Clinical and Translational Imaging: time for a major leap forward

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Clinical and translational imaging keeps growing: thanks to its board members, authors and readership

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La sindrome da calo di deposizione in allevamento di ovaiole

L'uovo è un alimento di grande valore nutritivo e di largo uso culinario e commerciale. Ne consegue che in ogni parte del mondo è presente un settore avicolo specifico per tale produzione zootecnica. Ad un prodotto sano deve corrispondere un allevamento avicolo sano, dal momento che molte sono le cause che possono portare ad una patologia che coinvolge l'apparato riproduttore e che si ripercuote negativamente sulla qualità dell'uovo. La nostra tesi tende a mettere in evidenza i vari fattori che possono determinare un calo della ovodeposizione ovvero quella patologia subdola che spesso elude anche i controlli sanitari più attenti. Fra cause non infettive, ancora importanti in alcune realtà zootecniche, quelle nutrizionali quali le carenze vitaminiche, minerali e proteiche, ma anche la contaminazione degli alimenti mal conservati da parte di funghi quali ad esempio Aspergillus spp. e Fusarium spp., produttori di micotossine. Le cause fisiche comprendono un errato fotoperiodo e le condizioni di umidità, temperatura e ventilazione che incidono sul benessere animale. Fra le malattie infettive virali più frequentemente riscontrate: la Bronchite Infettiva, per la variabilità antigenica che caratterizza i sierotipi diffusi in tutto il mondo, l’Encefalomielite Aviare e le infezioni da Paramixovirus. Fra le malattie batteriche, Salmonelle spp. ed E. coli quali agenti di importanti zoonosi ed i Micoplasmi quali responsabili di complicazioni in corso di patologie ad andamento cronico di natura infettiva o parassitaria. Le malattie da protozoi, elminti e atropodi sono ricollegabili a tecnologie avicole innovative quali la produzione biologica. Fra queste le coccidiosi, le verminosi e l'acariasi dermanissica, da sempre responsabili di calo dell’ovodeposizione nell'allevamento a terra in recinti e senza i trattamenti farmacologici chemioprofilattici propri dell'allevamento intensivo

Terapia della riacutizzazione di scompenso cardiaco : Levosimendan, effetti a breve e medio termine.

L’insufficienza cardiaca acuta è un problema di difficile gestione medica, con importante rischio di mortalità per i pazienti non solo durante il periodo di ospedalizzazione, ma anche successivamente, poiché il numero e la gravità degli eventi acuti che seguono la dimissione peggiorano notevolmente la prognosi. Il Levosimendan è un farmaco introdotto solo recentemente nella pratica clinica. Il suo peculiare meccanismo d’azione, che non comporta un incremento delle concentrazioni di calcio intracellulari, ma una sensibilizzazione della cellula a questo ione, ha fatto sì che venisse studiato come alternativa ai farmaci classici a disposizione per il trattamento delle sindromi da insufficienza cardiaca acuta. Nello studio descritto in questa tesi, i pazienti ospedalizzati per riacutizzazione di scompenso cardiaco sono stati sottoposti ad infusione di Levosimendan; un controllo clinico ed ecocardiografico è stato effettuato prima e dopo l’infusione del farmaco e dopo tre mesi dalla somministrazione. Inoltre, durante la degenza, è stata valutata la variazione della classe NYHA, del peso, del BNP e di altri parametri di laboratorio. Questi dati sono stati utilizzati per valutare l’efficacia del farmaco somministrato sia nel breve che nel medio termine. Tutti i pazienti studiati, dopo il trattamento con Levosimendan, hanno mostrato miglioramento in termini di classe NYHA, peso, BNP e di alcuni parametri ecocardiografici (frazione di eiezione e pressione sistolica in arteria polmonare). La maggior parte dei pazienti ha mantenuto tale beneficio nei controlli successivi. Dal punto di vista della sicurezza del farmaco, nella popolazione in studio non si sono osservate variazioni degli indici di funzionalità epatica e renale in risposta all’infusione del farmaco

Imaging techniques in ALS.

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of both upper and lower motor neuron located in the spinal cord and brainstem. Diagnosis of ALS is predominantly clinical, nevertheless, electromyography and Magnetic Resonance Imaging (MRI) may provide support. Several advanced MRI techniques have been proven useful for ALS diagnosis and, indeed, the combination of different MRI techniques demonstrated an improvement in sensitivity and specificity as far as 90%. This review focus on the imaging techniques currently used in the diagnosis and management of ALS with brief considerations on future applications

Atypical presentation of Non-Hodgkin Lymphoma (NHL): a case report

Lymphomas infrequently cause peripheral nerve complications. These syndromes mostly occur by direct compression or infiltration of nerves (neurolymphomatosis), but may also be due to a remote effect as paraneoplastic syndromes, neurotoxic complications of chemotherapy, antibody-mediated or autoimmune mechanisms.We report the case of a 60-year-old woman who presented with a complex peripheral nervous system involvement as initial manifestation of Non-Hodgkin Lymphoma (NHL). This case sheds light on "protean" mechanism of peripheral nerve complications during the course of NHL and related diagnostic dilemma

Introduzione

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The ketogenic diet increases in vivo glutathione levels in patients with epilepsy

The Ketogenic Diet (KD) is a high-fat, low-carbohydrate diet that has been utilized as the first line treatment for contrasting intractable epilepsy. It is responsible for the presence of ketone bodies in blood, whose neuroprotective effect has been widely shown in recent years but remains unclear. Since glutathione (GSH) is implicated in oxidation-reduction reactions, our aim was to monitor the effects of KD on GSH brain levels by means of magnetic resonance spectroscopy (MRS). MRS was acquired from 16 KD patients and seven age-matched Healthy Controls (HC). We estimated metabolite concentrations with linear combination model (LCModel), assessing differences between KD and HC with t-test. Pearson was used to investigate GHS correlations with blood serum 3-B-Hydroxybutyrate (3HB) concentrations and with number of weekly epileptic seizures. The results have shown higher levels of brain GSH for KD patients (2.5 ± 0.5 mM) compared to HC (2.0 ± 0.5 mM). Both blood serum 3HB and number of seizures did not correlate with GSH concentration. The present study showed a significant increase in GSH in the brain of epileptic children treated with KD, reproducing for the first time in humans what was previously observed in animal studies. Our results may suggest a pivotal role of GSH in the antioxidant neuroprotective effect of KD in the human brain

Hypoxia-Inducible Factor-1α Activity as a Switch for Glioblastoma Responsiveness to Temozolomide

RationaleThe activity of the transcription factor, hypoxia-inducible factor (HIF)-1α, is a common driver of a number of the pathways involved in the aggressiveness of glioblastomas (GBMs), and it has been suggested that the reduction in this activity observed, soon after the administration of temozolomide (TMZ), can be a biomarker of an early response in GBM models. As HIF-1α is a tightly regulated protein, studying the processes involved in its downregulation could shed new light on the mechanisms underlying GBM sensitivity or resistance to TMZ.MethodsThe effect of HIF-1α silencing on cell responsiveness to TMZ was assessed in four genetically different human GBM cell lines by evaluating cell viability and apoptosis-related gene balance. LAMP-2A silencing was used to evaluate the contribution of chaperone-mediated autophagy (CMA) to the modulation of HIF-1α activity in TMZ-sensitive and TMZ-resistant cells.ResultsThe results showed that HIF-1α but not HIF-2α activity is associated with GBM responsiveness to TMZ: its downregulation improves the response of TMZ-resistant cells, while blocking CMA-mediated HIF-1α degradation induces resistance to TMZ in TMZ-sensitive cells. These findings are in line with the modulation of crucial apoptosis-related genes.ConclusionOur results demonstrate the central role played by HIF-1α activity in determining the sensitivity or resistance of GBMs to TMZ, and we suggest that CMA is the cellular mechanism responsible for modulating this activity after TMZ treatment

Optical imaging probes in oncology

Cancer is a complex disease, characterized by alteration of different physiological molecular processes and cellular features. Keeping this in mind, the possibility of early identification and detection of specific tumor biomarkers by non-invasive approaches could improve early diagnosis and patient management.Different molecular imaging procedures provide powerful tools for detection and non-invasive characterization of oncological lesions. Clinical studies are mainly based on the use of computed tomography, nuclear-based imaging techniques and magnetic resonance imaging. Preclinical imaging in small animal models entails the use of dedicated instruments, and beyond the already cited imaging techniques, it includes also optical imaging studies. Optical imaging strategies are based on the use of luminescent or fluorescent reporter genes or injectable fluorescent or luminescent probes that provide the possibility to study tumor features even by means of fluorescence and luminescence imaging. Currently, most of these probes are used only in animal models, but the possibility of applying some of them also in the clinics is under evaluation.The importance of tumor imaging, the ease of use of optical imaging instruments, the commercial availability of a wide range of probes as well as the continuous description of newly developed probes, demonstrate the significance of these applications. The aim of this review is providing a complete description of the possible optical imaging procedures available for the non-invasive assessment of tumor features in oncological murine models. In particular, the characteristics of both commercially available and newly developed probes will be outlined and discussed