• Journal of Korean Neurosurgical Society
• /
• v.64 no.5
• /
• pp.693-704
• /
• 2021

Objective : Endovascular mechanical thrombectomy (MT) has been regarded as one of the standard treatments for acute ischemic stroke caused by large vessel occlusion. Despite the wide use of stent retrievers for MT, arterial intimal damage caused when deployed stent is pulled has been a certain disadvantage. We hypothesized that statin could protect and stabilize vessel damage after endovascular MT using a stent retriever. In this animal study, we observed the protective effects of the statins towards MT-induced vessel wall injury. Methods : Twenty-eight carotid arteries of fourteen rabbits were used in the experiments with MT using stent retriever. We divided the rabbits into four groups as follows : group 1, negative control; group 2, positive control; group 3, statin before MT; and group 4, statin after MT. After MT procedures, we harvested the carotid arteries and performed histomorphological and immunohistochemical analyses. Results : In histomorphological analysis with hematoxylin and eosin and Masson's trichrome stain, significant intimal thickening (p<0.05) was observed in the positive control (group 2), compared to in the negative control (group 1). Intimal thickening was improved in the statin-administered groups (groups 3 and 4 vs. group 2, p<0.05). We also observed that statin administration after MT (group 4) resulted in a more effective decrease in intimal thickness than statin administration before MT (group 3) (p<0.05). We performed immunohistochemical analysis with the antibodies for tumor necrosis factor-alpha (TNF-α), cluster of differentiation (CD)11b, and CD163. In contrast to the negative control (group 1), the stained percentage areas of all immunological markers were markedly increased in the positive control (group 2) (p<0.05). Based on statin administration, the percentage area of TNF-α staining was significantly reduced (p<0.05) in group 3, compared to the positive control group (group 2). However, significant differences were not observed for CD11b and CD163 staining. In group 4, no significant differences were observed for TNF-α, CD11b, and CD163 staining (p≥0.05). The differences in the percentage areas of the different markers between the statin-administered groups (groups 3 and 4) were also not revealed. Conclusion : We presented that statin administration before and after MT exerted protective effects towards vessel wall injury. The efficacy of statins was greater post-administration than pre-administration. Thus, statin administration in routine prescriptions in the peri-procedural period is strongly advised.

• BMB Reports
• /
• v.56 no.3
• /
• pp.196-201
• /
• 2023

Renal fibrosis is the final manifestation of chronic kidney disease (CKD) regardless of etiology. Hypoxia-inducible factor-2 alpha (HIF-2α) is an important regulator of chronic hypoxia, and the late-stage renal tubular HIF-2α activation exerts protective effects against renal fibrosis. However, its specific role in progressive renal fibrosis remains unclear. Here, we investigated the effects of the long-term tubular activation of HIF-2α on renal function and fibrosis, using in vivo and in vitro models of renal fibrosis. Progressive renal fibrosis was induced in renal tubular epithelial cells (TECs) of tetracycline-controlled HIF-2α transgenic (Tg) mice and wild-type (WT) controls through a 6-week adenine diet. Tg mice were maintained on doxycycline (DOX) for the diet period to induce Tg HIF-2α expression. Primary TECs isolated from Tg mice were treated with DOX (5 ㎍/ml), transforming growth factor-β1 (TGF-β1) (10 ng/ml), and a combination of both for 24, 48, and 72 hr. Blood was collected to analyze creatinine (Cr) and blood urea nitrogen (BUN) levels. Pathological changes in the kidney tissues were observed using hematoxylin and eosin, Masson's trichrome, and Sirius Red staining. Meanwhile, the expression of fibronectin, E-cadherin and α-smooth muscle actin (α-SMA) and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was observed using western blotting. Our data showed that serum Cr and BUN levels were significantly lower in Tg mice than in WT mice following the adenine diet. Moreover, the protein levels of fibronectin and E-cadherin and the phosphorylation of p38 MAPK were markedly reduced in the kidneys of adenine-fed Tg mice. These results were accompanied by attenuated fibrosis in Tg mice following adenine administration. Consistent with these findings, HIF-2α overexpression significantly decreased the expression of fibronectin in TECs, whereas an increase in α-SMA protein levels was observed after TGF-β1 stimulation for 72 hr. Taken together, these results indicate that long-term HIF-2α activation in CKD may inhibit the progression of renal fibrosis and improve renal function, suggesting that long-term renal HIF-2α activation may be used as a novel therapeutic strategy for the treatment of CKD.

• Journal of Korean Medicine Rehabilitation
• /
• v.33 no.2
• /
• pp.1-18
• /
• 2023

Objectives The purpose of this study was to evaluate the antioxidant, anti-inflammatory and wound healing effects of Samul-tang-ga-dansam water extract (SD) in wound-induced mice. Methods The mice were divided into five groups (n=7): the normal group, the control group, the positive control group, the low-dose SD group and the high-dose SD group. The normal group had no wounds and the other groups were wounded on the back with a leather punch. Distilled water was administered to the control group, 200 mg/kg of vitamin E was administered to the positive control group. In the low-dose SD group and the high-dose SD group, 1.23 g/kg and 2.47 g/kg of SD were administered, respectively. Antioxidant and anti-inflammatory protein levels were evaluated using western blot analysis. Skin tissue was analyzed by H&E, Masson's trichrome staining method. Results Oral administration of the SD significantly reduced the visible skin damage and decreased the reactive oxygen species and ONOO^- activity of the serum. It significantly increased heme oxygenase-1, superoxide dismutase, catalase, GPx-1/2, Nrf2 and Keap-1 which are antioxidant-related factors in skin tissue and reduced NF-κB p65, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor α, interleukin (IL)-1β, IL-6 which are inflammation-related factors. Also, SD significantly decreased NOX2, p22^phox and p47^phox and increased α-smooth muscle actin and COL1A1 protein expression in fibroblasts involved in connective tissue repair. According to histological examination, the thickened epithelial layer was thinned and collagen fibers were increased to accelerate wound healing. Conclusions It is suggested that Samul-tang-ga-dansam has antioxidant and anti-inflammatory effects and promotes wound tissue repair.

• Journal of Veterinary Clinics
• /
• v.40 no.2
• /
• pp.93-103
• /
• 2023

The tendon is a dense connective tissue that connects muscle to bone and plays an essential role in joint motion. The injured tendon heals slowly owing to its low cellularity and vascularity. This study aimed to evaluate and compare the effects of regenerative injection therapy (RIT), 20 % dextrose prolotherapy (DP), and platelet-rich plasma (PRP) injections that can promote tendon healing. Twenty-one New Zealand white rabbits were divided into the control, DP, and PRP treatment groups. The superficial digital flexor tendon (SDFT) of the right hindlimb of each rabbit was used. A round defect of 2 mm was induced. Approximately 0.2 mL of 20% dextrose and autologous PRP were injected into the proximal and distal ends of the SDFT mass. Radiographic and ultrasonographic examination and cross-sectional area (CSA) calculations were performed pre-operatively and at 2, 4, and 8 weeks. The SDFT of both limbs was transected for biomechanical and histomorphometric evaluations. The SDFT of the left limb was transected for intact control. Semi-quantitative analysis was performed to evaluate the histomorphometric properties. Additional analysis was performed using H&E, Masson's trichrome, and immunohistochemical staining. The biomechanical evaluation showed that the treatment groups had higher tensile strength compared to the defect control group, while the PRP group had higher tensile strength than the DP group. On histological examination, the treatment groups appeared to be relatively closer to the remodeling phase of the healing process than the defect control group; the characteristics of the PRP group were closer to the remodeling phase than those of the DP group. The ultrasonographic examination showed different tendencies. Increased values in the CSA were observed during the early period in the treatment groups. This study suggests that PRP and DP can promote the healing of tendon injury, and these effects were superior with PRP than that with DP.

• Korean Journal of Radiology
• /
• v.21 no.12
• /
• pp.1294-1304
• /
• 2020

Objective: To determine whether T1 mapping could monitor the dynamic changes of injury in myocardial infarction (MI) and be histologically validated. Materials and Methods: In 22 pigs, MI was induced by ligating the left anterior descending artery and they underwent serial cardiovascular magnetic resonance examinations with modified Look-Locker inversion T1 mapping and extracellular volume (ECV) computation in acute (within 24 hours, n = 22), subacute (7 days, n = 13), and chronic (3 months, n = 7) phases of MI. Masson's trichrome staining was performed for histological ECV calculation. Myocardial native T1 and ECV were obtained by region of interest measurement in infarcted, peri-infarct, and remote myocardium. Results: Native T1 and ECV in peri-infarct myocardium differed from remote myocardium in acute (1181 ± 62 ms vs. 1113 ± 64 ms, p = 0.002; 24 ± 4% vs. 19 ± 4%, p = 0.031) and subacute phases (1264 ± 41 ms vs. 1171 ± 56 ms, p < 0.001; 27 ± 4% vs. 22 ± 2%, p = 0.009) but not in chronic phase (1157 ± 57 ms vs. 1120 ± 54 ms, p = 0.934; 23 ± 2% vs. 20 ± 1%, p = 0.109). From acute to chronic MI, infarcted native T1 peaked in subacute phase (1275 ± 63 ms vs. 1637 ± 123 ms vs. 1471 ± 98 ms, p < 0.001), while ECV progressively increased with time (35 ± 7% vs. 46 ± 6% vs. 52 ± 4%, p < 0.001). Native T1 correlated well with histological findings (R² = 0.65 to 0.89, all p < 0.001) so did ECV (R² = 0.73 to 0.94, all p < 0.001). Conclusion: T1 mapping allows the quantitative assessment of injury in MI and the noninvasive monitoring of tissue injury evolution, which correlates well with histological findings.

• Journal of Life Science
• /
• v.28 no.2
• /
• pp.141-147
• /
• 2018

This study aimed to analyze the contents of rutin, procyanidin B3, quercetin, and kaempferol, known to have antioxidant, anti-inflammatory, and anti-carcinogenic effects, among the polyphenol types contained in grape pruning stem extracts (GPSE). It utilized grape stems discarded after harvest to measure the effects of GPSE on skin moisture, inhibition of skin cell proliferation, and anti-inflammatory activity on the damaged skin of HR-1 mice induced with ultraviolet B (UVB), and to verify the applicability of GPSE as a material for functional food and functional cosmetics. The polyphenol was extracted from grape pruning stems with 80% EtOH, and then the extract was used while storing at $-20^{\circ}C$, after filtering, concentrating, and freeze-drying it. The content of an active ingredient of GPSE was analyzed using high performance liquid chromatography (HPLC). From 53 kg of the grape pruning stem specimen, 2.34 kg of the EtOH fraction extracts were extracted to achieve a 4.42% yield ratio. Analysis of the active ingredients showed 0.28 mg/g of procyanidin B3, 12.81 mg/g of rutin, 0.51 mg/g of quercetin, and 8.24 mg/g of kaempferol. After UVB irradiation on the dermis, to confirm the degree of inhibition of collagen synthesis, we examined the protein expression of MMP-9 using immunohistochemical staining. The results of this study confirm the existence of active polyphenol types, such as rutin, kaempferol, quercetin, and procyanidin B3, in GPSE. Moreover, the study found that GPSE has anti-collagenase effects and it decreases the effects of UV damage on skin barrier function. GPSE is a functional ingredient with a potential for skin protection effects, and it has high utilization potential as an ingredient for functional cosmetics.

• The korean journal of orthodontics
• /
• v.29 no.5 s.76
• /
• pp.535-549
• /
• 1999

The Purposes of this study were to investigate the initial tissue changes on the teeth and surrounding tissues under contraction and intrusive force by contraction UTA. A control and experimental dogs, 10-months in age, were studied. Contraction and intrusive force(60gm) were applied at upper four incisors by contraction UTA. Experimental dogs were sacrificed at 2 weeks and 4 weeks after force application, respectively. In this study, 2 experimental groups were designed by the duration of force applied(E1, E2). The specimens were taken around the upper first and second incisor in each groups and were prepared for the H-E and MT stain for light microscopic observation. From the results of the study, the following conclusions may be drown. : 1. In control group, the periodontal ligament width was constant from apical third to cervical third of the root and periodontal fiber arrangement was horizontal or oblique in cervical third, oblique in middle third and apical third. In alveolar bond, smooth appearance was shown with osteoblast. 2. In experimental group 1, in proportion to force was concentrated at labial middle third and apical third of root of the upper first and second incisors, root of these tooth tipped labially and intruded at a time. 3. In experimental group 2, periodontal ligament width and arrangement was similar to control and observed strong calcified response at the labial middle third of root. But, alveolar bond resorption and cementum resorption were as before seen at labial middle third and apical third of root that force was concentrated.

• The korean journal of orthodontics
• /
• v.29 no.5 s.76
• /
• pp.551-562
• /
• 1999

This study was undertaken to investigate the relation between orthodontic force magnitude and the amount of tooth movement. And more light force application for reducing root resorption Twenty-four rats were divided into three experimental groups(A, B, C) based on force magnitude and application method. Springs of 50g force were applied to A group, springs of 100g force were applied to B group and springs of 25g force were applied to C group initially, and after 4 days springs of C group were changed to springs of 50g force. Two kinds of $sentally^{(R)}$(GAC U.S.A.) closed coil spring, 50g and 100g, were used. And we made 25g springs by heat treatment process of 50g springs. Each spring was inserted between the maxillary central incisor and the maxillary left first molar. Amounts of tooth movement were measured everyday by digital caliper($Digimatic^{(R)}$, Mitutoyo, Japan) under inhalation anesthesia for 15 days. After 15 days, all rats were sacrificed and histological samples were obtained with Hematoxyline-Eosin stain and Masson's trichrome stain. Following conclusion were made; 1. Group B showed the mean cumulative tooth movement of $2.19{\pm}0.41mm$ at 15th day, which was greatest among three groups, followed by group C($2.06{\pm}0.10mm$), group A($1.90{\pm}0.49mm$) respectively. however, there was no statistically difference among three groups. 2. All groups showed general tooth movement pattern and A, B, C group finished lag phase at 9th, 8th, 7th day, but there was no statistical significance. 3. Group A,B,C showed root resorption and especially group B showed the most severe root resorption and group C showed milder root resorption than other groups. According to the above results, large initial force with the development of a flirty widespread hyalinized zone may cause severe root resorption, so initial force should be applied lightly to reduce hyalinized area and eventually root resorption and then increased force will induce efficient tooth movement.

• The korean journal of orthodontics
• /
• v.28 no.1 s.66
• /
• pp.85-97
• /
• 1998

The purpose of this study was to observe the effects of sodium fluoride on the bony repair and regeneration processes after the rapid palatal expansion in the growing dogs. Eighteen dogs were divided into experimental and control groups. They were in the late mixed dentition. The rapid Palatal expansion was undertaken in all the animals($180^{\circ}$ turn/day) for ten days. The animals were sacrificed on 0, 15 and 45 days after the finish of expansion. One mg NaF/kg of body weight/day were given orally to the experimental group. Blood samples were drawn before and after expansion and the se겨m calcium, phosphate and alkaline phosphatase level were measured. The undecalcified bone section of midpalatal suture area was made, and observed under the light microscopy The results were as follows ; 1. The day after expansion, the infiltration of inflammatory cells were prominent and the new bone formation started at the edges of the two palatal plates bodering the midpalatal suture in both groups. Especially, the newly formed osteoid were very extensive and the osteoblasts lining the osteoid were very active in the experimental group. 2. At fifteen days after expansion, the active osteoblasts lining the osteold at the surface of trabecular bony spicules and active new bone formation were observed in the both groups. However, the cellular activity and new bone formation were more prominent In the experimental group. 3. At forty five days after expansion, the continuous osteoid and new bone formation and active osteoblasts were observed in the experimental group. But these phenomena were not observed in the control group. In the control group, the numerous osteoclasts were adjacent midpalatal suture and the bony remodeling process was begun. The serum alkaline phosphatase level was maintained highly in the experimental group, but decreased in the control. According to the above results, the author reached the conclusion that sodium fluoride has the stimulation effects on the osteoid production of the osteoblasts during the healing process after the rapid Palatal expansion more continuously.

• Tuberculosis and Respiratory Diseases
• /
• v.39 no.2
• /
• pp.131-140
• /
• 1992

In order to investigate the changes of hydroxyproline amount and pathologic finding in rat lung which were instilled the natural coal and free silica dust intratracheally, the subjects were divided into two groups as follows. The control group was only administered intratracheally 0.5 ml of normal saline, and the experimental groups were instilled at once the turbid solution containing 10 mg, 30 mg and 50 mg of natural coal and free silica dust each, subjects were sacrified at the 3rd and the 20th week each after the experiment. Hydroxyproline amount in the right upper lung was measured by Woessner method and HPLC (modified Dunphy) method, and the pathlogic finding of lung tissue were observed for hematoxylin-eosin staining, Bielschowski method and Masson's trichrome method. The results were as follows. 1) The wet lung weights of all experimental groups excluding in the groups instilled 10 mg and 30 mg of natural coal dust at 3rd week, were significantly increased (p<0.05) compared with control group. The weight in each free silica group was markedly increased (p<0.05) at 20th week compared with the same dose of natural coal dust group, while the weight in the same dose group of free silica dust was increased significantly at 20th week compared with at 3rd week. 2) The amount of hydroxyproline were significantly increased (p<0.05) in the natural coal and free silica groups at 20th week compared with the control groups, and in each experimental group instilled the same kind and dose of dust, its amount was markedly increased (p<0.05) at 20th week compared with at 3rd week. And also the hydroxyproline in 30 mg and 50 mg free silica groups increased markedly (p<0.05) at 20th week compared with the natural coal dust of the same dose. 3) The polymorphonuclear leukocytes, fibroblasts and macrophages in interstitium and alveolar space showed the increasing tendency in the free silica group more markedly than in the natural coal dust group. The exudate in alveolar space at 3rd week was disappeared at 20th week, and pneumoconiotic nodules observed microscopically in all experimental groups at 20th week, while the nodules apeared already at 3rd week in the 30 mg and 50 mg free silica dust groups. The significant increase of Hydroxyproline content in lung tissue and pneumoconiotic nodule formation in experimental groups found in this study indicate that the observation period, dust amount and kind of dust is important factors associated with pneumoconiosis. And these findings were generally more severe in free silica dust groups than in natural coal groups.