• Biomolecules & Therapeutics
• /
• 제25권1호
• /
• pp.12-25
• /
• 2017

G protein-coupled receptors (GPCRs) are a family of cell-surface proteins that play critical roles in regulating a variety of pathophysiological processes and thus are targeted by almost a third of currently available therapeutics. It was originally thought that GPCRs convert extracellular stimuli into intracellular signals through activating G proteins, whereas ${\beta}$-arrestins have important roles in internalization and desensitization of the receptor. Over the past decade, several novel functional aspects of ${\beta}$-arrestins in regulating GPCR signaling have been discovered. These previously unanticipated roles of ${\beta}$-arrestins to act as signal transducers and mediators of G protein-independent signaling have led to the concept of biased agonism. Biased GPCR ligands are able to engage with their target receptors in a manner that preferentially activates only G protein- or ${\beta}$-arrestin-mediated downstream signaling. This offers the potential for next generation drugs with high selectivity to therapeutically relevant GPCR signaling pathways. In this review, we provide a summary of the recent studies highlighting G protein- or ${\beta}$-arrestin-biased GPCR signaling and the effects of biased ligands on disease pathogenesis and regulation.

• 화약ㆍ발파
• /
• 제25권1호
• /
• pp.45-52
• /
• 2007

수직으로 12m 천공된 노천발파 현장에서 본당 1kg의 에멀젼 폭약을 자유낙하 하여 장약하면 117.6J의 낙하충격 에너지가 발생한다. 에멀젼이 강한 외부의 충격을 받으면 과포화 상태로 불연속상을 형성하고 있는 산화제 수용액 입자가 서로 뭉쳐서 결정으로 석출되고, 예감제의 일부가 파괴되어 비중이 상승된다. 산화제 수용액이 석출되어 에멀젼이 파괴되거나, 에멀젼 폭약의 비중이 높아지면 폭속 및 기폭감도가 저하된다. 본 연구에서는 직경 75mm, 길이 12m의 PVC 파이프를 수직과 $70^{\circ}$ 각도로 세우고, 약경 50mm 에멀젼 폭약을 낙하하여 충격에 의한 성능 변화를 평가하였는데 폭굉 에너지는 최대 26%까지 감소하나 전체 발파공에서 발파효율에 미치는 영향은 3% 이내인 것으로 조사되었다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제4권4호
• /
• pp.311-318
• /
• 2000

We cultured the rabbit inner medullary collecting duct (IMCD) cells as monolayers on collagen-coated membrane filters, and investigated distribution of the P2Y receptors by analyzing nucleotide-induced short circuit current $(I_{sc})$ responses. Exposure to different nucleotides of either the apical or basolateral surface of cell monolayers stimulated $I_{sc}.$ Dose-response relationship and cross-desensitization studies suggested that at least 3 distinct P2Y receptors are expressed asymmetrically on the apical and basolateral membranes. A $P2Y_2-like$ receptor, which responds to UTP and ATP, is expressed on both the apical and basolateral membranes. In addition, a uracil nucleotide receptor, which responds to UDP and UTP, but not ATP, is expressed predominantly on the apical membrane. In contrast, a $P2Y_1-like$ receptor, which responds to ADP and 2-methylthio-ATP, is expressed predominantly on the basolateral membrane. These nucleotides stimulated intracellular cAMP production with an asymmetrical profile, which was comparable to that in the stimulation of $I_{sc}.$ Our results suggest that the adenine and uracil nucleotides can interact with different P2Y nucleotide receptors that are expressed asymmetrically on the apical and basolateral membranes of the rabbit IMCD cells, and that both cAMP- and $Ca^{2+}-dependent$ signaling mechanisms underlie the stimulation of $I_{sc}$.

• Clinical and Experimental Reproductive Medicine
• /
• 제18권2호
• /
• pp.189-196
• /
• 1991

Long-term administration of luteinizing hormone-releasing hormone(LHRH) agonists, through a process of pituitary desensitization and down-regulation of receptors, inhibits the secretion of gonadotropin and sex-steroids and induces a reversible suppression of gonadal activity. This approach can be used as an effective endocrine therapy for some hormone-dependent tumors. We have used D-Trp6-LHRH, a long acting LHRH agonist, for the treatment of eleven patients with uterine leiomyomas, thereafter myomectomy was performed in seven cases and observed the ultrastructural changes of leiomyoma with an electron microscope. The use of LHRH agonist may be effective in reducing the size of a myoma considerably by primarily inducing medical hypophysectomy and would allow easier surgical removal. Electron microscopic findings of myoma cells after the use of LHRH agonist included the following: loss of cristae and swelling nuclear chromatin, perinuclear vacuolation in cytoplasm. Bone mineral density was slightly decreased, however, the difference was not statistically significant.

• 혜화의학회지
• /
• 제8권2호
• /
• pp.341-359
• /
• 2000

The following result are obtained through that comparative study on the psychotherapy of oriental and occidental medicine. 1. The shamanism(祝由) and active emotion therapy(移精變氣療法) are a primitive form of psychotherapy. It is an opinion that between active emotion therapy(移精變氣療法) and psychoanalytic therapy or supportive psychotherapy are similar. Also, the basic cognition pattern of shamanism(祝由) is projection. 2. Taoism is inseparably related to the psychotherapy of korean oriental medicine, the major thought has become the ideal base of oriental psychotherapy. 3. According to study of clinical document in relation to oriental psychotherapy, psychotherapy had been widely used by medical cure. 4. The five emotion restraint therapy is a high level psychotherapy of oriental medicine. Oriental psychotherapy that disease caused by surprising must be cure by surprising is like to systematic desensitization in western, and that pseudopsychosis must be cure by patient rely on doctor is like to suggestive therapy in western. 5. There are psychotherapy in western that Supportive psychotherapy, Short-term dynamic psychotherapy, Psychoanalytic therapy, Group psychotherapy, Family therapy, Morita therapy, Hypnotherapy, Autogenic training, Behavioral therapy, Milieu therapy, Occupational therapy, Psychodrama, the others. I think that they have wide application to the psychotherapy of korean oriental medicine.

• 동의신경정신과학회지
• /
• 제8권1호
• /
• pp.215-235
• /
• 1997

according to study of clinical document in relation to Neuropsychiatric disease in Ancient Chinese(Song, Keum, Won, Myung) clinical document the result were obtained as follows. 1. A main point is Jeul-Jin<切診> in diagnosis, that is Hyun-Maeg<弦脈> is liver disease, Whual Mag<滑脈> is gallbladder disease, Sag Mag<數脈> is fever.2. Doctors in Song<宋>, Keum<金>,Won<元> enumerationed many diseases are cause by emotion.3. Oriental psychotherapy that Diseases caused by surprising must be cure by surprising is like to systematic desensitization in Westem.4. Oriental psychotherapy that pseudopsychosis must be cure by patient rely on doctor is like to suggestive therapy in western.5. It is similar to suggestive therapy in western medicine that Sadness ,anguish and frustration induce disease.6. Headache is caused by fever, energy deficience and angry.7. Imsomnia is not caused by hsart disease, but gallbladder or liver.8. Schizophrenia is caused by shocking and a sort of fever.9. Epilepsy is caused by a sort of fever, shocking and fetal disease.10 Schizophrenia(in case of manic state) is caused by fever and shocking, and imaginary pregnancy is considered as schizophrenia.

• Biomolecules & Therapeutics
• /
• 제24권5호
• /
• pp.517-522
• /
• 2016

${\beta}$-Arrestins are one of the protein families that interact with G protein-coupled receptors (GPCRs). The roles of ${\beta}$-arrestins are multifaceted, as they mediate different processes including receptor desensitization, endocytosis, and G protein-independent signaling. Thus, determining the GPCR regions involved in the interactions with ${\beta}$-arrestins would be a preliminary step in understanding the molecular mechanisms involved in the selective direction of each function. In the current study, we determined the roles of the N-terminus, intracellular loops, and C-terminal tail of a representative GPCR in the interaction with ${\beta}$-arrestin2. For this, we employed dopamine $D_2$ and $D_3$ receptors ($D_2R$ and $D_3R$, respectively), since they display distinct agonist-induced interactions with ${\beta}$-arrestins. Our results showed that the second and third intracellular loops of $D_2R$ are involved in the agonist-induced translocation of ${\beta}$-arrestins toward plasma membranes. In contrast, the N- and C-termini of $D_2R$ exerted negative effects on the basal interaction with ${\beta}$-arrestins.

• 동의신경정신과학회지
• /
• 제29권1호
• /
• pp.1-8
• /
• 2018

Objectives: The purpose of this study is to compare the Korean-medical and the Western-medical psychotherapy on PTSD for improving the Korean-medical psychotherapy on this issue. Methods: We surveyed recent articles relating to psychotherapy on the incidence of PTSD. Results: Under the circumstances of this study, we note that applying the qigong therapeutics would be helpful when conducting relaxation training on the identified PTSD patients. We understand that taking a systematic desensitization style in the use of the kyungja-pyungji treatment is recommended. It would also be more effective to combine other treatments such as the use of the I-Jeong-Byeon-Gi Therapy and the five minds mutual restriction therapy. We have shown that by using the five minds mutual restriction therapy for the imagery rescripting has a better a synergy effect for optimum patient outcomes for patients who have been diagnosed with PTSD. Conclusions: Our study has shown that by improving the shortcomings of the Korean psychotherapy and utilizing Western psychotherapy's merits, we expect to increase the efficacy of the Korean psychotherapy with these recommendations for changes in this case.

• 대한불안의학회지
• /
• 제5권2호
• /
• pp.75-79
• /
• 2009

In this article, we review the efficacy of early interventions after traumatic incidents and during acute stress disorder (ASD). There are some evidences that psychopharmacological medications such as propronolol, morphine, and hydrocortisone are effective in the prevention of posttraumatic stress disorder (PTSD). Considering the role of selective serotonin reuptake inhibitors in hippocampal neurogenesis and an animal model of PTSD, early administration of selective serotonin reuptake inhibitors is also fairly promising. Other pharmacological treatments including benzodiazepines did not treat ASD nor prevent PTSD. There are good evidences that cognitive behavioral therapy including cognitive therapy and prolonged exposure is a valuable intervention for ASD and the most effective prevention for PTSD. No contolled researches on eye movement desensitization&reprocessing, psychodynamic psychotherapy and hypnotherapy have performed. Recent randomized controlled studies using psychological debriefing did not prove as a useful intervention for the prevention of PTSD until now, although the efficacy of debriefing has been at the centre of controversy.

• 수면정신생리
• /
• 제2권2호
• /
• pp.133-137
• /
• 1995

The author reviews current knowledge about what REM sleep is and where and how it is generated. REM sleep is the state in which our most vivid dreams occur. REM sleep is identified by the simultaneous presence of a desynchronized cortical EEG, an absence of activity in the antigravity muscles(atonia), and periodic bursts of rapid eye movements. Another characteristic phenomena of REM sleep are the highly synchronized hippocampal EEG of theta frequency and the ponto-geniculo-occipital(PGO) spike. All these phenomena can be explained in terms of changes in neuronal activity. Transection studies have determined that the pons is sufficient for generating REM sleep. Lesion studies have identified a small region in the lateral pontine tegmentum corresponding to lateral portions of the nucleus reticularis pontis oralis(RPO) and the region immediately ventral to the locus coeruleus, which is required for REM sleep. Unit recording studies have found a population of cells within this region that is selectively active in REM sleep. Cholinergic neurons of the giant cell field of pontine tegmentum(ETG), which is 'REM a sleep-on cells', has shown to be critically involved in the generation of REM sleep. Noradrenergic neurons of the locus coeruleus and serotonergic neurons of the dorsal raphe, which are called 'REM sleep-off cells', appear to act in a reciprocal manner to the cholinergic neurons. It is proposed that the periodic cessations of discharge of 'REM sleep-off cells' during REM sleep might be significant for the prevention of the desensitization of receptors of these neurons.