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Green tea, particularly epigallocatechin-3-gallate (EGCG), may affect body weight and composition, possibly by enhancing fat oxidation. The aim of this double-blind, randomized placebo-controlled cross-over study was to investigate whether 3-day supplementation with EGCG (282 mg/day) stimulates fat oxidation and lipolysis in 24 overweight subjects (age = 30 ± 2 yrs, BMI = 27.7 ± 0.3 kg/m(2)). Energy expenditure, substrate metabolism and circulating metabolites were determined during fasting and postprandial conditions. After 6 h, a fat biopsy was collected to examine gene expression. In 12 subjects, skeletal muscle glycerol, glucose and lactate concentrations were determined using microdialysis. EGCG-supplementation did not alter energy expenditure and substrate oxidation compared to placebo. Although EGCG reduced postprandial circulating glycerol concentrations (P = 0.015), no difference in skeletal muscle lipolysis was observed. Fasting (P = 0.001) and postprandial (P = 0.003) skeletal muscle lactate concentrations were reduced after EGCG-supplementation compared to placebo, despite similar tissue blood flow. Adipose tissue leptin (P = 0.05) and FAT/CD36 expression (P = 0.08) were increased after EGCG compared to placebo. In conclusion, 3-day EGCG-supplementation decreased postprandial plasma glycerol concentrations, but had no significant effects on skeletal muscle lipolysis and whole-body fat oxidation in overweight individuals. Furthermore, EGCG decreased skeletal muscle lactate concentrations, which suggest a shift towards a more oxidative muscle phenotype.

Purpose: There are indications that a history of allergy may offer some protection against cancer. We studied the relation of three objectively determined allergy markers with cancer mortality and hospitalization risk., Methods: Associations between three allergy markers (number of peripheral blood eosinophil counts, skin test positivity, and serum total IgE) with mortality and hospitalization from any type and four common types of cancer (lung, colorectal, prostate, and breast cancer) were assessed in the Vlagtwedde-Vlaardingen cohort (1965-1990), with follow-up of mortality until 31 December 2008. Hospitalization data were available since 1 January 1995., Results: There were no significant associations between objective allergy markers and cancer mortality or hospitalization. We found several associations in specific subgroups. A higher number of eosinophils was associated with a decreased risk of colorectal cancer mortality in ever smokers HR (95 % CI) = 0.61 (0.45-0.83) and in males 0.59 (0.42-0.83); however, no overall association was observed 0.84 (0.64-1.09). Skin test positivity was associated with a decreased risk of any cancer mortality only among females 0.59 (0.38-0.91) and showed no overall association 0.83 (0.67-1.04). Serum total IgE levels were associated with an increased risk of lung cancer mortality among females 4.64 (1.04-20.70), but with a decreased risk of cancer hospitalization in ever smokers 0.77 (0.61-0.97) and males 0.72 (0.55-0.93); however, no overall associations were observed [mortality 0.99 (0.79-1.25), and hospitalization 0.86 (0.71-1.04)]., Conclusions: We found no associations between objective allergy markers and cancer in the total population. However, skin test positivity and a high number of eosinophils were associated with a reduced risk to die of cancer in specific subgroups. Hence, it seems important to study specific subgroups defined by gender and smoking habits in order to identify allergy markers of predictive value for cancer mortality.

Background: Roflumilast is a targeted oral once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in chronic obstructive pulmonary disease (COPD). Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for the treatment of COPD., Methods: In a crossover study, 38 patients with COPD (mean (SD) age 63.1 (7.0) years, post-bronchodilator forced expiratory volume in 1 s (FEV(1)) 61.0 (12.6)% predicted) received 500 microg roflumilast or placebo once daily for 4 weeks. Induced sputum samples were collected before and after 2 and 4 weeks of treatment. Differential and absolute cell counts were determined in whole sputum samples. Markers of inflammation were determined in sputum supernatants and blood. Spirometry was performed weekly., Results: Roflumilast significantly reduced the absolute number of neutrophils and eosinophils/g sputum compared with placebo by 35.5% (95% CI 15.6% to 50.7%; p = 0.002) and 50.0% (95% CI 26.8% to 65.8%; p<0.001), respectively. The relative proportion of sputum neutrophils and eosinophils was not affected by treatment (p>0.05). Levels of soluble interleukin-8, neutrophil elastase, eosinophil cationic protein and alpha(2)-macroglobulin in sputum and the release of tumour necrosis factor alpha from blood cells were significantly reduced by roflumilast compared with placebo treatment (p<0.05 for all). Post-bronchodilator FEV(1) improved significantly during roflumilast compared with placebo treatment with a mean difference between treatments of 68.7 ml (95% CI 12.9 to 124.5; p = 0.018)., Conclusion: PDE4 inhibition by roflumilast treatment for 4 weeks reduced the number of neutrophils and eosinophils, as well as soluble markers of neutrophilic and eosinophilic inflammatory activity in induced sputum samples of patients with COPD. This anti-inflammatory effect may in part explain the concomitant improvement in post-bronchodilator FEV(1).

We investigated whether allergy is associated with increased all-cause mortality. Two allergy markers, peripheral blood eosinophilia (> or =275 eosinophilic cells per mm3) and positive skin tests (sum score > or =3), were available for 5,383 subjects of a cohort study on asthma and chronic obstructive pulmonary disease in general population samples of Vlagtwedde and Vlaardingen, the Netherlands, in 1965-1972. During 30 years of follow-up, 1,135 subjects died. In a Cox regression analysis, eosinophilia was associated with an increased risk (relative risk = 1.4; 95% confidence interval = 1.2-1.7) of all-cause mortality, independent of gender, age, smoking habits, percentage predicted forced expiratory volume in 1 second (FEV1 % predicted), and positive skin tests at the start of the study. Subjects with positive skin tests had only an increased risk of all-cause mortality in the subgroup of subjects with FEV1 <80% of predicted (relative risk = 1.7; 95% confidence interval = 1.0-2.8). These results remained essentially unchanged after exclusion of subjects with asthma. We conclude that eosinophilia is associated with increased all-cause mortality. An increased number of peripheral blood eosinophils may reflect an increased inflammatory response, resulting in tissue injury. It is possible that the association between a low FEV1% predicted and all-cause mortality is partly mediated by an atopic constitution.

We studied the association between allergy defined as eosinophilia (>/= 275 cells/mm(3)) and/or positive skin tests (sum score >/= 3) and mortality from chronic obstructive pulmonary disease (COPD) after adjustment for major risk factors. In addition, we investigated this association in subgroups of respiratory symptoms and lung function. We used data from 7,556 participants of the respiratory surveys in 1964 -1972 in the general populations of Vlagtwedde, Vlaardingen, and Meppel (The Netherlands; mean age +/- SD: 39.3 yr +/- 14 in the 1960s). In 1995, the vital status was available (5,135 alive, 106 lost to follow-up, 121 primary deaths from COPD, and 2,194 other primary causes of which 137 had a secondary death cause from COPD. Positive skin tests were not associated with increased COPD mortality. The association between eosinophilia and COPD mortality was restricted to those who had reported asthma attacks and was present for both COPD as a primary cause (relative risk [RR] = 4.80; 95% confidence interval [CI] 1.9 to 11.9) and combined primary and secondary causes of death (RR = 3. 90; 95% CI 2.05 to 7.40). We conclude that eosinophilia with asthma attacks is a risk factor for COPD mortality in addition to known risk factors also found in our study such as male gender, older age, current smoking, low lung function, underweight, and dyspnea.

The authors investigated whether two objective allergy markers, peripheral blood eosinophilia and skin tests for common aeroallergens, were associated with cardiovascular death. Of 5,382 subjects in the Vlagtwedde-Vlaardingen Study (the Netherlands) with data on allergy markers in 1965-1972, 507 subjects died from cardiovascular disease during 30 years of follow-up. Subjects with eosinophilia had an increased risk of cardiovascular death (relative risk (RR) = 1.7; 95% confidence interval (CI): 1.4, 2.2), including ischemic heart disease death (RR = 1.6; 95% CI: 1.2, 2.2) and cerebrovascular death (RR = 2.3; 95% CI: 1.4, 3.8), independent of major risk factors. This association was limited to subjects with a percentage of the predicted forced expiratory volume in 1 second (FEV1 % predicted) of <100%. Positive skin tests were associated with a significantly reduced cardiovascular mortality in subjects with normal lung function and weight who did not smoke (RR = 0.15; 95% CI: 0.05, 0.46). Conversely, when subjects with positive skin tests had a body mass index of > or =25 kg/m2, had an FEV1 % predicted of <80%, or smoked, they had an increased risk for cardiovascular mortality. These results were not restricted to asthmatics. Our data suggest a possible link between eosinophilia and positive skin tests and cardiovascular mortality, especially in combination with other risk factors associated with its mortality.