Circulating Omentin-1 levels and altered iron balance in chronic haemodialysis patients.

BACKGROUND: Iron deficiency is highly prevalent among patients undergoing chronic haemodialysis (HD) but its correct identification is often problematic as common biomarkers of iron status, such as transferrin saturation (TSAT) and ferritin, can be altered by inflammation or malnutrition. METHODS: In this pilot multicentre study, we aimed at evaluating circulating levels of Omentin-1, a novel fat depot-specific adipokine that is also involved in iron regulation, in a cohort of 85 chronic HD patients with relation to their iron status. RESULTS: Omentin-1 levels in HD were statistically higher than in healthy controls (P = 0.03) and there was a significant, growing trend in all iron parameters across Omentin-1 tertiles (P < 0.001). Compared with patients with optimal iron status, Omentin-1 levels were lower in subjects categorized according to TSAT ≤20% or serum ferritin ≤200 µg/L (both P < 0.001) and even more reduced in 19 patients (22%) simultaneously displaying low levels of both markers (P < 0.001). In this latter group, Omentin-1 levels increased in parallel to all other iron markers after iron correction by i.v. supplementation. At multivariate regression analyses, ferritin (ß = 0.71; P < 0.001) and TSAT (ß = 0.32; P = 0.03) remained the sole independent predictors of Omentin-1 levels. This biomarker also showed a remarkable diagnostic capacity at receiver operating characteristic analyses in identifying iron-depleted HD patients according to a criterion of TSAT ≤20% [area under the curve (AUC) 0.827], ferritin ≤200 µg/L (AUC 0.863) or low levels of both parameters (AUC 0.907). CONCLUSIONS: Findings obtained indicate that Omentin-1 is somewhat involved in iron balance regulation and might be a candidate biomarker for diagnosing and managing altered iron conditions in HD patients.

Immunocryosurgery is a safe and feasible treatment for basal cell carcinoma and Bowen disease in renal transplant recipients.

Keratinocyte skin carcinomas (squamous cell carcinoma, basal cell carcinoma [BCC], Bowen disease [BD]) inflict significant morbidity and constitute a treatment challenge in renal transplant recipients (RTR). Immunocryosurgery has shown efficacy >95% in the treatment of BCC and BD in immunocompetent patients. The present study evaluated the safety, feasibility and efficacy, of immunocryosurgery in the treatment of BCC and BD in a series of RTR. During a 3-year period, biopsy-confirmed cases of BCC and BD were treated with a standard immunocryosurgery cycle (5 weeks daily imiquimod and a session of cryosurgery at day 14). Safety was evaluated by comparing graft function markers between immunocryosurgery treated RTR patients and matched controls. Ten BCC (8 nodular, 1 basosquamous, 1 superficial; diameter 6-14 mm; mean 9.2 mm) and nine BD disease lesions in nine patients (7 men, 2 women; age range: 54-70 years, mean: 62.1 years) were treated with immunocryosurgery and followed-up for two to 5 years. Five BCC were located on the "H area" of the face. No patient showed clinical or laboratory signs of transplant dysfunction during treatment or follow-up. Seven out of 10 BCC lesions cleared completely after one 5-week immunocryosurgery cycle, two cleared after repeat and intensified treatment cycles and one responded only partially (clearance rate: 90%). Seven out of nine BD lesions cleared after one 5-week immunocryosurgery cycle and one lesion after two cycles (clearance rate: 88.9%). In conclusion, immunocryosurgery is a safe, feasible and effective minimally invasive treatment alternative to standard surgical modalities for BCC and BD in RTR.

The Association of Circulating CD14++CD16+ Monocytes, Natural Killer Cells and Regulatory T Cells Subpopulations With Phenotypes of Cardiovascular Disease in a Cohort of Peritoneal Dialysis Patients.

The altered expression of immune cells including monocyte subsets, natural killer (NK) cells and CD4+CD25+ regulatory T cells (Tregs) in end-stage kidney disease, affect the modulation of inflammation and immunity with significant clinical implications. The aim of this study was to investigate the profile of specific immune cells subpopulations and their correlations with phenotypes of established cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF) in peritoneal dialysis (PD) patients. Materials and Methods: 29 stable PD patients and 13 healthy volunteers were enrolled. Demographic, laboratory, bioimpedance measurements, lung ultrasound and echocardiography data were collected. The peripheral blood immune cell subsets analysis was performed using flow cytometry. Results: PD patients compared to normal controls had lower total lymphocytes (22.3 ± 6.28 vs. 31.3 ± 5.54%, p = <0.001) and B-lymphocytes (6.39 ± 3.75 vs. 9.72 ± 3.63%, p = 0.01) as well as higher CD14++CD16+ monocytes numbers (9.28 ± 6.36 vs. 4.75 ± 2.75%, p = 0.0002). PD patients with prevalent CAD had NK cells levels elevated above median values (85.7 vs. 40.9%, p = 0.04) and lower B cells counts (3.85 ± 2.46 vs. 7.2 ± 3.77%, p = 0.03). Patients with increased NK cells (>15.4%) had 3.8 times higher risk of CAD comparing with patients with lower NK cell levels (95% CI, 1.86 - 77.87; p = 0.034). B cells were inversely associated with the presence of CAD (increase of B-lymphocyte by 1% was associated with 30% less risk for presence of CAD (95% CI, -0.71 - 0.01; p = 0.05). Overhydrated patients had lower lymphocytes counts (18.3 ± 4.29% vs. 24.7 ± 6.18%, p = 0.006) and increased NK cells [20.5% (14.3, 23.6) vs. 13.21% (6.23, 19.2), p = 0.04)]. In multiple logistic regression analysis the CRP (OR 1.43; 95% CI, 1.00 - 2.05; p = 0.04)] and lymphocytes counts (OR 0.79; 95% CI, 0.63-0.99; p = 0.04)] were associated with the presence of lung comets. Patients with higher NK cells (>15.4%, n = 15) were more likely to be rapid transporters (D/P creatinine 0.76 ± 0.1 vs. 0.69 ± 0.08, p = 0.04). Patients displaying higher Tregs (>1.79%) were older (70.8 ± 10.7 years vs. 57.7 ± 14.7years, p = 0.011) and had higher nPCR (0.83 ± 0.14 vs. 0.91 ± 0.17, p = 0.09). Conclusion: Future research is required to evaluate the role of immune cells subsets as potential tools to identify patients at the highest risk for complications and guide interventions.

Acute bacterial sternoclavicular osteomyelitis in a long-term renal transplant recipient.

Kidney transplantation is the treatment of choice for a significant number of patients with end-stage renal disease. Although immunosuppression therapy improves graft and patient's survival, it is a major risk factor for infection following kidney transplantation altering clinical manifestations of the infectious diseases and complicating both the diagnosis and management of renal transplant recipients (RTRs). Existing literature is very limited regarding osteomyelitis in RTRs. Sternoclavicular osteomyelitis is rare and has been mainly reported after contiguous spread of infection or direct traumatic seeding of the bacteria. We present an interesting case of acute, bacterial sternoclavicular osteomyelitis in a long-term RTR. Blood cultures were positive for Streptococcus mitis, while the portal entry site was not identified. Magnetic resonance imaging of the sternoclavicluar region and a three-phase bone scan were positive for sternoclavicular osteomyelitis. Eventually, the patient was successfully treated with Daptomycin as monotherapy. In the presence of immunosuppression, the transplant physician should always remain alert for opportunistic pathogens or unusual location of osteomyelitis.

Side reactions in the SPPS of Cys-containing peptides.

Alkylation of sensitive amino acids during synthesis of biologically important peptides is a common and well-documented problem in Fmoc-based strategy. Herein, we probed for the first time an unexpected S-alkylation of Cys-containing peptides that occur during the final TFA cleavage of peptides from the Wang solid support. Through a battery of approaches (NMR, UV and LC-MS) the formed by-product was assigned as the alkylation of the cysteine sulfydryl group by the p-hydroxyl benzyl group derived from the acidic Wang linker decomposition. Factors affecting this side reaction were monitored and a protocol that minimizes the presence of the by-product is reported.

Hydrogen bonding probes of phenol -OH groups.

Correlations between hydrogen bonds and solvent effects on phenol -OH proton shieldings, temperature coefficients (Δδ/ΔT) and effects on OH diffusion coefficients for numerous phenolic acids, flavonols, flavones, and oleuropein derivatives of biological interest were investigated in several organic solvents and were shown to serve as reliable indicators of hydrogen bonding and solvation state of -OH groups. The temperature coefficients span a range of -0.5 to -12.3 ppb K(-1). Shielding differences of 2.0 to 2.9 ppm at 298 K were observed for solvent exposed OH groups between DMSO-d(6) and CD(3)CN which should be compared with a shielding range of ~7 ppm. This demonstrates that the solvation state of hydroxyl protons is a key factor in determining the value of the chemical shift. For -OH protons showing temperature gradients more positive than -2.5 ppb K(-1), shielding changes between DMSO-d(6) and CD(3)CN below 0.6 ppm, and diffusion coefficients significantly different from those of traces of H(2)O, there is an intramolecular hydrogen bond predictivity value of 100%. The C-3 OH protons of flavonols show very significant negative temperature coefficients and shielding changes between DMSO-d(6) and CD(3)CN of ~2.3 ppm, which indicate the absence of persistent intramolecular hydrogen bonds, contrary to numerous X-ray structures.

Urine of patients with nephrotic syndrome contains the plasma type of PAF-acetylhydrolase associated with lipoproteins.

BACKGROUND: Platelet-activating factor (PAF) is a proinflammatory phospholipid mediator involved in the pathogenesis of glomerulonephritis (GN). In plasma, PAF is hydrolyzed and inactivated by PAF-acetylhydrolase (PAF-AH), an enzyme associated with lipoproteins, mainly with the low-density lipoprotein. PAF-AH activity has been found in urine of patients with primary GN, however the source and type of urinary PAF-AH remain unknown. We characterized the type of PAF-AH excreted in the urine of patients with primary GN and studied the possible relationship of this enzyme with the lipiduria and proteinuria observed in these patients. METHODS: Eighteen patients with primary GN (8 with nephrotic syndrome (NS) and 10 with non-nephrotic range proteinuria (NNRP)) and 20 normolipidemic age- and sex-matched controls participated in the study. PAF-AH activity in plasma, in urine and in individual lipoprotein particles was determined by the trichloroacetic acid precipitation procedure, whereas the PAF-AH protein was detected by Western blotting analysis. Plasma and urine lipoproteins were fractionated by gradient ultracentrifugation and characterized by Western blotting analysis. RESULTS: Plasma PAF-AH activity was higher in NS patients compared with NNRP patients and controls, whereas the enzyme activity associated with high-density lipoprotein was significantly lower in both patient groups compared with controls. PAF-AH was detected only in the urine of NS patients. It was the plasma type of PAF-AH and was associated with lipoprotein particles. Enzyme activity was also positively correlated with urine cholesterol levels. CONCLUSION: Urine of NS patients contains the plasma type of PAF-AH, which is related to the extent of lipiduria and is associated with urine lipoproteins.