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1.
Eur J Orthop Surg Traumatol ; 33(7): 3081-3088, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37017739

RESUMO

BACKGROUND: A clinical trial comparing MB (mobile-bearing) versus FB (fixed-bearing) in medial partial knee arthroplasty (PKA) in octagenarians has been conducted. The focus of the present study was on PROMs, range of motion (ROM), implant positioning and implants survivorship. The hypothesis of the present study was that MB implants performed better than FB in PKA in octogenarians. METHODS: The first group received FB PKA-PPK®; the second received MB PKA-Oxford. Patients were not randomly allocated. The following PROMs were administered at T0 (pre-operatively), T1 (1 year after surgery), and T2 (3 years after surgery): visual analogue scale (VAS), Knee Society Score (KSS) and Oxford Knee Score (OKS). Data regarding the implant survivorship and ROM were also collected. Furthermore, the following radiographic parameters were measured: Femoral component varus/valgus; Tibial component varus/valgus; Anteroposterior slope. RESULTS: At T0, 28 patients were included in the FB and 33 in the MB group. The surgical time was shorter in the FB group (p < 0.001). No difference between FB and MB in ROM, VAS, KSS, and OKS at each follow-up (p > 0.05). No difference was found in implant positioning (p > 0.05). At last follow-up, FB group reported three failures caused by aseptic loosening. Four failures were observed in the MB cohort: two for bearing dislocation and two for aseptic loosening. The Kaplan-Meier Curve found no differences in implant survivorship. CONCLUSIONS: According to the main findings of the present clinical trial, MB implants performed similar to FB in PKA in octogenarians. The FB group demonstrated shorted surgical time. No difference was found in patient reported outcome measures, ROM, implant positioning, and survivorship. LEVEL OF EVIDENCE: Level II, prospective study.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Idoso de 80 Anos ou mais , Humanos , Artroplastia do Joelho/efeitos adversos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Octogenários , Osteoartrite do Joelho/cirurgia , Estudos Prospectivos , Desenho de Prótese , Amplitude de Movimento Articular , Resultado do Tratamento
2.
Int J Mol Sci ; 24(3)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36768948

RESUMO

Osteoarthritis (OA) is a chronic disease characterized by joint tissue disruption and inflammation with a paucity of therapeutic options. Chondrocyte in vitro models are commonly used as the first step in evaluating new approaches and rely on the stimulation of an OA-like phenotype with inflammation often the method of choice. Inflammatory priming is frequently based on cytokines used at concentrations very far from the reality in the patients' synovial fluid (SF). The aim of this work was to compare the transcriptional response of chondrocytes to different inflammatory conditions: the high levels of IL1ß that are used for standardized inflammation protocols, OA-SF, IL1ß, IL6 and IFNγ at SF-like concentrations both individually and simultaneously to mimic a simplified "in vitro" SF. Both high IL1ß and OA-SF strongly influenced chondrocytes, while SF-like concentrations of cytokines gave weak (IL1ß alone or in combination) or no (IL6 and IFNγ alone) outcomes. Chondrocytes under the two most powerful polarizing conditions had a clearly distinct fingerprint, with only a shared albeit molecularly divergent effect on ECM stability, with IL1ß mainly acting on ECM degrading enzymes and OA-SF accounting for a higher turnover in favor of fibrous collagens. Moreover, OA-SF did not induce the inflammatory response observed with IL1ß. In conclusion, although partially similar in the endpoint phenotype, this work intends to encourage reflection on the robustness of inflammation-based in vitro OA models for molecular studies on chondrocytes.


Assuntos
Osteoartrite , Líquido Sinovial , Humanos , Condrócitos , Interleucina-6/genética , Osteoartrite/tratamento farmacológico , Citocinas/uso terapêutico , Inflamação
3.
Biology (Basel) ; 11(11)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36358333

RESUMO

Bone marrow-derived mesenchymal stromal cells (BMSCs)-based therapies show a great potential to manage inflammation and tissue degeneration in osteoarthritis (OA) patients. Clinical trials showed the ability to manage pain and activation of immune cells and allowed restoration of damaged cartilage. To date, a molecular fingerprint of BMSC-secreted molecules in OA joint conditions able to support clinical outcomes is missing; the lack of that molecular bridge between BMSC activity and clinical results hampers clinical awareness and translation into practice. In this study, BMSCs were cultured in synovial fluid (SF) obtained from OA patients and, for the first time, a thorough characterization of soluble factors and extracellular vesicles (EVs)-embedded miRNAs was performed in this condition. Molecular data were sifted through the sieve of molecules and pathways characterizing the OA phenotype in immune cells and joint tissues. One-hundred and twenty-five secreted factors and one-hundred and ninety-two miRNAs were identified. The combined action of both types of molecules was shown to, first, foster BMSCs interaction with the most important OA immune cells, such as macrophages and T cells, driving their switch towards an anti-inflammatory phenotype and, second, promote cartilage homeostasis assisting chondrocyte proliferation and attenuating the imbalance between destructive and protective extracellular matrix-related players. Overall, molecular data give an understanding of the clinical results observed in OA patients and can enable a faster translation of BMSC-based products into everyday clinical practice.

4.
J Photochem Photobiol B ; 234: 112505, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35839543

RESUMO

Melanosomes have been considered crucial targets in melanoma treatments. In this study we explored the role of melanosomes in photodynamic therapy (PDT), employing the synthetic Zn(II) phthalocyanine Pc13, a potent photosensitizer that promotes melanoma cell death after irradiation. Phototoxic action is mediated by reactive oxygen species increase. The internalization mechanism of Pc13 and its consequent subcellular localization were evaluated in melanotic B16-F0 cells. Pharmacological inhibitors of dynamin or caveolae, but not of clathrin, decreased Pc13 cellular uptake and phototoxicity. Similar results were obtained when cells over-expressed dominant negative mutants of dynamin-2 and caveolin-1, indicating that Pc13 is internalized by caveolae-mediated endocytosis. Confocal microscopy analysis revealed that Pc13 targets melanosomes and damage of these structures after irradiation was demonstrated by transmission electron microscopy. Treatment of pigmented B16-F0 and WM35 melanoma cells with the melanin synthesis inhibitor phenylthiourea for 48 h led to cell depigmentation and enhanced cell death after irradiation, whereas a 3-h period of inhibition did not modify melanin content but produced a marked reduction of Pc13 phototoxicity, together with a decrease of oxidative melanin synthesis intermediates. In contrast, the effect of Pc13 in amelanotic A375 cells was not altered by phenylthiourea treatment. These results provide evidence that melanosomes have a dual role in the efficacy of PDT. While melanin antagonizes the phototoxic action of Pc13, the release of cytotoxic synthetic intermediates to cytosol after irradiation and melanosome damage is conducive to the phototoxic response. Based on these findings, we demonstrate that melanosome-targeted PDT could be an effective approach for melanoma treatment.


Assuntos
Dermatite Fototóxica , Melanoma , Caveolina 1/metabolismo , Caveolina 1/farmacologia , Caveolina 1/uso terapêutico , Endocitose , Humanos , Indóis/química , Isoindóis , Melaninas/metabolismo , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Melanossomas/metabolismo , Melanossomas/ultraestrutura , Feniltioureia/metabolismo , Feniltioureia/farmacologia , Feniltioureia/uso terapêutico
5.
Biomolecules ; 12(2)2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35204816

RESUMO

Bone-marrow-derived stromal cells (BMSCs) have emerged as promising therapeutic option for the treatment of osteoarthritis (OA) due to their tissue regenerative and anti-inflammatory features. BMSCs' clinical potential is mainly ascribed to their released factors and extracellular vesicles (EVs), whose therapeutic portfolio may be modulated by the environment in vivo or specific priming in vitro. Within the array of molecules shaping EVs' power, miRNAs are considered privileged players. In this frame, a correct EV-miRNA detection and quantification is mandatory to understand and possibly boost BMSCs potential, either when envisioned as cell therapeutics or when proposed as producer of cell-free and clinical grade EVs. The aim of this study is to identify reliable reference genes (RGs) to study miRNAs in BMSC-EVs cultivated under standard or OA synovial fluid (OA-SF). miR-23a-3p and miR-221-3p emerged as the best candidates, respectively. Moreover, when both conditions were analyzed together, miR-24-3p resulted the most stable RGs, allowing for a sharper comparison of EVs content, further validated on the OA-related miRNA-193b-5p. The different RG stability ranking depending on the culturing conditions, as well as its divergence with respect to adipose (ASCs) and amniotic (hAMSCs) MSCs, confirm that miRNA RG selection in EVs is a mandatory step and that the identification of the most reliable candidate is greatly depending on the cell type and culturing/environmental conditions.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Osteoartrite , Medula Óssea/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoartrite/genética , Osteoartrite/metabolismo , Líquido Sinovial
6.
Knee Surg Sports Traumatol Arthrosc ; 30(3): 890-898, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33550449

RESUMO

PURPOSE: To compare the rate of return to sports and body mass index (BMI) reduction in patients who underwent surgery for unicompartmental knee arthroplasty (UKA) with either Cobalt-Chromium (CoCr) alloy UKA or with hypoallergenic UKA, stratified by age, gender and BMI. METHODS: Two consecutive cohorts of patients with a total of 172 UKA and a minimum 2-year follow-up period were prospectively included in this comparative study. The first cohort consisted of 136 consecutive series of standard Cobalt-Chromium (CoCr Group). The second cohort consisted of 36 consecutive mobile-bearing hypoallergenic Titanium Niobium Nitride UKA, (TiNbN Group). The clinical evaluation was based on the University of California, Los Angeles (UCLA) activity scores and the High-Activity Arthroplasty Score (HAAS) evaluated on the day before surgery (T0) and after a minimum follow-up of 12 months (T1) and 24 months (T2). Radiographic evaluation performed at T2 included the femoral component position in varus/valgus, the tibial component in varus/valgus and the anteroposterior slope. RESULTS: No statistical differences were found between the groups at each follow-up, as shown by the UCLA and HAAS score (n.s.). Both groups showed a statistically significant improvement (p < 0.05) at each follow-up.. Both groups showed a statistically significant BMI reduction between T0 and T2 (p < 0.05). Radiographic analysis revealed no statistical differences between the two groups in terms of the three measures after the final follow-up (n.s.). All the subgroups showed a significant (p < 0.05) rate of return to sport if compared with the preoperative value (T2 versus T0), except for male in TiNbN group. CONCLUSIONS: Both TiNbN and CoCr medial mobile-bearing UKA enabled patients to return to sports after the final follow-up, regardless of age, BMI, gender and metal sensitivity. These findings inform shared decision making and can help to manage patient expectations after surgery, in particular, in active patients with an overt metal allergy, a specific hypoallergenic implant should be considered the gold standard implant in partial knee replacement surgery. LEVEL OF EVIDENCE: Cohort Study, Level III. REGISTRATION: researchregistry6250- www.researchregistry.com .


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Índice de Massa Corporal , Cromo , Cobalto , Estudos de Coortes , Humanos , Articulação do Joelho/cirurgia , Masculino , Osteoartrite do Joelho/cirurgia , Estudos Retrospectivos , Volta ao Esporte , Resultado do Tratamento
7.
Knee Surg Sports Traumatol Arthrosc ; 30(3): 1050-1056, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33751156

RESUMO

PURPOSE: The aim of this study was to assess the return to amateur sports of patients under 65 years, following medial unicompartmental knee arthroplasty (mUKA) versus lateral unicompartmental knee arthroplasty (lUKA). It was hypothesized that patients younger than 65 years who underwent lateral or medial unicondylar knee replacement will result in similar rates to amateur sports, at a minimum follow-up of 2 years. METHOD: Patients who underwent medial or lateral UKA participated in a 2-year follow-up program, where they were clinically evaluated for their return to amateur sports, using the University of California, Los Angeles (UCLA) activity scale and the High-Activity Arthroplasty Score (HAAS). Furthermore, subgroup analyses by gender and age were performed. Power analysis was performed to ensure sample size considering that lUKA is implanted ten times less frequently than its medial counterpart. RESULTS: There were 85 patients who completed the entire minimum 2-year follow-up of which 73 belonged to the mUKA group and 12 to the lUKA group. No preoperative differences were found between the groups regarding the gender, the affected side, age, and mean follow-up. Both groups showed statistically significant improvement (p < 0.05) in their return to amateur sports in all parameters (UCLA and HAAS). No differences among the two groups were found at T0 and T1 (n.s.). All subgroups showed a statistically significant improvement (p < 0.05) with respect to the preoperative value, except for UCLA for lUKA with less than 60 years and HAAS for males in the lUKA group (n.s.). No differences were found among subgroups both at To and T1 (n.s.). CONCLUSION: Both mUKA and lUKA procedures enabled all young and active patients a certain return to amateur sports 2 years after surgery, regardless of age and gender. UKA, medial or lateral, should always be considered for the treatment of isolated osteoarthritis in young and active patients with high functional demands. LEVEL OF EVIDENCE: Cohort Study, Level of Evidence III. REGISTRATION: Researchregistry6221 - Research Registry www.researchregistry.com .


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Artroplastia do Joelho/métodos , Estudos de Coortes , Humanos , Articulação do Joelho/cirurgia , Masculino , Osteoartrite do Joelho/cirurgia , Estudos Retrospectivos , Volta ao Esporte , Resultado do Tratamento
8.
Arch Orthop Trauma Surg ; 142(11): 3449-3460, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34669039

RESUMO

PURPOSE: The purpose of this study was to determine the changes in patellar heights by comparing standardised pre- and post-operative radiographs in a consecutive series of patients undergoing unicompartmental knee arthroplasty (UKA) with two different approaches and implant designs [fixed bearing (FB) vs mobile bearing (MB)] and to correlate the patellar heights with clinical outcomes. METHODS: One hundred and seventy-two UKA patients were prospectively enrolled in the study. 75 patients underwent a minimally invasive FB medial UKA (referred to hereinafter as the 'FB group'); 97 patients were treated with a minimally invasive MB medial UKA. The pre-operative and mid-term (1-year) post-operative patellar heights and clinical scores of these groups of patients were compared using the Insall-Salvati (IS) and Caton-Deschamps (CD) indices and the Oxford Knee Score (OKS). RESULTS: No differences were found between the two groups either with regard to the pre-operative data (p > 0.05) or between pre- and post-operative radiographic scores at the time of each follow-up (p > 0.05). Both the groups reported a significant clinical improvement (p<0.05) as did all the sub-groups (p < 0.05). In the MB group, a higher CD index in females was found at the final follow-up stage (p = 0.043) and a higher pre-operative CD index was found in patients with BMI ≥ 28 (p = 0.040). A statistically negative correlation was found between the pre-operative OKS and pre-operative IS index (rho=- 0.165; p=0.031). CONCLUSIONS: Both FB and MB arthroplastys with different surgical approaches did not change the patellar height regardless of the age, gender and BMI at short-medium-term follow-up. The post-operative patellar height seems not to be correlated with the clinical outcomes. A higher pre-operative IS index was correlated with knee pain and function. LEVEL OF EVIDENCE: Level II-prospective comparative study. STUDY REGISTRATION: Researchregistry6433- www.researchregistry.com .


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Artroplastia do Joelho/efeitos adversos , Feminino , Humanos , Articulação do Joelho/cirurgia , Prótese do Joelho/efeitos adversos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/cirurgia , Estudos Prospectivos , Resultado do Tratamento
9.
Lasers Surg Med ; 53(3): 344-358, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32525252

RESUMO

BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) is an antitumor procedure clinically approved for the treatment of different cancer types. Despite strong efforts and promising results in this field, PDT has not yet been approved by any regulatory authority for the treatment of colorectal cancer, one of the most prevalent gastrointestinal tumors. In the search of novel therapeutic strategies, we examined the in vivo effect of PDT with a lipophilic phthalocyanine (Pc9) encapsulated into polymeric poloxamine micelles (T1107) in a murine colon carcinoma model. STUDY DESIGN/MATERIALS AND METHODS: In vivo assays were performed with BALB/c mice challenged with CT26 cells. Pc9 tumor uptake was evaluated with an in vivo imaging system. Immunofluorescence, western blot, and flow cytometry assays were carried out to characterize the activation of apoptosis and an antitumor immune response. RESULTS: Pc9-T1107 effectively delayed tumor growth and prolonged mice survival, without generating systemic or tissue-specific toxicity. The induction of an apoptotic response was characterized by a decrease in the expression levels of Bcl-XL , Bcl-2, procaspase 3, full length Bid, a significant increment in the amount of active caspase-3 and the detection of PARP-1 cleavage. Infiltration of CD8+ CD107a+ T cells and higher levels of interferon-γ and tumor necrosis factor-α were also found in PDT-treated tumors. CONCLUSIONS: Pc9-T1107 PDT treatment reduced tumor growth, inducing an apoptotic cell death and activating an immune response. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.


Assuntos
Neoplasias do Colo , Fotoquimioterapia , Animais , Apoptose , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Imunidade , Isoindóis , Camundongos , Camundongos Endogâmicos BALB C , Compostos Organometálicos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Zinco/farmacologia , Zinco/uso terapêutico , Compostos de Zinco
10.
Free Radic Biol Med ; 152: 743-754, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-31962157

RESUMO

Melanoma is the most aggressive type of skin cancer, highly resistant to conventional therapies. Photodynamic therapy (PDT) is a minimally invasive treatment modality that combines the use of a photosensitizer, visible light and molecular oxygen, leading to oxidative stress in the specific site of irradiation. The cationic zinc(II) phthalocyanine Pc13 has shown to be a potent photosensitizer in different melanoma cell lines. In this study, we explored the intracellular signaling pathways triggered by Pc13 PDT and the role of these cascades in the phototoxic action of Pc13 in human melanoma A375 cells. Activation of MAPKs p38, ERK, JNK and PI3K-I/AKT was observed after treatment and prevented by using the antioxidant trolox. Inhibition of p38 reduced Pc13 phototoxicity, whereas blockage of JNK potentiated cell death. Results obtained indicate that p38 is involved in the cleavage of PARP-1, an important mediator of apoptosis. On the other hand, Pc13 irradiation induced the activation of an autophagic program, as evidenced by enhanced levels of Beclin-1, LC3-II and GFP-LC3 punctate staining. We also demonstrated that this autophagic response is promoted by JNK and negatively regulated by PI3K-I/AKT pathway. The blockage of autophagy increased Pc13 phototoxicity and enhanced PARP-1 cleavage, revealing a protective role of this mechanism, which tends to prevent apoptotic cell death. Furthermore, reduced susceptibility to treatment and increased activation of autophagy were detected in A375 cells submitted to repeated cycles of Pc13 PDT, indicating that autophagy could represent a mechanism of resistance to PDT. The efficacy of Pc13 PDT and an improved phototoxic action in combination with chloroquine were also demonstrated in tumor spheroids. In conclusion, we showed the interplay between apoptotic and autophagic signaling pathways triggered by Pc13 PDT-induced oxidative stress. Thus, autophagy modulation represents a promising therapeutic strategy to potentiate the efficacy of PDT in melanoma.


Assuntos
Melanoma , Fotoquimioterapia , Apoptose , Autofagia , Linhagem Celular Tumoral , Humanos , Indóis , Isoindóis , Melanoma/tratamento farmacológico , Estresse Oxidativo , Espécies Reativas de Oxigênio , Zinco
11.
J Am Podiatr Med Assoc ; 109(5): 351-356, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31599666

RESUMO

BACKGROUND: Sever's disease is a common cause of pain in growing kids. Many papers reported in the literature discuss this pathologic condition, but no consensus regarding its etiology has been found among researchers. The aim of the present study was to describe the epidemiologic profile and associated factors of 430 athletic children in a population-based sample of soccer (29.5%), basketball (48.1%), and volleyball (22.3%) players aged 6 to 14 years. METHODS: Every athlete was evaluated through physical examination, the Foot Posture Index (FPI), the Oxford Ankle Foot Questionnaire, and a custom-made sports questionnaire. RESULTS: These data show that body mass index, sex, terrain type, sports discipline, and FPI should not be considered as risk factors for calcaneal apophysitis, whereas a significantly higher risk has been found in younger individuals (P < .01), in those with fewer training sessions per week (P = .02), and in those with shorter training sessions (P < .01). CONCLUSIONS: The prevalence of Sever's disease in the athletic children evaluated in the present study was higher in younger and less active patients, whereas no differences were registered by sex, FPI, body mass index, terrain type, or sports discipline.


Assuntos
Doenças do Pé/epidemiologia , Calcanhar , Dor/epidemiologia , Esportes , Tendão do Calcâneo , Adolescente , Fatores Etários , Calcâneo , Criança , Feminino , Doenças do Pé/diagnóstico , Humanos , Masculino , Dor/etiologia , Exame Físico , Prevalência , Fatores de Risco , Inquéritos e Questionários
12.
J Clin Med ; 8(6)2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31159439

RESUMO

BACKGROUND: This study aims to investigate the clinical and radiological efficacy of three-dimensional acellular scaffolds (MaioRegen) in restoring osteochondral knee defects. METHODS: MEDLINE, Scopus, CINAHL, Embase, and Cochrane Databases were searched for articles in which patients were treated with MaioRegen for osteochondral knee defects. RESULTS: A total of 471 patients were included in the study (mean age 34.07 ± 5.28 years). The treatment involved 500 lesions divided as follows: 202 (40.4%) medial femoral condyles, 107 (21.4%) lateral femoral condyles, 28 (5.6%) tibial plateaus, 46 (9.2%) trochleas, 74 (14.8%) patellas, and 43 (8.6%) unspecified femoral condyles. Mean lesion size was 3.6 ± 0.85 cm2. Only four studies reported a follow-up longer than 24 months. Significant clinical improvement has been reported in almost all studies with further improvement up to 5 years after surgery. A total of 59 complications were reported of which 52 (11.1%) experienced minor complications and 7 (1.48%) major complications. A total of 16 (3.39%) failures were reported. CONCLUSION: This systematic review describes the current available evidence for the treatment of osteochondral knee defects with MaioRegen Osteochondral substitute reporting promising satisfactory and reliable results at mid-term follow-up. A low rate of complications and failure was reported, confirming the safety of this scaffold. Considering the low level of evidence of the study included in the review, this data does not support the superiority of the Maioregen in terms of clinical improvement at follow-up compared to conservative treatment or other cartilage techniques.

13.
Stem Cell Res Ther ; 10(1): 109, 2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30922413

RESUMO

BACKGROUND: Osteoarthritis (OA) is the most prevalent joint disease, and to date, no options for effective tissue repair and restoration are available. With the aim of developing new therapies, the impact of mesenchymal stem cells (MSCs) has been explored, and the efficacy of MSCs started to be deciphered. A strong paracrine capacity relying on both secreted and vesicle-embedded (EVs) protein or nucleic acid-based factors has been proposed as the principal mechanism that contributes to tissue repair. This work investigated the mechanism of internalization of extracellular vesicles (EVs) released by adipose-derived MSCs (ASCs) and the role of shuttled miRNAs in the restoration of homeostasis in an in vitro model of human fibroblast-like synoviocytes (FLSs) from OA patients. METHODS: ASC-EVs were isolated by differential centrifugation and validated by flow cytometry and nanoparticle tracking analysis. ASC-EVs with increased hyaluronan (HA) receptor CD44 levels were obtained culturing ASCs on HA-coated plastic surfaces. OA FLSs with intact or digested HA matrix were co-cultured with fluorescent ASC-EVs, and incorporation scored by flow cytometry and ELISA. ASC-EV complete miRNome was deciphered by high-throughput screening. In inflamed OA FLSs, genes and pathways potentially regulated by ASC-EV miRNA were predicted by bioinformatics. OA FLSs stimulated with IL-1ß at physiological levels (25 pg/mL) were treated with ASC-EVs, and expression of inflammation and OA-related genes was measured by qRT-PCR over a 10-day time frame with modulated candidates verified by ELISA. RESULTS: The data showed that HA is involved in ASC-EV internalization in FLSs. Indeed, both removal of HA matrix presence on FLSs and modulation of CD44 levels on EVs affected their recruitment. Bioinformatics analysis of EV-embedded miRNAs showed their ability to potentially regulate the main pathways strictly associated with synovial inflammation in OA. In this frame, ASC-EVs reduced the expression of pro-inflammatory cytokines and chemokines in a chronic model of FLS inflammation. CONCLUSIONS: Given their ability to affect FLS behavior in a model of chronic inflammation through direct interaction with HA matrix and miRNA release, ASC-EVs confirm their role as a novel therapeutic option for osteoarthritic joints.


Assuntos
Vesículas Extracelulares , Ácido Hialurônico/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Modelos Biológicos , Osteoartrite , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Humanos , Células-Tronco Mesenquimais/patologia , Osteoartrite/metabolismo , Osteoartrite/patologia
14.
Apoptosis ; 24(1-2): 119-134, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30603830

RESUMO

Melanoma is an aggressive form of skin carcinoma, highly resistant to traditional therapies. Photodynamic therapy (PDT) is a non-invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. In this work we evaluated the effect of a cationic zinc(II) phthalocyanine (Pc13) as photosensitizer on a panel of melanoma cells. Incubation with Pc13 and irradiation induced a concentration and light dose-dependent phototoxicity. In order to study the mechanism underlying Pc13-related cell death and to compare the effect of different doses of PDT, the most sensitive melanoma B16F0 cells were employed. By confocal imaging we showed that Pc13 targeted lysosomes and mitochondria. After irradiation, a marked increase in intracellular reactive oxygen species was observed and a complete protection from Pc13 phototoxicity was reached in the presence of the antioxidant trolox. Acridine orange/ethidium bromide staining showed morphological changes indicative of both apoptosis and necrosis. Biochemical hallmarks of apoptosis, including a significant decrease in the expression levels of Bcl-2, Bcl-xL and Bid and mitochondrial membrane permeabilization, were observed at short times post irradiation. The consequent release of cytochrome c to cytosol and caspase-3 activation led to PARP-1 cleavage and DNA fragmentation. Simultaneously, a dose dependent increase of lactate dehydrogenase in the extracellular compartment of treated cells revealed plasma membrane damage characteristic of necrosis. Taken together, these results indicate that a dual apoptotic and necrotic response is triggered by Pc13 PDT-induced oxidative stress, suggesting that combined mechanisms of cell death could result in a potent alternative for melanoma treatment.


Assuntos
Apoptose , Indóis/farmacologia , Melanoma/patologia , Compostos Organometálicos/farmacologia , Estresse Oxidativo , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Neoplasias Cutâneas/patologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Linhagem Celular Tumoral , Humanos , Indóis/efeitos da radiação , Raios Infravermelhos/uso terapêutico , Isoindóis , Melanoma/metabolismo , Melanoma/terapia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Necrose , Compostos Organometálicos/efeitos da radiação , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Fármacos Fotossensibilizantes/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/efeitos da radiação , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/terapia , Compostos de Zinco
15.
Joints ; 7(4): 222-227, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34235390

RESUMO

In this report, we present a case of a 57-year-old man complaining of pain in both his hips. Clinically, the patient reported lameness and reduction in the range of motion of the hips. Radiographic imaging showed a very narrow medullary femoral canal, confirmed by a computed tomography scan. In consideration of the narrowness of the femoral canal and cortex thickening, and due to the rarity of the clinical case, we opted to use a custom-made prosthesis. We performed total hip arthroplasty, initially on the right side. One year later, we repeated the procedure on the left side. One year after the last surgery, the patient reported well-being and continuous improvement in walking, with no complications. This case report highlights the features and the critical issues related to this kind of surgery in patients affected by Paget's disease of the bone and the importance of custom-made implants in challenging cases.

16.
World J Orthop ; 4(3): 154-6, 2013 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-23878785

RESUMO

Femoral artery pseudoaneurysms (FAPs) have been described following internal fixation of intertrocantheric, subtrocantheric and intracapsular femoral neck fractures as well as core decompression of the femoral head. The diagnosis of FAP is usually delayed because of non-specific clinical features like pain, haematoma, swelling, occasional fever and unexplained anaemia. Because of the insidious onset and of the possible delayed presentation of pseudoaneurysms, orthopaedic and trauma surgeons should be aware of this complication. We report a case of Profunda Femoris arterial branch pseudoaneurysm, diagnosed in a 40-year-old male 4 wk after revision with Kuntscher intramedullary nail of a femoral shaft nonunion. The diagnosis was achieved by computed tomography angiography and the lesion was effectively managed by endovascular repair. The specific literature and suggestions for treatment are discussed in the paper.

17.
Drugs R D ; 11(2): 137-45, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21545190

RESUMO

BACKGROUND AND OBJECTIVES: Stenosing tenosynovitis (trigger finger) is one of the most common causes of pain and disability in the hand, which may often require treatment with anti-inflammatory drugs, corticosteroid injection, or open surgery. However, there is still large room for improvement in the treatment of this condition by corticosteroid injection. The mechanical, visco-elastic, and antinociceptive properties of hyaluronic acid may potentially support the use of this molecule in association with corticosteroids for the treatment of trigger finger. This study examines the feasibility and safety of ultrasound-guided injection of a corticosteroid and hyaluronic acid compared, for the first time, with open surgery for the treatment of trigger finger. METHODS: This was a monocentric, open-label, randomized study. Consecutive patients aged between 35 and 70 years with ultrasound-confirmed diagnosis of trigger finger were included. Patients were randomly assigned to either ultrasound-guided injection of methylprednisolone acetate 40 mg/mL with 0.8 mL lidocaine into the flexor sheath plus injection of 1 mL hyaluronic acid 0.8% 10 days later (n = 15; group A), or to open surgical release of the first annular pulley (n = 15; group B). Clinical assessment of the digital articular chain was conducted prior to treatment and after 6 weeks, and 3, 6, and 12 months. The duration of abstention from work and/or sports activity, and any treatment complications or additional treatment requirements (e.g. physiotherapy, compression, medication) were also recorded. RESULTS: Fourteen patients (93.3%) in group A had complete symptom resolution at 6 months, which persisted for 12 months in 11 patients (73.3%), while three patients experienced recurrences and one experienced no symptom improvements. No patients in group A reported major or minor complications during or after corticosteroid injection, or required a compression bandage. All 15 patients in group B achieved complete resolution of articular impairment by 3 weeks after surgery, but ten patients were assigned to physiotherapy and local and/or oral analgesics for complete resolution of symptoms, which was approximately 30-40 days postsurgery. The mean duration of abstention from work and/or sport was 2-3 days in group A and 26 days in group B. CONCLUSIONS: Although the limited sample size did not allow any statistical comparison between treatment groups, and therefore all the findings should be regarded as preliminary, the results of this explorative study suggest that ultrasound-guided injection of a corticosteroid and hyaluronic acid could be a safe and feasible approach for the treatment of trigger finger. It is also associated with a shorter recovery time than open surgery, which leads to a reduced abstention from sports and, in particular, work activities, and therefore may have some pharmacoeconomic implications, which may be further explored. In light of the promising results obtained in this investigation, further studies comparing ultrasound-guided injection of corticosteroid plus hyaluronic acid with corticosteroid alone are recommended in order to clarify the actual benefits attributable to hyaluronic acid.


Assuntos
Corticosteroides/uso terapêutico , Ácido Hialurônico/uso terapêutico , Dedo em Gatilho/tratamento farmacológico , Dedo em Gatilho/cirurgia , Ultrassonografia de Intervenção , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Ácido Hialurônico/administração & dosagem , Injeções Intralesionais/efeitos adversos , Injeções Intralesionais/métodos , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Metilprednisolona/análogos & derivados , Metilprednisolona/uso terapêutico , Acetato de Metilprednisolona , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias , Resultado do Tratamento , Dedo em Gatilho/diagnóstico , Dedo em Gatilho/diagnóstico por imagem
18.
J Orthop Surg (Hong Kong) ; 17(2): 151-6, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19721141

RESUMO

PURPOSE: To report the clinical and radiographic results and complications of the Delta III reverse prosthesis. METHODS: 24 women and 2 men aged 62 to 84 (mean, 75) years underwent total shoulder replacement using the Delta III reverse prosthesis. Patient diagnoses were massive rotator cuff tear (n=20), disabling sequelae of proximal humeral fractures (n=3), and failure of an unconstrained arthroplasty (n=3). Clinical and functional results were assessed using the Constant scale. Active range of motion (ROM) was measured. Scapular notching and radiolucent lines around the humeral component were evaluated using radiographs. Patient satisfaction of the treatment was evaluated by a direct interview. RESULTS: 23 patients were followed up for 26 to 84 (mean, 42) months. Two patients had loosening of the glenoid component (at 6 months and 5 years) and underwent revision surgery. There were no instances of infection, instability, or acromial fracture. Only active elevation improved significantly after surgery, as did both the absolute and adjusted Constant scores. 12 patients were completely pain-free, 9 complained of slight pain, and one of moderate pain. The severity of scapular notching progressed with time. 15 patients were satisfied with the treatment, 6 were partially satisfied, and 2 were not satisfied. CONCLUSION: The Delta III prosthesis restores shoulder function but has biomechanical limits. Its use should be limited to elderly patients with severe impairment of the glenohumeral joint. Scapular notching is a main concern for the long-term survival of the implant.


Assuntos
Artroplastia de Substituição/métodos , Prótese Articular , Articulação do Ombro/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Entrevistas como Assunto , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/cirurgia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Complicações Pós-Operatórias , Falha de Prótese , Radiografia , Amplitude de Movimento Articular , Reoperação , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/cirurgia , Lesões do Manguito Rotador , Fraturas do Ombro/diagnóstico por imagem , Fraturas do Ombro/cirurgia , Articulação do Ombro/diagnóstico por imagem , Resultado do Tratamento
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