Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis

OBJECTIVES: To study the efficacy of vitamin E and C supplementation on the progression of carotid atherosclerosis, hypothesizing an enhanced preventive effect in men and in smokers and synergism between vitamins. DESIGN AND SUBJECTS: Double-masked two-by-two factorial trial, randomization in four strata (by gender and smoking status) to receive twice daily either 91 mg (136 IU) of d-alpha-tocopherol, 250 mg of slow-release vitamin C, a combination of these or placebo for three years. A randomized sample of 520 smoking and nonsmoking men and postmenopausal women aged 45-69 years with serum cholesterol >/= 5.0 mmol L-1 were studied. SETTING: The population of the city of Kuopio in Eastern Finland. INTERVENTION: Twice daily either a special formulation of 91 mg of d-alpha-tocopherol, 250 mg of slow-release vitamin C, a combination of these (CellaVie(R)) or placebo for three years. MEASUREMENTS: Atherosclerotic progression, defined as the linear regression slope of ultrasonographically assessed common carotid artery mean intima-media thickness (IMT), was calculated over semi-annual assessments. RESULTS: The average increase of the mean IMT was 0.020 mm year-1 amongst men randomized to placebo and 0.018 mm year-1 in vitamin E, 0.017 mm year-1 in vitamin C and 0.011 mm year-1 in the vitamin combination group (P = 0.008 for E + C vs. placebo). The respective means in women were 0.016, 0.015, 0.017 and 0.016 mm year-1. The proportion of men with progression was reduced by 74% (95% CI 36-89%, P = 0.003) by supplementation with the formulation containing both vitamins, as compared with placebo. CONCLUSIONS: Our study shows that a combined supplementation with reasonable doses of both vitamin E and slow-release vitamin C can retard the progression of common carotid atherosclerosis in men. This may imply benefits with regard to other atherosclerosis-based events.     

Trends in regional and socio-economic mortality differentials in Finland

Trends in mortality in Finland are reviewed over the past 20 years. The author notes that "Finnish female life expectancy has increased more than five years since 1965-1969 and it is now slightly higher than the average in Western Europe. It is also almost five years higher than the average life expectancy in Eastern Europe. The male life expectancy has also risen by more than five years...." However, the author also states that regional differences in mortality have not diminished over this period, despite prevention programs designed to reduce such differences. Furthermore "socio-economic differences in mortality have increased during the same period among men, but had been relatively stable among the women."     

Genomic sequence of <Emphasis Type="Italic">Wild potato mosaic virus</Emphasis> as compared to the genomes of other potyviruses

Summary.  The complete nucleotide sequence of Wild potato mosaic virus (WPMV) was determined, showing that it is a distinct member of the genus Potyvirus (family Potyviridae). The genome consists of 9853 nucleotides and encodes a single polyprotein of 3065 amino acids. The 5′- and 3′-non translated regions (NTR) were 182 and 472 nucleotides, respectively. Alignment of the predicted WPMV polyprotein sequence with other members of the genus Potyvirus revealed nine putative cleavage sites resulting in ten mature proteins. Amino acid and nucleotide sequence identities and the exceptionally long 3′-NTR indicated a close relationship between WPMV and Potato virus V (PVV). Phylogenetic analysis based on the polyprotein and coat protein amino acid sequences grouped WPMV, PVV, Pepper mottle virus and Potato virus Y in one cluster distinct from other potyviruses. Received July 12, 2002; accepted October 1, 2002     

Elimination of two viruses which interact synergistically from sweetpotato by shoot tip culture and cryotherapy

Sweet potato chlorotic stunt virus (SPCSV; Closteroviridae) and Sweet potato feathery mottle virus (SPFMV; Potyviridae) interact synergistically and cause severe diseases in co-infected sweetpotato plants (Ipomoea batatas). Sweetpotato is propagated vegetatively and virus-free planting materials are pivotal for sustainable production. Using cryotherapy, SPCSV and SPCSV were eliminated from all treated single-virus-infected and co-infected shoot tips irrespective of size (0.5-1.5mm including 2-4 leaf primordia). While shoot tip culture also eliminated SPCSV, elimination of SPFMV failed in 90-93% of the largest shoot tips (1.5mm) using this technique. Virus distribution to different leaf primordia and tissues within leaf primordia in the shoot apex and petioles was not altered by co-infection of the viruses in the fully virus-susceptible sweetpotato genotype used. SPFMV was immunolocalized to all types of tissues and up to the fourth-youngest leaf primordium. In contrast, SPCSV was detected only in the phloem and up to the fifth leaf primordium. Because only cells in the apical dome of the meristem and the two first leaf primordia survived cryotherapy, all data taken together could explain the results of virus elimination. The simple and efficient cryotherapy protocol developed for virus elimination can also be used for preparation of sweetpotato materials for long-term preservation.     

Synergistic interactions of a potyvirus and a phloem-limited crinivirus in sweet potato plants

When infecting alone, Sweet potato feathery mottle virus (SPFMV, genus Potyvirus) and Sweet potato chlorotic stunt virus (SPCSV, genus Crinivirus) cause no or only mild symptoms (slight stunting and purpling), respectively, in the sweet potato (Ipomoea batatas L. ). In the SPFMV-resistant cv. Tanzania, SPFMV is also present at extremely low titers, though plants are systemically infected. However, infection with both viruses results in the development of sweet potato virus disease (SPVD) characterized by severe symptoms in leaves and stunting of the plants. Data from this study showed that SPCSV remains confined to phloem and at a similar or slightly lower titer in the SPVD-affected plants, whereas the amounts of SPFMV RNA and CP antigen increase 600-fold. SPFMV was not confined to phloem, and the movement from the inoculated leaf to the upper leaves occurred at a similar rate, regardless of whether or not the plants were infected with SPCSV. Hence, resistance to SPFMV in cv. Tanzania was not based on restricted virus movement, neither did SPCSV significantly enhance the phloem loading or unloading of SPFMV. It is also noteworthy that SPVD is an unusual synergistic interaction in that the potyvirus component is not the cause of synergism but is the beneficiary. It is hypothesized that SPCSV is able to enhance the multiplication of SPFMV in tissues other than where it occurs itself, perhaps by interfering with systemic phloem-dependent signaling required in a resistance mechanism directed against SPFMV.     

C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men

Aims/hypothesis Low-grade inflammation has been implicated in the development of Type 2 diabetes and cardiovascular disease, but its role in the pathogenesis of the metabolic syndrome is unclear. We investigated the association between C-reactive protein (CRP) levels and the development of the metabolic syndrome and diabetes in men.Methods Serum CRP concentrations and factors related to insulin resistance were determined in middle-aged Finnish men who participated in a population-based cohort study and were free of diabetes at baseline.Results At the 11-year follow-up, 143 of 680 men had developed the metabolic syndrome as defined by the National Cholesterol Education Program (NCEP) and 103 of 598 men had developed the metabolic syndrome as defined by the World Health Organization (WHO). Our analyses excluded men with the metabolic syndrome by the respective definition at baseline. In all, 78 of 762 men developed diabetes over the same period. Men with CRP concentrations 3 mg/l had a several-fold higher age-adjusted risk of developing the metabolic syndrome (NCEP definition: odds ratio [OR]=3.2, 95% CI 1.9–5.5; WHO definition: OR=3.4, 95% CI 2.0–6.1) or diabetes (OR=4.1, 95% CI 2.1–8.0) than men whose CRP levels were <1.0 mg/l. Even after further adjustment for potentially confounding lifestyle factors and factors related to insulin resistance, the risk of diabetes (OR=2.3, 95% CI 1.0–5.1) was still increased in men with CRP concentrations 3 mg/l, but the association with the metabolic syndrome was no longer significant.Conclusions/interpretation Low-grade inflammation may increase the risk of the metabolic syndrome and diabetes in middle-aged men, but some of the risk is mediated through obesity and factors related to insulin resistance.Abbreviations CRP C-reactive protein - KIHD Kuopio Ischaemic Heart Disease Risk Factor Study - NCEP National Cholesterol Education Program - WHO World Health Organization     

Dose-dependent brain tin concentration in rats given stannous chloride in drinking water

Male Wistar rats were given either 100 mg SnCl2 X 2H2O per litre (0.44 mM), 250 mg/l (1.11 mM) or 500 mg/l (2.22 mM) in their drinking water for 1-18 weeks. Tin detected by a novel atomic absorption spectrophotometric method accumulated in the cerebrum at the highest dose level (2.22 mM) throughout the experiment. In brain, tin concentrations above the 1.11-mM dose were only found after 15 and 18 weeks. Tin did not increase in the brain at the 0.44-mM dose level. Blood tin increased promptly after one week at the highest dose (2.22 mM) without further accumulation. Blood tin at the 0.44 mM dose level did not differ from controls. Tin exposure caused a dose-dependent increase in the cerebral and muscle acetylcholinesterase activity at the two higher doses.     

Intense physical training decreases circulating antioxidants and endothelium-dependent vasodilatation in vivo.

Physical training increases free radical production and consumes antioxidants. It has previously been shown that acute exercise markedly increases the susceptibility of LDL to oxidation but whether such changes are observed during physical training is unknown. We measured circulating antioxidants, lipids and lipoproteins, and blood flow responses to intrabrachial infusions of endothelium-dependent (acetylcholine, ACh, L-N-monomethyl-arginine, L-NMMA) and -independent (sodium nitroprusside, SNP) vasoactive agents, before and after 3 months of running in 9 fit male subjects. Maximal aerobic power increased from 53 +/- 1 to 58 +/- 2 ml/kg min (P < 0.02). All circulating antioxidants (uric acid, SH-groups, alpha-tocopherol, beta-carotene, retinol) except ascorbate decreased significantly during training. Endothelium-dependent vasodilatation in forearm vessels decreased by 32-35% (P < 0.05), as determined from blood flow responses to both a low (10.8 +/- 2.1 vs. 7.3 +/- 1.5 ml/dl min, 0 vs. 3 months) and a high (14.8 +/- 2.6 vs. 9.6 +/- 1.8) ACh dose. The % endothelium-dependent blood flow (% decrease in basal flow by L-NMMA), decreased through training from 37 +/- 3 to 22 +/- 7% (P < 0.05). Blood flow responses to SNP remained unchanged. The decrease in uric acid was significantly correlated with the change in the % decrease in blood flow by L-NMMA (r = 0.74, P < 0.05). The lag time for the susceptibility of plasma LDL to oxidation in vitro, LDL size and the concentration of LDL cholestetol remained unchanged. We conclude that relatively intense aerobic training decreases circulating antioxidant concentrations and impairs endothelial function in forearm vessels.