Role of Metalloproteases in the Release of the IL-1 type II Decoy Receptor

The IL-1 type II receptor (decoy RII) is a nonsignaling molecule the only established function of which is to capture IL-1 and prevent it from interacting with signaling receptor. The decoy RII is released in a regulated way from the cell surface. Here, we reported that hydroxamic acid inhibitors of matrix metalloproteases inhibit different pathways of decoy RII release, including the following: (a) the slow (18 h) gene expression-dependent release from monocytes and polymorphonuclear cells exposed to dexamethasone; (b) rapid release (minutes) from myelomonocytic cells exposed to tumor necrosis factor, chemoattractants, or phorbol myristate acetate; (c) phorbol myristate acetate-induced release from decoy RII-transfected fibroblasts and B cells. Inhibition of release was associated with increased surface expression of decoy RII. Inhibitors of other protease classes did not substantially affect release. However, serine protease inhibitors increased the molecular mass of the decoy RII released from polymorphonuclear cells from 45 to 60 kDa. Thus, irrespective of the pathway responsible for release and of the cellular context, matrix metalloproteases, rather than differential splicing, play a key role in production of soluble decoy RII

Spinal Fusion Surgery: Epidemiologic and Economic Burden Attributable to First Intervention

IntroductionLow back pain (LBP) is the single most common cause for disability in individuals aged 50 years or younger with a high socioeconomic impact. In USA, LBP costs are estimated to exceed $1..

DENALI: il Data Warehouse di Sanità Pubblica della Regione Lombardia

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Metabolism disrupting chemicals and metabolic disorders

The recent epidemics of metabolic diseases, obesity, type 2 diabetes(T2D), liver lipid disorders and metabolic syndrome have largely been attributed to genetic background and changes in diet, exercise and aging. However, there is now considerable evidence that other environmental factors may contribute to the rapid increase in the incidence of these metabolic diseases. This review will examine changes to the incidence of obesity, T2D and non-alcoholic fatty liver disease (NAFLD), the contribution of genetics to these disorders and describe the role of the endocrine system in these metabolic disorders. It will then specifically focus on the role of endocrine disrupting chemicals (EDCs) in the etiology of obesity, T2D and NAFLD while finally integrating the information on EDCs on multiple metabolic disorders that could lead to metabolic syndrome. We will specifically examine evidence linking EDC exposures during critical periods of development with metabolic diseases that manifest later in life and across generations

Valutazione dei processi assistenziali e del carico economico dei soggetti con ospedalizzazione incidente di infarto acuto del miocardio mediante il Data Warehouse DENALI

Aims: this study wants to estimate the economic burden of incident Acute Myocardial Infarction (AMI) registered in Lombardy (about 9.2 million residents). Method and results: a longitudinal study was conducted using a Data Warehouse (DENALI) that organised Healthcare Administrative databases of Lombardy related to eligibility criteria, hospital discharges (HDs), pharmaceutical and outpatient claims of citizens. All individuals with a HD for a first event of AMI during 2003 were identified and followed for 12 months. During 2003 12,049 individuals (64% males, mean age 70 +/-13 y.o.) had a HD for incident AMI. The total cost during the first year was € 163 million, corresponding to the 1% of the healthca re budget of Lombardy. The monthly cost in the first year was € 1,249 per person (77% attributable to HDs, 15% to pharmaceuticals and 8% to outpatient care). While most of the uptake of drugs used in secondary prevention was quick and happened in the first 3 months after the index event, the phenomenon of non persistence at 12 months was relevant. Conclusion: this large study on the burden of AMI shows the epidemiologic, economic and clinical impact of the disease. DENALI, with its large population followed over time, is a powerful and dynamic tool for epidemiologic and health economic research