187,622 research outputs found
Brevi riflessioni sulla scrittura poetica di Alessandro Agostinelli
No full textObra ressenyada: Alessandro AGOSTINELLI, Scrittura poetic
La Nad chinasi, enzima chiave della biosintesi del Nad(P)+ in mycobacterium tubercolosis, quale target per la progettazione razionale di nuovi inibitori ad attività antibiotica
No full textGli enzimi coinvolti nel metabolismo del NAD(P) rappresentano interessanti target per la ricerca di farmaci antitubercolari.
La fosforilazione diretta del NAD da parte della NAD chinasi è l’unica via ad oggi conosciuta per la produzione di NADP in cellule sia procariotiche che eucariotiche. La validità di questo enzima come target farmacologico è basata sulla sua essenzialità nella vitalità di Mycobacterium tuberculosis, e sulle differenti caratteristiche fra gli enzimi batterico e umano.
Allo scopo di trovare un inibitore selettivo per la NAD chinasi di M. tuberculosis, sono state eseguite analisi strutturali di quest’enzima, per il design di analoghi modificati del NAD e del poli(P).
Gli analoghi dinucleoside disolfuro del NAD sono risultati inibitori innovativi selettivi per il sito attivo delle NAD chinasi. Gli analoghi dei dinucleotidi polifosfato invece, e del poli(P), hanno mostrato una debole selettività per la mtNADK in quanto, mentre l’enzima umano è strettamente ATP-dipendente, quello micobatterico è in grado di utilizzare anche il poli(P) come donatore di fosfato. Le differenze esistenti nel comportamento catalitico e nella specificità di substrato fra i due enzimi saranno sfruttate per l’identificazione di farmaci antitubercolari innovativi.
Anche gli inibitori dell’enzima umano sono interessanti in quanto possono essere usati per ridurre l’apporto di NADPH esogeno durante stress ossidativo e in cellule tumorali. Recentemente, è stato proposto che le specie reattive all’ossigeno (ROS) derivanti dalla NADPH ossidasi svolgono un ruolo importante nell’angiogenesi fisiologica e patologica, rendendo quest’enzima un eccellente target per la terapia anticancro. La soppressione della NADPH ossidasi tramite l’inibizione della NAD chinasi potrebbe quindi mostrare effetti antitumorali.
Infine è stata indagata l’esistenza di un altro gene umano codificante per una NAD chinasi. La proteina C5orf33, una putativa NAD chinasi, è stata clonata ed espressa in Escherichia coli e parzialmente purificata per indagarne l’attività chinasica
La donazione mista
No full textIl contributo ricostruisce la figura della donazione mista, a partire dal suo dibattuto inquadramento sistematico, indagando le caratteristiche con le quali il contratto è adottato nella prassi, e presentando le soluzioni più ricorrenti alle questioni applicative che il ricorso ad esso ingenera
A 12-month longitudinal study of calcium metabolism and bone turnover during valproate monotherapy.
No full textBackground and purpose: Treatment with valproate (VPA) can cause changes in bone mineral metabolism, but the real influences and the underlying pathologic mechanisms are still unclear and under discussion. The aim of this study was to examine the changes on calcium metabolism and bone turnover in post-pubertal male patients with newly diagnosed idiopathic generalized epilepsy (IGE) before (baseline evaluation) and 12 months after VPA monotherapy (second evaluation). Methods: Participants included 20 post-pubertal males with IGE, aged 16.5-22.1 years. Also 20 post-pubertal sex- and age-matched healthy controls were evaluated. Physical activity, calcium and vitamin D intake were determined. Laboratory samples were obtained to measure biochemical parameters of bone metabolism and bone turnover: serum calcium, phosphate, magnesium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, intact parathyroid hormone, total alkaline phosphatase, bone alkaline phosphatase (bone-ALP), osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP). Results: At baseline evaluation, there were no significant differences between controls and patients parameters. At second evaluation, patients showed both markers of bone formation and resorption significantly higher than baseline values (bone-ALP: 51.2 +/- 9.9 vs. 57.3 +/- 9.3 U/l, P < 0.01; OC: 8.1 +/- 1.1 vs. 10.4 +/- 1.5 mu g/l, P < 0.01; PICP: 138.7 +/- 16.4 vs. 152.6 +/- 17.1 mu g/l, P < 0.01; ICTP: 3.8 +/- 0.8 vs. 5.9 +/- 0.6 mu g/l, P < 0.01). Conclusions: Valproate monotherapy in epileptic post-pubertal males causes a significant increase of bone turnover
A novel comprehensive paradigm for the etiopathogenesis of multiple sclerosis: therapeutic approaches and future perspectives on its treatment
No full textIt is well recognized that variation in the geographical distribution of prevalence of multiple sclerosis (MS) exists: increasing the latitude its prevalence increases as well, but the underlying causes of such dissimilarity still remained elusive as of today. Currently, the most accredited hypothesis is that the closer to the equator the more pronounced is the amount of sunlight which, in turn, increases the production of vitamin D. Cholecalciferol is indeed deficient in MS patients, but this factor does not explain by itself the etiopathogenesis of the disease. In the present study, to search for a pattern and provide a model of the disease’s etiology consistent with this regional factor, as well with its changing ethnic, sex-ratio, lifestyle variations and the other unexplained aspects of MS, an extensive analysis of peer-reviewed literature and data was conducted. The arisen hypothesis was that, increasing the latitude, the factor that varies and can have the stronger effect on the human organism, is the continuous and ever-increasing diversity of the natural light–dark cycle. The consequent effort of the suprachiasmatic nucleus to entrain the organism’s circadian rhythm affects the hypothalamic–pituitary–adrenal axis resulting in desynchronizing the central and peripheral circadian clocks and pathologizing the immunitary system. To verify such hypothesis, a theoretical framework of the etiopathogenesis, coherent with the gathered literature, was conceived and a demonstration to corroborate it was eventually devised and performed. The results underscored that people living in countries subjected to a further circadian disruptive factor, as daylight saving time, have a 6.35 times higher prevalence of MS than States placed on their same latitude that do not observe it, thus strongly supporting the hypothesis. As further reinforcement of the conclusions, it is worth mentioning that the levels of polyamines rise abruptly in autoimmune diseases. Moreover, among their numerous roles, these polycations participate to the regulation of the circadian clock so their sudden variation might disrupt it. Following these interesting findings, new perspectives in therapies are, therefore, proposed
Resection-line involvement in gastric cancer patients undergoing curative resections: implications for clinical management.
No full textResection-line involvement has been suggested as an important prognostic factor for gastric cancer.The relationship between resection-line involvement and outcome was examined in patients undergoing potentially curative resection for gastric cancer.Tumor positive resection-lines were seen in 22 of the 259 evaluable patients (8.4\%). Resection-line involvement was associated with tumor location (P = 0.01) and tumor differentiation (P = 0.02). Positive margins were associated with worse survival. However, if both groups of patients are stratified according to lymph node metastases, resection-line involvement determined a shorter survival only in patients with N0 stage disease.Our data suggest, in the case of positive margins, that re-laparatomy should be considered only for patients with N0 stage disease, while patients with metastatic lymph nodes should be watched closely without the need for a more aggressive surgical approach
Supervisor development
No full textChapter 17, Supervisor Development, by Nadine Pelling and Elisa Agostinelli, asks the question: How does one become a supervisor and what factors relate to supervisory identity development? The authors explore the factors that relate to supervisory identity development. The Supervisor Complexity Model of Watkins is reviewed as are the personal and relational factors related to supervision. Counselling experience, supervision training, and supervisory experience are then reviewed and presented as having an impact on one’s development as a supervisor. If you are a new supervisor you will want to read this chapter as it illustrates common supervisory development factors and the stages of development many new supervisors will encounter as they become more proficient at supervision
Early-onset pure absence epilepsy: a distinct epileptic syndrome.
No full textEarly-onset pure absence epilepsy has not yet considered in the International League Against Epilepsy classification, but several reports have supported its existence as a distinct epileptic syndrome primarily manifesting with typical absences in early childhood. This review summarizes the current understanding on this epilepsy. Conclusions: Early-onset pure absence epilepsy is a distinct epilepsy characterized by absences starting from a few months to 4 years of age, normal early psychomotor development, good antiepileptic drug seizure control and normal intellectual outcome. © 2011 The Author(s)/Acta Pædiatrica © 2011 Foundation Acta Pædiatrica
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