9.10.2006

New articles - Uudet artikkelit 9.10.2006 - ISI Web of Knowledge & PubMed Search Alert



Coffee consumption and risk of total and cardiovascular mortality among patients with type 2 diabetes

Bidel, S., Hu, G., Qiao, Q., Jousilahti, P., Antikainen, R. and Tuomilehto, J.

Diabetologia. 2006; 49(11): 2618-26. IF 5.337

AIMS/HYPOTHESIS: Higher habitual coffee drinking has been associated with a lower risk of developing type 2 diabetes. The relation between coffee consumption and risk of cardiovascular disease (CVD) has been examined in many studies, but the issue remains controversial. This study was designed to assess the association between coffee consumption and CVD mortality among patients with type 2 diabetes.

METHODS: We prospectively followed 3,837 randomly ascertained Finnish patients with type 2 diabetes aged 25 to 74 years. Coffee consumption and other study parameters were determined at baseline. The International Classification of Diseases was used to identify CHD, CVD and stroke cases using computerised record linkage to the national Death Registry. The associations between coffee consumption at baseline and risk of total, CVD, CHD, and stroke mortality were analysed by using Cox proportional hazards models.

RESULTS: During the average follow-up of 20.8 years, 1,471 deaths were recorded, of which 909 were coded as CVD, 598 as CHD and 210 as stroke. The respective multivariate-adjusted hazard ratios in participants who drank 0-2, 3-4, 5-6, and >/=7 cups of coffee daily were 1.00, 0.77, 0.68 and 0.70 for total mortality (P<0.001 for trend), 1.00, 0.79, 0.70 and 0.71 for CVD mortality (P=0.006 for trend), 1.00, 0.78, 0.70 and 0.63 for CHD mortality (p=0.01 for trend), and 1.00, 0.77, 0.64 and 0.90 for stroke mortality (p=0.12 for trend).

CONCLUSIONS/INTERPRETATION: In this large prospective study we found that in type 2 diabetic patients coffee drinking is associated with reduced total, CVD and CHD mortality.


Time-activity relationships to VOC personal exposure factors

Edwards, R. D., Schweizer, C., Llacqu, V., Lai, H. K., Jantunen, M., Bayer-Oglesby, L. and Kunzli, N.

Atmospheric Environment. 2006; 40(29): 5685-5700. Article. IF 2.724

Social and demographic factors have been found to play a significant role in differences between time-activity patterns of population subgroups. Since time-activity patterns largely influence personal exposure to compounds as individuals move across microenvironments, exposure subgroups within the population may be defined by factors that influence daily activity patterns. Socio-demographic and environmental factors that define time-activity subgroups also define quantifiable differences in VOC personal exposures to different sources and individual compounds in the Expolis study. Significant differences in exposures to traffic-related compounds ethylbenzene, m- and p-xylene and o-xylene were observed in relation to gender, number of children and living alone. Categorization of exposures further indicated time exposed to traffic at work and time in a car as important determinants. Increased exposures to decane, nonane and undecane were observed for males, housewives and self-employed.

Categorization of exposures indicated exposure subgroups related to workshop use and living downtown. Higher exposures to 3-carene and a-pinene commonly found in household cleaning products and fragrances were associated with more children, while exposures to traffic compounds ethylbenzene, rn- and p-xylene and o-xylene were reduced with more children. Considerable unexplained variation remained in categorization of exposures associated with home product use and fragrances, due to individual behavior and product choice. More targeted data collection methods in VOC exposure studies for these sources should be used. Living alone was associated with decreased exposures to 2-methyl-1-propanol and 1-butanol, and traffic-related compounds.

Identification of these subgroups may help to reduce the large amount of unexplained variation in VOC exposure studies. Further they may help in assessing impacts of urban planning that result in changes in behavior of individuals, resulting in shifts in the patterns of exposure experienced by the population. (c) 2006 Elsevier Ltd. All rights reserved.


In vitro inflammatory and cytotoxic effects of size-segregated particulate samples collected during long-range transport of wildfire smoke to Helsinki

Jalava, P. I., Salonen, R. O., Halinen, A. I., Penttinen, P., Pennanen, A. S., Sillanpää, M., Sandell, E., Hillamo, R. and Hirvonen, M. R.

Toxicology and Applied Pharmacology. 2006; 215(3): 341-353. Article. IF 3.148

The impact of long-range transport (LRT) episodes of wildfire smoke on the inflammogenic and cytotoxic activity of urban air particles was investigated in the mouse RAW 264.7 macrophages.

The particles were sampled in four size ranges using a modified Harvard high-volume cascade impactor, and the samples were chemically characterized for identification of different emission sources. The particulate mass concentration in the accumulation size range (PM1-0.2) was highly increased during two LRT episodes, but the contents of total and genotoxic polycyclic aromatic hydrocarbons (PAH) in collected particulate samples were only 10-25% of those in the seasonal average sample.

The ability of coarse (PM10-2.5), intermodal size range (PM2.5-1), PM1-0.2 and ultrafine (PM0.2) particles to cause cytokine production (TNF alpha, IL-6, MIP-2) reduced along with smaller particle size, but the size range had a much smaller impact on induced nitric oxide (NO) production and cytotoxicity, or apoptosis. The aerosol particles collected during LRT episodes had a substantially lower activity in cytokine production than the corresponding particles of the seasonal average period, which is suggested to be due to chemical transformation of the organic fraction during aging.

However, the episode events were associated with enhanced inflammogenic and cytotoxic activities per inhaled cubic meter of air due to the greatly increased particulate mass concentration in the accumulation size range, which may have public health implications. (c) 2006 Elsevier Inc. All rights reserved.


Abstaining from alcohol and labour market underperformance - Have we forgotten the 'dry' alcoholics?

Johansson, E., Alho, H., Kiiskinen, U. and Poikolainen, K.

Alcohol and Alcoholism. 2006; 41(5): 574-579. Article. IF 2.040

Aims: To investigate whether abstainers fare worse than non-abstainers on the labour market because a subset of the abstainers are ex-drinkers with alcohol problems.

Methods: In the cross-sectional population survey 'health 2000 in Finland' (n = 10 000) carried out in 2000, alcohol dependency was measured using the DSM-IV diagnostic criteria for alcohol dependence. The CIDI (composite international diagnostic interview) was applied to ascertain lifetime DSM-IV diagnoses for substance abuse diagnoses, including alcohol dependence. Individuals were considered to be employed if they were working part-time or full-time.

Results: Male abstainers have on average 9.5 percentage points lower employment probability than non-abstainers. However, abstainers who have never drunk alcohol do not have lower employment probability than non-abstainers. Abstainers who are diagnosed as alcohol dependent have 27 percentage points lower employment probability than non-abstainers.

Conclusion: The underperformance of abstainers in a labour market sense is almost entirely due to the fact that some abstainers are ex-drinkers who in our study are identified as alcohol-dependent. Otherwise abstaining does not decrease employment probability.


Improving the world's health--the role of National Public Health Institutes

Jousilahti, P.

Cent Eur J Public Health. 2006; 14(1): 3-5. Full text


Early cytokine responses after percutaneous magnetic resonance imaging guided laser thermoablation of malignant liver tumors

Kallio, R., Sequeiros, R., Surcel, H. M., Ohtonen, P., Kiviniemi, H. and Syrjälä, H.

Cytokine. 2006; 34(5-6): 278-283. Article. IF 2.012

An early systemic response induced by magnetic resonance imaging (MRI)-guided interstitial percutaneous laser thermoablation was analyzed in 13 consecutive patients with malignant liver tumors by serum interleukin (IL)-1 beta, 11-6, IL-10, tumor necrosis factor (TNF)-alpha, its receptor TNFRI, and C-reactive protein (CRP) levels up to 72 It after the procedures. Only IL-6 (p = 0.033) and TNFRI (p < 0.001) increased statistically significantly after ablation, while the TNF-alpha, IL-1 beta, and IL-10 levels remained unchanged. The peak median CRP response was 92 mg/l. There was a dose-dependent correlation between the energy used and the maximum CRP values (tau = 0.68, p = 0.013). MRI-guided laser thermoablation induced an early systemic inflammatory reaction with statistically significantly elevated IL-6, TNFRI, and CRP levels but not TNF-alpha or IL-10 levels and without procedure-related complications, favoring this procedure as a safe therapeutic alternative for well-selected patients with liver tumors. (c) 2006 Elsevier Ltd. All rights reserved.


Structural and functional changes in peripheral vasculature of Fabry patients

Kalliokoski, R. J., Kalliokoski, K. K., Penttinen, M., Kantola, I., Leino, A., Viikari, J. S., Simell, O., Nuutila, P. and Raitakari, O. T.

Journal of Inherited Metabolic Disease. 2006; 29(5): 660-666. Article. IF 1.722

Objective: Fabry disease is a lysosomal storage disorder due to deficient alpha-galactosidase A activity, which leads to glycosphingolipid accumulation especially in vascular smooth-muscle and endothelial cells. Little is known about the effects of Fabry disease on peripheral artery function and structure. Therefore, we aimed to further characterize the peripheral vascular structural and functional changes in Fabry disease.

Methods and results: We measured structural and functional vascular parameters, including intima-media thickness (IMT) of brachial and carotid arteries and abdominal aorta, carotid and aortic compliance, and brachial artery flow-mediated dilatation (FMD) in 17 Fabry patients and 34 healthy controls matched for age, sex and smoking. Carotid IMT (0.64 +/- 0.15 vs 0.57 +/- 0.12 mm), brachial IMT (1.02 +/- 0.25 vs 0.74 +/- 0.18 mm), and aortic IMT (0.31 +/- 0.09 vs 0.26 +/- 0.04 mm) were significantly increased, and brachial FMD was significantly impaired (6.3 +/- 5.0 vs 9.7 +/- 3.9%) in Fabry patients compared to healthy controls (p < 0.05 in all comparisons after adjustments for age, LDL-cholesterol, and systolic blood pressure). No differences were observed in arterial compliance between the groups.

Conclusions: These data suggest that Fabry disease affects arterial function and structure by disturbing peripheral endothelial function and promoting intima-media thickening.


Can we identify sources of fine particles responsible for exercise-induced ischemia on days with elevated air pollution? The ULTRA study

Lanki, T., de Hartog, J. J., Heinrich, J., Hoek, G., Janssen, N. A., Peters, A., Stolzel, M., Timonen, K. L., Vallius, M., Vanninen, E. and Pekkanen, J.

Environ Health Perspect. 2006; 114(5): 655-60. IF 5.342

Epidemiologic studies have shown that ambient particulate matter (PM) has adverse effects on cardiovascular health. Effective mitigation of the health effects requires identification of the most harmful PM sources.

The objective of our study was to evaluate relative effects of fine PM [aerodynamic diameter0.1 mV, with odds ratios at 2-day lag of 1.53 [95% confidence interval (CI), 1.19-1.97] and 1.11 (95% CI, 1.02-1.20) per 1 microg/m3, respectively. In multipollutant models, where we used indicator elements for sources instead of source-specific PM2.5, only absorbance (elemental carbon), an indicator of local traffic and other combustion, was associated with ST segment depressions.

Our results suggest that the PM fraction originating from combustion processes, notably traffic, exacerbates ischemic heart diseases associated with PM mass.


Enteral virus infections in early childhood and an enhanced type 1 diabetes-associated antibody response to dietary insulin

Mäkelä, M., Vaarala, O., Hermann, R., Salminen, K., Vahlberg, T., Veijola, R., Hyöty, H., Knip, M., Simell, O. and Ilonen, J.

Journal of Autoimmunity. 2006; 27(1): 54-61. Article. IF 2.491

Enteral virus infections may trigger the development of beta-cell-specific autoimmunity by interacting with the gut-associated lymphoid system.

We analyzed the effect of three different virus infections on immunization to dietary insulin in children carrying increased genetic risk for type I diabetes. Forty-six of 238 children developed multiple diabetes-associated autoantibodies and 31 clinical diabetes (median follow-up time 75 months). Insulin-binding antibodies were measured with EIA method (median follow-up time 24 months). Antibodies to enteroviruses, rotavirus and adenovirus were measured with EIA in samples drawn at birth and the ages of 3 and 6 months. Nineteen enterovirus, 14 rotavirus and 8 adenovirus infections were diagnosed. At the ages of 6, 12, and 18 months, the concentrations of insulin-binding antibodies were higher in children with postnatal entero-, rota- and/or adenovirus infections than in children without these infections. Children who subsequently developed ICA or IA-2 antibodies or clinical type 1 diabetes had higher concentrations of insulin-binding antibodies than children who remained autoantibody negative.

Our data suggest that enteral virus infections can enhance immune response to insulin, induced primarily by bovine insulin in cow's milk. An enhanced antibody response to dietary insulin preceded the development of beta-cell specific autommumity and type I diabetes. (c) 2006 Elsevier Ltd. All rights reserved.


Negotiation over self-control and activity: an analysis of balancing in the repertoires of Finnish healthy lifestyles

Pajari, P. M., Jallinoja, P. and Absetz, P.

Soc Sci Med. 2006; 62(10): 2601-11. IF 2.619

This study analyses arguments for and against the notion of healthy lifestyles, and the construction of responsibility for health, in group discussions in Finland.

With data from four focus groups, we identified five interpretative repertoires: a strong activity repertoire reflects the dominant cultural value of health and emphasizes self-control. Three other repertoires--illness, external barriers, and weak character--share the underlying values of the activity repertoire, but exemplify situations where the individual lacks control, seeking to justify deviations from the norm of activity.

One counter-repertoire, the pleasure repertoire, questions the hegemonic value of health, and discusses other competing values. The discussion of health is an ongoing dialectical process drawing from the different repertoires. In order to avoid stigmatization and to save face in the social situation of a focus group, the subjects strive to balance their accounts of behaviours considered unhealthy by also claiming healthy behaviours. They also strike a balance between extreme rigidity and carelessness, emphasizing the ideal of moderation and harmony.

The findings point to a need to consider variations in and underpinnings of a "good life" at the individual level. Encouraging people to specify the meaning and content of moderation in their personal lives could provide a new perspective for health education and health promotion.


Developmental regulation of the adhesive and enzymatic activity of vascular adhesion protein-1 (VAP-1) in humans

Salmi, M. and Jalkanen, S.

Blood. 2006; 108(5): 1555-61. IF 10.131

Vascular adhesion protein-1 (VAP-1) is a homodimeric glycoprotein that belongs to a unique subgroup of cell-surface-expressed oxidases. In adults, endothelial VAP-1 supports leukocyte rolling, firm adhesion, and transmigration in both enzyme activity-dependent and enzyme activity-independent manner.

Here we studied the induction and function of VAP-1 during human ontogeny. We show that VAP-1 is already found in the smooth muscle at embryonic week 7. There are marked time-dependent switches in VAP-1 expression in the sinusoids of the liver, in the peritubular capillaries of the kidney, in the capillaries of the heart, and in the venules in the lamina propria of the gut. Fetal VAP-1 is dimerized, and it is enzymatically active. VAP-1 in fetal-type venules is able to bind cord blood lymphocytes. Also, adenovirally transfected VAP-1 on human umbilical vein endothelial cells is involved in rolling and firm adhesion of cord blood lymphocytes under conditions of physiologic shear stress.

We conclude that VAP-1 is synthesized from early on in human vessels and it is functionally intact already before birth. Thus, VAP-1 may contribute critically to the oxidase activities in utero, and prove important for lymphocyte trafficking during human ontogeny.


Association of transcription factor 7-like 2 (TCF7L2) variants with type 2 diabetes in a Finnish sample

Scott, L. J., Bonnycastle, L. L., Willer, C. J., Sprau, A. G., Jackson, A. U., Narisu, N., Duren, W. L., Chines, P. S., Stringham, H. M., Erdos, M. R., Valle, T. T., Tuomilehto, J., Bergman, R. N., Mohlke, K. L., Collins, F. S. and Boehnke, M.

Diabetes. 2006; 55(9): 2649-2653. Article. IF 8.028

Transcription factor 7-like 2 (TCF7L2) is part of the Wnt signaling pathway. Genetic variants within TCF7L2 on chromosome 10q were recently reported to be associated with type 2 diabetes in Icelandic, Danish, and American (U.S.) samples.

We previously observed a modest logarithm of odds score of 0.61 on chromosome 10q, similar to 1 Mb from TCF7L2, in the Finland-United States Investigation of NIDDM Genetics study. We tested the five associated TCF7L2 single nucleotide polymorphism (SNP) variants in a Finnish sample of 1,151 type 2 diabetic patients and 953 control subjects. We confirmed the association with the same risk allele (P value < 0.05) for all five SNPs. Our strongest results were for rs1255372 (odds ratio [OR] 1.36 [95% CI 1.15-1.61], P = 0.00026) and rs7903146 (1.33 [1.14-1.56], P = 0.00042). Based on the CEU HapMap data, we selected and tested 12 additional SNPs to tag SNPs in linkage disequilibrium with rs1255372. None of these SNPs showed stronger evidence of association than rs12255372 or rs7903146 (OR <= 1.26, P >= 0.0054).

Our results strengthen the evidence that one or more variants in TCF7L2 are associated with increased risk of type 2 diabetes.


Gender differences in health care use among the elderly population in areas of Norway and Finland. A cross-sectional analysis based on the HUNT study and the FINRISK Senior Survey

Suominen-Taipale, A. L., Martelin, T., Koskinen, S., Holmen, J. and Johnsen, R.

BMC Health Services Research. 2006; 6. Article. IF 1.625

Background: The aim of the study was to examine gender differences in the self-reported use of health care services by the elderly in rural and metropolitan areas of two Nordic countries with slightly different health care systems: Finland and Norway.

Methods: Population based, cross-sectional surveys conducted in Nord-Trondelag Norway ( 1995 - 97) and in rural and metropolitan areas of Finland ( 1997) were employed. In the Norwegian data, a total of 7,919 individuals, aged 65 - 74 years old were included, and the Finnish data included 1,500 individuals. The outcome variables comprised whether participants had visited a general practitioner or a specialist, or had received hospital care or physiotherapy during the past 12 months. Gender differences in the use of health care services were analysed by multiple logistic regression, controlling for health status and socio-demographic characteristics.

Results: In Norway, elderly women visited a specialist or were hospitalised less often than men. In Finland, elderly women used all health care services except hospital care more often than men. In Norway, less frequent use of specialist care by women was not associated with self-reported health or chronic diseases.

Conclusion: The findings revealed differences in self-reported use of secondary care among different genders in areas of Norway and Finland.


Dietary insulin as an immunogen and tolerogen

Tiittanen, M., Paronen, J., Savilahti, E., Virtanen, S. M., Ilonen, J., Knip, M., Åkerblom, H. K. and Vaarala, O.

Pediatr Allergy Immunol. 2006; 17(7): 538-43. IF 2.126

We have shown that exposure to bovine insulin (BI) in cow's milk (CM) formula induces an insulin-specific immune response in infants.

Here we studied the role of human insulin (HI) in breast milk as a modulator of the immune response to insulin. In a group of 128 children participating in the TRIGR pilot study, maternal breast milk samples were collected 3-7 days and/or 3 months after delivery. After exclusive breast-feeding, the children received either CM formula or casein hydrolysate during the first 6-8 months of life. Insulin concentration in breast milk and immunoglobulin G (IgG) antibodies to BI in plasma samples were measured by EIA. The levels of insulin in breast milk samples were higher in mothers affected by type 1 diabetes than in non-diabetic mothers (p = 0.007 and p < 0.001). The concentration of insulin in breast milk correlated inversely with the plasma levels of IgG antibodies to BI at 6 months of age in children who received CM formula (r = -0.39, p = 0.013), and at 12 months of age in all children (r = -0.25, p = 0.029). The levels of breast milk insulin were higher in the mothers of nine children who developed beta-cell autoimmunity when compared with autoantibody-negative children (p = 0.030); this holds true also when only children of diabetic mothers were included (p = 0.045). BI in CM induces higher levels of IgG to insulin in infants than does HI in breast-fed children. Instead, HI in breast milk seems to be tolerogenic and may downregulate the IgG response to dietary BI.

However, our results in infants who developed beta-cell autoimmunity suggest that in this subgroup of children breast milk insulin does not promote tolerance.


Mycobacteria and fungi in moisture-damaged building materials

Torvinen, E., Meklin, T., Torkko, P., Suomalainen, S., Reiman, M., Katila, M. L., Paulin, L. and Nevalainen, A.

Appl Environ Microbiol. 2006; 72(10): 6822-4. IF 3.818

In contrast to the growth of fungi, the growth of mycobacteria in moisture-damaged building materials has rarely been studied. Environmental mycobacteria were isolated from 23% of samples of moisture-damaged materials (n = 88). The occurrence of mycobacteria increased with increasing concentrations of fungi. Mycobacteria may contribute to indoor exposure and associated adverse health effects.


Protecting our unborn children: how to measure exposure to thousands of chemicals?

Tuomisto, J.

Arch Dis Child. 2006; 91(8): 627-8. IF 1.787

For 30 years cancers have been the most feared diseases linked to environmental chemicals. Recently developmental effects, especially those of the central nervous system, appear to have taken their place at least in part. Both the chemicals involved and the ways of exposure are manifold. Methyl mercury, polychlorinated biphenyls (PCBs), and dioxins derive from fish. Lead comes from multiple sources, historically from leaded gasoline and paints, in some countries also from plumbing. Polybrominated diphenylethers are added to synthetic materials as flame retardants. We are exposed to pesticide residues in our food as well as in our home environment.

Most of these potential new dangers are plagued with controversy. In many cases it is a question of dose. There is no doubt about the developmental neurotoxicity of lead or methyl mercury, but are the present environmental exposures high enough to cause risk?


The 2005 World Health Organization reevaluation of human and mammalian toxic equivalency factors for dioxins and dioxin-like compounds

Van den Berg, M., Birnbaum, L. S., Denison, M., De Vito, M., Farland, W., Feeley, M., Fiedler, H., Hakansson, H., Hanberg, A., Haws, L., Rose, M., Safe, S., Schrenk, D., Tohyama, C., Tritscher, A., Tuomisto, J., Tysklind, M., Walker, N. and Peterson, R. E.

Toxicological Sciences. 2006; 93(2): 223-241. Review. IF 3.088

In June 2005, a World Health Organization (WHO)-International Programme on Chemical Safety expert meeting was held in Geneva during which the toxic equivalency factors (TEFs) for dioxin-like compounds, including some polychlorinated biphenyls (PCBs), were reevaluated. For this reevaluation process, the refined TEF database recently published by Haws et al. (2006, Toxicol. Sci. 89, 4-30) was used as a starting point. Decisions about a TEF value were made based on a combination of unweighted relative effect potency (REP) distributions from this database, expert judgment, and point estimates. Previous TEFs were assigned in increments of 0.01, 0.05, 0.1, etc., but for this reevaluation, it was decided to use half order of magnitude increments on a logarithmic scale of 0.03, 0.1, 0.3, etc. Changes were decided by the expert panel for 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.3), 1,2,3,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.03), octachlorodibenzo-p-dioxin and octachlorodibenzofuran (TEFs = 0.0003), 3,4,4',5-tetrachlorbiphenyl (PCB 81) (TEF = 0.0003), 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) (TEF = 0.03), and a single TEF value (0.00003) for all relevant mono-ortho-substituted PCBs. Additivity, an important prerequisite of the TEF concept was again confirmed by results from recent in vivo mixture studies. Some experimental evidence shows that non-dioxin-like aryl hydrocarbon receptor agonists/antagonists are able to impact the overall toxic potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds, and this needs to be investigated further. Certain individual and groups of compounds were identified for possible future inclusion in the TEF concept, including 3,4,4'-TCB (PCB 37), polybrominated dibenzo-p-dioxins and dibenzofurans, mixed polyhalogenated dibenzo-p-dioxins and dibenzofurans, polyhalogenated naphthalenes, and polybrominated biphenyls. Concern was expressed about direct application of the TEF/total toxic equivalency (TEQ) approach to abiotic matrices, such as soil, sediment, etc., for direct application in human risk assessment. This is problematic as the present TEF scheme and TEQ methodology are primarily intended for estimating exposure and risks via oral ingestion (e.g., by dietary intake).

A number of future approaches to determine alternative or additional TEFs were also identified. These included the use of a probabilistic methodology to determine TEFs that better describe the associated levels of uncertainty and "systemic" TEFs for blood and adipose tissue and TEQ for body burden.


Dietary factors of one-carbon metabolism and prostate cancer risk

Weinstein, S. J., Stolzenberg-Solomon, R., Pietinen, P., Taylor, P. R., Virtamo, J. and Albanes, D.

Am J Clin Nutr. 2006; 84(4): 929-935. IF 5.853

BACKGROUND: Folate is hypothesized to be inversely associated with the risk of several cancers, but such a potential association has not been well studied for prostate cancer. Vitamin B-6, vitamin B-12, methionine, and alcohol can influence folate-related metabolism.

OBJECTIVE: The objective was to investigate the associations between dietary factors of one-carbon metabolism and prostate cancer risk within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study.

DESIGN: Of the cohort's 27 111 Finnish male smokers aged 50-69 y who had complete dietary data, 1270 had a diagnosis of incident prostate cancer between 1985 and 2002. Folate, vitamin B-6, vitamin B-12, methionine, and alcohol intakes were estimated from a 276-item modified dietary history questionnaire. Cox proportional hazard models, adjusted for age and vitamin supplement use, estimated relative risks (RR) and 95% CIs.

RESULTS: Vitamin B-6 intake was inversely associated with prostate cancer risk (RR for highest versus lowest quintile: 0.88; 95% CI: 0.72, 1.07; P for trend = 0.045), whereas vitamin B-12 intake was associated with significantly increased risk (RR = 1.36; 95% CI: 1.14, 1.96; P for trend = 0.01). No association between folate or alcohol intake and prostate cancer risk was observed. No differences were found in the above associations according to stage of disease or subgroups of several potential effect modifiers.

CONCLUSIONS: We found no convincing evidence for a protective role of one-carbon metabolism against prostate cancer, although these observations can be generalized only to smokers. The possible modest protective association with vitamin B-6 and the significantly elevated risk with vitamin B-12 intake warrant further investigation.


The detection of micromolar pericellular ATP pool on lymphocyte surface by using lymphoid ecto-adenylate kinase as intrinsic ATP sensor

Yegutkin, G. G., Mikhailov, A., Samburski, S. S. and Jalkanen, S.

Mol Biol Cell. 2006; 17(8): 3378-85. IF 6.520

Current models of extracellular ATP turnover include transient release of nanomolar ATP concentrations, triggering of signaling events, and subsequent ectoenzymatic inactivation. Given the high substrate specificity for adenylate kinase for reversible reaction (ATP + AMP <--> 2ADP), we exploited lymphoid ecto-adenylate kinase as an intrinsic probe for accurate sensing pericellular ATP. Incubation of leukemic T- and B-lymphocytes with [3H]AMP or [alpha-32P]AMP induces partial nucleotide conversion into high-energy phosphoryls. This "intrinsic" AMP phosphorylation occurs in time- and concentration-dependent fashions via nonlytic supply of endogenous gamma-phosphate-donating ATP, remains relatively resistant to bulk extracellular ATP scavenging by apyrase, and is diminished after lymphocyte pretreatment with membrane-modifying agents. This enzyme-coupled approach, together with confocal imaging of quinacrine-labeled ATP stores, suggests that, along with predominant ATP accumulation within cytoplasmic granules, micromolar ATP concentrations are constitutively retained on lymphoid surface without convection into bulk milieu. High basal levels of inositol phosphates in the cells transfected with ATP-selective human P2Y2-receptor further demonstrate that lymphocyte-surrounding ATP is sufficient for triggering purinergic responses both in autocrine and paracrine fashions. The ability of nonstimulated lymphocytes to maintain micromolar ATP halo might represent a novel route initiating signaling cascades within immunological synapses and facilitating leukocyte trafficking between the blood and tissues.