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Fabene P.F.,University of Verona | Bramanti P.,IRCCS Centro Neurolesi Bonino Pulejo | Constantin G.,University of Verona
Journal of Neuroimmunology | Year: 2010

Epilepsy has been considered mainly a neuronal disease, without much attention to non-neuronal cells. In recent years growing evidence suggest that astrocytes, microglia, blood leukocytes and blood-brain barrier breakdown are involved in the pathogenesis of epilepsy. In particular, leukocyte-endothelium interactions and eventually subsequent leukocyte recruitment in the brain parenchyma seem to represent key players in the epileptogenic cascade. Chemokines are chemotactic factors controlling leukocyte migration under physiological and pathological conditions. In the light of recent advances in our understanding of the role of inflammation mechanisms in the pathogenesis of epilepsy, pro-inflammatory chemokines may play a critical role in epileptogenesis. © 2010 Elsevier B.V.


Esposito E.,Messina University | Cuzzocrea S.,Messina University | Cuzzocrea S.,IRCCS Centro Neurolesi Bonino Pulejo
Current Neuropharmacology | Year: 2010

Melatonin is mainly produced in the mammalian pineal gland during the dark phase. Its secretion from the pineal gland has been classically associated with circadian and circanual rhythm regulation. However, melatonin production is not confined exclusively to the pineal gland, but other tissues including retina, Harderian glands, gut, ovary, testes, bone marrow and lens also produce it. Several studies have shown that melatonin reduces chronic and acute inflammation. The immunomodulatory properties of melatonin are well known; it acts on the immune system by regulating cytokine production of immunocompetent cells. Experimental and clinical data showing that melatonin reduces adhesion molecules and pro-inflammatory cytokines and modifies serum inflammatory parameters. As a consequence, melatonin improves the clinical course of illnesses which have an inflammatory etiology. Moreover, experimental evidence supports its actions as a direct and indirect antioxidant, scavenging free radicals, stimulating antioxidant enzymes, enhancing the activities of other antioxidants or protecting other antioxidant enzymes from oxidative damage. Several encouraging clinical studies suggest that melatonin is a neuroprotective molecule in neurodegenerative disorders where brain oxidative damage has been implicated as a common link. In this review, the authors examine the effect of melatonin on several neurological diseases with inflammatory components, including dementia, Alzheimer disease, Parkinson disease, multiple sclerosis, stroke, and brain ischemia/reperfusion but also in traumatic CNS injuries (traumatic brain and spinal cord injury). © 2010 Bentham Science Publishers Ltd.


Esposito E.,IRCCS Centro Neurolesi Bonino Pulejo | Cuzzocrea S.,IRCCS Centro Neurolesi Bonino Pulejo | Cuzzocrea S.,Messina University
Current Medicinal Chemistry | Year: 2010

The development of potential neuroprotective therapies for neurodegenerative diseases (Parkinson's and Alzheimer's Disease) must be based on understanding their molecular and biochemical pathogenesis. Many potential pathways of neuronal cell death have been implicated in a mouse model of neurodegenerative disease, including excitotoxicity, toxicity from reactive oxygen species (superoxide anion, nitric oxide, hydroxyl radical), apoptosis (caspase-dependent and -independent pathways), necrosis and glial injury. Some agents that act on these pathways may be available for protecting the brain against chronic neurodegenerative conditions like Parkinson's and Alzheimer's disease. Drugs currently used to treat neurological disease and injuries provide temporary relief of symptoms but do not stop or slow the underlying neurodegenerative process. Restorative therapies for Parkinson's Disease are currently focused on cell replacement and administration of growth factors and small-molecule neurotrophic agents. The new experimental drugs, by contrast, target the common, underlying cause of destructive process of brain cell death. For example, p53 inhibitors attack a key protein involved in nerve cell death and represent a new strategy for preserving brain function following sudden injury or chronic disease. Analogues of pifithrin-alpha (PFT), which was shown in previous studies to inhibit p53, were designed, synthesized and tested to see whether they would work against cultured brain cells and animal models of neurodegenerative disease. Moreover, several agents based on the predominant anti-amyloid strategy, targeting amyloid-beta (Aβ) peptide, which aggregates in the plaques that are a hallmark of Alzheimer's disease, would affect disease progression. Researchers are already making great strides in developing a vaccine for this progressive brain disorder. Immunization could offer a way to blunt or even prevent the deadly, memory-robbing disease. Here we review many of potential neuroprotective therapies, and strategies that might be suited to the development of innovative approaches that prevent degeneration and restore function in Parkinson's disease. © 2010 Bentham Science Publishers Ltd.


Ciurleo R.,IRCCS Centro Neurolesi Bonino Pulejo | Bramanti P.,IRCCS Centro Neurolesi Bonino Pulejo | Marino S.,IRCCS Centro Neurolesi Bonino Pulejo | Marino S.,Messina University
Pharmacological Research | Year: 2014

Statins as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase are widely prescribed for hypercholesterolemia treatment. In the last years, statins have also been shown to exert immunomodulatory and anti-inflammatory effects which appear to be related to inhibition of isoprenylation of small GTP-binding proteins and, at least in part, independent of their cholesterol-lowering effects. These "pleiotropic" effects make statins an attractive treatment option for immune-mediated disorders such as multiple sclerosis. Studies in vitro and in experimental autoimmune encephalomyelitis animal model seem to support not only the efficacy of statins as immunomodulatory agents but also their potential neuroprotective properties, although the exact mechanism with which statins exert these effects has not yet been fully understood. The immunomodulatory, anti-inflammatory and neuroprotective properties of statins provided the incentive for several clinical trials in multiple sclerosis, in which they were tested not only as mono-therapy but also in combination with interferon-β. However, the attempt to translate the results of animal model studies in humans produced conflicting results. Further large, prospective, randomized, double-blind, placebo-controlled trials, designed to evaluate the long-term effects of statins alone or in add-on to other disease-modifying therapies, are needed to support their routine clinical use in multiple sclerosis. © 2014 Elsevier Ltd.


Spina E.,Messina University | Spina E.,IRCCS Centro Neurolesi Bonino Pulejo | Trifiro G.,Messina University | Trifiro G.,IRCCS Centro Neurolesi Bonino Pulejo | Caraci F.,University of Catania
CNS Drugs | Year: 2012

After the introduction of selective serotonin reuptake inhibitors (SSRIs), other newer antidepressants with different mechanisms of action have been introduced in clinical practice. Because antidepressants are commonly prescribed in combination with other medications used to treat co-morbid psychiatric or somatic disorders, they are likely to be involved in clinically significant drug interactions. This review examines the drug interaction profiles of the following newer antidepressants: escitalopram, venlafaxine, desvenlafaxine, duloxetine, milnacipran, mirtazapine, reboxetine, bupropion, agomelatine and vilazodone.In general, by virtue of a more selective mechanism of action and receptor profile, newer antidepressants carry a relatively low risk for pharmacodynamic drug interactions, at least as compared with first-generation antidepressants, i.e. monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). On the other hand, they are susceptible to pharmacokinetic drug interactions. All new antidepressants are extensively metabolized in the liver by cytochrome P450 (CYP) isoenzymes, and therefore may be the target of metabolically based drug interactions. Concomitant administration of inhibitors or inducers of the CYP isoenzymes involved in the biotransformation of specific antidepressants may cause changes in their plasma concentrations. However, due to their relatively wide margin of safety, the consequences of such kinetic modifications are usually not clinically relevant. Conversely, some newer antidepressants may cause pharmacokinetic interactions through their ability to inhibit specific CYPs. With regard to this, duloxetine and bupropion are moderate inhibitors of CYP2D6. Therefore, potentially harmful drug interactions may occur when they are coadministered with substrates of these isoforms, especially compounds with a narrow therapeutic index. The other new antidepressants are only weak inhibitors or are not inhibitors of CYP isoforms at usual therapeutic concentrations and are not expected to affect the disposition of concomitantly administered medications. Although drug interactions with newer antidepressants are potentially, but rarely, clinically significant, the use of antidepressants with a more favourable drug interaction profile is advisable. Knowledge of the interaction potential of individual antidepressants is essential for safe prescribing and may help clinicians to predict and eventually avoid certain drug combinations.


Trifiro G.,Erasmus Medical Center | Trifiro G.,IRCCS Centro Neurolesi Bonino Pulejo
Current Infectious Disease Reports | Year: 2011

Antipsychotics are generally distinguished as atypical and typical agents, which are indicated in the treatment of acute and chronic psychoses and other psychiatric disorders. In April 2005, the US Food and Drug Administration issued a warning about the increased risk of all-cause mortality associated with atypical antipsychotic use in elderly patients with dementia. Pneumonia was one of the most frequently reported causes of death. The same warning was extended to typical antipsychotics in June 2008. In recent years, several observational studies have further explored the association between antipsychotic use, mainly in elderly patients, and the risk of fatal/nonfatal community-acquired pneumonia. The aim of this review is to revise and discuss the scientific evidence and biologic explanations for the association between atypical and typical antipsychotic use and pneumonia occurrence. Some general recommendations to clinicians are proposed to prevent the risk of pneumonia in patients requiring antipsychotic treatment. © 2011 The Author(s).


Di Paola R.,IRCCS Centro Neurolesi Bonino Pulejo
International journal of immunopathology and pharmacology | Year: 2010

This study tested the hypothesis that ethyl pyruvate (EP), a simple aliphatic ester with anti-inflammatory effects, can reduce type II collagen-induced mouse arthritis (CIA). DBA/1J mice were used for the study, developing erosive hind paw arthritis when immunized with CII in an emulsion in complete Freund?s adjuvant (CFA). The incidence of CIA was 100 percent by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint margins. EP-treatment (40 mg/kg/day i.p.) starting at the onset of arthritis (day 25) ameliorated the clinical signs at days 26-35 and improved histological status in the joint and paw. Immunohistochemical analysis for nitrotyrosine, poly (ADP-ribose) (PAR), inducible nitric oxide synthase (iNOS) revealed a positive staining in inflamed joints from mice subjected to CIA, while no staining was observed for HO-1 and Nrf-2 in the same group. The degree of staining for nitrotyrosine, PAR, iNOS, was significantly reduced in CII-challenged mice treated with the EP. Immuno-positive-staining for HO-1 and Nrf-2 was observed instead, in joints obtained from the EP-treated group. Plasma levels of TNF-α, IL-6 and the joint tissue levels of macrophage inflammatory protein (MIP)-1α and MIP-2 were also significantly reduced by EP treatment. Thirty-five days after immunization, EP-treatment significantly increased plasma levels of IL-10. These data demonstrate that EP treatment exerts an anti-inflammatory effect during chronic inflammation and is able to ameliorate the tissue damage associated with CIA.


Calabro R.S.,IRCCS Centro Neurolesi Bonino Pulejo | Marino S.,IRCCS Centro Neurolesi Bonino Pulejo | Bramanti P.,IRCCS Centro Neurolesi Bonino Pulejo
Expert Review of Neurotherapeutics | Year: 2011

The association between epilepsy and sexual disorders has long been known. However, the etiology remains uncertain, although it is likely to be multifactorial in origin involving neurological, endocrine, iatrogenic, psychiatric and psychosocial factors. Sexual disorders associated with epilepsy can be directly related to seizures (ictal), or unrelated in time to seizure occurrence (interictal). The most common sexual dysfunction is hyposexuality, even if hypersexuality and different paraphilias have been reported in males with epilepsy. Epilepsy and antiepileptic drugs can also alter sex hormone levels to promote the development of reproductive endocrine disorders. This article aims to explore the prevalence and etiology of sexual and reproductive dysfunctions in men with epilepsy, highlighting the pivotal role of antiepileptic drugs in their pathogenesis. © 2011 Expert Reviews Ltd.


The present invention relates to a phantom for periodical measurements of parameters allowing to ensure that performance of equipment for computed tomography and/or magnetic resonance tomography are compliant to established acceptability criteria, that is performance are constant in time. The main characteristic of such phantom is that the same phantom may be used for measurements of different physical parameters and for different machines, even of different type, such as machines for CT and/or MRT. The universal phantom described is made of a rectangular parallelepiped in PMMA made of different sections that may be filled with an appropriate liquid and/or contain different inserts according to the measurements to be performed, such as for example noise and uniformity, CT number linearity, high contrast spatial resolution, low contrast spatial resolution, layer thickness, etc.


Patent
Irccs Centro Neurolesi Bonino Pulejo | Date: 2010-07-07

A signal acquisition and conditioning system, specifically for bioelectric signals, comprising an acquisition and pre-conditioning device 2 comprising a chip adapted to process the input bioelectric signals in a differential manner, with a low use of additional circuitry. The system further comprises means for generating a sinusoidal-wave clock signal and means for converting said sinusoidal wave into a clock square-wave.

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