Guagnano Mt

Effect of Thyroid Function on LDL Oxidation

In this study, the effect of different levels of thyroid hormone and metabolic activity on low density lipoprotein (LDL) oxidation was investigated. Thus, in 16 patients with hyperthyroidism, 16 with hypothyroidism, and 16 age- and sex-matched healthy normolipidemic control subjects, the native LDL content in lipid peroxides, vitamin E, beta-carotene, and lycopene, as well as the susceptibility of these particles to undergo lipid peroxidation, was assessed. Hyperthyroidism was associated with significantly higher lipid peroxidation, as characterized by a higher native LDL content in lipid peroxides, a lower lag phase, and a higher oxidation rate than in the other two groups. This elevated lipid peroxidation was associated with a lower LDL antioxidant concentration. Interestingly, hypothyroid patients showed an intermediate behavior. In fact, in hypothyroidism, LDL oxidation was significantly lower than in hyperthyroidism but higher than in the control group. Hypothyroidism was also characterized by the highest beta-carotene LDL content, whereas vitamin E was significantly lower than in control subjects. In hyperthyroidism but not in the other two groups, LDL oxidation was strongly influenced by free thyroxine blood content. In fact in this group, the native LDL lipid peroxide content and the lag phase were directly and indirectly, respectively, related to free thyroxine blood levels. On the contrary, in hypothyroidism LDL oxidation was strongly and significantly related to serum lipids. In conclusion, both hypothyroidism and hyperthyroidism are characterized by higher levels of LDL oxidation when compared with normolipidemic control subjects. In hyperthyroid patients, the increased lipid peroxidation was strictly related to free thyroxine levels, whereas in hypothyroidism it was strongly influenced by serum lipids.

Large waist circumference and risk of hypertension

OBJECTIVE: To examine the relationship between 24 h ambulatory blood pressure monitoring and three commonest anthropometric measurements for obesity—body mass index (BMI), waist-to-hip ratio (WHR) and waist circumference (W).DESIGN: Cross-sectional survey among outpatients at the Obesity Research Center.SUBJECTS AND METHODS: Four-hundred and sixty-one overweight or obese subjects, non-diabetic, otherwise healthy, aged 20–70 y, of either sex, were consecutively recruited. All subjects underwent 24 h ambulatory blood pressure monitoring. The population study was separated in normotensive and hypertensive males and females and the possible risk factors for hypertension (W, WHR, BMI and age) were subdivided into different classes of values.RESULTS: Logistic regression shows that W is the most important anthropometric factor associated with the hypertensive risk. Among males with W≥102 cm the odds ratio (OR) for hypertension is three times that of males with W<94 cm using casual BP measure (OR 3.04), nearly four times higher using 24 h BP mean (OR 3.97), and even five times higher using day-time BP mean (OR 5.19). Females with W≥88 cm have a risk for hypertension twice that of females with W<80 cm, whatever BP measurement was take (casual, 24 h or day-time). Males with WHR≥0.96 and females with WHR≥0.86 show significant OR for hypertension only by 24 h BP measurement and by day-time BP measurement. BMI seems to have no significant relationship to hypertensive risk. Age shows a significant relationship to hypertensive risk only considering males aged ≥55 y and females aged ≥50 y.CONCLUSION: The waist circumference seems to have a strong association with the risk of hypertension, principally by the ambulatory BP monitoring, when compared with casual BP measurement.

Risk factors for hypertension in obese women. The role of weight cycling.

Objective: To study significant factors associated with the risk of hypertension among obese women, with and without a history of weight cycling (WC).Design: Case–control study.Setting: Obesity Clinic of Chieti University, Italy.Subjects: A group of 258 obese women aged 25–64 y (103 cases with hypertension and 155 controls) were recruited. All obese subjects had the same clinical characteristics, were without a family history for hypertension, were non-smokers, had normal lipidemic profiles and normal glucose tolerance, were not taking any medication and were otherwise healthy.Intervention: In the weight cycling women, the history of WC was established on the basis of at least five weight losses in the previous 5 y due to dieting, with a weight loss of at least 4.5 kg per cycle. A logistic regression model adjusted for confounding variables such as waist-to-hip ratio (WHR) and weight cycling history parameters was used and the odds ratio (OR) with 95% confidence intervals was calculated.Results: The risk of hypertension increases in subjects with larger WHR (OR 7.8; 95% CI 3.4–17.9) and with a positive history for WC (OR 4.1; 95% CI 2.4–6.9). Further, in obese patients with WC, the weight cycling index and the sum of the weight regained are also important risk factors for hypertension.Conclusions: These findings could support the hypothesis that it is the combined exposure of central-type obesity and WC that strongly raises the risk of hypertension.Sponsorship: This work has been financially supported by a grant of Ministero dell’Università e della Ricerca Scientifica e Tecnologica.European Journal of Clinical Nutrition (2000) 54, 356–360

Leptin increase is associated with markers of the hemostatic system in obese healthy women

Summary.  Background: Leptin, a hormone secreted by the adipose tissue, might be a link between obesity and increased morbidity for cardiovascular disease. Leptin exerts proinflammatory, pro‐angiogenic actions by activating a specific receptor (Ob‐Rb) which is expressed in human endothelial cells. Thus, a link may exist between leptin expression and endothelial dysfunction. Objectives: We sought to determine whether in obese women there is a correlation between leptin levels, endothelial perturbation and coagulative activation. Methods: Circulating levels of leptin, von Willebrand Factor (VWF), factor (F)VIIa, prothrombin fragment 1 + 2 (F1+2), were measured in 51 non‐diabetic, obese women and in 51 normal‐weight subjects, using immunoenzymatic assays. Results: Obese women had significantly higher levels of leptin, VWF, FVIIa, F1+2 compared with healthy women. Simple correlation coefficients showed significant correlation between leptin and either VWF, FVIIa, or F1+2 concentrations. A multiple linear regression analysis, performed to quantify further the relationship between leptin levels and the above‐mentioned variables as well as the inflammatory marker C‐reactive protein (CRP) and including age, body mass index (BMI), waist–hip ratio (WHR) and lipid parameters as potential confounders, revealed that only FVIIa and VWF were independently related to leptin levels. Reduction in adipose tissue after weight loss resulted in a decrease in both circulating leptin and endothelial and coagulative activation markers. Conclusions: We suggest that leptin might have pro‐atherogenic effects in vivo, with a mechanism involving endothelial cell activation.

Bronchial hyperresponsiveness in adults with seasonal and perennial rhinitis: is there a link for asthma and rhinitis?

Epidemiological studies have shown that asthma and rhinitis often coexist in the same patients and the prevalence of asthma is greater in patients with rhinitis. The aim of this study was to evaluate the differences in bronchial reactivity in subjects with seasonal and perennial rhinitis. We enrolled 128 subjects with seasonal or perennial allergic rhinitis divided into three groups: A with perennial rhinitis and allergy to “Dermatophagoides Pteronissynus”; B with seasonal rhinitis and allergy to “Graminae” and “Parietaria”, who underwent methacholine challenge test (MCHt) during the exposure period (fron March until May); C with seasonal rhinitis and allergy to “Graminae” and “Parietaria”, who underwent MCHt during the non exposure period (from June until February). The PC20 mean values of group A (1774.8 ± 20.7) and group B (1740.7 ± 38.8) were not significantly different, but significantly lower than those of group C (3010.0 ± 56.9) (p=0.001). The subjects with group A were positive to the MCHt in 54.54%, against 29.28% of group B and 11.62% of group C (p=0.007). The results show differences in the degree of bronchial responsiveness. The dose-response curves documented a lower value of PC20 in the group with perennial rhinitis and a statistically significant difference of bronchial hyperresponsiveness prevalence between the three groups (p=0.007).

Endogenous Secretory RAGE in Obese Women: Association with Platelet Activation and Oxidative Stress

CONTEXT The receptor for advanced glycation end-products (RAGE) has been implicated in obesity-related metabolic disease and accelerated atherothrombosis. OBJECTIVE We tested the hypothesis that changes in endogenous secretory (es)RAGE levels as a result of excess adiposity and oxidative stress may contribute to enhancing platelet activation in obese women, thus increasing the cardiovascular risk. PATIENTS Eighty otherwise healthy obese women and 20 nonobese women were studied. RESULTS esRAGE and plasma adiponectin were reduced in obese women [median (interquartile range), 0.18 (0.13-0.26) vs. 0.38 (0.20-0.48) ng/ml, P = 0.003; and 4.4 (2.8-6.4) vs. 10.0 (6.9-12.5) μg/ml, P < 0.0001, respectively] who also displayed higher urinary 11-dehydro-thromboxane B(2) (11-dehydro-TXB(2)) [795 (572-1089) vs. 211 (135-301) pg/mg creatinine; P < 0.0001] and 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)) [544 (402-698) vs. 149 (98-219) pg/mg creatinine; P < 0.0001] compared to nonobese women. Direct correlations between plasma adiponectin and esRAGE (Rho = 0.43; P < 0.0001) and between urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2) (Rho = 0.36; P = 0.001) were observed in obese women. Moreover, plasma esRAGE and urinary 11-dehdro-TXB(2) were inversely related (Rho = -0.29; P = 0.008). On multiple linear regression analysis, urinary 8-iso-PGF(2α) and plasma esRAGE were independent predictors of urinary 11-dehydro-TXB(2). In five obese women, a short-term weight loss program gave a significant increase in esRAGE and decrease in urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2). CONCLUSION In otherwise healthy obese women, low plasma esRAGE levels are associated with reduced circulating adiponectin and enhanced thromboxane biosynthesis, which is in part mediated by increased lipid peroxidation. Thus, excess adiposity may be implicated in RAGE hyperactivation and thromboxane-dependent platelet activation, contributing to obesity-related metabolic and vascular disease.

Comparison of montelukast and budesonide on bronchial reactivity in subjects with mild-moderate persistent asthma

We studied 51 atopic non-smoking subjects who were divided to four treatments groups: (A) montelukast 10mg daily, (B) budesonide 400 microg twice a day (bid), (C) montelukast 10 mg daily plus budesonide 400 microg bid and (D) budesonide 800 microg bid. Bronchial responsiveness was assessed before and after 12 weeks of treatment. The bronchial responsiveness, evaluated by means of PC(20) values, showed a strong significant increase in groups B, C and D, and a weak but significant rise in group A, when compared to basal data. Regarding other pulmonary parameters (FEV(1), PEF) there were no significant differences among the groups after 12 weeks of therapy. A statistical significance was founded after therapy between group A and C (p < 0.05), but not between the group B and D treated with only budesonide at different doses. No significant differences was observed in the side effect pattern among the various treatments. The study data demonstrated that administration of montelukast provided an important and additional effect on bronchial hyperresponsiveness. Oral administration represents a significant advantage over the majority of other anti-asthmatic drugs. Our results confirm the anti-inflammatory properties of both the inhaled corticosteroid (ICS) and montelukast and the possible role of these drugs can have on airway remodelling. While currently low dose ICS remains the reference drug as a controller in mild-moderate persistent asthma, montelukast may be viewed as a possible option, either in monotherapy or in association.

Association of low-grade inflammation and platelet activation in patients with hypertension with microalbuminuria.

Increased levels of sCD40L (soluble CD40 ligand) have been associated with enhanced in vivo platelet activation, and may represent a molecular link between inflammation and a prothrombotic state. The aim of the present study was to analyse the relationship between platelet activation, endothelial dysfunction, low-grade inflammation and sCD40L in patients with hypertension with or without MA (microalbuminuria). A cross-sectional comparison of sCD40L levels was performed in 25 patients with MH (essential hypertension with MA) pair-matched for gender and age with 25 patients with EH (essential hypertension) and 25 HS (healthy subjects with normotension). Circulating levels of CRP (C-reactive protein), a marker of inflammation, sP-selectin (soluble P-selectin), a marker of in vivo platelet activation, and ADMA (asymmetric dimethylarginine) and vWF (von Willebrand factor), markers of endothelial dysfunction, were analysed in each subject. sCD40L levels were increased in patients with MH compared with either patients with EH (P<0.001) or HS (P<0.0001). A highly significant correlation between plasma sCD40L and sP-selectin (P<0.0001), vWF (P<0.001) or CRP levels (P<0.05) was observed in patients with MH. Multivariate regression analysis showed that sP-selectin was the strongest independent predictor of sCD40L levels (P<0.0001) in patients with MH. Patients with hypertension with both vWF and CRP levels above the median had the highest sCD40L levels (P<0.0001). Factorial ANOVA of all of the patients with hypertension confirmed that only patients with MH with low-grade inflammation had elevated levels of sCD40L. In conclusion, sCD40L levels appear to discriminate a subset of patients characterized by MA and low-grade inflammation, suggesting that inhibition of the CD40/CD40L system may represent a potential therapeutic target in subjects with hypertension at a high risk of cardiovascular events.

Effectiveness of montelukast versus budesonide on quality of life and bronchial reactivity in subjects with mild-persistent asthma.

Insufficient data exist to evaluate the comparative effects of inhaled corticosteroids (ICS) versus leukotriene receptor antagonist (LTRA) on airway inflammation and quality of life (QoL). The aim of the study was to compare the effectiveness of montelukast compared to budesonide at different doses on QoL and bronchial reactivity in mild-asthmatic adult patients. 45 subjects with bronchial asthma were randomly assigned to a different treatment and divided in 3 treatment groups: A: 400 μg of budesonide twice a day; B: 10 mg of montelukast daily; C: 10 mg of montelukast daily plus 400 μg of budesonide twice a day. At the beginning of the study and at the end of the treatment period (16 weeks) all patients underwent complete clinical evaluation, pulmonary function testing and methacholine challenge test (MCHt). In group A the increase from baseline was 153.4%, in group C was 133.2%, and in group B 247.7%, the latter increase being statistically significant compared to that in the other 2 groups (p< 0.005 Wilcoxon test). In all domains the improvement in quality of life in the group treated with montelukast (group B) was significantly greater than that in the group treated with both medications (group C): in particular, the improvement was consistent in the symptoms (p< 0.01) and emotions (p< 0.01) domains, and weaker in the physical activity (p< 0.05). A similar difference was observed between group B and A, but only in the symptoms (p<0.01), emotions (p<0.01), and environmental stimuli domains (p<0.05). The personal perception of their own disease is important for a correct therapeutic management of asthma. In order to optimize the treatment, a complete adherence of the patient to the treatment itself is required, to be achieved through simplification of therapeutic schedule and easy administration of medications. Montelukast may be considered a valid alternative in the treatment of mild-persistent asthma, both for the clinical and functional benefits and for the great advantage of the once-daily dosage, which consistently improves the compliance with the chronic treatment of the disease.

Increased plasminogen activator inhibitor-1 levels in android obesity: correlation with oxidative stress

Obesity, in particular android obesity, has strong associations with cardiovascular disease through mechanisms possibly linking the metabolic disorder to a low-grade inflammation [1,2] and a prothrombotic hypofibrinolytic condition [3]. Indeed, adipose tissue represents a source of several molecules, including plasminogen activator inhibitor-1 (PAI-1) [4]. Moreover, visceral adipose tissue has a higher capacity to produce PAI-1 than subcutaneous adipose tissue [4]. Obesity is also accompanied by oxidative stress [2,5]. Using several mouse models of obesity, Furukawa et al. [5] recently demonstrated that increased oxidative stress in accumulated fat leads to dysregulated production of adipocytokines. In particular, in cultured adipocytes oxidative stress enhanced PAI-1 mRNA expression [5]. Treatment of obese mice with a 3 NADPH oxidase inhibitor reduced ROS production in adipose tissue and attenuated the dysregulation of adipocytokines [5]. These considerations prompted us to investigate the relationship between oxidative stress and PAI-1 levels in obese healthy women. To this purpose, we performed a cross sectional comparison of urinary 8-iso-prostaglandin (PG)F2a (an in vivo marker of oxidative stress) excretion rates and plasma PAI-1 levels in 46 women: 21 with android obesity; 15 with gynoid obesity; 10 non-obese women served as controls (Table 1). All women were recruited at the University of Chieti after they had provided written informed consent. The study was approved by the Medical Ethics Committee of the University Medical School. Women had to be in good general health and physical condition. Exclusion criteria were: clinical cardiovascular disease, diabetes mellitus, smoking, hypercholesterolemia, hypertension, hormonal contraception or replacement therapy, treatment with corticosteroids or nonsteroidal anti-inflammatory drugs and vitamin supplements. Women were also excluded if they were pregnant or had delivered in the previous 6 months. PAI-1 antigen was determined by ELISA (Imubind PAI-1 ELISA kit; American Diagnostica, Greenwich, CT, USA). Urinary 8-iso-PGF2a excretion rates were determined by a previously described radioimmunoassay [6]. Statistical analysis was performed by appropriate statistics using a computer software package (Statistica 6.0, StatSoft Inc.,). Data are presented as mean ± SD or median and interquartile range (IQR; 25th to 75th percentile). Only P-values <0.05 were regarded as statistically significant. PAI-1 levels were significantly higher in womenwith android obesity compared with either gynoid obese or non-obese women (Table 1). Oxidative stress, as reflected by urinary 8-isoPGF2a excretion, was enhanced in android obesity, whereas no differences were observed between gynoid obese and non-obese women (Table 1). Spearman rank correlation analysis of the values measured in all 46 women showed the presence of a relationship between PAI-1 levels and urinary 8-iso-PGF2a excretion rates (q 1⁄4 0.474, P < 0.001) and either body mass index (BMI, q 1⁄4 0.676, P < 0.0001) or waist-to-hip ratio (WHR, q 1⁄4 0.381, P < 0.01). These results were confirmed in a subgroup analysis of obese, but not in non-obese women. Thus, to better analyze the relationship of PAI-1 levels with all other variables, a multivariate linear regression analysis including age, BMI, WHR, total cholesterol, LDL and HDL-cholesterol, triglyceride levels and urinary 8-iso-PGF2a excretion rates was performed. The final model obtained by backward stepping revealed that urinary 8-iso-PGF2a excretion rates (b 1⁄4 0.64, P < 0.002) were independently related to PAI-1, but only in android obese women. These results are consistent with previous findings of increased oxidative stress and PAI-1 levels in obesity [2,3]. Moreover, they show, for the first time, a direct correlation between PAI-1 and urinary 8-iso-PGF2a and a close relationship between these analytical variables and android obesity, which is independent of other variables. The two groups of obese women were in fact comparable for age, overall obesity (BMI), systolic and diastolic blood pressure and plasma lipid levels. Thus, from the present results, a key involvement Correspondence: G. Davı́, G. D’Annunzio Foundation, University of Chieti, Via Colle dell’Ara, 66013 Chieti, Italy. Tel.: 0039 0871 541312; fax: 0039 0871 541313; e-mail: gdavi@unich.it