81 research outputs found
Participatory networks towards social change
No full textFoundation
The proposal is founded on the scientific contributions related to Participatory Network Analysis. It is aimed at analyzing the interest of not only international scholars but also community activists on this topic and discussing research and interventions for the enhancement of community psychology models towards collective processes of change. The multidisciplinary and fruitful proposals will be highlighted, as well as some critical aspects in defining the participatory approach. PNA has proven to be effective in many fields including health promotion; migrants’ integration; spaces for everyday life; policies; learning environments; disasters and critical events management (see: Chiodini, M., & Meringolo, P. (2022). Di cosa parliamo quando parliamo di Participatory network analysis?: una review sistematica. What do we talk about when we talk about Participatory Network Analysis? A systematic review. Psicologia di comunità, 1:11-42).
Particular attention will be paid to gender issues (and the feminist approach) and intersectional aspects of the topic.
Goals
The main goals will be to clarify the meaning of “Participatory network analysis”; explore the different approaches based on different (and often conflictual) theories of change; and propose instruments and tools for applying a real participatory approach, particularly in difficult situations (e.g. marginalized people; young people in jail or on probation...)
Dystonia: Are animal models relevant in therapeutics?
No full textDystonia refers to a heterogeneous group of movement disorders characterized by involuntary, sustained muscle contractions leading to repetitive twisting movements and abnormal postures. A better understanding of the etiology, pathogenesis and molecular mechanisms underlying dystonia may be obtained from animal models. Indeed, while studies in vitro using cell and tissue models are helpful for investigating molecular pathways, animal models remain essential for studying the pathogenesis of these disorders and exploring new potential treatment strategies. To date, the mouse is the most common choice for mammalian models in most laboratories, particularly when manipulations of the genome are planned. Dystonia animal models can be classified into two categories, etiological and symptomatic, although neither is able to recapitulate all features of these disorders in humans. Nevertheless, etiological and symptomatic animal models have advantages and limitations that should be taken into consideration according to the specific proposed hypothesis and experimental goals. Etiological mouse models of inherited dystonia can reproduce the etiology of the disorder and help to reveal biochemical and cellular alterations, although a large majority of them lack motor symptoms. Conversely, symptomatic models can partially mimic the phenotype of human dystonia and test novel pharmacological agents, and also identify the anatomical and physiological processes involved, although the etiology remains unknown. Thus, our brief survey aims to review the state of the art as regards most of the commonly used animal models available for dystonia research. (C) 2018 Elsevier Masson SAS. All rights reserved
Intermittent access heroin self-administration increases drug intake in both sexes and relapse vulnerability in female rats
No full textDrug seeking gradually increases during abstinence (incubation of craving). Most studies of this phenomenon used continuous access self-administration procedures. Recently, studies using intermittent access self-administration procedure, showed increased motivation to take and seek drugs. We compared the effect of these two procedures on heroin intake, pattern of self-administration, modeled brain levels of heroin and its metabolites and incubation of craving, after forced or voluntary abstinence. We trained male and female rats to self-administer a palatable solution and then heroin (0.075 mg/kg) either continuously (6-h/d; 10d) or intermittently (6-h/d; 5-m/30-m; 10d). Next, we tested heroin seeking after 1 or 21 abstinence days. Between tests, rats underwent either forced or voluntary abstinence. We modeled brain levels of heroin and its metabolites during self-administration and assessed female estrous cycle after relapse tests. Intermittent access increased heroin intake, induced higher spikes of heroin and 6-acetylmorphine brain levels and increased heroin seeking in early abstinence. In both sexes, continuous access determined incubation of craving after forced, but not voluntary abstinence. Heroin seeking was higher in females after intermittent but not continuous access, independently of the estrous cycle phase. Intermittent access mimics critical features of heroin addiction: drug bingeing and high relapse in early abstinence
A comparative study between spermine oxidase and bovine serum amine oxidase in differential scanning calorimetry and on cytotoxicity on cancer cell lines
No full textSpermine oxidase (SMO) is a FAD-containing enzyme while bovine serum amine-oxidase (BSAO) is a copper amine oxidase and both are able to oxidize polyamines. They play a dominant role in the highly regulated mammalian polyamines catabolism. Spermine oxidase specifically oxidizes spermine (SPM) producing spermidine (SPD), the reactive oxygen species H2O2 and the aldehyde 3-aminopropanal, each with the potential to produce cellular damages and pathologies (1). BSAO deaminates SPM and SPD to H2O2, aldehyde acrolein and ammonia. Since SPM represents a common substrate for SMO and BSAO enzymatic activities, a comparative study was performed on both enzymes in presence of SPM on several tumor cell lines melanoma (M14) and colon adenocarcinoma (LoVo) wild type and their MDR counterparts. SPM is a tetramine that plays mandatory roles in several cell functions, such as DNA synthesis, cellular proliferation, modulation of ion channels function and cellular signaling (1). Our previous studies demonstrated that BSAO and SPM added to human cancer cells induce cytotoxicity and overcome the MDR phenotype (2). We have performed in vitro experiments treating the above human cancer cell lines both phenotype wild type and MDR with SMO in presence of several concentrations of SPM (0-80 μM) for 60 min at 37°C. Cytotoxicity induced by SPM oxidation metabolites, such as H2O2 and the aldehyde 3-aminopropanal, was greater in MDR cells than in the corresponding wild-type ones (WT), maybe due to an increased mitochondrial activity. To get structural information a comparative study was also carried out on both enzymes, by differential Scanning Calorimetry (DSC) (3). The thermal stability of BSAO and SMO is studied by differential scanning calorimetry with a MicroCal MC-2D instrument. Differential scanning calorimetry permits detection of overall changes in protein structure correlated with changes in thermal stability of one or more calorimetric domains. This is particularly important in the case of BSAO and SMO, proteins for which only a little structural information is available. Our previous studies demonstrated that the thermal denaturation profile of the dimeric BSAO is characterized by three distinct endothermic peaks (Tm 58°C, 71.3°C, 77.9°C) (3). The deconvolution of the thermal profile required five two-state transitions, revealed for the dimeric protein a five domain structure, while the monomeric SMO displays one single, endothermic peak (Tm 63°C). The peak may be deconvoluted into two transitions and reveals the presents of two non similar size calorimetric domains: the lowest temperature domain is described by a non two-state transition and the highest temperature domain is described by a two-state transition. The thermal denaturation is irreversible after heating to 100°C.
Since the treatments with BSAO/SPM and SMO/SPM increased the amount of reactive oxygen species (ROS) inside the cells, higher in MDR than WT ones, we hypothesize that the enhancement of amine oxidase activity in tissues, undergoing pathological proliferative phenomena, may reasonably be exploited in the treatment of neoplastic diseases, mainly against MDR tumors.
References:
1- Cervelli M, Amendola R, Polticelli F, Mariottini P (2012). Spermine oxidase ten years later , AminoAcids 42 :441-450
2-Agostinelli, E., Condello, M., Molinari, A., Tempera, G., Viceconte, N., Arancia, G. (2009)
Cytotoxicity of spermine oxidation products to multidrug resistant melanoma M14 ADR2 cells:
Sensitization by the MDL 72527 lysosomotropic compound
International Journal of Oncology 35: 485-498
3) Giartosio A, Agostinelli E and Mondovì B (1988). Domains in bovine serum amine oxidase.
Biochem. Biophys. Res. Comm. 154: 66-72
Centrality of early synaptopathy in Parkinson's disease
No full textSignificant advances have been made in the understanding of the numerous mechanisms involved in Parkinson's disease (PD) pathogenesis. The identification of PD pathogenic mutations and the use of different animal models have contributed to better elucidate the processes underlying the disease. Here, we report a brief survey of some relevant cellular mechanisms, including autophagic-lysosomal dysfunction, endoplasmic reticulum stress, and mitochondrial impairment, with the main aim to focus on their potential convergent roles in determining early alterations at the synaptic level, mainly consisting in a decrease in dopamine release at nigrostriatal terminals and loss of synaptic plasticity at corticostriatal synapses. In a number of experimental models, this synaptopathy has been shown to be an initial, central event in PD pathogenesis, preceding neuronal damage, thereby representing a valuable tool for testing potential disease-modifying treatments
Leaflet: Operative Steps for Interventional Studies in Neuroscience
No full textBackground/Objectives: Drug development involves multiple stages, spanning from initial discovery to clinical trials. This intricate process entails understanding disease mechanisms, identifying potential drug targets, and evaluating the efficacy and safety of candidate drugs. Clinical trials are designed to assess the effects of drugs on humans, focusing on determining safety profiles, appropriate modes of administration, and comparative efficacy against placebos. Notably, neuroscience drug development encounters distinct challenges, including the complex nature of diseases, limitations imposed by the blood–brain barrier, the absence of reliable predictive preclinical models, and regulatory hurdles. Ethical and safety considerations are pivotal due to the potential cognitive and motor effects of CNS-active drugs. Methods: Our manuscript outlines the procedures for CNS clinical trials and highlights the key elements of study design, methodological considerations, and ethical frameworks. To achieve our objectives, we considered the official websites of regulatory authorities, the EQUATOR network, and recent publications in the field. The paper includes key elements such as criteria for subject selection, methods of evaluation, variable analysis, and statistical methodology approaches. Results: We want to furnish a concise and comprehensive guide tailored to individuals new to CNS clinical trials, providing foundational elements necessary for the design and execution of such trials. The manuscript seeks to outline sources of relevant materials and elucidate adaptability, particularly in instances where sponsors may be absent. Conclusions: By meeting the needs of less-experienced researchers or those with limited resources, the intention is to facilitate an understanding of the intricate nature of the process and offer guidance on appropriately navigating its complexities. It is essential to note that this manuscript does not aim to be exhaustive but endeavors to serve as a structured checklist. Through its approach, the manuscript aspires to offer guidance and support to individuals navigating the challenges inherent in this intricate domain
Chloroquine enhances cytotoxicity on human cancer cells induced by polyamines metabolites: Nanotechnology approaches for anticancer agents delivery
No full textPotentation of cytotoxicity induces apoptosis in tumor cells: new approach in cancer therapy by nanocarriers
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Lysosomotropic compounds sensitize apoptosis apoptosis in cancer cells caused by spermine metabolites. Use of nanoparticles as delivery system in therapy
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