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BACKGROUND: During inflammation, activated vascular endothelial cells and other cell types express various adhesion molecules, which facilitate the binding of circulating leukocytes and their extravasation in surrounding tissue (i.e. renal tissue). The serum concentration of circulating soluble adhesion molecules is supposed to reflect the degree of this activation. OBJECTIVE: In the first part of the study, we determined if the serum levels of the soluble intercellular adhesion molecule (sICAM)-1 and the soluble endothelial cell-leukocyte adhesion molecule (sELAM)-1, in patients affected by microscopic polyangiitis (MPA), associated with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibodies (ANCA), were related to the active and the inactive vasculitis phase. In the second part of the study, we examined the changes in circulating sICAM-1 and sELAM-1 levels and the clinical outcome of renal function in these patients. METHODS: We examined 20 MPO-ANCA-positive MPA patients in an acute phase and in a remission phase, after 6 months of treatment, and 50 subjects as controls, 30 with autosomal dominant polycystic kidney disease (ADPKD) in stable chronic renal failure (CRF) and 20 healthy volunteers (HS) with normal renal function. RESULTS: Regarding serum creatinine (Cr) concentration, no significant differences were found comparing active and inactive phases in the MPA group and the CRF group. Mean serum adhesion molecule levels in the MPA group were higher in the active phase compared to the inactive phase and to the CRF and HS groups. In addition, considering the outcome of serum Cr concentrations in the MPA group, the serum adhesion molecule levels were higher and decreased more slowly in patients with final high serum Cr concentrations than in patients with final normal serum Cr concentrations. CONCLUSION: Our data suggest that in MPO-ANCA-positive MPA patients, higher sICAM-1 and sELAM-1 levels during the active phase and their slower decline during the treatment period, could be a prognostic risk factor for CRF development.

Parkinson's disease (PD) is characterized by the progressive loss of substantia nigra dopaminergic neurons and the presence of cytoplasmic inclusions named Lewy bodies. Two missense mutations of the alpha-synuclein (alpha-syn; A30P and A53T) have been described in several families with an autosomal dominant form of PD. alpha-Syn also constitutes one of the main components of Lewy bodies in sporadic cases of PD. To develop an animal model of PD, lentiviral vectors expressing different human or rat forms of alpha-syn were injected into the substantia nigra of rats. In contrast to transgenic mice models, a selective loss of nigral dopaminergic neurons associated with a dopaminergic denervation of the striatum was observed in animals expressing either wild-type or mutant forms of human alpha-syn. This neuronal degeneration correlates with the appearance of abundant alpha-syn-positive inclusions and extensive neuritic pathology detected with both alpha-syn and silver staining. Lentiviral-mediated expression of wild-type or mutated forms of human alpha-syn recapitulates the essential neuropathological features of PD. Rat alpha-syn similarly leads to protein aggregation but without cell loss, suggesting that inclusions are not the primary cause of cell degeneration in PD. Viral-mediated genetic models may contribute to elucidate the mechanism of alpha-syn-induced cell death and allow the screening of candidate therapeutic molecules.

Parkinson's disease (PD) is characterized by a progressive loss of midbrain dopamine neurons and the presence of cytoplasmic inclusions called Lewy bodies. Mutations in several genes including alpha-synuclein and parkin have been linked to familial PD. The loss of parkin's E3-ligase activity leads to dopaminergic neuronal degeneration in early-onset autosomal recessive juvenile parkinsonism, suggesting a key role of parkin for dopamine neuron survival. To evaluate the potential neuroprotective role of parkin in the pathogenesis of PD, we tested whether overexpression of wild-type rat parkin could protect against the toxicity of mutated human A30P alpha-synuclein in a rat lentiviral model of PD. Animals overexpressing parkin showed significant reductions in alpha-synuclein-induced neuropathology, including preservation of tyrosine hydroxylase-positive cell bodies in the substantia nigra and sparing of tyrosine hydroxylase-positive nerve terminals in the striatum. The parkin-mediated neuroprotection was associated with an increase in hyperphosphorylated alpha-synuclein inclusions, suggesting a key role for parkin in the genesis of Lewy bodies. These results indicate that parkin gene therapy may represent a promising candidate treatment for PD.

SummaryBackgroundEpidemiologic studies have demonstrated that elderly patients with fixed airflow obstruction can be affected by asthma or chronic obstructive pulmonary disease (COPD).MethodsWe studied 49 consecutive elderly outpatients, presenting fixed airflow obstruction, by clinical history (smoking), pulmonary function tests, blood gas analysis, and induced sputum.ResultsThe age was not different in patients with COPD (n=28) and asthma (n=21) (70.2±3.9 years vs. 69.6±3.7 years), also the degree of fixed airflow obstruction was similar (FEV1: 58.3±1.5% vs. 59.0±1.4% of predicted). Patients with asthma had significantly more eosinophils in peripheral blood (0.43±0.05×10−3μL vs. 0.27±0.1×10−3μL, P