• Reproductive and Developmental Biology
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• 제35권2호
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• pp.143-149
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• 2011

Arthritis is a common disease in aged people, and is clinically divided into rheumatoid arthritis (RA) and osteoarthritis (OA). Although common symptoms such as pain are present, the underlying pathological mechanisms are slightly different. Therefore, the objectives of the present study were to compare joint damage induced by RA and OA by analyzing the major morphological and molecular differences, and to propose a suitable therapeutic intervention based on the pathophysiological conditions of bones and joints. For the RA animal model, 8-week-old DBA1/J mice were immunized with bovine type II collagen emulsified in complete Freund's adjuvant (CFA). Normal C57BL/6 mice (over 2 years of age) were used for OA. The clinical arthritis score was calculated using a subjective scoring system, and paw thicknesses were measured using calipers. The serum TNF ${\alpha}$ level was analyzed using an ELISA kit. Micro-CT was used to identify pathological characteristics and morphological changes. In collagen-induced RA mice, there were increased ankle joint volumes and clinical scores (p<0.01). The concentration of TNF ${\alpha}$ was significantly increased from 3 to 7 weeks after immunization. Micro-CT images showed trabecular bone destruction, pannus formation, and subchondral region destruction in RA mice. OA among aged mice showed narrowed joint spaces and breakdown of articular cartilage. This study suggests that a careful therapeutic intervention between RA and OA is required, and it should be based on morphological alteration of bone and joint.

• 대한한의학회지
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• 제24권3호
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• pp.108-117
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• 2003

Objective : The central opioid mechanism of acupuncture analgesia has been fairly well documented in acute behavioral experiments, but little electrophysiological study has been performed on the peripheral mechanism and subtypes of opioid receptors responsible for acupuncture-induced antinociception in chronic animal models. In the present electrophysiological experiment, we studied the peripheral mechanism and opioid receptor subtypes which Were implicated in electroacupuncture-induced antinociception in the rat with chronic inflammatory and neurogenic pain. Methods : In the rat with complete Freund's adjuvant-induced inflammation and spinal nerve injury, dorsal horn cell responses to afferent C fiber stimulation were recorded before and after electroacupuncture (EA) stimulation applied to the contralateral Zusanli point for 30 minutes. Also studied Were the effects of specific opioid receptor antagonists and naloxone methiodide, which can not cross the blood-brain barrier, on EA-induced inhibitory action. Results : EA-induced inhibitory action was significantly attenuated by naloxone methiodide, suggesting that EA-induced inhibition was mediated through peripheral mechanism. Pretreatment, but not posttreatment of naltrexone and spinal application significantly blocked EA-induced inhibitory actions. In inflammatory and neurogenic pain models, ${\mu}-$ and ${\delta}-opioid$ receptor antagonists (${\beta}-funaltrexamine$ & naltrindole) significantly reduced EA-induced inhibitory action, but ${\kappa}-opioid$ receptor antagonist had weak inhibitory effect on EA-induced antinociception. Conclusion : These results suggest that 2Hz EA-stimulation induced antinoeiceptive action is mediated through peripheral as well as central mechanism, and mainly through ${\mu}-$ and ${\delta}-opioid$ receptors.

• International Journal of Oral Biology
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• 제40권2호
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• pp.71-77
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• 2015

The activation of glial cells in the spinal cord has been contribute to the initiation and maintenance of pain facilitation induced by peripheral inflammation and nerve injury. The present study investigated effects of botulinum toxin type A (BoNT-A), injected subcutaneously or intracisternally, on the expression of microglia and astrocytes in rats. Complete Freund's Adjuvant (CFA)-induced inflammation was employed as an orofacial chronic inflammatory pain model. A subcutaneous injection of $40{\mu}L$ CFA into the vibrissa pad was performed under 3% isoflurane anesthesia in SD rats. Immunohistochemical analysis for changes in Iba1 (a microglia marker) and GFAP (an astrocyte marker), were performed 5 days after CFA injection. Subcutaneous injection of CFA produced increases in Iba1 and GFAP expression, in the ipsilateral superficial lamia I and II in the medullary dorsal horn of rats. Subcutaneous treatment with BoNT-A attenuated the up-regulation of Iba1 and GFAP expressions induced by CFA injection. Moreover, intracisternal injection of BoNT-A also attenuated the up-regulated Iba1 and GFAP expressions. These results suggest that the anti-nociceptive action of BoNT-A is mediated by modulation activation of glial cells, including microglia and astrocyte.

• 대한약침학회지
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• 제26권3호
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• pp.257-264
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• 2023

Objectives: The study was designed to evaluate anti-arthritic activity of Ajmodadi Churna (AC) and its effect on Complete freund's adjuvant (CFA)-induced arthritis in Wistar rats. Methods: Arthritis was induced by injecting 0.2 mL CFA into sub plantar surface of left hind paw. Test sample AC-1 and AC-2, 200 and 400 mg/kg, respectively was given to the animals for 21 consecutive days. The increase in swelling was observed after induction of arthritis. The paw edema was measured on 0, 3, 7, 14 and 21 day using Vernier caliper after the induction of arthritis. The collected blood samples further used for the estimation of red blood cells (RBC), white blood cells (WBC), erythrocytes sedimentation rate (ESR), and hemoglobin (Hb), using hematology analyzer. Serum concentration of IL-6 and TNF-α were also measured using rat ELISA kits. Results: Results showed that a significant reduction in paw edema was observed in AC-2 treated rats. The paw edema was restored on day 21 was 4.48 mm for AC-2, which is near to the control group. The arthritis score in treated rats was found to be considerably lower than in the control group i.e. 0.83 for AC-2 and 1.50 for AC-1. A decrease in levels of RBC and hemoglobin were observed in arthritic rats. Inflammation was significantly reduced and serum levels of IL-6 and TNF-α were lowered after treatment with the test drug. Conclusion: It can be concluded from the study that AC possess significant anti-arthritic activity. Furthermore, this condition was linked to a reduction in abnormal humoral immune responses.

• IMMUNE NETWORK
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• 제20권4호
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• pp.33.1-33.19
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• 2020

We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both T_H1 and T_H2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces T_H2 and T_H17 responses but reduces T_H1 and T_reg responses regardless of adjuvant type, whereas CFA but not alum increased follicular T_H response. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.

• Journal of Acupuncture Research
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• 제21권2호
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• pp.115-129
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• 2004

Objectives : To investigate the analgesic effect and its cholinergic mechanism of electroacupuncture(EA) in the rat model of collagen-induced arthritis(CIA). Methods : Immunization of male Sprague-Dawley rats with bovine typeII (CII) collagen emulsified in Freund's incomplete adjuvant, followed by a booster injection 14 days later, leads to development of arthritis in more than 70% of rats by 21 days postinjection. After three weeks of first immunization, EA stimulation(2 Hz, 0.07 mA, 0.3 ms) was delivered into Jogsamni($ST_{36}$) for 30 minutes. Analgesic effect was evaluated by tail flick latency(TFL). We compared the analgesic effect of EA with TFLs between pretreatment of normal saline and pretreatment of Atropine (1 mg/kg, intraperitoneal) and Neostigmine ($100{\mu}g/kg$, intraperitoneal) in CIA. Results : 1. TFLs were gradually decreased in CIA as increasing severity of arthritis. 2. Jogsamni($ST_{36}$) EA stimulation in CIA increased TFLs and the effect lasted for 60 minutes. 3. Increased TFLs with Jogsamni($ST_{36}$) EA stimulation were inhibited with pretreatment of atropine in CIA 4. Increased TFLs with Jogsamni($ST_{36}$) EA stimulation did not show an obvious synergistic effect with pretreatment of neostigmine in CIA. Conclusions: Jogsamni($ST_{36}$) EA showed analgesic effects in CIA. The analgesic effects of Jogsamni($ST_{36}$) EA were inhibited by atropine pretreatment and combined application of Jogsamni(ST36) EA and neostigmine did not show an synergistic effect. These observations suggest that intrinsic muscarinic cholinergic pathways represent an important modulating system in pain perception of inflammatory pain in CIA It is suggested that, the active mechanism of analgesic effect in EA may involve the release of acetylcholine in the spinal cord.

• 동의생리병리학회지
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• 제16권2호
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• pp.272-278
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• 2002

To investigate the anti-inflammatory and analgesic effects of Herba Chelidoniie, the extracts of Herba Chelidoniie treated in arthritic rat model. Complete Freund,s Adjuvant(CFA) were injected in the subcutaneous tissue of left foot paw of rats to induce arthritis. Herba Chelidonii extracts(HC) was administered immediately into the peritoneal cavity after CFA injection for 12 days. The immunohistochemical stainings for calcitonin gene-related peptide(CGRP) and substance P in the L4, L5 and L6 spinal dorsal horn and ganglia were done, and the paw swelling was measured with a micrometer and the blood leukocytes were counted. The results were as follows : The paw swelling of HC treated group was significantly decreased in 12th day after CFA injection compare to control group. The change of differential leukocytes counts of HC treated group increased the ratio of lymphocytes, and decreased the ratio of neutrophils compare to control group. The extent of CGRP immunoreactive nerve fiber of dorsal horn of HC treated group was weakly stained compare to control group. The number of CGRP immunoreactive neurons of L6 spinal cord of HC treated group was significantly decreased compare to control group. The extent of substance P immunoreactive nerve fiber of dorsal horn of He treated group was weakly stained compare to control group. The number of substance P immunoreactive neurons of L4, L5 and L6 spinal cord of HC treated group was significantly decreased compare to control group. These experimental results suggest that Herba Chelidonii extracts reduce the number of CGRP and substance P immunoreactive neurons and nerve fibers of spinal dorsal horns and ganglia, and decrease paw swelling in arthritic rat model, which may be closely related to analgesic and antiinflammatory effects of Herba Chelidonii.

• 대한의생명과학회지
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• 제2권1호
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• pp.13-20
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• 1996

최근 세포 표면의 다양한 항원들이 발견되고T세포 아형에 대한 정량적 측정이 가능하게 됨에 따라 세포성 면역기전의 규명과 이해에 획기적인 진전을 보이고 있다. T세포 아형의 phenotype은 실험 동물의 모델(model)이나 종(species)에 따라서 다양하며 차이가 나는 것으로 알려져 있다. 우리 나라의 경우 아직도 80만명 이상의 국민이 간 흡충에 감염되어 있을 것으로 추정되는 문제의 기생충이며 감염상태가 만성적일 때에는 간 경화나 간암으로까지 진행되는 흡충으로서 이에 대한 대책이 요구되고 있다. 그동안 간 흡충의 면역에 대한 연구는 체액성 면역에 대한 연구는 많은 규명과 진전이 있어 왔으나 세포성 면역에 대한 기전이나 특성에 대한 연구는 미미한 상태이다. 저자들은 이와 같은 사정을 감안하여 마우스를 실험 모델로 할 때에 요구되는 참고 자료와 기본 정보를 구하고자 하였다. 즉, 간흡충에 대한 세포 면역학적인 일부의 특성을 알아 보았으며,특히 비장 림프구 아형에 대한 phenotype의 특성을 알아 본 결과 다음과 같은 성적을 얻었다. 간흡충의 조항원을 면역증강제와 함께 복강 투여한 후 기간 별로 비장 림프구의 아형 특성을 flow cytometry로 측정한 결과, CD2, CD5 그리고 CD8는 투여 초기에는 감소하다가 투여 7주 후에 다시 증가하는 현상을 보였으며, CD4의 경우 투여 초기에는 약간 증가하다가 투여 7주 후에 다시 증가하는 성적을 보였다.

• The Journal of Korean Physical Therapy
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• 제21권2호
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• pp.117-124
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• 2009

Purpose: This study examined the effects of swimming exercise and Achyranthes Radix extracts on the inflammatory and behavioral responses in type II collagen-induced arthritic rats for 28 days. Methods: Sprague-Dawley rats were allocated randomly to one of the following four groups: only type II collageninduced (group Ⅰ), application of swimming exercise after type II collagen-induced (group II), application of Achyranthes Radix ointment after type II collagen-induced (group III), application of swimming exercise and Achyranthes Radix ointment after type II collagen-induced (group IV). Arthritis was established in SD rats by an intradermal injection of Chick type II collagen plus incomplete Freund's adjuvant at the base of the tail of the animals. The swimming exercise program consisted of a 25 min swimming session/day with a load corresponding to 5.5% of the weight bearing, three days/week for four weeks. The Achyranthes Radix ointment (0.1g) was applied twice a day for five days. The changes in behavior, H & E stain, and cyclooxygenase-2 (COX-2) level in the knee joint were assessed. Results: The gross and histological examination, after RA induction showed reddening, edema and erythema. The H & E stain revealed the destruction of articular cartilage, bony erosion and the infiltration of inflammatory cells after RA induction. The mechanical allodynia test results were significantly higher in group I than in groups II, III and IV (p<0.01). The immunohistochemistrical response of COX-2 in the knee joint showed that groups II, III, IV had a lower response effect than group I. Conclusion: Swimming exercise training and Achyranthes Radix ointment decreased the inflammatory responses and enhanced the behavioral responses in the arthritic rats.

• 동의생리병리학회지
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• 제24권6호
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• pp.983-988
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• 2010

The present study aims to investigate a possible mechanism of electroacupuncture (EA) in the spinal dorsal horn that may underlie N-methyl-D-aspartate (NMDA) receptor-associated extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling pathways. The hot plate latency of the ipsilateral hindpaw of EA-treated rats was significantly decreased compared with complete Freund's adjuvant (CFA)-injected ones. The expressions of NR1 and NR2B subuint mRNA of NMDA receptor in the whole L4-5 segments are decreased by CFA treatment, but NR2B subunit was significantly recovered by EA treatment. When we detected the expression of ERK, there were no significant difference between normal and CFA-treated rats with EA or NMDA receptor antagonist MK801. But phosphorylated ERK expressions were markedly induced by CFA, but these inductions were significantly modulated by EA treatment. Although hosphorylation of ERK was also arrested by MK801, these inductions of CFA-injected rats was markedly inhibited only by co-treatment with EA and MK801. Phosphorylated cAMP response element-binding protein (CREB), ERK-related transcriptional factor, showed a significant increase in CFA-treated rats and this increase was slightly inhibited by EA and MK801 treatments. But immunoreaction for phosphorylated CREB were significantly increased by CFA treatment in the superficial laminae of the dorsal horn and these inductions were significantly arrested by co-treatment of EA and MK801. Consequently, the hyperalgesia induced by CFA are associated NMDA receptor and EA and MK801 may showed anti-hyperalgesia via same mechanism for inhibition of ERK and CREB phosphorylation in the dorsal horn.