Altered glucose catabolism in the presynaptic and perisynaptic compartments of SOD1G93A mouse spinal cord and motor cortex indicates that mitochondria are the site of bioenergetic imbalance in ALS

Amyotrophic lateral sclerosis is an adult-onset neurodegenerative disease that develops due to motor neuron death. Several mechanisms occur supporting neurodegeneration, including mitochondrial dysfunction. Recently, we demonstrated that the synaptosomes from the spinal cord of SOD1G93A mice, an in vitro model of presynapses, displayed impaired mitochondrial metabolism at early pre-symptomatic stages of the disease, while perisynaptic astrocyte particles, or gliosomes, were characterized by mild energy impairment only at symptomatic stages. This work aimed to understand whether mitochondrial impairment is a consequence of upstream metabolic damage. We analysed the critical pathways involved in glucose catabolism at presynaptic and perisynaptic compartments. Spinal cord and motor cortex synaptosomes from SOD1G93A mice displayed high activity of hexokinase and phosphofructokinase, key glycolysis enzymes, and of citrate synthase and malate dehydrogenase, key Krebs cycle enzymes, but did not display high lactate dehydrogenase activity, the key enzyme in lactate fermentation. This enhancement was evident in the spinal cord from the early stages of the disease and in the motor cortex at only symptomatic stages. Conversely, an increase in glycolysis and lactate fermentation activity, but not Krebs cycle activity, was observed in gliosomes from the spinal cord and motor cortex of SOD1G93A mice although only at the symptomatic stages of the disease. The cited enzymatic activities were enhanced in spinal cord and motor cortex homogenates, paralleling the time-course of the effect observed in synaptosomes and gliosomes. The observed metabolic modifications might be considered an attempt to restore altered energetic balance and indicate that mitochondria represent the ultimate site of bioenergetic impairment. This article is protected by copyright. All rights reserved

Valvular leak after transcatheter aortic valve implantation: a clinician update on epidemiology, pathophysiology and clinical implications

During trascatheter aortic valve implantation (TAVI) the native valve is not removed but crushed. Thus, a slight prosthesis insufficiency is not uncommon and has been reported in about 70% of patients for both available types of percutaneous valves. However, the definition of clinically “significant” valve regurgitation is not fully established yet. In most cases, aortic insufficiency is mild and clinical acceptable, however, severe insufficiency can occur. Paravalvular insufficiency is usually prevalent, and it may be the consequence of prosthesis/patient mismatch due to an undersizing of the implanted device or to an incomplete expansion of the prosthesis stent frame, or also to incorrect site of prosthesis implantation. Thus, an accurate assessment of the aortic valve annulus before TAVI is mandatory in order to select the optimal size of the valve. The presence of large calcium burden or bicuspid valve as well as the correct implantation of the device are other key determinants of final valve insufficiency. When severe regurgitation is present, an integration of hemodynamic, angiographic, transthoracic and TEE data is necessary to tailor the best clinical decision on a per-patient basis

Transapical Deployment of Thoracic Stent Graft for Ascending Aorta Coronary Bypass Pseudoaneurysm in a Patient with Prosthetic Aortic Valve

The authors describe the transapical deployment of a thoracic endograft to exclude a saphenous vein graft proximal anastomotic pseudoaneurysm following coronary artery bypass grafting (CABG) in a 63-year-old male with a prosthetic aortic valve. A standard thoracic endograft has been deployed via transapical access after percutaneous transluminal coronary angioplasty of the native vessel perfused by the patent CABG. The procedure was uneventful; an 8-month computed tomography scan showed complete exclusion of the pseudoaneurysm with patency of supra-aortic trunks

Direct detection of free vitamin D as a tool to assess risk conditions associated with chronic plaque psoriasis: Free vitamin D in chronic plaque psoriasis patients

Introduction.Psoriasis is a major public health problem that results in high social and health costs. New approaches and methods are required to identify any conditions related to the disease and comorbidity development. The vitamin D deficiency is associated to psoriasis and could play an important role in its pathogenesis. However, the serum level of vitamin D is currently measured as total vitamin D, which is affected by wide variability. Therefore, the determination of the free form could be more significant, since it is independent of confounding factors. A cross-sectional study was performed to assess the association between chronic plaque psoriasis and serum level of free vitamin D, detected by a direct analytical method. Methods.The levels of bioavailable vitamin D, total vitamin D and other metabolic parameters whose homeostasis is regulated by vitamin D were evaluated in 72 psoriasis patients and in 48 healthy controls. A direct immunoassay method was used to directly measure serum free vitamin D level. Analysis of covariance was performed to calculate estimated marginal means (EMM) and 95% confidence interval (CI), after adjustment for age, sex and BMI, within the two groups. Results.Patients showed an EMM of 5.526±0.271pg/ml, 95% CI 4.989-6.063; while controls an EMM of 6.776±0.271 pg/ml, 95% CI 6.115-7.437. Conclusions.Chronic plaque psoriasis patients exhibited a serum level of free vitamin D lower than controls. The direct immunoassay method could represent a useful tool to assess vitamin D status and identify a risk condition associated with the onset of the pathology

Depressive symptoms, functional measures and long-term outcomes of high-risk ST-elevated myocardial infarction patients treated by primary angioplasty

The presence of major depressive symptoms is usually considered a negative long-term prognostic factor after an acute myocardial infarction (AMI); however, most of the supporting research was conducted before the era of immediate reperfusion by percutaneous coronary intervention. The aims of this study are to evaluate if depression still retains long-term prognostic significance in our era of immediate coronary reperfusion, and to study possible correlations with clinical parameters of physical performance. In 184 patients with recent ST-elevated AMI (STEMI), treated by immediate reperfusion, moderate or severe depressive symptoms (evaluated by Beck Depression Inventory version I) were present in 10 % of cases. Physical performance was evaluated by two 6-min walk tests and by a symptom-limited cardiopulmonary exercise test: somatic/affective (but not cognitive/affective) symptoms of depression and perceived quality of life (evaluated by the EuroQoL questionnaire) are worse in patients with lower levels of physical performance. Follow-up was performed after a median of 29 months by means of telephone interviews; 32 major adverse cardiovascular events (MACE) occurred. The presence of three vessels disease and low left ventricle ejection fraction are correlated with a greater incidence of MACE; only somatic/affective (but not cognitive/affective) symptoms of depression correlate with long-term outcomes. In patients with recent STEMI treated by immediate reperfusion, somatic/affective but not cognitive/affective symptoms of depression show prognostic value on long-term MACE. Depression symptoms are not predictors "per se" of adverse prognosis, but seem to express an underlying worse cardiac efficiency, clinically reflected by poorer physical performance