Background. Recent studies have shown that exogenous administration of vascular endothelial growth factor (VEGF) is protective against cyclosporine A (CsA) renal toxicity. No data are available, however, on the possible role of endogenous VEGF. Our objective was to examine whether endogenous VEGF has a significant role in the renal response against CsA toxicity. Methods. In vivo, we used high-dose (50–150 mg/kg/day) CsA ± specific goat anti-mouse VEGF blocking monoclonal antibody (α-VEGF) in mice. In vitro, we exposed mouse tubular cells (MCT) to CsA ± α-VEGF. Results. α-VEGF markedly enhanced CsA renal toxicity, inducing severe tubular damage and increased blood urea nitrogen. In animals treated with CsA + α-VEGF, damage progressed to generalized tubular injury (histology) and apoptosis (terminal deoxynucleotide transferase-mediated dUTP nick-end labeling) with associated anemia and reticulocytosis (18 days of treatment). CsA + α-VEGF treatments strikingly increased tubular VEGF and Bcl-xL proteins. In vitro, autocrine production of VEGF by MCT was identified by Western blot. Of specific interest, CsA toxicity in MCT increased significantly in the presence of α-VEGF. Conclusions. Endogenous VEGF has a relevant role in the renal tubular defense against CsA toxicity. Blockade of the VEGF effect by α-VEGF results in clear-cut intensification of the tubular injury and appearance of regenerative anemia in the CsA + α-VEGF–treated animals. The occurrence of both in vivo and in vitro effects of VEGF blockade provides evidence of a direct protective effect of VEGF on the tubular cell.

10.1097/00007890-200212150-00021

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Applying Natural Language Processing Techniques to International Safeguards

OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (2023)

Scott Stewart Nathan Martindale Carlos Soto Alejandro Michel Zuniga

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Epicardial Adipose Tissue, Adiponectin and Leptin: A Potential Source of Cardiovascular Risk in Chronic Kidney Disease

Luis D’Marco María Jesús Puchades José Luis Górriz María Romero-Parra Marcos M. Lima-Martínez

The importance of cardiometabolic factors in the inception and progression of atherosclerotic cardiovascular disease is increasingly being recognized. Beyond diabetes mellitus and metabolic syndrome, other factors may be responsible in patients with chronic kidney disease (CKD) for the high prevalence of cardiovascular disease, which is estimated to be 5- to 20-fold higher than in the general population. Although undefined uremic toxins are often blamed for part of the increased risk, visceral adipose tissue, and in particular epicardial adipose tissue (EAT), have been the focus of intense research in the past two decades. In fact, several lines of evidence suggest their involvement in atherosclerosis development and its complications. EAT may promote atherosclerosis through paracrine and endocrine pathways exerted via the secretion of adipocytokines such as adiponectin and leptin. In this article we review the current knowledge of the impact of EAT on cardiovascular outcomes in the general population and in patients with CKD. Special reference will be made to adiponectin and leptin as possible mediators of the increased cardiovascular risk linked with EAT.

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Inter-Observer Discordance With The Diagnosis Of Myelodysplastic Syndromes With Less Than 5% Bone Marrow Blasts: Unilineage Vs Multilineage Dysplasia and Reproducibility Of The Threshold Of 2% Blasts

Blood (2013)

Patricia Font Javier Loscertales Carlos Soto Pilar Ricard Carolina Muñoz Novas

Concordance

Cytopenia

Kappa

10.1182/blood.v122.21.2768.2768

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