6:00 in the morning after getting enough sleep according to his or her usual sleep-wake cycle. After awakening, subjects remained awake for 38 hours under continuous surveillance. During two consecutive study days, the subjects tested MPS at 7 AM and 7 PM each day, which means the MPS was done four times in total. During the experiment, anything that could affect the subjects' sleep such as coffee, tea, alcohol, a nap, tiring sports, and all medications were prohibited. Results: In MPS, the fine motor functions of both hands decreased after 38 hours of sleep deprivation. The decrement in motor performance was prominent in the dominant right hand. In the right hand, the total number of tapping was reduced (p<.005), and the number of misses (p<.05) and the length of misses (p<.05) of line tracking, the total length of inserting a short pin (p<.01), the total length of inserting a long pin (p<.05), and the number of misses in aiming (p<.05) increased. Such performance decrement was distinct in the morning sessions. Conclusions: These results suggest that fine motor performance decrement during sleep deprivation is predominant in the right hand, which exerts maximal motor function. The finding of decrement in motor function in tapping during sleep deprivation also suggested that the time required for exhaustion of muscles is shortened during sleep deprivation. More deterioration of motor performance was shown in the morning, which could be explained as circadian rhythm effects.

• Journal of Embryo Transfer
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• v.28 no.3
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• pp.177-184
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• 2013

The objective of this study was to analyze the accuracy of estrus detection of heat detector and analysis of estrus behavior (mounting and mounted), and the evaluation of conditions required for improving reproductive efficiency in Holstein dairy cows fitted with a estrous detector. The heat detection system consists of estrous detector based on wireless sensor and an electric bulletin board displayed estrus behavior data. When cow mounting other cows, the accuracy of estrus behavior displayed an electric bulletin board were 87.5% (mounting other cows only), 100% (mounting other cows but not standing), 80.0% (mounting other cows with standing for 1~4 seconds), 90.0% (mounting other cows but not standing for 1~4 seconds), 80% (mounting other cows with standing for more than 5 seconds) and 90.0% (mounting other cows but not standing for more than 5 seconds). When cow mounted other cows, the accuracy of estrus behavior displayed an electric bulletin board were 100% (mounted other cows but not standing), 100% (mounted other cows with standing for 1~4 seconds), 100% (mounted other cows but not standing for 1~4 seconds) and 100% (mounted other cows with standing for more than 5 seconds). Circadian distribution of first observed in estrus were 59.1% (am 8~pm 6) and 40.9% (pm 6~am 8). Distribution for the number of estrus behavior were 40.9% (less than 3 times), 36.4% (4~6 times) and 22.7% (more than 4 times). The conception rates relative to interval from first estrus behavior to insemination for estrus periods were 23.1% (less than 11 hours) and 55.6% (12~20 hours).