InsubriaSPACE
Not a member yet
702 research outputs found
Sort by
The dual face of the endocannabinoid system in schizofrenia: experimental evidence.
No full textInvestigating the association between Cannabis, the endogenous cannabinoid system and schizophrenia must take into account two aspects of major relevance.
On the one hand, Cannabis is the most widely used illegal drug and there is substantial evidence that its consumption has to be classified as an independent risk factor for psychosis that may lead to a worse outcome of the disease. On the other hand, there are several lines of evidence that clearly indicate the presence of a dysregulation in the endocannabinoid system in animal models of psychosis and at least in a subgroup of schizophrenic patients.
Concerning the first point, our recent studies in female rats demonstrated that chronic THC treatment during adolescence induced a complex phenotype in adulthood characterized by the presence of anhedonia, behavioral despair in the forced swim test, reduced sociability as well as significant deficits in spatial working and object recognition memory. Moreover, adolescent THC administration also sensitizes to the locomotor activating effect induced by acute psychostimulant administration in adulthood. This response is consistent with the presence of a psychotic-like phenotype. Thus, the simultaneous presence of pronounced depressive-like behaviors, cognitive deficits as well as psychotic-like signs suggests that adolescent THC exposure had led to a behavioral phenotype in adulthood that reflects the presence of complex schizoaffective-like disorder. Interestingly, when the same protocol of THC exposure was performed in adult animals, no behavioral alterations were observed, thus highlighting the specific vulnerability of the adolescent brain to the long-lasting adverse effects of THC.
The neurobiology of cannabis-induced schizophrenia is still unknown. However, we recently demonstrated that adolescent exposure to THC produces-long lasting alterations in the endocannabinoid system, that ultimately could result in imbalances of excitatory and inhibitory neurotransmission within specific brain regions. Accordingly, our data demonstrate that the schizoaffective-like disorder induced by adolescent THC exposure in female rats is strictly associated with alterations in the inhibitory neurotransmission which are particularly prominent within the prefrontal cortex, a brain region that has been found to be severely affected in schizophrenia.
With regard to the second aspect, there are several lines of evidence that clearly indicate the presence of a dysregulation in the endocannabinoid system in different animal models of psychosis and based on these observations, the pharmacological modulation of the endocannabinoid system has been taken into account as a new therapeutic possibility for psychotic disorders. In line with this, we demonstrated that chronic treatment with the cannabinoid CB1 receptor antagonist, AM251, counteracts the psychotic-like phenotype in a neurodevelopmental model of schizophrenia in rats. This recovery at behavioral level was paralleled by the normalization of the endocannabinoid system functionality both in terms of endocannabinoid levels and CB1 receptor/G protein coupling in all the brain areas analyzed, possibly suggesting that the ability of AM251 to restore normal endocannabinoid system may account for its antipsychotic action.
As a whole, data reported in this thesis, strongly suggest an association between an altered endocannabinoid tone and the development of psychotic symptoms, thus supporting the exploitation of compounds acting on the endocannabinoid system as new therapeutic agents in the treatment of schizophrenia and related disorders
β-glucuronidases in plants.
No full textIn the last decade, the interest for the presence and role of endogenous GUS in plants increased, being previously limited to the use of GUS from E. coli as a reporter gene. Three different GUS genes have been identified in A. thaliana and different roles have been suggested, mainly associated to plant cell wall remodelling and to the regulation of the presence in the active form of molecules with regulative functions.
This thesis investigated several aspects: A) artefacts in histochemical GUS detection, B) role of GUS in pollen tube germination and growth, C) GUS expression in N. tabacum and A. thaliana, D) identification of GUS genes in N. tabcum and their phylogenetic analysis in angiosperms.
A) Histochemical detection of E.coli GUS activity in transformed plants can be impaired by the presence of GUS inhibitors and by the solubility of an intermediate reaction product formed when X-glu is used as substrate. The expression of LAT52 has been revised.
B) The use of saccharolattone, a GUS inhibitor, suggests that GUS is involved in pollen tube germination and growth.
C) GUS expression was observed in all organs of N. tabacum and A. thaliana.
Expression studies, in collaboration with researchers of Calabria University, have been performed in Arabidopsis, by in situ mRNA hybridization: GUS3 is specifically expressed in border like cells and probably it is involved in their detachment from root tip; GUS1 and GUS2 are expressed in the root cup meristem, resulting perhaps involved in regulation of the mitotic cycle.
D) In N. tabacum GUS2 was completely sequenced and one GUS1 and two GUS3 have been partially sequenced. By bioinformatics analysis, GUS genes have been identified in other angiosperms species and a phylogenetic analysis have been conducted
Parkinson's disease biomarkers in peripheral blood T lymphocytes: identification through a proteomic approach
No full textAll the spots of the models or showing correlation with one of the mentioned parameters were excised from the gels and identified by LC-MS/MS fragmentation: some of the most important and recurring identification were beta fibrinogen and transaldolase; in particular, 4 spots correspond to beta fibrinogen and 2 spots correspond to transaldolase; all together, these 6 spots contribute to the prediction model in a very remarkable way.
For this reason, we validated by Western blot total beta fibrinogen and transaldolase changes to verify their proper identification and confirm the differences observed by 2-DE with another technique (Western blotting).
Worth of note, the level of some proteins was modified by levodopa and dopamine agonists therapy in T lymphocytes: this is a demonstration that these cells are sensitive to long term dopaminergic stimulation and that they are a valid tool to investigate dopaminergic imbalance at a peripheral level.
Additional experiments were conducted in order to deepen the role of fibrinogen in T cells, and the reason why its volume is reduced in PD patients: this study is currently going on, but preliminary results indicate that it is internalized by T cells from plasma.
In conclusion, in this thesis T lymphocyte proteome changes have been shown to be a valid tool to recognize and classify PD patients. It has been proposed a model using a rationale of similarity between affected cells (dopaminergic neurons) and probed system (T lymphocytes): we expect that our system will reasonably provide information on the effectiveness of future (or under development) drugs designed to interfere with specific cell death mechanisms targeting nigral neurons. Moreover, our system possess most features required for candidate PD biomarkers (specificity, indication of progression, accessibility).
Next step of this research is leading the current finding to the clinical practice. This objective will be reached only through large collaborative networks, that will allow us to select large cohorts of subjects with high heterogeneity in terms of gender, age, ethnicity, clinical phenotype; the use of a different and less time consuming technique in the clinical phase is advisable
Prescription of phytotherapy diets and supplements in unconventional medicine of ambulatory department: epidemiologist and clinician aspects.
No full textThe object of this plan is to investigate and to describe the modalities of MNC use, regarding the treatments that imply the employment of pharmacologic therapies, near an MNC ambulatory department that conducted in Local Sanitary Company.
The greater attention has been turned use of phytotherapy in the ambulatory department of bioactive herbal medicines, through the characterization of natural principles produced from plants and on the putting to point of therapeutic outlines of association between allopathic medicines and formulated alimentary integrators with extracted vegetables.
It’s been estimated the prescription of alimentary and phytotherapic supplements near a MNC ambulatory department, with detail attention to the prescription frequency, It has been had with regard to the subjective appraisal of the satisfaction in relation to the attended effects. Every patient has been included in the study only after they are informed of the purposes of the plan. The data have been collected through the employment of a card purposely predisposed.
They have been enlisted participants, 59.5% women with avarage age of 44,6 years. The use of herbal products for cured pathologies came declared of 67.2% of the cases.
Herbalist and pharmacist that advice to the people to use MNC, and physician with their conventional medicine, are the main interlocutors and point of reference I use for it of not conventional Medicines. Moreover, the medical officer usually get information from the patients about their use of the herbal medicine.At The same time use of conventional medicine and herbal medicine could give possibilities of drugs adverse effects
Utilizzo del nuovo antidepressivo agomelatina in pazienti affetti da disturbo depressivo maggiore: efficacia, tollerabilità, adesione al trattamento.
No full textmissin
QSAR models for the (eco-)toxicological characterization and prioritization of emerging pollutants: case studies and potential applications within REACH.
No full textUnder the European REACH regulation (Registration, Evaluation, Authorisation and Restriction of Chemical substances - (EC) No 1907/2006), there is an urgent need to acquire a large amount of information necessary to assess and manage the potential risk of thousands of industrial chemicals.
Meanwhile, REACH aims at reducing animal testing by promoting the intelligent and integrated use of alternative methods, such as in vitro testing and in silico techniques. Among these methods, models based on quantitative structure-activity relationships (QSAR) are useful tools to fill data gaps and to support the hazard and risk assessment of chemicals.
The present thesis was performed in the context of the CADASTER Project (CAse studies on the Development and Application of in-Silico Techniques for Environmental hazard and Risk assessment), which aims to integrate in-silico models (e.g. QSARs) in risk assessment procedures, by showing how to increase the use of non-testing information for regulatory decision-making under REACH. The aim of this thesis was the development of QSAR/QSPR models for the characterization of the (eco-)toxicological profile and environmental behaviour of chemical substances of emerging concern. The attention was focused on four classes of compounds studied within the CADASTER project, i.e. brominated flame retardants (BFRs), fragrances, prefluorinated compounds (PFCs) and (benzo)-triazoles (B-TAZs), for which limited amount of experimental data is currently available, especially for the basic endpoints required in regulation for the hazard and risk assessment.
Through several case-studies, the present thesis showed how QSAR models can be applied for the optimization of experimental testing as well as to provide useful information for the safety assessment of chemicals and support decision-making.
In the first case-study, simple multiple linear regression (MLR) and classification models were developed ad hoc for BFRs and PFCs to predict specific endpoints related to endocrine disrupting (ED) potential (e.g. dioxin-like activity, estrogenic and androgenic receptor binding, interference with thyroxin transport and estradiol metabolism). The analysis of modelling molecular descriptors allowed to highlight some structural features and important structural alerts responsible for increasing specific ED activities. The developed models were applied to screen over 200 BFRs and 33 PFCs without experimental data, and to prioritize the most hazardous chemicals (on the basis of ED potency profile), which have been then suggested to other CADASTER partners in order to focus the experimental testing.
In the second case-study, MLR models have been developed, specifically for B-TAZs, for the prediction of three key endpoints required in regulation to assess aquatic toxicity, i.e. acute toxicity in algae (EC50 72h Pseudokirchneriella subcapitata), daphnids (EC50 48h Daphnia magna) and fish (LC50 96h Onchorynchus mykiss). Also in this case, the developed QSARs were applied for screening purposes. Among over 350 B-TAZs lacking experimental data, 20 compounds, which were predicted as toxic (EC(LC)50 ≤ 10 mg/L) or very toxic (EC(LC)50 ≤ 1 mg/L) to the three aquatic species, were prioritized for further experimental testing.
Finally, in the third case-study, classification QSPR models were developed for the prediction of ready biodegradability of fragrance materials. Ready biodegradation is among the basic endpoints required for the assessment of environmental persistence of chemicals. When compared with some existing models commonly used for predicting biodegradation, the here proposed QSPRs showed higher classification accuracy toward fragrance materials. This comparison highlighted the importance of using local models when dealing with specific classes of chemicals.
All the proposed QSARs have been developed on the basis of the OECD principles for QSAR acceptability for regulatory purposes, paying particular attention to the external validation procedure and to the statistical definition of the applicability domain of the models. QSAR models based on molecular descriptors generated by both commercial (DRAGON) and freely-available (PaDELDescriptor, QSPR-Thesaurus) software have been proposed. The use of free tool allows for a wider applicability of the here proposed QSAR models.
Concluding, the QSAR models developed within this thesis are useful tools to support hazard and risk assessment of specific classes of emerging pollutants, and show how non-testing information can be
used for regulatory decisions, thus minimizing costs, time and saving animal lives.
Beyond their use for regulatory purposes, the here proposed QSARs can find application in the rational design of new safer compounds that are potentially less hazardous for human health and environment
Corpo, potere e rappresentazione. L'immagine della sovranità tra teologia politica e antropologia filosofica.
No full textmissin
L’ombra di Polemos, i riflessi del Bios. La prospettiva della cura a partire da Jan Patočka e Michel Foucault.
No full textA partire dalle riflessioni del fenomenologo ceco Jan Patočka e dagli studi del filosofo francese Michel Foucault, questa ricerca intende esplorare il tema della cura – di sé, dell’anima, degli altri, del mondo – in quanto forma di relazione etica. Nell’eclissi dei sistemi valoriali tradizionali, le ricerche sulla nozione di cura possono offrire una prospettiva etica capace di riformulare i termini della responsabilità collettiva.
Il punto di partenza è un passaggio dell’ultimo corso di Foucault al Collège de France (Il coraggio della verità), dove il filosofo fa riferimento al pensiero di Patočka. Foucault riconosce all’autore ceco di essere stato il solo autore contemporaneo ad aver approfondito il principio antico dell’epimeleia. Tuttavia, secondo Foucault, la propria personale ricerca – articolata attorno alla nozione di epimeleia heautou, cioè di cura come messa alla prova, problematizzazione e stilizzazione di sé – differirebbe da quella di Patočka, più interessata allo studio dell’epimeleia tes psyches, ossia all’anima sotto il profilo ontologico e gnoseologico.
Innanzitutto, la tesi di Foucault incoraggia un’analisi del significato del termine “anima” nel contesto della fenomenologia asoggettiva elaborata da Patočka. In secondo luogo, invita a studiare la nozione di “sé” presente negli ultimi testi di Foucault.
Indagando i rapporti tra i processi singolari di soggettivazione e il bios in quanto “modo di vita” o “stile di esistenza”, si arriva a porre il problema della vita in quanto orizzonte ontologico dell’essere in comune. Ci si interroga così sulla possibilità di una cura del bios che sia insieme “legame di vita” e “modo di vita”: cura del bios come ontologia critica delle condizioni che rendono possibile il riconoscimento della vita, intesa come dimensione della coappartenenza, e allo stesso tempo attitudine etica a farsi carico della sua vulnerabilità
Corbicula fluminea invasion in Lake Maggiore: a three years ecological study.
No full textThe number of reports of non-indigenous species (NIS) of the aquatic environments are increasing rapidly worldwide. The rate of invasions of freshwater environments is rising in many countries, mainly caused by an increase in human activities. The growing interest in invasive species is due to their negative impact on biodiversity and ecosystem functioning.
Some species are recognized among the most dangerous invasive species of freshwater ecosystems (eg C. fluminea, D. polymorpha and A. woodiana).
This study aims to evaluate the C. fluminea invasion in Lake Maggiore, inspecting different chraracteristics of populations settled in southern littoral part. Field and semi-natural condition observations are carried out to evaluate growth and reproductive rate of Corbicula in the environment recently colonized. Lab experiments were performed to measure filtration rate. To evaluate possible competitive interactions between alien and native species, dietary sources and trophic niche overlap were determined through measurements of the stable isotope compositions of C (δ13C) and N (δ15N) respectively.
Lake Maggiore offers a favorable environment for the establishment of the Asian clam Corbicula fluminea. The picture that emerges from the study of C. fluminea populations is quite complex, with differences among the five sampling sites. Larger size class organisms are well represented in Angera and Arona (southern sites), while are (still) almost absent in Feriolo and Monvalle (northern sites).
The density and biomass of C. fluminea observed are rather high, with peaks reaching up to 3000 ind.m-2 and 2500 g m-2.
The populations size structure provides clues to understand the process of invasion and its phases. The populations size structure in the different sites presents wide differences, indicative of different demographic dynamics. The timing of colonization of Lake Maggiore seems to follow this order: Monvalle <Feriolo <Brebbia <Angera <Arona. It is also possible to assume that the colonization of this environment began in 2007, for expansion of the population already established in its effluent, the river Ticino.
The reproductive period of C. fluminea in Lake Maggiore showed a single reproductive peak, from late Spring to Autumn. The recruitment of new organisms is scarce at the site of Arona, while the opposite situation is observed in Feriolo.
The number of larvae produced by each adult is highly variable, with values ranging from a few hundred to 16000 larvae per individual.
Generally in the sites of Angera, Brebbia, Feriolo and Monvalle mortality is rather low, while at Arona is considerably higher. At Angera was observed a phenomenon of mass mortality in Autumn 2012.
C. fluminea has a high growth rate and in this environment there are no factors able to limit the growth and spread of this species. The growth rates are affected by seasonal variations in temperature: in Summer and Autumn organisms show higher growth rate values than in the other seasons (almost 2 times higher). The growth rate is higher for small size organisms, as expected comparing young and adults organisms of the same species.
In spite of similar functional roles, Unionids and C. fluminea are likely to differ in filtering efficiency and trophic niche. Our preliminary results suggest that Corbicula has a noticeably higher filtration capacity than the most abundant Unionid species (U. elongatulus) and is able to shift its diet along the year. The results of stable isotope analysis highlight a niche overlap between C. fluminea and native species of bivalves, indicating that C. fluminea has lower trophic fidelity than native Unionids. Feeding plasticity of C. fluminea is likely of major importance for competing successfully indigenous bivalves in Lake Maggiore, thus promoting the overdomination of the alien species in the area. Indeed, Corbicula seems to stand already as a keystone littoral species in Lake Maggiore, likely being a strong competitor for space and food to native mussels.
However, besides the competition with bivalve invasive species the decline observed for the native species of Lake Maggiore (U. elongatulus abundance decreases about 90 % from 2004 and 2012) is likely due to several factors. Severe drought is responsible for periodical mass mortalities which affect both native Unionids and invasive clams, but these latter can recover and recolonize the environment more rapidly than native species.
The specimens that moving from one environment to another can bring along their parasites, which can find the conditions necessary to establish a new population. In the course of this study two new species of parasites of Unionids (cercariae of Bucephalidae and Rhodeus amarus) have been found. The infection of the gonads due to cercariae leads to the castration of bivalves and can be fatal, while the presence of the larvae of R. amarus in the gills reduces the rate of respiration and filtration.
The presence of D. polymorpha is recognized in the lake since the 1990’s and is often found anchored to the shell of other bivalve species. High infestation of Dreissena can cause the death by asphyxia.
The combination of all these factors provides sufficient explanation for the observed decline of native species, however, the invasion of C. fluminea appears to be a worrying phenomenon. After 3-4 years from the entry into the lake this clam had already colonized a third of the shoreline. To date, this bivalve is found in all suitable habitats distributed along the entire perimeter of the lake.
It is possible to conclude that eradication is an expensive solution and the methodologies used often have negative impacts on native species. Moreover, it is not possible to eradicate a species from the environment, in addiction the high growth rate and the plasticity of the alien species recorded in Lake Maggiore favour them respect native species. Mass mortality events can promote the replacement of the native by alien species
Cardiomyogenic differentiation of human multipotent stromal cells: a new approach fore regenerative medicine in cardiovascular disease.
No full textCardiovascular disease (CVD), which include hypertension, coronary heart disease (CHD), stroke, and congestive heart failure (CHF), are the leading and most common causes of mortality in both developing and industrialized countries, accounting for one third of all deaths globally.
Cardiomyocyte regeneration is limited in adult life and therefore the identification of a putative source of progenitors is of great interest to provide usable in vitro models and new perspectives for regenerative therapies. This appears to be a challenge due to the peculiar functional and anatomical heart properties. The goal of this project was to differentiate adult human Adipose tissue‐derived multipotent Stem Cells (ASCs) into cardiomyocytes or their close progenitors. Thus, the ultimate aim is to develop stem cell-based therapies for the cure of cardiovascular disease. More specifically, we investigated the application of two innovative approaches: the use of human growth factors in a well defined serum-free culture medium and the application of electrical and mechanical stimuli to mimic the physiological environment of the heart.
First of all, we developed a new protocol for the isolation of ASCs according with the standard GMP-procedure, which allows to extract a substantial number of cells for clinical application. The starting material was obtained from subcutaneous adipose tissue collected during an elective liposuction procedure. The isolated ASCs were characterized by flow cytometry and expanded until second passage. Several different cocktails of growth factors, cytokines and several culture conditions were tested for their ability to induce cardiomyogenesis. The goal was to identify the right combination of those factors and their time of application. One of the cardiogenic cocktails tested was indeed very effective in inducing the selected cardiac markers (e.g. NKX2-5 and MEF2C) and was chosen for the second part of this research work. The differentiation obtained was highly reproducible, as it was observed in 15 out of 15 samples from different patients. Interestingly, non induced ASCs expressed half of the selected cardiac markers (i.e. TBX5, GATA4 and BAF60C), suggesting the high Abstract V intrinsic potential and the inherent propensity of ASCs to differentiate into cardiac precursors. We further analysed the morphological changes that ASCs underwent during their differentiation by use of electron microscopy and immunofluorescence staining. By treating the cells with our selected induction cocktail, clear changes in their morphology were observed: the cells assumed a fusiform shape and became oriented.
The last milestone was to understand if the combination of the cardiac induction cocktail with a mechanical (and eventually electrical) stimulation on a scaffold would increase the efficiency of cardiogenic differentiation. For this, a customized device has been developed by the Swiss Stem Cell Foundation in collaboration with Scuola Universitaria Professionale della Svizzera Italiana (SUPSI) for the application of controlled mechanical and/or electrical stimuli to a scaffold over a desired lap of time. The scaffolds used were developed and characterized by Prof. Ciardelli’s Research Group (Materials in Bionanotechnology, Department of Mechanical and Aerospace Engineering, Politecnico di Torino). The preliminary results showed that the combination of growth factors, cytokines and mechanical stimulation for 10 days led to an at least 2 fold increase in mRNA expression of NKX2‐5, MEF2C, HAND2 and MHC when compared to the induction with cardiogenic cocktail alone on a simple 2D culture condition.
In conclusion, in this work we present a new protocol for the extraction of ASCs starting from adipose lipoaspirates, a new serum‐free based cardiogenic induction cocktail for ASCs and preliminary data about the differentiation in scaffold enhanced by mechanical stimulation opening a new perspective to cardiac regeneration