33 research outputs found

    Ncx3-induced mitochondrial dysfunction in midbrain leads to neuroinflammation in striatum of A53t-α-synuclein transgenic old mice

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    The exact mechanism underlying selective dopaminergic neurodegeneration is not completely understood. The complex interplay among toxic alpha-synuclein aggregates, oxidative stress, altered intracellular Ca2+-homeostasis, mitochondrial dysfunction and disruption of mitochondrial integrity is considered among the pathogenic mechanisms leading to dopaminergic neuronal loss. We herein investigated the molecular mechanisms leading to mitochondrial dysfunction and its relationship with activation of the neuroinflammatory process occurring in Parkinson’s disease. To address these issues, experiments were performed in vitro and in vivo in mice carrying the human mutation of α-synuclein A53T under the prion murine promoter. In these models, the expression and activity of NCX isoforms, a family of important transporters regulating ionic homeostasis in mammalian cells working in a bidirectional way, were evaluated in neurons and glial cells. Mitochondrial function was monitored with confocal microscopy and fluorescent dyes to measure mitochondrial calcium content and mitochondrial membrane potential. Parallel experiments were performed in 4 and 16-month-old A53T-α-synuclein Tg mice to correlate the functional data obtained in vitro with mitochondrial dysfunction and neuroinflammation through biochemical analysis. The results obtained demonstrated: 1. in A53T mice mitochondrial dysfunction occurs early in midbrain and later in striatum; 2. mitochondrial dysfunction occurring in the midbrain is mediated by the impairment of NCX3 protein expression in neurons and astrocytes; 3. mitochondrial dysfunction occurring early in midbrain triggers neuroinflammation later into the striatum, thus contributing to PD progression during mice aging

    A rare case of cerebral venous thrombosis and disseminated intravascular coagulation temporally associated to the covid-19 vaccine administration

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    Globally, at the time of writing (20 March 2021), 121.759.109 confirmed COVID-19 cases have been reported to the WHO, including 2.690.731 deaths. Globally, on 18 March 2021, a total of 364.184.603 vaccine doses have been administered. In Italy, 3.306.711 confirmed COVID-19 cases with 103.855 deaths have been reported to WHO. In Italy, on 9 March 2021, a total of 6.634.450 vaccine doses have been administered. On 15 March 2021, Italian Medicines Agency (AIFA) decided to temporarily suspend the use of the AstraZeneca COVID-19 vaccine throughout the country as a precaution, pending the rulings of the European Medicines Agency (EMA). This decision was taken in line with similar measures adopted by other European countries due to the death of vaccinated people. On 18 March 2021, EMA’s safety committee concluded its preliminary review about thromboembolic events in people vaccinated with COVID-19 Vaccine AstraZeneca at its extraordinary meeting, confirming the benefits of the vaccine continue to outweigh the risk of side effects, however, the vaccine may be associated with very rare cases of blood clots associated with thrombocytopenia, i.e., low levels of blood platelets with or without bleeding, including rare cases of cerebral venous thrombosis (CVT). We report the case of a 54-year-old woman who developed disseminated intravascular coagulation (DIC) with multi-district thrombosis 12 days after the AstraZeneca COVID-19 vaccine administration. A brain computed tomography (CT) scan showed multiple subacute intra-axial hemorrhages in atypical locations, including the right frontal and the temporal lobes. A plain old balloon angioplasty (POBA) of the right coronary artery was performed, without stent implantation, with restoration of distal flow, but with persistence of extensive thrombosis of the vessel. A successive thorax angio-CT added the findings of multiple contrast filling defects with multi-vessel involvement: at the level of the left upper lobe segmental branches, of left interlobar artery, of the right middle lobe segmental branches and of the right interlobar artery. A brain magnetic resonance imaging (MRI) in the same day showed the presence of an acute basilar thrombosis associated with the superior sagittal sinus thrombosis. An abdomen angio-CT showed filling defects at the level of left portal branch and at the level of right suprahepatic vein. Bilaterally, it was adrenal hemorrhage and blood in the pelvis. An evaluation of coagulation factors did not show genetic alterations so as the nasopharyngeal swab ruled out a COVID-19 infection. The patient died after 5 days of hospitalization in intensive care

    Mesoangioblasts at 20: from the embryonic aorta to the patient bed

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    In 2002 we published an article describing a population of vessel-associated progenitors that we termed mesoangioblasts (MABs). During the past decade evidence had accumulated that during muscle development and regeneration things may be more complex than a simple sequence of binary choices (e.g., dorsal vs. ventral somite). LacZ expressing fibroblasts could fuse with unlabelled myoblasts but not among themselves or with other cell types. Bone marrow derived, circulating progenitors were able to participate in muscle regeneration, though in very small percentage. Searching for the embryonic origin of these progenitors, we identified them as originating at least in part from the embryonic aorta and, at later stages, from the microvasculature of skeletal muscle. While continuing to investigate origin and fate of MABs, the fact that they could be expanded in vitro (also from human muscle) and cross the vessel wall, suggested a protocol for the cell therapy of muscular dystrophies. We tested this protocol in mice and dogs before proceeding to the first clinical trial on Duchenne Muscular Dystrophy patients that showed safety but minimal efficacy. In the last years, we have worked to overcome the problem of low engraftment and tried to understand their role as auxiliary myogenic progenitors during development and regeneration

    \u201cThe state of the heart\u201d: Recent advances in engineering human cardiac tissue from pluripotent stem cells

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    The pressing need for effective cell therapy for the heart has led to the investigation of suitable cell sources for tissue replacement. In recent years, human pluripotent stem cell research expanded tremendously, in particular since the derivation of human-induced pluripotent stem cells. In parallel, bioengineering technologies have led to novel approaches for in vitro cell culture. The combination of these two fields holds potential for in vitro generation of high-fidelity heart tissue, both for basic research and for therapeutic applications. However, this new multidisciplinary science is still at an early stage. Many questions need to be answered and improvements need to be made before clinical applications become a reality. Here we discuss the current status of human stem cell differentiation into cardiomyocytes and the combined use of bioengineering approaches for cardiac tissue formation and maturation in developmental studies, disease modeling, drug testing, and regenerative medicine

    The double tunnels technique: an alternative minimally invasive approach for carpal tunnel syndrome

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    OBJECT The purpose of this study was to assess the effectiveness and safety of an alternative minimally invasive technique for the treatment of carpal tunnel syndrome (CTS). METHODS This was designed as a prospective, randomized, open-label, blinded end point evaluation (PROBE) study. The active comparison was double tunnels technique (DTT) (Group A, 110 patients) versus standard open decompression of the median nerve (control [Group B], 110 patients). Patient recruitment started in January 2011. The primary outcomes were the functional Boston Carpal Tunnel Syndrome Questionnaire (BCTSQ) scores and visual analog scale (VAS) scores for pain (pVAS) at Weeks 2 and 4, and at Months 3, 6, and 12. The secondary outcome was the aesthetics (aVAS) score at Weeks 2 and 4, and at Months 3, 6, and 12. RESULTS The Student t-test and ANOVA were used, and the results were considered statistically significant if the p value was ≤ 0.05 for continuous variables. The DTT is a tissue-sparing approach that allows the surgeon to limit the length of the incision (0.6 ± 0.05 cm) and to respect the palmar fascia and the subcutaneous tissue. Recovery from wrist pain, night pain, numbness, stiffness, and weakness was achieved more effectively and quickly compared with the standard approach. Better BCTSQ, pVAS, and aVAS scores were observed in Group A. CONCLUSIONS The DTT is a safe and effective approach for the treatment of CTS. This technique entails faster recovery times, better aesthetic outcomes, and lower risks of complications

    Arthrodesis versus dynamic neutralization: A short/mid- and long-term retrospective evaluation in degenerative disk disease treatment

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    Study Design: This was a retrospective comparative study. Objectives: The aim of this study was to perform a clinical and radiological retrospective evaluation of the most used techniques for the lumbar degenerative disk disease (DDD) treatment: arthrodesis versus dynamic neutralization (DN)-Dynesys dynamic stabilization system. Methods: The study included 58 consecutive patients affected by lumbar DDD, 28 treated with rigid stabilization and 30 with DN at our department between 2003 and 2013. The clinical evaluation was performed through the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI). The radiographic evaluation was performed through standard and dynamic X-ray projections and magnetic resonance imaging. Results: Both techniques determined a clinical improvement in the postoperative period compared to the preoperative one. There were no significant differences between the postoperative VAS of the two techniques. The DN group postoperative ODI percentage showed a significant improvement (P = 0.026) compared to the arthrodesis group. During the follow-up, no clinically significant differences were highlighted between the two techniques. At a long term follow up period, radiographic results showed, in both groups, a L3-L4 disk mean height reduction and an increase of segmental and lumbar lordosis without significant differences between the two techniques. During an average of 96-month follow-up period, 5 (18%) patients developed an adjacent segment disease in the arthrodesis group and 6 (20%) patients developed this syndrome in the DN group. Conclusions: We are confident in recommending arthrodesis and DN as effective techniques for lumbar DDD treatment. Both techniques are potentially burdened, with similar frequency, by the development of long-term adjacent segment disease
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