Hydroxylation of d-phenylalanine as a novel approach to detect hydroxyl radicals: Application to cardiac pathophysiology

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Abnormalities of sodium handling and of cardiovascular adaptations during high salt diet in patients with mild heart failure.

BACKGROUND: Sodium retention and hormonal activation are fundamental hallmarks in congestive heart failure. The present study was designed to assess the ability of patients with asymptomatic to mildly symptomatic heart failure and no signs or symptoms of congestion to excrete ingested sodium and to identify possible early abnormalities of hormonal and hemodynamic mechanisms related to sodium handling. METHODS AND RESULTS: The effects of a high salt diet (250 mEq/day for 6 days) on hemodynamics, salt-regulating hormones, and renal excretory response were investigated in a balanced study in 12 untreated patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (NYHA class I-II, ejection fraction < 50%) (HF) and in 12 normal subjects, who had been previously maintained a 100 mEq/day NaCl diet. In normal subjects, high salt diet was associated with significant increases of echocardiographically measured left ventricular end-diastolic volume, ejection fraction, and stroke volume (all P < .001) and with a reduction of total peripheral resistance (P < .001). In addition, plasma atrial natriuretic factor (ANF) levels increased (P < .05), and plasma renin activity and aldosterone concentrations fell (both P < .001) in normals in response to salt excess. In HF patients, both left ventricular end-diastolic and end-systolic volumes increased in response to high salt diet, whereas ejection fraction and stroke volume failed to increase, and total peripheral resistance did not change during high salt diet. In addition, plasma ANF levels did not rise in HF in response to salt loading, whereas plasma renin activity and aldosterone concentrations were as much suppressed as in normals. Although urinary sodium excretions were not significantly different in the two groups, there was a small but systematic reduction of daily sodium excretion in HF, which resulted in a significantly higher cumulative sodium balance in HF than in normals during the high salt diet period (P < .001). CONCLUSIONS: These results show a reduced ability to excrete a sodium load and early abnormalities of cardiac and hemodynamic adaptations to salt excess in patients with mild heart failure and no signs or symptoms of congestion

Ethylene-norbornene copolymerization by carbon nanotube-supported metallocene catalysis: generation of high performances polyolefinic nanocomposites

peer reviewedHomogeneous surface coating of multi-walled carbon nanotubes is achieved for the first time by in situ copolymerization of ethylene (E) and 2-norbornene (N) as catalyzed directly from the nanotube surface previously treated by a highly active metallocene-based complex, i.e., rac-Et(Ind)2ZrCl2/MMAO-3A. The copolymerization reaction allows for the destructuration of the native nanotube bundles, which upon further melt blending with an ethylene-vinyl acetate copolymer (27 wt.-% vinyl acetate) matrix, leads to high-performance polyolefinic nanocomposites. The microstructural analysis of the surface-coating copolymer was carried out by 13C NMR spectroscopy and allowed determination of the actual N content incorporated along the chains. Depending on the experimental conditions used (e.g., E pressure, solvent, feed N concentration) the relative quantity of E-N copolymer can be tuned, as well as the N content in the formed copolymers and accordingly their glass transition temperature

Impaired performance of alpha7 nicotinic receptor knockout mice in the five-choice serial reaction time task

RATIONALE: Nicotinic receptors have been implicated in attentional performance. Nicotine can improve attention in animals and humans, but knowledge about relevant receptor subtypes is very limited. OBJECTIVES: The aim was to examine the role of α7 receptors in attentional performance of mice and in effects of nicotine. MATERIALS AND METHODS: Mice with targeted deletion of the gene coding for the α7 subunit of nicotinic receptors and wild-type controls were trained on a five-choice serial reaction time task with food reinforcers presented under varying parametric conditions. Nicotine was administered in a range of doses (0.001–1.0 mg/kg sc), including those reported to enhance attentional performance. RESULTS: Initially the α7(−/−) (knockout) mice responded less accurately and made more anticipatory responses. After task parameters were altered so that the time allowed for responding was reduced and anticipatory (impulsive) responses were punished by a time-out, the pattern of performance deficits changed; there were increased omission errors in α7(−/−) mice but normal levels of accuracy and anticipatory responding. Nicotine did not improve any measure of performance, either with the original training parameters or after retraining; the largest dose used (1.0 mg/kg) produced a general impairment of responding in α7(−/−) and wild-type mice. CONCLUSIONS: α7 nicotinic receptor knockout mice are impaired in performance of the 5-CSRTT, suggesting a possible role for α7 receptors in attentional processing. However, identification of a protocol for assessing attention-enhancing effects of nicotine in mice may require further modifications of test procedures or the use of different strains of animal

Vascular risk factors in glaucoma: the results of a national survey

Background The role of vascular risk factors in glaucoma is still being debated. To assess the importance of vascular risk factors in patients with primary open-angle glaucoma (POAG), data from the medical history of 2,879 POAG patients and 973 age-matched controls were collected and analyzed. Methods Design: observational survey. Setting: 35 Italian academic centers. Study population: POAG patients and age-matched controls. In order to reduce bias consecutive patients were included. Observation procedures: data concerning vascular risk factors were collected for all patients with a detailed questionnaire. A complete ophthalmological examination with assessment of intraocular pressure (IOP), visual field, optic disc, and systemic blood pressure was performed. Main outcome measures: the ESH-ESC (European Society of Hypertension-European Society of Cardiology) guidelines were used to calculate the level of cardiovascular risk. Crude and adjusted estimates of the odds ratios (OR) were calculated for all cardiovascular risk factors in POAG and controls. Results The study included 2,879 POAG patients and 973 controls. POAG cases had a significantly higher systolic and diastolic blood pressure (p=0.001) and systolic perfusion pressure (p=0.02) as compared with controls. Also mean IOP was significantly higher in the POAG group (p=0.01), while diastolic perfusion pressure was not significantly different in the two groups. Myopia was more prevalent in the POAG group (23 vs 18%, p=0.005) as well as a positive family history for glaucoma (26 vs 12%, p= 0.004). POAG patients tended to have a higher cardiovascular risk than controls: 63% of glaucoma cases vs 55% of controls (OR: 1.38, p=0.005) had a “high” or “very high” cardiovascular risk. Conclusions The level of cardiovascular risk was significantly higher in glaucoma patients than in controls

Oral squamous cell cancer: early detection and the role of alcohol and smoking

Objective: Oral squamous cell carcinoma has a remarkable incidence worldwide and a fairly onerous prognosis, encouraging further research on factors that might modify disease outcome. Data sources: A web-based search for all types of articles published was initiated using Medline/Pub Med, with the key words such as oral cancer, alcohol consumption, genetic polymorphisms, tobacco smoking and prevention. The search was restricted to articles published in English, with no publication date restriction (last update 2010). Review Methods: In this review article, we approach the factors for a cytologic diagnosis during OSCC development and the markers used in modern diagnostic technologies as well. We also reviewed available studies of the combined effects of alcohol drinking and genetic polymorphisms on alcohol-related cancer risk. Results: The interaction of smoking and alcohol significantly increases the risk for aero-digestive cancers. The interaction between smoking and alcohol consumption seems to be responsible for a significant amount of disease. Conclusion: Published scientific data show promising pathways for the future development of more effective prognosis. There is a clear need for new prognostic indicators, which could be used in diagnostics and, therefore a better selection of the most effective treatment can be achieved

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events