• Biomolecules & Therapeutics
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• 제27권6호
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• pp.514-521
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• 2019

G protein-coupled receptors (GPCRs) are membrane receptors whose agonist-induced dynamic conformational changes trigger heterotrimeric G protein activation, followed by GRK-mediated phosphorylation and arrestin-mediated desensitization. Cytosolic regions of GPCRs have been studied extensively because they are direct contact sites with G proteins, GRKs, and arrestins. Among various cytosolic regions, the role of helix 8 is least understood, although a few studies have suggested that it is involved in G protein activation, receptor localization, and/or internalization. In the present study, we investigated the role of helix 8 in dopamine receptor signaling focusing on dopamine D1 receptor (D1R) and dopamine D2 receptor (D2R). D1R couples exclusively to Gs, whereas D2R couples exclusively to Gi. Bioinformatic analysis implied that the sequences of helix 8 may affect GPCR-G protein coupling selectivity; therefore, we evaluated if swapping helix 8 between D1R and D2R changed G protein selectivity. Our results suggest that helix 8 is not involved in D1R-Gs or D2R-Gi coupling selectivity. Instead, we observed that D1R with D2R helix 8 or D1R with an increased number of hydrophobic residues in helix 8 relative to wild-type showed diminished ${\beta}$-arrestin-mediated desensitization, resulting in increased Gs signaling.

• 생물정신의학
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• 제17권2호
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• pp.94-102
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• 2010

Objectives : Eye movement desensitization and reprocessing(EMDR) is a novel, time-limited psychotherapy originally developed for treatment of psychological trauma. The effectiveness of this therapy has been validated only for posttraumatic stress disorder ; however, EMDR is often applied to other psychiatric illnesses, including other anxiety disorders and depression. This pilot study tested the efficacy of EMDR added to the routine treatment for individuals with acute stage schizophrenia. Methods : This study was conducted in the acute psychiatric care unit of a university-affiliated training hospital. Inpatients diagnosed with schizophrenia were randomly assigned to either three sessions of EMDR, three sessions of progressive muscle relaxation(PMR) therapy, or only treatment as usual(TAU). All the participants received concurrent typical treatments(TAU), including psychotropic medication, individual supportive psychotherapy and group activities in the psychiatric ward. The Positive and Negative Syndrome Scale(PANSS), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale were administered by a clinical psychologist who was blinded to the patients' group assignment. Results : Forty-five patients enrolled and forty patients(89%) completed the post-treatment evaluation. There were no between-group differences in the withdrawal rates of patients during the treatment or at the three-month follow-up session. All three groups improved significantly across each of the symptomatic domains including schizophrenia, anxiety, and depressive symptoms. However, a repeated measures ANOVA revealed no significant differences among the groups over time. Effect size for change in total PANSS scores was also similar across treatment conditions, but effect size for negative symptoms was large for EMDR(0.60 for EMDR, 0.39 for PMR and 0.21 for TAU only). Conclusion : These findings supported the use of EMDR in treating the acute stage of schizophrenia but the results failed to confirm the effectiveness of the treatment over the two control conditions in three sessions. Further studies with longer courses of treatment, more focused target dimensions of treatment, and a sample of outpatients are necessary.

• 대한소아치과학회지
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• 제6권1호
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• pp.35-41
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• 1979

Of 42 children, 21 in male and 21 in female, whose ages ranged from 2 to 5 years old, the response of young children to their initial series of dental visits was examined. The results were as follows; 1. With continued experience, the child's response improved, indicating desensitization to dental stress. 2. Experience may reduce the general amount of negative response by allowing the child to accurately distinguish between stressful and non-stressful procedures.

• International Journal of Oral Biology
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• 제33권1호
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• pp.1-5
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• 2008

Adenosine 5'-triphosphate (ATP) is an important extracellular signaling molecule which is involved in a variety of physiological responses in many different tissues and cell types, by acting at P2 receptors, either ionotropic (P2X) or G protein-coupled metabotropic receptors (P2Y). P2X receptors have seven isoforms designated as $P2X_{1^-}P2X_7$. In this study, we investigated the electrophysiological and pharmacological properties of rat $P2X_{1^-}P2X_4$ currents by using whole-cell patch clamp technique in a heterologous expression system. When ATP-induced currents were analyzed in human embryonic kidney (HEK293) cells following transient transfection of rat $P2X_{1^-}P2X_4$, the currents showed different pharmacological and electrophysiological properties. ATP evoked inward currents with fast activation and fast desensitization in $P2X_{^1-}$ or $P2X_{3^-}$ expressing HEK293 cells, but in $P2X_{2^-}$ or $P2X_{4^-}$ expressing HEK293 cells, ATP evoked inward currents with slow activation and slow desensitization. While PPADS and suramin inhibited $P2X_2$ or $P2X_3$ receptor-mediated currents, they had little effects on $P2X_4$ receptor-mediated currents. Ivermectin potentiated and prolonged $P2X_4$ receptor-mediated currents, but did not affect $P2X_2$ or $P2X_3$ receptor-mediated currents. We suggest that distinct pharmacological and electrophysiological properties among P2X receptor subtypes would be a useful tool to determine expression patterns of P2X receptors in the nervous system including trigeminal sensory neurons and microglia.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제13권1호
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• pp.24-29
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• 2002

본고는 최근 미국의 911 사태이후 정신의학 분야에서 관심사로 떠오르고 있는 재해정신의학 (Disaster Psychiatry)에대한 고찰을 통해 국내에서 대형재해 발생시 소아청소년 정신과 의사로서의 일정역할을 모색코자하는 목적의 일환이다. 우선 성인과 달리 소아청소년 재해환자에대한 치료를 다룰 때 어떤점을 고려하여야하는가에대한 연령 발달적 특이성를 살펴보고, 예방프로그램과 소아청소년 특유의 치료법은 무엇인가에대해 살펴보았다. 이를 요약하면 1) 소아는 타인에게 의존해야하는 존재로 부모 혹은 가족의 아이에대한 태도와 지지가 예후 결정에 가장 중요한 요소임으로 가족치료 부모교육의 중요성이 강조되며, 2) 개인치료에서는 인지행동적 요소가 여러 연구 문헌을 통해 가장 효과가 입증된 치료기법이고, 3) 놀이면담치료, fellow victim으로 구성된 집단치료 역시 효과적이며, 4) 1회성 재해를 당한 공포환자의 경우 특수기법인 EMDR(Eye Movement Desensitization and Reprocessing)의 시도가 추천되고, 5) 약물치료의 경우 2차적 혹은 보조치료수단이 되는데 성인에서 시도되는 다양한 약물의 적용이 가능하지만 부작용에대한 주의가 필요하다.

• 대한불안의학회지
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• 제12권2호
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• pp.69-78
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• 2016

Objective : Disaster causes psychological distress to a large number of people in a short period of time, by both direct and indirect exposure to traumatic events embedded in various realms of disaster experience. Optimal, well-planned treatment interventions should follow from the early acute period to recovery phase, extending up to several months later. In this context, there is an increasing need for systemic review to gain comprehensive insights for disaster interventions. These need to be added to public policy, and for the prevention and treatment of disaster-related psychopathology. Here, we review the published studies on psychological interventions for disaster-related posttraumatic stress disorder. Methods : Specific psychological interventions regarded as effective treatments for have been selected for this review, such as CBT (Cognitive-Behavior Therapy), Exposure Therapy, EMDR (Eye Movement Desensitization & Reprocessing), SIT (Stress Inoculation Therapy) and Psychoeducation. In addition, natural disasters, industrial disasters, and accidents involving aircraft and ships were also categorized as disasters, along with war and combat trauma. Results : Cognitive behavior therapy and exposure therapy had the strongest research support for effectiveness, and could be considered as the first-choice treatment for disaster-related PTSD. The second line of treatment is EMDR, although this treatment modality has the advantage of reaching certain treatment improvements in fewer sessions. However, the effects of SIT and psychoeducation to the survivors of disasters, remains unclear at this point. Additionally, we propose the possibilities of using virtual reality component and imagery rescripting as modified forms of traditional cognitive behavior therapy and exposure therapy. Conclusion : Cognitive behavior therapy and exposure therapy, deemed effective treatments for various trauma, are considered to be effective for survivors from disasters. However, the efficacy of other interventions has not yet been examined methodologically in well-designed studies, such as randomized controlled trials. In particular, future empirical studies are needed, since it is difficult to conclude that psychological interventions have similar effects on different types of disasters.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.287-287
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• 1994

In the present study, it was aimed to asses the possibility that calcitonin gene-related peptide (CGRP) released in response to transient hypotension may contribute to the reflex autoregulation of cerebral blood flow as a putative modulator. Changes in pial arterial diameter (mean, 33.0 ${\pm}$ 1.1 $\mu\textrm{m}$) with changes in systemic arterial blood pressure (mean, 101.9 ${\pm}$ 2.7 mmHg) were observed directly through a closed cranial window in anesthetized normotensive rats. Image of the pial vessels was captured with a stereoscope connected to a CCD video camera and the diameter was measured with a microscaler. In the capsaicin-treated rats (one day prior to experiment, 50 nmol capsaicin injected intracisternally), both vasodilater and vasoconstrictor responses evoked by a transient hypotension and the reverse of blood pressure were markedly attenuated or almost abolished. When changes in pial arterial diameter were plotted as a function of changes in blood pressure, the slopes of both regression lines (for vasodilators and vasoconstrictors ) were markedly reduced. Similar reductions were evidenced under treatment wi th the CGRP antibody serum (1:1,000) and following CGRP receptor desensitization. However, the autoregulatory mechanics were neither affected by treatment wi th spantide (1 ${\mu}$M), substance P antagonist, nor by substance P receptor desensitization. Suffusion wi th mock cerebrospinal fluid containing CGRP and cromakalim caused a vasodilatation in a concentration-dependent manner, respectively and their effects were antagonized by glibenclamide. Substance P produced a vasodilatation, which was, however, little affected by glibenclamide. These observations indicate that the CGRP released from the perivascular sensory fibers in response to a hypotension is implicated in the modulation of the autoregulation of cerebral blood flow.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.301-301
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• 1994

〔$^3$H〕Ouabain binding parameters(K$\_$D/ and B$\_$max/,) in homogenates prepared fpom control rat ventricular strip and Langendorff preparations which were not previously exposed to ouabain were compared to those in homogenates from ventricular strip and Langendorff preparations that had been first exposed to a complete ouabain dose-response curve(10$\^$-7/M to 10$\^$-4/ M). In rat ventricular strips and Langendorff perfused rat heart preparations, cumulative dose-response cruves of ouabain revealed biphasic positive inotropic effects, a "low-dose" and a "high-dose" effect with ED$\_$50/ values of 0.5${\mu}$M and 35${\mu}$M ouabain, respectively- The "low-dose" effect in rat ventricular strips disappeared or was diminished significantly when the ouabain dose-response curve wag repeated after the washout of the effects of the first curve, whereas the maximal "high-dose" effect was identical in both exposures to oubain. However, there was no change in the "low-dose" effects in both sets of the Langendorff perfused hearts. The contractile activity of the pre-exposed strips did not indicate the presence of residual ouabain since their basal contractile force was decreased 10% compared to initial control. 〔$^3$H〕Ouabain binding parameters, K$\_$D/ and B$\_$max/, were not changed comparing homogenate of control ventricular strips with that of strips pre-exposed to ouabain. These results suggest that digitalis receptor desensitization in the rat ventricular strip may due to the change of post-receptor events induced by ouabain binding to a high affinity site(${\alpha}$$_2$ isoform).

• The Korean Journal of Physiology and Pharmacology
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• 제18권6호
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• pp.461-467
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• 2014

The hypothesis of this study was that diabetes-induced desensitization of rat soleus (SOL) and extensor digitorum longus (EDL) to non-depolarizing muscle relaxants (NDMRs) depends on the stage of diabetes and on the kind of NDMRs. We tested the different magnitude of resistance to vecuronium, cisatracurium, and rocuronium at different stages of streptozotocin (STZ)-induced diabetes by the EDL sciatic nerve-muscle preparations, and the SOL sciatic nerve-muscle preparations from rats after 4 and 16 weeks of STZ treatment. The concentration-twitch tension curves were significantly shifted from those of the control group to the right in the diabetic groups. Concentration giving 50% of maximal inhibition ($IC_{50}$) was larger in the diabetic groups for all the NDMRs. For rocuronium and cisatracurium in both SOL and EDL, $IC_{50}$ was significantly larger in diabetic 16 weeks group than those in the diabetic 4 weeks group. For SOL/EDL, the $IC_{50}$ ratios were significantly largest in the diabetic 16 weeks group, second largest in the diabetic 4 weeks group, and smallest for the control group. Diabetes-induced desensitization to NDMRs depended on the stage of diabetes and on the different kind of muscles observed while was independent on different kind of NDMRs. The resistance to NDMRs was stronger in the later stage of diabetes (16 versus 4 weeks after STZ treatment). Additionally, when monitoring in SOL, diabetes attenuated the actions of neuromuscular blockade more intensely than that in EDL. Nonetheless, the hyposensitivity to NDMRs in diabetes was not relevant for the kind of NDMRs.

• International Journal of Contents
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• 제14권3호
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• pp.39-45
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• 2018

Purpose: Food Allergen Immunotherapy (Oral) is a form of immunotherapy administered to patients who are allergic to foods such as egg, milk, and peanut. The food allergen is orally administered to the patient in an escalating dose for desensitization or tolerance development. The safety and effectiveness of the therapy were assessed using a systematic literature review and meta-analysis. Methods: For a literature search, 8 national databases and a number of international databases including Ovid-MEDLINE, Ovid-EMBASE, and Cochrane Library were used; and 13 articles (all from international databases) were selected. The target of Food Allergen Immunotherapy (Oral) included patients with food allergy, and the intervention was food allergen immunotherapy without limiting the food type. The safety and effectiveness of Food Allergen Immunotherapy (Oral) were assessed by reviewing all the articles reporting on the therapy. The control group received standard therapies including aversion therapy, no treatment, anti-histamine treatment, and placebo. Safety was assessed through the incidence of complication and emergency medication. Effectiveness was assessed based on therapy success rate, symptomatic improvement, and quality of life. Results: Although Food Allergen Immunotherapy (Oral) was shown to have successful desensitization in patients with food allergy, the safety of the technique has not yet reached an acceptable level; the possible reason is due to the high rate of complication and frequency of emergency medication. Also, each study employed varying protocols while relying on a small number of participants and a short monitoring period. Conclusion: The results of assessment suggest that the level of evidence from current literature review is low and further research is necessitated for the verification of the safety and effectiveness of the therapy (Grade of Recommendation: A; Level of Technology: II-b).