Mitochondria hyperpolarization is an early event in oxidized low-density lipoprotein-induced apoptosis in Caco-2 intestinal cells

AbstractWe investigated the mechanisms underlying the pro-apoptotic activity exerted by oxidized low-density lipoproteins (oxLDL) in Caco-2 intestinal cells, a cell line which retains many morphological and enzymatic features typical of normal human enterocytes. We found that: (i) oxLDL induced mitochondrial-mediated apoptosis by provoking first an increase in mitochondrial membrane potential, followed, later, by the typical apoptosis-associated depolarization (type II apoptosis); accordingly, (ii) caspase-9 inhibition significantly hindered apoptosis while caspase-8 inhibition did not; and finally (iii) dietary phenolic antioxidizing compounds exerted a significant protective antiapoptotic activity. These results point to mitochondrial hyperpolarization as ‘sensitizing feature’ in apoptotic proneness of Caco-2 intestinal cells to oxLDL exposure

Modulatory Effects of Polyphenols on Apoptosis Induction: Relevance for Cancer Prevention

Polyphenols, occurring in fruit and vegetables, wine, tea, extra virgin olive oil, chocolate and other cocoa products, have been demonstrated to have clear antioxidant properties in vitro, and many of their biological actions have been attributed to their intrinsic reducing capabilities. However, it has become clear that, in complex biological systems, polyphenols exhibit several additional properties which are yet poorly understood. Apoptosis is a genetically controlled and evolutionarily conserved form of cell death of critical importance for the normal embryonic development and for the maintenance of tissue homeostasis in the adult organism. The malfunction of the death machinery may play a primary role in various pathological processes, since too little or too much apoptosis can lead to proliferative or degenerative diseases, respectively. Cancer cells are characterized by a deregulated proliferation, and/or an inability to undergo programmed cell death. A large body of evidence indicates that polyphenols can exert chemopreventive effects towards different organ specific cancers, affecting the overall process of carcinogenesis by several mechanisms: inhibition of DNA synthesis, modulation of ROS production, regulation of cell cycle arrest, modulation of survival/proliferation pathways. In addition, polyphenols can directly influence different points of the apoptotic process, and/or the expression of regulatory proteins. Although the bulk of data has been obtained in in vitro systems, a number of clinical studies suggesting a preventive and therapeutic effectiveness of polyphenols in vivo is available. However, a deeper knowledge of the underlying mechanisms responsible for the modulation of apoptosis by polyphenols, and their real effectiveness, is necessary in order to propose them as potential chemopreventive and chemotherapeutic candidates for cancer treatment

Early csf biomarkers and late functional outcomes in spinal cord injury. A pilot study

open9noThis research was funded by the Italian Ministry of Health—call “Ricerca Finalizzata 2010” (project code RF-2010-2315118).Although, biomarkers are regarded as an important tool for monitoring injury severity and treatment efficacy, and for predicting clinical evolution in many neurological diseases and disorders including spinal cord injury, there is still a lack of reliable biomarkers for the assessment of clinical course and patient outcome. In this study, a biological dataset of 60 cytokines/chemokines, growth factorsm and intracellular and extracellular matrix proteins, analyzed in CSF within 24 h of injury, was used for correlation analysis with the clinical dataset of the same patients. A heat map was generated of positive and negative correlations between biomarkers and clinical rating scale scores at discharge, and between biomarkers and changes in clinical scores during the observation period. Using very stringent statistical criteria, we found 10 molecules which correlated with clinical scores at discharge, and five molecules, which correlated with changes in clinical scores. The proposed methodology may be useful for generating hypotheses regarding “predictive” and “treatment effectiveness” biomarkers, thereby suggesting potential candidates for disease‐modifying therapies using a “bed‐to‐bench” approach.openCapirossi R.; Piunti B.; Fernandez M.; Maietti E.; Rucci P.; Negrini S.; Giovannini T.; Kiekens C.; Calza' L.Capirossi R.; Piunti B.; Fernandez M.; Maietti E.; Rucci P.; Negrini S.; Giovannini T.; Kiekens C.; Calza' L

Association Between Infectious Agents and Lesions in Post-Weaned Piglets and Fattening Heavy Pigs With Porcine Respiratory Disease Complex (PRDC)

Porcine Respiratory Disease Complex (PRDC) is a multifactorial syndrome that causes health problems in growing pigs and economic losses to farmers. The etiological factors involved can be bacteria, viruses, or mycoplasmas. However, environmental stressors associated with farm management can influence the status of the animal's health. The role and impact of different microorganisms in the development of the disease can be complex, and these are not fully understood. The severity of lesions are a consequence of synergism and combination of different factors. The aim of this study was to systematically analyse samples, conferred to the Veterinary Diagnostic Laboratory (IZSLER, Brescia), with a standardized diagnostic protocol in case of suspected PRDC. During necropsy, the lungs and carcasses were analyzed to determine the severity and extension of lesions. Gross lung lesions were classified according to a pre-established scheme adapted from literature. Furthermore, pulmonary, pleural, and nasal lesions were scored to determine their severity and extension. Finally, the presence of infectious agents was investigated to identify the microorganisms involved in the cases studied. During the years 2014–2016, 1,658 samples of lungs and carcasses with PRDC from 863 farms were analyzed; among them 931 and 727 samples were from weaned piglets and fattening pigs, respectively. The most frequently observed lesions were characteristic of catarrhal bronchopneumonia, broncho-interstitial pneumonia, pleuropneumonia, and pleuritis. Some pathogens identified were correlated to specific lesions, whereas other pathogens to various lesions. These underline the need for the establishment of control and treatment programmes for individual farms

Comparing post-crisis dynamics across Euro Area countries with the Global Multi-country model

Abstract Following the global financial crisis, the Euro Area (EA) has experienced a persistent slump and notable trade balance adjustments, but with pronounced differences across EA Member States. We estimate a multi-country structural macroeconomic model to assess and compare the main drivers of GDP growth and trade balance adjustment across Germany, France, Italy, and Spain. We find that the pronounced post-crisis slump in Italy and Spain was mainly driven by positive saving shocks ('deleveraging') and by an increase in investment and intra-euro risk premia. Fiscal austerity in Spain and the productivity slowdown in Italy have been additional sizable contributors to the economic downturn. The results further suggest that euro depreciation, heightened intra-euro risk premia and subdued investment had a sizable impact on the trade balance reversals in Italy and Spain, which has been offset in France by a strong increase in imports and lower exports

Regional differential effects of the novel histamine H3 receptor antagonist 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-Nmethyl-3-pyridinecarboxamide hydrochloride (GSK189254) on histamine release in the central nervous system of freely

ABSTRACT After oral administration, the nonimidazole histamine H 3 receptor antagonist, 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254), increased histamine release from the tuberomammillary nucleus, where all histaminergic somata are localized, and from where their axons project to the entire brain. To further understand functional histaminergic circuitry in the brain, dual-probe microdialysis was used to pharmacologically block H 3 receptors in the tuberomammillary nucleus, and monitor histamine release in projection areas. Perfusion of the tuberomammillary nucleus with GSK189254 increased histamine release from the tuberomammillary nucleus, nucleus basalis magnocellularis, and cortex, but not from the striatum or nucleus accumbens. Cortical acetylcholine (ACh) release was also increased, but striatal dopamine release was not affected. When administered locally, GSK189254 increased histamine release from the nucleus basalis magnocellularis, but not from the striatum. Thus, defined by their sensitivity to GSK189254, histaminergic neurons establish distinct pathways according to their terminal projections, and can differentially modulate neurotransmitter release in a brain region-specific manner. Consistent with its effects on cortical ACh release, systemic administration of GSK189254 antagonized the amnesic effects of scopolamine in the rat object recognition test, a cognition paradigm with important cortical components. The discovery of the histamine H 3 receptor (H 3 R) back in 1983 was a major scientific breakthrough that provided key new perspectives in histamine researc

The Italian open data meteorological portal: MISTRAL

AbstractAt the national level, in Italy, observational and forecast data are collected by various public bodies and are often kept in various small, heterogeneous and non‐interoperable repositories, released under different licenses, thus limiting the usability for external users. In this context, MISTRAL (the Meteo Italian SupercompuTing PoRtAL) was launched as the first Italian meteorological open data portal, with the aim of promoting the reuse of meteorological data sets available at national level coverage. The MISTRAL portal provides (and archives) meteorological data from various observation networks, both public and private, and forecast data that are generated and post‐processed within the Consortium for Small‐scale Modeling‐Limited Area Model Italia (COSMO‐LAMI) agreement using high performance computing (HPC) facilities. Also incorporated is the Italy Flash Flood use case, implemented with the collaboration of European Centre for Medium‐Range Weather Forecasts (ECMWF), which exploits cutting edge advances in HPC‐based post‐processing of ensemble precipitation forecasts, for different model resolutions, and applies those to deliver novel blended‐resolution forecasts specifically for Italy. Finally, in addition to providing architectures for the acquisition and display of observational data, MISTRAL also delivers an interactive system for visualizing forecast data of different resolutions as superimposed multi‐layer maps

Aging in multiple sclerosis: from childhood to old age, etiopathogenesis, and unmet needs: a narrative review

Multiple sclerosis (MS) primarily affects adult females. However, in the last decades, rising incidence and prevalence have been observed for demographic extremes, such as pediatric-onset MS (POMS; occurring before 18 years of age) and late-onset MS (corresponding to an onset above 50 years). These categories show peculiar clinical-pathogenetic characteristics, aging processes and disease courses, therapeutic options, and unmet needs. Nonetheless, several open questions are still pending. POMS patients display an important contribution of multiple genetic and environmental factors such as EBV, while in LOMS, hormonal changes and pollution may represent disease triggers. In both categories, immunosenescence emerges as a pathogenic driver of the disease, particularly for LOMS. In both populations, patient and caregiver engagement are essential from the diagnosis communication to early treatment of disease-modifying therapy (DMTs), which in the elderly population appears more complex and less proven in terms of efficacy and safety. Digital technologies (e.g., exergames and e-training) have recently emerged with promising results, particularly in treating and following motor and cognitive deficits. However, this offer seems more feasible for POMS, being LOMS less familiar with digital technology. In this narrative review, we discuss how the aging process influences the pathogenesis, disease course, and therapeutic options of both POMS and LOMS. Finally, we evaluate the impact of new digital communication tools, which greatly interest the current and future management of POMS and LOMS patients

Effect of protocatechuic acid on insulin responsiveness and inflammation in visceral adipose tissue from obese individuals: possible role for PTP1B

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Correlazione tra progressione neuroradiologica di malattia e parametri liquorali alla diagnosi in una popolazione di pazienti affetti da Sclerosi Multipla Recidivante Remittente in trattamento con "Disease Modifying Therapy" di prima linea: confronto tra farmaci orali e iniettivi.

La Sclerosi Multipla è una patologia infiammatoria cronica a carattere autoimmune del sistema nervoso centrale, caratterizzata dall’accumulo di lesioni demielinizzanti nella sostanza bianca dell’encefalo e del midollo spinale. La patologia, in base al suo decorso, può essere distinta in quattro diversi fenotipi: recidivante-remittente, primariamente progressiva, secondariamente progressiva e progressivo-recidivante. I pazienti affetti dalla forma recidivante-remittente vengono trattati con una terapia di fondo detta “disease modifying therapy” (DMT). Ad oggi, grazie al progresso scientifico, esistono numerosi farmaci appartenenti a questa categoria che possono essere utilizzati in prima, seconda o terza linea. Quelli di prima linea possono essere distinti in farmaci orali e iniettivi. Questo studio è stato condotto con l’obiettivo di confrontare l’efficacia dei DMT orali e iniettivi di prima linea nel ridurre la progressione neuroradiologica della patologia. Contemporaneamente, sono stati analizzati alcuni parametri liquorali come possibili fattori predittivi di gravità di patologia: le bande oligoclonali, le IgM e le IgG. Sono stati reclutati 118 pazienti afferenti all’ambulatorio per le malattie demielinizzanti, nel reparto di Neurologia dell’Azienda Ospedaliera Universitaria Pisana. 88 erano in terapia con DMT iniettivi (interferone β e glatiramer acetato) mentre 30 con DMT orali (teriflunomide e dimetilfumarato) e tutti avevano effettuato una risonanza magnetica encefalica e del midollo e la puntura lombare con esame del liquor in prossimità dell’episodio acuto che ha determinato la diagnosi di sclerosi multipla. Per questo studio poi, sono state considerate il numero di nuove lesioni iperintense in immagini T2-pesate alla risonanza che i pazienti avevano sviluppato nell’arco di tempo in cui erano in terapia con i DMT di prima linea. Dall’analisi statistica, non è emersa alcuna differenza significativa tra i due farmaci orali e il numero di nuove lesioni iperintense in T2. Allo stesso modo, interferone β e glatiramer acetato sono risultati di pari efficacia nel rallentare la progressione neuroradiologica della patologia. Successivamente è stato effettuato un confronto tra i pazienti che assumevano DMT orali e quelli in terapia con DMT iniettivi ed è stata dimostrata la maggior efficacia dei DMT orali nel determinare un minor numero di nuove lesioni in T2. Nonostante la maggior efficacia dei farmaci orali, bisogna tenere presente il loro profilo di tollerabilità: mentre interferone β e glatiramer acetato sono farmaci ben tollerati e conosciuti, le terapie orali sono in commercio da meno tempo e danno reazioni avverse più importanti, soprattutto legate agli effetti sul sistema immunitario. Per quanto riguarda i parametri liquorali, è emersa una tendenza da parte del numero di bande oligoclonali e dei valori di IgM nel correlare positivamente con il numero di nuove lesioni iperintense in immagini T2-pesate alla risonanza magnetica. Tuttavia, saranno necessari modelli statistici più complessi e su popolazioni più numerose per confermare queste correlazioni. Da quanto osservato, possiamo concludere che i parametri liquorali potrebbero aiutare nel differenziare i pazienti affetti da una patologia più aggressiva da quelli con sclerosi multipla più lieve o moderata e, in questo modo, guidare il medico nella scelta del trattamento più adatto per il paziente, al fine di ottimizzare il rapporto rischio-beneficio