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Safety and Efficacy of Paliperidone Extended-Release in Acute and Maintenance Treatment of Schizophrenia
Edoardo Spina and Rosalia Crupi
Journal of Central Nervous System Disease , 2012, DOI: 10.4137/JCNSD.S1607
Abstract: Paliperidone, the major active metabolite of risperidone, is a second-generation antipsychotic that has been developed as an extended-release (ER) tablet formulation that minimizes peak-trough fluctuations in plasma concentrations, allowing once-daily administration and constant drug delivery. Paliperidone ER has demonstrated efficacy in the reduction of acute schizophrenia symptoms in 6-week, placebo-controlled, double-blind trials and clinical benefits were maintained in the longer-term according to extension studies of up to 52 weeks in duration. Compared with quetiapine, paliperidone ER was associated with a more rapid symptom improvement. In addition, it was more effective than placebo in the prevention of symptom recurrence. Paliperidone ER is generally well tolerated with a predictable adverse event profile. Like risperidone, it is associated with a dose-dependent risk of extrapyramidal symptoms and prolactin elevation. Short- and longer-term studies have indicated a low liability for paliperidone ER to cause metabolic (ie, weight gain, hyperglycaemia and lipid dysregulation) or cardiovascular adverse effects. Available safety data from elderly patients appear to be promising. Due to negligible hepatic biotransformation, paliperidone ER is unlikely to be involved in clinically significant metabolic drug-drug interactions. Additional active comparator trials evaluating efficacy, tolerability and cost-effectiveness are required to better define the role of paliperidone ER in the treatment of schizophrenia in relation to other currently available second-generation antipsychotics, particularly risperidone.
Safety and Efficacy of Paliperidone Extended-Release in Acute and Maintenance Treatment of Schizophrenia
Edoardo Spina,Rosalia Crupi
Journal of Central Nervous System Disease , 2011,
Molecular evidence for the involvement of PPAR-δ and PPAR-γ in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma
Paterniti Irene,Impellizzeri Daniela,Crupi Rosalia,Morabito Rossana
Journal of Neuroinflammation , 2013, DOI: 10.1186/1742-2094-10-20
Abstract: Background Palmitoylethanolamide (PEA) is an endogenous fatty acid amide displaying anti-inflammatory and analgesic actions. Moreover, several data have suggested that PEA reduced inflammation and tissue injury associated with spinal cord trauma and showed a regulatory role for peroxisome proliferator-activated receptor (PPAR)-α signaling in the neuroprotective effect of PEA. However, several other mechanisms could explain the anti-inflammatory and anti-hyperalgesic effects of PEA, including the activation of PPAR-δ and PPAR-γ. The aim of the present study was to carefully investigate the exact contribution of PPAR-δ and PPAR-γ in addition to PPAR-α, in the protective effect of PEA on secondary inflammatory damage associated with an experimental model of spinal cord injury (SCI). Methods SCI was induced in mice through a spinal cord compression by the application of vascular clips (force of 24 g) to the dura via a four-level T5 to T8 laminectomy, and PEA (10 mg/kg, intraperitoneally, 1 and 6 hours after SCI) was injected into wildtype mice and into mice lacking PPAR-α (PPAR-αKO). To deepen the ability of specific PPAR-δ and PPAR-γ antagonists to reverse the effect of PEA, mice were administered GSK0660 or GW9662, 30 minutes before PEA injection. Results Genetic ablation of PPAR-α in mice exacerbated spinal cord damage, while PEA-induced neuroprotection seemed be abolished in PPARαKO mice. Twenty-four hours after spinal cord damage, immunohistological and biochemical studies were performed on spinal cord tissue. Our results indicate that PPAR-δ and PPAR-γ also mediated the protection induced by PEA. In particular, PEA was less effective in PPAR-αKO, GSK0660-treated or GW9662-pretreated mice, as evaluated by the degree of spinal cord inflammation and tissue injury, neutrophil infiltration, proinflammmatory cytokine, inducible nitric oxide synthase expression and motor function. PEA is also able to restore PPAR-δ and PPAR-γ expression in spinal cord tissue. Conclusion This study indicates that PPAR-δ and PPAR-γ can also contribute to the anti-inflammatory activity of PEA in SCI.
Absence of TLR4 Reduces Neurovascular Unit and Secondary Inflammatory Process after Traumatic Brain Injury in Mice
Akbar Ahmad, Rosalia Crupi, Michela Campolo, Tiziana Genovese, Emanuela Esposito, Salvatore Cuzzocrea
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057208
Abstract: Background Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. Toll-like receptors (TLRs) are signaling receptors in the innate immune system, although emerging evidence indicates their role in brain injury. We have therefore investigated the role played by TLR4 signaling pathway in the development of mechanisms of secondary inflammatory process in traumatic brain injury (TBI) differ in mice that lack a functional TLR4 signaling pathway. Methods/Principal Findings Controlled cortical impact injury was performed on TLR4 knockout (KO) mice (C57BL/10ScNJ) and wild-type (WT) mice (C57BL/10ScNJ). TBI outcome was evaluated by determination of infarct volume and assessment of neurological scores. Brains were collected at 24 h after TBI. When compared to WT mice, TLR4 KO mice had lower infarct volumes and better outcomes in neurological and behavioral tests (evaluated by EBST and rotarod test). Mice that lacked TLR4 had minor expression of TBI-induced GFAP, Chymase, Tryptase, IL-1β, iNOS, PARP and Nitrotyrosine mediators implicated in brain damage. The translocation of expression of p-JNK, IκB-α and NF-κB pathway were also lower in brains from TLR4 KO mice. When compared to WT mice, resulted in significant augmentation of all the above described parameters. In addition, apoptosis levels in TLR4 KO mice had minor expression of Bax while on the contrary with Bcl-2. Conclusions/Significance Our results clearly demonstrated that absence of TLR4 reduces the development of neuroinflammation, tissues injury events associated with brain trauma and may play a neuroprotective role in TBI in mice.
Hypericum perforatum treatment: effect on behaviour and neurogenesis in a chronic stress model in mice
Rosalia Crupi, Emanuela Mazzon, Angela Marino, Giuseppina La Spada, Placido Bramanti, Fortunato Battaglia, Salvatore Cuzzocrea, Edoardo Spina
BMC Complementary and Alternative Medicine , 2011, DOI: 10.1186/1472-6882-11-7
Abstract: CD1 mice were submitted to 7 weeks corticosterone administration and then behavioral tests as Open Field (OF), Novelty-Suppressed Feeding (NSF), Forced Swim Test (FST) were performed. Cell proliferation in hippocampal dentate gyrus (DG) was investigated by both 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX) immunohistochemistry techniques and stereological procedure was used to quantify labeled cells. Golgi-impregnation method was used to evaluate changes in dendritic spines in DG. Hypericum perforatum (30 mg/Kg) has been administered for 3 weeks and then neural development in the adult hippocampus and behavioral changes have been examined.The anxiety/depressive-like state due to chronic corticosterone treatment was reversed by exogenous administration of Hypericum perforatum; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment, whereas a long term treatment with Hypericum perforatum prevented the corticosterone-induced decrease in hippocampal cell proliferation. Corticosterone-treated mice exhibited a reduced spine density that was ameliorated by Hypericum perforatum administration.These results provide evidence of morphological adaptations occurring in mature hippocampal neurons that might underlie resilient responses to chronic stress and contribute to the therapeutic effects of chronic Hypericum perforatum treatment.Extracts of Hypericum perforatum (St. John's wort) have been traditionally recommended for a wide range of medical conditions [1]. The most common modern-day use of St. John's wort is the treatment of depression [2]. In this respect, different controlled trials have confirmed its efficacy in the treatment of mild-to-moderate depression [3]. In addition, several studies indicated that Hypericum perforatum demonstrated anxiolytic and anti-inflammatory effects [4,5]. Hypericum extract contains numerous compounds with documented biological activity such as the naphthodianthrone
Complex Systems Theory: Some Considerations for Sociology  [PDF]
Rosalia Condorelli
Open Journal of Applied Sciences (OJAppS) , 2016, DOI: 10.4236/ojapps.2016.67044
Abstract: This essay presents a reflection on the main implications of Complexity Theory for science in general, redefining and dispelling myths of traditional science, and Sociology in particular, suggesting a redefinition of Parsons’ classic concept of Social System, articulated around the property of self-maintenance of order rather than on its possible discontinuity and instability. It argues that Complexity Theory has established the limits of Classic Science, leading to a more realistic awareness of working and evolution mechanisms of Natural and Social Systems and showing the limits of our capacity to predict and control events. Dissipative structures have shown the creative role of time. Instability, emergence, surprise, unpredictability are the rule rather than the exception when systems move away from equilibrium (entropy), even if these processes are generated from a system’s deterministic working mechanisms. Therefore, we have come to realize how constructive the contribution of Complexity is, in regards to the long lasting problem of the relationship between order and disorder. Today, the terms of this relationship have been re-specified in its new configuration of inter-relationship link, according to a unicum which finds its synthesis in self-organization and deterministic chaos concepts. From this perspective, as Prigogine suggested, studies on Complex Systems are heading toward a historical, biological conception of Physics, and a new alliance between natural systems and living, social systems. Non-linearity, far from equilibrium self-organization, emergence and surprise meet at all levels, as this paper attempts to highlight. In Sociology, insights of Complexity Theory have contributed to a new way of thinking about social systems, by re-addressing some fundamental issues starting to social system, emergence and change concepts. The current social system conception as complex dynamical systems is supported by a profitable use of non-liner models (in particular, the Logistic map) in the study of social processes.
Gender Abuse in Intimate Relationships: From Structural Coupling Theory to Emergence of Couple System  [PDF]
Rosalia Condorelli
Sociology Mind (SM) , 2017, DOI: 10.4236/sm.2017.74013
Abstract: Is love predictable in its choices? Linear Determinism, Randomness or Complexity? By applying theoretical coordinates of current sociological interpretations of intimacy and conceptual categories of New General System Theory, the paper reflects on one-factor and linear determinism implicitly underlying mate selection processes in Structural Coupling Theory and its implications for Intimate Partner Violence (IPV). Assuming personality structure as the predictor of partner choice as well as victimization risk, SCT circumscribes victimization risk just to one category of women (insecure/avoidant women coupling with ambivalent partners). We propose that adaptive complex system and non-banal machine concepts are more effective to understand the mate selection process than linear deterministic approach, which appears too mechanistic for a process that exhibits an inextricable dimension of uncertainty and unpredictability. Research results on a sample of 100 victims of IPV do not corroborate the linear one-factor determinism underlying Structural Coupling Theory neither its implications. Rather they go in the direction of Complexity.
Cultural Differentiation and Social Integration in Complex Modern Societies Reflections on Cultural Diversity Management Strategies from a Sociological Point of View  [PDF]
Rosalia Condorelli
Sociology Mind (SM) , 2018, DOI: 10.4236/sm.2018.84019
Abstract: This paper reflects on foundations of integration in our differentiated and globalized society from a sociological point of view, and links this reflection to most recent scientific acquisitions of the New Systems Theory or Complexity Science about how all systems, natural as well as social systems, work and evolve. Incorporating the sociological tradition on differentiation processes as rule of social functioning, the contemporary sociology accepted emergent, far from equilibrium (entropy), self-organization, unpredictable and surprising organizational change processes, operative closure and autopoiesis concepts, as particularly adapting concepts to represent social systems and, above all, our contemporary society characterized by an increase of complexity due to differentiation, individualization and globalization processes. In this regard, strong and permanent migratory waves, due to economic and digital globalization processes, and increasing cultural differentiation processes, have led contemporary western societies to face a serious social organizational problem: how the recognition of cultural difference and the instance of social integration can be reconciled? In this regard, the characterization of all systems as able to adapt to environmental perturbations and survive by self-organizing, balancing organization integrative constraints and emergencies, that is, far from complete differentiation, without being even minimal connection (far from equilibrium or in the edge of the chaos), can constitute a valid point of reference for sociologically reflecting, starting from here, on current integration policies of cultural differences in our complex society (pluralism, multiculturalism, interculturalism) and their implications for social integration. About it, the paper accepts the perspective of those sociological and political theories according to which, from a theoretical and empirical point of view, the sufficiency of procedural foundations seems to show serious limits as integrative constraint. Therefore, the Complexity language can justify the caution with which the normative multiculturalism—which implies it—is believed that should be considered, by anchoring it to the vision of a society conceived so as to dangerously visit that range of maximum differentiation which should be avoided, being identified as the range of ungovernability. Islamic radicalism and nationalistic rejection signs in the West show that this is no a mere theoretical possibility. How to bridge this relationality deficit that normative
Subring of constants of a ring of characteristic p>0
Marilena Crupi
Le Matematiche , 1993,
Abstract: Let A be a local ring of characteristic p>0 which has a p-basis over a subring C, and B be the subring of constants of A for a derivation (or derivations ) of A over C. We give a sufficient condition for B to have a p-basis over C. We add some examples.
Progressive Familial Intrahepatic Cholestasis (PFIC) Type 3 in Two Sicilian Siblings of Nonconsanguineous Parents
Isodiana Crupi
The Scientific World Journal , 2010, DOI: 10.1100/tsw.2010.109
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