86 research outputs found
Editorial: Chronic autoimmune arthritis, infections and vaccines
No full textThe link between autoimmunity and infection continues to represent an intriguing immunologic conundrum for scientist and a frequent clinical challenge for patients and physicians.
Patients with chronic autoimmune arthritis indeed have an increased risk of infections, mainly due to the dysregulation of their immune system and the use of immunosuppressive therapy. Infections in these patients are more frequent, have a more severe clinical course, eventually with prolonged viral persistence, compared to the general population and represent a frequent cause of death.
Besides, infections can trigger autoimmune diseases via different immunologic mechanisms such as molecular mimicry, epitope spreading, by-stander activation and can also induce disease relapses.
SARS-CoV-2 infection represents a dramatic example of this complex connection.
It is known, indeed, that different autoimmune manifestations can complicate SARS-CoV-2 infection such as uncontrolled host-immune response leading to life-threatening condition known as cytokine release syndrome, or autoimmune hemolytic anemia, immune thrombocytopenic purpura, Guillain-Barre syndrome, and the detection of different autoantibodies.
This Research Topic includes seventeen contributions, fifteen original articles and two review articles, providing several new insights into the efficacy and safety of SARS-CoV-2 vaccine in autoimmune patients, immunologic biomarkers for diagnosis and therapeutic outcome of autoimmune arthritis
Monocytes of Patients with Systemic Sclerosis (Scleroderma) Spontaneously Release In Vitro Increased Amounts of Superoxide Anion
No full textIt has been suggested that toxic oxygen free radicals can be involved in the pathogenesis of systemic sclerosis (scleroderma) (SSc). Because the cells that contribute to the generation of free radicals are not known, our aim was (i) to evaluate the ability of unmanipulated and phorbol 12-myristate 13-acetate-stimulated monocytes and polymorphonucleate neutrophils of SSc patients to generate superoxide anion (O2·–); and (ii) to investigate whether the O2·– produced by these cells involved the activation of nicotinamide-adenine dinucleotide diphosphate oxidase biochemical pathway. Employing the superoxide dismutase-inhibitable reduction of cytochrome c to evaluate the generation of O2·–, unmanipulated monocytes of SSc patients generated more O2·– than primary Raynaud’s phenomenon patients and normal control monocytes (p= 0.0001), and the release was higher in patients with diffuse cutaneous involvement and 5 y or less disease duration (p = 0.02). The involvement of nicotinamide-adenine dinucleotide diphosphate oxidase in the enhanced O2·– production was demonstrated by the finding that the cytosolic components of the enzyme, p47phox and p67phox, were both translocated to the plasma membrane of enriched but otherwise unmanipulated monocytes of SSc patients. The involvement of mitochondrial oxidases was excluded by the lack of inhibition of O2·– production when monocytes were incubated in the presence of rotenone, a mitochondrial oxidase inhibitor. Upon stimulation with phorbol 12-myristate 13-acetate, monocytes of SSc patients produced more O2·– than controls. In SSc patients untreated polymorphonucleate neutrophils generated significantly less O2·– than monocytes (p = 0.0001) and only slightly more than polymorphonucleate neutrophils of primary Raynaud’s phenomenon patients and normal controls (p = 0.03). In conclusion, we demonstrate that in patients with scleroderma, unmanipulated and phorbol 12-myristate 13-acetate-stimulated monocytes release in vitro increased amounts of superoxide anion through the activation of nicotinamide-adenine dinucleotide diphosphate oxidase and, thus, contribute to the oxidative stress found in this disease
Collagen loss and impaired wound healing is associated with c-Myb deficiency
No full textData source: Supporting information, http://onlinelibrary.wiley.com.access.library.unisa.edu.au/doi/10.1002/path.2113/abstract#footer-support-infoCollagen type I serves as an abundant structural and signalling component of skin. It is also an established target gene of the transcription factor, c-Myb. When c-myb-/- embryos were examined it was observed that their skin was markedly thinner than normal. Importantly, immunohistochemical investigation showed complete absence of collagen type I. Although these homozygous knock-out embryos fail to develop beyond day 15, fibroblasts established from these embryos (mouse embryonic fibroblasts [MEFs]) show defective proliferative responses. Furthermore, in vitro scratch wound assays demonstrated that these c-myb-/- MEFs also exhibit slower closure than their wild-type counterparts. Embryonic lethality has meant that examination of the role of c-Myb in adult mouse skin has not been reported to date. However, in view of the abundance of collagen type I in normal skin, its role in skin integrity and the in vitro data showing proliferative and migration defects in c-myb-/- MEFs, we investigated the consequences of heterozygous c-myb loss in adult mice on the complex process of skin repair in response to injury. Our studies clearly demonstrate that heterozygous c-myb deficiency has a functional effect on wound repair, collagen type I levels and, in response to wounding, transforming growth factor-β1 (an important collagen stimulating factor) induction expression is aberrantly high. Manipulation of c-Myb may therefore provide new therapeutic opportunities for improving wound repair while uncontrolled expression may underpin some fibrotic disorders.Z Kopecki, MM Luchetti, DH Adams, X Strudwick, T Mantamadiotis, A Stoppacciaro, A Gabrielli, RG Ramsay, AJ Cowi
ACCURACY OF DUAL-ENERGY COMPUTED TOMOGRAPHY FOR THE DETECTION OF BONE MARROW EDEMA IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS
No full textEditorial: New insights into spondyloarthritis: from bench to bedside
No full textNo abstract availabl
Arthroscopic assisted bone grafting for early stages of Kienböck's disease
No full textKienböck's disease is known for its difficulty in being diagnosed and treated at early stages; option treatments are few and most of them quite aggressive. The author describes his experience with arthroscopic assisted lunate bone grafting. Three patients with diagnosis of stage I avascular necrosis of the lunate (average age: 45 years), were treated. Before surgical procedure, the patients underwent to a conservative treatment. After harvesting the bone graft from the volar surface of the radius, arthroscopic bone grafting was performed. At an average follow-up of 13.5 months (9-15), all the patients show a normal density of the lunate and no arthritic changes in radiographs. The MRI confirmed the lunate vascularity. The number of patients is definitely small, due also to the rarity of the disease and the difficulty in diagnosis, but, despite the very high learning curve, could be the proper first choice of treatment
El protagonismo del Poder Judicial en el marco del Derecho Procesal a través de las medidas cautelares: El debate entre el Eficientismo y Garantismo Procesal
No full textBy the study of the following lines, we will capture the leadership of Judicial Power in the frame of Processal Law. Firstly, describe the foregoings, including the controversial case of Luchetti. Furthermore, the author focus on the discussion between efficientism and Processal guarantees, this point relates in the case of the mentioned report.Mediante el estudio de las siguientes líneas, captaremos el protagonismo del Poder Judicial en el marco del Derecho Procesal. Primeramente, se describe los antecedentes, entre ellos el polémico caso Luchetti. Por otro lado, el autor, se centra en el debate entre el Eficientismo y Garantismo Procesal, este punto versa en el informe del caso mencionado
Melatonin reduces early changes in intramitochondrial cardiolipin during apoptosis in U937 cell line
No full textCardiolipin (CL) is found exclusively in the inner mitochondrial membrane. CL deficiency leads to an alteration in the stability of mitochondrial membranes, to an increased permeability as well as a decreased respiratory rate, and therefore to mitochondria which are completely dysfunctional. It is known that reactive oxygen species (ROS) cause a decrease and a variation in CL content, concomitantly the formation of the mitochondrial permeability transition pore facilitates the release of cytochrome c (cyt c) into the cytosol. Melatonin (Mel), the secretory product of the pineal gland, is a potent and efficient endogenous radical scavenger. It has been shown to protect, various biomolecules, such as DNA, membrane lipids, and cytosolic proteins from oxidative damage. To evaluate the protective role of Mel, we have studied U937 cells treated with UV-B irradiation. In our model, the administration of 1 mM Mel before UV-B irradiation showed a significant protection from apoptotic cell death, in particular, mitochondrial structure and function were preserved through apoptotic pathways when cells were preincubated with 1 mM Mel before UV-B exposure. The cardiolipin-sensitive probe 10-nonyl acridine orange (NAO) was used to monitor changes in mitochondrial lipids. Our data suggest that the Mel treatment protects CL from ROS and this suggests a possible link with the reduction of the apoptotic phenomenon. © 2006 Elsevier Ltd. All rights reserved
Allinside Anatomic Arthroscopic (3A) Reconstruction of Irreparable TFCC Tear
No full textBackground In recent years, new arthroscopic techniques have been introduced to address the irreparable tears of the triangular fibrocartilage complex (TFCC) (Palmer type 1B, Atzei class 4) by replicating the standard Adams-Berger procedure. These techniques, however, show the same limitations of the open procedure in relation to the anatomically defective location of the radial origins of the radioulnar ligaments (RUL) and the risk of neurovascular and/or tendon injury. Aiming to improve the quality of reconstruction and reduce surgical morbidity, a novel arthroscopic technique was developed, with the advantages of reproducing the anatomical origins of the RUL ligaments and providing all-inside tendon graft (TG) deployment and fixation.Description of Technique The Allinside anatomic arthroscopic (3A) technique is indicated for TG reconstruction of irreparable TFCC tears in the absence of distal radioulnar joint (DRUJ) arthritis. Standard wrist arthroscopy portals are used. A small incision in the radial metaphyseal area and arthroscopic control are required to set a Wrist Drill Guide and create two converging tunnels, whose openings are at the radial anatomical origins of the RUL. An ulnar tunnel is drilled at the fovea from inside-out via the 6U portal. A 3- mm tendon strip, from the palmaris longus or extensor carpi radialis brevis, is woven through the tunnels and then secured into the ulnar tunnel with an interference screw. Postoperative immobilization with restricted forearm rotation is discontinued at 5 weeks, and then postoperative rehabilitation is started.Patients and Methods The 3A technique was applied on 5 patients (2 females and 3 males), with an average age 42 years. DRUJ stability, range ofmotion (ROM), pain (0-10 visual analogue scale [VAS]), grip strength, modified Mayo wrist score (MMWS), and patient satisfaction were used for evaluation before surgery and at follow-up.Results No intraoperative or early complications were registered. At a mean follow- up of 26 months, DRUJ was stable in all patients, which recovered 99% ROM. Pain VAS decreased from 7 to 0.6. Grip strength increased from 38 to 48.8 Kgs. There were 4 excellent results and 1 good result on MMWS. All patient showed high satisfaction.Conclusions Although the 3A technique requires dedicated instrumentation and arthroscopic expertise, it takes advantage of improved intra-articular vision and minimized surgical trauma to reduce the risk of complications and obtain promising functional results
ERK MAPK activation mediates the antiapoptotic signaling of melatonin in UVB-stressed U937 cells.
No full textThe pineal gland hormone melatonin has been recently described to downregulate the intrinsic (or damage-induced) pathway of apoptosis in human leukocytes. These properties appear to depend on a specific mitochondrial signaling of melatonin which is associated with a lower generation of reactive oxygen species and a better control of redox-sensitive components such as the antiapoptotic protein Bcl-2. Other elements upstream in this signaling are expected to contribute regulatory roles that remain unexplored. The aim of this study was to investigate whether the extracellular signal-regulated kinase (ERK), which controls the balance between survival and death-promoting genes throughout the MAPK pathway, is involved in the antiapoptotic signaling of melatonin. Human monocytic U937 cells irradiated with UVB light were used as a model of stress-induced apoptosis. In this model we found that pharmacological concentrations of melatonin (1 mM) were able to decrease superoxide anion production, mitochondrial damage, and caspase-dependent apoptosis by improved Bcl-2 levels and decreased Cyt c release in the cytoplasm. Moreover, melatonin increased the phosphorylative activation of ERK 1/2 independently from the presence of UVB stress, and decreased the UVB-mediated activation of the stress kinases p38 MAPK and JNK. The ERK 1/2 inhibitor PD98059, but not the p38 MAPK inhibitor SB203580, abolished to different extents the effects that melatonin had on the UVB-induced ROS generation, mitochondrial dysfunction, and apoptosis. Using these inhibitors, a cross-talk effect between stress and survival-promoting kinases was tentatively identified, and confirmed the hierarchical role of ERK MAPK phosphorylation in the signaling of melatonin. In conclusion, melatonin sustains the activation of the survival-promoting pathway ERK MAPK which is required to antagonize UVB-induced apoptosis of U937 cells. This kinase mediates also the antioxidant and mitochondrial protection effects of this hormonal substance that may find therapeutic applications in inflammatory and immune diseases associated with leukocyte oxidative stress and accelerated apoptosis
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