Sudden cardiac death in young athletes: Literature review of molecular basis

Intense athletic training and competition can rarely result in sudden cardiac death (SCD). Despite the introduction of pre-participation cardiovascular screening, especially among young competitive athletes, sport-related SCD remains a debated issue among medical personnel, sports communities and laypersons alike, and generates significant media attention. The most frequent cause of SCD is a hidden inherited cardiomyopathy, the athletes may not even be aware of. Predictive medicine, by searching the presence of pathogenic alterations in cardiac genes, may be an integrative tool, besides the conventional ones used in cardiology (mainly electro and echocardiogram), to reach a definitive diagnosis in athletes showing signs/symptoms, even borderline, of inherited cardiomyopathy/ channelopathy, and in athletes presenting family history of SCD and/or of hereditary cardiac disease. In this review, we revised the molecular basis of the major cardiac diseases associated to sudden cardiac death and the clinical molecular biology approach that can be used to perform risk assessment at DNA level of sudden cardiac death, contributing to the early implementation of adequate therapy. Alterations can occur in ion channel genes, in genes encoding desmosomal and junctional proteins, sarcomeric and Z-disc proteins, proteins for the cytoskeleton and the nuclear envelope. The advent of next generation sequencing (NGS) technology has provided the means to search for mutations in all these genes, at the same time. Therefore, this molecular approach should be the preferred methodology for the aforementioned purpose

Design, synthesis and biological evaluation of new small molecules with anti-inflammatory activity

Per lipossigenasi (nota più comunemente con l'abbreviazione di LOX o LO) si intende una famiglia eterogenea di enzimi in grado di perossidare i lipidi e di causare l'ossigenazione di acidi grassi polinsaturi trasformandoli, così, nei corrispettivi derivati idroperossidici. Nello specifico, la 5-LO rappresenta l'enzima chiave nell'ossidazione dell'acido arachidonico (AA) in LTA4, intermedio indispensabile per la sintesi dei leucotrieni, potenti mediatori flogistici coinvolti in una serie di differenti processi patologici. Va da sé che l'inibizione, dell'attività di tale enzima, induce la diretta riduzione di LT, definendo la LOX come valido drug-target per la farmacoterapia di disturbi infiammatori quali asma, rinite allergica, aterosclerosi e alcune forme neoplastiche. [a cura dell'autore]XIII n.s

Comparison between optimal refueling infrastructures for zero emission waste transportation vehicles in Valle Camonica

The aim of this work is to conduct a comprehensive and fair comparison between fleets of vehicles powered by different technologies, namely electricity, compressed hydrogen, and liquid hydrogen. The study followed a well-defined methodology, starting with the development of a mixed-integer linear programming (MILP) model using MATLAB and the YALMIP toolbox. The primary objective of the model is to minimize the total annual cost associated with the infrastructure required for refuelling the fleet of zero-emission vehicles. The battery electric vehicle refuelling infrastructure is used as a benchmark, with a total annual cost of around 200000 euro/y. The compressed hydrogen and liquid hydrogen infrastructure are comprehensive of a solar photovoltaic field. The hydrogen refuelling facility are analysed varying the price of the electricity. In the most profitable configuration, the compressed hydrogen refuelling facility cost around 320000 euro/y and for the liquid hydrogen 480000 euro/y. The sensitivity analysis, performed varying the cost of electricity, shows that it is never convenient to use hydrogen vehicles even in condition of high electricity prices. When it is possible to use electric vehicles and there are no constraints related to payload, range or refueling logistics they must be employed, as they are the most cost-effective solution to cancel the vehicles emissions

Influencia de la fertilización en el crecimiento de radicchio "Rosso di Chioggia" cultivado en dos ambientes diferentes

Este trabajo evalúa la influencia de la fertilización en radicchio tipo "Rosso de Chioggia" (precocidad media) sobre algunos índices de crecimiento. Se realizaron ensayos durante dos campañas en Rovigo (Italia) y una en Mendoza (Argentina), aplicándose dosis crecientes de NPK, identificadas como N0P0K0, N1P1K1, N2P2K2, en Mendoza y en Rovigo, además, N3P2K2. Durante el cultivo se calcularon índices de crecimiento como: relative growth rate (RGR), net assimilation rate (NAR), leaf area ratio (LAR), specific leaf area (SLA), leaf weigh ratio (LWR), crop growth ratio (CGR), leaf area index (LAI) and leaf area duration (LAD). En Mendoza, el CGR estuvo fuertemente influenciado por NAR desde el trasplante hasta alcanzar 776 grados días (GDD); desde 1052 a 1653 GDD el CGR fue afectado por el LAI el cual aumentó marcadamente debido a las condiciones ambientales favorables. Entre los 1052 y 1653 GDD el incremento del LAI determinó una reducción en la eficiencia fotosintética. En Rovigo, la tendencia de los índices fue disímil en los dos años, encontrándose respuestas diferentes en LAR y en SLA. En el segundo año, el CGR siempre arrojó valores más altos, mientras que NAR no difirió en ninguno de los años. En la segunda mitad del ciclo, CGR estuvo fuertemente asociado a una menor eficiencia fotosintética, debido a la formación de la cabeza. Valores elevados de LAI indicaron una extensión del ciclo, retrasando la formación de la cabeza. Las plantas alcanzaron la madurez comercial con LWR entre 0,35 - 0,40 g g-1. En ambos ambientes, no se observó claramente el efecto de la fertilización sobre los índices; si bien las dosis más altas mostraron mayor actividad de crecimiento en las etapas tempranas.This study evaluated the influence of fertilization on some growth indexes in radicchio "Rosso di Chioggia". The trial was conducted in Rovigo (Italy) for two years and in Mendoza (Argentina) for one year. Increasing doses of macronutrients were considered, identified as N0P0K0, N1P1K1, N2P2K2 and, only in Rovigo, N3P2K2. Some indexes related to growth analysis: relative growth rate (RGR), net assimilation rate (NAR), leaf area ratio (LAR), specific leaf area (SLA), leaf weigh ratio (LWR), crop growth ratio (CGR), leaf area index (LAI) and leaf area duration (LAD) were calculated during the growing cycle. At Mendoza CGR was strongly influenced by NAR from transplant until 776 growth degree days (GDD). After that moment, CGR was affected by LAI that increased markedly due to favourable environmental conditions. From 1052 to 1653 GDD the high increase of LAI determined a reduction in photosynthetic efficiency. At Rovigo the trends in index values showed differences between the two years considered, especially in LAR and SLA. In the second year CGR had always higher values; mainly due to higher LAI values, since NAR did not differ significantly during the years. In the second half of the growing cycle, CGR was instead strongly linked to a contraction of photosynthetic effectiveness, due to head formation. High LAI values showed a growing cycle extension to the detriment of early head formation. It was also observed that when LWR is around 0.35 - 0.40 g g-1, the plant reaches marketable maturation and is ready to be harvested. In both environments, no clear effects of fertilization were observed on the growth indexes. In any case highly fertilized plants showed higher growing activity especially at the beginning of the growing cycle.Fil: Filippini, María Flavia. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Ingeniería AgrícolaFil: Nicoletto, Carlo. Università degli Studi di Padova (Italia). Dipartimento Territorio e Sistemi Agro-ForestaliFil: Sambo, Paolo. Università degli Studi di Padova (Italia). Dipartimento Territorio e Sistemi Agro-ForestaliFil: Cavagnaro, Juan Bruno. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Ciencias BiológicasFil: Pimpini, Ferdinando. Università degli Studi di Padova (Italia). Dipartimento Territorio e Sistemi Agro-Forestal

Analgesia induced by the epigenetic drug, L-acetylcarnitine, outlasts the end of treatment in mouse models of chronic inflammatory and neuropathic pain

Background: L-acetylcarnitine, a drug marketed for the treatment of chronic pain, causes analgesia by epigenetically up-regulating type-2 metabotropic glutamate (mGlu2) receptors in the spinal cord. Because the epigenetic mechanisms are typically long-lasting, we hypothesized that analgesia could outlast the duration of L-acetylcarnitine treatment in models of inflammatory and neuropathic pain. Results: A seven-day treatment with L-acetylcarnitine ( 100 mg/kg, once a day, i.p.) produced an antiallodynic effect in the complete Freund adjuvant mouse model of chronic inflammatory pain. L-Acetylcarnitine-induced analgesia persisted for at least 14 days after drug withdrawal. In contrast, the analgesic effect of pregabalin, amitryptiline, ceftriaxone, and N-acetylcysteine disappeared seven days after drug withdrawal. L-acetylcarnitine treatment enhanced mGlu2/3 receptor protein levels in the dorsal region of the spinal cord. This effect also persisted for two weeks after drug withdrawal and was associated with increased levels of acetylated histone H3 bound to the Grm2 gene promoter in the dorsal root ganglia. A long-lasting analgesic effect of L-acetylcarnitine was also observed in mice subjected to chronic constriction injury of the sciatic nerve. In these animals, a 14-day treatment with pregabalin, amitryptiline, tramadol, or L-acetylcarnitine produced a significant antiallodynic effect, with pregabalin displaying the greatest efficacy. In mice treated with pregabalin, tramadol or L-acetylcarnitine the analgesic effect was still visible 15 days after the end of drug treatment. However, only in mice treated with L-acetylcarnitine analgesia persisted 37 days after drug withdrawal. This effect was associated with an increase in mGlu2/3 receptor protein levels in the dorsal horns of the spinal cord. Conclusions: Our findings suggest that L-acetylcarnitine has the unique property to cause a long-lasting analgesic effect that might reduce relapses in patients suffering from chronic pain

Permissive role for mGlu1 metabotropic glutamate receptors in excitotoxic retinal degeneration

Neuroprotection is an unmet need in eye disorders characterized by retinal ganglion cell (RGC) death, such as prematurity-induced retinal degeneration, glaucoma, and age-related macular degeneration. In all these disorders excitotoxicity is a prominent component of neuronal damage, but clinical data discourage the development of NMDA receptor antagonists as neuroprotectants. Here, we show that activation of mGlu1 metabotropic glutamate receptors largely contributes to excitotoxic degeneration of RGCs. Mice at postnatal day 9 were challenged with a toxic dose of monosodium glutamate (MSG, 3g/kg), which caused the death of >70% of Brn-3a+ RGCs. Systemic administration of the mGlu1 receptor negative allosteric modulator (NAM), JNJ16259685 (2.5mg/kg, s.c.), was largely protective against MSG-induced RGC death. This treatment did not cause changes in motor behavior in the pups. We also injected MSG to crv4 mice, which lack mGlu1 receptors because of a recessive mutation of the gene encoding the mGlu1 receptor. MSG did not cause retinal degeneration in crv4 mice, whereas it retained its toxic activity in their wild-type littermates. These findings demonstrate that mGlu1 receptors play a key role in excitotoxic degeneration of RGCs, and encourage the study of mGlu1 receptor NAMs in models of retinal neurodegeneration

Quality of veiled olive oil: Role of turbidity components

This study investigated the effects of water and content of solid particles, taken together as well as separately, on stability of veiled olive oil. The following oil samples were obtained through four different separation treatments: veiled, filtered, \u2018solid-only\u2019, and \u2018water-only\u2019. Changes in chemical, microbial, and sensory characteristics were evaluated during storage (240 days). A significant effect of hydrolysis was shown in veiled and \u2018water only\u2019 oils; in \u2018solid-only\u2019 oils, a slow increase of phenols was observed. A notable microbial activity, with resulting formation of volatile metabolites and sensory defects, was observed in veiled samples. Filtered oils underwent less significant changes

Antioxidant activity of synthetic polymers of phenolic compounds

In recent years, developing potent antioxidants has been a very active area of research. In this context, phenolic compounds have been evaluated for their antioxidant activity. However, the use of phenolic compounds has also been limited by poor antioxidant activity in several in vivo studies. Polymeric phenols have received much attention owing to their potent antioxidant properties and increased stability in aqueous systems. To be truly effective in biological applications, it is important that these polymers be synthesized using benign methods. In this context, enzyme catalyzed synthesis of polymeric phenols has been explored as an environmentally friendly and safer approach. This review summarizes work in enzymatic syntheses of polymers of phenols. Several assays have been developed to determine the antioxidant potency of these polymeric phenols. These assays are discussed in detail along with structure-property relationships. A deeper understanding of factors affecting antioxidant activity would provide an opportunity for the design of versatile, high performing polymers with enhanced antioxidant activity

Manipulating DNA Conformation Using Intertwined Conducting Polymer Chains

In the field of inherently conducting polymers, polyaniline (Pani) has elicited tremendous interest due to its promising electrical properties and unique redox tunability. Synthetic routes involving the use of polyelectrolytes have significantly improved the processability of polyaniline. Recently, a template guided synthesis catalyzed by an enzyme, horseradish peroxidase (HRP), has provided a means of polymerizing aniline under milder pH conditions (pH 4.3) and subsequently widened the choice of templates to more delicate biological macromolecules. Here we report a strategy that exploits the inherent molecular order as well as the polyelectrolyte behavior of DNA to enzymatically synthesize and biologically assemble conducting polyaniline. This “wrapping” of polyaniline on DNA has been found to induce reversible changes in the secondary structure of DNA, leading to the formation of an over-wound polymorph. The polyaniline synthesized on the DNA also exhibited a template-induced macroasymmetry. This unique polyaniline/DNA intertwined complex has been used to “probe” and control the conformation of the DNA double helix

mGlu1 Receptors Monopolize the Synaptic Control of Cerebellar Purkinje Cells by Epigenetically Down-Regulating mGlu5 Receptors

In cerebellar Purkinje cells (PCs) type-1 metabotropic glutamate (mGlu1) receptors play a key role in motor learning and drive the refinement of synaptic innervation during postnatal development. The cognate mGlu5 receptor is absent in mature PCs and shows low expression levels in the adult cerebellar cortex. Here we found that mGlu5 receptors were heavily expressed by PCs in the early postnatal life, when mGlu1α receptors were barely detectable. The developmental decline of mGlu5 receptors coincided with the appearance of mGlu1α receptors in PCs, and both processes were associated with specular changes in CpG methylation in the corresponding gene promoters. It was the mGlu1 receptor that drove the elimination of mGlu5 receptors from PCs, as shown by data obtained with conditional mGlu1α receptor knockout mice and with targeted pharmacological treatments during critical developmental time windows. The suppressing activity of mGlu1 receptors on mGlu5 receptor was maintained in mature PCs, suggesting that expression of mGlu1α and mGlu5 receptors is mutually exclusive in PCs. These findings add complexity to the the finely tuned mechanisms that regulate PC biology during development and in the adult life and lay the groundwork for an in-depth analysis of the role played by mGlu5 receptors in PC maturation