subject:(Settore BIO 14 Farmacologia)

1. C. Pavanello. GENETIC LCAT DEFICIENCY AND ATHEROSCLEROSIS: STUDIES ON ENDOTHELIAL CELLS AND MONOCYTES.

Degree: 2018, Università degli Studi di Milano

► Introduzione La lecitin:cholesterol aciltransferasi (LCAT) è l’unico enzima nell’uomo in grado di esterificare il colesterolo nel plasma. Il deficit genetico di LCAT influenza il metabolismo… (more)

▼ Introduzione La lecitin:cholesterol aciltransferasi (LCAT) è l’unico enzima nell’uomo in grado di esterificare il colesterolo nel plasma. Il deficit genetico di LCAT influenza il metabolismo delle lipoproteine ad alta densità (HDL), portando a concentrazioni plasmatiche ridotte di queste lipoproteine. Si ritiene che LCAT sia un’importante driving force per il trasporto inverso del colesterolo (RCT) nei macrofagi e che pertanto giochi un ruolo importante nell’ateroprotezione. Nonostante i bassi livelli plasmatici di HDL-C, il grado di aterosclerosi preclinica non è risulta aumentato nel deficit di LCAT che addirittura sembra essere protettivo. Abbiamo quindi ipotizzato che questa discrepanza potesse essere spiegata da un aumento della funzionalità delle particelle HDL che sono più efficienti nel proteggere contro la disfunzione endoteliale. Metodi Le HDL sono state isolate da soggetti portatori di deficit di LCAT e testate in vitro per la loro capacità di stimolare la produzione di NO e di inibire l’espressione di molecole di adesione in cellule endoteliali. La misura della vasodilatazione flusso-mediata (FMD) è stata utilizzata come indice in vivo di disfunzione endoteliale. HDL ricostituite, contenenti solo apoA-I (LpA-I) o apoA-I e apoA-II (LpA-I:A-II) sono state utilizzate per dimostrare come quali modifiche strutturali siano responsabili dell’aumentata funzionalità. Analisi ex vivo del fenotipo e della funzionalità di monociti isolati da portatori di deficit di LCAT sono stati condotti tramite citometria a flusso, stimolazione e saggi di transmigrazione endoteliale. Portatori di altri deficit genetici di HDL sono stati utilizzati come confronto. Risultati Il deficit di LCAT genetico è caratterizzato da una deplezione selettiva di LpA-I: A-II e da alte concentrazioni di preβ-HDL immature. Le HDL isolate dai portatori si sono dimostrate più efficaci nel promuovere l'attivazione di eNOS in vitro mediante fosforilazione e, di conseguenza, la produzione di NO nelle cellule endoteliali, rispetto ai controlli, con un effetto gene-dose. Inoltre, le HDL dei portatori hanno una maggiore capacità di inibire l'espressione di VCAM-1. L'effetto è probabilmente dipendente dalla deplezione selettiva in lipoproteine LpA-I:A-II. Inoltre, i monociti dei portatori presentavano un fenotipo meno infiammatorio rispetto ai controlli, come evidenziato dalla ridotta espressione dell’integrina CD11c, dalla ridotta capacità di trasmigrazione e dalla minore produzione di citochine dopo stimolazione. Al contrario, nessuna variazione è stata individuata nell’immunofenotipo di monociti isolati in soggetti con altri deficit genetici di HDL. A conferma in vivo di quanto individuato precedentemente non è stata trovata alcuna differenza nella FMD tra portatori di deficit genetico di LCAT e controlli. Conclusioni Nonostante le ridotte concentrazioni plasmatiche di HDL-C, il deficit di LCAT non è associato a una maggiore disfunzione endoteliale dovuta all'aumentata efficacia delle particelle HDL nella stimolazione della produzione di… Advisors/Committee Members: tutor: L.Calabresi, coordinatore: A.L. Catapano, CALABRESI, LAURA, CATAPANO, ALBERICO LUIGI.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pavanello, C. (2018). GENETIC LCAT DEFICIENCY AND ATHEROSCLEROSIS: STUDIES ON ENDOTHELIAL CELLS AND MONOCYTES. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/597321

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Pavanello, C.. “GENETIC LCAT DEFICIENCY AND ATHEROSCLEROSIS: STUDIES ON ENDOTHELIAL CELLS AND MONOCYTES.” 2018. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/597321.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Pavanello, C.. “GENETIC LCAT DEFICIENCY AND ATHEROSCLEROSIS: STUDIES ON ENDOTHELIAL CELLS AND MONOCYTES.” 2018. Web. 19 Jan 2021.

Vancouver:

Pavanello C. GENETIC LCAT DEFICIENCY AND ATHEROSCLEROSIS: STUDIES ON ENDOTHELIAL CELLS AND MONOCYTES. [Internet] [Thesis]. Università degli Studi di Milano; 2018. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/597321.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Pavanello C. GENETIC LCAT DEFICIENCY AND ATHEROSCLEROSIS: STUDIES ON ENDOTHELIAL CELLS AND MONOCYTES. [Thesis]. Università degli Studi di Milano; 2018. Available from: http://hdl.handle.net/2434/597321

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

2. A. Luoni. BEHAVIORAL, MOLECULAR AND EPIGENETIC CONSEQUENCES OF EARLY LIFE STRESS EXPOSURE AND THEIR IMPACT ON ADULT PSYCHOPATHOLOGY.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/229411

► There is now consistent evidence that psychiatric diseases may often represent the consequence of exposure to adverse events early in life, which may disrupt the… (more)

▼ There is now consistent evidence that psychiatric diseases may often represent the consequence of exposure to adverse events early in life, which may disrupt the correct program of brain maturation thus leading to long-lasting changes in brain function. Accordingly, exposure to stress during gestation in rats has a strong impact on brain development and can cause long-term abnormalities in adult behavior (Fumagalli et al., 2007; Seckl, 1998). In this context, the study of environmental manipulations in animal models offers the possibility to investigate the mechanisms that may be responsible for functional deterioration, with the advantage of keeping the influence of various factors such as the timing and intensity of the adverse condition, the growth environment and the genetic background under control. Given all these premises, in this study we first set up and employed a paradigm of prenatal stress in rodents in order to reproduce early life adversities that may encompass pregnancy and early postnatal life. Indeed, gestational stress has long-lasting effects on the hypothalamic-pituitary-adrenal (HPA) axis and on the behavior of the dams, suggesting that alterations in maternal behavior following exposure to prenatal stress could also contribute to the long-term effects (Maccari et al., 2003; Maccari and Morley-Fletcher, 2007) of this environmental stressor. In particular, the paradigm we employed consisted in restraining the dams during the last week of gestation for 45 minutes three times a day under bright light, from gestation day 14 until delivery. We next sacrificed the pups, both males and females, at different postnatal time points, in order to create a time profile of the modifications under investigation. First, we tested the cognitive functionality of adult animals with the object recognition test, since cognitive disabilities are one of the common symptoms that characterize different psychiatric conditions (Disner et al., 2011; Lapiz-Bluhm et al., 2008; Lesh et al., 2011; Lewis et al., 2012). Next, we performed a detailed analysis of two candidate systems whose deterioration could contribute to the development of the diseased phenotype, namely the glucocorticoid receptor (GR) and the neurotrophin brain-derived neurotrophic factor (BDNF), through basal and functional analyses at gene and protein levels. These two systems have emerged as the most vulnerable elements of exposure to stress during development and can be considered markers of the dysfunctions associated with psychiatric disorders. The HPA axis is involved in the response to stressful events (Maccari et al., 2003), whereas neuronal plasticity represents an array of mechanisms involved in the adaptive capacity to environmental changes (Calabrese et al., 2009; Duman and Monteggia, 2006). We performed the analyses at various stages of development, trying to establish how early the molecular alterations become manifest and their persistence in time. Notably this bears the possibility to evaluate the potential of early pharmacological… Advisors/Committee Members: tutor: M. A. Riva, coordinatore: A. Panerai, RIVA, MARCO ANDREA, PANERAI, ALBERTO EMILIO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Luoni, A. (2014). BEHAVIORAL, MOLECULAR AND EPIGENETIC CONSEQUENCES OF EARLY LIFE STRESS EXPOSURE AND THEIR IMPACT ON ADULT PSYCHOPATHOLOGY. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/229411

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Luoni, A.. “BEHAVIORAL, MOLECULAR AND EPIGENETIC CONSEQUENCES OF EARLY LIFE STRESS EXPOSURE AND THEIR IMPACT ON ADULT PSYCHOPATHOLOGY.” 2014. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/229411.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Luoni, A.. “BEHAVIORAL, MOLECULAR AND EPIGENETIC CONSEQUENCES OF EARLY LIFE STRESS EXPOSURE AND THEIR IMPACT ON ADULT PSYCHOPATHOLOGY.” 2014. Web. 19 Jan 2021.

Vancouver:

Luoni A. BEHAVIORAL, MOLECULAR AND EPIGENETIC CONSEQUENCES OF EARLY LIFE STRESS EXPOSURE AND THEIR IMPACT ON ADULT PSYCHOPATHOLOGY. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/229411.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Luoni A. BEHAVIORAL, MOLECULAR AND EPIGENETIC CONSEQUENCES OF EARLY LIFE STRESS EXPOSURE AND THEIR IMPACT ON ADULT PSYCHOPATHOLOGY. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/229411

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. E. Assi. ROLE OF ACID SPHINGOMYELINASE IN THE TUMOUR MICROENVIRONMENT.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/229416

► Defective apoptosis represents one of the major causative factors in the development and progression of cancer. The ability of tumour cells to evade engagement of… (more)

▼ Defective apoptosis represents one of the major causative factors in the development and progression of cancer. The ability of tumour cells to evade engagement of apoptosis can play a significant role in their resistance to conventional therapeutic regimens. In the last few years, preclinical and clinical studies have indicated ceramide and the enzymes of its metabolism, in particular Acid Sphingomyelinase (A-SMase) which hydrolyzes sphingomyelin to ceramide and phosphocoline, as key players in tumour physiopathology. Different cancers have been shown to have reduced ceramide levels and, of interest, in our previous work we showed that A-SMase down-regulation was a key event in melanoma progression. This event is crucial for the tumours to become more aggressive, but the mechanisms responsible of it haven’t been investigated yet. Taking into account that there is a complex crosstalk between tumour cells and its immunological microenvironment, in this work we first investigated its possible role in A-SMase downregulation in a melanoma model. To this purpose we performed in vivo and in vitro experiments which led us to identify tumour associate macrophages (TAM) as possible responsible of A-SMase downregulation through the Ap2-α transcription factor. Moreover, we demonstrated that these molecular changes in tumour cells give, in turn, pro-tumoural and immunosuppressive features to the surrounding microenvironment, with the recruitment of Myeloid-derived suppressor (MDSCs) cells and Regulatory T lymphocytes (TREGS). From these and our previous data, we clearly showed that the ability to create this immunosuppression together with the acquisition of a more aggressive phenotype, both depend on the naturally occurring A-SMase decrease in melanoma cells during tumour progression. The broad role of A-SMase in tumour pathogenesis we identified, indicates that the enzyme is at the crossroad of key pathways in tumourigenesis. This aspects has clear potential in therapeutic perspective in which A-SMase overexpression or administration might be consider as an useful adjuvant for cancer therapy. Here we demonstrated for the first time that restoring A-SMase expression in melanoma cells not only reduces tumour growth and immunosuppression, but moreover accounts for a high, unexpected recruitment of immune cells with an anti-tumoural function in the tumour microenvironment, such as Dendritic cells (DCs) and CD4+ and CD8+ T lymphocytes. In conclusion our results reveal the central role of A-SMase expressed by melanoma cells in orchestrating the cross-talk with the surrounding microenvironment. These interactions are crucial for tumour fate, lying on its rejection or progression. Our observation that A-SMase overexpression “educate” tumour microenvironment against cancer cells, further encourage the use of this enzyme as an adjuvant for cancer therapy. Advisors/Committee Members: tutor: E. Clementi, correlatore: C. Perrotta, coordinatore: A. Panerai, CLEMENTI, EMILIO GIUSEPPE IGNAZIO, PANERAI, ALBERTO EMILIO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Assi, E. (2014). ROLE OF ACID SPHINGOMYELINASE IN THE TUMOUR MICROENVIRONMENT. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/229416

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Assi, E.. “ROLE OF ACID SPHINGOMYELINASE IN THE TUMOUR MICROENVIRONMENT.” 2014. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/229416.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Assi, E.. “ROLE OF ACID SPHINGOMYELINASE IN THE TUMOUR MICROENVIRONMENT.” 2014. Web. 19 Jan 2021.

Vancouver:

Assi E. ROLE OF ACID SPHINGOMYELINASE IN THE TUMOUR MICROENVIRONMENT. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/229416.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Assi E. ROLE OF ACID SPHINGOMYELINASE IN THE TUMOUR MICROENVIRONMENT. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/229416

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

4. P. Amadio. EMERGING ROLE OF NEUROTROPHINS IN CARDIOVASCULAR REGULATION:IMPACT AND CHARACTERIZATION OF GENETIC VARIANT BDNF (VAL66MET) POLYMORPHISM ON THROMBOTIC EVENTS.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/229417

► Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in neuron plasticity (Donovan, et al., 2000), and vascular development (Kermani, et al.,… (more)

▼ Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in neuron plasticity (Donovan, et al., 2000), and vascular development (Kermani, et al., 2007). A single nucleotide polymorphism in the BDNF gene (BDNF Val66Met) has been associated with depression (Ventriglia, et al., 2002) (Momose, et al., 2002) (Sen, et al., 2003) (Neves-Pereira, et al., 2002), and recently, it has also been proposed as genetic risk factor for cardiovascular disease (CVD) (Bozzini, et al., 2009) (Jiang, et al., 2009). Intriguingly, reduced BDNF levels are detected in both depressed patients and in subjects with BDNF Val66Met polymorphism, and seem associated with increased coronary events and mortality in patients affected by acute coronary syndrome (Bozzini, et al., 2009). In this study we have assessed the impact of BDNF Val66Met polymorphism on the levels or activity of haemostatic system in relation to experimentally induced thrombosis. Humanized Val66Met BDNF homozygote knock-in mice (BDNF Met/Met) have an alterated arterial and venous thrombosis compared to BDNF Val/Val control mice. Thromboelastometry analyses showed that BDNF Met/Met mice present a significant modification both in clot firmness, clot elasticity, and in the clot formation time compared to BDNF Val/Val mice, suggesting alteration in platelet reactivity and fibrinogen, but normal levels of coagulation factors. Importantly, Tissue Factor (TF), the key activator of blood coagulation, was modified in BDNF Met/Met mice. In addition, data obtained by proteomic analysis of the aorta secretome isolated from Val/Val and Met/Met mice, confirmed with different techniques, revealed several differentially expressed proteins involved in the regulation of coagulation and thrombosis in plasma and/or aorta tissue of BDNF Met/Met compared to control mice. Our results further confirmed the emerging role of neurotrophins in cardiovascular regulation. Advisors/Committee Members: tutor: E. Tremoli, co-tutor: S.S. Barbieri, coordinatore: A. Panerai, TREMOLI, ELENA, PANERAI, ALBERTO EMILIO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Amadio, P. (2014). EMERGING ROLE OF NEUROTROPHINS IN CARDIOVASCULAR REGULATION:IMPACT AND CHARACTERIZATION OF GENETIC VARIANT BDNF (VAL66MET) POLYMORPHISM ON THROMBOTIC EVENTS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/229417

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Amadio, P.. “EMERGING ROLE OF NEUROTROPHINS IN CARDIOVASCULAR REGULATION:IMPACT AND CHARACTERIZATION OF GENETIC VARIANT BDNF (VAL66MET) POLYMORPHISM ON THROMBOTIC EVENTS.” 2014. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/229417.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Amadio, P.. “EMERGING ROLE OF NEUROTROPHINS IN CARDIOVASCULAR REGULATION:IMPACT AND CHARACTERIZATION OF GENETIC VARIANT BDNF (VAL66MET) POLYMORPHISM ON THROMBOTIC EVENTS.” 2014. Web. 19 Jan 2021.

Vancouver:

Amadio P. EMERGING ROLE OF NEUROTROPHINS IN CARDIOVASCULAR REGULATION:IMPACT AND CHARACTERIZATION OF GENETIC VARIANT BDNF (VAL66MET) POLYMORPHISM ON THROMBOTIC EVENTS. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/229417.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Amadio P. EMERGING ROLE OF NEUROTROPHINS IN CARDIOVASCULAR REGULATION:IMPACT AND CHARACTERIZATION OF GENETIC VARIANT BDNF (VAL66MET) POLYMORPHISM ON THROMBOTIC EVENTS. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/229417

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

5. L. Pucci. CARATTERIZZAZIONE FARMACOLOGICA E FUNZIONALE DI NUOVI LIGANDI DEI RECETTORI COLINERGICI NICOTINICI NEURONALI CHE MODULANO IL RILASCIO DI DOPAMINA NELLA VIA MESOSTRIATALE, UNA VIA IMPORTANTE PER GLI EFFETTI COMPORTAMENTALI DELLA NICOTINA.

Degree: 2011, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/150270

► The α6β2∗ neuronal nicotinic acetylcholine receptor (nAChR) subtype expressed in the dopaminergic mesostriatal pathway mediates many behavioural effects of nicotine, and is selectively blocked by… (more)

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pucci, L. (2011). CARATTERIZZAZIONE FARMACOLOGICA E FUNZIONALE DI NUOVI LIGANDI DEI RECETTORI COLINERGICI NICOTINICI NEURONALI CHE MODULANO IL RILASCIO DI DOPAMINA NELLA VIA MESOSTRIATALE, UNA VIA IMPORTANTE PER GLI EFFETTI COMPORTAMENTALI DELLA NICOTINA. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/150270

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Pucci, L.. “CARATTERIZZAZIONE FARMACOLOGICA E FUNZIONALE DI NUOVI LIGANDI DEI RECETTORI COLINERGICI NICOTINICI NEURONALI CHE MODULANO IL RILASCIO DI DOPAMINA NELLA VIA MESOSTRIATALE, UNA VIA IMPORTANTE PER GLI EFFETTI COMPORTAMENTALI DELLA NICOTINA.” 2011. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/150270.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Pucci, L.. “CARATTERIZZAZIONE FARMACOLOGICA E FUNZIONALE DI NUOVI LIGANDI DEI RECETTORI COLINERGICI NICOTINICI NEURONALI CHE MODULANO IL RILASCIO DI DOPAMINA NELLA VIA MESOSTRIATALE, UNA VIA IMPORTANTE PER GLI EFFETTI COMPORTAMENTALI DELLA NICOTINA.” 2011. Web. 19 Jan 2021.

Vancouver:

Pucci L. CARATTERIZZAZIONE FARMACOLOGICA E FUNZIONALE DI NUOVI LIGANDI DEI RECETTORI COLINERGICI NICOTINICI NEURONALI CHE MODULANO IL RILASCIO DI DOPAMINA NELLA VIA MESOSTRIATALE, UNA VIA IMPORTANTE PER GLI EFFETTI COMPORTAMENTALI DELLA NICOTINA. [Internet] [Thesis]. Università degli Studi di Milano; 2011. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/150270.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Pucci L. CARATTERIZZAZIONE FARMACOLOGICA E FUNZIONALE DI NUOVI LIGANDI DEI RECETTORI COLINERGICI NICOTINICI NEURONALI CHE MODULANO IL RILASCIO DI DOPAMINA NELLA VIA MESOSTRIATALE, UNA VIA IMPORTANTE PER GLI EFFETTI COMPORTAMENTALI DELLA NICOTINA. [Thesis]. Università degli Studi di Milano; 2011. Available from: http://hdl.handle.net/2434/150270

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

6. S. Ancona. STUDIO BIOCHIMICO E FARMACOLOGICO DI CELLULE MUSCOLARI LISCE ISOLATE DA TESSUTI DI PAZIENTI AFFETTI DA TSC2 E LAM. MODIFICAZIONI EPIGENETICHE DEL GENE TSC2 NELLA PATOGENENESI DELLA TSC E DELLA LAM.

Degree: 2011, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/151779

► Tuberous sclerosis complex (TSC) and lymphangioleiomymatosis (LAM) are rare diseases. TSC is a genetic disease caused by mutation in TSC1 or TSC2 genes. TSC2 cells… (more)

▼ Tuberous sclerosis complex (TSC) and lymphangioleiomymatosis (LAM) are rare diseases. TSC is a genetic disease caused by mutation in TSC1 or TSC2 genes. TSC2 cells form hamartomas and might invade lungs causing the fatal diseases LAM. From an angiomylipoma (AML) of a TSC male patient we isolated a TSC2 smooth muscle (ASM) population. The growth of these cells was EGF-dependent. They showed a constitutive S6 phosphorylation, and lacked tuberin as the result of TSC2 promoter methylation (TSC2-/meth ASM cells). Chromatin remodeling agents, such as trichostatin–A and 5-azacytidine de-methylated TSC2-/meth ASM cell promoter and induced tuberin expression. The blockade of EGF-receptor with specific antibodies results in cell death as shown in TSC2-/- ASM cells, a population previously isolated from an AML of female TSC patient. LAM cells migrate or metastasize to other organs, in fact cells with TSC2 mutation have been found in AMLs and lung lesions of LAM patients. We isolated a population from chylous of a TSC/LAM patient, in which, as in TSC2-/meth cells, tuberin expression was induced by 5-azacytidine and trichostatin A treatments. These cells required the supplementation of EGF for proliferation, such as TSC2-/- and TSC2-/meth ASM cells. Chylous TSC/LAM cells expressed marker for identification of mesenchimal characteristics, such as vimentin and SNAIL, while E-cadherin, usually not expressed in metastatized cancer cells, was not detectable. The acquisition of mesenchymal characteristics for cancer cells is a transient event that might be important for migration and tissue invasion. Chylous TSC/LAM cells switched from a short floating stage, with low S6 phosphorylation levels, to a stage of adhesion with high S6 phosphorylation. These data suggest a novel therapeutic approach for the control of TSC and LAM abnormal cell growth using anti-EGFR antibody in addition to rapamycin, and, in some cases, the chromatin remodelling agents. Moreover, our data confirm the evidence that TSC2 pathogenesis might originate from an epigenetic defect. Advisors/Committee Members: tutor: Anna Maria Di Giulio, coordinatore: Anna Maria Di Giulio, DI GIULIO, ANNA MARIA, DI GIULIO, ANNA MARIA.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ancona, S. (2011). STUDIO BIOCHIMICO E FARMACOLOGICO DI CELLULE MUSCOLARI LISCE ISOLATE DA TESSUTI DI PAZIENTI AFFETTI DA TSC2 E LAM. MODIFICAZIONI EPIGENETICHE DEL GENE TSC2 NELLA PATOGENENESI DELLA TSC E DELLA LAM. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/151779

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ancona, S.. “STUDIO BIOCHIMICO E FARMACOLOGICO DI CELLULE MUSCOLARI LISCE ISOLATE DA TESSUTI DI PAZIENTI AFFETTI DA TSC2 E LAM. MODIFICAZIONI EPIGENETICHE DEL GENE TSC2 NELLA PATOGENENESI DELLA TSC E DELLA LAM.” 2011. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/151779.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ancona, S.. “STUDIO BIOCHIMICO E FARMACOLOGICO DI CELLULE MUSCOLARI LISCE ISOLATE DA TESSUTI DI PAZIENTI AFFETTI DA TSC2 E LAM. MODIFICAZIONI EPIGENETICHE DEL GENE TSC2 NELLA PATOGENENESI DELLA TSC E DELLA LAM.” 2011. Web. 19 Jan 2021.

Vancouver:

Ancona S. STUDIO BIOCHIMICO E FARMACOLOGICO DI CELLULE MUSCOLARI LISCE ISOLATE DA TESSUTI DI PAZIENTI AFFETTI DA TSC2 E LAM. MODIFICAZIONI EPIGENETICHE DEL GENE TSC2 NELLA PATOGENENESI DELLA TSC E DELLA LAM. [Internet] [Thesis]. Università degli Studi di Milano; 2011. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/151779.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ancona S. STUDIO BIOCHIMICO E FARMACOLOGICO DI CELLULE MUSCOLARI LISCE ISOLATE DA TESSUTI DI PAZIENTI AFFETTI DA TSC2 E LAM. MODIFICAZIONI EPIGENETICHE DEL GENE TSC2 NELLA PATOGENENESI DELLA TSC E DELLA LAM. [Thesis]. Università degli Studi di Milano; 2011. Available from: http://hdl.handle.net/2434/151779

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

7. L. Caffino. MODULAZIONE DI MECCANISMI DI PLASTICITA' NEURONALE DOPO SOMMINISTRAZIONE ACUTA O CRONICA DI COCAINA.

Degree: 2010, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/150094

► The major aim of this thesis was to assess the role of the neurotrophin BDNF and the imemdiate early gene Arc in the mechanism of… (more)

▼ The major aim of this thesis was to assess the role of the neurotrophin BDNF and the imemdiate early gene Arc in the mechanism of action of cocaine. To pursue this purpose we exposed the animals to various drug paradigms. We first injected the animals with different doses of cocaine and sacrificed the animals at different time points. These experiments revealed that acute injection of cocaine produced a finely tuned, time-dependent and regional-selective expression profile of both BDNF and Arc suggesting that they indie partecipate in the rapid action of the psychostimulant. The analysis of repente exposure of the animals to cocaine revealed that precursor (pro-) and mBDNF protein forms were markedly reduced 2 h and 72 h post-injection in the prefrontal cortex. Interestingly, in the striatum we found that repeated cocaine injection increased pro-BDNF levels without altering the mature form of the neurotrophin, thereby suggesting that cocaine differently affects BDNF transcription and translation in a region-selective manner, but might also alter neurotrophin processing. These data further support the notion that the corticostriatal network is highly vulnerable to the effects of cocaine, and suggest that abnormal regulation of BDNF expression could contribute, at least in part, to the functional defects observed in drug abusers. We then decided to evaluate whether repente stress, a major risk factor for cociane relapse, might alter the pattern of BDNF and Arc expression following acute administration of cocaine. we provide evidence that repeated stress prevents cocaine-induced activation of BDNF expression and signaling in rat prefrontal cortex. A single injection of cocaine up-regulates BDNF expression in sham (i.e. unstressed) rats but not in repeatedly stressed rats. Similarly, the expression as well as trafficking of the high affinity BDNF receptor trkB promoted by the psychostimulant is impaired in chronically-stressed rats challenged with cocaine. Moreover, among the different intracellular signaling pathways that can be activated by the neurotrophin, i.e. ERK1/2-, Akt- and PLCγ-pathway, we found that cocaine is able to selectively activate the ERK1/2 pathway in sham animals, but not in rats exposed to repeated stress. These data demonstrate that stress globally interferes with BDNF-mediated signaling responses to cocaine challenge, providing key insights into the molecular basis of stress-cocaine interaction and indicating the critical role of the prefrontal cortex in mediating such interaction. To follow up our studies we decided to employ a new administration paradimg of cocaine in order to separate the direct pharmacological effects of cocaine from those associated with active drug selfadministration. To this end, we employed a yoked control-operant paradigm and sacrificed the animals after a single intravenous (i.v.) cocaine self-administration session. Animals self-administering cocaine (SA, 0.25 mg/0.1 ml saline per infusion, 2-h session) did more active lever-presses than yoked-cocaine (YC) and… Advisors/Committee Members: docente guida: Fabio Fumagalli, coordinatore: Guido Franceschini, FUMAGALLI, FABIO, FRANCESCHINI, GUIDO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Caffino, L. (2010). MODULAZIONE DI MECCANISMI DI PLASTICITA' NEURONALE DOPO SOMMINISTRAZIONE ACUTA O CRONICA DI COCAINA. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/150094

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Caffino, L.. “MODULAZIONE DI MECCANISMI DI PLASTICITA' NEURONALE DOPO SOMMINISTRAZIONE ACUTA O CRONICA DI COCAINA.” 2010. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/150094.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Caffino, L.. “MODULAZIONE DI MECCANISMI DI PLASTICITA' NEURONALE DOPO SOMMINISTRAZIONE ACUTA O CRONICA DI COCAINA.” 2010. Web. 19 Jan 2021.

Vancouver:

Caffino L. MODULAZIONE DI MECCANISMI DI PLASTICITA' NEURONALE DOPO SOMMINISTRAZIONE ACUTA O CRONICA DI COCAINA. [Internet] [Thesis]. Università degli Studi di Milano; 2010. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/150094.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Caffino L. MODULAZIONE DI MECCANISMI DI PLASTICITA' NEURONALE DOPO SOMMINISTRAZIONE ACUTA O CRONICA DI COCAINA. [Thesis]. Università degli Studi di Milano; 2010. Available from: http://hdl.handle.net/2434/150094

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

8. V. Benedusi. THE ROLE OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS IN AMYOTROPHIC LATERAL SCLEROSIS: POTENTIAL MECHANISMS FOR NEUROPROTECTION.

Degree: 2011, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/150265

► The vast majority of neurodegenerative disorders are adult-onset, incurable diseases. Understanding the pathogenetic mechanisms underlying these disorders and finding molecules apt to correct such processes… (more)

▼ The vast majority of neurodegenerative disorders are adult-onset, incurable diseases. Understanding the pathogenetic mechanisms underlying these disorders and finding molecules apt to correct such processes are, therefore, among the hottest topics of biomedical research. Amyotrophic Lateral Sclerosis is one of the most common adult-onset neurodegenerative diseases characterized by progressive degeneration of upper and lower motor neurons leading to paralysis and death due to respiratory failure within 3-5 years from the onset. Only one drug, riluzole, has proved effective in extending the lifespan of patients with ALS, but only by 3-6 months. For this reason the development of effective therapies for this pathology is highly invocated, but to date all attempts to develop novel treatments have failed. In this context, two recent reports on the neuroprotective activity of the PPAR agonist Pioglitazione in ALS mice result of considerable interest: in these studies, two independent groups demonstrated that Pioglitazone, an agent which is currently used in therapy for the treatment of type II diabetes, is neuroprotective in a mouse model of Amyotrophic Lateral Sclerosis, the hSOD1-G93A transgenic mice. Pioglitazone treatment started before the appearance of the symptoms, improved the motor performance and reduced the weight loss, attenuated motor neuron death and increased the survival. In addition, Pioglitazone reduced microglial activation and gliosis in the spinal cord, decreasing the production of pro-inflammatory mediators, such as iNOS, NF-kB and COX2. On this ground, we decided to investigate the transcriptional activity of PPARs in the central nervous system of the hSOD1-G93A mouse line, a well-characterized animal model of Amyotrophic Lateral Sclerosis, with the aim of identifying the stage of the disease at which the activity of PPARs becomes relevant to the pathology. To this end, we took advantage of the transgenic mouse PPRE-Luc, available in the laboratory, in which the reporter gene luciferase is expressed under the control of a promoter responsive to PPARs. Thus, we crossed the PPRE-Luc mice with the hSOD1-G93A animals to obtain mice that are heterozygous for the PPRE-Luc transgene and heterozygous or null for the hSOD1-G93A transgene. The analysis of the enzymatic activity of luciferase in the spinal cord and the brain areas of PPRE-Luc;hSOD1-G93A mice shows an abrupt increase of PPAR activity at the end stage of the disease in the spinal cord, which is the organ principally involved in the pathology, and in all the brain areas analysed. We demonstrated that this phenomenon clearly depends on the pathology because it is not shared by the peripheral organs (e.g. kidney and liver). Furthermore, it is not dependent on the metabolic modifications induced from the starvation that the animals experience during the last days of their life when they are almost completely paralysed and, thus, unable to reach for food and water. We subsequently decided to further investigate this mechanism by identifying the… Advisors/Committee Members: docente guida: Adriana Maggi, coordinatore: Alberto Panerai, Francesca Guidobono Cavalchini, MAGGI, ADRIANA CATERINA, PANERAI, ALBERTO EMILIO, GUIDOBONO CAVALCHINI, FRANCESCA.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Benedusi, V. (2011). THE ROLE OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS IN AMYOTROPHIC LATERAL SCLEROSIS: POTENTIAL MECHANISMS FOR NEUROPROTECTION. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/150265

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Benedusi, V.. “THE ROLE OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS IN AMYOTROPHIC LATERAL SCLEROSIS: POTENTIAL MECHANISMS FOR NEUROPROTECTION.” 2011. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/150265.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Benedusi, V.. “THE ROLE OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS IN AMYOTROPHIC LATERAL SCLEROSIS: POTENTIAL MECHANISMS FOR NEUROPROTECTION.” 2011. Web. 19 Jan 2021.

Vancouver:

Benedusi V. THE ROLE OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS IN AMYOTROPHIC LATERAL SCLEROSIS: POTENTIAL MECHANISMS FOR NEUROPROTECTION. [Internet] [Thesis]. Università degli Studi di Milano; 2011. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/150265.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Benedusi V. THE ROLE OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS IN AMYOTROPHIC LATERAL SCLEROSIS: POTENTIAL MECHANISMS FOR NEUROPROTECTION. [Thesis]. Università degli Studi di Milano; 2011. Available from: http://hdl.handle.net/2434/150265

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

9. G. Monteleone. FUNCTIONAL ROLE OF ESTROGEN RECEPTORS DURING AGING AND THEIR INVOLVEMENT IN INFLAMMATORY PROCESSESS.

Degree: 2011, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/150266

► Estrogens are female sex hormones, belonging to a group of steroids, and they are responsible for the sexual characteristics of the female. They also have… (more)

▼ Estrogens are female sex hormones, belonging to a group of steroids, and they are responsible for the sexual characteristics of the female. They also have effects on bone, cardiovascular system, brain, and skin. The effects of estrogens are mediated by binding to their cognate receptors, the estrogen receptors (ERα and ERβ). ERs are transcription factors that regulate transcription by associating with estrogen-responsive-elements (EREs) located within the promoter of target genes. The aim of my studies was to evaluate the effect of aging and blockade of ovarian functions on estrogen receptor transcriptional activity and ER anti-inflammatory action . In specific aim1 we proposed to study genes driven by ERE-containing promoters: endogenous as well as surrogate reporters; within specific aim #2 we proposed to provide support to the theory that lack of estrogen anti-inflammatory activity is a major component for the onset of pathologies associated with menopause (osteoporosis, atherosclerosis, metabolic and neurological dysfunctions). In our study we evaluated ER activity during aging in ERE-Luc mice. The analysis showed that ERα is still synthesized during while with age, ovariectomy further increases ERα content in uterus, aorta and hippocampus, but not in the brain. To evaluate ER transcriptional activity in aging and after ovx we first studied the expression of the reporter luciferase (by measuring luciferase mRNA); next we evaluated the expression of ER endogenous genes such as Prothymosin alpha (PTMA) and Progesteron Receptor (PgR) known to be a direct target of ER. This study showed that the ER present in aged tissues is fully functional from the transcriptional point of view. In ovx animals the trend of ER activity is unclear. We were intrigued by the observation that, in aged female mice, a reduction of circulating levels of estrogens induced by ovariectomy was associated with an increased ER activity in several organs. To further study this phenomenon we gonadectomised male and female mice at the age of 5 months and we measured luciferase activity by in vivo imaging at 6 or 20 months of age. Luciferase activity is higher in females than in males in both groups of age, however gonadectomy does not affect luciferase activity in young males (with the exception of the chest), but clearly decreases photon emission in aged mice. In our study we also tested the hypothesis that with aging the loss of the anti-inflammatory activity of estrogens may explain the increased susceptibility to inflammatory disorders (i.e., osteoporosis, atherosclerosis, diabetes, certain neurodegenerative disorders), reported by epidemiological studies in women. Our analysis focused primarily on TNFα, IL1β, MCP1 and MIP2. The mRNA of all these inflammatory mediators was shown to increase progressively with aging. To evaluate the influence of estrogens on the expression of inflammatory genes, we measured the content of mRNA encoding for inflammatory mediators in different tissues of ovariectomized females. Due to the relevance of… Advisors/Committee Members: docente guida: Adriana Maggi, coordinatore: Alberto Panerai, Francesca Guidobono Cavalchini, MAGGI, ADRIANA CATERINA, PANERAI, ALBERTO EMILIO, GUIDOBONO CAVALCHINI, FRANCESCA.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA (6^th Edition):

Monteleone, G. (2011). FUNCTIONAL ROLE OF ESTROGEN RECEPTORS DURING AGING AND THEIR INVOLVEMENT IN INFLAMMATORY PROCESSESS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/150266

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Monteleone, G.. “FUNCTIONAL ROLE OF ESTROGEN RECEPTORS DURING AGING AND THEIR INVOLVEMENT IN INFLAMMATORY PROCESSESS.” 2011. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/150266.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Monteleone, G.. “FUNCTIONAL ROLE OF ESTROGEN RECEPTORS DURING AGING AND THEIR INVOLVEMENT IN INFLAMMATORY PROCESSESS.” 2011. Web. 19 Jan 2021.

Vancouver:

Monteleone G. FUNCTIONAL ROLE OF ESTROGEN RECEPTORS DURING AGING AND THEIR INVOLVEMENT IN INFLAMMATORY PROCESSESS. [Internet] [Thesis]. Università degli Studi di Milano; 2011. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/150266.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Monteleone G. FUNCTIONAL ROLE OF ESTROGEN RECEPTORS DURING AGING AND THEIR INVOLVEMENT IN INFLAMMATORY PROCESSESS. [Thesis]. Università degli Studi di Milano; 2011. Available from: http://hdl.handle.net/2434/150266

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

10. M. Marullo. NEW EVIDENCES OF TWO DIFFERENT KEY PATHOGENIC MECHANISMS IN HUNTINGTON'S DISEASE.

Degree: 2012, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/170272

► Huntington’s disease (HD) is an adult-onset neurodegenerative disorder characterized by several alterations in critical molecular and cellular pathways. Although genetic and experimental evidence has provided… (more)

▼ Huntington’s disease (HD) is an adult-onset neurodegenerative disorder characterized by several alterations in critical molecular and cellular pathways. Although genetic and experimental evidence has provided insights into HD pathogenesis, and many hypotheses concerning its underlying mechanisms have been proposed, a treatment that delays disease onset or slows its progression is still missing (Zuccato et al., 2010). During my PhD, my research activity was focused on the investigation of new aspects of two key pathogenic mechanisms of HD: i) the reduction of Brain-Derived Neurotrophic Factor (BDNF) and ii) the cholesterol dysfunction. Reduced BDNF levels have been described in a number of patho-physiological conditions, most notably, in HD. Since BDNF is also produced in blood, we have undertaken the measurement of its peripheral levels in the attempt to identify a possible link with HD prognosis and/or its progression. In the first part of my PhD, I evaluated BDNF level in 398 blood samples including 138 controls, 56 preHD, and 204 HD subjects. I found that BDNF protein levels were not reliably different between groups, whether measured in plasma (52 controls, 26 preHD, 105 HD) or serum (39 controls, 5 preHD, 29 HD). The analysis of the literature highlighted that intra-group variability and methodological aspects affect this measurement, especially in serum. Moreover during my PhD, I set up a novel strategy for mRNA normalization in quantitative real-time PCR that is based on expressed Alu repeat amplification as a measure for the mRNA fraction. I demonstrated that expressed Alu repeat amplification is a fast, accurate normalization tool that can be successfully used for quantification of selected mRNA in the human transcriptome. This result is particularly important for clinical diagnosis and biomarker validation studies based on mRNA detection in human blood. Based on this new normalization method, I measured BDNF mRNA levels in blood samples from 47 controls, 25 preHD, and 70 HD subjects, and found no differences among the groups. These results indicated that levels of BDNF in human blood were not informative (mRNA levels or plasma protein level) nor reliable (serum protein levels) as HD biomarkers. Brain cholesterol, which is synthesized locally, is a major component of myelin and cell membranes and participates in several neuronal activities, such as neurite outgrowth and synaptogenesis. In post-natal life, the cholesterol-dependent activities of neurons mainly rely on the transport of cholesterol from astrocytes on ApoE-containing lipoproteins. Mounting evidence indicates that reduced cholesterol biosynthesis occurs in the brain of several models of Huntington’s disease (HD) and is manifest in astrocytes (Valenza et al., J. Neurosci 2010). However, how mutation in huntingtin elicits changes in cholesterol biosynthesis pathway is still unknown. In the second part of my thesis, I explored the cross-talk between neurons and astrocytes to determine whether reduced cholesterol biosynthesis/secretion by HD… Advisors/Committee Members: tutor: E. Cattaneo, coordinatore: G. Franceschini, CATTANEO, ELENA, VALENZA, MARTA, ZUCCATO, CHIARA, FRANCESCHINI, GUIDO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Marullo, M. (2012). NEW EVIDENCES OF TWO DIFFERENT KEY PATHOGENIC MECHANISMS IN HUNTINGTON'S DISEASE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/170272

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Marullo, M.. “NEW EVIDENCES OF TWO DIFFERENT KEY PATHOGENIC MECHANISMS IN HUNTINGTON'S DISEASE.” 2012. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/170272.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Marullo, M.. “NEW EVIDENCES OF TWO DIFFERENT KEY PATHOGENIC MECHANISMS IN HUNTINGTON'S DISEASE.” 2012. Web. 19 Jan 2021.

Vancouver:

Marullo M. NEW EVIDENCES OF TWO DIFFERENT KEY PATHOGENIC MECHANISMS IN HUNTINGTON'S DISEASE. [Internet] [Thesis]. Università degli Studi di Milano; 2012. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/170272.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Marullo M. NEW EVIDENCES OF TWO DIFFERENT KEY PATHOGENIC MECHANISMS IN HUNTINGTON'S DISEASE. [Thesis]. Università degli Studi di Milano; 2012. Available from: http://hdl.handle.net/2434/170272

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

11. C. Bossio. TRANSDIFFERENZIAMENTO DI CELLULE STAMINALI MESENCHIMALI DI RODITORE IN CELLULE DEL SISTEMA NERVOSO CENTRALE.

Degree: 2012, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/171967

► One of the most important challenges in modern medicine is the identification of cell therapy protocols, enabling identification of personalized treatment strategies. WIthin this context,… (more)

▼ One of the most important challenges in modern medicine is the identification of cell therapy protocols, enabling identification of personalized treatment strategies. WIthin this context, adult stem cells (ASC) have a large applicative potential. Contrary to ESCs (embryonic stem cells) and IPSCs (induced pluripotent stem cells), ASCs can be easily extracted from different tissues (bone marrow, skin, adipose tissue, muscle) without raising ethical issues . Moreover, they can be used for autologous transplantation, eliminating the complications associated with autoimmune reactions. Mesenchymal stem cells (MSC,), are an ASC population present in the bone marrow, adipose tissue and other tissues. MSCs are readily available and are able to self-replicate and differentiate, supported by the presence of appropriate stimuli, into cell lines derived from mesodermal lineage (osteoblasts, chondrocytes, adipocytes, and muscle cells). In the last decade it has also been observed that MSCs are able to trans-differentiate into cell types of ectodermal and endodermal origin (transdifferentiation).. The purpose of my work was to develop and define the conditions which can induce trans-differentiation of MSCs extracted from rat adipose tissue toward the neuronal phenotype. The study is part of a major project of regenerative medicine focused on identifying new strategies aimed at restoring functionality in degenerated brain tissue. Initially, MSCs have been characterized by the induction of osteoblastic differentiation, one of their physiological differentiations, and their interaction with biocompatible materials ( titanium dioxide) was analyzed, in order to assess their possible application in medicine for the creation, for example, of prothesic solutions. Subsequently, we sought to devise a GMP compliant cell culturing medium for MSC proliferation, crucial in order to obtain a clinically relevant cell number to differentiate following isolation from adipose tissue. For that reason we tried to induce the differentiation of MSCs into a neural phenotype; a first approach has been to apply protocols already known in literature for the differentiation of different types of stem cells toward the neuronal phenotype.. We considered both the direct differentiation protocols, as well as those that encompassed intermediate stages (sphere-forming). The protocols of differentiation by sphere formation resulted in differentiated MSC expressing glial markers (GFAP), but the protocol was too long(30 days) and a number of differentiated cells very low.. A second approach has been to develop a proprietary differentiation medium (NZ4) using the knowledge and expertise gained from the literature and from the negative results previously obtained The cells maintained in NZ4 differentiation medium , showed a clear morphological change and a high vitality; moreover they expressed both markers of specific neurons in the early stages of development (nestin, doublecortin) as well as markers expressed by mature neurons (βIIItubulin,… Advisors/Committee Members: relatore: D.M.M. Fornasari, tutor: F. Bianco, FORNASARI, DIEGO MARIA MICHELE.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bossio, C. (2012). TRANSDIFFERENZIAMENTO DI CELLULE STAMINALI MESENCHIMALI DI RODITORE IN CELLULE DEL SISTEMA NERVOSO CENTRALE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/171967

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bossio, C.. “TRANSDIFFERENZIAMENTO DI CELLULE STAMINALI MESENCHIMALI DI RODITORE IN CELLULE DEL SISTEMA NERVOSO CENTRALE.” 2012. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/171967.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bossio, C.. “TRANSDIFFERENZIAMENTO DI CELLULE STAMINALI MESENCHIMALI DI RODITORE IN CELLULE DEL SISTEMA NERVOSO CENTRALE.” 2012. Web. 19 Jan 2021.

Vancouver:

Bossio C. TRANSDIFFERENZIAMENTO DI CELLULE STAMINALI MESENCHIMALI DI RODITORE IN CELLULE DEL SISTEMA NERVOSO CENTRALE. [Internet] [Thesis]. Università degli Studi di Milano; 2012. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/171967.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bossio C. TRANSDIFFERENZIAMENTO DI CELLULE STAMINALI MESENCHIMALI DI RODITORE IN CELLULE DEL SISTEMA NERVOSO CENTRALE. [Thesis]. Università degli Studi di Milano; 2012. Available from: http://hdl.handle.net/2434/171967

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

12. V. Cea. THE INHIBITION OF ILK-1 INCREASES THE EFFICACY OF ANTI-ANGIOGENIC THERAPIES.

Degree: 2013, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/214972

► The prognosis of the most common glial tumors, the glioblastoma (GBM; World Health Organization grade IV), remains poor with a 2-year survival rate in less… (more)

▼ The prognosis of the most common glial tumors, the glioblastoma (GBM; World Health Organization grade IV), remains poor with a 2-year survival rate in less than 20% of the patients despite significant advances in therapeutic options available. The dependence of tumor growth and metastasis on angiogenesis has provided powerful rationale for anti-angiogenic approaches to cancer therapy (Folkman J. 1971; Carmeliet P. et al. 2000). The main aim of this project was the characterization of tumour response to anti-angiogenic therapy and to find out new markers and better therapies to treat them. In a previous study we have demonstrated the role of Integrin Linked Kinase-1 (ILK-1), a kinase involved in cell cycle progression, inhibition of apoptosis, cell growth and migration, in the resistence of glioma to anti-angiogenic drugs. In fact, we found that the expression level of this protein decreases in the first part of the anti-angiogenic treatment and increases after 20 days of treatment in an in vivo model of glioblastoma. In addition we found that the expression levels of ILK-1 correlate with the worst outcome in patients. We demonstrated a strong reduction of tumour growth after the silencing of ILK-1 in our in vivo model. We want to analyze the effects of a small specific inhibitor of ILK-1: QLT0267 alone or in combination with two anti-angiogenic drugs already used in clinic: sorafenib and sunitinib that inhibit tyrosine kinase receptors. The combination of the pharmacologic inhibition of ILK-1 and angiogenesis lead to a significant decrease of tumour volume and vessels formation. We than investigated the molecular mechanism underling the effect of the combination of the inhibition of angiogenesis and ILK-1 studying what pathway is implicated. We speculate that the inhibition of tyrosine kinase receptors and the ILK-1 activity lead, through AKT pathway, to a downregulation of the pathways involved in angiogenesis. Interestingly, we found a strong decrease in glioma cells of HIF-1α protein after the combined treatments and we think that this can be related to the effects on vessel formation and on tumour growth that we have observed in vivo. Our data taken together indicate that the combinatorial administration of compounds that simultaneously inhibit angiogenesis and tumor cell proliferation by targeting specific signaling pathways might results in a significant increase in the therapeutic efficacy. Advisors/Committee Members: tutor: C.Sala, coordinator: A. Panerai, PANERAI, ALBERTO EMILIO, PANERAI, ALBERTO EMILIO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cea, V. (2013). THE INHIBITION OF ILK-1 INCREASES THE EFFICACY OF ANTI-ANGIOGENIC THERAPIES. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/214972

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Cea, V.. “THE INHIBITION OF ILK-1 INCREASES THE EFFICACY OF ANTI-ANGIOGENIC THERAPIES.” 2013. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/214972.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Cea, V.. “THE INHIBITION OF ILK-1 INCREASES THE EFFICACY OF ANTI-ANGIOGENIC THERAPIES.” 2013. Web. 19 Jan 2021.

Vancouver:

Cea V. THE INHIBITION OF ILK-1 INCREASES THE EFFICACY OF ANTI-ANGIOGENIC THERAPIES. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/214972.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cea V. THE INHIBITION OF ILK-1 INCREASES THE EFFICACY OF ANTI-ANGIOGENIC THERAPIES. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/214972

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

13. A. Raspa. RECUPERO MOTORIO IN MODELLO MURINO DI MORBO DI PARKINSON DOPO TRAPIANTO DI CELLULE STAMINALI POST-MORTEM.

Degree: 2013, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/217712

►

Abbiamo studiato una strategia per migliorare i sintomi motori di topi che avevano ricevuto lesioni con una neurotossina specifica, MPTP, un modello murino di morbo… (more)

▼

Abbiamo studiato una strategia per migliorare i sintomi motori di topi che avevano ricevuto lesioni con una neurotossina specifica, MPTP, un modello murino di morbo di Parkinson, attraverso il trapianto di precursori cellulari post mortem nello striato. I precursori cellulari neurali post-mortem (PM-NPC) sono stati isolati dalla zona subventricolare (SVZ) dei ventricoli laterali del topo, coltivati in vitro e la loro capacità di differenziarsi è stata studiata valutando l'espressione di diversi marcatori neurali. PM-NPC differenziano in neuroni e in gran parte a differenza di molti altri precursori, mantengono la capacità di migrazione e integrazione, quando trapiantate nel cervello adulto. Abbiamo eseguito il trapianto di PM-NPC nei gangli della base di topi MPTP lesionati. PM-NPC trapiantate sopravvivono, differenziano e si integrano nel circuito di accoglienza, e modificano il comportamento motorio nei topi MPTP lesionati. I nostri dati suggeriscono che il trapianto di PM-NPC nel corpo striato è un approccio promettente per investigare i potenziali benefici di rimodellamento dei circuiti dei gangli basali nelle malattie neurodegenerative.

We investigated a strategy to ameliorate the motor symptoms of mice that received MPTP lesions, a rodent model of Parkinson’s disease, through transplantation of adult precursor post-mortem cells into the striatum. Post mortem neural precursors (PM-NPCs) were isolated from the subventricular zone (SVZ), grown in vitro and their differentiation capability was investigated by evaluating the expression of different neuronal markers. PM-NPCs differentiate mostly in neurons and unlike most other precursor cells, retain the capacity for migration and integration when transplanted into the adult brain. We performed PM-NPCs transplantation into the basal ganglia of MPTP lesioned mice. Transplanted PM-NPCs survived, differentiated and integrated into host circuitry, and modified motor behavior in MPTP lesioned mice. Our data suggest that PM-NPCs transplantation into the the striatum is a promising approach to invenstigate the potential benefits of remodeling basal ganglia circuitry in neurodegenerative diseases.

Advisors/Committee Members: coordinatore: A. Gorio, docente guida: A. Gorio, GORIO, ALFREDO, GORIO, ALFREDO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Raspa, A. (2013). RECUPERO MOTORIO IN MODELLO MURINO DI MORBO DI PARKINSON DOPO TRAPIANTO DI CELLULE STAMINALI POST-MORTEM. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/217712

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Raspa, A.. “RECUPERO MOTORIO IN MODELLO MURINO DI MORBO DI PARKINSON DOPO TRAPIANTO DI CELLULE STAMINALI POST-MORTEM.” 2013. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/217712.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Raspa, A.. “RECUPERO MOTORIO IN MODELLO MURINO DI MORBO DI PARKINSON DOPO TRAPIANTO DI CELLULE STAMINALI POST-MORTEM.” 2013. Web. 19 Jan 2021.

Vancouver:

Raspa A. RECUPERO MOTORIO IN MODELLO MURINO DI MORBO DI PARKINSON DOPO TRAPIANTO DI CELLULE STAMINALI POST-MORTEM. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/217712.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Raspa A. RECUPERO MOTORIO IN MODELLO MURINO DI MORBO DI PARKINSON DOPO TRAPIANTO DI CELLULE STAMINALI POST-MORTEM. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/217712

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

14. S. Bolamperti. ESTROGEN- GROWTH HORMONE INTERACTION IN BONE CELLS OF THE OSTEOGENIC LINEAGE: GROWTH HORMONE ANABOLIC ACTIVITY ON HUMAN OSTEOBLASTS AND THEIR MESENCHYMAL PRECURSORS IS MODULATED BY 17ΒETA-ESTRADIOL THROUGH A POST RECEPTOR MECHANISM.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/229429

► In aging the loss of bone mass goes along with a decline of 17beta-estradiol (E2) and Growth Hormone (GH), which are known to be bone… (more)

▼ In aging the loss of bone mass goes along with a decline of 17beta-estradiol (E2) and Growth Hormone (GH), which are known to be bone anabolic factors. Recent evidence demonstrated in several cell lines an interplay between E2 and GH at a post receptor level. I thus evaluated the possible cross-talk between these two hormones in human osteoblast cells (hOBs) in primary culture and in their mesenchymal precursors (hMSCs). E2 (10-8M) given 60 min before GH (5ng/ml) enhanced both GH intracellular pathway in hOBs and the transcription of the evaluated GH target genes involved in osteoblast activity and matrix deposition, osteopontin (OPN), bone sialoprotein (BSP) and insulin like growth factor 2 (IGF2). E2 effects occurred by decreasing the protein levels of SOCS2, one of the main GH signaling inhibitors, through an increase in SOCS2 ubiquitination and consequent degradation. This effect was blunted by pre-treating the cells with the proteasome inhibitor MG132 (5µM). Interestingly this effect did not involve an E2 mediated genomic activity as Actinomycin D (5µM) pre-treatment did not prevent E2 modulation of SOCS2 levels (Bolamperti S. et al., 2013). Further experiments demonstrated that this short term effect on SOCS2 levels was maintained over time: after 3h of E2 treatment there was still a decrease in SOCS2 levels. Yet, at this time point, the effect occurred via an inhibition of the transcription of SOCS2 gene. The fact that E2 negative regulation of the GH inhibitor SOCS2 involves an initially rapid protein degradation maintained for a longer time by a decrease in its gene expression strengthens the importance and the physiological relevance of this modulation for osteoblast activity. I was therefore interested to investigate whether or not two SERMs often used in clinics, Tamoxifen (Tam) and Raloxifene (Ral), share the same effect on GH signaling as E2. Cells treated with Tam (10-10M) or Ral (10-8M) 60 min before GH showed a trend to increase STAT5 phosphorylation even though reaching statistical significance, despite an observed reduction of SOCS2 levels with the SERMs alone. After 3h treatment no modulation of SOCS2 transcription was detected with either Tam, or Ral. These data suggest that despite their general estrogen agonistic properties on bone, none of the two drugs displayed the same features as E2. The combined effect of E2 and GH was evaluated also in mesenchymal stem cells (MSCs) obtained from human bones. The cells were first tested for plastic adherence, for differentiation capability towards adipocytes or osteoblasts, and for the positivity to CD73, CD105, and CD90 following an NIH protocol. In these osteoblast precursors, pretreatment of E2 60 min before GH, increased STAT5 phosphorylation induced by GH and decreased SOCS2 levels, as shown in hOBs. Considering the lack of information about GH action in stromal precursors, we evaluated GH action in the isolated hMSCs, focusing on its possible role in both osteogenesis and adipogenesis. The results showed that … Advisors/Committee Members: tutor: F. Guidobono Cavalchini, I. Villa, coordinatore: A.Panerai, PANERAI, ALBERTO EMILIO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bolamperti, S. (2014). ESTROGEN- GROWTH HORMONE INTERACTION IN BONE CELLS OF THE OSTEOGENIC LINEAGE: GROWTH HORMONE ANABOLIC ACTIVITY ON HUMAN OSTEOBLASTS AND THEIR MESENCHYMAL PRECURSORS IS MODULATED BY 17ΒETA-ESTRADIOL THROUGH A POST RECEPTOR MECHANISM. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/229429

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bolamperti, S.. “ESTROGEN- GROWTH HORMONE INTERACTION IN BONE CELLS OF THE OSTEOGENIC LINEAGE: GROWTH HORMONE ANABOLIC ACTIVITY ON HUMAN OSTEOBLASTS AND THEIR MESENCHYMAL PRECURSORS IS MODULATED BY 17ΒETA-ESTRADIOL THROUGH A POST RECEPTOR MECHANISM.” 2014. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/229429.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bolamperti, S.. “ESTROGEN- GROWTH HORMONE INTERACTION IN BONE CELLS OF THE OSTEOGENIC LINEAGE: GROWTH HORMONE ANABOLIC ACTIVITY ON HUMAN OSTEOBLASTS AND THEIR MESENCHYMAL PRECURSORS IS MODULATED BY 17ΒETA-ESTRADIOL THROUGH A POST RECEPTOR MECHANISM.” 2014. Web. 19 Jan 2021.

Vancouver:

Bolamperti S. ESTROGEN- GROWTH HORMONE INTERACTION IN BONE CELLS OF THE OSTEOGENIC LINEAGE: GROWTH HORMONE ANABOLIC ACTIVITY ON HUMAN OSTEOBLASTS AND THEIR MESENCHYMAL PRECURSORS IS MODULATED BY 17ΒETA-ESTRADIOL THROUGH A POST RECEPTOR MECHANISM. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/229429.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bolamperti S. ESTROGEN- GROWTH HORMONE INTERACTION IN BONE CELLS OF THE OSTEOGENIC LINEAGE: GROWTH HORMONE ANABOLIC ACTIVITY ON HUMAN OSTEOBLASTS AND THEIR MESENCHYMAL PRECURSORS IS MODULATED BY 17ΒETA-ESTRADIOL THROUGH A POST RECEPTOR MECHANISM. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/229429

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

15. S. Carelli. DEVELOPING A REGENERATIVE MEDICINE APPROACH FOR THE TREATMENT OF PARKINSON'S DISEASE.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/230550

► Parkinson’s disease (PD) is the second most common neurodegenerative disease, after Alzheimer’s disease, and the most common movement disorder. Drug treatment and deep brain stimulation… (more)

▼ Parkinson’s disease (PD) is the second most common neurodegenerative disease, after Alzheimer’s disease, and the most common movement disorder. Drug treatment and deep brain stimulation can ameliorate symptoms, but the progressive degeneration of dopaminergic neurons in the substantia nigra eventually leads to severe motor dysfunction. While some effective treatments for patients with PD exist, these treatment strategies are mainly symptomatic and aimed at increasing dopamine levels in the degenerating nigrostriatal system. Existing drugs are limited in their relief and decrease in effectiveness as PD progresses.The transplantation of stem cells has emerged as a promising approach to replace lost neurons in order to restore dopamine levels in the striatum and reactivate functional circuits. Post mortem neural precursor cells (PM-NPCs) are a subclass of sub ventricular zone (SVZ)-derived neural progenitors, capable of surviving many hours (16 hours) after donor death. The in vitro differentiation yields more neurons (about 30-40%) compared to regular NPCs (Marfia et al., 2011). Recently from the SVZ of a transgenic mouse strain expressing green fluorescent protein (GFP) under the promoter C of the ubiquitin gene [(C57BL/6-Tg(UBC-GFP)30Scha/J)] we isolated GFP PM-NPCs, from mice at 6 hours after the donor death. These cells were characterized and their potential of in terms of replacement therapy was investigated in a mouse model of Parkinson disease. The degeneration of dopaminergic neurons was obtained through the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at the dosage of 36 mg/kg intraperiteoneally (i.p.). After 1 week the lesion was stabilized by a second administration (i.p.) of the neurotoxin at the dosage of 20 mg/kg. 1x 105 of PM-PCs-GFP were injected unilaterally into the striatum of C57/BL mice by using specific stereotaxic coordinates 3 days after the second MPTP administration. The effects of transplanted cells were determined by means of performance tests aimed at detecting behavioral improvements. Moreover, the neurochemical changes were also studied by high performance liquid chromatography (HPLC). In order to study the in vivo fate of grafted GFP PM-NPCs animals were perfused 2 weeks after transplantation and immunohistochemistry studies were performed. Our results show that animals grafted with GFP PM-NPCs determined a remarkable improvement of behavioral parameters measured by means of both horizontal and vertical grid tests (forepaw fault and time required to grab on the grids while turning and climbing down) since the third day after transplantation. These improvements were very significant and the average values were close to control animals. This was maintained during all the two weeks of experimental observation. By means of immunofluorescence staining we observed that the majority of transplanted GFP-PM-NPCs were vital and able to migrate ventrally and caudally from the injection site lengths as far as 1000 microns into the striatum, and could reach the… Advisors/Committee Members: coordinatore: A. Gorio, docente guida: A.M. Di Giulio, DI GIULIO, ANNA MARIA, GORIO, ALFREDO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Carelli, S. (2014). DEVELOPING A REGENERATIVE MEDICINE APPROACH FOR THE TREATMENT OF PARKINSON'S DISEASE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/230550

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Carelli, S.. “DEVELOPING A REGENERATIVE MEDICINE APPROACH FOR THE TREATMENT OF PARKINSON'S DISEASE.” 2014. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/230550.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Carelli, S.. “DEVELOPING A REGENERATIVE MEDICINE APPROACH FOR THE TREATMENT OF PARKINSON'S DISEASE.” 2014. Web. 19 Jan 2021.

Vancouver:

Carelli S. DEVELOPING A REGENERATIVE MEDICINE APPROACH FOR THE TREATMENT OF PARKINSON'S DISEASE. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/230550.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Carelli S. DEVELOPING A REGENERATIVE MEDICINE APPROACH FOR THE TREATMENT OF PARKINSON'S DISEASE. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/230550

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

16. V. Galbiati. ASSESSMENT OF THE ALLERGENIC POTENTIAL OF XENOBIOTICS: IN VIVO IN VITRO A BACK-AND-FORTH APPROACH.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/246102

► Allergic contact dermatitis (ACD) is an important occupational and environmental disease caused by topical exposure to low molecular weight chemical allergens. The development of ACD… (more)

▼ Allergic contact dermatitis (ACD) is an important occupational and environmental disease caused by topical exposure to low molecular weight chemical allergens. The development of ACD requires the activation of innate immune cells, such as keratinocytes (KC), necessary for the maturation and the migration of dendritic cells (DC), which in turn are required for the activation of specific T cells. Human KC constitutively express several cytokines, including pro IL-1 alpha, pro IL-1 beta and pro IL-18. In vivo it has been demonstrated that IL-18 plays a key proximal role in the induction of allergic contact sensitization, favoring Th-1 type immune response by enhancing the secretion of pro-inflammatory mediators such as TNF-α, IL-8 and IFN-γ (Shornick et al., 1996; Wang et al., 1999, Cumberbatch et al., 2001). Toxicologists have the responsibility of identifying and characterizing the skin and respiratory allergenic potential of chemicals, and estimating the risk they pose to human health. Growing political and practical resistance to toxicity testing in animals has driven the development of animal-free methods for screening and prioritization of toxicants, including those causing allergic hypersensitivity. The purpose of this thesis was to develop an alternative in vitro test based on the keratinocytes and IL-18 to characterize the allergenic potential of low molecular weight chemicals, and to understand the molecular mechanism(s) underlying chemical allergen-induced IL-18 production. In addition to human keratinocytes cell lines (NCTC2544, HaCaT, HPKII), commercially available reconstituted human epidermis 3D-epidermal models were also used as experimental model. Due to their anatomical location and critical role in skin inflammatory and immunological reactions, the use of the KC and skin organotypic culture as a simplified in vitro model to evaluate the potential toxicity of chemicals destined for epicutaneous application is amply justified. To perform these studies 22 contact allergens, 12 photoallergens/photoirritant compounds, 3 respiratory allergens and 9 irritants chemicals were used. The choice of chemicals was dictated by the SENS-IT-IV programme as relevant and representative of the ‘universe’ of irritants, respiratory and contact allergens. Phototoxic chemicals were selected based on compounds used in similar published studies and reported to cause phototoxicity. Results obtained indicate that the NCTC2544 IL-18 assay is able to discriminate contact allergens and photoallergens from irritants/photoirritants and respiratory allergens. Important factors including compound solubility, chemical reactivity and metabolic activation, which may mask the potential allergenicity of some chemicals, must be considered in the development of in vitro tests. Submerged cell culture may be unfavourable for many of the respiratory sensitizers, due to chemical instability; for this reason we have tested IL-18 production also in reconstituted human epidermis, which allows application in organic solvent, i.e. acetone: olive… Advisors/Committee Members: tutor: C.L. Galli, correlatore: A. Panerai, CORSINI, EMANUELA.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Galbiati, V. (2014). ASSESSMENT OF THE ALLERGENIC POTENTIAL OF XENOBIOTICS: IN VIVO IN VITRO A BACK-AND-FORTH APPROACH. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/246102

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Galbiati, V.. “ASSESSMENT OF THE ALLERGENIC POTENTIAL OF XENOBIOTICS: IN VIVO IN VITRO A BACK-AND-FORTH APPROACH.” 2014. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/246102.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Galbiati, V.. “ASSESSMENT OF THE ALLERGENIC POTENTIAL OF XENOBIOTICS: IN VIVO IN VITRO A BACK-AND-FORTH APPROACH.” 2014. Web. 19 Jan 2021.

Vancouver:

Galbiati V. ASSESSMENT OF THE ALLERGENIC POTENTIAL OF XENOBIOTICS: IN VIVO IN VITRO A BACK-AND-FORTH APPROACH. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/246102.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Galbiati V. ASSESSMENT OF THE ALLERGENIC POTENTIAL OF XENOBIOTICS: IN VIVO IN VITRO A BACK-AND-FORTH APPROACH. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/246102

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

17. S. Pambianco. PERSISTENT INHIBITION OF MITOCHONDRIAL BIOGENESIS IN DYSTROPHIC MICE: IDENTIFICATION OF NITRIC OXIDE-DEPENDENT SALVAGE PATHWAY.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/246809

► Muscular dystrophies are a group of genetic diseases showing muscle degeneration characterized by progressive skeletal muscle weakness, defects in muscle proteins fiber necrosis, and progressive… (more)

▼ Muscular dystrophies are a group of genetic diseases showing muscle degeneration characterized by progressive skeletal muscle weakness, defects in muscle proteins fiber necrosis, and progressive substitution of fibers with connective and adipose tissue. The therapeutic protocols currently in use, based on corticosteroid administration, provide some delay in the progression of the disease, but they are associated with severe side effects. The genetic approaches (exon skipping and antisense oligonucleotides) currently being investigated show some degree of success, however they are directed to specific subsets of population and cannot restore fully the damage already caused by the disease to the muscle. Several studies had demonstrate that the pathophysiology of muscular dystrophies correlates with an altered synthesis of nitric oxide (NO), in fact neuronal nitric oxide synthase (nNOS) is absent from the sarcolemma and relocated to the cytosol, with total muscle NOS activity being thus reduced. During the years, nitric oxide donors were identified as good candidate molecules for Duchenne Muscular dystrophy therapy and recently, our group found that a NO donor, molsidomine, is able to slow disease progression and to restore the functional capacity of damaged muscle, significantly enhancing spontaneous and forced motor activities1. Nitric oxide regulates some mitochondrial functions, such as morphology and complexes activity; moreover mitochondrial dysfunction has long been suspected to be an important pathogenetic feature in muscular dystrophies even if their role is not fully understood. The aim of this project is to analyze the mitochondrial profile of alpha-Sarcoglican-null (a-SG) mice, a mouse model for Limb Girdle muscular dystrophy 2D (LGMD 2D) and to evaluate a possible effect of molsidomine on mitochondrial function. Our long term aim is to define approaches that limit muscle wasting, with a dual finality, on the one hand to ameliorate the dystrophic symptoms per se, on the other to increase the efficiency of cell/gene therapies, in a combined therapy for the disease. To this end elucidation of novel possible targets is necessary and this is the final goal of this project. We find out a severe reduction in mitochondrial content in both tibialis anterior and diaphragm accounting for a lower OxPhos capacity of these muscles. The respiratory rates relative to mitochondrial DNA suggest that mitochondrial content is the major determinant of the lower oxidative capacity of a-SG null muscles. The low mitochondrial content in dystophyc mice is due to a persistent inhibition of the mitochondrial biogenesis pathway. Unexpectedly, the treatment with the NO-donor molsidomine is not able to restore mitochondrial content in a-SG-/- mice, but it is able to improve significantly their oxidative capacity, triggering a therapeutic fiber switch and stimulating fatty acid oxidation rather than improving mitochondrial function per se. Molsidomine promotes in fact an important deacetylation and activation of peroxisome… Advisors/Committee Members: tutor: E. Clementi, correlatore: C. De Palma, coordinatore: A. Panerai, CLEMENTI, EMILIO GIUSEPPE IGNAZIO, PANERAI, ALBERTO EMILIO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pambianco, S. (2014). PERSISTENT INHIBITION OF MITOCHONDRIAL BIOGENESIS IN DYSTROPHIC MICE: IDENTIFICATION OF NITRIC OXIDE-DEPENDENT SALVAGE PATHWAY. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/246809

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Pambianco, S.. “PERSISTENT INHIBITION OF MITOCHONDRIAL BIOGENESIS IN DYSTROPHIC MICE: IDENTIFICATION OF NITRIC OXIDE-DEPENDENT SALVAGE PATHWAY.” 2014. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/246809.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Pambianco, S.. “PERSISTENT INHIBITION OF MITOCHONDRIAL BIOGENESIS IN DYSTROPHIC MICE: IDENTIFICATION OF NITRIC OXIDE-DEPENDENT SALVAGE PATHWAY.” 2014. Web. 19 Jan 2021.

Vancouver:

Pambianco S. PERSISTENT INHIBITION OF MITOCHONDRIAL BIOGENESIS IN DYSTROPHIC MICE: IDENTIFICATION OF NITRIC OXIDE-DEPENDENT SALVAGE PATHWAY. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/246809.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Pambianco S. PERSISTENT INHIBITION OF MITOCHONDRIAL BIOGENESIS IN DYSTROPHIC MICE: IDENTIFICATION OF NITRIC OXIDE-DEPENDENT SALVAGE PATHWAY. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/246809

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

18. C. Vicidomini. POSITIVE MODULATION OF MGLU5 REVERSES ASD-LIKE BEHAVIORS FOUND IN SHANK3 KNOCK-OUT MICE.

Degree: 2016, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/353045

► Shank proteins are the major scaffold proteins that organize the postsynaptic density at the excitatory synapses. Shank1-3 proteins are associated with type I mGluRs via… (more)

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Vicidomini, C. (2016). POSITIVE MODULATION OF MGLU5 REVERSES ASD-LIKE BEHAVIORS FOUND IN SHANK3 KNOCK-OUT MICE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/353045

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Vicidomini, C.. “POSITIVE MODULATION OF MGLU5 REVERSES ASD-LIKE BEHAVIORS FOUND IN SHANK3 KNOCK-OUT MICE.” 2016. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/353045.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Vicidomini, C.. “POSITIVE MODULATION OF MGLU5 REVERSES ASD-LIKE BEHAVIORS FOUND IN SHANK3 KNOCK-OUT MICE.” 2016. Web. 19 Jan 2021.

Vancouver:

Vicidomini C. POSITIVE MODULATION OF MGLU5 REVERSES ASD-LIKE BEHAVIORS FOUND IN SHANK3 KNOCK-OUT MICE. [Internet] [Thesis]. Università degli Studi di Milano; 2016. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/353045.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Vicidomini C. POSITIVE MODULATION OF MGLU5 REVERSES ASD-LIKE BEHAVIORS FOUND IN SHANK3 KNOCK-OUT MICE. [Thesis]. Università degli Studi di Milano; 2016. Available from: http://hdl.handle.net/2434/353045

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

19. C.A. Elia. EFFECTS OF MICROVESICLES DERIVED FROM BONE MARROW MESENCHYMAL STEM CELLS IN EXPERIMENTAL MODELS OF ALZHEIMER¿S DISEASE.

Degree: 2016, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/351930

► Alzheimer's disease (AD) is the most common form of neurodegenerative illness leading to dementia characterized by the accumulation of abnormally folded β-Amyloid (Aβ) and tau… (more)

▼ Alzheimer's disease (AD) is the most common form of neurodegenerative illness leading to dementia characterized by the accumulation of abnormally folded β-Amyloid (Aβ) and tau proteins, forming amyloid plaques and neurofibrillary tangles, respectively. Recent evidences have highlighted that inflammation plays a critical role in AD, even though it remains unclear whether it represents a cause or a consequence of the pathology. Deposition of Aβ peptides and tangles are able to stimulate a chronic inflammatory reaction, involving microglial activation and production of inflammatory cytokines likely contributing to neuronal dysfunction and cell death per se. Regarding immunomodulatory strategy development, during the last years, it has been shown that Mesenchymal Stem Cells (MSCs) play a strongly immunomodulatory role, protecting the injured tissue and guiding anti-inflammatory processes by the secretion of cytokines and microvesicles (MVs), involved in their paracrine effects. Furthermore many clinical studies are now performing therapies with MSCs and some phase I and phase II clinical trials in the oncology field are also studying MSC derived MVs (Dai et al, 2008 and Chaput and Théry, 2011). Since the possibility that inflammation is not a mere consequence but a primary contributing factor in AD is becoming concrete, and given upregulation of inflammatory molecules (pro-inflammatory cytokines and chemokines) and activated glial cells surrounding the senile plaques in AD patients brains and AD transgenic animal models are now recognized as typical features of AD, the aim of this project is to assess the anti-inflammatory effects of MVs released by Bone Marrow Mesenchymal Stem Cells (BM-MSCs) in an AD context. Both in vitro and in vivo experimental approaches are used to investigate the MV immunomodulatory effect and their ability to affect Aβ deposition and degradation. Pro- inflammatory (TNFα and IL6) and anti-inflammatory cytokines (IL10) release was investigated by in vitro experiments performed on both microglial N9 cell line and on primary cortical cells exposed to human-Aβ1-42 (h- Aβ1-42 ) and MSC derived MVs. For a more complete analysis of the cell inflammatory state, the microglia phenotype was assessed in order to determine whether a change from M1 to M2 cell phenotype was detectable. The in vivo approach consisted of MV intracranial injections in a well-established transgenic AD chimeric murine model (APPswe/PS1dE9) that recapitulates many of the aspects of the human disease; to investigate whether MVs effects could be effective on the clearance and production of Aβ, possibly ameliorating the neurodegenerative context, we analyzed Aβ load, plaque area and density in three different brain areas: cerebral cortex, hippocampus and cerebellum. The results obtained in vitro indicate that i) the administration of MVs promotes in vitro the secretion of anti-inflammatory cytokines, such as IL10; ii) MVs promote the switch of microglial cell to M2 phenotype, characterized by the typical amoeboid morphology,… Advisors/Committee Members: tutor: F. Gardoni, co-tutor: E. Menna, coordinatore: A. Corsini, GARDONI, FABRIZIO, CORSINI, ALBERTO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Elia, C. (2016). EFFECTS OF MICROVESICLES DERIVED FROM BONE MARROW MESENCHYMAL STEM CELLS IN EXPERIMENTAL MODELS OF ALZHEIMER¿S DISEASE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/351930

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Elia, C.A.. “EFFECTS OF MICROVESICLES DERIVED FROM BONE MARROW MESENCHYMAL STEM CELLS IN EXPERIMENTAL MODELS OF ALZHEIMER¿S DISEASE.” 2016. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/351930.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Elia, C.A.. “EFFECTS OF MICROVESICLES DERIVED FROM BONE MARROW MESENCHYMAL STEM CELLS IN EXPERIMENTAL MODELS OF ALZHEIMER¿S DISEASE.” 2016. Web. 19 Jan 2021.

Vancouver:

Elia C. EFFECTS OF MICROVESICLES DERIVED FROM BONE MARROW MESENCHYMAL STEM CELLS IN EXPERIMENTAL MODELS OF ALZHEIMER¿S DISEASE. [Internet] [Thesis]. Università degli Studi di Milano; 2016. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/351930.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Elia C. EFFECTS OF MICROVESICLES DERIVED FROM BONE MARROW MESENCHYMAL STEM CELLS IN EXPERIMENTAL MODELS OF ALZHEIMER¿S DISEASE. [Thesis]. Università degli Studi di Milano; 2016. Available from: http://hdl.handle.net/2434/351930

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

20. M. Tamborini. A NANOTECHNOLOGY APPROACH FOR GLIOBLASTOMA TARGETED THERAPY.

Degree: 2016, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/351946

► Glioblastoma multiforme (GBM) is an extremely aggressive type of glioma. Life expectancy is around two years after diagnosis, due to recidivism and to the presence… (more)

▼ Glioblastoma multiforme (GBM) is an extremely aggressive type of glioma. Life expectancy is around two years after diagnosis, due to recidivism and to the presence of the blood brain barrier (BBB) restricting the amount of drugs which arrive at the residual cancer cells, thus contributing to chemotherapies failure. To overcome the impediment imposed by the BBB, we have investigated the use of nanotechnologies in synergy with radiotherapy as a prospective strategy for GBM treatment. We have used poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PNP) conjugated to the peptide chlorotoxin (CTX), which has been shown to recognize and selectively bind to glioma cells. Silver nanoparticles have been encapsulated inside the functionalized nanoparticles (Ag-PNP-CTX), to allow detection of cellular uptake and quantification by means of confocal microscopy, both in vitro and in vivo. In vitro experiments, involving 3 different human glioblastoma cell lines, have shown that the cytoplasmic uptake of Ag-PNP-CTX is higher than that of non-functionalized nanoparticles. Experiments performed in vivo have shown high efficiency of Ag-NP-CTX particles in targeting tumor cells; however, they have been shown to be scarcely able to cross the blood brain barrier at the healthy brain level, where scattered metastatic cells are present too. A single x-rays administration on the whole brain, carried out twenty hours before the injection of the nanoparticles, has been shown to increase the levels of expression of the CTX targets MMP-2 e ClC-3. Moreover, through an alteration of BBB permeability, it has been shown to potentially increase the quantity of internalized Ag-PNP-CTX also in dispersed cells, and to lead to significant results in inhibiting tumor growth in vivo. Notably, the administration of Ag-PNP-CTX to irradiated tumor cells decreases the MMP-2 extracellular activity. By targeting scattered GBM cells and limiting MMP-2 activity, the synergic use of nanovectors conjugated with CTX and radiotherapy may represent an efficient therapeutic approach to GBM treatment. Advisors/Committee Members: tutor: A. Panerai, co-tutor: C. Gotti, directeur of studies: A. Corsini, PANERAI, ALBERTO EMILIO, CORSINI, ALBERTO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tamborini, M. (2016). A NANOTECHNOLOGY APPROACH FOR GLIOBLASTOMA TARGETED THERAPY. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/351946

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tamborini, M.. “A NANOTECHNOLOGY APPROACH FOR GLIOBLASTOMA TARGETED THERAPY.” 2016. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/351946.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tamborini, M.. “A NANOTECHNOLOGY APPROACH FOR GLIOBLASTOMA TARGETED THERAPY.” 2016. Web. 19 Jan 2021.

Vancouver:

Tamborini M. A NANOTECHNOLOGY APPROACH FOR GLIOBLASTOMA TARGETED THERAPY. [Internet] [Thesis]. Università degli Studi di Milano; 2016. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/351946.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tamborini M. A NANOTECHNOLOGY APPROACH FOR GLIOBLASTOMA TARGETED THERAPY. [Thesis]. Università degli Studi di Milano; 2016. Available from: http://hdl.handle.net/2434/351946

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

21. E. DI PAOLO. TESTING THE EFFICACY OF BRAIN CHOLESTEROL SUPPLEMENTATION AS A POSSIBLE THERAPEUTIC APPROACH FOR HUNTINGTON'S DISEASE.

Degree: 2017, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/503284

► Huntington's disease (HD) is a progressive, fatal, adult-onset, neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene, which encodes an abnormally long… (more)

▼ Huntington's disease (HD) is a progressive, fatal, adult-onset, neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene, which encodes an abnormally long polyglutamine repeat in the huntingtin protein. Clinical features of Huntington's disease include progressive motor dysfunction, cognitive decline, and psychiatric disturbance. Currently, the available drugs are used only for symptomatic management of Huntington's disease, but there is no effective therapy. Several studies indicate that brain cholesterol biosynthesis is reduced in several HD rodent models (Valenza et al. 2005) (Valenza et al. 2007) (Valenza et al. 2010) and data from HD patients also suggested a similar reduction (Leoni et al. 2008) (Leoni et al. 2013). This dysfunction may be detrimental for neuronal cells, especially given that locally synthesized cholesterol is implicated in neurite outgrowth, synapses formation and maintenance, synaptic activity and integrity, and optimal neurotransmitter release (Pfrieger et al. 2003). Based on these evidences, we supposed that in vivo supplying of exogenous cholesterol could rescue aspects of neuronal dysfunction. To verify our hypothesis we used different approaches to deliver exogenous cholesterol to the brain of R6/2 mice (Mangiarini et al. 1996), since peripheral cholesterol is not able to cross the blood brain barrier (BBB). In our first study, the delivery of cholesterol via brain-permeable polymeric nanoparticles (g7-NPs- Chol) rescued synaptic communication, protected from cognitive decline and partially improved global activity in HD mice (Valenza et al. 2015). In a second study we tested the efficacy of increasing doses of cholesterol directly infused into mouse brain by osmotic minipumps. Results demonstrated that high amounts of cholesterol have to be delivered to observe both cognitive and motor functional recovery in R6/2 mice. More recently, we started to investigate a third innovative non-invasive strategy based on intranasal delivery of cholesterol and preliminary results will be discussed. Advisors/Committee Members: scientific tutor: E. Cattaneo, CATTANEO, ELENA, VALENZA, MARTA.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

PAOLO, E. D. (2017). TESTING THE EFFICACY OF BRAIN CHOLESTEROL SUPPLEMENTATION AS A POSSIBLE THERAPEUTIC APPROACH FOR HUNTINGTON'S DISEASE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/503284

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

PAOLO, E. DI. “TESTING THE EFFICACY OF BRAIN CHOLESTEROL SUPPLEMENTATION AS A POSSIBLE THERAPEUTIC APPROACH FOR HUNTINGTON'S DISEASE.” 2017. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/503284.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

PAOLO, E. DI. “TESTING THE EFFICACY OF BRAIN CHOLESTEROL SUPPLEMENTATION AS A POSSIBLE THERAPEUTIC APPROACH FOR HUNTINGTON'S DISEASE.” 2017. Web. 19 Jan 2021.

Vancouver:

PAOLO ED. TESTING THE EFFICACY OF BRAIN CHOLESTEROL SUPPLEMENTATION AS A POSSIBLE THERAPEUTIC APPROACH FOR HUNTINGTON'S DISEASE. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/503284.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

PAOLO ED. TESTING THE EFFICACY OF BRAIN CHOLESTEROL SUPPLEMENTATION AS A POSSIBLE THERAPEUTIC APPROACH FOR HUNTINGTON'S DISEASE. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/503284

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

22. A.C. Rossetti. INFLAMMATION AND VULNERABILITY FOR MAJOR DEPRESSION: IN SEARCH OF COMMON MOLECULAR PATHWAYS.

Degree: 2017, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/468721

► The comprehension of the molecular mechanisms underpinning Major Depression (MD) is becoming a crucial issue in public health, considering that this psychiatric disorder has been… (more)

▼ The comprehension of the molecular mechanisms underpinning Major Depression (MD) is becoming a crucial issue in public health, considering that this psychiatric disorder has been estimated to become the leading cause of disability within 2020. To sustain the critical relevance of the investigation of the molecular bases of this pathology, it is important to underline that a high percentage of patients do not respond to the current pharmacological treatments, despite the number of antidepressant drugs available in the market. MD is a very complex and invalidating pathology, characterized by neuro-vegetative and cognitive symptoms. Among them, the most relevant are alterations in mood and anhedonia, the latter defined as the incapability of feeling pleasure in pleasant circumstances. Although the causes of MD are not fully understood, it is known that the insurgence of this pathology is ascribable to the interaction between a genetic background of susceptibility and environmental factors. Among these factors, stress exposure play a pivotal role in the development of the psychopathology. However, it is important to mention that not all the subjects exposed to stressful situations develop a mental illness, indeed only a small percentage become affected by MD after stress exposure. In this context, people capable to cope with the consequences of stress are defined as resilient and the term “Stress-Resilience” refers to the ability of the subject to actively respond against adverse stimuli. The investigation and the identification of the molecular mechanisms underpinning stress vulnerability and stress resilience appear, thus, of critical importance to identify new therapeutic targets. Among the molecular mechanisms involved in depression pathophysiology, compelling clinical and preclinical evidence support a role for alteration of the inflammatory system, which is also affected by stressful experiences. With these premises, the general aim of my study was to investigate the relationship between major depression and neuroinflammation, in order to provide new information about the molecular background of this pathology. In particular, by the use of different experimental approaches, we evaluated the impact of stress on neuroinflammation and the potential anti-inflammatory properties of pharmacological treatment with the antidepressants agomelatine and imipramine or the antipsychotic lurasidone. Our results demonstrated that neuroinflammation is strictly associated with the insurgence of stress-induced behavioral alterations in adult male rats tested for sucrose consumption. Indeed anhedonic-like animals showed increased levels of pro-inflammatory cytokines and markers of microglia activation, especially in the dorsal hippocampus. Moreover, we found that chronic pharmacological treatment with agomelatine, imipramine and lurasidone was not only able to normalize the alterations in sucrose intake, but also to modulate the pro-inflammatory effects of chronic stress exposure. In this context, we found that agomelatine was… Advisors/Committee Members: tutor: R. MOLTENI, coordinatore: A. CORSINI, MOLTENI, RAFFAELLA, CORSINI, ALBERTO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rossetti, A. (2017). INFLAMMATION AND VULNERABILITY FOR MAJOR DEPRESSION: IN SEARCH OF COMMON MOLECULAR PATHWAYS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/468721

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rossetti, A.C.. “INFLAMMATION AND VULNERABILITY FOR MAJOR DEPRESSION: IN SEARCH OF COMMON MOLECULAR PATHWAYS.” 2017. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/468721.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rossetti, A.C.. “INFLAMMATION AND VULNERABILITY FOR MAJOR DEPRESSION: IN SEARCH OF COMMON MOLECULAR PATHWAYS.” 2017. Web. 19 Jan 2021.

Vancouver:

Rossetti A. INFLAMMATION AND VULNERABILITY FOR MAJOR DEPRESSION: IN SEARCH OF COMMON MOLECULAR PATHWAYS. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/468721.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rossetti A. INFLAMMATION AND VULNERABILITY FOR MAJOR DEPRESSION: IN SEARCH OF COMMON MOLECULAR PATHWAYS. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/468721

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

23. G.L. Pepe. THE PHYSIOLOGICAL RESPONSE OF RESIDENT MACROPHAGES TO THE ESTROGEN SURGE.

Degree: 2017, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/469243

► I macrofagi sono cellule immunitarie che risiedono in quasi tutti i tessuti dell’organismo e svolgono un ruolo chiave nella difesa dell'organismo contro le infezioni dovute… (more)

▼ I macrofagi sono cellule immunitarie che risiedono in quasi tutti i tessuti dell’organismo e svolgono un ruolo chiave nella difesa dell'organismo contro le infezioni dovute a patogeni e nelle risposte infiammatorie e un’importante funzione nel rimodellamento tissutale fisiologico. Essi sono in grado di rispondere ad una varietà di stimoli microambientali, adottando diversi stati di attivazione a seconda del contesto e del segnale di attivazione, con il fine di eliminare l’agente patogeno e ripristinare l’omeostasi. L’uomo mostra forti differenze legate al sesso nella risposta immunitaria alle infezioni e nell’autoimmunità, suggerendo che gli ormoni sessuali svolgono un importante ruolo nel modulare la risposta immunitaria. In effetti, gli estrogeni regolano diversi pathways del sistema immunitario innato e adattativo, nonché lo sviluppo delle cellule immunitarie. Studi precedenti hanno dimostrato che il 17β-estradiolo (E2) è in grado di modulare la reattività dei macrofagi durante l'infiammazione, down-regolando l'espressione di geni infiammatori. Tuttavia, non sono ancora del tutto chiari i dettagli molecolari attraverso cui gli estrogeni esercitano la loro attività anti-infiammatoria. Al fine di colmare questa lacuna, abbiamo effettuato un’analisi di trascrittomica, seguita da saggi biologici, dei macrofagi peritoneali isolati da topi femmina, sia in seguito a diversi livelli di estrogeni endogeni, sia in seguito a trattamento con estrogeni per breve e lungo termine. L’analisi dei dati bioinformatici ha mostrato che E2 modula importanti processi biologici coinvolti nella fisiologia dei macrofagi; tra questi emergono come più significativi la proliferazione e l'induzione di un fenotipo anti-infiammatorio e pro-risolutivo. Abbiamo quindi confermato questi dati dimostrando, attraverso l'analisi di espressione genica, l’analisi citofluorimetrica e l’incorporazione di BrdU, che l'indice di proliferazione e il numero di macrofagi residenti aumentano in seguito ad un incremento dei livelli di estrogeno. Inoltre, abbiamo dimostrato che il trattamento con estrogeno induce nei macrofagi un processo di attivazione dinamico che evolve verso un fenotipo pro-risolutivo attraverso la sintesi di IL10. Inoltre questa azione dell’ormone sui macrofagi è mantenuta anche durante il corso di un’infiammazione peritoneale. Al fine di estendere le nostre osservazioni ad una diversa popolazione di macrofagi, abbiamo analizzato la risposta della microglia al trattamento con estrogeni mediante l'analisi di espressione genica. I risultati hanno evidenziato la diversità nella risposta a E2 dei macrofagi che risiedono nei diversi tessuti e l’influenza del microambiente sulla reattività dei macrofagi a E2, inoltre, forniscono un elenco di geni bersagli dell’estrogeno che possono essere utilizzati come biomarcatori per studi farmacologici e traslazionali. Complessivamente, questi risultati approfondiscono la nostra conoscenza sulle interazioni del sistema endocrino-immunitario e permettono studi futuri sulla loro rilevanza nella patogenesi e… Advisors/Committee Members: tutor: E. Vegeto, coordinatore: A. Corsini, VEGETO, ELISABETTA, CORSINI, ALBERTO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pepe, G. (2017). THE PHYSIOLOGICAL RESPONSE OF RESIDENT MACROPHAGES TO THE ESTROGEN SURGE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/469243

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Pepe, G.L.. “THE PHYSIOLOGICAL RESPONSE OF RESIDENT MACROPHAGES TO THE ESTROGEN SURGE.” 2017. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/469243.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Pepe, G.L.. “THE PHYSIOLOGICAL RESPONSE OF RESIDENT MACROPHAGES TO THE ESTROGEN SURGE.” 2017. Web. 19 Jan 2021.

Vancouver:

Pepe G. THE PHYSIOLOGICAL RESPONSE OF RESIDENT MACROPHAGES TO THE ESTROGEN SURGE. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/469243.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Pepe G. THE PHYSIOLOGICAL RESPONSE OF RESIDENT MACROPHAGES TO THE ESTROGEN SURGE. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/469243

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

24. A. DI MINNO. DIET, OXIDATIVE STRESS STATUS AND INFLAMMATION IN PATIENTS WITH CARDIOVASCULAR DISEASE: IN SEARCH FOR A LINK.

Degree: 2018, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/544432

► BACKGROUND. Previous studies have provided a rationale for understanding the health benefits of Mediterranean Diet (MD) against a variety of chronic diseases. OBJECTIVES AND EVIDENCE… (more)

▼ BACKGROUND. Previous studies have provided a rationale for understanding the health benefits of Mediterranean Diet (MD) against a variety of chronic diseases. OBJECTIVES AND EVIDENCE ANALYZED. We have used new data from the IMPROVE Study -a multicenter, longitudinal, observational study, carried out in five European countries- and fresh information from the RISMED, a study carried out in our Institution in subjects with a recent history of coronary revascularization to address: 1) the relationship between MD adherence and carotid intima-media thickness (c-IMT) progression; 2) whether such relationship is similar in populations with different nutritional patterns, and 3) whether the relationship between MD, baseline carotid IMT, and clinical events involves changes in inflammation, oxidative stress, and fatty acid [FA] composition. FINDINGS. In the analysis of the IMPROVE Study we have found: 1) a significant negative trend between most of the c-IMT-progression variables and a new relatively simple food frequency questionnaire to evaluate a Mediterranean-like dietary pattern (MLPD) score, validated a priori vs VEs in different European Countries; 2) that the significant association between MLDP adherence and VEs is independent of baseline c-IMT and c-IMT progression, and 3) that MLDP score adherence is associated to changes both in inflammatory markers and white blood cells counts. Information from the RISMED Study documented that: 1) MD adherence significantly affects indices of inflammation and oxidative stress balance; 2) blood FA profile is an index of the quality of food intake which might be used to estimate diet quality and compliance with nutritional advices; 3) it is possible to favorably modify patients’ plasma FA profiles by consuming a MD, and 4) a relationship exists between inflammatory markers/oxidative stress status and modifications of the blood FA pattern. CONCLUSIONS AND RELEVANCE. MD adherence is key to reduce oxidative stress, inflammation and VEs in subjects at risk of cardiovascular events. Since common approaches that simultaneously target old and new risk factors for cardiovascular disease enhance cardio-protection and longevity, the need for evaluating MD as a strategy for a better health at older ages should be explored thoroughly. Advisors/Committee Members: tutor: M. Camera, coordinatore: A. L. Catapano, CATAPANO, ALBERICO LUIGI.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

MINNO, A. D. (2018). DIET, OXIDATIVE STRESS STATUS AND INFLAMMATION IN PATIENTS WITH CARDIOVASCULAR DISEASE: IN SEARCH FOR A LINK. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/544432

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

MINNO, A. DI. “DIET, OXIDATIVE STRESS STATUS AND INFLAMMATION IN PATIENTS WITH CARDIOVASCULAR DISEASE: IN SEARCH FOR A LINK.” 2018. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/544432.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

MINNO, A. DI. “DIET, OXIDATIVE STRESS STATUS AND INFLAMMATION IN PATIENTS WITH CARDIOVASCULAR DISEASE: IN SEARCH FOR A LINK.” 2018. Web. 19 Jan 2021.

Vancouver:

MINNO AD. DIET, OXIDATIVE STRESS STATUS AND INFLAMMATION IN PATIENTS WITH CARDIOVASCULAR DISEASE: IN SEARCH FOR A LINK. [Internet] [Thesis]. Università degli Studi di Milano; 2018. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/544432.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

MINNO AD. DIET, OXIDATIVE STRESS STATUS AND INFLAMMATION IN PATIENTS WITH CARDIOVASCULAR DISEASE: IN SEARCH FOR A LINK. [Thesis]. Università degli Studi di Milano; 2018. Available from: http://hdl.handle.net/2434/544432

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

25. F.M. Fasoli. RECETTORI COLINERGICI NICOTINICI NEURONALI E NON-NEURONALI: ANALISI DEGLI EFFETTI DEL TRATTAMENTO CRONICO CON NICOTINA IN CONDIZIONI FISIOLOGICHE E PATOLOGICHE.

Degree: 2016, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/347546

►

I nAChRs sono largamente espressi nel sistema nervoso centrale (SNC) e periferico (SNP), dove funzionano come i classici canali ionici attivati da ligando, facilitando l’ingresso… (more)

▼

I nAChRs sono largamente espressi nel sistema nervoso centrale (SNC) e periferico (SNP), dove funzionano come i classici canali ionici attivati da ligando, facilitando l’ingresso di calcio e promuovendo il rilascio di neurotrasmettitori. L’esposizione cronica alla nicotina, agonista che mima l’azione del ligando endogeno acetilcolina e componente additiva presente nel tabacco, determina una serie di adattamenti cellulari, che sono responsabili dell’instaurarsi della dipendenza da fumo di sigaretta e degli effetti neurobiologici e fisiologici ad essa associati. L’eterogeneità funzionale di questa famiglia recettoriale, ha stimolato negli anni interesse per il loro studio e per approfondire gli effetti del trattamento cronico e dell’astinenza da nicotina. Nella prima parte di questo lavoro, ci siamo focalizzati sugli effetti in vivo dell’esposizione cronica a nicotina. In particolare, abbiamo analizzato gli effetti sul recettore nativo α4β2; tale sottotipo può esistere in due differenti stechiometrie, con due o tre copie della subunità α nel pentamero, che presentano diverse proprietà funzionali e sono differentemente regolate dal trattamento cronico con nicotina. Gli effetti addittivi della nicotina, sostanza di per se non cancerogena, incentivano il consumo di tabacco, e la presenza nel fumo di sigaretta di sostanze che sono potenti agenti cancerogeni, quali le nitrosamine NNN e NNK e le amine eterocicliche, determinano la comparsa nel DNA di mutazioni, che portano alla trasformazione neoplastica e allo sviluppo di cancro. La correlazione consumo di tabacco-insorgenza di tumore, è particolarmente evidente nel caso del tumore polmonare, dove la nicotina sostiene la crescita tumorale e partecipa alla fase di metastatizzazione, regolando signaling intracellulari che mediano proliferazione cellulare, apoptosi e angiogenesi. La recente scoperta che i nAChRs sono espressi anche in cellule non-neuronali, quali cellule endoteliali, cheratinociti, cellule del sistema immunitario e cellule gliali, ha spinto numerosi gruppi a indagare il ruolo dei nAChRs anche in tessuti extra-neuronali e in condizioni patologiche. La seconda parte di questo progetto ha avuto lo scopo di determinare quale fosse l’effetto del trattamento con nicotina e con antagonisti nicotinici sulla crescita di cellule di glioma e su colture primarie umane di glioblastoma, poiché rimane ancora da chiarire il ruolo del fumo sull’eziologia dei gliomi.

Neuronal nicotinic acetylcholine receptors (nAChRs) are a heterogeneous family of ligand-gated ion channels expressed in the central nervous system (CNS) that by responding to the endogenous neurotransmitter acetylcholine (ACh) are implicated in a variety of physiological and pathophysiological processes. nAChRs have a very widespread and non-uniform distribution; the majority have a presynaptic and/or pre-terminal localisation, where they modulate the release of many neurotransmitters, but some of them also have a somatodendritic, post-synaptic localisation, where they depolarise neurons, increase their…

Advisors/Committee Members: coordinatore: A. Corsini, relatore: M. Sala, correlatore: C. Gotti, CORSINI, ALBERTO.

Subjects/Keywords: NICOTINE; Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fasoli, F. (2016). RECETTORI COLINERGICI NICOTINICI NEURONALI E NON-NEURONALI: ANALISI DEGLI EFFETTI DEL TRATTAMENTO CRONICO CON NICOTINA IN CONDIZIONI FISIOLOGICHE E PATOLOGICHE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/347546

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fasoli, F.M.. “RECETTORI COLINERGICI NICOTINICI NEURONALI E NON-NEURONALI: ANALISI DEGLI EFFETTI DEL TRATTAMENTO CRONICO CON NICOTINA IN CONDIZIONI FISIOLOGICHE E PATOLOGICHE.” 2016. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/347546.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fasoli, F.M.. “RECETTORI COLINERGICI NICOTINICI NEURONALI E NON-NEURONALI: ANALISI DEGLI EFFETTI DEL TRATTAMENTO CRONICO CON NICOTINA IN CONDIZIONI FISIOLOGICHE E PATOLOGICHE.” 2016. Web. 19 Jan 2021.

Vancouver:

Fasoli F. RECETTORI COLINERGICI NICOTINICI NEURONALI E NON-NEURONALI: ANALISI DEGLI EFFETTI DEL TRATTAMENTO CRONICO CON NICOTINA IN CONDIZIONI FISIOLOGICHE E PATOLOGICHE. [Internet] [Thesis]. Università degli Studi di Milano; 2016. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/347546.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fasoli F. RECETTORI COLINERGICI NICOTINICI NEURONALI E NON-NEURONALI: ANALISI DEGLI EFFETTI DEL TRATTAMENTO CRONICO CON NICOTINA IN CONDIZIONI FISIOLOGICHE E PATOLOGICHE. [Thesis]. Università degli Studi di Milano; 2016. Available from: http://hdl.handle.net/2434/347546

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

26. C. Vitali. EXAMINING THE DIVERSE CONTRIBUTIONS OF EL TO SYSTEMIC LIPID METABOLISM.

Degree: 2017, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/468488

► La Lipasi Endoteliale (EL) è l’ultimo membro identificato della famiglia delle lipasi plasmatiche dei trigliceridi (plasma triglyceride lipase). EL ha una maggior specificità per i… (more)

▼ La Lipasi Endoteliale (EL) è l’ultimo membro identificato della famiglia delle lipasi plasmatiche dei trigliceridi (plasma triglyceride lipase). EL ha una maggior specificità per i fosfolipidi (PL) che trigliceridi (TG) ed è un enzima chiave nella regolazione dei livelli di HDL sia in vitro che in vivo. Studi più recenti hanno indicato che EL è in anche grado di promuovere il catabolismo delle lipoproteine contenenti apoB. Nell’uomo, varianti nel gene che codifica per EL, sono state associate a più elevati livelli di colesterolo HDL ma sorprendentemente ciò non si traduce in un ridotto rischio cardiovascolare. Studi clinici hanno evidenziato che la concentrazione e attività di EL sono positivamente associate alla severità dei tratti tipici della sindrome metabolica come indice di massa corporea, obesità centrale, infiammazione, insulino resistenza e profilo lipoproteico più aterogenico. Quale sia il nesso causale di questa associazione non è noto e ad oggi non è possibile stabilire se elevati livelli di EL siano alla base dell’eziologia del profilo osservato o se, al contrario, siano un tratto secondario. Scopo di questa tesi è di stabilire quale sia il ruolo di EL nel metabolismo delle lipoproteine ricche in trigliceridi (TRL) e di investigare la relazione tra attività di EL, metabolismo lipidico epatico e sviluppo dei tratti caratteristici della sindrome metabolica in vivo. Al fine di poter comparare non solo la severità ma anche il tempo di insorgenza della sindrome metabolica, in presenza o assenza di EL, sono stati utilizzati topi controllo (wild type, WT) e topi con deficit di EL (EL-KO), sottoposti ad una dieta ricca di grassi a lungo termine. I risultati hanno dimostrato che i topi EL-KO accumulano significativamente più peso rispetto ai WT, sviluppano una più severa intolleranza al glucosio, e uno stato metainfiammatorio. La comparsa di questi tratti è accompagnata da una severa dislipidemia, ancora una volta più marcata nei topi EL-KO rispetto ai WT. La differenza più significativa, tuttavia, è lo sproporzionato aumento dei livelli di TG in risposta alla dieta. All’origine di questo fenotipo vi è l’accumulo di lipoproteine post-prandiali ricche di TG. Esperimenti cinetici in vivo hanno dimostrato che la clearance di TRL radiomarcate è molto ridotta nei topi EL-KO e questo fenomeno è dovuto a una ridotta lipolisi, mentre la secrezione epatica di TG non è affetta. Quando l’attività di EL nei confronti delle TRL marcate è stata testata in vitro, è emerso che EL potrebbe fungere da facilitatore dell’attività della lipasi lipoproteica (LPL). Di conseguenza, EL potrebbe rivestire un ruolo importante nel ridurre I livelli di TG nel contesto dell’iperlipemia postprandiale e questo effetto potrebbe essere mediato sia da un’attività lipolitica diretta, sia dalla facilitazione dell’attività lipolitica di LPL. Infine, la valutazione della funzionalità epatica ha rivelato che i topi EL-KO sviluppano una franca steatosi. La capacità del fegato di captare gli acidi grassi derivanti dai TG, è ridotta nei topi con deficit… Advisors/Committee Members: Tutor: L.Calabresi, Coordinatore: A.Corsini, CALABRESI, LAURA, CALABRESI, LAURA, CORSINI, ALBERTO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Vitali, C. (2017). EXAMINING THE DIVERSE CONTRIBUTIONS OF EL TO SYSTEMIC LIPID METABOLISM. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/468488

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Vitali, C.. “EXAMINING THE DIVERSE CONTRIBUTIONS OF EL TO SYSTEMIC LIPID METABOLISM.” 2017. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/468488.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Vitali, C.. “EXAMINING THE DIVERSE CONTRIBUTIONS OF EL TO SYSTEMIC LIPID METABOLISM.” 2017. Web. 19 Jan 2021.

Vancouver:

Vitali C. EXAMINING THE DIVERSE CONTRIBUTIONS OF EL TO SYSTEMIC LIPID METABOLISM. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/468488.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Vitali C. EXAMINING THE DIVERSE CONTRIBUTIONS OF EL TO SYSTEMIC LIPID METABOLISM. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/468488

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

27. C. Vanetti. SEX-DEPENDENT PROPERTIES OF HUMAN ENDOTHELIAL CELLS: FOCUS ON ENOS.

Degree: 2017, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/469139

► Nonostante le malattie cardiovascolari siano percepite come malattie in prevalenza maschili, numerosi dati clinici ed epidemiologici dimostrano che riguardano anche le donne. Quello che differenzia… (more)

▼ Nonostante le malattie cardiovascolari siano percepite come malattie in prevalenza maschili, numerosi dati clinici ed epidemiologici dimostrano che riguardano anche le donne. Quello che differenzia i due generi è che nelle donne si presentano con un ritardo di almeno 10 anni rispetto agli uomini in quanto si ritiene che le donne siano protette, perlomeno fino alla menopausa, dagli estrogeni. La solidità dei dati clinici ed epidemiologici non si associa però a un’altrettanto approfondita conoscenza dei meccanismi biologici e molecolari che stanno alla base di queste differenze. Va ricordato che nella complessa serie di eventi che sfocia nell’aterosclerosi e nella malattia cardiovascolare, il primo passaggio è rappresentato da una perdita di funzionalità dell’endotelio, la cosiddetta disfunzione endoteliale. Poiché molto poco si conosce sulle proprietà innate di cellule endoteliali (EC) maschili e femminili ci è parso particolarmente interessante indagare le caratteristiche di EC umane in coltura primaria derivate da cordoni ombelicali di donatori di sesso maschile o femminile (HUVECs, abbreviate rispettivamente in M-EC e F-EC). Nostro primo obiettivo è stato lo studio dell’influenza degli estrogeni sulle proprietà delle M-EC e F-EC. A tale scopo, abbiamo utilizzato un terreno di coltura privo di ormoni contenente siero fetale bovino sottoposto a procedura di stripping (CS-FBS). In queste condizioni, sia le M-EC che le F-EC hanno mostrato una riduzione della crescita e delle proprietà angiogeniche in vitro che la riaggiunta degli ormoni sessuali nel mezzo di coltura non è stata in grado di prevenire. Poiché l’effetto inibitorio di CS-FBS è revertito dall’aggiunta di FBS normale al terreno di coltura, ci siamo focalizzati sugli acidi grassi (FA) per due ragioni: i) non sono presenti nel CS-FBS; ii) la loro ossidazione è necessaria per la crescita delle EC e per l’angiogenesi. Infatti, l’aggiunta di acetato, un donatore di acetil-CoA, o di acido palmitico è stata in grado di revertire significativamente in entrambi i sessi l’inibizione della crescita e dello sprouting indotta da CS-FBS. Questi risultati confermano il ruolo centrale degli FA nella fisiologia delle EC sia maschili che femminili, e suggeriscono cautela nell’utilizzo di terreni contenenti CS-FBS per lo studio delle EC. In una successiva serie di esperimenti, abbiamo rivolto la nostra attenzione all’espressione e all’attività di eNOS in M-EC e F-EC, considerato il ruolo cruciale dell’enzima e del suo prodotto NO nella fisiologia dell’endotelio. Abbiamo innanzitutto osservato che le F-EC esprimono costitutivamente una maggiore quantità di eNOS, a livello sia di mRNA che di proteina, rispetto alle M-EC. Alla ricerca del significato biologico di questa differenza, abbiamo osservato che le F-EC hanno maggiori capacità migratorie rispetto alle M-EC, e soprattutto che la motilità di F-EC e M-EC differisce in maniera significativa nella dipendenza da eNOS. La migrazione delle F-EC è infatti ridotta dal silenziamento e dall’inibizione farmacologica di eNOS,… Advisors/Committee Members: tutor: M.G. Cattaneo, coordinatore: A. Corsini, CATTANEO, MARIA GRAZIA, CORSINI, ALBERTO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Vanetti, C. (2017). SEX-DEPENDENT PROPERTIES OF HUMAN ENDOTHELIAL CELLS: FOCUS ON ENOS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/469139

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Vanetti, C.. “SEX-DEPENDENT PROPERTIES OF HUMAN ENDOTHELIAL CELLS: FOCUS ON ENOS.” 2017. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/469139.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Vanetti, C.. “SEX-DEPENDENT PROPERTIES OF HUMAN ENDOTHELIAL CELLS: FOCUS ON ENOS.” 2017. Web. 19 Jan 2021.

Vancouver:

Vanetti C. SEX-DEPENDENT PROPERTIES OF HUMAN ENDOTHELIAL CELLS: FOCUS ON ENOS. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/469139.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Vanetti C. SEX-DEPENDENT PROPERTIES OF HUMAN ENDOTHELIAL CELLS: FOCUS ON ENOS. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/469139

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

28. S. Carnevali. THROMBOXANE PROSTANOID RECEPTOR: FUNCTION, ACTIVATION AND POSSIBLE TARGET FOR CARDIOVASCULAR PROTECTION.

Degree: 2017, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/468658

► Abstract In the last few years cardiovascular diseases are considered one of the major cause of death, and one of the main player is TXA2… (more)

▼ Abstract In the last few years cardiovascular diseases are considered one of the major cause of death, and one of the main player is TXA2 (Thromboxane A2), a product of arachidonic acid metabolism generated from the activity of thromboxane synthase on prostaglandin H2 intermediate via cyclooxygenase (COX). TXA2 is responsible for platelets activation and aggregation, thrombus formation, and thus it can cause stroke and myocardial infarction. TXA2 exerts its actions through the TP receptor, a widely expressed GPCR (G protein coupled receptor) present in many cell types among different organ systems. During my thesis I worked to shed light on the mechanism of activation of TP receptor WT (wild type), and two of its mutants (TPαE129V and TPαR130V) of the highly conserved motif E/DRY, in order to assign each receptor state to the CTC (Cubic Ternary Complex) model. In particular, using the new technique SPASM (Systematic Protein Affinity Strength Modulation), the goal was to understand the conformational state of TPαWT and mutants in basal condition, i.e. their coupling or uncoupling states with G proteins. The results obtained suggest that TPαE129V (SAM-super active mutant) is in an ‘active-like’ conformation corresponding to the RG state (inactive, coupled to G protein), on the contrary, TPαR130V (loss of function mutant) seems to display an inactive R conformation (uncoupled to G protein), as envisioned by CTC model. The study of TPα receptor induced us to consider a second focus in my thesis: TPα receptor as a possible target for new chemical entities with both COX-2 selectivity (COXIB) and TP antagonist activity. New compounds were obtained modulating the structure of existing drugs (lumiracoxib and RC 0) to obtain novel multitarget NSAIDs (Nonsteroidal Anti-inflammatory Drug) endowed with balanced COXIB and TP receptor antagonist properties. Antagonistic activity on the TP receptor was examined for all compounds by evaluating the inhibition of platelets aggregation induced by the stable TXA2 receptor agonist U46619. COX-1 and COX-2 inhibition were assessed in human washed platelets (challenged by the calcium ionophoreA23187) and human lympho-monocytes suspension (stimulated with lipopolysaccharides), respectively. COX selectivity was determined by calculating IC50 values ratio (COX-2/COX-1) obtained from concentration-response curves. Among the lumiracoxib derivatives, the tetrazole compound 18 and the trifluoromethan sulfonamido-isoster 20 were the more active antagonists at the TP receptor, preventing human platelet aggregation and intracellular signalling, with pA2 values statistically higher than lumiracoxib. Comparative data regarding COX- 2/COX-1 selectivity showed that while compounds 18 and 7 were rather potent and selective COX-2 inhibitors, compound 20 was somehow less potent and selective for COX-2. Among the RC 0 derivatives, of particular interest resulted compounds SWE 74, CP 7 and CP 8, because they demonstrated to be fairly selective for COX-2 enzyme, but they… Advisors/Committee Members: tutor: A. Sala, coordinatore: A. Corsini, SALA, ANGELO, CORSINI, ALBERTO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Carnevali, S. (2017). THROMBOXANE PROSTANOID RECEPTOR: FUNCTION, ACTIVATION AND POSSIBLE TARGET FOR CARDIOVASCULAR PROTECTION. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/468658

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Carnevali, S.. “THROMBOXANE PROSTANOID RECEPTOR: FUNCTION, ACTIVATION AND POSSIBLE TARGET FOR CARDIOVASCULAR PROTECTION.” 2017. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/468658.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Carnevali, S.. “THROMBOXANE PROSTANOID RECEPTOR: FUNCTION, ACTIVATION AND POSSIBLE TARGET FOR CARDIOVASCULAR PROTECTION.” 2017. Web. 19 Jan 2021.

Vancouver:

Carnevali S. THROMBOXANE PROSTANOID RECEPTOR: FUNCTION, ACTIVATION AND POSSIBLE TARGET FOR CARDIOVASCULAR PROTECTION. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/468658.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Carnevali S. THROMBOXANE PROSTANOID RECEPTOR: FUNCTION, ACTIVATION AND POSSIBLE TARGET FOR CARDIOVASCULAR PROTECTION. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/468658

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

29. S.C. Pelucchi. INTEGRATION OF DIFFERENT PATHWAYS IN EARLY STAGE OF ALZHEIMER'S DISEASE PATHOGENESIS, FROM ACTIN REMODELLING TO AΒ FORMATION.

Degree: 2017, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/469829

► Alzheimer disease (AD) pathogenesis is the result of an interplay of crossing pathways, as amyloid cascade and synaptic failure. It has been shown that Aβ… (more)

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pelucchi, S. (2017). INTEGRATION OF DIFFERENT PATHWAYS IN EARLY STAGE OF ALZHEIMER'S DISEASE PATHOGENESIS, FROM ACTIN REMODELLING TO AΒ FORMATION. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/469829

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Pelucchi, S.C.. “INTEGRATION OF DIFFERENT PATHWAYS IN EARLY STAGE OF ALZHEIMER'S DISEASE PATHOGENESIS, FROM ACTIN REMODELLING TO AΒ FORMATION.” 2017. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/469829.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Pelucchi, S.C.. “INTEGRATION OF DIFFERENT PATHWAYS IN EARLY STAGE OF ALZHEIMER'S DISEASE PATHOGENESIS, FROM ACTIN REMODELLING TO AΒ FORMATION.” 2017. Web. 19 Jan 2021.

Vancouver:

Pelucchi S. INTEGRATION OF DIFFERENT PATHWAYS IN EARLY STAGE OF ALZHEIMER'S DISEASE PATHOGENESIS, FROM ACTIN REMODELLING TO AΒ FORMATION. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/469829.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Pelucchi S. INTEGRATION OF DIFFERENT PATHWAYS IN EARLY STAGE OF ALZHEIMER'S DISEASE PATHOGENESIS, FROM ACTIN REMODELLING TO AΒ FORMATION. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/469829

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

30. L. Culotta. DECIPHERING THE ROLE OF SULFOTRANSFERASE 4A1 IN BRAIN DEVELOPMENT AND NEURONAL FUNCTIONING.

Degree: 2018, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/545256

► Cytosolic sulfotransferases (SULTs) are enzymes that transfer a sulfuryl group from the obligate donor PAPS (3’-phosphoadenosine 5’-phosphosulfate) onto a variety of exogenous and endogenous substrates… (more)

▼ Cytosolic sulfotransferases (SULTs) are enzymes that transfer a sulfuryl group from the obligate donor PAPS (3’-phosphoadenosine 5’-phosphosulfate) onto a variety of exogenous and endogenous substrates (Negishi 2001). In 2000, a novel member of this family (SULT4A1) was isolated from human and rat brain (Falany 2000). To date, the exact substrate and function of SULT4A1 are not fully addressed but since it is highly conserved and expressed extensively, and almost exclusively, in the brain, it is possible that SULT4A1 may have an important role in the central nervous system. Moreover, some recent reports have associated polymorphisms in the SULT4A1 gene with susceptibility to schizophrenia (Brennan 2005; Meltzer 2008); SULT4A1 has been suggested to be associated with neurological symptoms of Phelan-McDermid Syndrome (Disciglio 2014) and altered levels of SULT4A1 protein have been observed in bipolar and Alzheimer’s patients (Wang 2003; Ryan 2006). Given this background, we decided to investigate the still unknown role of SULT4A1 within neuron development and functioning. We started evaluating the physiological expression of SULT4A1 in the brain areas mainly involved in neuropsychiatric and neurodevelopmental disorders. To this purpose, we performed western blot analyses of total lysates of hippocampus, striatum, cerebral cortex and cerebellum dissected from adult mice (P60). Our results showed that SULT4A1 is highly expressed in all the analyzed areas, especially in cortex and in cerebellum. Moreover, area-specific expression of SULT4A1 appears to be similar between adult male and female mice. Considering the possible implication of SULT4A1 in the pathogenesis of neurodevelopmental disorders, a major point for our study was the evaluation of SULT4A1 expression during physiological neuronal maturation. To this purpose, we analyzed by western blot rat primary neuronal cultures at different stages of neuron maturation, which are Day-In-Vitro (DIV) 1, 7 and 14. From the results of these analyses, it was inferable that the expression of SULT4A1 appreciably rises during neuronal maturation, going from an almost undetectable level at DIV1 to an almost 4-fold greater level at DIV14 in cortical cultures. This result was confirmed by immunofluorescence (IF) staining of the same cultures where the protein showed a cytoplasmic localization and its level of expression steadily increased from DIV1 to DIV14. IF results also suggested that SULT4A1 is mainly expressed in GAD67-positive inhibitory neurons, in particular in Calbindin- and Parvalbumin-positive neurons. Therefore, to better determine SULT4A1 expression in human neurons, we obtained peripheral blood mononuclear cells (PBMCs) from control healthy individuals and reprogrammed them into induced Pluripotent Stem Cells (iPSCs). iPSC-derived neural stem cells (NSC) were differentiated into neurons for at least 50 days, time necessary to obtain MAP2-positive mature neurons. SULT4A1 expression was evaluated during neuronal maturation from NSC stage to mature neuron and the… Advisors/Committee Members: tutor: M. Di Luca, co-tutor: C. Verpelli, coordinatore: A. L. Catapano, DILUCA, MONICA MARIA GRAZIA, CATAPANO, ALBERICO LUIGI.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA (6^th Edition):

Culotta, L. (2018). DECIPHERING THE ROLE OF SULFOTRANSFERASE 4A1 IN BRAIN DEVELOPMENT AND NEURONAL FUNCTIONING. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/545256

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Culotta, L.. “DECIPHERING THE ROLE OF SULFOTRANSFERASE 4A1 IN BRAIN DEVELOPMENT AND NEURONAL FUNCTIONING.” 2018. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/545256.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Culotta, L.. “DECIPHERING THE ROLE OF SULFOTRANSFERASE 4A1 IN BRAIN DEVELOPMENT AND NEURONAL FUNCTIONING.” 2018. Web. 19 Jan 2021.

Vancouver:

Culotta L. DECIPHERING THE ROLE OF SULFOTRANSFERASE 4A1 IN BRAIN DEVELOPMENT AND NEURONAL FUNCTIONING. [Internet] [Thesis]. Università degli Studi di Milano; 2018. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/545256.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Culotta L. DECIPHERING THE ROLE OF SULFOTRANSFERASE 4A1 IN BRAIN DEVELOPMENT AND NEURONAL FUNCTIONING. [Thesis]. Università degli Studi di Milano; 2018. Available from: http://hdl.handle.net/2434/545256

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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