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Accrescimento, stato ponderale e immagine di sé, in età pre-puberale (6-11 anni), a Cento (provincia di Ferrara): studio trasversale e longitudinaleSemproli, Samantha <1976> 17 June 2008 (has links)
No description available.
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Azione antiossidante del sulforafane: analisi in cellule cardiache in coltura ed in un modello animale di esercizio fisicoMalaguti, Marco <1979> 17 June 2008 (has links)
Oxidative stress is considered to be of major relevance for a variety of pathological processes. Thus,
it is valuable to identify compounds, which might act as antioxidants, i.e. compounds that
antagonize the deleterious action of reactive oxygen species (ROS) on biomolecules. The mode of
action of these compounds could be either to scavenge ROS directly or to trigger protective
mechanisms inside the cell, thereby resulting in improved defense against ROS. Sulforaphane (SF)
(1-isothiocyanato-(4R)-(methylsulfinyl)butane) is a naturally occurring cancer chemopreventive
agent found as a precursor glucosinolate in Cruciferous vegetables like broccoli. Although SF is not
a direct-acting antioxidant, there is substantial evidence that SF acts indirectly to increase the
antioxidant capacity of animal cells and their abilities to cope with oxidative stress. Induction of
phase 2 enzymes is one means by which SF enhances the cellular antioxidant capacity. Enzymes
induced by SF include Glutathione S-transferases (GST) and NAD[P]H:quinone oxidoreductase
(NQO1) which can function as protectors against oxidative stress. To protect themselves from
oxidative stress, cells are equipped with reducing buffer systems including the GSH and thioredoxin
(Trx) reductase. GSH is an important tripeptide thiol which in addition to being the substrate for
GSTs maintains the cellular oxidation– reduction balance and protects cells against free radical
species.
Aim of the first part of this thesis was to investigate the ability of SF to induce the expression and
the activity of different phase 2 and antioxidant enzymes (such as GST, GR, GPx, NQO1, TR,
SOD, CAT) in an in vitro model of rat cardiomyocytes, and also to define if SF treatment supprts
cells in counteracting oxidative stress induced by H2O2
It is well known that acute exhaustive exercise causes significant reactive oxygen species
generation that results in oxidative stress, which can induce negative effects on health and well
being. In fact, increased oxidative stress and biomarkers (e.g., protein carbonyls, MDA, and 8-
hydroxyguanosine) as well as muscle damage biomarkers (e.g. plasmatic Creatine cinase and
Lactate dehydrogenase) have been observed after supramaximal sprint exercises, exhaustive longdistance
cycling or running as well as resistance-type exercises, both in trained and untrained
humans. Markers of oxidative stress also increase in rodents following exhaustive exercise.
Moreover, antioxidant enzyme activities and expressions of antioxidant enzymes are known to
increase in response to exhaustive exercise in both animal and human tissues.
Aim of this project was to evaluate the effect of SF supplementation in counteracting oxidative
stress induced by physical activity through its ability to induce phase 2, and antioxidant enzymes in
rat muscle.
The results show that SF is a nutraceutical compound able to induce the activity of different phase 2
and antioxidant enzymes in both cardiac muscle and skeletal muscle. Thanks to its actions SF is
becoming a promising molecule able to prevent cardiovascular damages induced by oxidative stress
and muscle damages induced by acute exhaustive exercise.
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L'infiammazione intestinale nell'animale sperimentale come modello per lo sviluppo di nuovi farmaci: ruolo della via tachichininergica nelle malattie infiammatorie intestinaliUrsino, Maria Grazia <1979> 27 March 2008 (has links)
Background: Several lines of evidence showed that inflammation is associated with changes
in the expression of tachykinins both in human and animal models. Tachykinins, including
substance P (SP), are small peptides expressed in the extrinsic primary afferent nerve fibres
and enteric neurons of the gut: they exert their action through three distinct receptors, termed
NK1, NK2 and NK3. SP modulates intestinal motility and enteric secretion, acting
preferentially through the NK1 receptor. SP neural network and NK1 receptor expression are
increased in patients with inflammatory bowel disease, and similar changes were observed in
experimental models of inflammation. The 2,4 Dinitrobenzene Sulphonic Acid (DNBS) model
of colitis is useful to study innate immunity, non-specific inflammation and wound healing; it
has been suggested that the transmural inflammation seen in this model resembles that found
in Crohns disease and can therefore be used to study what cells and mediators are involved in
this type of inflammation.
Aim: To test the possible protective effect of the NK1 receptor antagonist SSR140333 on:
1) acute model of intestinal inflammation; 2) reactivation of DNBS-induced colitis in rats.
Methods: Acute colitis was induced in male SD rats by intrarectal administration of DNBS
(15 mg/rat in 50% ethanol). Reactivation of colitis was induced by intrarectal injections of
DNBS on day 28 (7.5 mg/rat in 35% ethanol). Animals were sacrificed on day 6 (acute colitis)
and 29 (reactivation of colitis). SSR140333 (10 mg/kg) was administered orally starting from
the day before the induction of colitis for 7 days (acute colitis) or seven days before the
reactivation of colitis. Colonic damage was assessed by means of macroscopic and
microscopic scores, myeloperoxidase activity (MPO) and TNF-α tissue levels. Enzyme
immunoassay was used to measure colonic substance P levels. Statistical analysis was
performed using analysis of variance (one-way or two-way, as appropriate) with the
Bonferronis correction for multiple comparisons.
Results: DNBS administration impaired body weight gain and markedly increased all
inflammatory parameters (p<0.01). Treatment with SSR140333 10 mg/kg significantly
counteracted the impairment in body weight gain, decreased macroscopic and histological
scores and reduced colonic myeloperoxidase activity (p<0.01). Drug treatment counteracted
TNF-α tissue levels and colonic SP concentrations (acute model). Similar results were
obtained administering the NK1 receptor antagonist SSR140333 (3 and 10 mg/kg) for 5 days,
starting the day after the induction of colitis. Intrarectal administration of DNBS four weeks
after the first DNBS administration resulted in reactivation of colitis, with increases in
macroscopic and histological damage scores and increase in MPO activity. Preventive
treatment with SSR140333 10 mg/kg decreased macroscopic damage score, significantly
reduced microscopic damage score but did not affect MPO activity.
Conclusions: Treatment with SSR140333 significantly reduced intestinal damage in acute
model of intestinal inflammation in rats. The NK1 receptor antagonist SSR140333 was also
able to prevent relapse in experimental colitis. These results support the hypothesis of SP
involvement in intestinal inflammation and indicate that NK receptor antagonists may have a
therapeutic potential in inflammatory bowel disease.
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Messa a punto di metodi per lo studio della plasticità neuronale del sistema nervoso entericoAlessandri, Marco <1976> 27 March 2008 (has links)
No description available.
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Nuove strategie farmacologiche per il superamento della farmacoresistenza in chemioterapia antitumoraleSciuscio, Davide <1979> 27 March 2008 (has links)
No description available.
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Effects of cannabidiol and cannabis extracts in models of convulsion and excitotoxicityUtan, Aneli <1974> 27 March 2008 (has links)
No description available.
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Isotiocianati come potenziali farmaci antileucemici: identificazione in vitro ed ex vivo del profilo molecolare e cellulareLenzi, Monia <1977> 27 March 2008 (has links)
Il presente studio ha come obbiettivo lo sviluppo di composti di origine naturale come potenziali farmaci antitumorali, attraverso la definizione dei loro specifici target cellulari e molecolari su diversi modelli cellulari ad alta predittività.
Gli isotiocianati, contenuti nei vegetali appartenenti alla famiglia delle Crucifereae, sono dotati di una comprovata capacità di inibire la formazione di tumori in modelli animali preventivamente trattati con cancerogeni. Questa attività è riconducibile principalmente alla modulazione degli enzimi coinvolti nell’attivazione/detossificazione di xenobiotici e ad effetti citostatici e citossici, osservati su numerose linee cellulari.
Un isotiocianato particolarmente promettente è il sulforafane (SFN). La ricerca condotta durante il periodo di dottorato si è, quindi, focalizzata sull’isotiocianato SFN e in particolare sulla sua capacità di modulare specifici eventi cellulari e molecolari coinvolti nel processo di leucemogenesi.
Inizialmente è stato indagato il potenziale citostatico e citotossico del SFN su una linea cellulare T linfoblastoide (cellule Jurkat), con particolare attenzione agli effetti sulla proliferazione cellulare, all’induzione di apoptosi/necrosi e all’analisi di alcuni dei meccanismi molecolari coinvolti negli effetti citostatici e citotossici dell’isotiocianato ( livelli proteici di p53, bax e bcl-2).
Successivamente, poiché requisiti fondamentali di un antitumorale sono selettività d’azione e scarsa tossicità, è stato indagato il potenziale citostatico e citotossico dell’isotiocianato SFN sulla controparte non trasformata delle cellule leucemiche T linfoblastoidi, analizzando gli stessi eventi studiati su cellule tumorali e alcuni dei meccanismi molecolari coinvolti (livelli proteici di ciclina D2, ciclina D3, chinasi ciclina dipendente (CDK) 4 e CDK6 ).
Il SFN si è dimostrato in grado di indurre apoptosi sulle cellule Jurkat e di inibirne la proliferazione, mediante un blocco in fase G2/M del ciclo cellulare e un incremento dei livelli di p53 e bax. Il SFN è in grado di indurre effetti citostatici e citotossici anche su linfociti T non trasformati. Tuttavia, le dosi necessarie per esibire tali effetti sono ben più elevate di quelle attive su cellule leucemiche.
Una tappa importante nello sviluppo di un farmaco antitumorale è, la definizione, dove possibile, dei suoi effetti in un modello ex vivo, altamente predittivo di quella che sarà la risposta farmacologica in vivo. Sono stati quindi valutati gli effetti del SFN su colture primarie di blasti provenienti da pazienti affetti da diversi tipi di leucemia , sia mieloide che linfoblastica.
Il SFN non sembra possedere alcuna attività su campioni da pazienti affetti da LLC, mentre un importante attività proapoptotica si registra nei campioni da pazienti affetti da LMA, dove l’effetto del SFN è sorprendentemente marcato anche su campioni da pazienti multiresistenti.
L’attività dell’isotiocianato sui campioni da pazienti affetti da LLA è decisamente più marcata sul campione da paziente affetto da LLA a cellule B, mentre sul campione di Leucemia Acuta Bifenotipica l’effetto proapoptotico del SFN si registra dopo tempi di trattamento brevi piuttosto che dopo tempi di trattamento più lunghi.
In conclusione, i risultati ottenuti evidenziano che il SFN possiede un’interessante attività antileucemica in vitro e, dato di particolare rilevanza, anche ex vivo.
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Strategie di monitoraggio mediante biomarker e organismi sentinella applicate a zone umide e costiereDonnini, Filippo <1975> 13 June 2008 (has links)
No description available.
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Peripheral arterial disease and diabetes: effects on endothelial progenitor cell differentiation and nitric oxide metabolismBasile, Ilaria <1979> 16 April 2008 (has links)
In the recent years it is emerged that peripheral arterial disease (PAD) has become a growing health
problem in Western countries. This is a progressive manifestation of atherothrombotic vascular
disease, which results into the narrowing of the blood vessels of the lower limbs and, as final
consequence, in critical leg ischemia. PAD often occurs along with other cardiovascular risk factors,
including diabetes mellitus (DM), low-grade inflammation, hypertension, and lipid disorders.
Patients with DM have an increased risk of developing PAD, and that risk increases with the
duration of DM. Moreover, there is a growing population of patients identified with insulin
resistance (IR), impaired glucose tolerance, and obesity, a pathological condition known as
“metabolic syndrome”, which presents increased cardiovascular risk.
Atherosclerosis is the earliest symptom of PAD and is a dynamic and progressive disease arising
from the combination of endothelial dysfunction and inflammation. Endothelial dysfunction is a
broad term that implies diminished production or availability of nitric oxide (NO) and/or an
imbalance in the relative contribution of endothelium-derived relaxing factors. The secretion of
these agents is considerably reduced in association with the major risks of atherosclerosis,
especially hyperglycaemia and diabetes, and a reduced vascular repair has been observed in
response to wound healing and to ischemia. Neovascularization does not only rely on the
proliferation of local endothelial cells, but also involves bone marrow-derived stem cells, referred to
as endothelial progenitor cells (EPCs), since they exhibit endothelial surface markers and
properties. They can promote postnatal vasculogenesis by homing to, differentiating into an
endothelial phenotype, proliferating and incorporating into new vessels. Consequently, EPCs are
critical to endothelium maintenance and repair and their dysfunction contributes to vascular disease.
The aim of this study has been the characterization of EPCs from healthy peripheral blood, in terms
of proliferation, differentiation and function. Given the importance of NO in neovascularization and
homing process, it has been investigated the expression of NO synthase (NOS) isoforms, eNOS,
nNOS and iNOS, and the effects of their inhibition on EPC function. Moreover, it has been
examined the expression of NADPH oxidase (Nox) isoforms which are the principal source of
ROS in the cell. In fact, a number of evidences showed the correlation between ROS and NO
metabolism, since oxidative stress causes NOS inactivation via enzyme uncoupling. In particular, it
has been studied the expression of Nox2 and Nox4, constitutively expressed in endothelium, and
Nox1.
The second part of this research was focused on the study of EPCs under pathological conditions.
Firstly, EPCs isolated from healthy subject were cultured in a hyperglycaemic medium, in order to
evaluate the effects of high glucose concentration on EPCs. Secondly, EPCs were isolated from the
peripheral blood of patients affected with PAD, both diabetic or not, and it was assessed their
capacity to proliferate, differentiate, and to participate to neovasculogenesis. Furthermore, it was
investigated the expression of NOS and Nox in these cells.
Mononuclear cells isolated from peripheral blood of healthy patients, if cultured under
differentiating conditions, differentiate into EPCs. These cells are not able to form capillary-like
structures ex novo, but participate to vasculogenesis by incorporation into the new vessels formed
by mature endothelial cells, such as HUVECs. With respect to NOS expression, these cells have
high levels of iNOS, the inducible isoform of NOS, 3-4 fold higher than in HUVECs. While the
endothelial isoform, eNOS, is poorly expressed in EPCs. The higher iNOS expression could be a
form of compensation of lower eNOS levels. Under hyperglycaemic conditions, both iNOS and
eNOS expression are enhanced compared to control EPCs, as resulted from experimental studies in
animal models.
In patients affected with PAD, the EPCs may act in different ways. Non-diabetic patients and
diabetic patients with a higher vascular damage, evidenced by a higher number of circulating
endothelial cells (CECs), show a reduced proliferation and ability to participate to vasculogenesis.
On the other hand, diabetic patients with lower CEC number have proliferative and vasculogenic
capacity more similar to healthy EPCs. eNOS levels in both patient types are equivalent to those of
control, while iNOS expression is enhanced. Interestingly, nNOS is not detected in diabetic patients,
analogously to other cell types in diabetics, which show a reduced or no nNOS expression.
Concerning Nox expression, EPCs present higher levels of both Nox1 and Nox2, in comparison
with HUVECs, while Nox4 is poorly expressed, probably because of uncompleted differentiation
into an endothelial phenotype. Nox1 is more expressed in PAD patients, diabetic or not, than in
controls, suggesting an increased ROS production. Nox2, instead, is lower in patients than in
controls. Being Nox2 involved in cellular response to VEGF, its reduced expression can be
referable to impaired vasculogenic potential of PAD patients.
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Effects of environmental complexity on neurogenesis in the hippocampal dentate gyrusRizzi, Simona <1971> 30 May 2008 (has links)
Introduction. Postnatal neurogenesis in the hippocampal dentate gyrus, can be modulated by numerous determinants, such as hormones, transmitters and stress. Among the factors positively interfering with neurogenesis, the complexity of the environment appears to play a particularly striking role. Adult mice reared in an enriched environment produce more neurons and exhibit better performance in hippocampus-specific learning tasks. While the effects of complex environments on hippocampal neurogenesis are well documented, there is a lack of information on the effects of living under socio-sensory deprivation conditions. Due to the immaturity of rats and mice at birth, studies dealing with the effects of environmental enrichment on hippocampal neurogenesis were carried out in adult animals, i.e. during a period of relatively low rate of neurogenesis. The impact of environment is likely to be more dramatic during the first postnatal weeks, because at this time granule cell production is remarkably higher than at later phases of development.
The aim of the present research was to clarify whether and to what extent isolated or enriched rearing conditions affect hippocampal neurogenesis during the early postnatal period, a time window characterized by a high rate of precursor proliferation and to elucidate the mechanisms underlying these effects. The experimental model chosen for this research was the guinea pig, a precocious rodent, which, at 4-5 days of age can be independent from maternal care.
Experimental design. Animals were assigned to a standard (control), an isolated, or an enriched environment a few days after birth (P5-P6). On P14-P17 animals received one daily bromodeoxyuridine (BrdU) injection, to label dividing cells, and were sacrificed either on P18, to evaluate cell proliferation or on P45, to evaluate cell survival and differentiation.
Methods. Brain sections were processed for BrdU immunhistochemistry, to quantify the new born and surviving cells. The phenotype of the surviving cells was examined by means of confocal microscopy and immunofluorescent double-labeling for BrdU and either a marker of neurons (NeuN) or a marker of astrocytes (GFAP). Apoptotic cell death was examined with the TUNEL method. Serial sections were processed for immunohistochemistry for i) vimentin, a marker of radial glial cells, ii) BDNF (brain-derived neurotrofic factor), a neurotrophin involved in neuron proliferation/survival, iii) PSA-NCAM (the polysialylated form of the neural cell adhesion molecule), a molecule associated with neuronal migration. Total granule cell number in the dentate gyrus was evaluated by stereological methods, in Nissl-stained sections.
Results. Effects of isolation. In P18 isolated animals we found a reduced cell proliferation (-35%) compared to controls and a lower expression of BDNF. Though in absolute terms P45 isolated
animals had less surviving cells than controls, they showed no differences in survival rate and phenotype percent distribution compared to controls. Evaluation of the absolute number of surviving cells of each phenotype showed that isolated animals had a reduced number of cells with neuronal phenotype than controls. Looking at the location of the new neurons, we found that while in control animals 76% of them had migrated to the granule cell layer, in isolated animals only 55% of the new neurons had reached this layer. Examination of radial glia cells of P18 and P45 animals by vimentin immunohistochemistry showed that in isolated animals radial glia cells were reduced in density and had less and shorter processes. Granule cell count revealed that isolated animals had less granule cells than controls (-32% at P18 and -42% at P45). Effects of enrichment. In P18 enriched animals there was an increase in cell proliferation (+26%) compared to controls and a higher expression of BDNF. Though in both groups there was a decline in the number of BrdU-positive cells by P45, enriched animals had more surviving cells (+63) and a higher survival rate than controls. No differences were found between control and enriched animals in phenotype percent distribution. Evaluation of the absolute number of cells of each phenotype showed that enriched animals had a larger number of cells of each phenotype than controls. Looking at the location of cells of each phenotype we found that enriched animals had more new neurons in the granule cell layer and more astrocytes and cells with undetermined phenotype in the hilus. Enriched animals had a higher expression of PSA-NCAM in the granule cell layer and hilus Vimentin immunohistochemistry showed that in enriched animals radial glia cells were more numerous and had more processes.. Granule cell count revealed that enriched animals had more granule cells than controls (+37% at P18 and +31% at P45).
Discussion. Results show that isolation rearing reduces hippocampal cell proliferation but does not affect cell survival, while enriched rearing increases both cell proliferation and cell survival. Changes in the expression of BDNF are likely to contribute to he effects of environment on precursor cell proliferation. The reduction and increase in final number of granule neurons in isolated and enriched animals, respectively, are attributable to the effects of environment on cell proliferation and survival and not to changes in the differentiation program. As radial glia cells play a pivotal role in neuron guidance to the granule cell layer, the reduced number of radial glia cells in isolated animals and the increased number in enriched animals suggests that the size of radial glia population may change dynamically, in order to match changes in neuron production. The high PSA-NCAM expression in enriched animals may concur to favor the survival of the new neurons by facilitating their migration to the granule cell layer.
Conclusions. By using a precocious rodent we could demonstrate that isolated/enriched rearing conditions, at a time window during which intense granule cell proliferation takes place, lead to a
notable decrease/increase of total granule cell number. The time-course and magnitude of postnatal granule cell production in guinea pigs are more similar to the human and non-human primate condition than in rats and mice. Translation of current data to humans would imply that exposure of children to environments poor/rich of stimuli may have a notably large impact on dentate neurogenesis and, very likely, on hippocampus dependent memory functions.
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