Comparative total mortality in 25 years in Italian and Greek middle aged rural men.
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STUDY OBJECTIVE: Mortality over 25 years has been low in the Italian and very low in the Greek cohorts of the Seven Countries Study; factors responsible for this particularity were studied in detail. PARTICIPANTS AND SETTINGS: 1712 Italian and 1215 Greek men, aged 40-59 years, cohorts of the Seven Countries Study, representing over 95% of the populations in designated rural areas. DESIGN: Entry (1960-61) data included age, systolic blood pressure (SBP), smoking habits, total serum cholesterol, body mass index (BMI), arm circumference, vital capacity (VC), and forced expiratory volume in 3/4 seconds (FEV); the same data were obtained 10 years later. Multivariate Cox analysis was performed with all causes death in 25 years as end point. MAIN RESULTS: Italian men had higher entry levels of SBP, arm circumference, BMI, and VC; Greek men had higher cholesterol levels, smoking habits, and FEV. Mortality of Italian men was higher throughout; at 25 years cumulative mortality was 48.3% and 35.3% respectively. Coronary heart disease and stroke mortality increased fivefold in Italy and 10-fold in Greece between years 10 and 25. The only risk factor with a significantly higher contribution to mortality in Italian men was cholesterol. However, differences in entry SBP (higher in Italy) and FEV (higher in Greece) accounted for, according to the Lee method, 75% of the differential mortality between the two populations. At 10 years increases in SBP, cholesterol, BMI, and decreases in smoking habits, VC, FEV, and arm circumference had occurred (deltas). SBP increased more and FEV and VC decreased more in Italy than in Greece. Deltas, fed stepwise in the original model for the prediction of 10 to 25 years mortality, were significant for SBP, smoking, arm circumference, and VC in Greece, and for SBP and VC in Italy. CONCLUSION: Higher mortality in Italian men is related to stronger positive effects of entry SBP and weaker negative (protective) effects of FEV; in addition 10 year increases in SBP are higher and 10 year decreases in FEV are larger in Italy. Unaccounted factors, however, related to, for example, differences in the diet, may also have contributed to the differential mortality of these two Mediterranean populations. (+info)
The amyloid precursor protein interacts with Go heterotrimeric protein within a cell compartment specialized in signal transduction.
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The function of the beta-amyloid protein precursor (betaAPP), a transmembrane molecule involved in Alzheimer pathologies, is poorly understood. We recently reported the presence of a fraction of betaAPP in cholesterol and sphingoglycolipid-enriched microdomains (CSEM), a caveolae-like compartment specialized in signal transduction. To investigate whether betaAPP actually interferes with cell signaling, we reexamined the interaction between betaAPP and Go GTPase. In strong contrast with results obtained with reconstituted phospholipid vesicles (Okamoto et al., 1995), we find that incubating total neuronal membranes with 22C11, an antibody that recognizes an N-terminal betaAPP epitope, reduces high-affinity Go GTPase activity. This inhibition is specific of Galphao and is reproduced, in the absence of 22C11, by the addition of the betaAPP C-terminal domain but not by two distinct mutated betaAPP C-terminal domains that do not bind Galphao. This inhibition of Galphao GTPase activity by either 22C11 or wild-type betaAPP cytoplasmic domain suggests that intracellular interactions between betaAPP and Galphao could be regulated by extracellular signals. To verify whether this interaction is preserved in CSEM, we first used biochemical, immunocytochemical, and ultrastructural techniques to unambiguously confirm the colocalization of Galphao and betaAPP in CSEM. We show that inhibition of basal Galphao GTPase activity also occurs within CSEM and correlates with the coimmunoprecipitation of Galphao and betaAPP. The regulation of Galphao GTPase activity by betaAPP in a compartment specialized in signaling may have important consequences for our understanding of the physiopathological functions of betaAPP. (+info)
Allyl-containing sulfides in garlic increase uncoupling protein content in brown adipose tissue, and noradrenaline and adrenaline secretion in rats.
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The effects of garlic supplementation on triglyceride metabolism were investigated by measurements of the degree of thermogenesis in interscapular brown adipose tissue (IBAT), and noradrenaline and adrenaline secretion in rats fed two types of dietary fat. In Experiment 1, rats were given isoenergetic high-fat diets containing either shortening or lard with or without garlic powder supplementation (8 g/kg of diet). After 28 d feeding, body weight, plasma triglyceride levels and the weights of perirenal adipose tissue and epididymal fat pad were significantly lower in rats fed diets supplemented with garlic powder than in those fed diets without garlic powder. The content of mitochondrial protein and uncoupling protein (UCP) in IBAT, and urinary noradrenaline and adrenaline excretion were significantly greater in rats fed a lard diet with garlic powder than in those fed the same diet without garlic. Other than adrenaline secretion, differences due to garlic were significant in rats fed shortening, also. In Experiment 2, the effects of various allyl-containing sulfides present in garlic on noradrenaline and adrenaline secretion were evaluated. Administration of diallyldisulfide, diallyltrisulfide and alliin, organosulfur compounds present in garlic, significantly increased plasma noradrenaline and adrenaline concentrations, whereas the administration of disulfides without allyl residues, diallylmonosulfide and S-allyl-L-cysteine did not increase adrenaline secretion. These results suggest that in rats, allyl-containing sulfides in garlic enhance thermogenesis by increasing UCP content in IBAT, and noradrenaline and adrenaline secretion. (+info)
The food matrix of spinach is a limiting factor in determining the bioavailability of beta-carotene and to a lesser extent of lutein in humans.
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Carotenoid bioavailability depends, amongst other factors, on the food matrix and on the type and extent of processing. To examine the effect of variously processed spinach products and of dietary fiber on serum carotenoid concentrations, subjects received, over a 3-wk period, a control diet (n = 10) or a control diet supplemented with carotenoids or one of four spinach products (n = 12 per group): whole leaf spinach with an almost intact food matrix, minced spinach with the matrix partially disrupted, enzymatically liquefied spinach in which the matrix was further disrupted and the liquefied spinach to which dietary fiber (10 g/kg wet weight) was added. Consumption of spinach significantly increased serum concentrations of all-trans-beta-carotene, cis-beta-carotene, (and consequently total beta-carotene), lutein, alpha-carotene and retinol and decreased the serum concentration of lycopene. Serum total beta-carotene responses (changes in serum concentrations from the start to the end of the intervention period) differed significantly between the whole leaf and liquefied spinach groups and between the minced and liquefied spinach groups. The lutein response did not differ among spinach groups. Addition of dietary fiber to the liquefied spinach had no effect on serum carotenoid responses. The relative bioavailability as compared to bioavailability of the carotenoid supplement for whole leaf, minced, liquefied and liquefied spinach plus added dietary fiber for beta-carotene was 5.1, 6.4, 9.5 and 9.3%, respectively, and for lutein 45, 52, 55 and 54%, respectively. We conclude that the bioavailability of lutein from spinach was higher than that of beta-carotene and that enzymatic disruption of the matrix (cell wall structure) enhanced the bioavailability of beta-carotene from whole leaf and minced spinach, but had no effect on lutein bioavailability. (+info)
Improvement of factor VII clotting activity following long-term NCPAP treatment in obstructive sleep apnoea syndrome.
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Obstructive sleep apnoea syndrome (OSAS) is a very common disorder. Patients with OSAS are at an increased risk for cardiovascular events. It has also been reported that a 25% rise in factor VII clotting activity (FVIIc) is associated with a 55% increase in ischaemic heart disease death during the first 5 years. We examined the effects of nasal continuous positive airway pressure (NCPAP) treatment on FVIIc in patients with OSAS. FVIIc was investigated prospectively in 15 patients with OSAS before (mean +/- SEM apnoea and hypopnoea index (AHI) 61.5 +/- 4.2 and after (AHI 3.0 +/- 0.9) NCPAP treatment for immediate relief, at 1 month after treatment and at over 6 months. FVIIc levels gradually decreased after NCPAP treatment. After 6 months of NCPAP treatment, FVIIc levels had decreased significantly (before 141.1 +/- 11.7% vs. after 6 months 110.7 +/- 6.2%; p < 0.01). Six of the seven patients whose FVIIc levels were over 140% before the NCPAP treatment had FVIIc levels below 130% after 6 months or 1 year of NCPAP treatment. This decrease in FVIIc after long-term NCPAP treatment could improve mortality in OSAS patients. If patients, especially obese ones, present with high FVIIc of unknown origin, it would be prudent to check for OSAS. (+info)
Gallstones: an intestinal disease?
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Current evidence suggests that impaired intestinal motility may facilitate gallstone formation by influencing biliary deoxycholate levels or by modulating interdigestive gall bladder motility (fig 2), although a primary intestinal defect in gallstone pathogenesis has not yet been demonstrated. In the cold war period, most interesting events, from a political point of view, occurred at the border between capitalist and communist systems, near the iron curtain. Similarly, the gall bladder and biliary tract can be viewed as the border between liver and intestinal tract, where many interesting things occur with profound impact on both systems. Combined efforts by researchers in the field of hepatology and gastrointestinal motility should brake down the Berlin wall of ignorance of one of the most common diseases in the Western world. (+info)
Chlamydia pneumoniae antibodies are associated with an atherogenic lipid profile.
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OBJECTIVE: To determine, within a representative population group of men and women, whether alteration of the lipid profile might underlie the reported association between Chlamydia pneumoniae and ischaemic heart disease. DESIGN AND SETTING: Cross sectional survey in an area with a high incidence of ischaemic heart disease. SUBJECTS: 400 randomly selected participants in the World Health Organisation MONICA project's third population survey in Northern Ireland. MAIN OUTCOME MEASURES: Stored sera were examined by microimmunofluorescence for IgG antibodies to C pneumoniae at a dilution of 1 in 64. Mean total and high density lipoprotein (HDL) cholesterol were compared between seropositive and seronegative individuals with adjustment for age, measures of socioeconomic status, smoking habit, alcohol consumption, body mass index, and the season during which blood had been taken. RESULTS: In seropositive men, adjusted mean serum total cholesterol and HDL cholesterol were 0.5 mmol/l (9.2%) higher and 0.11 mmol/l (9.3%) lower, respectively, than in seronegative men. Differences in women did not achieve statistical significance, but both total cholesterol and HDL cholesterol were higher (3.6% and 5.8%, respectively) in seropositive than in seronegative individuals. CONCLUSIONS: There is serological evidence that C pneumoniae infection is associated with an atherogenic lipid profile in men. Altered lipid levels may underlie the association between C pneumoniae and ischaemic heart disease. (+info)
Chronic infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus: population based study of coronary heart disease.
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OBJECTIVE: To study possible associations between coronary heart disease and serological evidence of persistent infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus. DESIGN: Population based, case-control study, nested within a randomised trial. SETTING: Five general practices in Bedfordshire, UK. INDIVIDUALS: 288 patients with incident or prevalent coronary heart disease and 704 age and sex matched controls. RESULTS: High concentrations of serum IgG antibodies to H pylori were present in 54% of cases v 46% of controls, with corresponding results for C pneumoniae seropositivity (33% v 33%), and cytomegalovirus seropositivity (40% v 31%). After adjustments for age, sex, smoking, indicators of socioeconomic status, and standard risk factors, the odds ratios (95% confidence intervals) for coronary heart disease of seropositivity to these agents were: 1.28 (0.93 to 1.75) for H pylori, 0.95 (0.66 to 1.36) for C pneumoniae, and 1.40 (0.96 to 2. 05) for cytomegalovirus. CONCLUSIONS: There is no good evidence of strong associations between coronary heart disease and serological markers of persistent infection with H pylori, C pneumoniae, or cytomegalovirus. To determine the existence of moderate associations between these agents and disease, however, larger scale studies will be needed that can keep residual confounders to a minimum. (+info)