Adriana Arena

Neutrophil Gelatinase-Associated Lipocalin Reflects the Severity of Renal Impairment in Subjects Affected by Chronic Kidney Disease

Neutrophil gelatinase-associated lipocalin (NGAL) is a small 25-kDa protein released from kidney tubular cells after harmful stimuli. It represents one of the most promising future biomarkers in the diagnostic field of acute kidney injury (AKI), as the increase in NGAL levels is a good predictor of a brief-term onset of AKI, notably anticipating the resulting increase in serum creatinine. However, recent studies also suggest a possible role for NGAL in chronic kidney disease (CKD). For this reason we evaluated serum (sNGAL) and urinary NGAL (uNGAL) in a cohort of CKD patients in order to verify the relationship with the severity of renal impairment. In CKD patients sNGAL, uNGAL and the fractional excretion of this protein were notably increased as compared to controls. Furthermore both sNGAL and uNGAL were correlated with serum creatinine and, inversely, with residual glomerular filtration rate (GFR): this last relationship was found to be even closer than that found between GFR and serum creatinine. Multivariate models validate these correlations as independent, confirming that in these patients NGAL is a better predictor of GFR than serum creatinine. The results confirm NGAL as an important biomarker in clinical nephrology, extending to CKD the pathophysiological role of this protein in tubular adaptations to renal damage.

Antimicrobial potential of polyphenols extracted from almond skins.

Aims:  To evaluate the antimicrobial properties of flavonoid‐rich fractions derived from natural and blanched almond skins, the latter being a by‐product from the almond processing industry.

Serum TNFα in mouse typhoid and enhancement of a salmonella infection by anti-TNFα antibodies

Tumour necrosis factor α (TNFα) was detected by the L929 cell assay in the sera of mice 1 h after large i.v. inocula of virulent Salmonella typhimurium C5. TNFα was not detectable in sera from innately susceptible BALB/c mice during the course of a lethal infection commencing from a low inoculum, or from resistant A/J mice during the course of a lethal or sublethal infection, but only 1 h after i.v. challenge with large numbers of organisms. Administration of a single dose of rabbit polyclonal anti-TNFα antiserum on day 1 had no effect on the early course of a lethal infection in A/J mice. However, the same treatment exacerbated a sublethal infection in A/J mice. Anti-TNFα treatment did not accelerate the early bacterial net growth rate in the RES. Instead, the cfu count in treated mice continued to increase past the point at which the host response suppressed a further increase in bacterial numbers (the plateau phase) in normal controls. A second dose of anti-TNFα antiserum on day 4 together with a higher but still sublethal challenge caused a lethal infection in A/J mice. The results indicate that TNFα is important in mediating the plateau phase in a salmonella infection, and its effect may be local.

An exopolysaccharide produced by Geobacillus thermodenitrificans strain B3-72: Antiviral activity on immunocompetent cells

The immunomodulatory and antiviral effects of an extracellular polysaccharide (EPS-2), produced by a strain of Geobacillus thermodenitrificans isolated from a shallow marine vent of Vulcano Island (Italy), were evaluated. In the present study, we show for the first time that EPS-2 treatment hinder HSV-2 replication in human peripheral blood mononuclear cells (PBMC) but not in WISH cells. In fact, high levels of IFN-alpha, IL-12, IFN-gamma, TNF-alpha, IL-18 were detected in supernatants of EPS-2 treated PBMC. Moreover, this effect was dose-dependent. Taken together, our results confirm that the immunological disorders determined by HSV-2 could be partially restored by treatment with EPS-2.

Humidity sensing properties of Li–iron oxide based thin films

Abstract Li-doped iron oxide thin films deposited on a porous ceramic substrate by a liquid-phase method (LPD) were investigated as humidity sensors. Large variations in the resistance, up to about 4–5 order of magnitude, were observed by changing the relative humidity (RH) between 10 and 90%. The investigated sensors show a quick and reversible response to cyclic variations in the RH. The effects of pretreatment and Li content were investigated. The role of Li on the response to water vapour of iron oxide thin films is discussed.

Can Neutrophil Gelatinase–associated Lipocalin Help Depict Early Contrast Material–induced Nephropathy?

PURPOSE To evaluate the utility of serum and urinary neutrophil gelatinase-associated lipocalin (NGAL) in depicting an event of contrast material-induced nephropathy (CIN) in patients who received iodinated contrast media, gadoterate meglumine, or radiopharmaceutical technetium-99m ((99m)Tc) and to evaluate the protective effect exerted by isotonic saline infusion, sodium bicarbonate administration, or N-acetylcysteine administration. MATERIALS AND METHODS Institutional ethics committee approval was given, and informed consent was obtained. One hundred twenty patients were enrolled in a prospective study and divided into three groups: iomeprol group, magnetic resonance (MR) imaging group (gadoterate meglumine), and renal scintigraphy group ((99m)Tc). They randomly received N-acetylcysteine, physiologic saline, or sodium bicarbonate. Receiver operating characteristic (ROC) analysis, Kaplan-Meier curves, and Cox proportional hazard regression analysis were used. RESULTS In the MR imaging and renal scintigraphy groups, there were significant changes in serum creatinine and NGAL levels, and there were no cases of CIN. In the iomeprol group, an early rise in NGAL was found, while serum creatinine level changes occurred 24 hours after contrast material administration. At ROC analysis, NGAL showed high sensitivity and specificity (serum NGAL: area under the curve, 0.995; 95% confidence interval [CI]: 0.868, 0.992; urinary NGAL: area under the curve, 0.992; 95% CI: 0.925, 1.000) in identifying CIN 8 hours after iomeprol administration. Regression analysis showed that NGAL independently predicted CIN. Administration of N-acetylcysteine, sodium bicarbonate, or physiologic saline did not influence NGAL level. CONCLUSION NGAL depicted CIN in patients who received iodinated contrast material within 8 hours of contrast material administration. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120578/-/DC1.

Dialysis-related genotoxicity: sister chromatid exchanges and DNA lesions in T and B lymphocytes of uremic patients. Genomic damage in patients on hemodiafiltration.

Background/Aims: Patients with chronic renal failure show the presence of massive oxidative genome damage but the role played by dialysis is still a controversial issue. The aim of our study was to verify the genomic damage in B- and T-lymphocyte subpopulations of uremic patients after a single hemodiafiltration session. Methods: We enrolled 30 patients on maintenance acetate-free biofiltration and 25 age-matched healthy volunteers and studied chromosomal alterations. Results: Our data show that the basal levels of DNA damage, the number of sister chromatid exchanges and basal high-frequency cells levels are significantly higher in patients on hemodiafiltration than in controls and in T lymphocytes than in B cells. Conclusions: These findings suggest that hemodialytic treatment could represent a potential source of damage, maybe through the oxidative action of the extracorporeal circuit components, which might explain the well-known T-specific immunodeficiency correlated with uremia.

Interleukin-12 and interleukin-10 production by mononuclear phagocytic cells from breast cancer patients.

Interleukin-10 (IL-10) and Interleukin 12 (IL-12) generation may be regulated by a complex monocyte and macrophage-derived cytokine network and an impairment of the immune system can be observed in neoplastic disease. In this study, we examined the production of these cytokines by phagocytic cells, obtained from breast cancer (BCa)-bearing patients. Our results suggest that an increased IL-10 formation may represent an important regulatory pathway of IL-12 production by BCa mononuclear cells. In this report, we show that mononuclear cells of patients affected by breast cancer have a defective IL-12 production capability while generating higher amounts of IL-10.

Immunomodulatory and antiviral activity of almond skins

The elimination of a viral infection requires a proinflammatory host response (type 1 immunity), characterized by activation of mononuclear cells and production of proinflammatory cytokines, such as interferons (IFNs), tumor necrosis factor (TNF)-alpha and interleukin (IL)-12. On the other hand, IL-4 and IL-10 play a role in decreasing the inflammatory response supported by helper T (Th)1 cells. In this study we evaluated the effects of almond skins on the release of cytokines by peripheral blood mononuclear cells (PBMC), either infected or not with herpes simplex virus type 2 (HSV-2). Natural (NS) and blanched almond skins (BS) were subjected to simulated gastric and duodenal digestion and used at not cytotoxic concentrations. NS induced a significant decrease in HSV-2 replication, whereas extracts obtained from BS did not significantly influence the viral replication. High levels of cytokines production, such as IFN-alpha (38+/-5.3 pg/ml), IL-12 (215+/-17.1 pg/ml), IFN-gamma (5+/-0.7 IU/ml), TNF-alpha (3940+/-201.0 pg/ml), were detected. Moreover, IL-10 (210+/-12.2 pg/ml) and IL-4 (170+/-21.4 pg/ml), representative of Th2 responses, were found. Our data suggest that almond skins improve the immune surveillance of PBMC towards viral infection, both by triggering the Th1 and Th2 subsets.

2/4-Substituted-9-fluorenones and their O-glucosides as potential immunomodulators and anti-herpes simplex virus-2 agents. Part 5

In pursuing a research on the antiviral and immunomodulatory activity of tilorone congeners, two new series of compounds were prepared and pharmacologically explored: 9-fluorenone carboxyhydroxyesters, indicated as AG, and 9-fluorenone carboxyhydroxamides, indicated as MG. Two of them, AG17 and MG3, were used as sugar acceptors in the transglycosylation reactions performed by alpha- and beta-glucosidases extracted from the marine mollusc Aplysia fasciata providing different alpha- and beta-, mono- and oligosaccharides. Then aglycons and saccharides were assayed for cytotoxicity, for anti-herpes virus-2 properties on peripheral blood mononuclear cells (PBMC) and for their capability to trigger human cells to produce antiviral cytokines such as IFNalpha and TNFalpha. Some promising compounds were individuated whereas the utility of the biocatalytic procedures in the preparation of pure anomeric material was further focused.