Treatment of Stifle Joint Luxation in a Cat Using a Temporary Trans-Articular Locking Plate

AbstractThe aim of this study was to report the surgical treatment of stifle joint luxation through temporary immobilization of the joint with locking plates in a cat. Stifle joint was immobilized using a temporary trans-articular locking plate applied medially. Return to function was assessed by physical and radiographic follow-up examinations. The cat had good return to function despite a reduction in range of motion. Moderate chronic gonarthritis developed, as seen radiographically. Under the limitation of this single case, temporary trans-articular plating may be considered as useful method for the treatment of long-standing, severely displaced stifle joint luxations in cats

Treatment of Y-T Humeral Fractures with Polyaxial Locking Plate System (PAX) in 14 Dogs

The aim of this study is to report the results and to review the outcome of 14 cases of Y-T humeral fractures repair using paired polyaxial locking system (PAX) plates through a combined medial and lateral approach. Fourteen consecutive dogs, with traumatic humeral Y-T fractures, met the inclusion criteria. This study includes signalment, preoperative radiographs, type of implants, radiographic bone healing assessment, complications, range of motion (ROM) of the elbow and limb function evaluated at 120 days after surgery. Postoperative radiographs revealed adequate anatomic reconstruction, and in all cases, bone healing has been achieved. No implant failure was observed. Functional outcome was excellent in 7 dogs (no lameness and preserved ROM), good in 4 (slight lameness and moderate ROM reduction) and discrete in 2 (mild lameness and severe ROM reduction). Complications were encountered in 2/14 patients with implant-associated infection resolved after long-term antibiotic treatment and implant removal. The PAX system is shown to be a valid alternative for the treatment of Y-T humeral fractures, offering the benefit of polyaxial insertion of locking screws. The possibility of angle locking screws is helpful in the distal humeral bicondylar fractures, providing additional options for screw placement in juxtarticular fractures, avoiding fracture lines or other implants

Comparison between Areas of Bone Visualization Using Radiolucent Hybrid Fixator Frames and Graphically Simulated Metallic Frames: An Ex Vivo Study

The objective of this study is to evaluate the difference between the amount of bone visible with the superimposition of a radiolucent hybrid external fixator and a graphically simulated metallic frame. Eighteen frames were applied to eighteen bone specimens. The fracture area (FA), the radiolucent area (RLA) and the radiopaque area (ROA) inside the FA were calculated for each construct on both postoperative views. The ratio between the RLA and FA and between the ROA and FA was used to evaluate the amount of bone visible in the FA with a radiolucent and a radiopaque fixator, respectively. Finally, the areas of RLA and ROA were compared using the Wilcoxon test and Friedman test to evaluate the effect of the radiolucent material on the amount of bone visible. Differences were considered significant if p < 0.5. In every specimen p was <0.5. The amount of bone visible was significantly higher with the radiolucent frame compared to the radiopaque frame. Based on the results of this study, the use of radiolucent materials can be a valuable option for external fixation, in order to decrease the radiographic interference of the frame, allowing better assessment of fracture reduction and bone healing on postoperative radiographs

Lactate dehydrogenase-A inhibition induces human glioblastoma multiforme stem cell differentiation and death

Therapies that target the signal transduction and metabolic pathways of cancer stem cells (CSCs) are innovative strategies to effectively reduce the recurrence and significantly improve the outcome of glioblastoma multiforme (GBM). CSCs exhibit an increased rate of glycolysis, thus rendering them intrinsically more sensitive to prospective therapeutic strategies based on the inhibition of the glycolytic pathway. The enzyme lactate dehydrogenase-A (LDH-A), which catalyses the interconversion of pyruvate and lactate, is up-regulated in human cancers, including GBM. Although several papers have explored the benefits of targeting cancer metabolism in GBM, the effects of direct LDH-A inhibition in glial tumours have not yet been investigated, particularly in the stem cell subpopulation. Here, two representative LDH-A inhibitors (NHI-1 and NHI-2) were studied in GBM-derived CSCs and compared to differentiated tumour cells. LDH-A inhibition was particularly effective in CSCs isolated from different GBM cell lines, where the two compounds blocked CSC formation and elicited long-lasting effects by triggering both apoptosis and cellular differentiation. These data demonstrate that GBM, particularly the stem cell subpopulation, is sensitive to glycolytic inhibition and shed light on the therapeutic potential of LDH-A inhibitors in this tumour type

THE HISTORY OF BETA THALASSAEMIA IN SARDINIA: THE CONTRIBUTION OF THE ITALIAN SCHOOLS OF PEDIATRICS

La beta thalassemia rappresenta una delle più comuni patologie autosomiche recessive nel mondo. I Paesi mediterranei, del Medio Oriente e del Sud Est Asiatico sono regioni ad alta prevalenza di beta thalassemia. Le più alte incidenze sono riportate a Cipro, nel Sud Est Asiatico e in Sardegna, correlate molto probabilmente alla pressione selettiva esercitata dal Pl. falciparum, agente eziologico della malaria. In Sardegna, per la rilevanza sanitaria della patologia e in seguito alla pubblicazione dei primi studi scientifici sul morbo di Cooley, sono fiorite importanti scuole di pediatria e genetica medica, che contribuiranno alla definizione dei criteri diagnostici, della terapia e della prevenzione, anche neonatale, dell’anemia mediterranea e delle emoglobinopatie.Beta thalassaemia represents one of the most common autosomal recessive disorders worldwide. High prevalence is present in the Mediterranean, Middle East and Far East. The highest incidences are reported in Cyprus, South East Asia and Sardinia and are most likely related to the selective pressure from Pl. falciparum, the causative agent of malaria. In Sardinia, because of the health relevance of beta thalassaemia and haemoglobinopathies and after the publication of the first scientific research on Cooley’s anaemia, important Schools of Paediatrics and Clinical Genetics have been set up, which have contributed to defining diagnostic criteria, therapeutic and preventive measures (especially, newborn screening). The aim of the present study is to examine the results of the first scientific research made by the Sardinian Schools of Paediatrics and Clinical Genetics, from 1929 to 1957

Negative effects of a high tumour necrosis factor-α concentration on human gingival mesenchymal stem cell trophism: The use of natural compounds as modulatory agents

Background: Adult mesenchymal stem cells (MSCs) play a crucial role in the maintenance of tissue homeostasis and in regenerative processes. Among the different MSC types, the gingiva-derived mesenchymal stem cells (GMSCs) have arisen as a promising tool to promote the repair of damaged tissues secreting trophic mediators that affect different types of cells involved in regenerative processes. Tumour necrosis factor (TNF)-α is one of the key mediators of inflammation that could affect tissue regenerative processes and modify the MSC properties in in-vitro applications. To date, no data have been reported on the effects of TNF-α on GMSC trophic activities and how its modulation with anti-inflammatory agents from natural sources could modulate the GMSC properties. Methods: GMSCs were isolated and characterized from healthy subjects. The effects of TNF-α were evaluated on GMSCs and on the well-being of endothelial cells. The secretion of cytokines was measured and related to the modification of GMSC-endothelial cell communication using a conditioned-medium method. The ability to modify the inflammatory response was evaluated in the presence of Ribes nigrum bud extract (RBE). Results: TNF-α differently affected GMSC proliferation and the expression of inflammatory-related proteins (interleukin (IL)-6, IL-10, transforming growth factor (TGF)-β, and cyclooxygenase (COX)-2) dependent on its concentration. A high TNF-α concentration decreased the GMSC viability and impaired the positive cross-talk between GMSCs and endothelial cells, probably by enhancing the amount of pro-inflammatory cytokines in the GMSC secretome. RBE restored the beneficial effects of GMSCs on endothelial viability and motility under inflammatory conditions. Conclusions: A high TNF-α concentration decreased the well-being of GMSCs, modifying their trophic activities and decreasing endothelial cell healing. These data highlight the importance of controlling TNF-α concentrations to maintain the trophic activity of GMSCs. Furthermore, the use of natural anti-inflammatory agents restored the regenerative properties of GMSCs on endothelial cells, opening the way to the use and development of natural extracts in wound healing, periodontal regeneration, and tissue-engineering applications that use MSCs

In Chronic Lymphocytic Leukemia the JAK2/STAT3 Pathway Is Constitutively Activated and Its Inhibition Leads to CLL Cell Death Unaffected by the Protective Bone Marrow Microenvironment

The bone marrow microenvironment promotes proliferation and drug resistance in chronic lymphocytic leukemia (CLL). Although ibrutinib is active in CLL, it is rarely able to clear leukemic cells protected by bone marrow mesenchymal stromal cells (BMSCs) within the marrow niche. We investigated the modulation of JAK2/STAT3 pathway in CLL by BMSCs and its targeting with AG490 (JAK2 inhibitor) or Stattic (STAT3 inhibitor). B cells collected from controls and CLL patients, were treated with medium alone, ibrutinib, JAK/Signal Transducer and Activator of Transcription (STAT) inhibitors, or both drugs, in the presence of absence of BMSCs. JAK2/STAT3 axis was evaluated by western blotting, flow cytometry, and confocal microscopy. We demonstrated that STAT3 was phosphorylated in Tyr705 in the majority of CLL patients at basal condition, and increased following co-cultures with BMSCs or IL-6. Treatment with AG490, but not Stattic, caused STAT3 and Lyn dephosphorylation, through re-activation of SHP-1, and triggered CLL apoptosis even when leukemic cells were cultured on BMSC layers. Moreover, while BMSCs hamper ibrutinib activity, the combination of ibrutinib+JAK/STAT inhibitors increase ibrutinib-mediated leukemic cell death, bypassing the pro-survival stimuli derived from BMSCs. We herein provide evidence that JAK2/STAT3 signaling might play a key role in the regulation of CLL-BMSC interactions and its inhibition enhances ibrutinib, counteracting the bone marrow niche

P2‐239: POTENTIAL DIAGNOSTIC VALUE OF RED BLOOD CELLS α‐SYNUCLEIN HETEROAGGREGATES IN ALZHEIMER'S DISEASE

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α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson's Disease Patients and Correlate with Disease Severity

Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1-42(Aβ1-42) and tau, in both brain and peripheral tissues. In addition to oligomers, the role of the interactions of α-syn with Aβ or tau has gradually emerged. Nevertheless, despite intensive research, NDs have no accepted peripheral markers for biochemical diagnosis. In this respect, Red Blood Cells (RBCs) are emerging as a valid peripheral model for the study of aging-related pathologies. Herein, a small cohort (N= 28) of patients affected by Parkinson's disease (PD) and age-matched controls were enrolled to detect the content of α-syn (total and oligomeric), Aβ1-42and tau (total and phosphorylated) in RBCs. Moreover, the presence of α-syn association with tau and Aβ1-42was explored by co-immunoprecipitation/western blotting in the same cells, and quantitatively confirmed by immunoenzymatic assays. For the first time, PD patients were demonstrated to exhibit α-syn heterocomplexes with Aβ1-42and tau in peripheral tissues; interestingly, α-syn-Aβ1-42concentrations were increased in PD subjects with respect to healthy controls (HC), and directly correlated with disease severity and motor deficits. Moreover, total-α-syn levels were decreased in PD subjects and inversely related to their motor deficits. Finally, an increase of oligomeric-α-syn and phosphorylated-tau was observed in RBCs of the enrolled patients. The combination of three parameters (total-α-syn, phosphorylated-tau and α-syn-Aβ1-42concentrations) provided the best fitting predictive index for discriminating PD patients from controls. Nevertheless further investigations should be required, overall, these data suggest α-syn hetero-aggregates in RBCs as a putative tool for the diagnosis of PD

α-Synuclein Aggregates with β-Amyloid or Tau in Human Red Blood Cells: Correlation with Antioxidant Capability and Physical Exercise in Human Healthy Subjects

Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1–42 (Aβ), and tau, in both brain and peripheral tissue. In addition to homo-oligomers, the role of α-syn interactions with Aβ or tau has gradually emerged. The altered protein accumulation has been related to both oxidative stress and physical activity; nevertheless, no correlation among the presence of peripheral α-syn hetero-aggregates, antioxidant capacity, and physical exercise has been discovered as of yet. Herein, the content of α-syn, Aβ, tau, and of their heterocomplexes was determined in red blood cells (RBCs) of healthy subjects (sedentary and athletes). Such parameters were related to the extent of the antioxidant capability (AOC), a key marker of oxidative stress in aging-related pathologies, and to physical exercise, which is known to play an important preventive role in NDs and to modulate oxidative stress. Tau content and plasma AOC toward hydroxyl radicals were both reduced in older or sedentary subjects; in contrast, α-syn and Aβ accumulated in elderly subjects and showed an inverse correlation with both hydroxyl AOC and the level of physical activity. For the first time, α-syn heterocomplexes with Aβ or tau were quantified and demonstrated to be inversely related to hydroxyl AOC. Furthermore, α-syn/Aβ aggregates were significantly reduced in athletes and inversely correlated with physical activity level, independent of age. The positive correlation between antioxidant capability/physical activity and reduced protein accumulation was confirmed by these data and suggested that peripheral α-syn heterocomplexes may represent new indicators of ND-related protein misfolding