The progression of hemophilic arthropathy: The role of biomarkers

Background: Hemophilia A and B are X-linked congenital bleeding disorders characterized by recurrent hemarthroses leading to specific changes in the synovium and cartilage, which finally result in the destruction of the joint: this process is called hemophilic arthropathy (HA). This review highlights the most prominent molecular biomarkers found in the literature to discuss their potential use in the clinical practice to monitor bleeding, to assess the progression of the HA and the effectiveness of treatments. Methods: A review of the literature was performed on PubMed and Embase, from 3 to 7 August 2020. Study selection and data extraction were achieved independently by two authors and the following inclusion criteria were determined a priori: English language, available full text and articles published in peer-reviewed journal. In addition, further articles were identified by checking the bibliography of relevant articles and searching for the studies cited in all the articles examined. Results: Eligible studies obtained at the end of the search and screen process were seventy-three (73). Conclusions: Despite the surge of interest in the clinical use of biomarkers, current literature underlines the lack of their standardization and their potential use in the clinical practice preserving the role of physical examination and imaging in early diagnosis

Biomarkers for ehlers-danlos syndromes: There is a role?

Ehlers-Danlos syndromes (EDS) are an inherited heterogeneous group of connective tissue disorders characterized by an abnormal collagen synthesis affecting skin, ligaments, joints, blood vessels, and other organs. It is one of the oldest known causes of bruising and bleeding, and it was described first by Hippocrates in 400 BC. In the last years, multiple gene variants involved in the pathogenesis of specific EDS subtypes have been identified; moreover, new clinical diagnostic criteria have been established. New classification models have also been studied in order to differentiate overlapping conditions. Moreover, EDS shares many characteristics with other similar disorders. Although distinguishing between these seemingly identical conditions is difficult, it is essential in ensuring proper patient care. Currently, there are many genetic and molecular studies underway to clarify the etiology of some variants of EDS. However, the genetic basis of the hypermobile type of EDS (hEDS) is still unknown. In this review, we focused on the study of two of the most common forms of EDS—classic and hypermobile—by trying to identify possible biomarkers that could be of great help to confirm patients’ diagnosis and their follow up

Pulsed electromagnetic fields in bone healing: Molecular pathways and clinical applications

In this article, we provide an extensive review of the recent literature of the signaling pathways modulated by Pulsed Electromagnetic Fields (PEMFs) and PEMFs clinical application. A review of the literature was performed on two medical electronic databases (PubMed and Embase) from 3 to 5 March 2021. Three authors performed the evaluation of the studies and the data extraction. All studies for this review were selected following these inclusion criteria: studies written in English, studies available in full text and studies published in peer‐reviewed journal. Molecular biology, identifying cell membrane receptors and pathways involved in bone healing, and studying PEMFs target of action are giving a solid basis for clinical applications of PEMFs. However, further biology studies and clinical trials with clear and standardized parameters (intensity, frequency, dose, duration, type of coil) are required to clarify the precise dose–response relationship and to understand the real applications in clinical practice of PEMFs

MPFL reconstruction and tibial tuberosity transposition in patients with patellar instability: May it troubleshots also trochlear dysplasia?

Purpose: This study aimed to highlight short- and medium-term outcomes of combined medial patello-femoral ligament (MPFL) reconstruction and anterior tibial tuberosity (ATT) transposition surgery in patients with recurrent patellar instability and different degrees of trochlear dysplasia. Methods: Between January 2014 and May 2019, 25 patients with patellar instability underwent a surgical procedure combining the lowering/transposition of the ATT and the MPFL reconstruction. Each patient were preoperative assessed by Kujala score, International Knee Documentation Committee (IKDC), Tegner activity level scale. The assessment of instability predisposing factors was carried out with patellar height, tibial tuberosity-trochlear groove (TT-TG) distance, trochlear dysplasia, sulcus angle, patellar tilt and MPFL injuries. Functional outcomes were evaluated with Kujala, IKDC and Tegner scores at 3, 6 and 12 months after surgery. Results: The average age of the patients was 20 years (range 13–43 years). Pre- operative Caton–Deschamps index was pathological in 10 (40%). Sulcus angle was elevated in 13 patients (52%) and TT-TG distance was irregular in 17 patients (68%). Trochlear dysplasia was present in 13 patients (9 type A, 3 type B, 1 type C according to Dejour’s Classification). No re-dislocation occurred during the follow-up. There was a significant increase in the Kujala, IKDC and Lysholm scores after 3, 6 and 12 months, and the results were compared for the different follow-up times and patient’s trochlear dysplasia degree. Conclusion: This prospective observational longitudinal study identified good clinical outcomes in patients who underwent MPFL reconstruction and ATT transposition for patellar instability. Finally, the different risk factors for patellar instability examined, particularly the presence of trochlear dysplasia, did not significantly influence the final functional results, which range from good to excellent without re-dislocation episodes

Double-tapered conical taper in primary and revision surgery: rationale and short-term follow-up

Background: The new double-conical tapered stem is a novel cementless modular system, which is indicated for both primary and revision surgeries. It has been designed with different angles at the proximal (5°) and distal sections (1° 36’) in order to obtain optimal fixation by proximal and distal fit and fill of the femoral canal. Aim: The aim of this prospective study was to evaluate the short-term clinical and radiographic outcomes of primary and revision hip surgery with the new double-conical stem. Methods: 61 stems were implanted (December 2013 to September 2016) in 42 cases of primary and in 19 cases of revision surgery. The mean age of patients was 64.7 (17–94; standard deviation [SD] 21.9) years. Results: The mean body mass index of the patients was 24.6 (17–34.6). In 3 cases of developmental dysplasia of the hip we performed femoral shortening osteotomy. The mean follow-up was 26 (8–40) months. 3 patients died due to causes unrelated to surgery. Postoperative complications included 3 hip dislocations, 2 infections and 1 case of stem explant for metastatic tumour. For all other cases, at the last follow-up radiographs showed no loosening, no radiolucent lines nor subsidence. The mean Harris Hip Score significantly improved from 45 (range 35–58) preoperatively to 87 (range 75–94). Leg length discrepancy was found in 10% of cases but never >1 cm. Conclusions: Radiographic analysis showed the bone-stem contact full at 2 levels of taper. The double-tapered prosthetic stem can therefore be usefully employed both in primary and in revision surgeries

Hormonal control of subcutaneous adipose tissue aquaglyceroporins

Glycerol metabolism in normal condition and in metabolic disorders like type-2 diabetes and obesity could depend at least in part on the transmembrane transport mechanisms of glycerol. Aquaglyceroporins (AQPs) are integral membrane protein belonging to the water channel proteins family (aquaporins) that are permeable to glycerol as well as water. Adipose tissue, the main source of plasma glycerol, expresses high levels of AQP7 but also AQP3, 9, 10. Recently, in adipose tissue was also found AQP11, whose permeability to glycerol is uncertain. However, the hormonal regulation of AQPs in the adipose tissue is not completely characterized. To this purpose we evaluated the effect of insulin, isoproterenol, thyroxin, dexamethasone in human isolated adipose tissue by real time RT-PCR. Immunocytochemistry was also performed to define the localization of the AQPs. Results showed that all the AQPs investigated are expressed in the human subcutaneous adipose tissue with a localization of AQP3,7 and 10 in both plasma membranes and in lipid droplets membranes, AQP9 mainly in the plasma membrane and AQP11 in the lipid droplets membrane. Generally, lipolytic and lipogenic stimuli differently affected the AQPs expression which depicts a complex situation involving, probably, different signaling pathway. These results and other recently described by the literature seem support the existence of different AQPs that under hormonal control and in pathological conditions can modify their expression levels and cellular localization, suggesting them as potential therapeutic targets in obesity and metabolic syndrome

ENDOTHELIAL PROGENITOR CELL ADHESION, GROWTH AND CHARACTERIZATION ON TRABECULAR TITANIUM AND TRABECULAR TITANIUM COATED WITH COLLAGEN OR DECELLULARIZED ECM

Adequate blood supply is essential for prosthesis osteointegration and bone healing as it supplies oxygen, nutrition and progenitor cells. The bone healing process and vascularization depend upon the endothelial cells, which speed up implant osteointegration. Endothelial Progenitor Cells (EPC) are a population of stem cells that can reproduce, migrate and acquire mature endothelial phenotype. Their recruitment occurs in the tissue lesion to enhance neovascularization. Trabecular TitaniumTM (TTTM) is a new biomaterial with very interesting biomechanical characteristics and fast osteointegration. This study has investigated adhesion, proliferation and characteristics of EPC on three types of biomaterial: unmodified trabecular titanium, trabecular titanium coated with the ECM deposited by human mesenchymal stem cells isolated from subcutaneous adipose tissue and decellularized and trabecular titanium coated with type I collagen (control scaffold). MTT assay showed similar percentages of EPCs seeded on the different kinds of scaffold: 67% on TT, 70% on decellularized scaffolds and 82% on collagen-coated scaffolds. There were no statistically significant differences between the three groups. We therefore conclude that TTTM allows EPC adhesion and proliferation and, consequently, by permitting vascularization, it favours prosthesis osteointegration

Some natural compounds exert their antioxidant effect by altering aquaporins functional properties

The ability of some aquaporins (AQPs) to facilitate the diffusion of H2O2 from the producing cells to the extracellular fluid has been recently demonstrated. Accordingly, this significant AQPs property may have a beneficial effect in promoting Reactive Oxygen Species (ROS) scavenging. Nevertheless, some AQPs aspects remain unsolved and, in this scenario, the identification and localization of different AQPs acting as peroxiporins, their functional role in eustress and distress, as well as the identification of chemical antioxidant compounds capable to regulate AQP gating are still the main features to disclose. In light of these considerations, this study aimed at investigating the potential effect of well-known natural compounds in modulating the activity of AQPs. From an experimental standpoint, in this work the expression of mRNA and proteins of different AQPs in HeLa cells, the functional experiments of water (and H2O2) permeability using stopped-flow light scattering method and the gating of AQPs in the presence/absence of oxidative stress have been evaluated. The obtained results suggest that oxidative stress reduced water AQP-mediated permeability and the effectiveness of the analyzed compounds to promote AQPs gating. Therefore, this study could lead to the identification of a novel therapeutic target for the treatment of cancer and degenerative diseases, since the positive regulation of AQPs avoids the accumulation of ROS within the cells

HPV infection inhibits aquaporin-mediated hydrogen peroxide elimination and affects human sperm function

Aquaporins (AQPs) 3, 7, 8, and 11 are expressed in human sperm cells and are localized in the plasma membrane and in intracellular structures. AQPs are involved in cell volume regulation, cytoplasm removal during sperm maturation and ROS (H2O2) elimination. Recently, AQP-mediated H2O2 permeability was found to be reduced by oxidative stress and related to a decrease in sperm number and motility. We studied the possible effect of Human Papillomavirus (HPV) on the expression and function of AQPs in human sperm cells of patients undergoing infertile couple evaluation. ELISA experiments showed that HPV infection is associated to an increased AQPs expression in normospermic patients and to a decreased one in sub-fertile patients. Functional experiments demonstrated that HPV infection heavily reduces water permeability of sperm cells of both normospermic and sub-fertile patients. Confocal IF experiments showed colocalization of HPV L1 protein with AQP8. Docking of HPV L1 and AQP8 atomic models suggested a distant effect of L1 on the pore NPA region. Present findings suggest that HPV infection affects AQPs expression and directly inhibits their function, probably by making sperm cells more sensitive to oxidative stres