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1.
Eur J Transl Myol ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656261

RESUMO

The impact of COVID-19 on sport and physical activity has been a subject of considerable interest and concern. Padel satisfies the desire for social interaction and a return to sport after a period of inactivity. The aim of this study is to show a correlation between return to sport and related injuries in a population of Padel players. The study was carried out in a survey mode, consisting of a questionnaire with four sections and fifty questions on the biographical data of the individual, lifestyle before and after the pandemic, knowledge and playing level of Padel and injuries. The self-administered online questionnaire was developed and validated by a panel of physiotherapists, orthopaedic surgeons, and physiatrists with experience in clinical practice and/or musculoskeletal research. The study was conducted in a survey mode from a smartphone or computer via a link to a multiple-choice document. The link to the questionnaire was distributed via mailing lists, social media, and chat applications.

2.
J Clin Med ; 12(14)2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37510924

RESUMO

BACKGROUND: Adverse local tissue reactions to metal debris are due to a metal-on-metal bearing complication caused by micromotions at modular interfaces that induce corrosion of the protective oxide layer. This process could lead to wear, fretting, and abrasion with the release of metal ions locally and systemically, which may cause adverse local reactions in nearby tissues. The aim of this study is to describe a series of patients with painful local adverse tissue reactions secondary to corrosion at the modular neck-body interface, to document the clinical presentation, diagnostic workup, and surgical findings of our research, and to search for a possible correlation between metallosis and infection. METHODS: A retrospective study of patients with adverse local tissue reactions due to metal surface corrosion was performed. Blood samples were collected to identify erythrocyte sedimentation rate, C reactive protein, and procalcitonin, and a magnetic resonance imaging protocol was performed. RESULTS: Serum cobalt and chromium levels of the 43 patients tested were significantly higher on average. However, both erythrocyte sedimentation rate and C-reactive protein were significantly elevated. Magnetic resonance imaging showed adverse reactions to metal debris with large soft tissue masses and surrounding tissue damage. CONCLUSIONS: Corrosion in hip prosthesis can lead to the release of metal ions and debris locally and systemically, resulting in local soft tissue changes. A "tumor-like" debridement can reduce this complication.

3.
J Clin Orthop Trauma ; 43: 102223, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37520268

RESUMO

Purpose: The treatment of periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is still under debate. Two-stage exchange arthroplasty is the most common surgical procedure performed. This study analyzed a new functional articulating hip spacer called "Spaceflex" regarding the mechanical-related complications, the recurrent/persistent infection during the interval period, the overall infection-free survivorship after reimplantation, the overall complication/reoperation after reimplantation and the evaluation of patient-reported outcome measures (PROMs) at three intervals of time: before the first stage, during the interval period, and at the final follow-up after reimplantation. Methods: A consecutive series of 56 patients with chronic hip PJI undergoing two-stage prosthetic revision using a new intraoperatively molded articulating hip spacer design implanted by the same experienced surgeons was examined from January 2017 to December 2021. The demographic and clinical characteristics of the included patients were analyzed. Specifically, PROMs before the first stage, during the interval period, and at the final follow-up after reimplantation and complications reported during the interval period and after reimplantation were examined. Results: The new functional articulating hip spacer was characterized by a low mechanical complication rate (5.8%) and an overall two-stage procedure success rate of 90.6% at the last follow-up. PROMs improved with the spacer during the interval period and at the final follow-up. Furthermore, the reinfection rate was in line with other case series with different spacer designs. Finally, low postoperative complication rates after reimplantation have been demonstrated. Conclusions: Two-stage revision performed with a modular articulating spacer allows patients to preserve satisfactory functional and quality-of-life outcomes in the postoperative period, with a low risk of mechanical complications and without increasing the reinfection rate.

4.
J Clin Med ; 12(13)2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37445579

RESUMO

BACKGROUND: C-reactive protein (CRP) to Albumin ratio (CAR) has been used in multiple clinical settings to predict early mortality. However, there is a lack of evidence on the predictive role of CAR in 30-day mortality after a hip fracture. The purpose of this study was to establish a potential association between CAR and 30-day mortality and to assess if the CAR Receiving Operating Characteristics curve (ROC) can be a reliable predictor of early mortality. METHODS: We retrospectively reviewed the charts of 676 patients (>65 years) treated for hip fracture between 2006 and 2018. All hip fractures were included. Treatment strategies included closed reduction and internal fixation, open reduction and internal fixation, hemiarthroplasty, or total joint arthroplasty. Statistical analysis included T-test, Pearson correlation for CAR and other markers, ROC curves and area under the curve, Youden Model, and Odds Ratio. RESULTS: The 30-day mortality rate analysis showed that higher preoperative levels of CAR were associated with higher early mortality. When analyzing the area under the ROC curve (AUROC) for 30-day mortality, the reported value was 0.816. The point of the ROC curve corresponding to 14.72 was considered a cut-off with a specificity of 87% and a sensibility of 40.8%. When analyzing values higher than 14.72, the 30-day mortality rate was 17.9%, whilst, for values lower than 14.72, the 30-day mortality rate was 1.8%. CONCLUSIONS: Patients older than 65 years affected by a hip fracture with increased preoperative levels of CAR are associated with higher 30-day mortality. Despite a moderate sensibility, considering the low cost and the predictivity of CAR, it should be considered a standard predictive marker.

5.
Mult Scler Relat Disord ; 69: 104405, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36417812

RESUMO

BACKGROUND: Limb apraxia is an acquired cognitive-motor disorder characterized by spatial and temporal disorganization of limb movements, negatively affecting the quality of life of patients, including those with multiple sclerosis (MS). Although recent studies have shown the potential role of VR in increasing cognitive and motor functions, only a few studies have been carried out on the rehabilitation of upper limb apraxia. Hence, our study aims to evaluate the potential efficacy of VR training to improve upper limb ideomotor apraxia in patients with MS. METHODS: One hundred and six patients, affected by secondary progressive MS, who attended our Robotic and Behavioral Neurorehabilitation Service from March 2019 to February 2020, were enrolled in this study and randomly divided into two groups: the control group (CG: 53 patients) performed traditional therapy whereas the experimental group (EG:53 patients) received training using semi-immersive VR. All patients underwent the same amount of cognitive training, 3 times a week for 8 weeks. They were submitted to a specific neuropsychological assessment before (T0) and after the rehabilitation treatment (T1). RESULTS: The VR training led to a significant improvement in global cognitive functions, with regard to constructive and ideomotor apraxia. On the contrary, the CG achieved significant improvements only in ideomotor apraxia. Moreover, only in the EG, we observed an improvement in the mood at the end of training. CONCLUSION: The present study demonstrates that VR rehabilitation can be an effective tool for the treatment of apraxia, which is a neuropsychological problem often underestimated in MS patients. Further studies with long-term follow-up periods are needed to confirm the effect of this promising approach.


Assuntos
Apraxia Ideomotora , Esclerose Múltipla Crônica Progressiva , Reabilitação Neurológica , Humanos , Apraxia Ideomotora/reabilitação , Neuropsicologia , Qualidade de Vida , Recuperação de Função Fisiológica , Realidade Virtual , Reabilitação Neurológica/métodos , Esclerose Múltipla Crônica Progressiva/complicações , Esclerose Múltipla Crônica Progressiva/reabilitação
6.
Ann Jt ; 8: 36, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38529221

RESUMO

Background: Hip revision surgery in extensive acetabular bone defects represents a complex challenge for hip surgeons. The primary goal is to obtain a stable acetabular component and restore the hip biomechanics. Through the years, different prosthetic implants have been developed to perform acetabular revision depending on bone loss location and extension. This systematic review aims to summarize the clinical outcomes and complications reported with trabecular titanium (TT) cups in hip revision surgery. Methods: A literature search of four databases (PubMed, Embase, Scopus and the Cochrane Database of systematic reviews) was performed according to the PRISMA guideline from January 2008 to December 2022. All studies written in English and reporting the clinical outcome of patients undergoing revision total hip arthroplasty using Delta TT cups were included. The initial screening identified 378 studies. Each eligible clinical article was analyzed according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence (LoE), and the papers' methodological quality was evaluated using The Methodological Index for Non-Randomized Studies Criteria (MINORS) score. Results: Eight clinical studies were included in the analysis. A total of 523 hip revisions were analyzed. Delta TT cups were used in 3.9%, Delta TT one cups in 46.8%, and Delta TT revisions in 49.3%. Paprosky IIIa was the most frequent acetabular bone defect reported in 26.4% of cases. The overall survival rate of TT cups was 93.4%. The dislocation was the most frequent complication in 4.1% of patients, while the prevalence of aseptic loosening was 1.5. Conclusions: Managing severe acetabular bone defects remains a complex challenge for hip surgeons. Since their introduction, TT cups have exhibited good clinical results, with complication rates in line with or lower than those reported by similar implants.

7.
Medicine (Baltimore) ; 101(48): e32181, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36482525

RESUMO

Adipose tissue (AT) is an endocrine metabolically dynamic active tissue that plays a central role in the systemic energy balance and metabolic regulation. Brown AT represents approximately 1% of adult human AT, with an energy-burning function that uses fat to create heat. Brown AT activity was measured using 18F-fluorodeoxyglucose positron emission tomography/computed tomography. It has been shown that cold exposure could promote brown AT activation. However, many factors, such as aging and body mass index, may interfere with this activity. Many authors have discussed the role of factors specifically secreted by the AT in response to cold exposure. The aim of this review is to properly understand the effects of cold on AT and biomarkers and their possible application in rehabilitation medicine. A comprehensive literature review was performed to identify published studies regarding biomarkers of cold effects on Brown AT searching the following databases: PubMed, Science Direct, and Web of Science, from 2012 to 2022. After evaluation of the inclusion and exclusion criteria, 9 studies were included in this review. We reported the overall influence of cold exposure on brown AT activity, its related biomarkers, and metabolism, demonstrating that the therapeutic role of cold exposure needs to be better standardized. From our data, it is important to design proper clinical trials because most cold applied protocols lack a common and homogeneous methodology.


Assuntos
Tecido Adiposo Marrom , Humanos , Tecido Adiposo Marrom/diagnóstico por imagem
8.
J Equine Vet Sci ; 106: 103753, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34670693

RESUMO

A deep knowledge on metabolic response of athlete horse to exercise is of paramount importance for the development of optimal training programs to attain equilibrium between good performance and animal welfare. This study investigated the dynamic change of metabolic, clotting times and peripheral indices of central fatigue in horses competing in an official 44 km endurance race.  From 6 horses blood samples were collected at rest (TPRE), within 5 minutes from the end of race (TPE5), after 30, 60 minutes after the end of race (TPE30 and TPE60) to investigate the values of blood lactate, glucose, platelets (PLTs), serum leucine, isoleucine, valine, tryptophan, the ratio between tryptophan and branched-chain amino acids (BCAAs) levels (Try/BCAAs), total proteins, non-esterified fatty acids, plasma thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time and fibrinogen (Fb). Lactate, PLTs, non-esterified fatty acids, BCAAs and Try/BCAAs showed higher values at TPE5, TPE30and TPE60than TPRE(P < .0001); glucose showed lower values at TPE5, TPE30and TPE60than TPRE(P < .0001). Higher TT values were found at TPE5, TPE30and TPE60than TPRE, and at TPE5than TPE30 and TPE60(P < .0001); Fb was higher at TPE5than TPRE, T PE30and TPE60(P < .0001). This survey confirms that horses performing prolonged physical exercise experienced glycolysis, lipid mobilization and amino acid metabolism to provide substrates as fuel for muscle contraction.


Assuntos
Aminoácidos de Cadeia Ramificada , Condicionamento Físico Animal , Animais , Fadiga/veterinária , Cavalos , Isoleucina , Leucina
9.
J Clin Neurosci ; 92: 159-164, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34509244

RESUMO

BACKGROUND: In the last decade, the number of people over 60 has increased, leading to various healthcare problems. The aim of this retrospective study is to evaluate the effects of robotic rehabilitation in elderly patients as well as their perception of usability and adaptation to intensive robotic neurorehabilitation. METHODS: This is a retrospective case-control study. Eighty elderly stroke patients were included in the analysis using an electronic data retrieval system. The enrolled patients were divided into two groups: the experimental group (EG) underwent rehabilitation training with Lokomat FreeD, equipped with a VR screen, while the control group (CG) performed traditional rehabilitation training. The two groups matched for age, sex, education, brain injury, stroke interval. The rehabilitation protocol included a total of 40 training sessions. RESULTS: Both types of rehabilitation led to an improvement in the perceived level of disability (FIM) and in the performance in gait and balance (TT), highlighting a significant improvement especially in the EG. However, only in the EG, Lokomat training had induced an increase in the distance covered in 10 min (10 m walk test), and a significant improvement in mood (HRS-D). Moreover, Lokomat-FreeD was well tolerated by patients with high levels of usability. CONCLUSIONS: Our results suggest that elderly patients may benefit from high-intensity robotic neurorehabilitation using the Lokomat-Pro FreeD.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Idoso , Estudos de Casos e Controles , Terapia por Exercício , Marcha , Humanos , Estudos Retrospectivos
10.
Geriatr Orthop Surg Rehabil ; 12: 21514593211023996, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471568

RESUMO

BACKGROUND: Periprosthetic fractures are a rare complication after total knee arthroplasty (TKA). However, the incidence of these fractures is growing after the increasing number of TKAs performed every year and the progressive aging of the population. In addition, the surgical treatment and peri-operative management of these complications are demanding, representing a challenge for the orthopedic surgeon. SIGNIFICANCE: A thorough understanding of these fractures and a correct classification are necessary in order to select the most suitable surgical treatment. The aim of this review was to analyze the epidemiology, classification, diagnosis, surgical treatment, and outcomes of periprosthetic knee fractures in order to give an exhaustive overview. RESULTS: Reduction and internal fixation with locking plates or intramedullary nails represents the preferred option in case of a stable prosthetic implant. Conversely, in case of loose tibial and/or femoral component, implant revision is mandatory. Conservative treatment is rarely indicated. CONCLUSION: A deep understanding of the characteristics and patterns of periprosthetic knee fractures, and the determination of the stability of the prosthetic implant are necessary in order to establish the correct treatment.

11.
Medicina (Kaunas) ; 57(3)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802325

RESUMO

Background and objectives: Knee osteoarthritis (KO) is one of the most common joint diseases, determining knee pain and reduction of mobility, with a negative effect on quality of life. Intra-articular injections of different formulations of platelet-rich plasma (PRP) are an increasingly common non-surgical treatment for KO. Recently, in order to combine the anti-inflammatory effect of platelet rich plasma and the viscosupplementation effect of hyaluronic acid, a formulation of PRP combined with hyaluronic acid (PRP + HA) has been proposed. The purpose of this study is to retrospectively compare the effectiveness of plasma with high concentration of platelets and leukocytes (L-PRP) with PRP + HA in patients with mild to moderate (Kellgren-Lawrence scale II-III grade) KO. Materials and Methods: Among the 51 patients included, 28 have been treated with L-PRP, while 23 with PRP + HA. A retrospective evaluation at baseline (T0), after 3 months (T1) and 1 year (T2) has been performed. The outcome analyzed are the Knee Society Score (KSS), the Visuo Analogic Scale (VAS) (at T0, T1, and T2) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) (T0 and T2). We evaluated change in mean scores within and between groups among different time points using repeated measures ANCOVA. Results: Although the two treatments have been both effective in reducing VAS, the group treated with PRP + HA showed a significantly lower KSS. Conclusions: Our results show that the use of both treatments may help to reduce pain in patients with mild to moderate KO. PRP + HA showed better results in improving knee mobility and function. These results should be considered only preliminary: Further research is needed to completely describe the clinical effectiveness of these formulations.


Assuntos
Osteoartrite do Joelho , Plasma Rico em Plaquetas , Tratamento Conservador , Humanos , Ácido Hialurônico/uso terapêutico , Leucócitos , Osteoartrite do Joelho/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
12.
Arch Cardiovasc Dis ; 113(5): 308-320, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32359859

RESUMO

BACKGROUND: Epidemiological data suggest that air pollutants are risk factors for cardiovascular disease. Recent studies have questioned the adequacy of current legal pollutant limits, because concentrations lower than those recommended still affect cardiovascular morbidity and mortality. AIM: To investigate the association between short-term exposure to air pollutants and the daily diagnosis of acute coronary syndrome (ACS) at the emergency department (ED) of S. Croce Hospital (Cuneo, Italy), between 2011 and 2015. METHODS: We evaluated the effect of particulate matter (PM2.5-10), nitrogen dioxide and ozone as primary exposure, together with temperature and relative humidity as climatological control variables, on ED admissions for ACS (response variables). We studied residents aged ≥35 years, classified into three age groups (35-64, 65-74 and ≥75 years). Environmental data were analysed according to Poisson's regression, and conventional cardiovascular risk factors (CRFs; hypertension, diabetes, coronary artery disease, smoking and dyslipidaemia) were included as control variables. RESULTS: ED admissions for ACS were 1625/391,689, with 298 in 2011 (0.183%), 305 in 2012 (0.188%), 347 in 2013 (0.214%), 341 in 2014 (0.21%) and 334 in 2015 (0.206%), with a general growth rate of 2.08% (from 2011 to 2015). The CRFs examined were confirmed to be highly associated with occurrence of ACS. Our study identified PM2.5 and temperature in all age groups to be additional risk factors, with PM2.5 exposure (P<0.01) being a particular risk for those aged ≥75 years. Dose-response models confirmed only PM2.5 as the main environmental risk factor in elderly patients (relative risk 1.06, 95% confidence interval 1.02-1.11; lag time 0-3 days). We also found a consistent relative risk for temperature in all age groups. CONCLUSION: This study confirms the importance of PM2.5 as a risk factor for ACS, mostly in elderly patients, even in a city with low annual pollution rates.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Material Particulado/efeitos adversos , Saúde da População Urbana , Síndrome Coronariana Aguda/diagnóstico , Adulto , Fatores Etários , Idoso , Monitoramento Ambiental , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
13.
Int. arch. otorhinolaryngol. (Impr.) ; 24(1): 38-46, Jan.-Mar. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1090545

RESUMO

Abstract Introduction The clinical relevance of the anatomy and variations of the anterior ethmoidal artery (AEA) is outstanding, considering its role as a landmark in endoscopic surgery, its importance in the therapy of epistaxis, and the high risks related to iatrogenic injuries. Objective To provide an anatomical description of the course and relationships of the AEA, based on direct computed-tomography (CT)-based 3D volume rendering. Methods Direct volume rendering was performed on 18 subjects who underwent (CT) with contrast medium for suspected cerebral aneurism. Results The topographical location of 36 AEAs was assessed as shown: 10 dehiscent (27.8%), 20 intracanal (55.5%), 6 incomplete canals (16.7%). Distances from important topographic landmarks are reported. Conclusion This work demonstrates that direct 3D volume rendering is a valid imaging technique for a detailed description of the anterior ethmoidal artery thus representing a useful tool for head pre-operatory assessments.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Artérias/anatomia & histologia , Artérias/diagnóstico por imagem , Seio Etmoidal/irrigação sanguínea , Seio Etmoidal/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Tomografia Computadorizada por Raios X/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Estudos Retrospectivos , Base do Crânio/anatomia & histologia , Base do Crânio/irrigação sanguínea , Base do Crânio/diagnóstico por imagem , Meios de Contraste , Imageamento Tridimensional
14.
Int Arch Otorhinolaryngol ; 24(1): e38-e46, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31929832

RESUMO

Introduction The clinical relevance of the anatomy and variations of the anterior ethmoidal artery (AEA) is outstanding, considering its role as a landmark in endoscopic surgery, its importance in the therapy of epistaxis, and the high risks related to iatrogenic injuries. Objective To provide an anatomical description of the course and relationships of the AEA, based on direct computed-tomography (CT)-based 3D volume rendering. Methods Direct volume rendering was performed on 18 subjects who underwent (CT) with contrast medium for suspected cerebral aneurism. Results The topographical location of 36 AEAs was assessed as shown: 10 dehiscent (27.8%), 20 intracanal (55.5%), 6 incomplete canals (16.7%). Distances from important topographic landmarks are reported. Conclusion This work demonstrates that direct 3D volume rendering is a valid imaging technique for a detailed description of the anterior ethmoidal artery thus representing a useful tool for head pre-operatory assessments.

15.
Hip Int ; 28(2_suppl): 54-60, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30755123

RESUMO

INTRODUCTION:: This study evaluates mid-term results of acetabular revision using a hemispherical acetabular cup in Trabecular Titanium with a cage construct. METHODS:: We reviewed 36 acetabular revisions performed with the Delta Revision TT cup in 34 patients (mean age = 75, range: 45-92 years). Acetabular defect types (Paprosky classification) included (1) 2B ( n = 5), (2) 2C ( n = 7), (3) 3A ( n = 15), and (4) 3B ( n = 9). Morcellised bone allografts were used in 24 cases, and synthetic bone used in 11. Outcomes were evaluated using the Harris Hip Score (HHS), and the Verbal Rating Scale (VRS) for pain measurement. X-ray visualisation of cup position was used to discern signs of mobilisation and bone graft incorporation. Survivorship at post-revision follow-up (mean = 39.8; range 12-91.5 months) was calculated. RESULTS:: HHS increased from 40.5 to 87 ( p < 0.01). 68% of cases were pain free; by comparison, 32% had an average VRS score of 1.9 (range 1-3). The average cup inclination angle was 40.8° (30-52°) postoperatively, compared with 41.2° (30-52°) at follow-up; there were no signs of loosening or mobilisation. Centre of rotation was fully restored in 21 (58.3%) hips. According to Gie classification; bone graft incorporation grades were (1) 3 ( n = 21), (2) 2 ( n = 12) and (3) 1 ( n = 2). The survival rate was 100% for aseptic loosening and 91.7% for any cause of revision. CONCLUSIONS:: The Delta Revision TT cup promises good clinical and radiographic results at short- to mid-term follow-up, with high rates of survival rate and bone integration.


Assuntos
Acetábulo/cirurgia , Artroplastia de Quadril/métodos , Articulação do Quadril/diagnóstico por imagem , Prótese de Quadril , Radiografia/métodos , Acetábulo/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Articulação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Desenho de Prótese , Falha de Prótese , Reoperação
16.
Histochem Cell Biol ; 143(5): 531-43, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25511416

RESUMO

Recent studies have found that the inactivation of small hyaluronan (HA) fragments originating from native HA during inflammation reduced the inflammatory response in models of experimental arthritis. The stimulation of adenosine receptors A2A reduced inflammation by inhibiting NF-kB activation. The combination of both treatments was significantly more effective than either of the individual treatments. The aim of this study was to further investigate the effects of a combined treatment using the HA inhibitor Pep-1 and a selective A2AR agonist (CV-1808) on the structure and ultrastructure of the articular cartilage and on apoptosis in a model of collagen-induced arthritis (CIA) in mice. Arthritic mice were treated with Pep-1 and/or CV-1808 intraperitoneally daily for 20 days. At day 35, the hind limbs were processed for light microscopy (hematoxylin/eosin and Safranin-O-Fast Green) and for transmission and scanning electron microscopy. CIA increased IL-6, caspase-3 and caspase-7 mRNA expression and the related protein levels in arthritic articular cartilage, and significantly increased concentrations of Bcl-2-associated X protein (Bax), while B cell-lymphoma-2 protein (Bcl-2) was markedly reduced. The combined Pep-1/CV-1808 treatment significantly reduced CIA injury, particularly at the highest doses, demonstrated by the presence of Safranin-O-positive cartilage, with a smooth surface and normal chondrocytes in the superficial, intermediate and deep zones. Morphological data and histological scoring were strongly supported by the reduction in inflammation and apoptotic markers. The results further support the role of HA degradation and A2A receptors in arthritis.


Assuntos
Agonistas do Receptor A2 de Adenosina/farmacologia , Adenosina/análogos & derivados , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Artrite Experimental/tratamento farmacológico , Cartilagem Articular/efeitos dos fármacos , Ácido Hialurônico/antagonistas & inibidores , Articulações/efeitos dos fármacos , Peptídeos/farmacologia , Receptor A2A de Adenosina/efeitos dos fármacos , Adenosina/farmacologia , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Cartilagem Articular/metabolismo , Cartilagem Articular/ultraestrutura , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Colágeno Tipo II , Quimioterapia Combinada , Adjuvante de Freund , Ácido Hialurônico/metabolismo , Mediadores da Inflamação/metabolismo , Articulações/metabolismo , Articulações/ultraestrutura , Masculino , Camundongos Endogâmicos DBA , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Receptor A2A de Adenosina/metabolismo , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
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