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Background Several evidence show that elevated plasma levels of uric acid (UA) are associated with the increased risk of developing atherothrombotic cardiovascular events. Hyperuricemia is a risk factor for endothelial dysfunction (ED). ED is involved in the pathophysiology of atherothrombosis since dysfunctional cells lose their physiological, antithrombotic properties. We have investigated whether UA might promote ED by modulating the tissue factor (TF)/TF pathway inhibitor (TFPI) balance by finally changing the antithrombotic characteristics of endothelial cells. Methods Human umbilical vein endothelial cells were incubated with increasing doses of UA (up to 9 mg/dL). TF gene and protein expressions were evaluated by real-time polymerase chain reaction (PCR) and Western blot. Surface expression and procoagulant activity were assessed by FACS (fluorescence activated cell sorting) analysis and coagulation assay. The mRNA and protein levels of TFPI were measured by real-time PCR and Western blot. The roles of inflammasome and nuclear factor-κB (NF-κB) as possible mechanism(s) of action of the UA on TF/TFPI balance were also investigated. Results UA significantly increased TF gene and protein levels, surface expression, and procoagulant activity. In parallel, TFPI levels were significantly reduced. The NF-κB pathways appeared to be involved in modulating these phenomena. Additionally, inflammasome might also play a role. Conclusion The present in vitro study shows that one of the mechanisms by which high levels of UA contribute to ED might be the imbalance between TF/TFPI levels in endothelial cells, shifting them to a nonphysiological, prothrombotic phenotype. These UA effects might hypothetically explain, at least in part, the relationship observed between elevated plasma levels of UA and cardiovascular events.

Staging and monitoring of multiple myeloma (MM) is mainly based on monoclonal component quantification; the absence of such a parameter renders difficult follow up of patients with nonsecretory MM (nsMM). In this study our aims were to determine the specificity and sensitivity of Tc99m-sestaMIBI scintigraphy at diagnosis and during follow up of nsMM patients. Nine nsMM patients were prospectively studied at diagnosis and during treatment for a mean time of 33 months (range: 12 - 65 þ ). Tc99m-sestaMIBI (MIBI) scintigraphy was compared to conventional imaging (CI: X ray with CAT or NMR details) at diagnosis and during follow up. At diagnosis, CI and MIBI were concordant in three patients; CI showed more focal lesions than MIBI in four patients, while MIBI revealed more focal lesions than CI in two patients. During the follow up, MIBI uptake was normal in the four patients who achieved remission. Five patients did not achieve remission: CI and MIBI were concordant in three, while MIBI was falsely negative in two patients. In conclusion, Tc99m-sestaMIBI scintigraphy has high sensitivity (no false positive cases) and 78% specificity (2/9 false negative cases) in tracing active nsMM lesions; it should be considered complementary to CI for monitoring this rare disease.

Hepatitis flare-up due to hepatitis B virus (HBV) is a well-recognized complication associated with chemotherapy. Data on the clinical impact of HBV DNA in liver tissue of HB-surface antigen (sAg)-negative patients undergoing immunosuppression are scanty.

Background. Increased serum leptin has been described after various organ transplants, with a mechanism that is still unclear. Methods. We measured serum leptin in 60 patients before and after allogeneic (allo) or autologous (auto) stem cell transplant (SCT) and in 60 healthy controls, matched for age and body mass index (BMI). Results. Serum leptin was higher in patients after SCT than before and in controls. Leptin production was higher after allo- than after auto-SCT; the presence of chronic graft-versus-host disease (cGVHD) was associated with the highest values. The physiological correlation with BMI was lost in the allogeneic setting, indicating a strong influence of factors other than the nutritional status on circulating leptin. No relationship was found between serum leptin levels and time from transplant, age, cortisol, C-reactive protein, and T-lymphocyte CD4-to-CD8 ratio. Among the cytokines secreted by type-1/type-2 T-helper lymphocytes, only serum interferon-gamma significantly correlated with serum leptin levels. Anti-leptin blocking antibodies partially inhibited T-cell activation in mixed lymphocyte reaction, suggesting a link between leptin and T-lymphocyte activation in the allo-SCT setting. Conclusion. Taken together, these findings suggest that increased serum leptin concentrations may contribute to T-cell activation during development of cGVHD.

Osteoporosis and avascular necrosis (AVN) are long-lasting and debilitating complications of hematopoietic stem cell transplantation (HSCT). We describe the magnitude of bone loss, AVN and impairment in osteogenic cell compartment following autologous (auto) and allogeneic (allo) HSCT, through the retrospective bone damage revaluation of 100 (50 auto- and 50 allo-HSCT) long-term survivors up to 15 years after transplant. Current treatment options for the management of these complications are also outlined. We found that auto- and allo-HSCT recipients show accelerated bone mineral loss and micro-architectural deterioration during the first years after transplant. Bone mass density (BMD) at the lumbar spine, but not at the femur neck, may improve in some patients after HSCT, suggesting more prolonged bone damage in cortical bone. Phalangeal BMD values remained low for even more years, suggesting persistent bone micro-architectural alterations after transplant. The incidence of AVN was higher in allo-HSCT recipients compared to auto-HSCT recipients. Steroid treatment length, but not its cumulative dose was associated with a higher incidence of bone loss. Allo-HSCT recipients affected by chronic graft versus host disease seem to be at greater risk of continuous bone loss and AVN development. Reduced BMD and higher incidence of AVN was partly related to a reduced regenerating capacity of the normal marrow osteogenic cell compartment. Our results suggest that all patients after auto-HSCT and allo-HSCT should be evaluated for their bone status and treated with anti-resorptive therapy as soon as abnormalities are detected.