scholarly journals Triamcinolone Acetonide-Loaded Nanoparticles Encapsulated By CD90+ MCSs-Derived Microvesicles Drive Anti-Inflammatory Properties and Promote Cartilage Regeneration After Osteoarthritis

Author(s):  
Yuanlong Li ◽  
Qingqiang Tu ◽  
Dongmei Xie ◽  
Shurui Chen ◽  
Kai Gao ◽  
...  

Abstract Background: Osteoarthritis (OA) is a highly prevalent human degenerative joint disorder that has long plagued patients. Glucocorticoid injection into the intra-articular (IA) cavity provides potential short-term analgesia and anti-inflammation, but long-term IA causes loss of cartilage content. Synovial mesenchymal stem cells (MSCs) reportedly promote cartilage proliferation and increase cartilage content. Methods: The CD90+ MCSs-derived micro-vesicle (CD90@MV)-coated nanoparticle (CD90@NP) was developed. CD90+ MCSs were extracted from human synovial tissue. Cytochalasin B (CB) relaxed the interaction between the cytoskeleton and the cell membranes of CD90+ MCSs, stimulating CD90@MV secretion. The poly (lactic-co-glycolic acid) (PLGA) nanoparticle was coated with CD90@MV, and a model glucocorticoid, triamcinolone acetonide (TA), was encapsulated in CD90@NP (T-CD90@NP). Results: CD90@MV membrane proteins were similar to CD90+ MCSs, indicating that the CD90@MV bio-activity is similar to the cartilage proliferation-inducing CD90+ MCSs. The CD90@NP binding to injury cartilage primary cells was significantly stronger than the erythrocyte membrane-coated nanoparticles (RNP). In the rabbit OA model, long-term IA of T-CD90@NP showed significantly enhanced repair of damaged cartilage than TA and CD90+ MCSs treatments. In the rat OA model, short-term IA of T-CD90@NP showed effective anti-inflammatory ability similar to TA treatment. Moreover, long-term IA of T-CD90@NP induced cartilage to restart the cell cycle and reduced cartilage apoptosis. T-CD90@NP promotes regeneration of chondrocytes, reduces apoptosis via the FOXO pathway, and influences type 2 macrophage polarization to regulate inflammation through IL-10. Conclusion: This study confirms that T-CD90@NP promotes chondrocyte proliferation and anti-inflammation, improving the clinical glucocorticoid treatment plan.

2016 ◽  
Vol 31 (1) ◽  
pp. 45
Author(s):  
Dasaiev M. Dutra ◽  
Maria Auxiliadora G do Nascimento ◽  
Maria Sueli Marques Soares

Objective: This article presents a case report of actinic cheilitis with an acute inflammatory process and need for anti- inflammatory treatment.Case Report: Triamcinolone acetonide in Orabase was prescribed 3 times a day for 15 days, and the patient was advised to use sunscreen and hats. After 7 days, there was a significant improvement in the acute phase and the patient was kept under observation.Conclusion: It is emphasized that it is important to intervene in the evolution of the inflammatory process in premalignant lesions in order to prevent its long-term maintenance.


2009 ◽  
Vol 297 (6) ◽  
pp. H2109-H2119 ◽  
Author(s):  
S. Ares-Carrasco ◽  
B. Picatoste ◽  
A. Benito-Martín ◽  
I. Zubiri ◽  
A. B. Sanz ◽  
...  

The aim of this paper is to study the myocardial damage secondary to long-term streptozotocin-induced type 1 diabetes mellitus (DM1). Normotensive and spontaneously hypertensive rats (SHR) received either streptozotocin injections or vehicle. After 22 or 6 wk, DM1, SHR, DM1/SHR, and control rats were killed, and the left ventricles studied by histology, quantitative PCR, Western blot, ELISA, and electromobility shift assay. Cardiomyocyte cultures were also performed. The expression of profibrotic factors, transforming growth factor-β (TGF-β1), connective tissue growth factor, and matrix proteins was increased, and the TGF-β1-linked transcription factors phospho-Smad3/4 and activator protein-1 were activated in the DM1 myocardium. Proapoptotic molecules FasL, Fas, Bax, and cleaved caspase-3 were also augmented. Myocardial injury in long-term hypertension shared these features. In addition, hypertension was associated with activation of NF-κB, increased inflammatory cell infiltrate, and expression of the mediators [interleukin-1β (IL-1β), tumor necrosis factor-α, monocyte chemoattractant protein 1, vascular cell adhesion molecule 1, angiotensinogen, and oxidants], which were absent in long-term DM1. At this stage, the combination of DM1 and hypertension resulted in nonsignificant additive effects. Moreover, the coexistence of DM1 blunted the inflammatory response to hypertension. Anti-inflammatory IL-10 and antioxidants were induced in long-term DM1 and DM1/SHR hearts. Myocardial inflammation was, however, observed in the short-term model. In cultured cardiomyocytes, IL-10, TGF-β1, and catalase blocked the glucose-stimulated expression of proinflammatory genes. Fibrosis and apoptosis are features of long-term myocardial damage in experimental DM1. Associated hypertension does not induce additional changes. Myocardial inflammation is present in hypertension and short-term DM1, but is not a key feature in long-term DM1. Local reduction of proinflammatory factors and expression of anti-inflammatory and antioxidant molecules may underlie this effect.


2013 ◽  
Vol 6 (7) ◽  
pp. 675-685 ◽  
Author(s):  
Carol D. Mikulec ◽  
Joyce E. Rundhaug ◽  
Melissa S. Simper ◽  
Ronald A. Lubet ◽  
Susan M. Fischer

2020 ◽  
Vol 26 (2) ◽  
pp. 120-127
Author(s):  
B. V. Zavodovskiy ◽  
E. V. Papichev ◽  
L. E. Sivordova ◽  
Yu. V. Polyakova ◽  
Yu. R. Akhverdyan

Objective. To compare the efficacy and tolerability of long-term and short-term continuous NSAIDs in patients with knee osteoarthritis with insufficient efficacy “on demand” NSAIDs and SYSADOA.Study design. 12-week, prospective, comparative, randomized, single-center study.Materials and Methods. 180 patients with primary knee osteoarthritis aged 40 to 85 years with insufficient efficacy of “on demand” NSAIDs and SYSADOA were examined. Anti-inflammatory drugs were recommended for everyone: 56 people took Naproxen (31.11%), 63 — Etoricoxib (35%), 61 — Ketoprofen (33.89%). Patients were randomized into two groups: 1st group — with 8-week continuous intake of NSAIDs, 2nd group — with a 2-week continuous course of NSAIDs.Results. There was a positive dynamics of pain syndrome according to VAS and decrease in the level of the WOMAC index in both groups after 2 weeks of therapy. The pain level (VAS) and WOMAC indices in 1st group achieved after 8 weeks significantly differed from the ones after 2 weeks of therapy (VAS dynamics —10.93±2.43 mm, t = 42.64; p<0.001). In both groups we noted gradual significant increase in the average pain level according to VAS and WOMAC indices after NSAIDs cancellation. However, there was better control of pain in 1st group with long-term NSAID than in 2nd one. Safety profile of drug therapy was similar in both groups.Conclusion. The long-term 8-week use of NSAIDs in patients with knee osteoarthritis with insufficient efficacy “on demand” NSAIDs and SYSADOA provides better dynamics of the pain syndrome than with 2-week therapy. After treatment is canceled longer prior NSAID therapy contributes to better control of the pain syndrome. Continuous use of NSAIDs demonstrated good tolerance and safety, did not require dose reduction and/or discontinuation of therapy. Thus, anti-inflammatory therapy of osteoarthritis in this group of patients may be prescribed for a longer period with continuous use of NSAIDs.


2009 ◽  
Vol 12 (11) ◽  
pp. 1113-1121 ◽  
Author(s):  
Tomoyoshi Shibuya ◽  
Toshifumi Ohkusa ◽  
Tetsuji Yokoyama ◽  
Akira Harada ◽  
Kazuko Beppu ◽  
...  

2018 ◽  
Vol 79 (4) ◽  
pp. 411-423 ◽  
Author(s):  
Allison K. Masters ◽  
Darren J. Berger ◽  
Wendy A. Ware ◽  
Natalie R. Langenfeld ◽  
Johann F. Coetzee ◽  
...  

2000 ◽  
Vol 59 (4) ◽  
pp. 601-608 ◽  
Author(s):  
Mary Moloney

Numerous dietary treatments that purport to promote something unique for stimulating weight loss have been published. These treatments include fad diets, diets formulated by various commercial slimming clubs, very-low-energy diets (VLCD) and conventional diets. Fad diets may possibly reduce some weight short-term; however, there is no scientific basis to their long-term use. Commercial slimming clubs may be suitable for some individuals but they need to be properly assessed professionally. There are specific guidelines for the use of VLCD, which are only appropriate for short-term use. There is scientific evidence to suggest that conventional diets can produce both short- and long-term weight loss. A successful weight-loss programme depends on a multidisciplinary team approach. Management strategies should be devised for addressing issues such as goals, monitoring, follow-up, relapse and evaluation. Initial assessments should include medical, laboratory and anthropometric data, fitness level and dietary and behavioural attitudes. These results will form the basis of the treatment plan. Frequent visits to the clinic are fundamental in promoting continuing weight loss during the long-term maintenance stage of treatment. The visits should be made worthwhile for the patient. Realistic and attainable goals for diet, exercise and behaviour modification should be made. The diet should have a novel approach and be tailored to the needs of the patient. It should be adequate nutritionally, low in energy and fat. The overall aim should be to promote lifelong changes in lifestyle, improvement in quality of life and health risks.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 825.1-825
Author(s):  
M. Jansen ◽  
S. Mastbergen ◽  
T. D. Turmezei ◽  
J. W. Mackay ◽  
F. Lafeber

Background:Knee joint distraction (KJD) is a joint-preserving treatment option for younger (age <65 years) knee osteoarthritis (OA) patients. It has shown clinical improvement for up to nine years after treatment. Radiographs and MRI scans have previously shown cartilage regeneration activity, especially in the first two years after treatment. However, MRIs have not been evaluated more than five years after this treatment.Objectives:To evaluate MRI cartilage thickness up to ten years after KJD treatment.Methods:Patients (n=20) with end-stage knee OA, indicated for total knee arthroplasty (TKA) but <60 years old, were treated with KJD. 3T MRIs with 3D spoiled gradient recalled imaging sequence with fat suppression (SPGR-fs) were acquired before and one, two, five, seven and ten years after surgical treatment. Stradview v6.0 was used for semi-automatic cartilage segmentation; wxRegSurf v18 was used for surface registration. MATLAB R2020a and the SurfStat MATLAB package were used for data analysis and visualization. For changes over time, linear mixed models were used. Two separate linear regression models were used to show the influence of baseline Kellgren-Lawrence grade and sex on the changes over time. Statistical significance was calculated with statistical parametric mapping; a p-value <0.05 was considered statistically significant. Since KJD has previously shown significant results mostly in the patients’ most affected compartment (MAC), patients were separated in two groups based on whether their MAC was the medial or lateral compartment.Results:The MAC was predominantly the medial side (medial MAC n=18; lateral n=2). The 18 patients with a medial MAC all had MRI scans at baseline, one and two years after treatment. After two years, some patients were lost to follow-up, decreasing data availability at five (n=15), seven (n=11) and ten years (n=7). Figure 1 (top) shows the average cartilage thickness at the different time points for all medial MAC patients together. One and two years after treatment the cartilage in the medial weight-bearing region was on average thicker than before treatment. While from five years after treatment the cartilage thickness gradually decreased, even at ten years the medial cartilage thickness seemed slightly higher than pre-treatment. Figure 1 (bottom) shows cartilage thickness changes compared to baseline for patients with a medial MAC. Patients with a lateral MAC showed a similar pattern, with the biggest changes showing on the lateral side. As indicated by the dark blue areas, the medial femoral cartilage thickness increase, which was up to 0.5 mm after one year and 0.6 mm after two years, was largely statistically significant at both these time points. While the medial tibia showed an increase of up to 0.5 mm at these time points as well, this was not statistically significant at two years. Surprisingly, long-term results showed areas of the lateral (less affected) compartment were significantly thicker, up to 0.7 mm, compared to pre-treatment in both the femur and tibia compared to baseline. Kellgren-Lawrence grade and sex were shown to influence the changes, albeit not statistically significantly. Patients with a higher Kellgren-Lawrence grade and male sex showed a higher short-term (one and two year) but a lower long-term (seven and ten year) cartilage thickness increase.Conclusion:KJD treatment results in significant short-term cartilage regeneration in the most affected compartment. While after two years this initial gain in cartilage thickness is gradually lost, likely as a result of natural progression, even ten years after treatment the cartilage is thicker than before treatment. In the less affected compartment, a delayed cartilage response seems to take place, with significantly increased cartilage thickness in the long term. In conclusion, in these young OA patients indicated for TKA, KJD results in femoral and tibial cartilaginous tissue regeneration both short- and long-term and in both sides of the joint.Disclosure of Interests:None declared.


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