Search

Stimation of investment costs for a case study: the storm drain and pipe drain in the santafesina central regione. [ABSTRACT FROM AUTHOR]

Background and Purpose: Peroxisome proliferator-activated receptor (PPAR) agonists exert anti-albuminuric effects. However, the nephroprotective effects of these drugs remain to be fully understood. We have investigated whether gemfibrozil, GW0742 and pioglitazone protect human podocytes against nutrient deprivation (ND)-induced cell death and the role of mitochondrial biogenesis as a cytoprotective process.Experimental Approach: Immortalized human podocytes were pre-treated with the PPAR agonists and exposed to ND (5 h) under normoxia, hypoxia or in the presence of pyruvate. Cell death was measured at the end of the ND and of the recovery phase (24 h). Mitochondrial mass, cytochrome c oxidase (COX) subunits 1 and 4 were measured as markers of mitochondrial cell content, while membrane potential as an index of mitochondrial function. PGC-1α, NRF1 and Tfam expression was studied, as crucial regulators of mitochondrial biogenesis.Key Results: Cell pre-treatment with gemfibrozil, GW0742, or pioglitazone significantly decreased the ND-induced cell loss, necrosis and apoptosis. These effects were attenuated by hypoxia and potentiated by pyruvate. Pre-treatment with these drugs significantly increased mitochondrial cell content, while it did not affect mitochondrial function. In all these experiments pioglitazone exerted significantly larger effects than gemfibrozil or GW0742.Conclusions and Implications: Gemfibrozil, GW0742 and pioglitazone may exert direct protective effects on human podocytes. Mitochondrial biogenesis is a cell response to the PPAR agonists related to their cytoprotective activity. These results provide a mechanistic support to the clinical evidence indicating PPAR agonists as disease-modifying agents for glomerular diseases. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy is characterised by mesangial extracellular matrix accumulation. Monocyte chemoattractant protein-1 (MCP-1), a chemokine promoting monocyte infiltration, is upregulated in the diabetic glomerulus. We performed in vitro and in vivo studies to examine whether MCP-1 may have prosclerotic actions in the setting of diabetes, presumably via its receptor, chemokine (C-C motif) receptor 2 (CCR2), which has been described in mesangial cells. Human mesangial cells were exposed to recombinant human (rh)-MCP-1 (100 ng/ml) for 12, 24 and 48 h and to rh-MCP-1 (10, 100 and 200 ng/ml) for 24 h. Fibronectin, collagen IV and transforming growth factor, beta 1 (TGF-β1) protein levels were measured by ELISA and pericellular polymeric fibronectin levels by western blotting. The intracellular mechanisms were investigated using specific inhibitors for CCR2, nuclear factor kappa B (NF-κB), p38 mitogen-activated protein kinase and protein kinase C, and an anti-TGF-β1 blocking antibody. In both non-diabetic and streptozotocin-induced diabetic mice that were deficient or not in MCP-1, glomerular fibronectin accumulation was examined by immunohistochemistry, while cortical Tgf-β1 (also known as Tgfb1) and fibronectin mRNA and protein levels were examined by real-time PCR and western blotting. In mesangial cells, MCP-1 binding to CCR2 induced a 2.5-fold increase in fibronectin protein levels at 24 h followed by a rise in pericellular fibronectin, whereas no changes were seen in collagen IV production. MCP-1-induced fibronectin production was TGF-β1- and NF-κB-dependent. In diabetic mice, loss of MCP-1 diminished glomerular fibronectin protein production and both renal cortical Tgf-β1 and fibronectin mRNA and protein levels. Our in vitro and in vivo findings indicate a role for the MCP-1/CCR2 system in fibronectin deposition in the diabetic glomerulus, providing a new therapeutic target for diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Background. Studies in experimental animals have suggested that platelet-activating factor (PAF) is a mediator of sepsis-associated acute renal failure (ARF). In the present study we have evaluated whether an increased concentration of PAF within circulation of urine of septic patients correlated with the worsening of renal function. [ABSTRACT FROM PUBLISHER]

Tumour necrosis factor-α (TNFα) is a pleiotropic cytokine which is overproduced in rheumatoid joints primarily by macrophages. This cytokine has a potential pathogenic role in the establishment of rheumatoid synovitis, in the formation of pannus tissue and in the process of joint destruction, as it increases synoviocyte proliferation and triggers a cascade of secondary mediators involved in the recruitment of inflammatory cells, in neo-angiogenesis and in the process of joint destruction. These findings made TNFα a potential target for anticytokine therapy. Experimental studies have shown that TNFα blockade by monoclonal antibodies or by soluble TNF receptor reduced the extent and severity of arthritis both in collagen-induced arthritis in mice and in transgenic mice overexpressing TNFα, which develop a rheumatoid-like destructive arthritis. Clinical studies based on the use of anti-TNFα antibodies or soluble receptors have suggested a potential beneficial effect of TNFα-blocking therapy in inducing amelioration of inflammatory parameters in patients with long-standing active disease. In these patients anti-TNFα therapy induces a rapid improvement in multiple clinical assessment of disease activity, including morning stiffness, pain score, Ritchie articular index and swollen joint count. The clinical benefits are associated with an improvement in some serological parameters, such as C-reactive protein and serum amyloid-A, erythrocyte sedimentation rate, blood cytokine levels, haemoglobin, white cells and platelet counts, rheumatoid factor titre and histological features of the synovium. However, it remains to be determined whether anti-TNFα therapy may be useful in the long term management of rheumatoid patients and in the achievement of better outcomes of disease. Because TNFα production also serves a specific function in host defence against infections and tumours, the adverse effects of long term anti-TNFα therapy must be carefully evaluated. In addition, targeting a single mediator may be not sufficient to block the complex inflammatory response in rheumatoid arthritis. For these reasons therapeutic strategies aimed at concomitantly interfering with multiple pathogenic pathways are currently under investigation. [ABSTRACT FROM AUTHOR]

This study reports the results of in vitro and in vivo investigations on the effect of prostacyclin (PGI2) on polymorphonuclear neutrophils (PMN) challenged with immune complexes (IC). In vitro, PGI2 does not affect the interaction of IC with PMN membrane receptors, but prevents the ensuing PMN aggregation and secretion of platelet-activating factor, a lipid mediator responsible for immune-induced PMN aggregation. In vivo, the infusion of PGI2 in New Zealand white rabbits injected with IC prevents IC-induced neutropenia and thrombocytopenia as well as the embolization of PMN into the pulmonary peripheral capillary network. These results suggest a physiological role for PGI2 in modulating the interaction between IC and PMN. [ABSTRACT FROM AUTHOR]

The origin of platelet activating factor (PAF) from human leucocytes was investigated. Purified monocytes release PAF passively at pH 10.6, when challenged with Ionophore A 23187 or under phagocytic stimuli. Pure preparations of polymorphonuclear neutrophils liberate PAF passively, when challenged with C5a, neutrophil cationic proteins (CP), their carboxypeptidase B derived products (CSa des Arg, CP des Arg) or under phagocytic stimuli. Basophil rich buffy coat cells release PAF when challenged with C5a, CP, anti-IgE (in low amount) or Synacthen concomitantly with basophil degranulation and histamine release. Electron microscopy studies, carried out on Synacthen-stimulated basophil rich buffy coat, provide morphological evidence for platelet-basophil interaction. In conclusion our data demonstrate that PAF can be released from different leucocyte populations. However, the stimuli able to trigger such release appear to have some specificity for the cell target. [ABSTRACT FROM AUTHOR]

Examines the effect of immune complexes (IC), complement and neutrophils on human and rabbit mastocytes and basophils. Effect of IC of triggering the degranulation of basophils/mastocytes in rabbit and man, thus releasing histamine and platelet-activating-factor; Observation that anaphylatoxins and cationic proteins were active on human and rabbit mastocytes and on human basophils but not on rabbit basophils.