The renal damage consequent to cyclosporine A (CsA) administration ranges from hemodynamic alterations to irreversible chronic lesions. The initial vasoconstriction depends upon the imbalance between the various modulators of the renal vascular tone, among which the most powerful are endothelins and nitric oxide (NO). CsA could play a crucial role by inhibiting the Ca++/calmodulin-mediated activation of the constitutive NO synthase (NOS) isoform, which converts L-arginine (L-Arg) into NO and citrulline, with a 1:1 stoichiometry. To investigate the possibility of modulating CsA nephrotoxicity with L-Arg we studied six groups (G) of Lewis rats treated with daily gavage up to eight weeks: G1, CsA 40 mg/kg; G2, G1 plus L-Arg 300 mg/kg; G3, G2 plus the competitive inhibitor of NOS, NG-nitro-L-Arg (L-NNA); G4, L-Arg alone; G5, L-NNA alone; and G6, controls receiving vehicle alone. After eight weeks L-Arg treated rats were protected against the toxic effects of CsA [creatinine (Cr) values, G2, 0.62 +/- 0.05 mg/dl vs. G1, 0.99 +/- 0.16 mg/dl, P < 0.001; proteinuria (P), G2, 7.2 +/- 1.02 mg/day vs. G1, 15.1 +/- 1.9 mg/day, P < 0.01]. The administration of L-NNA abolished the protective effect of L-Arg (G3, Cr 1.23 +/- 0.16 mg/dl; P 16.9 = 2.3; P < 0.02 and P < 0.005, respectively vs. G2). The levels of Cr in G2 rats were superimposable to control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

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Chromium-51 ethylene diamine tetra-acetic acid (51Cr-EDTA) total plasma clearance was evaluated using a multi-sample method (i.e. 12 blood samples) as the reference compared with several simplified methods which necessitated only one or few blood samples. The following 5 methods were evaluated: terminal slope-intercept method with 3 blood samples, simplified method of Bröchner-Mortensen and 3 single-sample methods (Constable, Christensen and Groth, Tauxe). Linear regression analysis was performed. Standard error of estimate, bias and imprecision of different methods were evaluated. For 51Cr-EDTA total plasma clearance greater than 30 ml.min-1, the results which most approximated the reference source were obtained by the Christensen and Groth method at a sampling time of 300 min (inaccuracy of 4.9%). For clearances between 10 and 30 ml.min-1, single-sample methods failed to give reliable results. Terminal slope-intercept and Bröchner-Mortensen methods were better, with inaccuracies of 17.7% and 16.9%, respectively. Although sampling times at 180, 240 and 300 min are time-consuming for patients, 51Cr-EDTA total plasma clearance can be accurately calculated for values greater than 10 ml.min-1 using the Bröchner-Mortensen method. In patients with clearance greater than 30 ml.min-1, single-sample techniques provide a good alternative to the multi-sample method; the choice of the method to be used depends on the degree of accuracy required.

Context Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome, usually caused by small, benign and slow-growing phosphaturic mesenchymal tumors. Clinically, TIO is characterized by renal phosphate leak, causing hypophosphatemia and osteomalacia. This review was performed to assess the clinical characteristics of TIO patients described worldwide so far. Evidence acquisition On 06/26/2021, a systematic search was performed in Medline, Google Scholar, Google book, and Cochrane Library using the terms: “tumor induced osteomalacia”, “oncogenic osteomalacia”, “hypophosphatemia”. There were no language restrictions. This review was performed according to PRISMA criteria Evidence Results Overall, 1725 TIO cases were collected. TIO was more frequent in adult men, who showed a higher incidence of fractures compared to TIO women. The TIO causing neoplasms were identified in 1493 patients. The somatostatin receptor-based imaging modalities have the highest sensitivity for the identification of TIO-causing neoplasms. TIO causing neoplasms were equally located in bone and soft tissues; these latter showed a higher prevalence of fractures and deformities. The surgery is the preferred TIO definitive treatment (successful in &gt;90% of patients). Promising non-surgical therapies are treatments with burosumab in TIO patients with elevated Fibroblast Growth Factor-23 levels, and with radiolabeled somatostatin analogs in patients with TIO-causing neoplasm identified by somatostatin receptor-based imaging techniques. Conclusion TIO occurs preferentially in adult men. The TIO clinical expressiveness is more severe in men as well as in patients with TIO-causing neoplasms located to soft tissues. Treatments with burosumab and with radiolabeled somatostatin analogs are the most promising non-surgical therapies

The synthesis of PAF by endothelial cells at the site of plasmin generation and the endothelial expression of P-selectin may render the endothelial cell surface proadhesive for neutrophils and may favor a local increase in vascular permeability.