1,721,075 research outputs found
Clinical management of renovascular hypertension : practical recommendations from the Italian Society of Hypertension (SIIA)
No full textRenovascular hypertension (RVH) is one of the most frequent forms of secondary hypertension but this diagnosis is often missed because of insufficient care taken in collecting patient's history and clinical signs. Herein we summarize the clinical, instrumental and laboratory clues which should raise the suspicion of RVH. In addition we briefly discuss the available evidence in favour and against the revascularization therapy and, at the light of the uncertain benefit of this procedure, the alternative approach with pharmacological treatment
Renal angioplasty for treatment of hypertensive patients with fibromuscular dysplasia : no country for old men
No full textAre the antagonists of the renin-angiotensin system also anticancer agents?
No full texthe antagonists of the renin–angiotensin system (RAS) have gained increasing popularity in the last two decades due to their indisputable efficacy in a number of cardiovascular disorders, coupled with an unsurpassed tolerability. However some years ago a partial and non-predefined meta-analysis raised the possibility that angiotensin receptor antagonists in particular may increase the incidence of cancer. This observation, although not confirmed by subsequent, larger analyses, caused a remarkable and understandable concern even outside the medical community. Herein we will summarize the available evidence pro and con the hypothesis of a carcinogenetic activity of RAS antagonists coming to the conclusion that these drugs may actually exert an anticancer action
MODIFICAZIONI FENOTIPICHE DELL¿ARTERIA BASILARE E RIPERCUSSIONI PERIFERICHE DURANTE EMORRAGIA SUBARACNOIDEA. POTENZIALE TERAPEUTICO DELLE MELANOCORTINE
Full text linkBackground: L'emorragia subaracnoidea (ESA) è una condizione patologica caratterizzata da un accumulo di sangue nello spazio subaracnoideo conseguente a trauma cranico o rottura di un aneurisma. Il decorso clinico è gravato da complicanze cerebrovascolari e sistemiche che peggiorano significativamente la prognosi del paziente. La complicanza più comune e grave dell’ESA è il vasospasmo dell’arteria basilare, che può 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’asse ipotalamo-ipofisi-surrene, il sistema nervoso simpatico e la via anti-infiammatoria colinergica. Ciò causa l’induzione di uno stato di immunodepressione che aumenta la suscettibilità dell'organismo alle infezioni. Contemporaneamente, nei tessuti periferici, si verifica l'attivazione della risposta flogistica e dell’infiltrazione leucocitaria. Ad oggi, non esiste ancora una strategia risolutiva per il trattamento dell’ESA. Le melanocortine potrebbero costituire un'opportunità terapeutica innovativa. Tali peptidi, derivati dal precursore pro-opiomelanocortina, sono rappresentati principalmente dall’l'ormone -melanocitostimolante (-MSH) e dalll'adrenocorticotropina (ACTH). Essi esercitano potente attività anti-infiammatoria, anti-piretica e immunomodulante. Gli effetti delle melanocortine si esplicano attraverso la modulazione dell’espressione di mediatori pro-infiammatori e l’attivazione di circuiti neurali immunomodulanti endogeni.
Obiettivi Della Ricerca: L'obiettivo generale è proporre un nuovo approccio terapeutico per il trattamento dell’ESA. 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 è articolato in 3 fasi: 1) Sviluppo del modello di ESA nel ratto; 2) Analisi molecolare delle ripercussioni precoci e tardive nell’arteria basilare e in periferia; 3) Valutazione dell’efficacia terapeutica delle melanocortine.
Risultati:
Ottimizzazione e standardizzazione della procedura basata su singola iniezione di sangue autologo in cisterna magna per indurre l’ESA nel ratto.
L’analisi di gene profiling indica che l’ESA induce già a 4 ore una profonda alterazione del profilo di espressione dell’arteria 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 capacità dell’ESA di attivare una risposta extracerebrale e incoraggiano il proseguimento della ricerca allo scopo di caratterizzare in maniera più approfondita tale fenomeno. Il trattamento sistemico con la melanocortina sintetica NDP-MSH ha prevenuto molte delle alterazioni indotte dall’ESA nell’arteria basilare. L’effetto protettivo sembra essere esercitato attraverso la modulazione di diverse vie di segnalazione. NDP-MSH ha ridotto significativamente la vasocostrizione dell’arteria 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 2-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 -melanocyte-stimulating hormone (-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
Full text linkBackground: 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
Aliskiren: the first direct renin inhibitor available for clinical use
No full textThe idea of blocking the renin-angiotensin system (RAS) with the inhibition of the enzymatic activity of renin has been pursued for half a century, but it became a reality only recently, with the synthesis of aliskiren, the first direct renin inhibitor available for clinical use. The upstream blockade of the system induced by aliskiren, in combination with its unique pharmacological properties (inhibiting potency, high plasma concentration, long half-life and preferential partitioning in the kidney) makes this compound the ideal tool to achieve a complete blockade of the RAS. Consistent with expectations, present evidence indicates that aliskiren, at the licensed dosages of 150-300 mg/day, lowers blood pressure to the same extent as other first-line antihypertensive agents, with the additional advantage of a longer duration of action which persists for several days after the cessation of treatment. Moreover, aliskiren was found to act synergically not only with diuretics but also with other drug classes, including angiotensinconverting enzyme inhibitors and angiotensin II receptor antagonists. In addition, results of recent clinical trials have shown that aliskiren possesses cardiovascular and renal protective properties which may contribute to the beneficial effects of this drug beyond the reduction of blood pressure. Finally, aliskiren has an excellent, placebo-like tolerability profile, a feature which is very relevant for improving compliance of patients
- …
