La teoria economica dell'associazionismo tra enti locali

La gestione associata di servizi locali riguarda tutte quelle forme di cooperazione tra enti locali che comportano una gestione unitaria di uno o piu' servizi ed e' anche uno degli strumenti principali per affrontare e cercare di risolvere il problema della polverizzazione dei piccoli comuni e della ripartizione delle competenze tra piu' livelli di governo. Infatti, la costruzione di un efficiente sistema di governo decentrato richiede la presenza di attori locali adeguati e quindi, data la prevalenza nel nostro paese di comuni di piccole dimensioni, la via della gestione unitaria dei servizi per piu' enti locali sembra essere quella da perseguire. Tra le forme associative previste dal Testo unico delle leggi sull'ordinamento degli enti locali per la gestione associata di servizi si annoverano le convenzioni, i consorzi, le unioni di comuni, l'esercizio associato di funzioni e gli accordi di programma. In questo lavoro l'analisi e' focalizzata sull'unione, che sembra essere considerata dalla maggior parte degli studiosi lo strumento piu' adeguato a rivitalizzare i comuni di minori dimensioni. Inoltre, all'interno del concetto piu' ampio di aggregazione abbiamo tenuta separata la fusione, da intendersi tra giurisdizioni dello stesso livello, e la cooperazione, che puo' essere orizzontale o verticale. Nel discutere di questi temi le questioni economiche che abbiamo considerato riguardano le economie di scala, le economie di varieta' , l'equivalenza fiscale e gli effetti di traboccamento, a cui si puo' aggiungere la problematica connessa con la semplificazione amministrativa e con i costi di adempimento che la pubblica amministrazione, nel suo complesso, impone agli operatori.

Cytotoxic activity of a plant extract on cancer cells

Chemoprevention by natural products may be considered a promising approach to cancer control and management [1]. Many studies have demonstrated antiproliferative, cytostatic and cytotoxic activities of phytochemicals against cancer cells [2]. In this study, a plant extract from Arctium lappa, Berberis vulgaris and Eschscholtia californica was tested as potential anticancer agent. The antitumoral activity of this plant extract was tested on four human cancer cell lines: MCF-7 (breast carcinoma cells), Huh-7 (hepatic carcinoma cells), HTB-43 (oropharyngeal carcinoma cells) and ECV- 304 (urinary bladder carcinoma cells). The efficacy of the extract was compared to the common chemotherapeutic agent cyclophosphamide. Three plant extract concentrations were tested: 800, 650 and 450 ng/ml; for cyclophosphamide, three concentrations were assayed, according to literature data: 1300, 1000 and 850 ng/ml [3]. In addition, plant extract and cyclophosphamide were tested on two primary cell lines as controls, human gingival fibroblasts and human mammary fibroblasts. Cell viability was evaluated by the MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Sigma] colorimetric assay and the new xCELLigence system (Roche) for real-time monitoring of cell viability. All concentrations of plant extract exhibited a high level of cytotoxicity on MCF-7, Huh-7, HTB-43 and ECV-304 cancer cells, similar to cyclophosphamide, though they slightly reduced viability of human gingival and mammary fibroblasts. Conversely, the conventional chemotherapeutic drug showed a marked cytotoxicity on control cells. The potential of the plant extract has been demonstrated in vitro on various types of cancers, suggesting a possible use of this natural product as a promising anticancer agent. Further studies are needed to ascertain its efficacy in vivo and to elucidate its mechanism(s) of action at molecular and biochemical levels

Current and emerging treatments for the management of osteogenesis imperfecta

Osteogenesis imperfecta (OI) is the most common bone genetic disorder and it ischaracterized by bone brittleness and various degrees of growth disorder. Clinical severityvaries widely; nowadays eight types are distinguished and two new forms have been recentlydescribed although not yet classified. The approach to such a variable and heterogeneousdisease should be global and therefore multidisciplinary. For simplicity, the objectives oftreatment can be reduced to three typical situations: the lethal perinatal form (type II), inwhich the problem is survival at birth; the severe and moderate forms (types III–IX), in whichthe objective is ‘autonomy’; and the mild form (type I), in which the aim is to reach ‘normallife’. Three types of treatment are available: non-surgical management (physical therapy,rehabilitation, bracing and splinting), surgical management (intramedullary rod positioning,spinal and basilar impression surgery) and medical-pharmacological management (drugs toincrease the strength of bone and decrease the number of fractures as bisphosphonates or growthhormone, depending on the type of OI). Suggestions and guidelines for a therapeutic approachare indicated and updated with the most recent findings in OI diagnosis and treatment

Mechanisms of changes to the liver pigmentary component during the annual cycle (activity and hibernation) of Rana esculentaL.

The present study was performed to elucidate the mechanisms responsible for the changes of melanin content/distribution we had previously discovered in the liver parenchyma of Rana esculenta during natural hibernation. Melanomacrophagic component response was analysed using morphocytochemical methods. The results demonstrated that during the prehibernation period (October–November) the melanomacrophages reach the highest proliferative activity (BrdU, PCNA labelling) which is accompanied by an evident melanosynthesis (dopa-oxidase activity). In contrast, after hibernation, the decrease of liver pigmentation was the consequence of a partial cell loss by apoptotic mechanisms (TUNEL labelling, pyknosis-karyorhexis) accompanied by a decrease of melanosome content by autophagy and low melanosynthetic activity. On the basis of these findings, there is evidence that liver melanomacrophages represent a metabolically (melanin synthesis/degradation) and cytokinetically (proliferation/death) active cell population during the annual cycle of the frog. The results are also discussed in relation to the functional synergism between hepatocytes and pigment cells in the adaptation to environmental changes

Ligand efficacy and potency at recombinant human MT(2) melatonin receptors: evidence for agonist activity of some mt(1)-antagonists

1. NIH3T3 fibroblast cells transfected with the full-length coding region of the MT(2) human melatonin receptor stably expressed the receptor that is coupled to a pertussis toxin-sensitive G protein and exhibits high affinity for melatonin (K(I)=261 pM). 2. The order of apparent affinity for selected compounds was: 4-phenyl-2-propionamidotetralin (4P-PDOT)>2-phenylmelatonin>2-iodomelatonin>2-bromomelatonin>6-chloromelatonin⩾melatonin>luzindole>N-acetyl-tryptamine⩾N-[(2-phenyl-1H-indol-3-yl)ethyl]cyclobutanecarboxamide (compound 6)>N-acetylserotonin. 3. 4P-PDOT exhibited a very high selectivity (∼22,000 times) for the MT(2) receptor with respect to the mt(1) receptor subtype, as tested in comparative experiments with membrane preparations from NIH3T3 cells stably transfected with the human mt(1) receptor. 4. MT(2) melatonin receptors mediated incorporation of [(35)S]-GTPγS into isolated membranes via receptor catalyzed exchange of [(35)S]-GTPγS for GDP. The relative intrinsic activity and potency of the compounds were subsequently studied by using [(35)S]-GTPγS incorporation. The order of potency was equal to the order of apparent affinity. Melatonin and full agonists increased [(35)S]-GTPγS binding by 250% over basal (taken as 100%). Luzindole did not increase basal [(35)S]-GTPγS binding but competitively inhibited melatonin-stimulated [(35)S]-GTPγS binding, thus exhibiting antagonist action. 5. The other two mt(1) antagonists used here, 4P-PDOT and N-[(2-phenyl-1H-indol-3-yl)ethyl]cyclobutanecarboxamide, behaved as partial agonists at the MT(2) subtype, with relative intrinsic activities of 0.37 and 0.39, respectively. 6. These findings show, for the first time, important differences in the intrinsic activity of analogues between the human mt(1) and MT(2) melatonin receptor subtypes

Glucocorticoids Increase In Vitro and In Vivo Activities of Antibiotics against Chlamydophila pneumoniae

The in vitro and in vivo antichlamydial activities of dexamethasone and beclomethasone alone and in combination with an antibiotic were tested. In vitro, dexamethasone and beclomethasone decreased the number of inclusion-forming units versus the control number (P < 0.001). The combination of glucocorticoids with azithromycin, telithromycin, or levofloxacin was more active than antibiotics used alone (P < 0.001). The combination, tested in a murine Chlamydophila pneumoniae infection model, produced similar results