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Biomedical subjects

Fausta Micheletta

Publications and source records attributed to Fausta Micheletta.

5 recordsLinked to original sources

Baseline oxysterols and other markers of oxidative stress, inflammation and malnutrition in the vitamin e and intima media thickness progression in end-stage renal disease (VIPER) cohort.

BACKGROUND AND OBJECTIVES: Oxysterols are markers of oxidative stress, levels of which have not yet been reported in hemodialysis (HD) patients. This study was designed to compare levels of the oxysterols 7-ketocholesterol (7KC) and 7beta-hydroxycholesterol (7betaOH) between a cohort of HD patients and healthy controls. METHODS: This nested cross-sectional study reflects baseline (pre-intervention) values for markers of oxidative stress, inflammation and nutrition status in the 160-member vitamin E and carotid intima media thickness progression in end-stage renal disease (VIPER) cohort (age 64.1 +/- 8.8, 33.5% female). Age- and sex-matched healthy volunteers served as controls. Plasma oxysterols 7KC and 7betaOH were determined by isotope dilution gas chromatography/mass spectrometry. RESULTS: Despite higher plasma alpha-tocopherol levels in HD patients than controls (36.0 +/- 9.3 vs. 31.8 +/- 8.4 micromol/l, p = 0.007), 7KC levels (9.8 +/- 6.9 vs. 5.9 +/- 2.8 nmol/mmol cholesterol, p < 0.0001) and 7betaOH levels (8.7 +/- 4.3 vs. 2.7 +/- 1.6 nmol/mmol cholesterol, p < 0.0001) were higher in HD patients. The oxysterol 7betaOH was significantly, inversely associated with prealbumin (r = -0.18, p = 0.03), though neither oxysterol was significantly associated with any other marker of oxidative stress, inflammation or nutrition status and did not discriminate for CVD in HD patients. CONCLUSIONS: Elevated levels of the oxysterols 7KC and 7betaOH indicate that HD patients are in a state of oxidative stress compared to healthy controls. However, oxysterols 7KC and 7betaOH did not appear to contribute additional information about oxidative stress among HD patients.

Adult↗

High preoperative recipient plasma 7beta-hydroxycholesterol is associated with initial poor graft function after liver transplantation.

Oxidative stress is implicated in the pathogenesis of hepatic ischemia-reperfusion injury, a major determinant of initial poor graft function (IPGF) after orthotopic liver transplantation (OLT). We prospectively investigated the association between the recipient plasma preoperative oxidative stress and the occurrence of IPGF after deceased-donor OLT and indirectly studied the source-hepatic or extra-hepatic-of systemic oxidative stress in vivo in cirrhosis. We used a recently developed specific and sensitive mass spectrometry assay to measure 7beta-hydroxycholesterol and 7-ketocholesterol (oxysterols), markers of oxidative stress, in biological matrices. At univariate analysis, preoperative recipient 7beta-hydroxycholesterol plasma concentration was significantly higher in transplants with subsequent IPGF (n = 9) compared with those with initial good graft function (IGGF; n = 23) [mean +/- SD: 30.63 +/- 26.42 and 11.57 +/- 15.76 ng/mL, respectively] (P = 0.017). In a logistic regression model, which included also the Model for End-Stage Liver Disease (MELD) score, 7beta-hydroxycholesterol plasma concentration was an independent predictor of IPGF with an odds ratio of 1.17 (95% CI, 1.02-1.33, P = 0.028). Patients with cirrhosis (n = 32) had increased oxysterol plasma levels compared with healthy controls (n = 49); livers with cirrhosis (n = 21), however, had oxysterol content comparable with normal livers obtained from organ donors (n = 19). Oxysterols persisted elevated in plasma 1 month after OLT (n = 23). In conclusion, cirrhosis presents upregulated systemic oxidative stress likely of extrahepatic source that is associated with graft failure after OLT.

Biomarkers↗

Vitamin E supplementation in patients with carotid atherosclerosis: reversal of altered oxidative stress status in plasma but not in plaque.

OBJECTIVE: Oxidative stress is believed to play a pivotal role in the initiation and progression of atherosclerosis. We analyzed whether vitamin E supplementation influences oxidative stress in plasma and atherosclerotic plaques of patients with severe atherosclerosis. METHODS AND RESULTS: In 16 patients who were candidates for carotid endarterectomy and in 32 age- and sex-matched controls, plasma levels of 7beta-hydroxycholesterol, 7-ketocholesterol, cholesterol, and vitamin E were measured. Patients were randomly allocated to standard treatment with or without 900 mg/d vitamin E. After 6 weeks of treatment, the reported variables were measured in plasma and plaques. The plasma vitamin E/cholesterol ratio was significantly lower in patients than in controls (3.05+/-0.6 versus 6.3+/-1.7 micromol/mmol cholesterol, P<0.001). Plasma 7beta-hydroxycholesterol was significantly higher in patients than in controls (5.0+/-1.04 versus 4.4+/-0.6 ng/mL, P<0.05). Patients who were given vitamin E supplementation showed a significant increase of plasma vitamin E with concomitant decrease of 7beta-hydroxycholesterol. Conversely, no treatment dependence was observed in oxysterol or vitamin E content of plaques. CONCLUSIONS: An imbalance between oxidative stress and antioxidant status is present in patients with advanced atherosclerosis. Vitamin E supplementation improves this imbalance in plasma but not in plaques.

Adolescent↗