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1.
J Clin Med ; 9(5)2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32413997

RESUMO

To assess the long-term effects of tadalafil, a therapeutic agent for fetal growth restriction (FGR), we evaluated the developmental progress of 1.5-year-old infants whose mothers had taken tadalafil during pregnancy. Twenty-four infants were assessed. We evaluated infant body weight, height, and head circumference, and performed the Kyoto Scale of Psychological Development (KSPD) test, a standardized developmental assessment covering Postural-Motor (P-M), Cognitive-Adaptive (C-A), and Language-Social (L-S) functions. The sum score was converted to a developmental quotient (DQ). The mean gestational week of the included cases was 36.1 (29-39) weeks, and the mean birth weight was 1841 (874-2646) g. Twenty-one and 20 out of the 24 cases, respectively, attained body weight and height similar to those of age-matched normal infants (within the 3rd percentile); all cases caught up in head circumference. KSPD was performed for 18 cases at 1.5 years of corrected age. The mean DQ scores were 87 (in total): 82 in P-M, 90 in C-A, and 88 in L-S. The total DQ score in one case (5.6%) was less than 70, and ranged from 70 to 85 in five cases (27.7%), and was more than 85 in 11 cases (61.1%). The growth and development of infants born of tadalafil-treated mothers seem to show good progress at a corrected age of 1.5 years.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32359130

RESUMO

An analysis is presented of four short-term retrieved highly crosslinked polyethylene (HXLPE) hip liners grafted with 2-methacryloyloxyethyl phosphorylcholine (MPC) on their bearing surfaces, which were recently commercialized as a new generation of artificial hip joints. Straightforward evidences by X-ray photoelectron spectroscopy (XPS) confirmed that the MPC layer peeled off on the bearing surface of all short-term liners in both main wear and nonwear zones. Analyses by Fourier-transform infrared spectroscopy with attenuated total reflection assessed the extent of surface oxidation and revealed the type of oxidative species. Electron spin resonance analyses, which compared retrievals and as-received samples, revealed the presence of different species of alkoxyl CO• radicals. This study suggests that MPC grafts on polyethylene do not offer any additional protection from oxidation and can delaminate prematurely after short-term in vivo exposure.

3.
Int J Mol Sci ; 21(10)2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32429268

RESUMO

Interleukin-6 (IL-6) is widely accepted to stimulate osteoclasts. Our aim in this study was to examine whether the inhibitory effect of IL-6 on bone loss and skeletal pain associated with osteoporosis in hindlimb-unloaded (HU) mice in comparison with bisphosphonate. Eight-week-old male ddY mice were tail suspended for 2 weeks. Starting immediately after reload, vehicle (HU group), alendronate (HU-ALN group), or anti-IL-6 receptor antibody (HU-IL-6i group) was injected subcutaneously. After a 2-week treatment, pain-related behavior was examined using von Frey filaments. The bilateral distal femoral and proximal tibial metaphyses were analyzed three-dimensionally with micro-computed tomography. Calcitonin gene-related peptide (CGRP) expressions in dorsal root ganglion (DRG) neurons innervating the hindlimbs were examined using immunohistochemistry. HU mice with tail suspension developed bone loss. The HU mice showed mechanical hyperalgesia in the hindlimbs and increased CGRP immunoreactive neurons in the L3-5 DRG. Treatment with IL-6i and ALN prevented HU-induced mechanical hyperalgesia and upregulation of CGRP expressions in DRG neurons. Furthermore, ALN but not IL-6i prevented HU-induced bone loss. In summary, treatment with IL-6i prevented mechanical hyperalgesia in hindlimbs and suppressed CGRP expressions in DRG neurons of osteoporotic models. The novelty of this research suggests that IL-6 is one of the causes of immobility-induced osteoporotic pain regardless improvement of bone loss.

4.
J Foot Ankle Surg ; 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32345509

RESUMO

Dorsal dislocation of the interphalangeal joint of the great toe is quite rare. Closed reduction is often attempted in the emergency setting, but this measure is seldom successful because of invagination of the sesamoid-plantar plate complex into the interphalangeal space. Generally, open reduction is indicated when closed reduction fails. In this report, percutaneous reduction of the incarcerated sesamoid was performed under local and intraarticular anesthesia at our outpatient clinic, leading to successful reduction.

5.
J Orthop Sci ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32173180

RESUMO

BACKGROUND: The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. METHODS: We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. RESULTS: The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. CONCLUSION: The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex.

6.
Cartilage ; : 1947603520912300, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32204600

RESUMO

OBJECTIVE: TNIIIA2 is a peptide of the extracellular matrix glycoprotein tenascin-C. We evaluated whether intra-articular injection of TNIIIA2 could prevent articular cartilage degeneration without inducing synovitis in an osteoarthritis mice model. DESIGN: Ten micrograms per milliliter of TNIIIA2 were injected into the knee joint of mice (group II) to evaluate the induction of synovitis. The control group received an injection of phosphate buffered saline (group I). Synovitis was evaluated using synovitis score 2 and 4 weeks after injection. The ligaments of knee joints of mice were transected to make the osteoarthritis model. After transection, 10 µg/mL of TNIIIA2 was injected into the knee joint (group IV). The control group received an injection of phosphate buffered saline after transection (group III). Histologic examinations were made using hematoxylin and eosin and safranin-O staining at 2, 4, 8, and 12 weeks postoperatively. An in vitro study was also performed to determine the mechanism by which TNIIIA2 prevents cartilage degeneration. Human chondrocytes were isolated, cultured, and treated with TNIIIA2. The expressions of various mRNAs, including inflammatory cytokines, and anabolic and catabolic factors for cartilage were compared using real-time polymerase chain reaction. RESULTS: There were no differences between groups in the study of intra-articular injection of mice (group I vs. group II). In the osteoarthritis model, we found development of osteoarthritis was suppressed in group IV at 4 and 8 weeks. TNIIIA2 upregulated the expressions of tumor necrosis factor-α, matrix metalloproteinase 3, and basic fibroblast growth factor. CONCLUSION: We demonstrated that TNIIIA2 could prevent cartilage degeneration without synovitis.

7.
Biol Pharm Bull ; 43(2): 266-271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32009116

RESUMO

Bleeding is a life-threating side effect of thromboprophylaxis with fondaparinux sodium (FPX) injection. The purpose of this retrospective study was to assess the risk factor for bleeding-related event following thromboprophylaxis with FPX after total knee arthroplasty (TKA) or total hip arthroplasty (THA). Adult patients undergoing TKA or THA at a single university hospital were administered FPX for thromboprophylaxis by subcutaneous injection of 1.5 or 2.5 mg per day. The risk factor for bleeding-related event was identified by propensity score-adjusted multivariate logistic analysis, and survival analysis was performed retrospectively in consideration of the identified risk factors. Two hundred and twenty-six patients who underwent TKA (n = 62) or THA (n = 164) were enrolled. Anaemia on postoperative day (POD) 1 was identified as a risk factor for bleeding-related event (odds ratio: 3.75, 95% confidence interval: 1.02-24.5, p = 0.04). Eighty of 226 patients were selected using a propensity score matching and patients with anaemia on POD1 in this population had a significantly higher incidence of bleeding-related event than those without anaemia (p = 0.0016, Ghen-Breslow-Wilcoxon test; p = 0.0015, log-rank test). These results suggest that anaemia on POD1 is an independent risk factor for bleeding-related event following thromboprophylaxis with FPX after TKA or THA.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32049932

RESUMO

STUDY DESIGN: Biochemical and immunohistochemical analyses by the human intervertebral disc (IVD) cells and tissues. OBJECTIVE: To examine the expression of glial cell line-derived neurotrophic factor (GDNF) and its receptors, GDNF family receptor (GFR) α1 and rearranged during transfection (RET) in the human IVD cells and the tissues with the early and advanced stages of degeneration. SUMMARY OF BACKGROUND DATA: The neurotrophin family, including nerve growth factor (NGF), has been reported to be expressed in the IVDs and plays a role in hyperalgesia and neuronal sensitization. Despite having properties similar to the NGF, the expression of GDNF in the IVD remains unknown. METHODS: Human IVD cells were cultured in monolayer. Immunohistochemical analyses and western blotting were performed to examine the protein levels of GDNF and its receptors. To examine the effect of proinflammatory cytokines, cells were cultured in the presence of interleukin-1ß (IL-1ß). The immunohistochemical expression of these proteins was also evaluated using human IVD tissues with different stages of degeneration. RESULTS: Immunofluorescent reactivity against anti-GDNF, GFRα1, and RET antibodies was identified in human IVD cells. In protein extracts from IVD cells, those protein expressions were also identified by Western blot. IL-1ß significantly stimulated the mRNA expression of GDNF compared to that of the control group. There was no significant effect of IL-1ß on the mRNA expression of GFRα1 and RET. The percentage of GDNF-immunopositive cells in advanced degenerated discs was significantly higher than that in early degenerated discs, whereas those of GFRα1 and RET showed no significant differences. CONCLUSIONS: GDNF and its receptors were constitutively expressed in the human IVD cells. GDNF expression was significantly enhanced by proinflammatory stimuli, and in the microenvironment with advanced tissue degeneration. LEVEL OF EVIDENCE: N/A.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32030502

RESUMO

PURPOSE: The purpose of this study was to evaluate whether tendoscopic peroneal retinaculum repair for patients with recurrent peroneal tendon dislocation (RPTD) is more useful than an open procedure. METHODS: Twenty-five patients with RPTD were retrospectively reviewed. Twelve patients (13 ankles) with RPTD underwent the open procedure (Group A) between 2008 and 2014, and 13 patients (14 ankles) underwent the tendoscopic procedure (Group B) between 2014 and 2017. Evaluation parameters included clinical results [the Japanese Society for Surgery of the Foot (JSSF) ankle-hind foot scale], operation time, complications, return to sports, and recurrence. RESULTS: Postoperative JSSF ankle/hindfoot scale scores were significantly better than the pre-surgical scores in both groups. The mean operation time was significantly longer in Group B than in Group A (75.7 ± 20.5 vs 38.4 ± 10.5 min). There was one recurrence in Group A, but none in Group B. Group A had no complications, and Group B had one wound infection. Group B, excluding the case of infection, could return to sports earlier than Group A, excluding the recurrent case (13.4 ± 1.5 vs 12.2 ± 0.6 weeks). CONCLUSIONS: This tendoscopic procedure needs longer operation time and is more technically demanding, but it is a useful procedure, because it is less invasive and can accelerate return to sports. LEVEL OF EVIDENCE: III.

10.
Arch Osteoporos ; 15(1): 7, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898803

RESUMO

Here, we report the case of a 69-year-old female who discontinued denosumab to undergo dental treatment. She subsequently suffered rebound-associated vertebral fractures (RVFs) twice. Denosumab is approved in several countries for osteoporosis treatment. Its discontinuation can result in bone turnover rebound increase and rapid bone mineral density loss. Rebound-associated vertebral fractures (RVFs) after discontinuing denosumab have been widely reported. We previously reported the case of a patient who suffered RVFs after discontinuing denosumab to undergo dental treatment. A 69-year-old female suffered five acute VFs 10 months after the last denosumab injection. The current report identifies the risks associated with denosumab discontinuation to undergo dental treatment. The patient described in this report also underwent an additional clinical course after the first RVFs. Next month after the first RVFs, she developed severe back pain when she changed her posture. Magnetic resonance imaging showed new RVFs at T9 and T12 levels. This case indicates that RVFs may occur more than once. In addition, it suggests that additional denosumab injections do not completely eliminate the risk of RVFs.

11.
Mod Rheumatol ; 30(1): 178-183, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30501428

RESUMO

Background: Previous epidemiological studies on locomotive syndrome (LS) have been mainly conducted in retired elderly people. However, from the view point of its prevention, it is important to assess currently working younger people. The purpose of this study was to examine the status of the level of LS in young and middle-aged adult workers.Methods: This cross-sectional study was performed at four companies. We used the two-step test, stand-up test, and 25-question Geriatric Locomotive Function Scale (GLFS-25) as screening tools of LS. We also questioned the subjects for knee pain and low back pain.Results: A total of 715 workers participated in this study. The percentage of females with LS increased with age. However, the percentage of males with LS was approximately 20% in each age category. Two-step and stand-up test scores worsened in an age-dependent manner, although GLFS-25 scores varied independently of age. Knee pain, low back pain and physical activity were significantly related to LS-level.Conclusion: Our results suggest that there is some degree of LS even in young and middle-aged adults. Knee pain, low back pain and physical activity levels are key factors related to LS even in young and middle-aged adults.

12.
J Orthop Surg (Hong Kong) ; 28(1): 2309499019893194, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31833446

RESUMO

PURPOSE: The aim of this study was to examine the inhibitory effect of teriparatide (TPTD) on pain and on bone loss in ovariectomized (OVX) mice. The mechanism of osteoporotic pain in OVX mice was evaluated through an examination of pain-related behavior as well as immunohistochemical examinations. METHODS: Eight-week-old female ddY mice were OVX and assigned to one of three groups: (1) OVX mice treated with vehicle (OVX), (2) OVX mice treated with teriparatide (OVX-TPTD), or (3) SHAM-operated mice treated with vehicle (SHAM). Starting immediately after surgery, vehicle or TPTD was injected subcutaneously. After a 4-week treatment, mechanical sensitivity was tested using von Frey filaments. The proximal tibial metaphyses were analyzed three-dimensionally by microcomputed tomography (µCT). Calcitonin gene-related peptide (CGRP) and transient receptor potential channel vanilloid 1 (TRPV1) expressions in L3-5 dorsal root ganglion (DRG) neurons were examined using immunohistochemistry. RESULTS: Ovariectomy induced bone loss and mechanical hyperalgesia in the hind limbs with upregulation of CGRP and TRPV1 expressions in DRG neurons innervating the hind limbs. Bone loss was prevented more effectively in the OVX-TPTD mice than in the OVX mice. Furthermore, mechanical hyperalgesia and upregulation of CGRP and TRPV1 expressions were significantly lower in the OVX-TPTD mice than in the OVX mice. CONCLUSION: TPTD treatment prevented ovariectomy-induced bone loss and ovariectomy-induced mechanical hyperalgesia in hind limbs, and it suppressed CGRP and TRPV1 expressions in DRG neurons. These results suggest that TPTD is useful for the treatment of osteoporotic pain in postmenopausal women.

13.
Anticancer Res ; 39(12): 6871-6875, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810955

RESUMO

BACKGROUND/AIM: The aim of the present study was to determine whether serum lactate dehydrogenase (LDH) levels before treatment could predict the disease-specific and event-free survival in adult patients with STS. PATIENTS AND METHODS: A total of 142 adult patients with primary STS were reviewed. The average follow-up was 73 months with a minimum 2-year follow-up. RESULTS: Age was significantly associated with LDH. Tumor grade, sex, tumor size, tumor depth, CRP levels, Hb levels and albumin levels were not related. LDH levels were not significantly related to the oncological outcome including disease-specific survival and event-free survival in multivariate analysis. CRP levels were significantly related to the oncological outcome including event-free survival. CONCLUSION: Elevated LDH levels prior to initial treatment were not found to be a poor prognostic factor of oncological outcome in adult STS, in both the univariate and multivariate analyses. We recommend routine measurement of the CRP levels for predicting oncological outcome.


Assuntos
Biomarcadores Tumorais/sangue , Lactato Desidrogenases/sangue , Sarcoma/metabolismo , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sarcoma/sangue , Sarcoma/patologia , Análise de Sobrevida , Adulto Jovem
14.
Anticancer Res ; 39(10): 5605-5610, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570456

RESUMO

BACKGROUND/AIM: We analyzed the process of healing at osteotomy sites and timing of achievement of full weight-bearing in sarcoma patients who underwent hemicortical or intercalary reconstruction using the extracorporeal irradiated autologous bone graft technique. PATIENTS AND METHODS: We studied 10 patients who had undergone tumor resection and reconstruction with hemicortical extracorporeal irradiated autologous bone graft at mid-shaft femur or tibia. The control group consisted of 30 patients who received the reconstruction using intercalary bone graft. RESULTS: Full weight-bearing was achieved in all 10 patients at a median time of 4.8 months. Function was excellent in all patients. When comparing the clinical outcome among the patients who received intercalary and hemicortical grafts, the duration to full weight-bearing achievement in patients who received hemicortical graft was shorter than that in those with intercalary graft. CONCLUSION: Early full weight-bearing may be achieved in patients undergoing hemicortical resection and reconstruction using extracorporeal irradiated autologous bone graft.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Sarcoma/patologia , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transplante Ósseo/métodos , Osso e Ossos/patologia , Osso e Ossos/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia , Transplante Autólogo/métodos , Resultado do Tratamento
15.
PLoS One ; 14(9): e0222188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31513634

RESUMO

BACKGROUND: Environmental and endogenous factors under genetic predisposition are considered to initiate the human intervertebral disc (IVD) degeneration. DNA methylation is an essential mechanism to ensure cell-specific gene expression for normal development and tissue stability. Aberrant epigenetic alterations play a pivotal role in several diseases, including osteoarthritis. However, epigenetic alternations, including DNA methylation, in IVD degeneration have not been evaluated. The purpose of this study was to comprehensively compare the genome-wide DNA methylation profiles of human IVD tissues, specifically nucleus pulpous (NP) tissues, with early and advanced stages of disc degeneration. METHODS: Human NP tissues were used in this study. The samples were divided into two groups: early stage degeneration (n = 8, Pfirrmann's MRI grade: I-III) and advanced stage degeneration (n = 8, grade: IV). Genomic DNA was processed for genome-wide DNA methylation profiling using the Infinium MethylationEPIC BeadChip array. Extraction of raw methylation data, clustering and scatter plot of each group values of each sample were performed using a methylation module in GenomeStudio software. The identification of differentially methylated loci (DMLs) and the Gene Ontology (GO) analysis were performed using R software with the ChAMP package. RESULTS: Unsupervised hierarchical clustering revealed that early and advanced stage degenerated IVD samples segregated into two main clusters by their DNA methylome. A total of 220 DMLs were identified between early and advanced disc degeneration stages. Among these, four loci were hypomethylated and 216 loci were hypermethylated in the advanced disc degeneration stage. The GO enrichment analysis of genes containing DMLs identified two significant GO terms for biological processes, hemophilic cell adhesion and cell-cell adhesion. CONCLUSIONS: We conducted a genome-wide DNA methylation profile comparative study and observed significant differences in DNA methylation profiles between early and advanced stages of human IVD degeneration. These results implicate DNA methylation in the process of human IVD degeneration.

16.
J Orthop Surg (Hong Kong) ; 27(3): 2309499019874470, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31549573

RESUMO

PURPOSE: The purpose of this study was to evaluate local and systemic pathology in a murine model of ischemia-reperfusion (I/R) injury induced by long-term application of a tourniquet on the hind limbs and to assess the protective effects of edaravone, a potent systemic scavenger of free radicals, using this model. METHODS: Sixty C57BL6 mice were divided in two groups, with one group receiving a 3 mg/kg intraperitoneal injection of edaravone and the other group receiving an identical amount of saline 30 min before ischemia under deep anesthesia. The left thigh of each animal was constricted for 4 h with a 4.5-oz. orthodontic rubber band to induce ischemia; 4 h was the critical duration for skeletal muscles. After ischemia, specimens of skeletal muscles, both kidneys, and plasma were collected at 0, 2, 12, 24, 48, and 72 h. Injury to the skeletal muscles and vacuolar degeneration of the kidneys were histologically assessed. Additionally, apoptosis of skeletal muscle cells was assessed by analysis of caspase 3/7 activity and TUNEL staining. Plasma tumor necrosis factor (TNF)-α levels were measured using an enzyme-linked immunosorbent assay kit. RESULTS: Skeletal muscles exhibited prominent injury of myofibers at 12 h after I/R injury, with clear upregulation of plasma TNF-α expression and histologic evidence of tubular dysfunction of the kidneys. Plasma TNF-α levels declined and histologic renal damage was ameliorated in edaravone-treated mice, but treatment did not protect skeletal muscle following ischemia for 4 h. Nonetheless, compared with group S, expression of the apoptosis marker caspase 3/7 was significantly inhibited in the skeletal hind limb muscles of Ed-group mice affected by reperfusion injury following ischemia for 4 h. CONCLUSION: The present study demonstrated that edaravone is a potentially useful drug for systemic or local treatment of reperfusion injury resulting from long-term ischemia.

17.
Cancer Biomark ; 26(2): 163-170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31356193

RESUMO

BACKGROUND: Thrombomodulin (TM) has multiple biological functions and modulates not only anti-coagulation, but also cell proliferation, adhesion, and anti-inflammation activities. The main function of TM is to activate the anticoagulant pathway of protein C. Soluble TM is related to metastasis by its inactivation of thrombin. OBJECTIVES: To clarify the correlation between serum TM levels and clinicopathological parameters. METHODS: The plasma TM levels (FU/ml) of 135 primary soft tissue tumors (benign, 67; soft tissue sarcoma (STS), 68) were measured before biopsy or treatment. TM levels were analyzed and compared to various clinicopathological parameters. Log-rank test and Cox proportional analysis were used to evaluate recurrence-free survival, metastasis-free survival, and overall survival. RESULTS: STS tumors had significantly higher TM values (15.9) than benign tumors (13.7) (p= 0.0138). 5-year MFS was 81.1% in low TM and 40.0% in high TM (p= 0.00671), and 5-year OS was 85.5% in low and 52.5% in high TM in grades 1-3 (p= 0.0673). In multivariate COX proportional analysis, high-TM showed a significant difference (MFS: HR 4.37, p= 0.0147; OS: HR 3.60, p= 0.0557) in grades 1-3. CONCLUSIONS: We demonstrated that a high level of soluble TM has the potential to be a significant predictor of metastasis and poor prognosis in STS patients. TM is a candidate molecular marker for high metastatic potential and can be clinically useful for guiding therapeutic strategy.

18.
BMC Musculoskelet Disord ; 20(1): 347, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351455

RESUMO

BACKGROUND: Impaired lumbar artery flow has been reported in clinical and epidemiological studies to be associated with low back pain and lumbar disc degeneration. However, it has not been experimentally demonstrated that impaired lumbar artery flow directly induces intervertebral disc (IVD) degeneration by affecting IVD matrix metabolism. The purpose of this study was to evaluate whether ligation of the lumbar artery can affect degenerative changes in the rabbit IVD. METHODS: New Zealand White rabbits (n = 20) were used in this study. Under general anesthesia, the third and fourth lumbar arteries were double-ligated using vascular clips. The blood flow to the L3/L4 disc (cranial disc) was reduced by ligation of the third lumbar artery and that of the L5/L6 disc (caudal disc) by ligation of the fourth lumbar artery. The blood flow to the L4/L5 disc (bilateral disc) was decreased by ligation of both the third and fourth lumbar arteries. The L2/L3 disc was used as the control. Disc height was radiographically monitored biweekly until 12 weeks after surgery. The rabbits were sacrificed at 4, 8, and 12 weeks after surgery and magnetic resonance imaging (MRI) T2-mapping, histology and immunohistochemistry were assessed. RESULTS: Lumbar artery ligation did not induce significant changes in disc height between control and ischemic discs (cranial, bilateral and caudal discs) during the 12-week experimental period. T2-values of ischemic discs had no significant trend to be lower than those of the control L2/L3 discs. Histologically, Safranin-O staining changed following ligation of corresponding IVD lumbar arteries. Histological grading scores for disc degeneration, which correlated significantly with MRI T2-values, had significant changes after the surgery. Immunohistochemical analysis showed that the ligation of lumbar arteries significantly affected a change in the percentage of HIF-1α immunoreactive cells of ischemia discs compared to that of control discs four weeks after the surgery (p < 0.05). CONCLUSIONS: The MRI and histology results suggest that diminished flow in lumbar arteries induce mild changes in the extracellular matrix metabolism of rabbit IVDs. These matrix changes, however, were not progressive and differed from the degenerative disc changes seen in the process of human IVD degeneration.


Assuntos
Artérias/diagnóstico por imagem , Degeneração do Disco Intervertebral/etiologia , Disco Intervertebral/irrigação sanguínea , Vértebras Lombares/irrigação sanguínea , Animais , Artérias/cirurgia , Modelos Animais de Doenças , Matriz Extracelular/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/diagnóstico por imagem , Ligadura , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Imagem por Ressonância Magnética , Coelhos , Fluxo Sanguíneo Regional
19.
Mod Rheumatol ; : 1-8, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31339809

RESUMO

Objectives: Rebamipide is a protective drug used for gastric mucosal injuries, and it also exerts protective effects for a variety of other tissues. In this study, murine post-traumatic (PT) osteoarthritis (OA) models in vivo and human OA chondrocytes in vitro were used to examine the effects of rebamipide on articular cartilage degeneration. Methods: Male BALB/c mice were used. The knee ligaments were transected in both knees. Mice were injected with rebamipide into the knee joint every week. Human chondrocytes were stimulated with IL-1ß, then treated with or without rebamipide. The levels of mRNA expression of COL2A, IL-1ß, TNFα, NF-κB, MMP3, MMP13, ADAMTS5, TIMP3, FGF2, and TGFß were estimated using real-time PCR. Results: Histological scores were significantly better in the rebamipide 1 mg/mL and 10 mg/mL groups than in the control group. Rebamipide up-regulated the mRNA expressions of COL2A, TIMP3, TGFß, and FGF2 in chondrocytes and down-regulated IL-1ß, TNFα, NF-κB, MMP3, MMP13, and ADAMTS5. Conclusion: Intra-articular injection of rebamipide prevents articular cartilage degeneration for 6 weeks in murine models of OA in vivo. Rebamipide down-regulates inflammatory cytokines and catabolic factors and up-regulates anabolic factors in human chondrocytes in vitro. Rebamipide could be an important treatment for prevention of articular cartilage degeneration.

20.
BMC Musculoskelet Disord ; 20(1): 336, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324243

RESUMO

BACKGROUND: The endplate-intervertebral disc (IVD) complex is closely interrelated with the vertebral body (VB) in the structural integrity of the anterior spinal column, including biomechanical and biological functions. Endplate and IVD injuries are usually found in association with vertebral fractures (VFs); however, little is known about their relevance to the healing of osteoporotic VFs (OVFs). The first purpose of this study was to evaluate the incidence and occurrence pattern of endplate and IVD injuries associated with single- and acute-OVFs, and the second was to evaluate the influence of endplate and IVD injuries on the occurrence of delayed union. METHODS: Endplate and IVD injuries associated with single- and acute-OVFs were retrospectively evaluated using magnetic resonance imaging (MRI). Vertebrae of 168 patients were included in the study. The occurrence rate and type of endplate and IVD injuries were radiologically evaluated, and the association between endplate and IVD injuries was statistically analyzed. Vertebrae of 85 patients, who received conservative treatment for acute OVFs, were included in the study and classified into two groups, union and delayed union, at 6 months after injury. To identify factors predicting delayed union, uni- and multivariate statistical analyses were performed. Vertebral MRI signal alternation patterns and endplate and IVD injuries were included as candidate factors in the logistic model. RESULTS: In association with OVFs, endplate injuries were observed in 103 of the 168 vertebrae (61%), and IVDs lesions were observed in 101 of 168 OVFs (60%); the occurrence of both injuries was significantly associated. Although no significant association with endplate and IVD injuries was identified, multivariate analysis demonstrated that intravertebral signal alternation (focal high signal intensity) and posterior wall injury were independent risk factors that predicted delayed union. CONCLUSIONS: The results of this study showed that endplate and IVD injuries were found in approximately 60% of single and acute OVFs. These results suggest that fracture healing of OVFs would be mainly attributed to vertebral factors, including mechanical stress and metabolic status, among the three components of the anterior spinal column.


Assuntos
Consolidação da Fratura , Disco Intervertebral/lesões , Fraturas por Osteoporose/complicações , Fraturas da Coluna Vertebral/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares , Imagem por Ressonância Magnética , Masculino , Fraturas por Osteoporose/patologia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/patologia , Vértebras Torácicas
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