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1.
Adv Rheumatol ; 64(1): 46, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849923

ABSTRACT

BACKGROUND: Fibroblast-like synoviocytes (FLSs) are involved in osteoarthritis (OA) pathogenesis through pro-inflammatory cytokine production. TAK-242, a TLR4 blocker, has been found to have a significant impact on the gene expression profile of pro-inflammatory cytokines such as IL1-ß, IL-6, TNF-α, and TLR4, as well as the phosphorylation of Ikßα, a regulator of the NF-κB signaling pathway, in OA-FLSs. This study aims to investigate this effect because TLR4 plays a crucial role in inflammatory responses. MATERIALS AND METHODS: Ten OA patients' synovial tissues were acquired, and isolated FLSs were cultured in DMEM in order to assess the effectiveness of TAK-242. The treated FLSs with TAK-242 and Lipopolysaccharides (LPS) were analyzed for the mRNA expression level of IL1-ß, IL-6, TNF-α, and TLR4 levels by Real-Time PCR. Besides, we used western blot to assess the protein levels of Ikßα and pIkßα. RESULTS: The results represented that TAK-242 effectively suppressed the gene expression of inflammatory cytokines IL1-ß, IL-6, TNF-α, and TLR4 which were overexpressed upon LPS treatment. Additionally, TAK-242 inhibited the phosphorylation of Ikßα which was increased by LPS treatment. CONCLUSION: According to our results, TAK-242 shows promising inhibitory effects on TLR4-mediated inflammatory responses in OA-FLSs by targeting the NF-κB pathway. TLR4 inhibitors, such as TAK-242, may be useful therapeutic agents to reduce inflammation and its associated complications in OA patients, since traditional and biological treatments may not be adequate for all of them.


Subject(s)
Cytokines , Interleukin-1beta , Interleukin-6 , Lipopolysaccharides , NF-kappa B , Signal Transduction , Sulfonamides , Synoviocytes , Toll-Like Receptor 4 , Tumor Necrosis Factor-alpha , Humans , Signal Transduction/drug effects , Synoviocytes/drug effects , Synoviocytes/metabolism , NF-kappa B/metabolism , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Toll-Like Receptor 4/metabolism , Cytokines/metabolism , Interleukin-6/metabolism , Interleukin-1beta/metabolism , Tumor Necrosis Factor-alpha/metabolism , Lipopolysaccharides/pharmacology , Fibroblasts/metabolism , Fibroblasts/drug effects , Osteoarthritis/metabolism , Osteoarthritis/drug therapy , Cells, Cultured , Phosphorylation , RNA, Messenger/metabolism , Male , Female , Middle Aged
2.
Proc Inst Mech Eng H ; : 9544119241242968, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38591839

ABSTRACT

This study investigated the effect of anterior cruciate ligament (ACL) injury on relative acceleration of the tibia and femur during a number of tests/activities, in order to assess the feasibility of acceleration-based diagnosis of ACL injury using inertial sensors. First, a detailed finite element model of the knee joint was developed to simulate the target tests/activities, and identify those in which a large difference between the maximum acceleration peaks (MAPs) of the healthy and ACL injured knees is likely to be observed. The promising tests/activities were entered in an experimental study, where the relative accelerations of the tibiae and femurs of 20 individuals with unilateral ACL injury, allocated randomly to two groups of conscious and unconscious test conditions, were recorded. Model predictions indicated MAP ratios>1.5 for the ACL-injured to healthy knees, during the anterior drawer, Lachman, and pivot-shift tests, as well as the lunge activity. The experimental MAP results indicated acceptable test-retest reliabilities for all tests (coefficient of variation<0.25), and significant MAP differences (p < 0.05) in the anterior drawer and pivot-shift tests, in both coconscious and unconscious conditions. The individualized MAP results indicated side-to-side differences>2 m/s2 for all subjects during unconscious pivot shift tests, and >0.5 m/s2 for eight cases out of ten during conscious anterior drawer tests. It was concluded that the pivot shift test had a great repeatability and discriminative ability for acceleration-based diagnosis of ACL injury in unconscious condition. For the conscious condition, however, the anterior drawer test was appeared to be most promising.

3.
JBJS Case Connect ; 13(4)2023 10 01.
Article in English | MEDLINE | ID: mdl-37917765

ABSTRACT

CASE: A 70-year-old woman presented with knee pain and instability and was diagnosed with advanced knee osteoarthritis and bifocal tibial deformities. The complexity of the case challenged our team to perform a significant sagittal correction (>60°) and restore her ability to walk independently. We performed ipsilateral total knee arthroplasty and anterior closed wedge tibial osteotomy using virtual planning and 3D-printed patient-specific instrumentation. CONCLUSION: Using 2 separate 3D-printed patient-specific cutting guides for this patient with a complex deformity and managing the whole planning process in close collaboration between the surgeons and engineers resulted in a satisfactory postoperative outcome, optimal implant positioning and leg alignment, and minimal soft-tissue damage.


Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Female , Humans , Aged , Arthroplasty, Replacement, Knee/methods , Knee Joint/surgery , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/surgery , Osteotomy/methods , Printing, Three-Dimensional
4.
Trauma Case Rep ; 48: 100937, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37810537

ABSTRACT

The use of customized 3D-printed structures has been gaining popularity in non-union management, as it allows for bypassing the defect while promoting osseointegration. Additionally, porous titanium implants minimize stress shielding due to their stiffness and elastic modulus being closer to that of bone. The interconnected channels increase the surface area and provide space for cell adhesion and proliferation. This study presents the case of a 62-year-old female patient with concomitant knee osteoarthritis recalcitrant aseptic atrophic nonunion in the tibial proximal metaphysis. Due to the small distance between the nonunion site and the joint line, nonunion treatment had to be included in the treatment plan, as it would result in a lack of mechanical stability of the tibial component, and techniques such as plating were not an option. A customized 3D-printed porous titanium cone was used to bypass the fracture site and support the stem used with the CCK prosthesis, allowing for simultaneous nonunion and osteoarthritis management.

5.
BMC Med Educ ; 23(1): 436, 2023 Jun 13.
Article in English | MEDLINE | ID: mdl-37312117

ABSTRACT

BACKGROUND: After the Coronavirus pandemic, many educational routines were stopped for the safety of medical staff. To achieve educational goals, we have implemented new policies in our hospitals. In this study, we aimed to evaluate the effect of such strategies. METHOD: This survey-based study uses questionnaires to assess newly implemented educational strategies. We surveyed 107 medical staff of the orthopedic department of Tehran University of Medical Sciences, including faculty members, residents, and students. The survey contained three series of questionnaires for these groups. RESULTS: The maximum satisfaction for all three groups was observed in the platform and facilities for using e-classes, and the cost- and time-saving capabilities (Respectively, faculty members (FM): 81.8%, residents (R): 95.2%, students/interns (S/I): 87.0%; FM: 90.9%, R: 88.1%, S/I: 81.5%). The new policies have been shown to reduce the stress level of most trainees, increase the quality of knowledge-based education, increase the opportunity for reexamining educational content, expand discussion and research opportunities, and improve work conditions. There was a broad acceptance of the virtual journal clubs and morning reports. However, there were discrepancies between residents and faculty members on issues such as the evaluation of trainees, the new educational curriculum, and flexible shift schedules. Our strategies failed to improve skill-based education and patient treatment status. Most participants indicated that e-learning should be used with face-to-face training post-pandemic (FM: 81.8%, R: 83.3%, S/I: 75.9%). CONCLUSION: Our efforts to optimize the educational system during this crisis have generally improved trainees' work conditions and educational experience. Most participants believed that e-learning and virtual methods should be used alongside traditional training as a complementary component after the pandemic.


Subject(s)
COVID-19 , Education, Medical , Humans , COVID-19/epidemiology , Pandemics , Iran/epidemiology , Educational Status
6.
Adv Rheumatol ; 63(1): 27, 2023 06 27.
Article in English | MEDLINE | ID: mdl-37370181

ABSTRACT

BACKGROUND: Previous studies has shown that nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) is expressed in Fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) patients which is stimulated by muramyl dipeptide (MDP) present in the joint environment and induces inflammation via the NF-κB pathway. Also, other studies have shown that curcumin inhibits proliferation, migration, invasion, and Inflammation and on the other hand increases the apoptosis of RA FLSs. In this study, we aim to evaluate the effect of curcumin, a natural anti-inflammatory micronutrient, on the expression of NOD2 and inflammatory cytokines. METHODS: Synovial membranes were collected from ten patients diagnosed with RA and ten individuals with traumatic injuries scheduled for knee surgery. The FLSs were isolated and treated with 40 µM curcumin alone or in combination with 20.3 µM MDP for 24 h. mRNA was extracted, and real-time PCR was performed to quantitatively measure gene expression levels of NOD2, p65, IL-6, TNF-α, and IL-1ß. RESULTS: The study findings indicate that administering MDP alone can significantly increase the mRNA expression levels of IL-6 and IL-1ß in the trauma group and TNF-α in the RA group. Conversely, administering curcumin alone or in combination whit MDP can significantly reduce mRNA expression levels of P65 and IL-6 in FLSs of both groups. Moreover, in FLSs of RA patients, a single curcumin treatment leads to a significant reduction in NOD2 gene expression. CONCLUSION: This study provides preliminary in vitro evidence of the potential benefits of curcumin as a nutritional supplement for RA patients. Despite the limitations of the study being an investigation of the FLSs of RA patients, the results demonstrate that curcumin has an anti-inflammatory effect on NOD2 and NF-κB genes. These findings suggest that curcumin could be a promising approach to relieve symptoms of RA.


Subject(s)
Arthritis, Rheumatoid , Curcumin , Synoviocytes , Humans , NF-kappa B/metabolism , NF-kappa B/pharmacology , NF-kappa B/therapeutic use , Cytokines , Curcumin/pharmacology , Curcumin/therapeutic use , Curcumin/metabolism , Tumor Necrosis Factor-alpha , Interleukin-6/metabolism , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/genetics , Inflammation/drug therapy , Anti-Inflammatory Agents , Fibroblasts/metabolism , RNA, Messenger/metabolism , RNA, Messenger/pharmacology , RNA, Messenger/therapeutic use , Nod2 Signaling Adaptor Protein/metabolism , Nod2 Signaling Adaptor Protein/pharmacology
7.
Inflammopharmacology ; 31(1): 385-394, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36350424

ABSTRACT

Fibroblast-like synoviocytes (FLSs), the main pathological cells in rheumatoid arthritis (RA), display tumor-like phenotype, including hyper-proliferation, apoptosis resistance, and aggressive phenotype. Excessive proliferation and insufficient apoptosis of RA-FLSs can lead to hyperplastic synovial pannus tissue, excess production of inflammatory mediators, and destruction of joints. In this article, we investigate the effect of PRIMA-1MET on the apoptosis induction and inhibition of pro-inflammatory cytokines in RA-FLSs. Synovial tissue samples were obtained from 10 patients with RA. The FLSs were treated with different concentrations of PRIMA-1MET. The rate of apoptosis and cell survival was assessed by flow cytometry and MTT assay and Real-time quantitative PCR was performed to evaluate the transcription of p53, IL-6, IL-1ß, TNF-α, Noxa, p21, PUMA, Bax, Survivin, and XIAP in treated RA-FLSs. The protein level of p53, IκBα, and phospho-IκBα were measured using Western blotting. The results showed that PRIMA-1MET induced apoptosis in RA-FLSs and increased significantly the expression of Noxa, and decreased significantly IL-6, IL-1ß, p53, and phospho-IκBα expression. PRIMA-1MET can induce apoptosis in RA-FLSs through induction of Noxa expression while p53 was downregulated. Furthermore, PRIMA-1MET treatment results in the suppression of pro-inflammatory cytokine production and NF-κB inhibition. Given the role of p53 and NF-κB in RA-FLSs, PRIMA-1MET can be considered as a new therapeutic strategy for rheumatoid arthritis.


Subject(s)
Arthritis, Rheumatoid , Synoviocytes , Humans , NF-kappa B/metabolism , NF-KappaB Inhibitor alpha/metabolism , NF-KappaB Inhibitor alpha/pharmacology , Tumor Suppressor Protein p53/metabolism , Interleukin-6/metabolism , Arthritis, Rheumatoid/metabolism , Fibroblasts , Anti-Inflammatory Agents/pharmacology , Cells, Cultured , Cell Proliferation
8.
Adv Rheumatol ; 63: 27, 2023. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1447145

ABSTRACT

Abstract Background Previous studies has shown that nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) is expressed in Fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) patients which is stimulated by muramyl dipeptide (MDP) present in the joint environment and induces inflammation via the NF-κB pathway. Also, other studies have shown that curcumin inhibits proliferation, migration, invasion, and Inflammation and on the other hand increases the apoptosis of RA FLSs. In this study, we aim to evaluate the effect of curcumin, a natural antiinflammatory micronutrient, on the expression of NOD2 and inflammatory cytokines. Methods Synovial membranes were collected from ten patients diagnosed with RA and ten individuals with traumatic injuries scheduled for knee surgery. The FLSs were isolated and treated with 40 μM curcumin alone or in combination with 20.3 μM MDP for 24 h. mRNA was extracted, and real-time PCR was performed to quantitatively measure gene expression levels of NOD2, p65, IL-6, TNF-α, and IL-1β. Results The study findings indicate that administering MDP alone can significantly increase the mRNA expression levels of IL-6 and IL-1β in the trauma group and TNF-α in the RA group. Conversely, administering curcumin alone or in combination whit MDP can significantly reduce mRNA expression levels of P65 and IL-6 in FLSs of both groups. Moreover, in FLSs of RA patients, a single curcumin treatment leads to a significant reduction in NOD2 gene expression. Conclusion This study provides preliminary in vitro evidence of the potential benefits of curcumin as a nutritional supplement for RA patients. Despite the limitations of the study being an investigation of the FLSs of RA patients, the results demonstrate that curcumin has an anti-inflammatory effect on NOD2 and NF-κB genes. These findings suggest that curcumin could be a promising approach to relieve symptoms of RA.

9.
Iran J Allergy Asthma Immunol ; 21(4): 418-428, 2022 Aug 12.
Article in English | MEDLINE | ID: mdl-36243930

ABSTRACT

Fibroblast-like synoviocytes (FLSs) play a major role in the pathogenesis of rheumatoid arthritis (RA). Endoplasmic reticulum (ER) stress and dysregulation of unfolded protein response are involved in the resistance to apoptosis of FLSs in RA (RA-FLSs). MicroRNA (MiR)-211 plays an important role in controlling ER stress and apoptotic genes in a PKR-like ER kinase (PERK)-activating transcription factor 4 (ATF4)-dependent manner. We investigated the effect of miR-211-5p overexpression on ER stress and apoptotic genes in RA-FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients. MiR-211-5p and mRNA expression of the selected genes involved in the PERK pathway and apoptosis regulation were measured in RA, trauma, and thapsigargin (Tg)-treated RA-FLSs. Afterward, Tg-treated RA-FLSs following miR-211-5p overexpression were evaluated for miR-211-5p and mRNA levels of the study genes. The expression of miR-211-5p, PERK, BAX, and BCL2 showed no differences between RA and trauma. However, the expression of ATF4 and BCL-XL showed a significant increase in trauma. In addition, the levels of C/EBP homologous protein (CHOP) and MCL1 indicated a significant increase in RA-FLSs. Tg treatment significantly increased the expression of PERK, ATF4, and CHOP in RA-FLSs with no effect on miR-211-5p, BAX, BCL2, BCL-XL, and MCL1. Furthermore, Tg treatment following miR-211-5p overexpression in RA-FLSs showed a significant increase in levels of miR-211-5p with no changes in apoptotic genes. MiR-211-5p overexpression in stimulated RA-FLSs did not alter the levels of selected genes involved in apoptosis regulation. However, more investigations are necessary to determine the ER stress role in apoptosis regulation in RA-FLSs.


Subject(s)
Arthritis, Rheumatoid , MicroRNAs , Synoviocytes , Activating Transcription Factor 4/genetics , Activating Transcription Factor 4/metabolism , Activating Transcription Factor 4/pharmacology , Apoptosis/genetics , Arthritis, Rheumatoid/genetics , Cell Proliferation , Cells, Cultured , Endoplasmic Reticulum Stress/genetics , Fibroblasts , Humans , MicroRNAs/genetics , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , RNA, Messenger/metabolism , Synoviocytes/metabolism , Synoviocytes/pathology , Thapsigargin/metabolism , Thapsigargin/pharmacology , bcl-2-Associated X Protein/metabolism , bcl-2-Associated X Protein/pharmacology
10.
BMC Musculoskelet Disord ; 23(1): 753, 2022 Aug 05.
Article in English | MEDLINE | ID: mdl-35932028

ABSTRACT

BACKGROUND: Corona virus infectious pandemic makes outdoors rehabilitation a potential hazard. Patient education to perform simple home-based exercises seems to be an interesting and sometimes a mandatory option. This study provides a comparison between the conventional and home-based virtual rehabilitation after surgical repair of medial meniscus root tears. METHODS: In this prospective study, all patients who underwent medial meniscus posterior root repair with a modified trans-tibial pull-out technique from March 2019 to March 2021 were evaluated. Those who underwent surgery after December 2019 were trained to perform self-rehabilitation. The rest had undergone outdoors specialized rehabilitation according to a unified protocol and these were used as a historical control group. All patients were followed up for a minimum of 2 year after surgery. Final Lysholm scores were utilized to compare functional outcomes after considering the effect of age, body mass index and time from surgery by multivariate linear regression analysis. RESULTS: Forty-three consecutive patients with medial meniscal root tears were studied. Thirty-nine (90.7%) were women and 4 (9.3%) were men. The mean age of participants was 53.2 ± 8.1 years. The total Lysholm knee score, and all its items were significantly improved in both groups at a two-year follow-up (p < 0.05), except the "Using cane or crutches" item (p = 0.065). Nevertheless, the final Lysholm knee score improvement was higher in patients who performed outdoors specialized rehabilitation and in patients with shorter time-to-surgery. CONCLUSION: Regardless of age and gender, home-based rehabilitation after meniscal root repair with the modified trans-tibial pull-out technique improved the patients' function at a two-year follow-up. Nonetheless, this effect was still significantly lower than that of the outdoors specialized rehabilitation. Future work is required to clarify basic protocols for home-based tele-rehabilitation programs and determine clinical, radiological and functional results. LEVEL OF EVIDENCE: Level IV, therapeutic, historically controlled study.


Subject(s)
Cartilage Diseases , Knee Injuries , Tibial Meniscus Injuries , Arthroscopy/adverse effects , Arthroscopy/methods , Female , Humans , Knee Injuries/surgery , Male , Menisci, Tibial/surgery , Middle Aged , Prospective Studies , Retrospective Studies , Tibial Meniscus Injuries/surgery
11.
Injury ; 53(7): 2389-2394, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35644641

ABSTRACT

Significant work has been done in recent years on treatment strategies for distal femur fractures. Inclusive reviews on periprosthetic fractures of distal femur have been carried out recently, but there is a lack of such reviews on the subject of native distal femur fractures in the recent literature. In this narrative review, we are set out to address the latest updates on geriatric non-periprosthetic distal femur fractures, and perform a rapid review over different treatment options, arriving at a summarized proposed treatment algorithm.


Subject(s)
Femoral Fractures , Periprosthetic Fractures , Aged , Bone Plates , Femoral Fractures/surgery , Femur , Fracture Fixation, Internal , Humans , Periprosthetic Fractures/surgery
12.
J Ultrasound Med ; 41(11): 2715-2723, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35137975

ABSTRACT

OBJECTIVES: It is essential to know the normal extrusion measures in order to detect pathological ones. In this study, we aimed to define some normal reference values for meniscal extrusion in the normal knees during different ranges of motion. METHODS: The amount of anterior and posterior portion of meniscal extrusion among 21 asymptomatic volunteers (42 knees) were tracked in 0, 45, and 90° of knee flexion using an ultrasound machine. The repeated measures analysis of variance (ANOVA) was used to show the interaction between the amounts of meniscal extrusion and the different degrees of knee flexion. RESULTS: The anterior portion of the lateral menisci at full knee extension (0.59 ± 1.40) and the posterior portion of the medial menisci during 90° flexion (3.06 ± 2.36) showed the smallest and the highest mean amount of extrusion, respectively. The normal average amounts of anterior extrusion were 1.12 ± 1.17 and 0.99 ± 1.34 mm for medial and lateral menisci, respectively. The posterior meniscal normal extrusions were significantly increasing in both medial and lateral menisci during the survey (F = 20.250 and 11.298; both P values <.001) as they were measured 2.37 ± 2.16 and 1.53 ± 2.18 mm in order. CONCLUSIONS: The medial meniscus can extrude 1.74 ± 1.84 mm normally while this amount was 1.26 ± 1.82 mm for the lateral meniscus. These measures commonly increased with the rising of knee flexion motion. Likewise, the posterior portion showed more extrusion than the anterior portion on both sides. These measures commonly increased with higher knee flexion.


Subject(s)
Knee Joint , Menisci, Tibial , Humans , Feasibility Studies , Reference Values , Menisci, Tibial/diagnostic imaging , Range of Motion, Articular , Knee Joint/diagnostic imaging , Ultrasonography , Magnetic Resonance Imaging
13.
Iran J Allergy Asthma Immunol ; 20(4): 453-464, 2021 Aug 07.
Article in English | MEDLINE | ID: mdl-34418899

ABSTRACT

Fibroblast-like synoviocytes (FLSs) produce lots of inflammatory molecules that trigger immune responses and intensification the inflammation and thereby play important roles in Rheumatoid Arthritis )RA( pathogenesis. Due to the important roles of toll-like receptor 4 (TLR4) in cytokine production and inflammation, we aimed to evaluate the effects of TAK-242 (Resatorvid) on interleukin (IL)1-ß, IL-6, TNF-α, and TLR4 expression and two important proteins of nuclear factor-κB (NF-κB) signaling pathway (Ikßα and pIkßα) in RA and trauma FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients and cultured in Dulbecco's Modified Eagle Medium (DMEM). 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the cytotoxicity effects of TAK-242 on the RA FLSs. Real-time PCR was performed to measure the expression level of IL1-ß, IL-6, TNF-α, and TLR4 genes in Lipopolysaccharide (LPS) and TAK-242 treated FLSs. Furthermore, the treated FLSs were evaluated for protein levels of Ikßα and pIkßα by western blot. The baseline expression of IL1-ß, IL-6, TNF-α, and TLR4 showed no significant differences between healthy and RA FLSs. LPS stimulated FLSs significantly increased mRNA levels of IL-1ß, IL-6, TNF-α, and TLR4 genes in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. Furthermore, LPS-stimulated FLSs significantly increased the level of pIkßα in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. We provide the data that TAK-242 through inhibiting the NF-κB signaling pathway may modulate TLR4-mediated inflammatory responses and could be considered as a potential therapeutic agent for RA patients.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Arthritis, Rheumatoid/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Sulfonamides/pharmacology , Synoviocytes/drug effects , Synoviocytes/metabolism , Anti-Inflammatory Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/etiology , Arthritis, Rheumatoid/pathology , Biomarkers , Cells, Cultured , Cytokines/genetics , Cytokines/metabolism , Disease Susceptibility , Gene Expression Regulation , Humans , Inflammation Mediators/metabolism , NF-kappa B/metabolism , Signal Transduction , Sulfonamides/therapeutic use , Synoviocytes/pathology
14.
Iran J Allergy Asthma Immunol ; 20(3): 338-349, 2021 Jun 06.
Article in English | MEDLINE | ID: mdl-34134455

ABSTRACT

Fibroblast-like synoviocytes (FLSs) have been introduced in recent years as a key player in the pathogenesis of rheumatoid arthritis (RA), but the exact mechanisms of their transformation and intracellular pathways have not yet been determined. This study aimed to investigate the role of fibroblast activation protein-alpha (FAP-α) in the regulation of genes involved in the transformation and pathogenic activity of RA FLSs. Synovial FLSs were isolated from RA patients and non-arthritic individuals (n=10 in both groups) and characterized; using immunocytochemistry and flow cytometry analysis. FLSs were divided into un-treated and Talabostat-treated groups to evaluate the FAP-α effect on the selected genes involved in cell cycle regulation (p21, p53, CCND1), apoptosis (Bcl-2, PUMA), and inflammatory and destructive behavior of FLSs (IL-6, TGF-ß1, MMP-2, MMP-9, P2RX7). Gene expression analysis was performed by quantitative real-time polymerase chain reaction (qRT-PCR), and immunoblotting was carried out to evaluate FAP-α protein levels. The basal level of FAP-α protein in RA patients was significantly higher than non-arthritic control individuals. However, no differences were observed between RA and non-arthritic FLSs, at the baseline mRNA levels of all the genes. Talabostat treatment significantly reduced FAP-α protein levels in both RA and non-arthritic FLSs, however, had no effect on mRNA expressions except an upregulated TGF-ß1 expression in non-arthritic FLSs. A significantly higher protein level of FAP-α in FLSs of RA patients compared with that of healthy individuals may point to the pathogenic role of this protein in RA FLSs. However, more investigations are necessary to address the mechanisms mediating the FAP-α pathogenic role in RA FLSs.


Subject(s)
Arthritis, Rheumatoid/metabolism , Endopeptidases/metabolism , Fibroblasts/metabolism , Membrane Proteins/metabolism , Synoviocytes/metabolism , Adult , Aged , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/pathology , Case-Control Studies , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cells, Cultured , Female , Fibroblasts/pathology , Gene Expression Regulation , Humans , Inflammation Mediators/metabolism , Male , Middle Aged , Signal Transduction , Synoviocytes/pathology
15.
J Orthop Surg Res ; 16(1): 199, 2021 Mar 17.
Article in English | MEDLINE | ID: mdl-33731164

ABSTRACT

BACKGROUND: Utilizing intrawound vancomycin powder in TKA surgery has yielded rather contrasting results in the current literature. Furthermore, CDC criteria, although effective in general, are not specifically designed for post-TKA infections. Here, we present a 7-year experience of vancomycin use in primary TKA in a high-volume tertiary knee center in Iran. Also, new criteria are proposed to detect suspected superficial post-TKA infections. METHODS: This is a retrospective analysis of primary total knee arthroplasties performed in a tertiary knee center, from March 2007 to December 2018, by a single senior knee surgeon. All patients with follow-up periods of less than 1 year were excluded from the study. Since March 2011, all patients received vancomycin (powder, 1 g) before water-tight closure of the joint capsule. A comparison was made between this group and historical control subjects (operated from March 2007 to March 2011). RESULTS: Altogether, 2024 patients were included in the study. The vancomycin and the control groups included 1710 and 314 cases respectively. Patients were mostly women (male to female ratio, 1 to 4), with a mean age of 65.20 (SD = 10.83) years. In the vancomycin group, the rate of suspected SII (1.87%) and PJI (0.41%) was significantly lower than the control group (P = 0.002). CONCLUSIONS: Our experience shows that application of local vancomycin during TKA surgery could be a reasonable infection prevention measure, although prospective randomized studies are required to evaluate its efficacy.


Subject(s)
Arthroplasty, Replacement, Knee/adverse effects , Prosthesis-Related Infections/prevention & control , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control , Vancomycin/administration & dosage , Aged , Arthroplasty, Replacement, Knee/statistics & numerical data , Biosimilar Pharmaceuticals , Drug Utilization/statistics & numerical data , Female , Humans , Intraoperative Care , Iran/epidemiology , Male , Middle Aged , Retrospective Studies , Surgical Wound Infection/etiology , Time Factors
16.
Auto Immun Highlights ; 12(1): 3, 2021 Feb 05.
Article in English | MEDLINE | ID: mdl-33546769

ABSTRACT

Swelling and the progressive destruction of articular cartilage are major characteristics of rheumatoid arthritis (RA), a systemic autoimmune disease that directly affects the synovial joints and often causes severe disability in the affected positions. Recent studies have shown that type B synoviocytes, which are also called fibroblast-like synoviocytes (FLSs), as the most commonly and chiefly resident cells, play a crucial role in early-onset and disease progression by producing various mediators. During the pathogenesis of RA, the FLSs' phenotype is altered, and represent invasive behavior similar to that observed in tumor conditions. Modified and stressful microenvironment by FLSs leads to the recruitment of other immune cells and, eventually, pannus formation. The origins of this cancerous phenotype stem fundamentally from the significant metabolic changes in glucose, lipids, and oxygen metabolism pathways. Moreover, the genetic abnormalities and epigenetic alterations have recently been implicated in cancer-like behaviors of RA FLSs. In this review, we will focus on the mechanisms underlying the transformation of FLSs to a cancer-like phenotype during RA. A comprehensive understanding of these mechanisms may lead to devising more effective and targeted treatment strategies.

17.
Knee ; 27(5): 1300-1309, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33010742

ABSTRACT

BACKGROUND: The objective of this pilot clinical trial study was to evaluate safety and effectiveness of the newly engineered tissue composed of autologous chondrocytes and collagen/fibroin scaffold in repair of osteochondral defects. METHODS: We implemented a pilot clinical study in two patients with knee osteochondral lesions using engineered tissue composed of scaffold and autologous chondrocytes. Patients were clinically evaluated using the International Repair Cartilage Society score and magnetic resonance imaging (MRI) for one year. RESULTS: Improved clinical outcomes and objective scores indicated a normal or nearly normal knee in both patients. International Knee Documentation Committee score was upgraded from 34.5 at baseline to 72.4 in the first patient, and 28.7 to 81.6 in the second patient. Visual analogue scale, showing the suffering pain score, was lowered from 8 to 0 in both patients, Western Ontario and McMaster Universities Osteoarthritis Index score representing the physical ability of the patients was changed from 68.1 to 87.1 in Patient 1 and 58.3 to 87.1 in Patient 2, the knee function score, related to the functional ability of the knee, was improved from 70 to 100 in the first patient and from 45 to 91 in the second patient. MRI showed great coverage and integration of the graft in patients, with no effusion, decreased edema and cartilage formation signals. CONCLUSIONS: The functional and clinical outcomes alongside MRI data showed promising results for regenerating osteochondral defects. A randomized clinical trial study is required to confirm feasibility of this novel engineered tissue in repair of osteochondral defects.


Subject(s)
Cartilage, Articular/surgery , Chondrocytes/transplantation , Collagen , Fibroins , Tissue Scaffolds , Adult , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/injuries , Female , Humans , Magnetic Resonance Imaging , Microscopy, Electron, Scanning , Patient Outcome Assessment , Pilot Projects , Transplantation, Autologous , Visual Analog Scale
18.
Arch Bone Jt Surg ; 8(4): 524-530, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32884974

ABSTRACT

BACKGROUND: The ultimate goal of the treatment of infectious knee arthritis is to protect the articular cartilage from adverse effects of infection. Treatment, however, is not always hundred percent successful and has a 12% failure rate. Persistent infection is more likely to happen in elderly patients and those with underlying joint diseases, particularly osteoarthritis. Eradication of infection and restoration of function in the involved joint usually are not possible by conventional treatment strategies. There are few case series reporting two-stage primary knee arthroplasty as the salvage treatment of the septic degenerative knee joint; however, the treatment protocol remains to be elucidated. METHODS: Based on a proposed approach, patients with failure of common interventions for treatment of septic knee arthritis and underlying joint degeneration were treated by two-stage TKA and intervening antibiotic loaded static cement spacer. Suppressive antibiotic therapy was not prescribed after the second stage. RESULTS: Complete infection eradication was achieved with mean follow up of 26 months. All cases were balanced with primary total knee prosthesis. The knee scores and final range of motions were comparable to other studies. CONCLUSION: The two-stage total knee replacement technique is a good option for management of failure of previous surgical treatment in patients with septic arthritis and concomitant joint degeneration. Our proposed approach enabled us to use primary prosthesis in all of our patients with no need for suppressive antibiotic therapy.

19.
Arch Bone Jt Surg ; 8(4): 545-549, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32884977

ABSTRACT

Surgical reattachment of medial meniscus posterior root tear (MMPRT) with transtibial sutures can delay the presence of medial knee joint compartment osteoarthritis. Most suture configurations are placed five mm away from the torn margin in the meniscal substance which is already degenerated and may decrease the pull out strengths of repair construct. The number of meniscus penetration may also be important considering meniscus tissue damage with more complex suture techniques impose the risk of suture cut out through the meniscus substance. We introduce our loop postsuture construct technique which is simple, cheap and reproducible.

20.
Arch Bone Jt Surg ; 8(Suppl1): 295-296, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32607399

ABSTRACT

The first pandemic of the coronavirus family was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019. As a result of the pandemic critical condition, specialized orthopedic services were obviously affected. To respond properly, we initiated a series of strategic measures, aiming at the safety of staff, minimizing the exposure, and prevention of possible disruption in providing services.

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