PDGF and TGF-β contribute to the natural course of human IgA glomerulonephritis

PDGF and TGF-β contribute to the natural course of human Ig-A glomerulonephritis. PDGF and TGF-β are known mediators of mesangial cell proliferation and matrix expansion. The presence of these regulatory factors was examined in 30 renal biopsies from patients with IgA glomerulonephritis (IgA-GN) at the mRNA and protein level. Normal renal tissue served as control. The mRNA expression of PDGF A/B chains, PDGF-βR and TGF-β1 was evaluated by means of RT/PCR with subsequent Southern blot hybridization and/or non-radiactive in situ hybridization. In addition, PDGF-AB/BB, PDGF-βR, TGF-β isoforms (β1, β1+2, β2+3), the small TGF-β1 latency associated peptide (TGF-β1 LAP) and the extracellular matrix proteins tenascin and decorin were analyzed by immunocytochemistry. The expression of growth factors was correlated with light microscopic and clinical features. Compared to normal control kidneys, an increased expression of PDGF-BB/PDGF-βR mRNAs and the corresponding proteins was observed in all biopsies with IgA-GN. Up-regulation was related to the degree of glomerular proliferation and the extent of fibrosing interstitial lesions. In contrast, there was a discordance between TGF-β1 mRNA and protein expression (evaluated by immunocytochemistry). In all biopsies, irrespective of the stage of the disease, abundant TGF-β1 transcripts were detected, whereas TGF-β1 immunoreactivity was expressed to a lesser degree and disclosed a more variable staining pattern. In patients with significant proliferative glomerular lesions and minor tubulointerstitial alterations, TGF-β1 positivity was confined to areas of glomerular proliferation, whereas in cases with more severe histology including sclerosing lesions TGF-β1 immunoreactivity was less prominent. The distribution and the intensity of TGF-β1 LAP staining commonly exceeded the positivity noted for TGF-β1, indicating only limited TGF-β1 activation. A decreased reactivity for tenascin accompanied the morphological features of glomerular sclerosis. The staining patterns and the fact that only very few inflammatory cells, particularly CD68 positive monocytes/macrophages, were detected in glomeruli confirm that predominantly resident glomerular cells (mesangial and endothelial cells) are the major source of up-regulated growth factor production in IgA-GN. Since the expression of PDGF-AB/BB paralleled the severity of proliferative glomerular changes, PDGF seems to represent a potential indicator of activity in this condition. It is suggested that an imbalance between PDGF and TGF-β (by restricted translation and/or activation) production contribute to the progressive nature of IgA-GN

Polypharmacy in Polish older adult population - a cross-sectional study : results of the PolSenior project

Polypharmacy is a challenging issue in geriatrics. The aim of the study was to characterize correlates of polypharmacy in the PolSenior project. The PolSenior project, was a comprehensive survey in a large and longitudinal representative sample of thePolish older population. The project was conducted by the International Institute of Molecular and Cell Biology in Warsaw between 2008 and 2011. All medications consumed during the week preceding the survey were evaluated for each participant (n = 4793, including 2314 females (48.3%)). Thereafter, the percentage of those with polypharmacy (at least 5 medications) and excessive polypharmacy (at least 10 medications) was calculated, and their correlates were determined. The average number of medications used by participants was 5.1 ± 3.6, and was higher in females than in males (5.5 ± 3.5 vs. 4.8 ± 3.5; p < 0.001). Polypharmacy characterized 2650 participants (55.3%) and excessive polypharmacy—532 of them (11.1%). The independent correlates associated withpolypharmacy were: age over 70 years, female sex, higher than primary education, living in an urban area, comorbidities, any hospitalization during past five years, and visiting general practicioners at least yearly. As for correlates with excessive polypharmacy, they were: age 80–84 years, female sex, living in an urban area, diagnosis of at least four chronic diseases, and at least two hospitalizations in the last five years. This study serves as a starting place to understand patient characteristics associated with polypharmacy, excessive polypharmacy, and identify targeted interventions