• Journal of Periodontal and Implant Science
• /
• 제51권6호
• /
• pp.374-385
• /
• 2021

Purpose: The aim of this study was to evaluate the effects of locally delivered 1% alendronate (ALN) gel used as an adjunct to non-invasive periodontal therapy. Methods: Ligature-induced periodontitis was performed in 96 rats. The ligature was tied in the cervical area of the mandibular left first molar. The animals were randomly divided into 4 groups: 1) NT, no treatment; 2) SRP, scaling and root planning; 3) SRP/PLA, SRP followed by filling the periodontal pocket with placebo gel (PLA); and 4) SRP/ALN, SRP followed by filling the periodontal pockets with 1% ALN gel. Histomorphometric (percentage of bone in the furcation region [PBF]) and immunohistochemical (receptor activator of nuclear factor-κB ligand, osteoprotegerin, and tartrate-resistant acid phosphatase) analyses were performed. Data were statistically analyzed, with the threshold of statistical significance set at P≤0.05. Results: The SRP, SRP/PLA, and SRP/ALN groups presented a higher PBF than the NT group (P≤0.01) at 7, 15, and 30 days. The SRP/ALN group presented a higher PBF than the SRP/PLA group in all experimental periods, as well as a higher PBF than the SRP group at 15 and 30 days. No differences were observed in the immunohistochemical analyses (P>0.05 for all). Conclusions: Locally delivered 1% ALN gel used as an adjunct to SRP enhanced bone regeneration in the furcation region in a rat model of experimental periodontitis.

• Korean Journal of Radiology
• /
• 제19권6호
• /
• pp.1161-1171
• /
• 2018

Objective: The aim of this study was to investigate diffusion tensor (DT) imaging-derived properties of benign oligemia, true "at risk" penumbra (TP), and the infarct core (IC) during the first 3 hours of stroke onset. Materials and Methods: The study was approved by the local animal care and use committee. DT imaging data were obtained from 14 rats after permanent middle cerebral artery occlusion (pMCAO) using a 7T magnetic resonance scanner (Bruker) in room air. Relative cerebral blood flow and apparent diffusion coefficient (ADC) maps were generated to define oligemia, TP, IC, and normal tissue (NT) every 30 minutes up to 3 hours. Relative fractional anisotropy (rFA), pure anisotropy (rq), diffusion magnitude (rL), ADC (rADC), axial diffusivity (rAD), and radial diffusivity (rRD) values were derived by comparison with the contralateral normal brain. Results: The mean volume of oligemia was $24.7{\pm}14.1mm^3$, that of TP was $81.3{\pm}62.6mm^3$, and that of IC was $123.0{\pm}85.2mm^3$ at 30 minutes after pMCAO. rFA showed an initial paradoxical 10% increase in IC and TP, and declined afterward. The rq, rL, rADC, rAD, and rRD showed an initial discrepant decrease in IC (from -24% to -36%) as compared with TP (from -7% to -13%). Significant differences (p < 0.05) in metrics, except rFA, were found between tissue subtypes in the first 2.5 hours. The rq demonstrated the best overall performance in discriminating TP from IC (accuracy = 92.6%, area under curve = 0.93) and the optimal cutoff value was -33.90%. The metric values for oligemia and NT remained similar at all time points. Conclusion: Benign oligemia is small and remains microstructurally normal under pMCAO. TP and IC show a distinct evolution of DT-derived properties within the first 3 hours of stroke onset, and are thus potentially useful in predicting the fate of ischemic brain.

• 생명과학회지
• /
• 제29권8호
• /
• pp.888-894
• /
• 2019

류마티스관절염(rheumatoid arthritis)과 골관절염(osteoarthritis) 같은 관절질환은 연골세포(chondrocytes) 감소와 관절연골(articular cartilage)의 분해를 수반한다. 최근, 연골세포의 활성과 연골 항상성(cartilage homeostasis)에 염증성 ROS (reactive oxygen species) burst 및 나이와 관련된 산화적 스트레스(oxidative stress)의 증가와 관련된 연구가 활발히 진행되고 있다. 본 연구는 관절연골로부터 분리한 연골세포의 노화 과정과 나이대별 관절연골에서 항산화 인자들(antioxidants)의 변화를 조사함으로써, 연골세포와 관절연골의 노화 과정 동안 산화적 스트레스로부터 조직을 보호하는 항산화 인자들의 역할을 규명하는데 목적이 있다. 쥐의 관절연골로부터 분리한 연골세포의 연속 계대배양을 통한 노화 과정에서 산화적 스트레스가 증가함을 관찰하였다. 그리고, 노화 유도한 연골세포는 세포내 총 glutathione (GSSG/GSH) 양과 항산화 효소 superoxide dismutase (SOD)와 heme oxygenase-1 (HO-1)의 발현이 증가하였다. 다음으로, 나이대별 쥐로부터 분리한 관절연골에서 항산화 인자의 발현을 분석하였다. 항산화 인자 glutathione의 양은 40주령에서 발현이 가장 높게 관찰되었으며 72주령에 다소 감소하였고, SOD와 HO-1의 발현은 나이대별로 현저히 증가되는 경향을 보였다. 이를 종합해 볼 때, 세포내 항산화 인자들은 과도한 양의 ROS에 반응하여 연골세포의 노화와 나이와 관련된 관절연골의 퇴화 과정에서 중요한 역할을 하는 것으로 보인다.

• 생명과학회지
• /
• 제29권5호
• /
• pp.614-620
• /
• 2019

본 연구는 성장 유도 인자가 포함된 여러 가지의 한약재의 조성물을 활용하여 성장기 흰쥐에서 골성장판 길이, 대퇴부 길이, 골밀도(Bone mineral density) 및 혈액분석을 통해 키 성장 효과를 검증하고자 한다. 먼저, 골성장판 길이 분석 결과, N군에 비해 PC군과 Gh-199군 및 Sh-188군의 골성장판 길이가 전반적으로 증가하였고, 특히 Gh-199군의 경우 PC군보다 더 우수한 골성장판 길이 성장률을 보였다. 대퇴부 길이 및 골밀도 경우 Gh-199군에서 보다 긍정적인 효과를 나타내었다. 반면에 황기분말을 급여한 PC군의 경우, Gh-199군 및 Sh-188군과 달리 높은 혈중 AST 및 ALT 수치를 나타내었다. 성장호르몬 인자 중 하나인 IGF-1의 결과, PC군과 Sh-188군은 비슷한 경향이었으며, Gh-199군에서 보다 증가한 것으로 나타났다. 따라서, 이상의 결과 골성장판, 대퇴부길이, 골밀도 및 혈액분석 결과 모두 Gh-199군에서 긍정적인 결과를 나타내어 본 실험에 사용한 한약재 조성물은 키 성장에 효과가 있을 것으로 기대된다.

• 생명과학회지
• /
• 제31권3호
• /
• pp.346-355
• /
• 2021

이 연구의 목적은 Bacillus polyfermentricus KJS-2 (BP2)와 Bacillus mojavensis KJS-3 (Moja3) 및 이들 균주 복합물의 투여가 혈청 지질 수준을 조절할 수 있는지에 대한 가능성을 밝히기 위한 것이다. 고지질혈증 유발 설치류를 대상으로 균주를 2주 동안 경구 투여한 후 혈액 내 세포수준의 변화, 대사기능 평가, 혈중 지질 수준의 변화를 관찰하였다. 백혈구내 주요세포변화를 측정한 결과 균주 투여에 따른 혈중 백혈구(WBC) 수준에는 크게 영향을 미치지는 않았다. 단위 혈액 내 혈소판(PLT) 수치는 Triton WR-1339처리시 18.4% 감소하였고 약물투여그룹 및 균주 투여그룹에서 다시 정상 그룹 수준으로 회복되었다(p<0.05). Triton WR-1339로 유도된 고지혈증에 의해 적혈구의 기능적인 변화는 초래하지 않았다. 혈중 AST, ALT, BUN, Creatinine 수치는 혼합 균주투여 그룹에서 모두 회복하여 간기능, 신장기능에 영향을 미치지 않았다. 혈중 지질수준 변화는 미생물 균주 투여그룹에서 트리글리세라이드(TG)와 총콜레스테롤(TC) 혈청 수치가 감소했고, 혈청 HDL 콜레스테롤 수치는 증가했다. BP2가 생산하는 SMA의 HMG-CoA reductase 저해율은 atorvastatin에 비해 1,000배 낮은 농도에서 비슷한 활성을 보였다. 또한, 고지혈증 유발 설치류에 미생물 균주의 복합투여는 식이에 영향을 미치지 않으면서 체중증가율은 감소시켰다. 따라서 BP2와 Moja3 균주 복합투여시 혈청 지질 수치를 조절함으로써 혈액 순환을 개선시킬 수 있을 것이다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제25권1호
• /
• pp.59-68
• /
• 2021

Arterial thrombosis and its associated diseases are considered to constitute a major healthcare problem. Arterial thrombosis, defined as blood clot formation in an artery that interrupts blood circulation, is associated with many cardiovascular diseases. Oxidative stress is one of many important factors that aggravates the pathophysiological process of arterial thrombosis. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ref-1) has a multifunctional role in cells that includes the regulation of oxidative stress and anti-inflammatory function. The aim of this study was to investigate the therapeutic effect of adenovirus-mediated Ref-1 overexpression on arterial thrombosis induced by 60% FeCl3 solution in rats. Blood flow was measured to detect the time to occlusion, thrombus formation was detected by hematoxylin and eosin staining, reactive oxygen species (ROS) levels were detected by high-performance liquid chromatography, and the expression of tissue factor and other proteins was detected by Western blot. FeCl3 aggravated thrombus formation in carotid arteries and reduced the time to artery occlusion. Ref-1 significantly delayed arterial obstruction via the inhibition of thrombus formation, especially by downregulating tissue factor expression through the Akt-GSK3β-NF-κB signaling pathway. Ref1 also reduced the expression of vascular inflammation markers ICAM-1 and VCAM-1, and reduced the level of ROS that contributed to thrombus formation. The results showed that adenovirus-mediated Ref-1 overexpression reduced thrombus formation in the rat carotid artery. In summary, Ref-1 overexpression had anti-thrombotic effects in a carotid artery thrombosis model and could be a target for the treatment of arterial thrombosis.

• The Korean Journal of Pain
• /
• 제34권1호
• /
• pp.58-65
• /
• 2021

Background: Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism. Methods: Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague-Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed. Results: Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine. Conclusions: These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.

• 한방재활의학과학회지
• /
• 제31권1호
• /
• pp.17-32
• /
• 2021

Objectives The present study was designed to find out the therapeutic effects and possible underlying mechanism of Buja-tang, a herbal complex formula on experimental monosodium iodoacetate (MIA)-induced osteoarthritis. Methods Osteoarthritis models were created via intra-joint injection of MIA (50 μL with 80 mg/mL) in rats. Rats were divided into five groups and each group consisted of seven. Normal group was not injected MIA and did a normal diet. Control group injected MIA and received distilled water. Indo injected MIA and oral administration of 5 mg/kg of indomethacin. BJTL injected MIA and oral administration of 100 mg/kg of Buja-tang. BJTH injected MIA and oral administration of 200 mg/kg of Buja-tang. We analyzed weight-bearing ability of hind paws, oxidative stress related factor, antioxidant protein, inflammatory protein, inflammatory messenger and cytokine in joint tissue. Pathological observation of knee cartilage tissue structures was also performed with hematoxylin & eosin and safranin-O chromosomes. Results Weight-bearing ability of hind paws showed a tendency to reduce pain. The incidence of nicotinamide adenine dinucleotide phosphate oxidase and p22phox in articular tissue was significantly reduced, and the incidence of nuclear factor-erythroid 2-related factor 2 and heme oxygenase-1 and superoxide dismutases was significantly increased. The incidence of phosphorylated inhibitor of κBα, nuclear factor-kappa B p65, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β decreased significantly. In pathological observation, cartilage tissue damaged by MIAs in biopsy has significantly recovered from Buja-tang administration. Conclusions Buja-tang has anti-inflammation, antioxidation and pain relief effects. So this is thought to inhibit the progress of osteoarthritis in rat caused by the MIA.

• 한방재활의학과학회지
• /
• 제31권1호
• /
• pp.81-93
• /
• 2021

Objectives The objective of the study was to investigate effects of ChondroT by improvement of blood metabolites in high-fat diet (HFD)-induced hyperlipidemia rat model. Methods Sprague-Dawley rats were randomly assigned to intact, control, simvastatin, and CT100, CT200 and CT400 (each n=6). For observing cholesterol change, animals were first fed high fat diet for 5 weeks and then high fat diet and drugs for 3 weeks. At the end of the experiment, total cholesterol, triglyceride, high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were analyzed by obtained blood collection. Further, amplified leptin, peroxisome proliferator activated receptor (PPAR) and adiponectin DNA were observed by reverse transcription polymerase chain reaction analysis. Results Observing the effect of ChondroT on the change of lipid metabolism in hyperlipidemia-induced rats, triglyceride and total cholesterol were significantly decreased in SV100 group, HDL-C was significantly increased in SV100, CT100 and CT200 groups, and LDL-C was significantly decreased in SV100, CT100, CT200 and CT400 groups, compared to the control group. Leptin level in hyperlipidemia-induced rats was significantly decreased in CT100 and CT200 groups, compared to the control group. The effect of ChondroT on adiponectin level in hyperlipidemia-induced rats was significantly increased in SV100, CT100 and CT200 groups. PPAR level in hyperlipidemia-induced rats was significantly decreased in SV100, CT200 and CT400 groups. Platelete activating factor level in hyperlipidemia-induced rats was significantly decreased in CT100 and CT200 groups. Conclusions Based on these results, it could be suggested that ChondroT has certain effects of improving blood metabolites in HFD-induced hyperlipidemia.

• 한국응용과학기술학회지
• /
• 제38권2호
• /
• pp.368-377
• /
• 2021

본 연구는 방사선 형질전환 차조기와 백출복합물(차조기 복합물)이 퇴행성관절염 관련 매개체에 미치는 영향을 확인하고자 MIA(monosodium iodoacetate)로 퇴행성관절염을 유도한 랫드로 평가하였다. 차조기 복합추출물을 2주 동안 25, 50, 100 mg/kg/day의 용량으로 경구 투여하고 랫드의 우측관절 내 공간에 MIA를 주입한 후 동일 용량을 4주 동안 지속 투여하였다. 이후, 혈청 바이오마커와 무릎 관절 분석의 형태학 및 조직병리학적 분석에 기초한 치료 효과를 평가하였다. 대조군 랫드와 비교하였을 때 차조기 복합추출물은 혈청 내 염증 및 골 대사 마커(TNF-α, MMP-3, COX-2, PGE₂, COMP, Aggrecan)의 생성량을 유의하게 감소시켰다. 이와는 반대로 연골 흡수 매개체인 CTX-2 생성을 증가시켰으며, 방사선 형질전환 차조기는 무릎 연골과 활막을 효과적으로 보존하였다. 그 결과, 차조기 복합물은 퇴행성관절염 증상을 개선하였다. 따라서, 차조기 복합물은 퇴행성관절염 관리를 위한 식품소재로 사용될 수 있다.