• Title/Summary/Keyword: Desensitization

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Phosphorylation by $Ca^{+2}$/calmodulin-dependent Kinase II Regulates Binding of Capsaicin to VR1

  • Koo, Jae-Yeon;Kim, Sang-Sung;Kim, Man-Soo;Park, Seung-Pyo;Shim, Won-Sik;Yang, Young-Duk;Cho, Hwa-Won;Kim, Mi-Sook;Kim, Byung-Moon;Oh, Uh-Taek
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.128.1-128.1
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    • 2003
  • VR1, a capsaicin receptor, is now known to playa major role in mediating inflammatory thermal nociception. Although the physiological role or biophysical properties of VR1 are known, its activation mechanisms by ligands are poorly understood. Here, we show that VR1 requires phosphorylation by $Ca^{2+}$-calmodulin-dependent kinase II (CaMKII) for its activation by capsaicin. In contrast, dephosphorylation by calcineurin, leads to desensitization of the receptor. Point mutation of VR1 at two putative consensus sites for CaMKII fails to elicit capsaicin-sensitive currents with concomitant reduction in phosphorylation of VR1 in vivo. (omitted)

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Acyclic Vanilloid Receptor Antagonist Based on Capsazepine

  • Park, Hyeung-Geun;Park, Mi-Kyoung;Choi, Ji-Yeon;Choi, Se-Hoon;Lee, Ji-Hye;Suh, Young-Ger;Oh, Uh-Taek;Kim, Hee-Doo;Lee, Jee-Woo;Park, Young-Ho;Jeong, Yeon-Su;Choi, Jin-Kyu;Jew, Sang-Sup
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.349.1-349.1
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    • 2002
  • Capsaicin. the pungent component of chili pepper. opens a novel cation selective ion channel in the plasma membrane of peripheral sensory neurons. Capsaicin channel agonists induce pain upon topical application in the early stage. which is followed by a period of desensitization. Although the agonists have been studied as a analgesics, their initial irritancy became sever side effect. So competive antagonists have been pursued as a novel pharmacological agent for analgesics, rather than agonists. (omitted)

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Recent Advances in Allergen-Specific Immunotherapy in Humans: A Systematic Review

  • Sang Pyo Lee;Yoo Seob Shin;Sung-Yoon Kang;Tae-Bum Kim;Sang Min Lee
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.12.1-12.13
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    • 2022
  • Allergen-specific immunotherapy (AIT) is presumed to modulate the natural course of allergic disease by inducing immune tolerance. However, conventional AITs, such as subcutaneous immunotherapy and sublingual immunotherapy, require long treatment durations and often provoke local or systemic hypersensitivity reactions. Therefore, only <5% of allergy patients receive AIT as second-line therapy. Novel administration routes, such as intralymphatic, intradermal and epicutaneous immunotherapies, and synthetic recombinant allergen preparations have been evaluated to overcome these limitations. We will review the updated views of diverse AIT methods, and discuss the limitations and opportunities of the AITs for the treatment of allergic diseases in humans.

Sodium Salicylate Activates p38MAPK Though a Specific-Sensing Mechanism, Distinct from Pathways Used by Oxidative Stress, Heat Shock, and Hyperosmotic Stress

  • Kim, Jung-Mo;Oh, Su-Young;Kim, Min-Young;Seo, Myoung-Suk;Kang, Chi-Duk;Park, Hye-Gyeong;Kang, Ho-Sung
    • Biomedical Science Letters
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    • v.9 no.4
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    • pp.241-248
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    • 2003
  • Sodium salicylate, a plant stress hormone that plays an important role(s) in defenses against pathogenic microbial and herbivore attack, has been shown to induce a variety of cell responses such as anti-inflammation, cell cycle arrest and apoptosis in animal cells. p38MAPK plays a critical role(s) in the cell regulation by sodium salicylate. However, the signal pathway for sodium salicylate-induced p38MAPK activation is yet unclear. In this study, we show that although sodium salicylate enhances reactive oxygen species (ROS) production, N-acetyl-L-cysteine, a general ROS scavenger, did not prevent sodium salicylate-induced p38MAPK, indicating ROS-independent activation of p38MAPK by sodium salicylate. Sodium salicylate-activated p38MAPK appeared to be very rapidly down-regulated 2 min after removal of sodium salicylate. Interestingly, sodium salicylate-pretreated cells remained fully responsive to re-induction of p38MAPK activity by a second sodium salicylate stimulation or by other stresses, $H_2O$$_2$ and methyl jasmonate (MeJA), thereby indicating that sodium salicylate does not exhibit both homologous and heterologous desensitization. In contrast, pre-exposure to MeJA, $H_2O$$_2$, heat shock, or hyperosmotic stress reduced the responsiveness to subsequent homologous stimulation. Sodium salicylate was able to activate p38MAPK in cells desensitized by other heterologous p38MAPK activators. These results indicate that there is a sensing mechanism highly specific to sodium salicylate for activation of p38MAPK, distinct trom pathways used by other stressors such as MeJA, $H_2O$$_2$ heat shock, and hyperosmotic stress.

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Expression of Dopamine D2 Receptor in Response to Apomorphine Treatment in the Striatum of the Rat with Experimentally Induced Parkinsonism (파킨슨병 모형 흰쥐의 줄무늬체에서 Apomorphine 투여 방법에 따른 도파민 D2 수용체의 발현)

  • Choi, Seung Jin;Sung, Jae Hoon;Son, Byung Chul;Park, Choon Keun;Kwon, Sung Oh;Kim, Moon Chan;Lee, Sang Won
    • Journal of Korean Neurosurgical Society
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    • v.29 no.7
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    • pp.868-876
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    • 2000
  • Objective : Parkinsonian rat models have generally been characterized by unilateral destruction of both the nigrostriatal pathway and the mesolimbic pathway using the neurotoxin 6-hydroxydopamine. The induction of contraversive turning by apomorphine in these models is thought to reflect the stimulation of supersensitive dopamine D2 receptor or receptor-mediated mechanisms in denervated neostriatum. The present study was undertaken to investigate the expression of dopamine D2 receptor in denervated striatum according to modalities of apomorphine(dopamine agonist) treatment after creating a hemiparkinsonian rat model in which there is 6-hydroxydopamine induced destruction of the unilateral dopaminergic nigrostriatal pathway. Methods : After making complete lesion in left side substantia nigra pars compacta(SNpc) by stereotactic injection of 6-hydroxydopamine into medial and lateral areas of SNpc, and confirming successful animal model by apomorphine induced contraversive turning behavior without recovery and complete destruction of ipsilateral SNpc with tyrosine hydroxylase immunostaining in 7th day after operation, 15 rats of parkinsonian model were studied with or without administration of apomorphine at varying doses and durations. According to the modalities of apomorphine treatment for 4 days, these rats were divided into 3 groups, as not-treated group, intermittently treated group and constantly treated group. For investigating the extent of the expression of dopamine D2 receptor in denervated striatum, immunohistochemical staining by dopamine D2 receptor antibody and Western blot were performed. Results : In the D2 receptor antibody immunohistochemical staining, the mean number of positive stained neurons was highest in not-treated group($20.5{\pm}1.14$) of 3 groups. In constantly treated group, the mean number of positive stained neurons was less($3.9{\pm}1.79$) than intermittently treated group(p<0.05). The Western blotting with the D2 receptor antibody revealed that expression of receptors was also highest in not-treated group and less in constantiy treated group than intermittently treated group. Conclusion : Dopamine D2 receptors in denervated striatum of parkinsonian rat models, which were not treated with apomorphine, revealed to be most highly expressed. And, according to doses and durations of apomorphine administration, desensitization of the receptor was more apt to develop with constant treatment than intermittent treatment. In clinical setting, the authors believe that, in long-term treated parkinsonian patients, desensitization of dopamine receptors due to chronic dopaminergic stimulation seems to be partially related to mechanisms of drug tolerance.

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Existence of Cholinergic and Purinergic Receptor on the Detrusor Muscle of Rat Urinary Bladder (흰쥐 적출 배뇨근에서 콜린성 및 퓨린성 수용체의 존재)

  • Choi, Tae-Su;Kwon, Oh-Cheol;Ha, Jeoung-Hee;Lee, Kwang-Youn;Kim, Won-Joon
    • Journal of Yeungnam Medical Science
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    • v.8 no.2
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    • pp.138-149
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    • 1991
  • This study was aimed at investigation of the stimulatory innervations on the rat urinary bladder. Detrusor muscle strips of 15 mm long were suspended in isolated muscle chambers containing 1 ml of PSS maintained at $37^{\circ}C$ and aerated with 95% $O_2/5%CO_2$. Isometric myography was perfomed, and the results were as followings : Muscle strips showed "on-contraction" by electric field stimulation (EFS) frequency-dependently. The EFS-induced contraction was not affected by hexamethonium, a ganglion blocker, but abolished, by tetrodotoxin, a nerve conduction blocker. Physostigmine, a cholinesterase inhibitor enhanced the EFS-induced contraction which was inhibited by hemicholinium, an inhibitor of choline uptake at the cholinergic nerve ending. Such an EFS-induced contraction was antagonized by atropine only partially, and the atropine-resistant portion was completely abolished by the desensitization of purinergic receptors by prolonged incubatin of the strips in the presence of high concentratin of ATP. Bethanechol, a cholinergic agonist, elicited concentration-dependent contraction. Adenosine triphosphate (ATP), a purinergic agonist, induced a weak but concentration-dependent contraction of short duration. Bethanechol-induced contraction was not affected by ATP-desensitization, and ATP-induced contraction was not affected by tetrodotoxin. These results suggest that there are at least two main stimulatory components of innervations in the detrusor muscle, cholinergic muscarinic and purinergic ; and those receptors are independent each other.

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Management of prosthodontic patients with severe gag reflex using the questionaire and behavior technique: A case report (심한 구역반사를 보이는 환자에서 문진표와 행동 요법을 이용한 임플란트 고정성 보철 수복 증례)

  • Sohn, Changmo;Kim, Yu-Jin;Lee, Cheon-Seo;Choi, Na-Rae;Kwon, Eun-Young;Kim, So-Yeun
    • The Journal of Korean Academy of Prosthodontics
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    • v.59 no.3
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    • pp.333-340
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    • 2021
  • Although gag reflex is an essential function and a useful physiological defense mechanism, it can become an obstacle in a dental treatment. In this case, a questionnaire was designed and used in consultations to objectify the factors associated with gag reflex. Based on the questionnaire, various treatment protocols were planned, such as behavioral control, which is a systematic desensitization that adapts by placing dental instruments in the oral cavity, and habit control to eliminate vomiting habits after drinking. Except for the placement of the implant fixture under general anesthesia, all restoration procedures were performed in the outpatient clinic in the same manner as the conventional implant fixed prosthetic restoration. The systematic desensitization and behavior technique were repeated until the patient was able to endure discomfort and relieve gag reflex in dental treatment. The patient was successfully received the implant-fixed prosthetic restoration in the partial edentulous region.

A Systematic Review of effect on Heat-sensitive Moxibustion for Benign Prostatic Hyperplasia (전립선비대증에 대한 열민구(熱敏灸)의 효과에 관한 체계적 문헌 고찰)

  • Kim, MinSeok;Ju, HongMin;Kim, MinHwa;Park, SunYoung;Yun, YoungJu;Park, SeongHa
    • The Journal of Korean Medicine
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    • v.42 no.3
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    • pp.153-164
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    • 2021
  • Objectives: The aim of this study is to investigate the effect of Heat-sensitive Moxibustion on Benign Prostatic Hyperplasia Methods: We searched articles from Academic Journals(CAJ) online databases, Oriental Medicine Advanced Searching Integrated System (OASIS), Searching key words were '前列腺增生', '熱敏灸' and '열민구', '전립선비대'. The search range included randomized controlled trials (RCTs). Among the articles published to 2020, 10 articles were found. After review the title, abstract and original, 3 articles were selected finally to rule out treatment combined with completely different treatments. Result: The Heat-sensitive moxibustion at acupoints in the treatment of Benign prostatic hyperplasia were significantly superior to control group after treatment in the symptoms of patients, IPSS, QOL, PVR and Qmax(P<0.05). The Heat-sensitive moxibustion can significantly reduce the incidence of temporary urinary incontinence after Transurethral resection of the prostate(TURP) and improve life quality and satisfaction of patients(P<0.05). The individualized desensitization saturated time and amount of Heat-sensitive moxibustion is superior effective to general amount and time of traditional moxibustion in the total effective rate, IPSS, Ru and Qmax(P<0.01) for Benign prostatic hyperplasia. Conclusion: Heat sensitive moxibustion directly transfer heat to the source of a disease. So it can be considered as a good treatment for Benign prostate hypertrophy. It was also shown a better effect on BPH compared to traditional moxibustion, According to the thermo principles of tumor, if the tumor cell's death temperature of 43℃ is reached, that can cause tumor degeneration. Therefore I think Heat sensitive moxibustion can be applied to various tumor disease. The results of this study could be applied to clinical treatment of BPH. However, additional large-scale clinical researches should be conducted.

The Experience of Nursing Students' Moral Distress in Clinical Practice (임상실습 현장에서 간호대학생이 경험하는 도덕적 고뇌)

  • Kim, Chanhee;Choi, Heeseung
    • The Journal of Korean Academic Society of Nursing Education
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    • v.22 no.3
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    • pp.355-365
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    • 2016
  • Purpose: This study explores the moral distress that nursing students experience during their clinical practice in Korea. Methods: Data were collected using focus group interviews, and analyzed using qualitative content analysis. Participants were recruited from three nursing schools in three different cities; each focus group interview lasted between one to two hours. Results: Twenty-two nursing students with more than one year of clinical practice experience participated. Three categories and ten themes were extracted. The following situational categories: "unprotected patients' right and dignity," "clinical settings in which standards of care are not upheld," "disrespectful hospital culture," and "inconsistent and unsystematic clinical education" caused moral distress. Types of responses to moral distress included: "shock and confusion over the gap between reality and moral standards," "powerlessness when cannot advocate patients," "fear and doubts about nursing career," and "moral desensitization and disappointment in oneself." "Expressions of moral distress and the need for advice" and "a search for meaning and hope" were identified as coping strategies. Conclusion: These results demonstrate the need for systematic clinical practicum and education programs to minimize moral distress. These programs may offer opportunities for students to turn moral distress into opportunities for learning and growth in the future.

The Inhibitory Effect of Apigenin on the Agonist-Induced Regulation of Vascular Contractility via Calcium Desensitization-Related Pathways

  • Je, Hyun Dong;Kim, Hyeong-Dong;La, Hyen-Oh
    • Biomolecules & Therapeutics
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    • v.22 no.2
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    • pp.100-105
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    • 2014
  • Apigenin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of apigenin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Apigenin significantly relaxed fluoride-, thromboxane $A_2$ mimetic- or phorbol ester-induced vascular contraction, which suggests that apigenin could be an anti-hypertensive that reduces agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, apigenin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels, which suggests the mechanism involving the inhibition of Rho-kinase and MEK activity and the subsequent phosphorylation of MYPT1 and ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of apigenin on agonist-induced vascular contraction regardless of endothelial function.