• 한국임상약학회지
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• 제31권1호
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• pp.27-34
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• 2021

Objective: To analyze osteoporosis treatment patterns and teriparatide prescription-associated factors in Korea by using a national health insurance claims database. Methods: We utilized the Health Insurance Review & Assessment Service National Patients Sample claims database to identify patients (aged ≥50 years) with at least one osteoporosis claim (International Classification of Disease 10th revision code: M80, M81, M82) and at least one prescription for osteoporosis medication (antiresorptive agents: bisphosphonates, selective estrogen receptor modulators, denosumab, and calcitonin; bone-forming agent: teriparatide) in 2018. Demographic characteristics and healthcare utilization patterns were analyzed. Factors associated with teriparatide prescriptions were assessed using a multivariate logistic regression model. Results: Records showed that 44,815 patients were prescribed osteoporosis medications in 2018; the percentage of patients prescribed each treatment was as follows: 86.6% bisphosphonates, 13.9% selective estrogen receptor modulators, 3.1% calcitonin, 2.1% denosumab, and 0.7% teriparatide. A greater proportion of patients prescribed teriparatide were ≥75 years (53.4% vs. 33.8%) and had fractures (63.9% vs. 12.8%) compared to the same for antiresorptives (p<0.001). Patients prescribed teriparatide had higher Charlson comorbidity index values (1.2±1.3 vs. 0.9±1.2) and were more frequently hospitalized (0.8±1.3 vs. 0.1±0.5) than those prescribed antiresorptives (p<0.001). Elderly patients (≥75 years old; adjusted OR=1.66; 95% CI 1.16-2.38) and those with fractures (adjusted OR=6.23; 95% CI 4.76-8.14) were more likely to be prescribed teriparatide than antiresorptives. Conclusion: Patients prescribed teriparatide were older and more likely to have severe osteoporosis than those prescribed antiresorptives.

• The Korean Journal of Pain
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• 제35권2호
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• pp.173-182
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• 2022

Background: Neurokinin-1 (NK1) and calcitonin gene-related peptide (CGRP) play a vital role in pain pathogenesis, and these proteins' antagonists have attracted attention as promising pharmaceutical candidates. The authors investigated the anti-nociceptive effect of co-administration of the CGRP antagonist and an NK1 antagonist on pain models compared to conventional single regimens. Methods: C57Bl/6J mice underwent sciatic nerve ligation for the neuropathic pain model and were injected with 4% formalin into the hind paw for the inflammatory pain model. Each model was divided into four groups: vehicle, NK1 antagonist, CGRP antagonist, and combination treatment groups. The NK1 antagonist aprepitant (BIBN4096, 1 mg/kg) or the CGRP antagonist olcegepant (MK-0869, 10 mg/kg) was injected intraperitoneally. Mechanical allodynia, thermal hypersensitivity, and anxiety-related behaviors were assessed using the von Frey, hot plate, and elevated plus-maze tests. The flinching and licking responses were also evaluated after formalin injection. Results: Co-administration of aprepitant and olcegepant more significantly alleviated pain behaviors than administration of single agents or vehicle, increasing the mechanical threshold and improving the response latency. Anxiety-related behaviors were also markedly improved after dual treatment compared with either naive mice or the neuropathic pain model in the dual treatment group. Flinching frequency and licking response after formalin injection decreased significantly in the dual treatment group. Isobolographic analysis showed a meaningful additive effect between the two compounds. Conclusions: A combination pharmacological therapy comprised of multiple neuropeptide antagonists could be a more effective therapeutic strategy for alleviating neuropathic or inflammatory pain.

• 대한본초학회지
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• 제32권2호
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• pp.41-47
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• 2017

Objective : The aim of this study is to investigate anti-arthritis activity using a korea's natural monument No. 265 designate 'Yeonsan-Ogye'. In this study, research by using extracts from different concentration of the Yeonsan-Ogye through an MIA-induced arthritis animal model was being conducted in vivo and scientifically verifying the efficacy of medicinal food. Methods : Yeonsan-Ogye was administered 500 mg/kg/day, 1000 mg/kg/day, 2000 mg/kg/day to SD-Rat, where arthritis was induced by monosodium iodoacetate (MIA) at $60mg/m{\ell}$. MMP-9, COMP, CTXII, calcitonin and glycosaminoglycan level in serum were measured by ELISA. The changes of relative hind paw weight bearing ratio by Incapacitance Test Meter and The cartilage of meniscus volume was examined and 3-D high-resolution reconstructions of the cartilage of meniscus were obtained using a Micro-CT system. Also, the histopathological analysis of knee was observed by H&E and safranin-O staining. Results : Production of MMP-9, COMP (all groups) and CTXII (500, 1000 mg/kg/day) level in serum was decreased, respectively, in comparison with control. The other way, production of calcitonin (500, 1000 mg/kg/day) and glycosaminoglycan (all groups) level in serum, Hind paw weight bearing ratio (all groups) was increased, espectively, in comparison with control. The cartilage of patella volume in micro-CT increased significantly. In addition, all groups showed a increase in the cartilage volume and proteoglycan. Conclusion : The results for Yeonsan-Ogye showed significant antiarthritis activity in serum and the cartilage. Therefore, it is thought to be that Yeonsan Ogye can be utilized as a variety of new korea medicie and health foods against arthritis diseases.

• 대한본초학회지
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• 제32권6호
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• pp.63-69
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• 2017

Objectives : The purpose of this study is to investigate the preventive and therapeutic efficacy of osteoarthritis using a Yeonsan-Ogye egg. so, we researched at effects of Yeonsan-Ogye egg extract on MIA-induced Osteoarthritis animal models. Methods : Yeonsan-Ogye egg extract was administered 500 mg/kg/day, 1000 mg/kg/day and 2000 mg/kg/day to SD-Rat for 2 weeks. After that, osteoarthritis was induced with $60mg/m{\ell}$ of monosodium iodoacetate (MIA) and futher administration was continued for 4 weeks. 3D imaging of cartilage patella were obtained using a Micro-CT system and the pathology change of knee was observed by H&E and safranin-O staining. The weight bearing ratio was measured by incapacitance test meter. MMP-2, MMP-9, COMP, CTX II, calcitonin and glycosaminoglycan level in serum were measured using a ELISA. Results : Micro-CT and Histopathological analysis showed the volume of the patella cartilage and the proteoglycan contents were increased in all groups. also weight bearing ratio was decreased in all groups compared with control group. Calcitonin production was increased in and 2000 mg/kg/day group and glycosaminoglycan production was increased in all groups. In addition, MMP-2, MMP-9, COMP and CTX II production were decreased in 1000 and 2000 mg/kg/day groups respectively in comparison with control. Conclusions : The results for Yeonsan-Ogye egg showed prevention and treatment efficacy against arthritis at serum and the cartilage. These results may be used a remedy for new korea medicine to ease the symptoms mentioned above. also, suggest that Yeonsan-Ogye egg can be used preventive and therapeutic material for osteoarthritis.

• Restorative Dentistry and Endodontics
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• 제31권3호
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• pp.153-160
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• 2006

본 연구는 치수조직, 치은, 치주인대로부터 배양된 조직을 SP (Substance P)로 4시간 SP, CGRP (Calcitonin Gene-related Peptide) , Tumor necrosis factor-$\alpha$ (TNF-$\alpha$)로 8시간 자극 후 RNase Protection Assay를 시행하고, IL-8의 분비량을 측정해 다음 결과를 얻었다. 1. IL-8 mRNA는 모든세포에서 발현됐다. 2. IL-8 mRNA 발현은 SP ($10^{-5}M$)와 SP ($10^{-8}M$)로 4시간 자극 시 증가되지 않았다. 3. IL-8 mRNA 발현은 SP ($10^{-4}M$)와 CGRP ($10^{-6}M$)로 8시간 자극 시 증가되지 않았다. 4. TNF-$\alpha$ (2 ng/ml) 자극 시, IL-8 mRNA 발현이 증가됐다. 5. 치은 세포를 CGRP ($10^{-6}M$)로 8시간 자극 시, IL-8 분비량이 증가했다 (p<0.05). 6. 치주인대 세포를 SP ($10^{-4}M$)로 8시간 자극 시 IL-8 분비량이 증가했다 (p<0.05).

• 한국가축번식학회지
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• 제24권2호
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• pp.179-188
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• 2000

본 연구는 골다공증유발 rat에 녹용추출물의 투여가 예방 및 치료효과에 미치는 영향을 구명하고자, 양측 난소를 적출한 후 골다공증이 유발된 rat에 암, 수녹용 추출물 625, 1,250 mg/kg을 5 주간 투여하면서 혈청중 estradiol, progesterone, calcitonin, osteocalcin 농도와 Ca, P 및 ALP 함량변화등을 조사하였다. 1. 난소적출 후 골다공증이 유발된 rat에 암, 수녹용 추출물 625mg/kg, 1,250 mg/kg을 각각 투여했을 때 혈청내 estradiol 수준은 난소적출군이 20.80$\pm$1.86~40.50$\pm$pg/$m\ell$로서 정상대조군의 49.50 :t2. 70-50.80 :t3.13 pg/$m\ell$에 비하여 유의한 감소를 나타냈다 (p<0.05). 2. 골다공증 유발 rat 에 암 수녹용 추출물 625 mg/kg, 1,250 mg/kg을 각각 투여했을 때 혈청중 progesterone 수준은 정상대조군의 50.90$\pm$3.63~53.40$\pm$2.74 ng/$m\ell$에 비하여 큰 차이를 나타내지 않았다. 3. 골다공증 유발 rat 에 암, 수녹용 추출물 625 mg/kg, 1,250 mg/kg을 투여했을 때 혈청중 calcitonin 수준은 정상대조군의 0.64$\pm$0.03~0.68$\pm$0.04 pg/$m\ell$에 비 하여 약간 높은 증가를 나타냈으며 특히, 난소적출군은 대조군에 비해 현저한 감소를 나타냈다. 4. 골다공증 유발 rat 에 암, 수녹용 추출물 625 mg/kg, 1,250 mg/kg을 각각 투여했을 때 혈청중 osteocalcin 수준은 정상대 조군의 0.28$\pm$0.02 ~0.31$\pm$0.02 ng/$m\ell$에 비하여 약간 높은치를 나타냈다. 한편, 암, 수녹용 추출물의 처리군의 osteocalcin 치는 암컷녹용 추출물처리군이 약간 높았으나 유의성은 인정되지 않았다. 5. 골다공증유발 rat에 암, 수녹용 추출물을 투여했을 때 혈청중 Ca, P 함량은 각각 정상대조군에 비하여 약간 높은 치를 나타냈으며, 난소적출 무처치군은 대조군에 비해 유의한 증가를 나타냈다 (p＜0.05). 6. 골다공증유발 rat에 암, 수녹용 추출물을 투여했을 때 혈청중 ALP 함량은 정상대조군에 비하여 증가치를 나타냈으며, 암, 수사슴녹용 추출물의 처리군중 대조군과 FA1,250 처리군과 MA625 처리군간에 유의한 변화가 인정되었다 (p＜0.05). 위의 결과들에서 암, 수녹용 추출액은 난소제거후의 estrogen의 감소를 억제시키고 골소실을 억제하므로 골다공증의 예방과 치료에 효과가 있는 것으로 판단된다.

• Journal of Yeungnam Medical Science
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• 제16권2호
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• pp.155-168
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• 1999

Osteoporosis is one of the most important public health problems facing the aging population. Drug therapy for osteoporosis can be divided operationally into two main categories: drugs that inhibit bone resorption, and thus reduce bone turnover, and those that stimulate bone formation, exerting an anabolic effect. Antiresorptive agents such as estrogens, calcitonin, and bisphosphonates are most effective in the prevention of osteoporosis. Formation-stimulating agents such as sodium fluoride or monofluorophosphate, parathyroid hormone fragments, and anabolic steroids are of potential value in the treatment of established osteoporosis, where bone mass is already low and benefit from antiresorptive drugs is likely to be small Recently, raloxifene, a selective estrogen receptor modulator, has become available in various countries for clinical use in the treatment of involutional osteoporsis. This paper will review the use of these drugs in postmenopausal woman.

• The Korean Journal of Physiology and Pharmacology
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• 제10권6호
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• pp.323-327
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• 2006

Despite the wealth of data concerning the roles of ${\alpha}-CGRP$ in nociceptive behaviors, ${\alpha}-CGRP-null$ mice showed no obvious phenotypic differences in nociceptive behaviors from wild type. The present studies specifically demonstrate that ${\alpha}-CGRP$ null mice showed no CGRP immunoreactivity from the spinal cord, implying that CGRPs in the mice spinal cord are mainly a-isoforms. However, the nociceptive behaviors of the null mice are not significantly different from the wild type mice in thermal nociceptive behaviors on hotplate, chemical nociception tests to intraplantar capsaicin or formalin injection, and visceral pain behaviors to intraperitoneal acetic acid or magnesium sulfate injections. These data suggest that ${\alpha}-CGRP$ is dispensable for nociceptive behaviors or that compensatory mechanisms may exist to overcome the absence of this peptide.

• BMB Reports
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• 제56권4호
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• pp.209-215
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• 2023

Maintaining internal homeostasis and regulating innate behaviors are essential for animal survival. In various animal species, a highly conserved neuroendocrine system integrates sensory inputs and regulates physiological responses to environmental and internal changes. Diuretic hormones 44 and 31, which are homologs of mammalian corticotropin-releasing factor (CRF) and calcitonin gene-related peptide (CGRP), respectively, control body fluid secretion in Drosophila. These neuropeptides and their receptors have multiple physiological roles, including the regulation of body-fluid secretion, sleep:wake cycle, internal nutrient-sensing, and CO₂-dependent response. This review discusses the physiological and behavioral roles of DH44 and DH31 signaling pathways, consisting of neuroendocrine cells that secrete DH44 or DH31 peptides and their receptor-expressing organs. Further research is needed to understand the regulatory mechanisms of the behavioral processes mediated by these neuroendocrine systems.

• Restorative Dentistry and Endodontics
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• 제24권1호
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• pp.100-115
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• 1999

The purpose of this study was to investigate the distribution of calcitonin gene-related peptide containing nerve fibers in rat pulp after dentinl injury by means of immunohistochemistry and confocal laser scanning microscope. The Spague-Dawley rats weighing about 250-300gm were used. The animals were devided into normal control and experimental groups. Experimental animals were sacrified 1, 2, 4, 7, 10, 21days after dentinal injury (dentin cutting, and then acid etching with 35% phosphoric acid) on the maxillary molar teeth. The maxillary teeth and alveolar bone were removed and immersed in the 4% paraformaldehyde in 0.1M phosphate buffer (pH 7.4), then were decalcified with 15% formic acid for 10 days. Serial frozen $50{\mu}m$ thick sections were cut on a cryostat. The rabbit CGRP antibody was used as a primary antibody with a dilution of 1:2000 in 0.01M PB. The sections were incubated for 48 hours at $4^{\circ}C$, and placed into biotinylated antirabbit Ig G as a secondary anti body with dilution of 1:200 in 0.01M PB and incubated in ABC(avidin-biotin complex). The peroxidase reaction was visualized by incubating the sections in 0.05% 3,3 diaminobenzidine tetrahydrochloride containing 0.02% $H_2O_2$. For the confocal laser scanning microscopic examination, Primary antibody reaction was same as immunoperoxidase stainning, but fluorescein isothiocyanate(FITC)-conjugate antirabbit IgG as a secondary antibody was used. The confocal laser scanning microscope was used for the examination. A series of images of optical sections was collected with a 20x objective at $3{\mu}m$ intervals throughout the depth of specimen. FITC fluerescence was registrated through a 488nm and 568nm excitation filter, and images were saved on optical disk. The stereoscopic images and three dimentionnal images were reconstructed by computer software, and then were analyzed. The results were as follows : 1. In normal control group, CGRP containing nerve fibers were coursed through the root with very little branching, and then formed a dense network of terminals in coronal pulp. 2. A slight increase in CGRP containing nerve fibers at 1 and 2day postinjury was noted subjacent to the injury site. In the 4day group, there were an extensive increase in the number of reactive fibers, followed by a partial return toward normal levels at 7~10 day postinjury, and return by 21days. 3. The sprouting of the CGRP containing nerve fibers was evident within 2day after dentinal injury, and by 4days there was a maximal increased, but was decreased at 7days and returned to normal 10~21 day postinjury. 4. In confocal laser scanning microscopic exammination, the distinct distribution pattern and sprouting reaction of CGRP containing nerve fibers were observed in stereoscopic images and three dimentional images. These results suggest that CGRP containing nerve fiber can be important role in the response to dental injury and pain regulation.