MODIFICAZIONI FENOTIPICHE DELL¿ARTERIA BASILARE E RIPERCUSSIONI PERIFERICHE DURANTE EMORRAGIA SUBARACNOIDEA. POTENZIALE TERAPEUTICO DELLE MELANOCORTINE

Background: L'emorragia subaracnoidea (ESA) \ue8 una condizione patologica caratterizzata da un accumulo di sangue nello spazio subaracnoideo conseguente a trauma cranico o rottura di un aneurisma. Il decorso clinico \ue8 gravato da complicanze cerebrovascolari e sistemiche che peggiorano significativamente la prognosi del paziente. La complicanza pi\uf9 comune e grave dell\u2019ESA \ue8 il vasospasmo dell\u2019arteria basilare, che pu\uf2 causare ischemia cerebrale. L'intensa reazione infiammatoria che si sviluppa nello spazio subaracnoideo costituisce un importante fattore patogenetico del vasospasmo. Le complicanze periferiche infettive e infiammatorie,assai frequenti in pazienti con ESA, sembrano essere anche una conseguenza diretta del danno cerebrale. Infatti, il rilascio di citochine nel SNC attiva in modo incontrollato l\u2019asse ipotalamo-ipofisi-surrene, il sistema nervoso simpatico e la via anti-infiammatoria colinergica. Ci\uf2 causa l\u2019induzione di uno stato di immunodepressione che aumenta la suscettibilit\ue0 dell'organismo alle infezioni. Contemporaneamente, nei tessuti periferici, si verifica l'attivazione della risposta flogistica e dell\u2019infiltrazione leucocitaria. Ad oggi, non esiste ancora una strategia risolutiva per il trattamento dell\u2019ESA. Le melanocortine potrebbero costituire un'opportunit\ue0 terapeutica innovativa. Tali peptidi, derivati dal precursore pro-opiomelanocortina, sono rappresentati principalmente dall\u2019l'ormone \uf061-melanocitostimolante (\uf061-MSH) e dalll'adrenocorticotropina (ACTH). Essi esercitano potente attivit\ue0 anti-infiammatoria, anti-piretica e immunomodulante. Gli effetti delle melanocortine si esplicano attraverso la modulazione dell\u2019espressione di mediatori pro-infiammatori e l\u2019attivazione di circuiti neurali immunomodulanti endogeni. Obiettivi Della Ricerca: L'obiettivo generale \ue8 proporre un nuovo approccio terapeutico per il trattamento dell\u2019ESA. Gli scopi specifici erano: A) Identificare e caratterizzare le modificazioni molecolari indotte a livello dell'arteria basilare e negli organi periferici (milza, fegato e intestino) durante ESA sperimentale; B) Valutare l'efficacia della terapia con una melanocortina sintetica nel prevenire o attenuare le alterazioni associate all'ESA. Lo studio \ue8 articolato in 3 fasi: 1) Sviluppo del modello di ESA nel ratto; 2) Analisi molecolare delle ripercussioni precoci e tardive nell\u2019arteria basilare e in periferia; 3) Valutazione dell\u2019efficacia terapeutica delle melanocortine. Risultati: Ottimizzazione e standardizzazione della procedura basata su singola iniezione di sangue autologo in cisterna magna per indurre l\u2019ESA nel ratto. L\u2019analisi di gene profiling indica che l\u2019ESA induce gi\ue0 a 4 ore una profonda alterazione del profilo di espressione dell\u2019arteria basilare. La valutazione del calibro dell'arteria a 5 giorni mostra una riduzione del diametro vascolare del 50%. I risultati preliminari in organi periferici forniscono indicazioni circa la capacit\ue0 dell\u2019ESA di attivare una risposta extracerebrale e incoraggiano il proseguimento della ricerca allo scopo di caratterizzare in maniera pi\uf9 approfondita tale fenomeno. Il trattamento sistemico con la melanocortina sintetica NDP-MSH ha prevenuto molte delle alterazioni indotte dall\u2019ESA nell\u2019arteria basilare. L\u2019effetto protettivo sembra essere esercitato attraverso la modulazione di diverse vie di segnalazione. NDP-MSH ha ridotto significativamente la vasocostrizione dell\u2019arteria basilare a 5 giorni post-ESA.Background: Subarachnoid hemorrhage (SAH) is a pathological condition caused by bleeding into the subarachnoid space. Central and peripheral complications worsen patient outcome. Vasospasm is a severe central complication of SAH. It can cause ischemia and permanent brain damage or death. Bleeding-induced inflammation in the subarachnoid space contributes to vasospasm pathogenesis. In addition, peripheral organs develop inflammatory and infectious complications that seem to be a direct consequence of central injury. Indeed, cytokine production induced by brain damage causes activation of hypothalamic-pituitary-adrenal axis, sympathetic nerve signalling and cholinergic anti-inflammatory pathway. These signals induce immunodepression that could partly account for SAH-related increased susceptibility to infection. In peripheral tissues, activation of \uf0612-adrenoreceptors triggers local inflammatory response and leukocyte recruitment. No consistently efficacious therapies have been identified and implemented in clinical practice for this dire condition. Treatment with melanocortins could constitute an innovative therapeutic strategy. Melanocortin peptides, such as \uf061-melanocyte-stimulating hormone (\uf061-MSH) and adrenocorticotropic ormone (ACTH), are pro-opiomelanocortin derivatives that exert potent anti-inflammatory, immunodulatory, and antipyretic action. These molecules can directly modulate expression of pro-inflammatory molecules in responsive cells and activate endogenous anti-inflammatory neural circuits. Objectives: The general aim in the present research is to implement a novel therapeutic approach for SAH treatment. Specific goals were: A) To identify and characterize SAH-induced molecular alterations in the basilar artery and in the spleen, large intestine and liver; B)To evaluate whether melanocortin treatment can attenuate SAH-associated central and peripheral complications. The present research is divided in 3 phases: 1) Development of an experimental model to induce SAH in the rat; 2) Analysis of SAH-associated molecular alterations in the basilar artery and in peripheral organs at 4 hours and 5 days post-hemorrhage; 3) Evaluation of the potential protective action of melanocortin treatment. Results: Optimization and standardization of surgical procedure based on single autologous blood injection into the cisterna magna to induce SAH in the rat. Gene profiling analysis indicates that SAH induced a profound gene expression alteration in the basilar artery at 4 h. Morphometric analysis shows a marked vasoconstriction in the basilar arteries from the SAH group relative to controls. Preliminary data indicate that hemorrhage exerts detrimental effects in the spleen and liver. Further investigations are required to better analyze peripheral consequences of central injury. Systemic administration of the synthetic melanocortin NDP-MSH prevented most of SAH-induced alterations in the basilar artery. Protective effect is exerted through modulation of different signaling pathways. In addition, NDP-MSH significantly attenuated basilar artery vasoconstriction at 5 days post-SAH

DOSAGGIO DIRETTO DELLA RENINA CON METODICA CHEMILUMINOMETRICA:CONFRONTO CON LA TECNICA ENZIMATICA ED UTILIZZO NELLO SCREENINGDELL¿IPERALDOSTERONISMO PRIMITIVO

Background: Direct plasma renin concentration determined with chemiluminometric immunoassay (CliR, mU/l) is progressively replacing plasma renin activity (PRA, ng/ml/h) for clinical use but the conversion factors (CF) between the two methods are still unsettled as well as their influence on the calculation of aldosterone/renin ratio (ARRD and ARRP). Methods: CliR, PRA and aldosterone (A, ng/dl) were measured in plasma samples collected in the supine position (S) and after 1 hour of active standing (AS) in 88 patients with essential hypertension (EH) on treatment with various antihypertensive drugs including ACEIs and ARBs. The same determinations were made in S in 10 patients with primary hyperaldosteronism (PHA) due to adrenal adenoma histologically confirmed. Results: In EH the median values (range) of CliR in S and AS were 18 (2-255) and 28 (4-471) respectively, the corresponding values of PRA being 0.6 (0.2-11.2) and 1.3 (0.3-16.0). Supine and upright CliR and PRA were highly correlated with a Spearman rs of 0.85 and 0.84 respectively. The linear non parametric Passing-Bablok regression on all logarithmic values in S and AS gave a slope of 1.01, an intercept of 3.2 and a CF of 24.6 between PRA and CliR on the natural scale. In EH the median values (range) of A in S and AS were 7.8 (0.3-31) and 18.4 (2.3-60). In PHA patients the median values of CliR, PRA and A in S were 0.8 (0.2-10.2), 0.1 (0.1-0.6) and 36.8 (11.8-122). In EH the median values of ARRD in S and AS were 0.4 (0.01-3) and 0.5 (0.02-7.8) respectively, the corresponding values of ARRP being 12 (0-71) and 13 (0-80). ARRD and ARRP were strongly correlated, with an rs of 0.88 and 0.92 in S and AS respectively. The regression analysis of all logarithmic values in S and AS showed a slope of 1.12, an intercept of -3.53 and a CF of 0.03 between ARRP and ARRD on the natural scale. In PHA patients the median value of ARRD in S was 34 (2.8-244) and that of ARRP 298 (48-1222). Assuming as cut-off values of normalcy those recommended by guidelines (Funder et al, JCEM 2008; 93: 3266) i.e. 30 for ARRP and 3.7 for ARRD, there were 13 false positives in S and 18 in AS for ARRP with a specificity of 0.85 (CI95% 0.76-0.92) and of 0.78 (0.68-0.87) respectively while with ARRD there were only 0 and 4 false positives with a specificity of 1 (0.96-1) and of 0.95 (0.88-0.99). Conclusions: In EH on treatment CliR and PRA, as well as ARRD and ARRP, are highly correlated. However, using the conventional cut-off values, for the diagnosis of PHA the specificity of ARRD is better than that of ARRP. Moreover the specificity of ARRD appears to be minimally affected by antihypertensive treatment

Trattamento dell’ipertensione arteriosa nel paziente nefropatico

Stadtarchiv Solingen, Bergische Arbeiterstimme 16. Mai 1917 Gräfraths Bürgermeister Bartlau nimmt Stellung zu den Unterschieden der Versorgung in Gräfrath und der Stadt Solingen     Gräfrath. Die Versorgung im Stadkreise und im Landkeise Solingen. Zu dieser in unserer Samstagsnummer ausführlich besprochenen Angelegenheit nahm in der gestrigen Sitzung des Lebensmittelausschusses, zu der zum ersten Male auch Vertreter der Firmen Gottl[ieb] Hammesfahr, F. W. Rauh und Karl Engels, so- wie Ve..

Situated Learning with Bebras Tasklets

A Bebras short task, a tasklet, is designed to provide a source for exploring a computational thinking concept: at the end of the contest it could be used as a starting point to delve deeper into a computing topic. In this paper we report an experience which aims at taking full advantage of the potential of Bebras tasklets. A math teacher asked her pupils to act as Bebras \u201ctrainers\u201d for younger mates. The pupils, in pairs, were assigned to design and prepare a tangible game inspired by a Bebras tasklet, devised for the younger pupils to practice. They also had to explain the game to the younger pupils, make them play and support them in solving it. In carrying out this assignment the pupils acting as trainers had to deeply explore the Bebras tasklet and face its computational thinking challenge, and also practiced soft skills as collaborating with peers towards a common goal, adapting language and communicative style to engage with younger mates, devising and designing a tangible object, and planning its creation. The experience proved that using Bebras tasklets as the social and cultural context for situated learning of computational thinking competencies is indeed quite productive

Application Studies for the Implementation of the Sustainability Charter in the Metropolitan City of Genoa

Starting from Agenda 2030 and existing tools in the field of sustainability, this research defines the guidelines for a new Sustainability Charter created for a metropolitan-level city. These guidelines are then applied to the case study of the metropolitan city of Genoa. The paper reports, therefore, application studies for the implementation of the Sustainability Charter in the metropolitan city of Genoa. Funded by the Ministry of the Environment and the Protection of Territory and Sea, the Sustainability Charter of the Metropolitan City of Genoa, which we present here, is developed as part of \u201cAgenda 2030, the Sustainable Metropolitan Agenda of the Metropolitan City of Genoa: moving towards sustainable metropolitan spaces\u201d. This research has led to the implementation of a concrete product the entire citizenship can benefit from. The new proposed tool is oriented towards the application of sustainability in urban planning and management in order to reduce environmental impacts and promote a proper and better quality of life: a driving force for sustainable urban development. Sustainability as a tool to safeguard the cultural and environmental heritage and the economic system, which can represent a new opportunity for the development of competitiveness, innovation and employment

Changes in pasture and cow milk compositions during a summer transhumance in the western Italian Alps

The changes occurring in pasture and milk compositions during summer grazing were studied following a transhumance of a dairy cattle herd in the western Italian Alps. During three consecutive grazing periods (P1, P2, and P3) the cows exploited, in sequence, mountain pastures located at 1200-1260 m a.s.l. (A1), alpine pastures at 2000-2200 m a.s.l. (A2), and then returned to A1 pastures. The botanical and nutritional compositions of pastures, as well as cow milk yield, gross composition and fatty acid (FA) profi le were assessed during the transhumance. Within the pastures, a cluster analysis allowed the recognition of five vegetation types and seven vegetation sub-types; their allocation and plant species composition differed among the exploited grazing areas. The average Pastoral Values were signifi cantly higher in the mountain (A1P1, A1P3) than in the alpine pastures (A2P2) due to the abundance of high- and medium-quality forage species such as Dactylis glomerata L., Polygonum bistorta L., and Festuca rubra s.l.. Nevertheless, the nutritional quality of the herbage offered to the animals did not differ between A1P1 and A2P2, while it was significantly higher in A1P3 due to a younger vegetation phenological stage. The nutritional parameters were found to be correlated to the pasture botanical composition and phenology: organic matter digestibility and net energy for lactation were correlated negatively to the phenological stage and the Specific Contribution (SC) of Poaceae and positively to the SC of Fabaceae and Asteraceae. Milk yield significantly declined while milk protein increased during the grazing season, following the advance of cows’ stage of lactation. Milk fat and lactose percentages did not vary significantly among the grazing periods. The same was also observed for milk FA, with the exception of palmitic acid, whose level was lower in A2P2 if compared to the other two periods. Significant correlations were found between the percentages of some FA in milk and the SC of the main botanical families of the grazed pastures. In particular, linoleic acid was negatively correlated with the SC of Poaceae and positively correlated with the SC of Fabaceae. Results showed that the changes in the nutritional composition of pastures depended on variations in pasture botanical composition and phenology at the time of grazing, and that such factors concurred with animal-related factors in affecting milk quality during the grazing season

Monitoring and modeling the invasion of the fast spreading alien Senecio inaequidens DC. in an alpine region

We modeled the distribution of the South African alien Senecio inaequidens DC. in the Aosta Valley, Western Italian Alps, using data extracted from the Regional floristic database and from an intensive field survey carried out in years 2009-2010. The aims of the work were (1) to evaluate whether the species is in the introduction, colonization, or establishment stage of invasion, (2) to detect the environmental factors that drive the invasion process, and (3) to highlight the potential range of distribution of the alien species. The modeling framework was a stepwise generalized linear model (GLM), using gridded presence/absence data and environmental predictors such as topography, climate, land use, and anthropogenic and natural disturbances. GLM were fit both with and without an additional independent variable to take into account current dispersal limitations. S. inaequidens displayed a very fast spread in the Aosta Valley in the years 1990-2010. The species was positively associated with roads and rivers, southern slopes, and negatively with elevation. However, it was found at an elevation of 1600 m, showing the ability to reach higher elevations than those observed for other invasive alien species, and confirming to be pre-adapted to mountain conditions. The difference between the species distribution models, with and without dispersal constraints, suggested that the availability of seed sources still limits the potential distribution of the species, rather than the environmental variables, and that the realized regional niche differs to a great extent from the equilibrium niche. When limitations to the seed source cease (i.e., in the establishment stage), the species will likely invade large areas that are currently characterized by pastures and grasslands with native species of high agricultural importance. The invasion of S. inaequidens should therefore be considered a serious threat, due to its potential to invade mountain regions, and in particular to colonize habitats used for grazing and forage, thus leading to a high risk for cattle and human health. We discuss the relevance of the results both concerning communication with the public and to support local eradication and control activities. The inclusion of S. inaequidens in the "black list" of the regional law for the conservation of alpine flora (L.R. 45/2009) will help to transfer the information and support invasion control, in particular at medium elevations