A Multicenter, Randomized Clinical Trial to Assess the Efficacy of a Therapeutic Intervention Program for Caregivers of People with Dementia

유라영,염지영,김건하,박희경,강연욱,황지혜,최성혜,나해리,조수진,유경호,김도훈,이재홍,정지향 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.2

Background and Purpose Caregivers experience tremendous social, financial, physical, and psychological burdens in caring for people with dementia. This study aimed to determine the efficacy of a multicomponent therapeutic intervention program for the caregivers of people with dementia (CGPWD) through a multicenter clinical trial: the intervention programcaregivers of people with dementia study. Methods The 38 caregivers of dementia patients at 8 sites were randomized into 2 groups: treatment (n=19) and control (n=19). The treatment group received the intervention program for 8–10 weeks, including one group session for dementia education and three individual sessions (on cognitive behavioral therapy, coping with stress, and stress management) and single targeted training for daily activities. The Korean version of the Zarit Burden Interview (ZBI-K) and the Geriatric Depression Scale (GDS) were evaluated at pre- and postintervention as primary efficacy measures. Results The treatment group displayed significant improvements in scores on the ZBI-K and GDS. The ZBI-K score at postintervention was significantly reduced in the treatment group compared to that in the control group [6.2-point decrease vs. 3.7-point increase, t(37)=-2.9, p< 0.01]. There was a significant difference in the GDS score between the treatment and control groups [2.2-point decrease vs. 1.3-point increase, t(18)=2.5, p<0.05]. Conclusions The findings of this study imply that a multicomponent therapeutic intervention program is effective in reducing the burden experienced by and depression among CGPWD. Further research is warranted to investigate the long-term effects of the intervention program for CGPWD.

불면 증상으로 내원한 65세 이상 노인 환자들의 임상적 양상

이진산,신원철,유라영,성민지,남효정,권영남,조한아,차현극 대한수면연구학회 2013 Journal of sleep medicine Vol.10 No.1

Objective: Sleeping problems and disorders generally increase with aging, and these changes influence elderly functioning and well-being. We studied the clinical characteristics of the elderly patients with insomnia symptoms for the appropriate diagnosis in Korea. Methods: Patients with insomnia symptoms aged over 65 years were recruited from who visited the Sleep center of Kyung Hee University Hospital at Gangdong, from January 2010 to April 2013. General characteristics of sleep patterns, past medical history, previous medication related sleep, sleep diary, and the Minnesota Multiphasic Personality Inventory-2(MMPI-2) were analyzed to understand the sleep pattern and the clinical characteristics in the elderly patients with insomnia symptoms. Results: The study population included 143 patients(45 men, 98 female), and their mean age was 71.41± 5.32 years. These patients were classified according to the cause of insomnia symptoms, the primary cause was 39.1%(92.8% psychophysiological insomnia, 7.2% paradoxical insomnia), the secondary cause was 34.2%(depression, anxiety, associated medical illness, obstructive sleep apnea syndrome, restless legs syndrome), and circadian rhythm sleep disorder was 26.6%. The MMPI-2 profiles were not significant differences in the study population. Conclusion: The clinical characteristics in our study population were different in variable parameters from the general population. It is necessary to understand these differences in the elderly patients for approaching the appropriate diagnosis and medical care.

Nitric Oxide-mediated Relaxation by High K^+ in Human Gastric Longitudinal Smooth Muscle

김영철,윤효영,성노현,유라영,윤세진,최웅,박선미,김미정,송영진,Wen-Xie Xu,이상진 대한약리학회 2011 The Korean Journal of Physiology & Pharmacology Vol.15 No.6

This study was designed to elucidate high-K^+ induced response of circular and longitudinal smooth muscle from human gastric corpus using isometric contraction. Contraction from circular and longitudinal muscle stripes of gastric corpus greater curvature and lesser curvature were compared. Circular smooth muscle from corpus greater curvature showed high K^+ (50 mM)-induced tonic contraction. On the contrary, however, longitudinal smooth muscle strips showed high K^+ (50 mM)-induced sustained relaxation. To find out the reason for the discrepancy we tested several relaxation mechanisms. Protein kinase blockers like KT5720, PKA inhibitor, and KT5823, PKG inhibitor, did not affect high K^+ -induced relaxation. K^+ channel blockers like tetraethylammonium (TEA), apamin (APA), glibenclamide (Glib) and barium (Ba2+) also had no effect. However, N(G)-nitro-L-arginine (L-NNA) and 1H-(1,2,4) oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC) and 4-AP (4-aminopyridine), voltage-dependent K^+ channel (KV) blocker, inhibited high K^+ -induced relaxation, hence reversing to tonic contraction. High K^+-induced relaxation was observed in gastric corpus of human stomach, but only in the longitudinal muscles from greater curvature not lesser curvature. L-NNA, ODQ and KV channel blocker sensitive high K^+-induced relaxation in longitudinal muscle of higher portion of corpus was also observed. These results suggest that longitudinal smooth muscle from greater curvature of gastric corpus produced high K^+-induced relaxation which was activated by NO/sGC pathway and by KV channel dependent mechanism.

Relaxation Patterns of Human Gastric Corporal Smooth Muscle by Cyclic Nucleotides Producing Agents

김영철,최웅,성노현,김헌,유라영,박선미,윤세진,김미정,송영진,Wen-Xie Xu,이상진,윤효영 대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.6

To elucidate the mechanism of cyclic nucleotides, such as adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP), in the regulation of human gastric motility, we examined the effects of forskolin (FSK), isoproterenol (ISO) and sodium nitroprusside (SNP) on the spontaneous, high K+ and acetylcholine (ACh)-induced contractions of corporal circular smooth muscle in human stomach. Gastric circular smooth muscle showed regular spontaneous contraction, and FSK, ISO and SNP inhibited its phasic contraction and basal tone in a concentration-dependent manner. High K+ (50 mM) produced sustained tonic contraction, and ACh (10μM) produced initial transient contraction followed by later sustained tonic contraction with superimposed phasic contractions. FSK, ISO and SNP inhibited high K+-induced tonic contraction and also ACh-induced phasic and tonic contraction in a reversible manner. Nifedipine (1μM), inhibitor of voltage-dependent L-type calcium current (VDCCL), almost abolished ACh-induced phasic contractions. These findings suggest that FSK, ISO and SNP, which are known cyclic nucleotide stimulators, inhibit smooth muscle contraction in human stomach partly via inhibition of VDCCL.

Relaxant Effect of Spermidine on Acethylcholine and High K+-induced Gastric Contractions of Guinea-Pig

김영철,최웅,김찬형,유라영,심재훈,이상진,Wen-Xie Xu 대한약리학회 2008 The Korean Journal of Physiology & Pharmacology Vol.12 No.2

In our previous study, we found that spermine and putrescine inhibited spontaneous and acetylcholine (ACh)-induced contractions of guinea-pig stomach via inhibition of L-type voltage- dependent calcium current (VDCCL). In this study, we also studied the effect of spermidine on mechanical contractions and calcium channel current (IBa), and then compared its effects to those by spermine and putrescine. Spermidine inhibited spontaneous contraction of the gastric smooth muscle in a concentration-dependent manner (IC50=1.1±0.11 mM). Relationship between inhibition of contraction and calcium current by spermidine was studied using 50 mM high K+-induced contraction: Spermidine (5 mM) significantly reduced high K+ (50 mM)-induced contraction to 37±4.7% of the control (p< 0.05), and inhibitory effect of spermidine on IBa was also observed at a wide range of test potential in current/voltage (I/ V) relationship. Pre- and post-application of spermidine (5 mM) also significantly inhibited carbachol (CCh) and ACh-induced initial and phasic contractions. Finally, caffeine (10 mM)-induced contraction which is activated by Ca²+-induced Ca²+ release (CICR),` was also inhibited by pretreatment of spermidine (5 mM). These findings suggest that spermidine inhibits spontaneous and CCh-induced contraction via inhibition of VDCCL and Ca²+ releasing mechanism in guinea-pig stomach. In our previous study, we found that spermine and putrescine inhibited spontaneous and acetylcholine (ACh)-induced contractions of guinea-pig stomach via inhibition of L-type voltage- dependent calcium current (VDCCL). In this study, we also studied the effect of spermidine on mechanical contractions and calcium channel current (IBa), and then compared its effects to those by spermine and putrescine. Spermidine inhibited spontaneous contraction of the gastric smooth muscle in a concentration-dependent manner (IC50=1.1±0.11 mM). Relationship between inhibition of contraction and calcium current by spermidine was studied using 50 mM high K+-induced contraction: Spermidine (5 mM) significantly reduced high K+ (50 mM)-induced contraction to 37±4.7% of the control (p< 0.05), and inhibitory effect of spermidine on IBa was also observed at a wide range of test potential in current/voltage (I/ V) relationship. Pre- and post-application of spermidine (5 mM) also significantly inhibited carbachol (CCh) and ACh-induced initial and phasic contractions. Finally, caffeine (10 mM)-induced contraction which is activated by Ca²+-induced Ca²+ release (CICR),` was also inhibited by pretreatment of spermidine (5 mM). These findings suggest that spermidine inhibits spontaneous and CCh-induced contraction via inhibition of VDCCL and Ca²+ releasing mechanism in guinea-pig stomach.

Regional Distribution of Interstitial Cells of Cajal (ICC) in Human Stomach

윤효영,김영철,성노현,김영철,최웅,김훈식,김헌,이광주,유라영,박선미,윤세진,김미정,김원섭,송영진,Wen-Xie Xu,이상진 대한약리학회 2010 The Korean Journal of Physiology & Pharmacology Vol.14 No.5

We elucidated the distribution of interstitial cells of Cajal (ICC) in human stomach, using cryosection and c-Kit immunohistochemistry to identify c-Kit positive ICC. Before c-Kit staining, we routinely used hematoxylin and eosin (HE) staining to identify every structure of human stomach, from mucosa to longitudinal muscle. HE staining revealed that the fundus greater curvature (GC) had prominent oblique muscle layer, and c-Kit immunostaining c-Kit positive ICC cells were found to have typical morphology of dense fusiform cell body with multiple processes protruding from the central cell body. In particular, we could observe dense processes and ramifications of ICC in myenteric area and longitudinal muscle layer of corpus GC. Interestingly, c-Kit positive ICC-like cells which had morphology very similar to ICC were found in gastric mucosa. We could not find any significant difference in the distribution of ICC between fundus and corpus, except for submucosa where the density of ICC was much higher in gastric fundus than corpus. Furthermore, there was no significant difference in the density of ICC between each area of fundus and corpus, except for muscularis mucosa. Finally, we also found similar distribution of ICC in normal and cancerous tissue obtained from a patient who underwent pancreotomy and gastrectomy. In conclusion, ICC was found ubiquitously in human stomach and the density of ICC was significantly lower in the muscularis mucosa of both fundus/corpus and higher in the submucosa of gastric fundus than corpus.

Mechanism of Relaxation Via TASK-2 Channels in Uterine Circular Muscle of Mouse

홍승화,성노현,김영철,최웅,박연진,지일운,김찬형,명순철,이무열,강동묵,유라영,이광주,임승운,윤효영,송영진,Wen Xie Xu,김학순,이상진,Hikaru Suzuki 대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.4

Plasma pH can be altered during pregnancy and at labor. Membrane excitability of smooth muscle including uterine muscle is suppressed by the activation of K+ channels. Because contractility of uterine muscle is regulated by extracellular pH and humoral factors, K+ conductance could be connected to factors regulating uterine contractility during pregnancy. Here, we showed that TASK-2inhibitors such as quinidine, lidocaine, and extracellular acidosis produced contraction in uterine circular muscle of mouse. Furthermore, contractility was significantly increased in pregnant uterine circular muscle than that of non-pregnant muscle. These patterns were not changed even in the presence of tetraetylammonium (TEA) and 4-aminopyridine (4-AP). Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretchactivated channels in myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed increased immunohistochemical expression of TASK-2. Therefore, TASK-2, seems to play a key role during regulation of myometrial contractility in the pregnancy and provides new insight into preventing preterm delivery.

H2 Receptor-Mediated Relaxation of Circular Smooth Muscle in Human Gastric Corpus: the Role of Nitric Oxide (NO)

이상억,김대훈,김영철,한정호,최웅,김찬형,정혜원,박선미,윤세진,최송이,성노현,김영호,유라영,선박희,김현,송영진,Wen-Xie Xu,윤효영,이상진 대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.5

This study was designed to examine the effects of histamine on gastric motility and its specificreceptor in the circular smooth muscle of the human gastric corpus. Histamine mainly produced tonicrelaxation in a concentration-dependent and reversible manner, although histamine enhanced contractilityin a minor portion of tissues tested. Histamine-induced tonic relaxation was nerve-insensitivebecause pretreatment with nerve blockers cocktail (NBC) did not inhibit relaxation. Additionally, K+channel blockers, such as tetraethylammonium (TEA), apamin (APA), and glibenclamide (Glib), hadno effect. However, NG-nitro-L-arginine methyl ester (L-NAME) and 1H-(1,2,4)oxadiazolo (4,3-A)quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), did inhibit histamine-inducedtonic relaxation. In particular, histamine-induced tonic relaxation was converted to tonic contractionby pretreatment with L-NAME. Ranitidine, the H2 receptor blocker, inhibited histamine-induced tonicrelaxation. These findings suggest that histamine produced relaxation in circular smooth muscle ofhuman gastric smooth muscle through H2 receptor and NO/sGC pathways.