Symposium: Italian Industrial Districts In The I99Os

This paper reviews the scholarship concerning the rise to economic prominence of the Italian industrial districts, and the causes of some of the difficulties in which some districts have found themselves since the mid-1980s. The paper develops the main lines of the economic advantages that districts enjoyed during a period of rapid growth, resulting from the operation of a market in common which blends competition and cooperation. The effects of globalisation are changing this somewhat ‘idyllic’ picture, as the structure of linkages between firms comes under pressure. Prospects for the Italian districts in these new circumstances are discussed.     

Retinoic acid conjugates as potential antitumor agents: synthesis and biological activity of conjugates with Ara-A, Ara-C, 3(2H)-furanone, and aniline mustard moieties

In a dual targeting approach, to explore the ability of tretinoin (all-trans-retinoic acid) to behave as a covalent carrier for cytotoxic entities, conjugates of retinoic acid with a few representative molecules, being important examples of antitumor pharmacophores (i.e., nucleoside analogues and alkylating agents), have been synthesized and tested for their cytostatic and differentiating activity. All compounds were stable to in vitro hydrolysis in human plasma and more lipophilic than the parent compounds, thus consenting enhanced uptake into the cells. Among the nucleoside analogues the Ara-C derivatives 3 and 6 and the Ara-A derivative 7 proved the most cytostatic (IC50 < 0.32 microgram/mL) resulting from 25- to > 144-fold more active (Ara-A derivatives) or at least as equally active (Ara-C derivatives) as compared to the parent nucleosides. Compound 3, endowed with a highly lipophilic silyl moiety at the 3' and 5' positions, showed the highest differentiating activity (54% and 44% differentiated HL-60 cells at 0.2 and 0.05 microgram/mL respectively). With regard to the retinoic acid conjugates of alkylating agents, compound 10 was the most cytostatic agent (IC50 < 0.32 microgram/mL) and the most potent differentiating agent (33-34% at 0.32 and 0.08 microgram/mL). These structures may also be regarded as analogs of either retinoic acid or the cytotoxic compound.     

From hospital to municipal cogeneration systems: an Italian case study

A mixed integer linear programming model combined with a more traditional design by scenarios is proposed to optimize facilities size and operation mode of a municipal energy system involving significant civil centres and a hospital. Moving from the need of a new heat and power station for the local hospital due to the construction of new pavilions, the opportunity of involving other centres in the neighbourhood in a distributed cogeneration system is analysed, increasing system complexity step by step. Smaller cogeneration units tailored to hospital needs are rewarding ventures with relatively low risks but, in a country whose traditional power generation systems heavily rely on fossil fuels and where energy policy and market conditions can make it profitable to sell surplus power, district heating systems foster the installation of larger cogenerators and lead thereby to higher profits and to better performance as for primary energy savings and greenhouse gases emission reduction. Copyright © 2006 John Wiley & Sons, Ltd.     

Confocal Blood Flow Videomicroscopy of Thrombus Formation over Human Arteries and Local Targeting of P2X7

Atherothrombosis exposes vascular components to blood. Currently, new antithrombotic therapies are emerging. Herein we investigated thrombogenesis of human arteries with/without atherosclerosis, and the interaction of coagulation and vascular components, we and explored the anti-thrombogenic efficacy of blockade of the P2X purinoceptor 7 (P2X7). A confocal blood flow videomicroscopy system was performed on cryosections of internal mammary artery (IMA) or carotid plaque (CPL) determining/localizing platelets and fibrin. Blood from healthy donors elicited thrombi over arterial layers. Confocal microscopy associated thrombus with tissue presence of collagen type I, laminin, fibrin(ogen) and tissue factor (TF). The addition of antibodies blocking TF (aTF) or factor XI (aFXI) to blood significantly reduced fibrin deposition, variable platelet aggregation and aTF + aFXI almost abolished thrombus formation, showing synergy between coagulation pathways. A scarce effect of aTF over sub-endothelial regions, more abundant in tissue TF and bundles of laminin and collagen type I than deep intima, may suggest tissue thrombogenicity as molecular structure-related. Consistently with TF-related vascular function and expression of P2X7, the sections from CPL but not IMA tissue cultures pre-treated with the P2X7 antagonist A740003 demonstrated poor thrombogenesis in flow experiments. These data hint to local targeting studies on P2X7 modulation for atherothrombosis prevention/therapy.     

The Contribution of Small Vessel Disease to Neurodegeneration: Focus on Alzheimer’s Disease,Parkinson’s Disease and Multiple Sclerosis

Brain small vessel disease (SVD) refers to a variety of structural and functional changes affecting small arteries and micro vessels, and manifesting as white matter changes, microbleeds and lacunar infarcts. Growing evidence indicates that SVD might play a significant role in the neurobiology of central nervous system (CNS) neurodegenerative disorders, namely Alzheimer’s disease (AD) and Parkinson’s disease (PD), and neuroinflammatory diseases, such as multiple sclerosis (MS). These disorders share different pathophysiological pathways and molecular mechanisms (i.e., protein misfolding, derangement of cellular clearance systems, mitochondrial impairment and immune system activation) having neurodegeneration as biological outcome. In these diseases, the actual contribution of SVD to the clinical picture, and its impact on response to pharmacological treatments, is not known yet. Due to the high frequency of SVD in adult-aged patients, it is important to address this issue. In this review, we report preclinical and clinical data on the impact of SVD in AD, PD and MS, with the main aim of clarifying the predictability of SVD on clinical manifestations and treatment response.     

Selective Complexation and Membrane Transport of Guanidinium Salts by Calix[6]arene Amides

The p-tert-butylcalix[6]arene hexamide 2 and syn-1,3,5–trimethoxy-2,4,6-triamide 4 were synthesized by reaction of α-chloro-N,N-diethylacetamide and the corresponding calix[6]arenes 1 and 3 , respectively. ¹H NMR spectroscopy shows that 2 is a mixture of different conformations whereas 4 is fixed in a cone conformation. Extraction experiments, (S-L) and (H₂O–CDCl₃) with picrate salts, indicate that 2 complexes both alkali metal (1:2 complex) and guanidinium salts (1:1 complex) but 4 complexes only guanidinium (1:1 complex). Incorporated in supported liquid membranes (Accurel^® / o-nitrophenyl n-octyl ether) the calixarenes 2 and 4 transport guanidinium salts. The hexamide 2 is a more efficient carrier of guanidinium but the syn-1,3,5-trimethoxy-2,4,6-triamide 4 is much more selective. Both 2 and 4 are sufficiently lipophilic to give membranes that are stable over longer periods (weeks).