Papers by Julio Fernandes
Current Rheumatology Reports, 1999
International Journal of Nanomedicine, 2013
Genetically modified mesenchymal stem cells (MSCs) have great potential in the application of reg... more Genetically modified mesenchymal stem cells (MSCs) have great potential in the application of regenerative medicine and molecular therapy. In the present manuscript, we introduce a nanopolymer, polyethylenimine600-β-cyclodextrin (PEI600-β-CyD), as an efficient polyplex-forming plasmid delivery agent with low toxicity and ideal transfection efficiency on primary MSCs. PEI600-β-CyD causes significantly less cytotoxicity and apoptosis on MSCs than 25 kDa high-molecular-weight PEI (PEI25kDa). PEI600-β-CyD also exhibits similar transfection efficiency as PEI25kDa on MSCs, which is higher than that of PEI600Da. Quantum dot-labeled plasmids show that PEI600-β-CyD or PEI25kDa delivers the plasmids in a more scattered manner than PEI600Da does. Further study shows that PEI600-β-CyD and PEI25kDa are more capable of delivering plasmids into the cell lysosome and nucleus than PEI600Da, which correlates well with the results of their transfection-efficiency assay. Moreover, among the three vectors, PEI600-β-CyD has the most capacity of enhancing the alkaline phosphatase activity of MSCs by transfecting bone morphogenetic protein 2, 7, or special AT-rich sequence-binding protein 2. These results clearly indicate that PEI600-β-CyD is a safe and effective candidate for the nonviral gene delivery of MSCs because of its ideal inclusion ability and proton sponge effect, and the application of this nanopolymer warrants further investigation.
Current Rheumatology Reviews, 2005
Journal of Biomechanics, 2010
The pivot shift test reproduces a complex instability of the knee joint following rupture of the ... more The pivot shift test reproduces a complex instability of the knee joint following rupture of the anterior cruciate ligament. The grade of the pivot shift test has been shown to correlate to subjective criteria of knee joint function, return to physical activity and long-term outcome. This severity is represented by a grade that is attributed by a clinician in a subjective manner, rendering the pivot shift test poorly reliable.
Knee, 2011
The pivot shift test is the only clinical test which correlates with knee function following rupt... more The pivot shift test is the only clinical test which correlates with knee function following rupture of the ACL. A grade is given to the pivot shift in a subjective manner, leading to efforts to quantify the bone movements and correlate them to the grade. However, the dynamic and unconstrained nature of the manoeuvre introduces important kinematic variability.Our main objective was to develop a method to lessen the variability attributable to clinician technique, therefore increasing inter-grade differences.Three different orthopaedic surgeons each performed the pivot shift test on 12 subjects. Knee joint kinematics were recorded using electromagnetic motion capture devices. Inter-clinician variability was quantified and a method was developed to diminish it, using the angular velocity of flexion. This method was then applied to a larger population composed of 127 knees with various degrees of instability, evaluated by one of eight different orthopaedic surgeons.The clinical grades given by the clinicians were in almost perfect agreement (kappa = 0.83). Normalization of kinematic parameters using the angular velocity of knee joint flexion produced by the clinicians reduced the intra-clinician variability by 20%, resulting in an intra-class correlation coefficient (ICC) of 0.52, up from 0.41 before normalization. This allowed for more significant differences between the grades of pivot shift.Simple normalisation of pivot shift kinematics using the angular velocity of flexion reduces clinician-related variability and allows for significant differences between the different grades. These results are an important step towards developing an objective measurement tool for the pivot shift phenomenon.
Journal of Biomechanics, 2010
The pivot shift test reproduces a complex instability of the knee joint following rupture of the ... more The pivot shift test reproduces a complex instability of the knee joint following rupture of the anterior cruciate ligament. The grade of the pivot shift test has been shown to correlate to subjective criteria of knee joint function, return to physical activity and long-term outcome. This severity is represented by a grade that is attributed by a clinician in a subjective manner, rendering the pivot shift test poorly reliable.
Immunobiology, 2009
The concept of using mesenchymal stem cells (MSCs) in bone repair has progressively evolved, and ... more The concept of using mesenchymal stem cells (MSCs) in bone repair has progressively evolved, and the goal of cell-mediated therapy is to prolong the natural physiological abilities of healing, or substitute them, when these are lacking, failing, or progressing too slowly. The future application of MSCs in human therapies depends on the establishment of preclinical studies with other mammals, such as mouse. Surprisingly, the immunologic properties of murine MSCs remain poorly documented. In the present study, flow cytometry revealed that undifferentiated murine MSCs and osteogenic cells differentiated from MSCs (DOCs) express major histocompatibility complex (MHC) class I (H-2(b)), but not class II (I-A(b)). After exposure to interferon-gamma (IFN-gamma) for 48h, MHC class II and costimulatory molecules (B7-1 and B7-2) on the cell surface showed evident up-regulation. Undifferentiated MSCs and DOCs proved to be poor stimulators of T cell proliferation, eliciting alloreactive lymphocyte proliferative responses as low-allogenic stimulators. Initial results show that the expression of MHC class I, MHC class II, B7-1 and B7-2 was similar on human bone morphogenetic protein 2 (BMP2)-expressing recombinant adenoviral vector (AdBMP2) transduced MSCs (30 MOI) when compared with non-transduced cells. However, AdBMP2 gene transfected MSCs elicited significant stimulatory responses. The findings will be important for studying the in vivo behaviour and the fate of MSCs after grafting in mouse pathology models in bone regeneration.
Journal of Arthroplasty, 2011
The purpose of this study was to evaluate the outcome of trabecular metal (TM) acetabular compone... more The purpose of this study was to evaluate the outcome of trabecular metal (TM) acetabular components used in revision hip arthroplasty with major bone deficiency. We retrospectively reviewed the records of 46 patients undergoing revision hip arthroplasty with severe acetabular bone loss. Clinical outcomes were assessed using Harris Hip Score, Western Ontario and McMaster Universities, and Short-Form 12. Mean follow-up was 50 months. All patients had Paprosky type IIc or III acetabular bone deficiency. Major complications included 1 infection, 2 dislocations, and 1 arterial bleeding. Average Harris Hip Score was 78.2. Short-Form 12 scores were within population-based age-matched averages. Western Ontario and McMaster Universities scores were mainly in the 2 lowest disability categories. Porous tantalum shows promising results in revision arthroplasty with severe acetabular bone loss.
European Journal of Radiology, 1991
A retrospective analysis of the MR findings in 92 cases of acoustic neuromas is presented. The me... more A retrospective analysis of the MR findings in 92 cases of acoustic neuromas is presented. The method of examination included in all cases intravenous injection of Gadolinium (Gd-DTPA or DOTA) with realization of sections in the axial and coronal planes. In 21 cases native MR studies were performed in the axial plane, before Gadolinium injection, with TlWI (n = 21), and T2WI (n = 6) images. Tumors were strictly intracanalar in 19 cases (20.7%), only localized in the cerebellopontine angle (CPA) in 5 cases (5.4%), and in 68 cases (73.9%) the tumors had intra-and extracanalar components. In this last group of lesions, 63.2% completely filled the internal auditory canal (IAC), and 36.8% occupied the internal portion of the IAC. In most cases (85.3 %) the mean diameter of the CPA component was less than or equal to 2.5 cm. Lesions were more frequently homogeneous (58.8%) after Gd iv.-enhancement.
Clinical Orthopaedics and Related Research, 2000
Morphologic changes observed in osteoarthritis include cartilage erosion and a variable degree of... more Morphologic changes observed in osteoarthritis include cartilage erosion and a variable degree of synovial inflammation. Proinflammatory cytokines such as interleukin-1 beta, locally produced by the inflamed synovium, also likely contribute to these alterations. Despite an extensive armamentarium and numerous surgical options, osteoarthritis remains incurable, and an improved approach in the treatment of this disease is imperative. Drug delivery is a major weakness of existing antiarthritic therapies. Local delivery of antiinflammatory cytokines or the in vivo induction of their expression using gene transfer may provide a novel approach for the treatment of osteoarthritis. Evidence of the efficacy of gene therapy in osteoarthritis remains very scarce. To the authors' knowledge, there is no clinical research protocol en route for the treatment of osteoarthritis using gene therapy. The authors present the only two studies that have proved successful in treating animal models of osteoarthritis using gene therapy, and propose an overview of several strategies for the development of gene therapy in osteoarthritis treatment in the future.
Biomacromolecules, 2006
A polymer analogous synthesis involving the reductive amination of phosphorylcholine (PC)-glycera... more A polymer analogous synthesis involving the reductive amination of phosphorylcholine (PC)-glyceraldehyde with primary amines of deacetylated chitosan (M(w) approximately 57000 g mol(-1)) was used to prepare phosphorylcholine-substituted chitosans (PC-CH) with a degree of substitution (DS) ranging from approximately 11 to approximately 53 mol % PC-substituted glucosamine residues. The PC-CH derivatives were characterized by (1)H NMR spectroscopy, FTIR spectroscopy, and multiangle laser light scattering gel permeation chromatography (MALLS-GPC). The pK(a) of the PC-substituted amine groups (pK(a) approximately 7.20) was determined by (1)H NMR titration. The PC-CH samples (1.0 g L(-1)) were shown to be nontoxic using an MTT assay performed with human KB cells. Aqueous solutions of PC-CH samples (4.0 g L(-1)) of DS >or= 22 mol % PC-substituted glucosamine residues remained clear, independently of pH (4.0 < pH < 11.0). The remarkable water solubility and nontoxicity displayed by the new PC-CH samples open up new opportunities in the design of chitosan-based biomaterials and nanoparticles.
Arthritis & Rheumatism, 1995
To examine the effects of tenidap and diclofenac on osteoarthritic lesions and metalloprotease ac... more To examine the effects of tenidap and diclofenac on osteoarthritic lesions and metalloprotease activity in experimental osteoarthritis (OA). The anterior cruciate ligament of the right stifle joint of 25 mongrel dogs was sectioned by a stab wound. Seven dogs received no treatment, 6 were treated with oral omeprazole (20 mg/day), another 6 were treated with diclofenac (0.25 mg/kg/twice daily) plus omeprazole (20 mg/day), and 6 received oral tenidap (3 mg/kg/twice daily) plus omeprazole (20 mg/day). The dogs received medication for 8 weeks; all dogs were killed at the end of this period. Eight normal dogs were used as controls. Lesions were evaluated macroscopically for the incidence and size of osteophytes and the area and grade of cartilage erosions on the condyles and plateaus, along with histologic evaluation of the severity of the cartilage lesions and synovial inflammation. Stromelysin and collagenase activities and the collagenase messenger RNA (mRNA) level were measured in cartilage and synovial membrane. Compared with the untreated or omeprazole-treated OA groups, the dogs treated with tenidap exhibited significant reduction in the incidence (P < or = 0.001) and size (P < or = 0.0001) of osteophytes. Tenidap also significantly decreased the size and grade of cartilage macroscopic lesions, as well as the histologic severity of cartilage lesions on both condyles and plateaus. The histologic severity of synovial inflammatory reaction was also significantly reduced (P < or = 0.003) in the tenidap group. Tenidap markedly decreased stromelysin and collagenase activity in both cartilage (stromelysin P < or = 0.003; collagenase P < or = 0.01) and synovial membrane (stromelysin P < or = 0.003; collagenase P < or = 0.005). Moreover, tenidap also decreased the collagenase mRNA level in cartilage (P < or = 0.005) and synovial membrane (P < or = 0.002). Diclofenac slightly reduced the incidence and size of osteophytes and cartilage lesions, but these changes were not statistically significant. Diclofenac had no effect on the severity of synovial inflammation, metalloprotease activity, or collagenase expression. This study showed that tenidap had a more potent anti-osteoarthritic effect than diclofenac in this model. The effect of the drug in suppressing metalloprotease synthesis, a process known to play a major role in the pathophysiology of osteoarthritic lesions, may explain its mechanism of action.
Aesthetic Plastic Surgery, 2007
Background: The malar region has been a crucial target in many facial rejuvenation techniques bec... more Background: The malar region has been a crucial target in many facial rejuvenation techniques because the beauty and youthful contour of a convex midface and a smooth eye-lidÀcheek sulcus are key features of a pleasing face-lift result. The full midface subperiosteal lift has helped to address these issues. However, the desire of patients currently for a rapid recovery and return to work with a natural-looking result has influenced procedural selection. Another concern is for safer procedures with reduced potential risk. Progressively fewer invasive techniques, such as the minimal access cranial suspension (MACS) lift, have been a response to these core concerns. Methods: After 3 years of performing the conventional three purse-string suture MACS lift, the author developed a practical procedural modification. For a total of 17 patients, the author combined limited regional subperiosteal lift and periosteal fixation with a simple sling approach to the more fully released malar tissue mass to make a singlepoint suspension just above the lateral orbital rim. Results: The percutaneous sling lift appears to offer a degree and naturalness of rejuvenation of the malar region similar to those of the MACS lift and the full subperiosteal midface lift, but with fewer suspension points and less undermining. Also, the author observed less ecchymosis and edema than with the full midface subperiosteal lift, as would be expected. In all 17 cases, the need for the second and third purse-string sutures was eliminated. Conclusions: The early results for the percutaneous sling lift indicate that it offers promising results, rapid recovery, and reduced risk of serious complications.
Aesthetic Plastic Surgery, 2013
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Papers by Julio Fernandes