• 제목/요약/키워드: Therapeutic blockade

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신경병증성 통증 환자에서 지속적 진통을 위한 5% 리도카인의 사용 (The Use of 5% Lidocaine for Prolonged Analgesia in Neuropathic Pain Patients)

  • 박성욱;김동옥;김건식;최영규;권무일;신광일;이두익
    • 대한치과마취과학회지
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    • 제3권1호
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    • pp.6-9
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    • 2003
  • Background: The use of neurolytic agents to control neuropathic pain has been described from the last century Phenol and ethyl alcohol have been widely used as neurolytic agents, however, their neurolytic effect is variable in efficacy and duration of action, and infrequently accompanied with grave complications. It has been found that 5% lidocaine causes irreversible conduction blockade in animal studies. The goal of this study was to evaluate the neurolytic effect of 5%o lidocaine on various neuropathic pain syndromes for prolonged analgesia. Methods: Twenty-five patients with a diagnosis of neuropathic pain including trigeminal neuralgia (n = 7), postherpetic neuralgia (n = 10), and postsurgical neuralgia (n = 8) were selected after failure of routine therapeutic regimens. After performing a diagnostic nerve block with 1% lidocaine and 5% lidocaine was injected. The patients were followed for 6 months. Visual analog scale (VAS) scores and side effects were recorded for each patients. Results: A significant decrease in pain scores after neurolytic blockade with 5% lidocaine was seen in all of three pain groups. All the patients reported immediate and prolonged pain relief lasting from 4 weeks to 6 months. None of patients exhibited any appreciable side effects or complications. Conclusions: We suggest that 5% lidocaine may be used safely and effectively for the purpose of prolonged analgesia in selected patients with intractable neuropathic pain syndromes.

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Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors

  • Kim, Nayoung;Lee, Dong-Hee;Choi, Woo Seon;Yi, Eunbi;Kim, HyoJeong;Kim, Jung Min;Jin, Hyung-Seung;Kim, Hun Sik
    • BMB Reports
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    • 제54권1호
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    • pp.44-58
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    • 2021
  • Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers.

Renal Artery Embolization Using a New Liquid Embolic Material Obtained by Partial Hydrolysis of Polyvinyl Acetate (Embol): Initial Experience in Six Patients

  • Sung Il Park;Do Yun Lee;Jong Yoon Won;Sangsoo Park
    • Korean Journal of Radiology
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    • 제1권3호
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    • pp.121-126
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    • 2000
  • Objective: To evaluate the therapeutic efficacy of a new liquid embolic material, Embol, in embolization of the renal artery. Materials and Methods: Embol is a new embolic material obtained by partial hydrolysis of polyvinyl acetate mixed in absolute ethanol and Iopromide 370 and manufactured by Schering Korea, Kyonggido, Korea. Six patients who underwent embolization of the renal artery using Embol were evaluated. Four were male and two were female and their ages ranged from 11 to 70 (mean, 53) years. Clinical and radiologic diagnoses referred for renal artery embolization were renal cell carcinoma (n = 3), renal angiomyolipoma (n = 2) and pseudoaneurysm of the renal artery (n = 1). After selective renal angiography, Embol was injected through various catheters, either with or without a balloon occlusion catheter. Changes in symptoms and blood chemistry which may have been related to renal artery embolization with Embol were analyzed. Results: The six patients showed immediate total occlusion of their renal vascular lesions. One of the three in whom renal cell carcinoma was embolized with Embol underwent radical nephrectomy, and the specimen thus obtained revealed 40% tumor necrosis. In the two patients with angiomyolipomas, the tumors decreased in size and abdominal pain subsided. Bleeding from pseudoaneurysm of the renal artery was successfully controlled. Four patients showed symptoms of post-embolization syndrome, and one of these also showed increased levels of blood urea nitrogen and creatinine. One patient experienced transient hypertension. Conclusion: Embol is easy to use, its radiopacity is adequate and it is a safe and effective embolic material which provides immediate and total occlusion of renal vascular lesions.

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Blockade of Retinol Metabolism Protects T Cell-Induced Hepatitis by Increasing Migration of Regulatory T Cells

  • Lee, Young-Sun;Yi, Hyon-Seung;Suh, Yang-Gun;Byun, Jin-Seok;Eun, Hyuk Soo;Kim, So Yeon;Seo, Wonhyo;Jeong, Jong-Min;Choi, Won-Mook;Kim, Myung-Ho;Kim, Ji Hoon;Park, Keun-Gyu;Jeong, Won-Il
    • Molecules and Cells
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    • 제38권11호
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    • pp.998-1006
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    • 2015
  • Retinols are metabolized into retinoic acids by alcohol dehydrogenase (ADH) and retinaldehyde dehydrogenase (Raldh). However, their roles have yet to be clarified in hepatitis despite enriched retinols in hepatic stellate cells (HSCs). Therefore, we investigated the effects of retinols on Concanavalin A (Con A)-mediated hepatitis. Con A was injected into wild type (WT), Raldh1 knockout ($Raldh1^{-/-}$), $CCL2^{-/-}$ and $CCR2^{-/-}$ mice. For migration study of regulatory T cells (Tregs), we used in vivo and ex vivo adoptive transfer systems. Blockade of retinol metabolism in mice given 4-methylpyrazole, an inhibitor of ADH, and ablated Raldh1 gene manifested increased migration of Tregs, eventually protected against Con A-mediated hepatitis by decreasing interferon-${\gamma}$ in T cells. Moreover, interferon-${\gamma}$ treatment increased the expression of ADH3 and Raldh1, but it suppressed that of CCL2 and IL-6 in HSCs. However, the expression of CCL2 and IL-6 was inversely increased upon the pharmacologic or genetic ablation of ADH3 and Raldh1 in HSCs. Indeed, IL-6 treatment increased CCR2 expression of Tregs. In migration assay, ablated CCR2 in Tregs showed reduced migration to HSCs. In adoptive transfer of Tregs in vivo and ex vivo, Raldh1-deficient mice showed more increased migration of Tregs than WT mice. Furthermore, inhibited retinol metabolism increased survival rate (75%) compared with that of the controls (25%) in Con A-induced hepatitis. These results suggest that blockade of retinol metabolism protects against acute liver injury by increased Treg migration, and it may represent a novel therapeutic strategy to control T cell-mediated acute hepatitis.

기분장애에서 risperidone의 양면성 (Risperidone as a Janus in Mood Disorder)

  • 윤도준
    • 생물정신의학
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    • 제4권2호
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    • pp.198-210
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    • 1997
  • To examine the double-faced thymoleptic(antidepressant and antimanic) effects of risperidone in mood disorders, this article reviews the psychotropic-induced mania, thymoleptic effects of antipsychotics, therapeutic effects of risperidone and risperidone(RIS)-induced mania(RIM) in mood disorders, risk factors of RIM, possible neurochemical mechanism of these thymoleptic effects, pathophysiological and clinical significance of thymoleptic effects, and suggestive clinical guideline of RIS in mood disorders. RIS appeared effective for bipolar disorder at a lower dose than that recommended for schizophrenia, especially in the cases of maintenance of mood stabilizers, and gradual titration from low doses. Manic induction/exacerbation can occur by chance during RIS treatment in mood disorders, schizoaffective disorders, and schizophrenias. The possible risk factors for RIM are refractory mood disorder, especially in bipolar I disorder with poor initial response ; refractory schizoaffective disorders, especially in bipolar type with poor initial response ; refractory chronic schizophrenias, especially with initial responses ; psychotic features ; higher initial doses ; rapid titration ; combined therapy with antidepressants in refractory depression ; and RIS monotherapy in mania/hypomania. RIS is a drug that preferentially block 5-HT2 receptors. The effects of low dose are due mainly to the blockade of 5-HT2 receptors. There are more gradual increase in D2 blockade with increasing dose and this D2 blocking properties become apparent at higher doses. This may be related to a modulation of dopaminergic transmission by 5-HT2 antagonism at lower doses with the direct action of RIS on DA receptors coming into play at higher dose. The serotonergic antagonistic effect may be important for its effects on depressive symptoms. This, together with adequate blo-ckade of D2 receptors, may not necessarily lead to destabilization of mood disorder, but rather to more therapeutic effects. Therefore, this dose-receptor affinity relationship with both antidepressant and antimanic effects according to treatment duration can explain a continuum of antidepressant effect, antimanic effect, behavioral stimulation, and manic/hypomanic induction/exacerbation. It was the recognition of a useful psychiatric side effects by a thoughtful observer with fertile minds that led to their ultimate utilization as psychotropic drugs, i.e., phenothiazine, MAOI, TCA, and lithium. And, in vivo pharmacological challenge by novel psychotropics, as a neurochemical probe, with more specific actions is a useful tool to select pharmacologically homogeneous subgroup of the same phenotypical(clinical) condition, to further study the unknown underlying pathogenesis of various mental illnesses. Finally, RIS may be a useful alternative or adjunctive drug for patients with mood disorders without psychotic features or refractory to treatment with standard antipsychotic drugs. The more conservative doses(tirated slowly from 1-3 mg/d) of RIS, and maintenance of mood stabilizer in the cases with risk factors of RIM are recommended in mood disorder.

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Blockade of STAT3 in T Cells Inhibits Germinal Center Reactions against Intranasal Allergens

  • Choi, Garam;Chung, Yeonseok
    • Biomolecules & Therapeutics
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    • 제24권3호
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    • pp.244-251
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    • 2016
  • Understanding the developmental mechanisms of humoral immunity against intranasal antigens is essential for the development of therapeutic approaches against air-borne pathogens as well as allergen-induced pulmonary inflammation. Follicular helper T (Tfh) cells expressing CXCR5 are required for humoral immunity by providing IL-21 and ICOS costimulation to activated B cells. However, the regulation of Tfh cell responses against intranasal antigens remains unclear. Here, we found that the generation of Tfh cells and germinal center B cells in the bronchial lymph node against intranasal proteinase antigens was independent of $TGF-{\beta}$. In contrast, administration of STAT3 inhibitor STA-21 suppressed the generation of Tfh cells and germinal center B cells. Compared with wild-type OT-II T cells, STAT3-deficient OT-II T cells transferred into recipients lacking T cells not only showed significantly reduced frequency Tfh cells, but also induced diminished IgG as well as IgE specific for the intranasal antigens. Cotransfer study of wild-type OT-II and STAT3-deficient OT-II T cells revealed that the latter failed to differentiate into Tfh cells. These findings demonstrate that T cell-intrinsic STAT3 is required for the generation of Tfh cells to intranasal antigens and that targeting STAT3 might be an effective approach to ameliorate antibody-mediated pathology in the lung.

Failed Back Surgery Syndrome 환자에서 시행한 제2 요추 신경근 차단술 -증례 보고- (L2 Root Block in Failed Back Surgery Syndrome -A case report-)

  • 한승문;김태형;임영진;이상철
    • The Korean Journal of Pain
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    • 제13권2호
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    • pp.247-250
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    • 2000
  • Recently, some authors reported that discogenic low back pain should be regarded as a referred pain in respect of neural pathway. The afferent pathways of discogenic low back pain is transmitted mainly by sympathetic afferent fibres from the sinuvertebral nerves in the second lumbar nerve root. This pain arises from the lumbar intervertebral discs, and it had been transmitted mainly through the sympathetic afferent fibres contained in the second lumbar spinal nerve root. Second lumbar dermatome corresponds to the low back area. We experienced a case of low back pain which could not be controlled by conventional therapy and progressed wax and wane. The CT finding showed bulging disc between $L_4$ and $L_5$ and spinal stenosis in $L_4$ area. And epiduroscopic feature showed severe adhesion in $L_4$, $L_5$ and $S_1$. After we blocked $L_2$ root, pain score decreased 10 to 2. Therefore, the $L_2$ root block may be a useful diagnostic procedure as well as provide therapeutic value.

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Construction, and In Vitro and In Vivo Analyses of Tetravalent Immunoadhesins

  • Cho, Hoonsik;Chung, Yong-Hoon
    • Journal of Microbiology and Biotechnology
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    • 제22권8호
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    • pp.1066-1076
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    • 2012
  • Previous observations demonstrated that various immunosuppressive agents and their combination therapies can increase allograft survival rates. However, these treatments may have serious side effects and cannot substantially improve or prolong graft survival in acute graft-versus-host disease (GVHD). To improve the therapeutic potency of divalent immunoadhesins, we have constructed and produced several tetravalent forms of immunoadhesins comprising each of cytotoxic T-lymphocyte-associated antigen-4 (CTLA4), CD2, and lymphocyte activation gene-3 (LAG3). Flow cytometric and T cell proliferation analyses displayed that tetravalent immunoadhesins have a higher binding affinity and more potent efficacy than divalent immunoadhesins. Although all tetravalent immunoadhesins possess better efficacies, tetravalent forms of CTLA4-Ig and LAG3-Ig revealed higher inhibitory effects on T cell proliferation than tetravalent forms of TNFR2-Ig and CD2-Ig. In vitro mixed lymphocytes reaction (MLR) showed that combined treatment with tetravalent CTLA4-Ig and tetravalent LAG3-Ig was highly effective for inhibiting T cell proliferation in both human and murine allogeneic stimulation. In addition, both single tetravalent-form and combination treatments can prevent the lethality of murine acute GVHD. The results of this study demonstrated that co-blockade of the major histocompatibility complex class (MHC)II:T cell receptor (TCR) and CD28:B7 pathways by using tetravalent human LAG3-Ig and CTLA4-Ig synergistically prevented murine acute GVHD.

위축성 비염 환자에서 성상신경절 블록의 치료효과 -증례 보고- (Stellate Ganglion Blocks in Atrophic Rhinitis)

  • 김승준;이우창;장원석;윤덕미
    • The Korean Journal of Pain
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    • 제14권2호
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    • pp.231-233
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    • 2001
  • Atrophic rhinitis is characterized by mucosal atrophy, bony absorption, persistent fetid odor and resistance to medical and surgical treatment. Stellate ganglion block (SGB) can be used as a therapeutic modality by improving the regional blood flow through sympathetic blockade. We present a case of a 57 year-old male patient who had been treated unsuccessully for atrophic rhinitis for several years by surgical and conservative measures. The patient presented at our pain clinic with shoulder pain and received stellate ganglion block once or twice a week. He received more than 75 SGBs in addition to the routine conservative treatment for atrophic rhinitis. As the number of blocks performed increased, the patient demonstrated subjective symptom relief. We measured regional mucosal blood flow using a laser doppler flowmeter after the 28th, 63rd and 75th blocks. Nasal mucosal blood flow was improved by 4.9%, 28.8% and 36.3% respectively. We also were able to observe the recovery of mucosal atrophy to an almost normal level by nasal endoscopy. The patient is currently free of symptoms and is being followed up on an outpatient bases.

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CTLA-4-Tg/CD-28-KO Mice Exhibit Reduced T Cell Proliferation in vivo Compared to CD-28-KO Mice in a Graft-versus-host Disease Model

  • Yoo, Jong-Sun;Lee, Yun-Jung;Yoon, Joo-Won;Hyung, Kyeong-Eun;Hwang, Kwang-Woo
    • The Korean Journal of Physiology and Pharmacology
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    • 제16권5호
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    • pp.349-353
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    • 2012
  • Activated T cells express inhibitory receptors such as CTLA-4 that can downregulate immune responses. Blockade of or genetic deficiency in CTLA-4 can result in autoimmunity. Therefore, strategies to increase the inhibitory function of CTLA-4 may be attractive in settings of undesirable T cell responses such as autoimmunity or transplant rejection. We have tested the hypothesis that transgenic constitutive expression of CTLA-4 can further attenuate immune responses when compared with normal inducible expression. Our results indicate that transgenic expression of CTLA-4 in mouse T cells (CTLA-4-Tg T cells) results in reduced cell cycle progression and increased apoptosis of TCR-stimulated T cells. CTLA-4-Tg T cells display reduced T cell proliferation in an in vivo model of graft versus host disease (GVHD). These results further our understanding of how CTLA-4 can be manipulated to inhibit immune responses and may help development of new therapeutic strategies for clinical settings of autoimmunity and transplantation.