Possible role of alpha-lipoic acid in the treatment of peripheral nerve injuries

Recent findings on the antioxidant effects of pretreatment with α-lipoic acid (α-LA) on the crush injury of rat sciatic nerve confirm the possible usefulness of α-LA administration in humans with peripheral nerve injuries. We discussed this issue in relation with our recent results in which the combined employment of α-LA and γ-linolenic acid with a rehabilitation program for six weeks reduced sensory symptoms and neuropathic pain in patients with compressive radiculopathy syndrome from disc-nerve root conflict in comparison with patients submitted to rehabilitation program alone for six weeks

Musculoskeletal Pain in Gymnasts: A Retrospective Analysis on a Cohort of Professional Athletes

Gymnastics athletes are exposed to a high risk of injury, but also of developing muscu- loskeletal pain. These data are still little investigated in the available scientific literature. An online survey was distributed to 79 professional athletes who practiced artistic and rhythmic gymnastics. The survey collected demographic and anthropometric data, information about the sport practice, the training sessions, the prevalence of musculoskeletal pain gymnastics-related, and lifestyle habits. Musculoskeletal pain had a high prevalence, involving 65 of 79 athletes (82.3%). A significant correla- tion was found between musculoskeletal pain and the duration of sports practice, both for general pain (p = 0.041) and for specific districts: right wrist pain (p = 0.031), left wrist pain (p = 0.028), right shoulder (p = 0.039), left hip (p = 0.031), right thigh (p = 0.031), and left knee (p = 0.005). Another statistical association was found between right wrist pain and BMI (p = 0.001), and hip pain and BMI (p = 0.030). Hours spent in a sitting position were also correlated with the incidence of pain (p = 0.045). Wrist pain and right shoulder pain had a statistically significant association with the age of the athletes (right wrist pain: p = 0.038; left wrist pain: p = 0.004; right shoulder pain: p = 0.035). The more the gymnasts practice this sport, the more likely they are to develop musculoskeletal pain. Increased age and a higher BMI, as well as daily prolonged sitting position, seem to be potential risk factors for the onset of musculoskeletal pain. Future studies could plan training strategies aimed at preventing musculoskeletal pain associated with gymnastics, in order to promote its further spread

Expression of miRNA-33 and miRNA-155 in symptomatic and asymptomatic carotid artery stenosis

Background: The aim of this study was to evaluate miRNA-33 and miRNA-155 expression in Peripheral Blood Mononuclear Cells (PBMC) and carotid specimens of patients affected by Critical Carotid Artery stenosis (CAS). Material and Methods: We selected 17 asymptomatic (CAS-A group) and 10 symptomatic (CAS-S group) patients with CAS. Ten patients with traditional cardiovascular risk factors (RF group), matched for age and sex, were used as control group. Results: A significant increase in miRNA-33 expression was observed both in peripheral blood and in carotid specimens of CAS-A patients (p 0.04) in comparison with CAS-S and RF, whereas no significant difference were found among the groups regarding miRNA-155 expression both in peripheral blood and in carotid specimens. Conclusions: This is to our knowledge the first report on miRNAs expression in human PBMCs from CAS patients. Results of this study suggest that miRNA-33 in involved in the process underling plaque formation and growth, but not is plaque instability and ischemic brain damage, whereas miRNA-155 is expressed during all the phases of atherosclerotic disease

Tyr78Phe Transthyretin Mutation with Predominant Motor Neuropathy as the Initial Presentation

Transthyretin (TTR) amyloidosis, the most frequent form of hereditary amyloidosis, is caused by dominant mutations in the TTR gene. More than 100 mutations have been identified. Clinical manifestations of TTR amyloidosis are usually induced by extracellular amyloid deposition in several organs. The major neurological manifestation is motor-sensory neuropathy associated with dysautonomic impairment. Here, we describe a 63-year-old man who came to our institution due to a suspected motor neuron disease. During a 4-year follow-up period, he underwent extensive clinical examination, electromyographic studies, sural nerve biopsy and TTR gene analysis by direct sequencing. Despite the predominant motor involvement, the detailed clinical examination also showed some mild sensory and dysautonomic signs. In addition, his clinical and family history included multiorgan disorders, such as carpal tunnel syndrome, as well as conditions with cardiac, renal, eye, and hepatic involvement. The sural nerve biopsy disclosed amyloid deposition, and the sequence analysis of the TTR gene detected a heterozygous Tyr78Phe substitution. The TTR gene variant found in our patient had only been described once so far, in a French man of Italian origin presenting with late-onset peripheral neuropathy and bilateral carpal tunnel syndrome. The predominant motor involvement presented by our patient is an uncommon occurrence and demonstrates the clinical heterogeneity of TTR amyloidosis

Tracking and Alignment with the Silicon Strip Tracker at the CMS Magnet Test Cosmic Challenge

Data were collected with a custom-built sub-structure of the silicon strip tracker, both during the preparation of the Magnet Test Cosmic Challenge and during the challenge itself. These data were used to evaluate performance of track reconstruction and detector alignment algorithms, both with and without magnetic field. The track reconstruction algorithm is described in detail and its performance presented, in terms of its efficiency, resolution and consistency with the results from other sub-detectors. A study of detector alignment is shown, including the use tracker construction information. The effect of alignment on track quality is discussed

Circulating plasma factors induce tubular and glomerular alterations in septic burns patients

Background Severe burn is a systemic illness often complicated by sepsis. Kidney is one of the organs invariably affected, and proteinuria is a constant clinical finding. We studied the relationships between proteinuria and patient outcome, severity of renal dysfunction and systemic inflammatory state in burns patients who developed sepsis-associated acute renal failure (ARF). We then tested the hypothesis that plasma in these patients induces apoptosis and functional alterations that could account for proteinuria and severity of renal dysfunction in tubular cells and podocytes. Methods We studied the correlation between proteinuria and indexes of systemic inflammation or renal function prospectively in 19 severe burns patients with septic shock and ARF, and we evaluated the effect of plasma on apoptosis, polarity and functional alterations in cultured human tubular cells and podocytes. As controls, we collected plasma from 10 burns patients with septic shock but without ARF, 10 burns patients with septic shock and ARF, 10 non-burns patients with septic shock without ARF, 10 chronic uremic patients and 10 healthy volunteers. Results Septic burns patients with ARF presented a severe proteinuria that correlated to outcome, glomerular (creatinine/urea clearance) and tubular (fractional excretion of sodium and potassium) functional impairment and systemic inflammation (white blood cell (WBC) and platelet counts). Plasma from these patients induced a pro-apoptotic effect in tubular cells and podocytes that correlated with the extent of proteinuria. Plasma-induced apoptosis was significantly higher in septic severe burns patients with ARF with respect to those without ARF or with septic shock without burns. Moreover, plasma from septic burns patients induced an alteration of polarity in tubular cells, as well as reduced expression of the tight junction protein ZO-1 and of the endocytic receptor megalin. In podocytes, plasma from septic burns patients increased permeability to albumin and decreased the expression of the slit diaphragm protein nephrin. Conclusion Plasma from burns patients with sepsis-associated ARF contains factors that affect the function and survival of tubular cells and podocytes. These factors are likely to be involved in the pathogenesis of acute tubular injury and proteinuria, which is a negative prognostic factor and an index of renal involvement in the systemic inflammatory reaction

Multicentric Molecular and Pathologic Study On Canine Adenovirus Type 1 in Red Foxes (Vulpes vulpes) in Three European Countries

Canine adenovirus type 1 (CAdV-1) is the agent of infectious canine hepatitis, a severe frequently fatal disease affecting primarily dogs (Canis lupus familiaris). The virus has been detected in many wild carnivore species. Our aim was to evaluate the prevalence and genetic and histopathologic features of CAdV-1 in wild red foxes (Vulpes vulpes). Kidney and liver samples were obtained from 86 subjects, coming from the UK (n\ubc21), Italy (n\ubc36), and Germany (n\ubc29). We used PCR, targeting the viral E3 gene and flanked regions, to detect the presence of the virus; viral E3, fiber, and E4 genes were sequenced and their sequences were compared with published sequences. Kidneys and liver from foxes in Italy and Great Britain (n\ubc57) were prepared for histologic and immunohistochemical examination for CAdV-1. Viral DNA was detected in 22% (19 of 86) kidney samples, with E3 and E4 genes showing reported and unreported single nucleotide changes. No pathologic changes or viral immunopositive signals were detected in the examined tissues. Our study suggests that red foxes could be considered potential shedders of CAdV-1, as they showed a relatively high prevalence without related pathologic changes in the organs examined

Hepatitis E virus infection in wild rabbit (Oryctolagus cuniculus) in Italy and in the UK: a serological, molecular, and pathological study

A novel animal strain of HEV demonstrating zoonotic potential rabbit HEV (rHEV) has been recently identified in farmed rabbits in China. To investigate the presence of rHEV in wild rabbit population, serum and tissue samples were taken from 65 rabbits, 35 Italian and 30 from UK. Sera were submitted to a double antigen sandwich ELISA, whereas hepatic tissues and other organs to molecular and pathological investigations. Sixteen serum samples (24.6%) scored positive for anti-HEV antibodies, and six samples (9%) of hepatic tissue were positive for HEV RT-PCR, while the other organs were negative. Sequencing and phylogenetic analysis of HEV RNA-positive samples indicated that while two Italian rabbits were infected with strains closely related to wild boar and swine strains (HEV-3), the other four (2 Italian and 2 English) were clustered within rHEV clade. Megalocytosis and multifocal areas of hepatocytes degeneration and necrosis with a pericentrilobular pattern were observed in rHEV-infected rabbits. In those infected by the strain analogous to HEV-3, the lesions were mainly localized in the periportal areas and were less severe. In both cases, inflammatory infiltrates were predominantly composed of CD3-positive lymphocytes and a reduced number of macrophages. By immunohistochemistry, only liver samples taken from HEV RNA-positive rabbits scored positive for viral antigen. Our results indicated that HEV infection is present in rabbit population with different clades and is endemic in the Italian and English wild rabbit population, suggesting the possibility that this species may be infected with rHEV or swine HEV-3 strains

Atrial natriuretic peptide stimulates autophagy/mitophagy and improves mitochondrial function in chronic heart failure

Mitochondrial dysfunction, causing increased reactive oxygen species (ROS) production, is a molecular feature of heart failure (HF). A defective antioxidant response and mitophagic flux were reported in circulating leucocytes of patients with chronic HF and reduced ejection fraction (HFrEF). Atrial natriuretic peptide (ANP) exerts many cardiac beneficial effects, including the ability to protect cardiomyocytes by promoting autophagy. We tested the impact of ANP on autophagy/mitophagy, altered mitochondrial structure and function and increased oxidative stress in HFrEF patients by both ex vivo and in vivo approaches. The ex vivo study included thirteen HFrEF patients whose peripheral blood mononuclear cells (PBMCs) were isolated and treated with αANP (10-11 M) for 4 h. The in vivo study included six HFrEF patients who received sacubitril/valsartan for two months. PBMCs were characterized before and after treatment. Both approaches analyzed mitochondrial structure and functionality. We found that levels of αANP increased upon sacubitril/valsartan, whereas levels of NT-proBNP decreased. Both the ex vivo direct exposure to αANP and the higher αANP level upon in vivo treatment with sacubitril/valsartan caused: (i) improvement of mitochondrial membrane potential; (ii) stimulation of the autophagic process; (iii) significant reduction of mitochondrial mass-index of mitophagy stimulation-and upregulation of mitophagy-related genes; (iv) reduction of mitochondrial damage with increased inner mitochondrial membrane (IMM)/outer mitochondrial membrane (OMM) index and reduced ROS generation. Herein we demonstrate that αANP stimulates both autophagy and mitophagy responses, counteracts mitochondrial dysfunction, and damages ultimately reducing mitochondrial oxidative stress generation in PBMCs from chronic HF patients. These properties were confirmed upon sacubitril/valsartan administration, a pivotal drug in HFrEF treatment