Effects of structured home-based exercise training on circulating endothelial progenitor cells and endothelial function in patients with intermittent claudication.

INTRODUCTION: Exercise training improves walking capacity in patients with intermittent claudication (IC). Endothelial progenitor cells (EPCs), endothelial microparticles (EMPs), and endothelial dysfunction could play a role in this process. METHODS: We measured EPCs and EMPs in a group of 60 patients with IC, and in a control group of 20 individuals without IC, before a treadmill test and 2, 24, and 48 hours after the test. Thirty patients with IC were randomly assigned to perform a 12-week home-based exercise training program. The EPC count, flow-mediated dilation (FMD) of the brachial artery, pain-free walking time (PFWT), and maximum walking time (MWT) were measured at the baseline and after the exercise training program. RESULTS: In patients with IC, EMPs significantly increased 2 hours after the treadmill test, whereas EPCs significantly increased after 24 hours. Among the subjects assigned to complete the training program, we observed a significant increase in the number of EPCs after 12 weeks, as well as an improvement in FMD, PFWT, and MWT. A significant correlation between the variation of EPCs, FMD, and MWT was found. The increase of EPCs and FMD were independent determinants of the walking capacity improvement, without significant interaction. CONCLUSION: Our results suggest that EPCs mobilization contributes to the improvement of walking capacity in patients with IC undergoing structured physical training. A number of different, partly independent, mechanisms are involved in this process, and our results highlight the potential role of EMPs release and endothelial function improvement. ClinicalTrials.gov Identifier: NCT04302571.

Very Low-Carbohydrate Ketogenic Diet for the Treatment of Severe Obesity and Associated Non-Alcoholic Fatty Liver Disease: The Role of Sex Differences.

Very low-carbohydrate ketogenic diets (VLCKDs) are an emerging nutritional treatment for severe obesity and are associated with a significant improvement in non-alcoholic fatty liver disease (NAFLD). Little is known about the effect of sex differences on weight loss induced by following a VLCKD. The aim of this study was to investigate the effects of sex differences on weight loss and NAFLD improvement in patients with severe obesity undergoing a VLCKD. Forty-two females and 28 males with severe obesity underwent a 25-day VLCKD. Anthropometric parameters, bioimpedentiometry, degree of liver steatosis measured by ultrasonography, liver function tests, and glucose homeostasis were measured before and after the VLCKD. Males experienced a significantly larger excess body weight loss (EBWL) and a greater reduction in γ-glutamyl transferase (γGT) than females. Dividing the female group by menopausal status, a significant difference between males and pre-menopausal females was found for both EBWL and γGT. No significant difference between groups was observed for improvement in the Edmonton stage or in the degree of steatosis. We conclude that the efficacy of following a VLCKD in severe obesity is affected by sex differences and, for females, by menopausal status. Males seem to experience larger benefits than females in terms of EBWL and NAFLD improvement. These differences are attenuated after menopause, probably because of changes in hormonal profile and body composition.

Hematological and Biochemical Reference Intervals for 5 Adult Hunting Dog Breeds Using a Blood Donor Database.

Numerous studies have shown the importance of breed-related differences between hematological and biochemical results in veterinary medicine. The aim of this study is to determine hematologic and biochemical Reference Intervals (RIs) for 5 hunting dog breeds from a blood donor database, adopting an indirect sampling method, and to compare them with laboratory established and published RIs to identify possible breed and attitude-related differences. The study analyzed the blood parameters of 445 adults (222 females and 223 male, with age ranging from 2 to 8 years, mean age 5.3 years), client-owned, clinically healthy blood donor dogs of 5 breeds: 156 Ariégeois, 52 Bleu de Gascogne, 64 Bracco italiano, 123 Segugio italiano, and 50 Briquet Griffon Vandeen. Statistical analysis was performed as recommended by the American Society of Veterinary Clinical Pathology (ASVCP) guidelines. RIs for red blood cells (RBC), hematocrit (HCT), hemoglobin (HB), main corpuscular volume (MCV), main corpuscular hemoglobin (MCH), main corpuscular hemoglobin concentration (MCHC), red distribution widht (RDW), white blood cells (WBC), and differential leukocytes count, PLT, Albumin, Total Protein, Urea, Creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) for each of the 5 breeds were performed, and significant differences with the established RIs were detected. We found significant differences in 12 hematologic and serum biochemical analytes for which a breed-specific variation appears to be the most plausible explanation. New RIs for HCT, MCH, MCHC, RDW, PLT, Monocytes, Eosinophils, Albumin, Urea, Creatinine, AST, and ALT are provided for at least 1 breed. Breed-specific RIs for adult hunting dogs will help avoid misinterpretation of laboratory results in these breeds.

Chemerin predicts carotid intima-media thickening in severe obesity.

BACKGROUND AND AIMS: Chemerin is an adipokine with an emerging role in the crosstalk between adipose tissue and immune system. It is overexpressed in severe obesity, affects adipogenesis and glucose homeostasis and it correlates with early vascular damage. The aim of this study is to investigate the correlation between circulating levels of chemerin and early vascular damage in subjects with severe obesity, before and after laparoscopic sleeve gastrectomy (LSG). METHODS: Fifty-six obese subjects eligible for LSG were enrolled in the study. The following parameters were evaluated: body mass index (BMI), glycemia, insulinemia, glycated haemoglobin, lipid profile, plasma chemerin levels and carotid intima-media thickness (cIMT). Fifty-four subjects were evaluated 1 year after the intervention. RESULTS: Univariate analysis showed a direct and significant correlation between chemerin and waist circumference, insulin resistance, glycated haemoglobin and cIMT. Chemerin was a better predictor of intima-media thickening than waist circumference and glycated haemoglobin at the ROC curve analysis, with a cut-off value for chemerin of 140 ng/mL. The reduction of chemerin is independently associated with the reduction of cIMT and the improvement of insulin sensitivity after LSG. CONCLUSION: Chemerin is involved in the development and progression of early vascular damage and insulin resistance in subjects with severe obesity, and in their healing after bariatric surgery. Chemerin could also have a role in the assessment of cardiovascular risk in subjects with severe obesity.

Increased plasmatic NETs by-products in patients in severe obesity.

Neutrophil extracellular traps (NETs) are DNAs products involved in immune process. Obesity through a low-grade chronic inflammation determines neutrophil activation, but it is still unclear its role in NETs formation. Here we analyzed the NETs levels in healthy and morbid obese, their association with anthropometric and glyco-metabolic parameters and their changes after bariatric surgery. For this study, we enrolled 73 patients with morbid obesity (BMI ≥40 kg/m2 or ≥35 kg/m2 + comorbidity) eligible to sleeve gastrectomy. In parallel, 55 healthy subjects and 21 patients with severe coronary artery disease were studied as controls. We evaluated anthropometric parameters, peripheral blood pressure, biochemical and serum analysis at the enrollment and at twelve months after surgery. Plasmatic levels of MPO-DNA complexes were assessed by ELISA. NETs levels were higher in obese than in control group (p < 0.001) and correlated with the main anthropometric variable (BMI, waist, hip), glyco-metabolic variables and systolic blood pressure. NETs trend after intervention was uneven. The reduction of NETs correlated with the entity of reduction of BMI (ρ = 0.416, p < 0.05), visceral fat area (ρ = 0.351, p < 0.05), and glycemia (ρ = 0.495, p < 0.001). In medical history of patients in whom NETs increased, we observed a higher number of thromboembolic events. Our observations indicate that severe obesity is associated with increased generation of NETs, which in turn could influence the patients' systemic inflammatory state. Weight loss and in particular, loss of adipose tissue after bariatric surgery does not in itself correct NET's dysregulated production. Finally, patients in whom NETs accumulation persists after surgery are probably those at the highest risk of cardiovascular events.

Lysosomal Acid Lipase as a Molecular Target of the Very Low Carbohydrate Ketogenic Diet in Morbidly Obese Patients: The Potential Effects on Liver Steatosis and Cardiovascular Risk Factors.

A very low carbohydrate ketogenic diet (VLCKD) is an emerging technique to induce a significant, well-tolerated, and rapid loss of body weight in morbidly obese patients. The low activity of lysosomal acid lipase (LAL) could be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is a common feature in morbidly obese patients. Fifty-two obese patients suitable for a bariatric surgery intervention underwent a 25-day-long VLCKD. The biochemical markers of glucose and lipid metabolism, and flow-mediated dilation (FMD) of the brachial artery were measured before and after VLCKD. LAL activity was measured using the dried blood spot technique in 20 obese patients and in a control group of 20 healthy, normal-weight subjects. After VLCKD, we observed a significant reduction in body mass index, fasting glucose, insulinemia, and lipid profile parameters. No significant variation in FMD was observed. The number of patients with severe liver steatosis significantly decreased. LAL activity significantly increased, although the levels were not significantly different as compared to the control group. In conclusion, VLCKD induces the activity of LAL in morbidly obese subjects and reduces the secretion of all circulating lipoproteins. These effects could be attributed to the peculiar composition of the diet, which is particularly poor in carbohydrates and relatively rich in proteins.

Combined aerobic and resistance training improves microcirculation in metabolic syndrome.

BACKGROUND: Exercise intervention improves macrovascular function in metabolic syndrome (MeS) patients, but few studies have evaluated the effect of exercise on microcirculatory dysfunction, which plays a key role in the development of MeS and its correlated organ damage. We carried out this intervention study to evaluate the influence of an aerobic and resistance training on skin microvascular reactivity in MeS patients. METHODS: Postocclusive reactive hyperemia (PORH) of the forearm skin was evaluated, by laser-Doppler flowmetry, before and after a 12-week program of aerobic and resistance training in 15 MeS patients referring to our Lipid Metabolism Outpatients Clinic, together with anthropometric, fitness and metabolic parameters; 15 matched MeS patients who did not exercise, served as a control group. The exercise training consisted of 2 sessions/week of aerobic and resistant exercise. RESULTS: Following exercise program, we observed a significant reduction in body weight, fat mass, fasting blood glucose, serum HbA1c and triglycerides, while HDL-cholesterol significantly increased. The exercise-treated group experienced a significant improvement in the area of hyperemia (AH) after PORH, and in all fitness parameters: VO2max, strength on the pulldown lat machine, chest press, leg press and leg extension. A significant correlation emerged between the increase in AH and the reduction in HbA1c and between increase in AH and strength at the chest press, and at the leg extension. CONCLUSIONS: Our study showed that a short-term combined aerobic-resistance training positively affects microvascular reactivity in MeS patients. This improvement is correlated with the reduction of HbA1c and fitness parameters, and particularly with increased muscle strength at the upper and lower limbs.

A silent mutation of Niemann-Pick C1-like 1 and apolipoprotein E4 modulate cholesterol absorption in primary hyperlipidemias.

OBJECTIVE: To investigate the influence of the silent mutation c.816C > G (L272) of Niemann-Pick C1-like 1 (NPC1L1) and of apolipoprotein (APO) E alleles on cholesterol absorption markers, sitosterol and campesterol, in 87 patients with primary hyperlipidemias. METHODS: In all subjects genotyped for silent polymorphism in NPC1L1 gene c.816C > G (L272L) and for APO E polymorphism, campesterol and sitosterol were measured by gas chromatography coupled to mass spectrometry. RESULTS: Thirty-eight patients carrying the G allele of NPC1L1 showed significantly greater concentrations (log values) of campesterol (1.86 ± 0.3 vs 1.61 ± 0.3 10(2) µmol/mmol cholesterol, p < .001) and sitosterol (2.03 ± 0.2 vs 1.94 ± 0.2 10(2) µmol/mmol cholesterol, P = .05). Patients with at least one E4 allele showed values of sitosterol greater than those carrying E3E3 or E3E2 (2.05 ± 0.2 10(2) µmol/mmol cholesterol vs 1.95 ± 0.2 10(2) µmol/mmol cholesterol, P = .004). The presence of the G allele (ß = .379, P < 0.001) and high-density lipoprotein cholesterol (ß = .242, P = .019) was an independent predictor of campesterol values (R of the model = 0.473, P < .001). The E4 allele (ß = .293, P = .005) and high-density lipoprotein cholesterol (ß = .311, P = .003) were independent predictors of sitosterol values (R 0.416, P of the model <.001). CONCLUSIONS: In patients with hyperlipidemias, G allele of NPC1L1 and APO E4 could account for some of the inter-individual variability in cholesterol absorption.

Cholesterol metabolism differs after statin therapy according to the type of hyperlipemia.

AIM: Non-cholesterol sterols reflect cholesterol metabolism. Statins reduce cholesterol synthesis usually with a rise in cholesterol absorption. Common hyperlipemias have shown different patterns of cholesterol metabolism. We evaluated whether cholesterol absorption and synthesis may differ after statin therapy in primary hyperlipemias. MAIN METHODS: We determined lipid profile, apoprotein B and serum sterols (lathosterol, sitosterol, campesterol by gas chromatography/mass spectrometry) before and after statins in 80 untreated hyperlipemic patients, 40 with polygenic hypercholesterolemia (PH) and 40 with familial combined hyperlipemia (FCH). KEY FINDINGS: At baseline in FCH lathosterol was significantly higher while campesterol and sitosterol were significantly lower than in PH. After statins, the reduction in LDL-C did not significantly differ between the two groups; in PH there was a significant decrease of lathosterol from 96.1 to 52.6 102 µmol/mmol cholesterol (p=0.0001) with no significant modifications in campesterol and sitosterol; on the opposite, in FCH lathosterol decreased from 117 to 43 102 µmol/mmol cholesterol (p=0.0001) and campesterol and sitosterol significantly increased from 38 to 48 102 µmol/mmol cholesterol (p=0.0001), and from 75 to 86 102 µmol/mmol cholesterol, (p=0.022), respectively. After statin therapy only in FCH Δ-LDL-C showed a significant inverse correlation with Δ-sitosterol and with Δ-campesterol. SIGNIFICANCE: Primary hyperlipemias show different patterns of response to statins: in PH LDL reduction appears completely "synthesis inhibition" dependent, while in FCH LDL decrease appears to be synthesis dependent, partially limited by absorption increase. Studying cholesterol metabolism before and after hypolipemic therapy might be useful in identifying the best tailored treatment.

Visceral fat positively correlates with cholesterol synthesis in dyslipidaemic patients.

BACKGROUND: Quantification of plasma noncholesterol sterols allows the study of cholesterol absorption and synthesis. A pattern of low cholesterol absorption and high synthesis has been demonstrated in patients with obesity and insulin resistance. To understand the relationship between cholesterol absorption/synthesis and visceral obesity, we investigated surrogate markers of cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol) in dyslipidaemic patients with different representation of abdominal fat, estimated by ultrasonographic measurement of visceral fat area (VFA). METHODS: In 126 patients with primary hyperlipaemias, plasma sitosterol, campesterol and lathosterol were determined by gas chromatography coupled with mass spectrometry. Visceral and subcutaneous fats were evaluated by ultrasonography. The study population was divided into two groups on the basis of VFA median values, below/equal and above 154 cm(2) . RESULTS Patients with higher VFA had significantly higher lathosterol levels (median 109 vs. 76 × 10(2) µmol/mmol cholesterol P < 0·004), body mass index, waist circumference, blood pressure, triglycerides, insulin, homoeostatic model assessment (HOMA)-IR and lower high-density lipoprotein (HDL)-C. VFA was positively correlated with lathosterol (ρ = 0·35, P < 0·001) and negatively with HDL-C (ρ = -0·43, P < 0·001), campesterol (ρ = -0·23, P = 0.01) and sitosterol (ρ = -0·35, P < 0·001). VFA was an independent predictor of lathosterol values (ß = 0·389, P < 0·0001, P of the model < 0·0001);age, systolic blood pressure, BMI, waist circumference, triglycerides, HDL-C and HOMA failed to enter the final equation. CONCLUSIONS: In hyperlipidaemic patients, the amount of visceral fat correlates with cholesterol synthesis; the use of ultrasonographic detection of abdominal adiposity allows a better characterization of cholesterol pathway, potentially useful for a tailored therapeutic approach.

Cardiovascular risk factors and recommended lipid goals attainment among patients referred in a tertiary care lipid clinic.

BACKGROUND: Many adults are not at recommended lipid levels and the extent of treatment of dyslipidemia remains poor. We investigated the burden of cardiovascular risk and the distance of lipid fractions from the recommended targets by statin therapy and risk status in patients referred to a tertiary care lipid clinic. METHODS: Assessment of cardiovascular risk factors was performed in 1657 patients, mostly dyslipidemics, referred by family physicians to our Lipid Clinic, 393 patients being under statin therapy. The shortfall of lipid fractions from the National Cholesterol Education Program Adult Treatment Panel-III (NCEP ATP-III) recommended goals was evaluated. RESULTS: A high prevalence of cardiovascular risk factors was found. LDL cholesterol target was reached by 20% and 45% of untreated and statin treated patients, whereas non-HDL cholesterol target by 13% and 45% of untreated and statin treated patients, respectively. LDL cholesterol was over the goal by 27% in untreated patients and by 25% in statin treated patients. More than 40% and 65% statin treated patients were taking either a low statin dose or statins with low-to-moderate LDL cholesterol lowering efficacy (<30%). A decrease in the proportion of patients at target and greater shortfalls from recommended goals were found from low to high risk categories. CONCLUSION: The shortfall in reaching lipid targets, particularly among high risk statin untreated patients, may be partly explained by delayed or even inadequate lipid lowering therapy. Shortfalls in reaching the targets are not necessarily high and might be possibly managed at a primary care level.

Semi-quantitative analysis of perfusion of Brodmann areas in the differential diagnosis of cognitive impairment in Alzheimer's disease, fronto-temporal dementia and mild cognitive impairment.

Different perfusion defects reflect neurological damage characteristics of different kinds of dementia. Our aim was to investigate the role of brain single photon emission tomography (SPET) with semiquantitative analysis of Brodmann areas in dementia, by technetium-99m - hexamethyl-propylenamine- oxime ((99m)Tc-HMPAO) brain SPET with semiquantitative analysis of Brodmann areas in patients with Alzheimer's disease (AD), frontotemporal dementia (FTD) and mild cognitive impairment (MCI). We studied 75 patients, 25 with AD (NiNCDS ADRDA criteria), 25 with FTD (Lund and Manchester criteria), 25 with MCI (EADC criteria). After i.v. injection of 740MBq of (99m)Tc-HMPAO, each patient underwent brain SPET. A software application was used able to map the SPET brain image to a stereotaxic atlas (Talairach), providing an affine co-registration by blocks of data defined in the Talairach space. A normal database calculating voxel by voxel the mean and the standard deviation of the measured values was built. Functional SPET data of 3D regions of interest (ROI) of predefined Brodmann's area templates were compared with those of a database of healthy subjects of the same age and gender. Mean values obtained in the Brodmann area ROI in the different groups of patients studied were evaluated. Our results showed that different Brodmann areas were significantly impaired in the different categories of dementia subjects. Both areas 37 (temporal gyrus) and 39 (angular gyrus) of AD patients (mean+/-SD: 37L= -1.6+/-1.0; 37R= -1.5+/-1.1; 39L= -2.3+/-1.3; 39R= -1.9+/-1.2) showed significant hypoperfusion (P<0.05) versus MCI (37L= -0.9 +/-0.7; 37R= -1.1+/-0.9; 39L= -1.4+/-1.1; 39R= -1.6+/-1.6.) and FTD (37L= -1.1+/-0.8; 37R= -1.0+/-0.9; 39L= -1.4+/-1.0; 39R= -1.2+/-1.2) subjects. AD patients showed significantly (P<0.01) decreased perfusion in areas 40 (supramarginal gyrus) (40L= -2.6+/-1.0; 40R= -2.3+/-1.1) with respect to MCI patients (40L= -1.8+/-0.9; 40R= -1.7+/-1.2). Finally, FTD patients showed significant hypoperfusion (P<0.05) in both areas 47 (frontal association cortex) (47L= -1.8+/-0.8; 47R= -1.1+/-0.8) in comparison with MCI subjects (47L= -1.2+/-0.9; 47R= -0.9+/-0.9). In conclusion, our results suggest that semiquantitative analysis of single Brodmann areas identify frontal area hypoperfusion in FTD patients and also parietal and temporal impairment in AD patients. In MCI patients, no hypoperfusion pattern is identified.

Cerebrospinal fluid neuron-specific enolase: a further marker of Alzheimer's disease?

To investigate whether neuron-specific enolase (NSE) plays a role in dementia, we measured cerebrospinal fluid (CSF) concentrations of NSE, Abeta42 and total protein tau (h-tau) in different dementia patients. We studied 159 patients: 76 with Alzheimer's disease (AD), 35 with mild cognitive impairment (MCI), 28 with frontotemporal dementia (FTD), and 20 with Lewy body disease (LBD). Thirty healthy age-matched subjects were studied as controls. NSE was measured by immunoradiometric assay, Abeta42 and h-tau were dosed by ELISA assay. Mean CSF NSE was significantly higher in AD (15.1+/-9.9 ng/ml) than in controls (8.3+/-3.5 ng/ml, p<0.01), FTD (9.1+/-6.1 ng/ml, p<0.05) and MCI (9.7+/-7.8 ng/ml, p<0.05). Ab42 was significantly lower in AD (413.8+/-163.7 pg/ml) than in MCI (708.4+/-422.1 pg/ml, p<0.001) and controls (914.4+/-277.1 pg/ml, p<0.05); it was also significantly reduced in FTD (497.1+/-221.9 pg/ml) versus MCI (p<0.05) and controls (p<0.001); and in LBD patients (477.1+/-225.7 pg/ml) compared with MCI (p<0.05) and controls (p<0.001). H-tau concentration was significantly higher in AD (607.9+/-372.3 pg/ml, p<0.001) than in MCI (383.8+/-277.9 pg/ml, p<0.05), controls (176.6+/-43.9 pg/ml, p<0.001) and LBD (472.3+/-357.7 pg/ml, p<0.05); it was also increased in FTD (541.76+/-362.8 pg/ml) versus contro s (176.6+/-43.9 pg/ml, p<0.001). Furthermore, NSE was inversely correlated with Ab42 (r=-0.333, p=0<0001) and directly correlated with h-tau (r=0.370, p=0<0001). In conclusion, CSF NSE emerged as a specific indicator of AD and showed the same behaviour as the other accepted markers of AD, being correlated with both biomarkers.

Preclinical vascular damage in white postmenopausal women: the relevance of osteoprotegerin.

Osteoprotegerin (OPG) has recently been implicated in human atherogenesis. Abdominal obesity represents an established risk factor for the onset and development of atherosclerotic damage. The aim of the present study was to investigate the link between OPG and abdominal fat and the relationship to precocious features of atherosclerotic disease such as brachial flow-mediated vasodilation (FMV) and the intima-media thickening (IMT) in 195 white postmenopausal women (age range, 43-75 years). The study population was divided into 2 groups: group 1-waist circumference <80 cm and group 2-waist circumference > or = 80 cm. Group 2 had higher menopausal years, body mass index, low-density lipoprotein cholesterol, triglycerides, C-reactive protein, and carotid IMT. High-density lipoprotein cholesterol was higher in group 1. Afterward, these groups were divided on the basis of a cutoff value of OPG (6.85 pmol/L) that was the median of its distribution: patients with OPG < or = 6.85 pmol/L were OPG(-), and those with OPG >6.85 pmol/L were OPG(+). The OPG(+) subjects in both had lower brachial FMV and higher carotid IMT in comparison with OPG(-) subjects. At the multivariate regression analysis, waist circumference, high-density lipoprotein cholesterol, C-reactive protein, and OPG were predictors of carotid mean IMT (beta = 0.55, P = .001; beta = -0.14, P = .001; beta = 0.16, P = .001; and beta = 0.14, P = .05, respectively) and age, OPG, low-density lipoprotein cholesterol, and brachial diameter of brachial FMV (beta = -0.13, P = .05; beta = -0.25, P = .001; beta = -0.14, P = .024; and beta = 0.48, P = .001, respectively). The conclusions are as follows: first, OPG levels did not appear to be conditioned by a risk factor such as abdominal obesity; and second, OPG levels are mainly linked to the evidence of vascular damage. On this basis, we could speculate that OPG levels may be considered not a cardiovascular risk condition but a defense against atherosclerotic progression.

Human endothelial impairment in sepsis.

The onset of sepsis is often non-specific, and its severity is cryptic. The pathophysiological mechanism of sepsis development involves vascular alteration and, in particular, the impairment of endothelial function. Aim of the study was to evaluate the potential implications of brachial endothelial function assessment in patients affected by Gram-negative sepsis. Forty-five young patients (mean age 41+/-8 years, 18 males) with Gram-negative sepsis were included; at admission time (T0) signs and symptoms, clinical and laboratory data were collected; the Sequential Organ Failure Assessment (SOFA) score was assessed at the time of the access along with the evaluation of brachial flow-mediated vasodilation (FMV). The same parameters were repeated 3 days after hospitalization (T1). Study population at the hospitalization time was divided on the basis of a brachial FMV cut off: at the T0 subjects with FMV<7.5% had lower white blood cell count in comparison to subjects with FMV> or =7.5% (6693+/-1559 mmc versus 14,270+/-2399 mmc); subjects with FMV<7.5% had a significant increase in SOFA score at T1 (4+/-1 versus 6+/-1) and a significant reduction of brachial FMV at T1 (4.8+/-2.7% versus 3.7+/-2.6%) (all p<0.05). FMV at the admission time was predicted by white blood cells (beta=0.65; p<0.001) and brachial diameter (beta=-0.292; p<0.05); Delta changes in FMV were predicted by changes in SOFA score (beta=-0.41; p<0.05). In conclusion, the present study indicates that in the initial phase of sepsis an impairment of brachial FMV anticipated the progression in organ failures; these considerations support the potential utility of brachial FMV in clinical practice in acute pathologies as septic state.

Metabolic syndrome and preclinical atherosclerosis: focus on femoral arteries.

Several evidences revealed the relationship between the earliest stages of atherosclerosis and the components of metabolic syndrome. The aim of this study was to disclose preclinical atherosclerotic lesions in a cross-sectional observational study involving 147 patients with metabolic syndrome by the assessment of brachial flow-mediated vasodilation (FMV) and intima-media thickening at both carotid and femoral sites. The purpose was to investigate the association of this metabolic disorder with prevalent atherosclerotic damage in different vascular sites. A control group of 87 healthy subjects was also investigated. Patients had lower values of FMV and a higher mean intima-media thickness (IMT) at both the carotid and femoral sites with respect to controls. Flow-mediated vasodilation had a positive correlation with high-density lipoprotein (HDL) cholesterol and a negative one with low-density lipoprotein (LDL) cholesterol, glycemia, and insulinemia. Carotid mean IMT was directly related to LDL cholesterol and age, and inversely with HDL cholesterol; femoral mean IMT had a direct association with LDL cholesterol, triglycerides, glycemia, and insulinemia and an inverse correlation with HDL cholesterol and LDL size. LDL cholesterol, HDL cholesterol, insulin, and brachial artery diameter were predictive of brachial FMV (beta=-0.17, 0.21, -0.27, and -0.29, respectively; P<.05), whereas age, LDL cholesterol, and HDL cholesterol were independent predictors of mean carotid IMT (beta=0.19, 0.37, and -0.27, respectively; P<.05); on the other hand, LDL cholesterol, triglycerides, and insulin were independent predictors of mean femoral IMT (beta=0.32, 0.26, and 0.25, respectively; P<.05). In conclusion, the present study documented an altered endothelial function and intima-media thickening in patients with metabolic syndrome without overt cardiovascular disease. Moreover, it focused on the strong influence of metabolic syndrome on preclinical atherosclerotic lesions at the femoral site.

Effects of rosuvastatin on 3-nitrotyrosine and aortic stiffness in hypercholesterolemia.

BACKGROUND AND AIMS: Early atherosclerosis is characterized by reduced large artery distensibility, paralleled by an increased peroxynitrite formation and nitration of tyrosine in proteins. The aim of the present study was to investigate the short-term effect of cholesterol lowering with rosuvastatin on 3-nitrotyrosine (3-NT), a marker of peroxynitrite-mediated oxidative stress, and on arterial stiffness. METHODS AND RESULTS: 71 outpatients with primary hypercholesterolemia were recruited for this randomized open-label intervention study; 35 patients were assigned to 4-week rosuvastatin therapy (10mg daily) with a low-fat diet, and 36 patients to a low-fat diet only. Within the cohort of 71 hypercholesterolemic patients, there was a significant correlation between cholesterol levels, 3-NT and aortic pulse wave velocity (aPWV), that is a reliable measure of aortic stiffness. Among those patients who received rosuvastatin, significant reductions in plasma cholesterol, 3-NT and aPWV were observed. Reductions in both aPWV and 3-NT levels correlated significantly with the decrease in plasma cholesterol. Reduction of plasma cholesterol was the only independent predictor for reduced arterial stiffness following rosuvastatin therapy. CONCLUSION: Cholesterol reduction achieved following short-term rosuvastatin therapy is associated with a decrease in peroxynitrite-mediated oxidative stress and an improvement in large artery distensibility; reduction in arterial stiffness is directly attributable to rosuvastatin-induced cholesterol lowering and not to reduction of plasma 3-NT levels.

Racial difference in endothelial function: role of the infective burden.

There is much evidence to suggest the existence of racial differences between blacks and whites in the behaviour of endothelial function. Infective state, sustained by viral or bacterial agents, may injure the endothelial surface favouring the onset and progression of atherosclerotic process, mainly by an inflammatory mechanism. The aim of the study was to investigate endothelial function, expressed as brachial flow-mediated vasodilation (FMV), in black and white healthy subjects, along with antibody titer to cytomegalovirus, hepatitis virus (B, C), herpes virus-1 and 2, Epstein-Barr, Chlamydia pneumoniae and the expression of adhesion molecules. We enrolled 22 young (mean age 27+/-8 years) healthy subjects of black race (10 males) and 20 healthy young subjects (10 males, mean age 28+/-9 years) of white race. Total infectious burden (TIB) was defined as the number of serological positive infections. Black subjects have a reduced brachial FMV (6.9+/-3.5% versus 11.6+/-3.0%, p<0.01) and increased values of hsCRP (0.35+/-0.15 mg/dL versus 0.07+/-0.08 mg/dL, p<0.05), white cells (8578+/-1041/mmc versus 5833+/-998/mmc, p<0.01) and adhesion molecules (respectively: sVCAM-1 945+/-142 versus 779+/-93, sICAM-1 534+/-107 ng/mL versus 325+/-80 ng/mL; both p<0.01) in comparison to white subjects. The total infectious burden in black race was significantly higher than in white race (5+/-1 versus 2+/-1, p<0.01). At the univariate analysis, brachial FMV was significantly related to the levels of adhesion molecules (respectively: sVCAM-1 r=-0.49; sICAM-1 r=-0.50, both p<0.05), hsCRP (r=-0.47, p<0.05) and white blood cells (r=-0.43, p<0.05). TIB was associated with brachial FMV (r=-0.64, p<0.05), sVCAM-1 (r=0.55, p<0.05) and hsCRP (r=0.47, p<0.05). At the multivariate analysis the only predictive variables for brachial FMV were hsCRP, TIB and brachial diameter (respectively: beta=-0.49, -0.19, -0.54, all p<0.05). This study confirms that endothelial reactivity is impaired in young African black patients; moreover its behavior is strictly related to the inflammatory state and to the total infectious burden.

Different impact of the metabolic syndrome on left ventricular structure and function in hypertensive men and women.

Metabolic syndrome (MS) is increasingly recognized as an important cardiovascular risk factor in hypertension, but its influence on left ventricular (LV) mass and function in the 2 genders has not been specifically addressed. Among 618 nondiabetic, untreated hypertensive subjects, echocardiographically detected LV mass was significantly greater in subjects with MS. A significant interaction was observed between sex and the MS (P<0.003 for the multiplicative interaction term). Compared with women without the MS, those with the syndrome had a 24% greater LV mass (49.5+/-12 versus 40.0+/-10 g x m(-2.7); P<0.001), whereas the difference was only 9% in men (50.3+/-12 versus 46.1+/-10 g x m(-2.7); P=0.003). A greater prevalence of LV hypertrophy was found in women (37% versus 14%; P<0.001) but not in men (39% versus 29%; P=0.09) with the MS. After adjustment for the effect of age, body mass index, 24-hour systolic blood pressure, and several confounders, the MS was independently associated with a greater LV mass index in women (regression coefficient, 4.80; P<0.001) but not in men. Women with the MS also had a greater LV relative wall thickness (0.42+/-0.07 versus 0.39+/-0.07; P=0.004) and a depressed afterload-corrected midwall fractional shortening (94.0+/-12% versus 101.0+/-13%; P<0.001) than women without the syndrome, whereas no differences emerged in men. We conclude that, in untreated hypertension, MS has a different impact on LV hypertrophy and function in men and women. The effect of MS is more pronounced in women and is partly independent from the effect of several hemodynamic and nonhemodynamic determinants of LV mass.

Association of 99mTc-MIBI brain SPECT and proton magnetic resonance spectroscopy (1H-MRS) to assess glioma recurrence after radiotherapy.

AIM: The aim of this study was to compare 99mTc-MIBI brain SPECT and proton magnetic resonance spectroscopy (1H-MRS) findings and to evaluate their association. METHODS: Both exams were performed on 30 glioma patients, previously operated and treated with radiotherapy, having MRI doubtful between recurrence and radiotherapy effects. SPECT images were acquired 15 minutes after radiopharmaceutical administration with a dual-head gamma camera. T1/B1 uptake ratio was calculated between a tumor ROI (T1) and a normal mirror symmetric ROI (B1) and T2/B2 ratio was obtained between a ROI in the hottest neoplastic part (T2) and a normal mirror symmetric ROI (B2). 1H-MRS was performed using a 1.5 T system equipped with a spectroscopy package. SPECT and 1H-MRS data were compared with histology after new surgery or with follow-up. RESULTS: SPECT and 1H-MRS showed recurrence in 18 patients (confirmed by biopsy, coinciding only in 17 cases) and were negative in 10 (1 false negative). SPECT and 1H-MRS disagreed in 2 cases of recurrence (1 diagnosed by brain SPECT, 1 by 1H-MRS). T1/B1 ratio mean value (4.26+/-2.5) was significantly lower than T2/B2 (4.93+/-2.81; P<0.001). SPECT and 1H-MRS sensitivity in detecting recurrence was 90%, specificity 100%, accuracy 93%, negative predictive value (NPV) 83% and positive predictive value (PPV) 100%; the associated exams sensitivity was 95%, specificity 100%, accuracy 96.6%, NPV 90.9%, PPV 100%. CONCLUSIONS: Brain SPECT and 1H-MRS have equivalent values of diagnostic parameters in differentiating tumor recurrence and radiation effects, and their association might provide additional information.