10.12.2007

Badeau, R. M., Metso, J., Tikkanen, M. J. and Jauhiainen, M.

Biochim Biophys Acta. 2007; 1771(10): 1329-34. IF 3.117

17beta-estradiol (E2) fatty acyl esters naturally incorporate into high-density lipoprotein (HDL).

The objective was to elucidate mechanisms involved in HDL-associated E2 cellular uptake and to determine the intracellular distribution of E2 and its fatty acyl esters (E2-FAE) after uptake. [3H]E2 or [3H] cholesterol was incubated with human serum for 24 h to allow for fatty acyl esterification. Total-HDL containing [3H]E2-FAE or [3H]cholesterol esters was isolated by sequential density ultracentrifugation and then incubated with Fu5AH rat hepatoma cells for various time points. Cellular uptake was determined by intracellular radioactivity as a percentage of total radioactivity. Chemical inhibition of scavenger receptor class B, type I and low-density lipoprotein (LDL) receptor competition assays were performed to determine cellular uptake mechanisms. Compared to HDL-[3H]cholesterol, cellular uptake of HDL-[3H]E2 occurred at an initially rapid rate. SR-BI inhibition resulted in a decrease in HDL-E2 uptake and LDL impaired this uptake in a concentration-dependent manner. Accordingly, pretreatment of cells with BLT-1 combined with LDL addition significantly attenuated HDL-E2 uptake. HDL-E2-FAE was hydrolyzed into free E2 with the maximum at 24 h. Fu5AH cells facilitate HDL-E2 uptake by at least SR-BI and LDL receptor pathways and intracellular hydrolysis of E2-FAE into free E2 ensues.

Long-term effects of fenofibrate on VLDL and HDL subspecies in participants with type 2 diabetes mellitus (vol 50, pg 2611, 2007)

Hiukka, A., Leinonen, E., Jauhiainen, M., Sundvall, J., Ehnholm, C., Keech, A. C. and Taskinen, M. R.

Diabetologia. 2007; 50(12): 2611-2613. Correction. IF 5.247

The density of negative charge in the cell wall influences two-component signal transduction in Bacillus subtilis

Hyyrylainen, H. L., Pietiainen, M., Lunden, T., Ekman, A., Gardemeister, M., Murtomaki-Repo, S., Antelmann, H., Hecker, M., Valmu, L., Sarvas, M. and Kontinen, V. P.

Microbiology. 2007; 153(Pt 7): 2126-36. IF 3.139

The Dlt system modulates the density of negative charge in the cell wall of Gram-positive bacteria by substituting anionic polymers (wall and lipoteichoic acids) with d-alanine. The htrA and htrB genes, regulated by the CssRS two-component system (TCS) and encoding membrane-associated protein quality control proteases, were expressed at strongly decreased levels in a mutant with defective Dlt (dltD : : miniTn10) as compared to the dlt(+) wild-type strain under a secretion stress condition (hypersecretion of AmyQ alpha-amylase). The level of HtrA protein in the extracellular proteome of the dltD mutant was decreased consistently. Expression from the promoter of the liaIHGFSR (yvqIHGFEC) operon (P(liaI)) is dependent on the LiaRS TCS. The Dlt defect increased the expression from P(liaI) under two stress conditions, AmyQ hypersecretion and treatment with a cationic antimicrobial peptide (LL-37), but decreased the expression in vancomycin-treated cells. Furthermore, Dlt inactivation enhanced the expression of the YxdJK-regulated yxdL gene in LL-37-treated cells. The increased net negative charge of the cell wall seems to cause varied and opposite effects on the expression of CssRS-, LiaRS- and YxdJK-regulated genes under different stress conditions.

The results suggest that TCSs which sense misfolded proteins or peptides are modulated by the density of negative charge in the cell wall. The density of negative charge on the outer surface of the cell membrane did not have a similar effect on TCSs.

Antimicrobial use in Finnish acute care hospitals: data from national prevalence survey, 2005

Kanerva, M., Ollgren, J. and Lyytikainen, O., Finnish Prevalence Survey Study Group

J Antimicrob Chemother. 2007; 60(2): 440-4. IF 3.891

OBJECTIVES: In Finland, use of antimicrobials in ambulatory care is moderate, but some reports suggest that hospital use is higher than in other European countries. We evaluated the amount and type of antimicrobials administered in Finnish acute care hospitals.

PATIENTS AND METHODS: We analysed data collected in the national prevalence survey of nosocomial infections (NIs) during February-March 2005 in all tertiary care, all secondary care and 25% of other acute care hospitals. All inpatients present on the study day in acute care wards for adults were included (n=8234). The names and use-days of antimicrobials in Anatomical Therapeutic Class groups J01-J05 were collected on the study day and retrospectively for the previous 6 days.

RESULTS: On the study day, 39% of patients had received at least one, 14% at least two and 3% at least three antimicrobials; patients with NI represented 21%, 29% and 45% of these groups, respectively. The prevalence of patients receiving any antimicrobial was 53% in intensive care patients and varied in other specialties from 0% in ophthalmology to 63% in dental and oral surgery. Within a 7 day period, the total use of antibacterial agents (J01) was 64 use-days per 100 patient-days. Cephalosporins were the most frequently used antimicrobials, followed by quinolones and metronidazole.

CONCLUSIONS: The prevalence and spectrum of antimicrobial use in Finnish acute care hospitals were high. NI patients contributed markedly to the total usage. The NI survey with a 7 day data collection period provided insights into the use-density of antimicrobials.

Organohalogen pollutants in herring from the northern Baltic Sea: Concentrations, congener profiles and explanatory factors

Koistinen, J., Kiviranta, H., Ruokojarvi, P., Parmanne, R., Verta, M., Hallikainen, A. and Vartiainen, T.

Environ Pollut. 2007. IF 2.769

Organohalogen contaminants were investigated in Baltic herring caught from three catchment areas in the Baltic Sea, off the coasts of Finland. Pools of both small and large herring were analysed for polychlorinated biphenyls (PCB), dibenzo-p-dioxins, dibenzofurans, naphthalenes, camphenes (toxaphene), polybrominated diphenyl ethers and the pesticide DDT and its metabolites. PCB concentrations per fresh weight in small herring were at the same level in all catchment areas, i.e. the Bothnian Bay, the Bothnian Sea and the Gulf of Finland, revealing no hot spots and reflecting most likely long term emissions and atmospheric deposition. Differences in the levels and/or congener profiles of other contaminants between catchment areas may be explained by point sources.

Similar concentrations in small and large herring in the Gulf of Finland were possibly due to their common nutrition. In the other areas, differences between small and large herring most likely reflected their different food sources.

Increased physical activity is a cornerstone in the prevention of type 2 diabetes in high-risk individuals

Laaksonen, D. E., Lindstrom, J., Tuomilehto, J. and Uusitupa, M.

Diabetologia. 2007; 50(12): 2607-2608. Letter. IF 5.247

The effect of birth order and parental age on the risk of type 1 and 2 diabetes among young adults

Lammi, N., Moltchanova, E., Blomstedt, P., Eriksson, J. G., Taskinen, O., Sarti, C., Tuomilehto, J. and Karvonen, M.

Diabetologia. 2007; 50(12): 2433-2438. Article. IF 5.247

Aims/hypothesis The aim of this study was to examine the effects of birth order and parental age on the risk of type 1 and type 2 diabetes among Finnish individuals aged 15 39 years.

Methods Data on all cases of type 1 diabetes (n= 1,345) and type 2 diabetes (n= 1,072), diagnosed between 1992 and 1996, were collected from four sources: standardised national reports from diabetes nurses, the National Hospital Discharge Register, the Drug Prescription Register and the Drug Reimbursement Register. Information on matched controls and the family members of all study subjects were obtained from the National Population Registry. The odds ratios (ORs) for both types of diabetes were estimated using a conditional logistic regression model.

Results There was a U-shaped relationship between maternal age and the risk of type 2 diabetes in the offspring: the risk was higher in children born to young and old mothers compared with children born to mothers aged around 30 years. The children born second (OR 0.76, 95% CI 0.62-0.94), third (OR 0.73, 95% CI 0.55-0.95), or fourth (OR 0.66, 95% CI 0.47-0.94) had a lower risk of type 2 diabetes than the first-born children. Maternal age, paternal age, and birth order did not have an effect on the risk of type 1 diabetes in the individuals aged 15-39 years at the time of diagnosis.

Conclusions/interpretation Maternal age and birth order are both associated with the risk of early-onset type 2 diabetes. However, part of these associations may be due to low birthweight. In this study neither parental age nor birth order showed a significant association with the risk of type 1 diabetes diagnosed after 15 years of age.

Association of ADRB1 and UCP3 Gene Polymorphisms with Insulin Sensitivity but Not Obesity

Mottagui-Tabar, S., Hoffstedt, J., Brookes, A. J., Jiao, H., Arner, P. and Dahlman, I.

Horm Res. 2007; 69(1): 31-36. IF 1.385

Background: The uncoupling proteins (UCPs) and beta-adrenoceptors (ADRBs) are important for energy balance and may be involved in the pathogenesis of insulin resistance. Obesity is strongly hunted by insulin resistance and susceptibility genes for the two conditions could be separate or common. Variations within the UCPs and ADRBs genes may give important clues to their involvement in disease.

Methods: A total of four single nucleotide polymorphisms (SNPs) in the genes UCP1, UCP2, UCP3, and ADRB1 were examined for association with obesity and insulin sensitivity (HOMA(IR)) in obese (n = 292) and healthy non-obese (n = 481) females.

Results: None of the SNPs was associated with obesity status or body mass index. However, ADRB1 (rs1801253) was nominally associated with serum insulin (nominal p = 0.034) and HOMA(IR) (nominal p = 0.022). UCP3 (rs1800006) was in post-hoc analysis nominally associated with serum insulin and HOMA(IR) (nominal p = 0.013 and 0.048, respectively). UCP1 and UCP2 showed no association with insulin sensitivity.

Conclusion: Polymorphisms in ADRB1 and UCP3 may contribute to insulin resistance rather than obesity among Swedish women. Copyright (c) 2007 S. Karger AG, Basel.

Education and dementia - What lies behind the association?

Ngandu, T., von Strauss, E., Helkala, E. L., Winblad, B., Nissinen, A., Tuomilehto, J., Soininen, H. and Kivipelto, M.

Neurology. 2007; 69(14): 1442-1450. Article. IF 5.690

Background: Low education seems to be associated with an increased risk of dementia and Alzheimer disease ( AD). People with low education have unhealthier lifestyles and more cardiovascular risk factors, but it is unclear how this affects the association between education and dementia.

Methods: Participants of the Cardiovascular Risk Factors, Aging and Dementia ( CAIDE) study were derived from random, population- based samples previously studied in a survey in 1972, 1977, 1982, or 1987. After an average follow- up of 21 years, 1,449 individuals ( 72%) aged 65 to 79 participated in a re- examination in 1998.

Results: Compared to individuals with formal education of 5 years or less, those with 6 to 8 years of education had OR of 0.57 ( 95% CI 0.29 to 1.13), and those with 9 years of education or more had OR of 0.16 ( 95% CI 0.06 to 0.41) for dementia. The corresponding ORs for AD were 0.49 ( 0.24 to 1.00) and 0.15 ( 0.05 to 0.40). The associations remained unchanged after adjustments for several demographic, socioeconomic, vascular, and lifestyle characteristics. The results were similar among both men and women. ApoE4 did not modify the association, but the risk of dementia and AD was very low among ApoE4 noncarriers with high education.

Conclusions: The association between low education and dementia is probably not explained by the unhealthy lifestyles of the less educated compared with higher educated persons. Higher educated persons may have a greater cognitive reserve that can postpone the clinical manifestation of dementia. Unhealthy lifestyles may independently contribute to the depletion of this reserve or directly influence the underlying pathologic processes.

Asthmatic persons are prone to the persistence of Chlamydia pneumoniae antibodies

Paldanius, M., Juvonen, R., Leinonen, M., Bloigu, A., Silvennoinen-Kassinen, S. and Saikku, P.

Diagn Microbiol Infect Dis. 2007; 59(2): 117-22. IF 2.553

Acute Chlamydia pneumoniae infection may initiate asthma or worsen asthmatic symptoms. In crowded conditions, such as military service, young men are susceptible to respiratory infections, including C. pneumoniae.

We recruited 127 asthmatic and 391 nonasthmatic military conscripts, followed up their respiratory tract infections and the kinetics of serum C. pneumoniae antibodies, and assessed the association between C. pneumoniae and asthma during 6 months of military service in 2 intake groups. During the 6-month period, in the July intake group, IgG antibody prevalence decreased from 60.3% to 43.8% in asthmatic and from 55.6% to 22.6% in nonasthmatic conscripts. In the January intake group, IgG antibody prevalence increased from 38.3% to 48.4% in asthmatic and from 37.2% to 43% in nonasthmatic recruits. IgG and IgA antibodies persisted more often in the asthmatic groups. In conclusion, the prevalence of IgG antibodies showed seasonal variation.

Military recruits seem to be most vulnerable to C. pneumoniae infections during the period from January to June. The antibody titer changes were more rapid than previously thought.

Association of distinct allelic haplotypes of DISC1 with psychotic and bipolar spectrum disorders and with underlying cognitive impairments

Palo, O. M., Antila, M., Silander, K., Hennah, W., Kilpinen, H., Soronen, P., Tuulio-Henriksson, A., Kieseppa, T., Partonen, T., Lonnqvist, J., Peltonen, L. and Paunio, T.

Human Molecular Genetics. 2007; 16(20): 2517-2528. Article. IF 8.099

Bipolar disorder (BPD) and schizophrenia (SCZ) have at least a partially convergent aetiology and thus may share genetic susceptibility loci. Multiple lines of evidence emphasize the role of disrupted-in-schizophrenia-1 (DISC1) gene in psychotic disorders such as SCZ. We monitored the association of allelic variants of translin-associated factor X (TSNAX)/DISC1 gene cluster using 13 single-nucleotide polymorphisms ( SNPs) in 723 members of 179 Finnish BPD families. Consistent with an earlier finding in Finnish SCZ families, the haplotype T-A of rs751229 and rs3738401 at the 5' end of DISC1 was over-transmitted to males with psychotic disorder (P = 0.008; for an extended haplotype P = 0.0007 with both genders). Haplotypes at the 30 end of DISC1 associated with bipolar spectrum disorder (P = 0.0002 for an under-transmitted haplotype T-T of rs821616 and rs1411771, for an extended haplotype P = 0.0001), as did a two-SNP risk haplotype at the 50 end of TSNAX (P = 0.007). The risk haplotype for psychotic disorder also associated to perseverations (P = 0.035; for rs751229 alone P = 0.0012), and a protective haplotype G-T-G with rs1655285 in addition to auditory attention (P = 0.0059). The 30 end variants associated with several cognitive traits, with the most robust signal for rs821616 and verbal fluency and rs980989 and psychomotor processing speed (P = 0.011 for both). These results support involvement of DISC1 in the genetic aetiology of BPD and suggest that its distinct variants contribute to variation in the dimensional features of psychotic and bipolar spectrum disorders.

Finding of alternative associating haplotypes in the same set of BPD families gives evidence for allelic heterogeneity within DISC1, eventually leading to heterogeneity in the clinical outcome as well.

IFN-alpha regulates Toll-like receptor-mediated IL-27 gene expression in human macrophages

Pirhonen, J., Siren, J., Julkunen, I. and Matikainen, S.

J Leukoc Biol. 2007; 82(5): 1185-92. IF 4.572

IL-27 is a novel member of the IL-12 cytokine family. IL-27 has pro- and anti-inflammatory properties, and it controls the responses of adaptive immunity. It promotes the differentiation of naive Th cells and suppresses the effector functions of Th17 cells. Biologically active IL-27 is a heterodimer composed of EBV-induced gene 3 (EBI3) and p28 proteins.

We report that TLR-dependent expression of IL-27 in human macrophages is mediated by IFN-alpha. Stimulation of macrophages with agonists for TLR3 {polyinosinic:polycytidylic acid [poly(I:C)]}, TLR4 (LPS), or TLR7/8 (R848) results in concurrent expression of EBI3 and p28. The p28 expression is inhibited with neutralizing anti-IFN-alpha antibodies. Unlike poly(I:C), LPS, and R848, TLR2 agonist (S)-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-N-palmitoyl-(R)-Cys-(S)-Ser(S)-Lys4-OH trihydrochloride does not stimulate macrophages to produce IFN-alpha, and therefore, it is not able to turn on the expression of p28. There is an IFN-stimulated response element (ISRE) in the p28 gene promoter. IFN-alpha enhances the expression of IFN regulatory factor 1 (IRF-1) in macrophages and induces binding of IRF-1 to the p28 ISRE site. The data provide a mechanistic basis for the IFN-alpha-mediated activation of IL-27.

The data emphasize a role of IFN-alpha in immune responses, which rely on the recognition of pathogens by TLRs.

Gender differences in the consumption of meat, fruit and vegetables are similar in Finland and the Baltic countries

Prattala, R., Paalanen, L., Grinberga, D., Helasoja, V., Kasmel, A. and Petkeviciene, J.

European Journal of Public Health. 2007; 17(5): 520-525. Article. IF 1.481

Background: Womens diets are healthier than mens. Finnish women eat more fruits and vegetables but less meat than men. Gender differences may be larger in the Baltic countries, which represent Eastern European transition societies than in Finland, a society characterized by the Scandinavian welfare ideology and a high degree of gender equality.

Methods: The data are based on questionnaires to random samples of adults in Finland, Estonia, Latvia and Lithuania. The data provide a way of addressing gender differences at the turn of the century in the economically and culturally different countries. The purpose is to explore whether the consumption of foods classified as masculine or feminine - meat, fruits and vegetables - follow a similar gender pattern in Finland and the Baltic countries.

Results: Men ate meat more often while women ate fruits and vegetables. A high educational level was associated with frequent consumption of fruits and vegetables. Educational differences in the consumption of meat were few and inconsistent. The consumption of fruits and vegetables was more common in urban areas except in Finland. Gender differences were similar in all countries throughout age and educational groups and in rural and urban areas.

Conclusion: The consistent association of gender and food and the similarity of gender patterning in population subgroups point to the stability of masculine versus feminine food habits. The similarity suggests that food habits contribute equally to the gender gap in health in the Baltic countries as they do in Finland.

Attitudes of general hospital emergency room personnel towards attempted suicide patients

Suominen, K., Suokas, J. and Lonnqvist, J.

Nordic Journal of Psychiatry. 2007; 61(5): 387-392. Article. IF 0.789

The aim of this study was to compare the attitudes of emergency room staff towards patients who have attempted suicide between two general hospitals, one with psychiatric consultation available and the other without.

The Understanding Suicidal Patients (USP) Questionnaire was given to all staff in the emergency rooms of Jorvi Hospital ( in the city of Espoo, with routine psychiatric consultation) and Malmi Hospital ( in the city of Helsinki, without routine psychiatric consultation) (n = 115).

There were clear differences in staff attitudes between the hospitals. Female gender, older age and working in Malmi Hospital without routine psychiatric consultation were associated with more positive attitudes towards attempted suicide patients. Surprisingly, only working in Jorvi Hospital was associated with more negative attitudes.

Differences in attitudes towards suicide attempters between personnel working in the different hospitals were found. Further investigation is needed to find the ideal psychiatric consultation arrangement for suicide attempters in good cooperation with emergency room staff.

Liability to anxiety and severe life events as predictors of new-onset sleep disturbances

Vahtera, J., Kivimaeki, M., Hublin, C., Korkeila, K., Suominen, S., Paunio, T. and Koskenvuo, M.

Sleep. 2007; 30(11): 1537-1546. Article. IF 5.126

Study Objectives: This study examined the effects of liability to anxiety and stressful life events on the onset of sleep disturbances.

Design: A 5-year longitudinal observational cohort study.

Participants: A population sample of 16,627 men and women with undisturbed sleep and 2572 with disturbed sleep at baseline.

Interventions: N/A.

Measurements and Results: Liability to anxiety, as indicated by a general feeling of stressfulness (the Reeder stress inventory) and symptoms of sympathetic nervous system (SNS) hyperactivity, was assessed at baseline. The occurrence of post-baseline life events and sleep disturbances was measured at follow-up five years later. Both liability to anxiety and exposure to negative life events were strongly associated with sleep disturbances, Among the men liable to anxiety, the odds of sleep disturbances were 3.11 (95% CI 1.90-5.10) times higher for those who had experienced a severe life event within 6 months than for the others. For the men not liable to anxiety, the corresponding odds ratio was only 1.13 (95% CI 0.403.18). For the men and women liable to anxiety, the odds ratio for sleep disturbance 0-6 months after divorce was 2.05 (95% CI 1.38-3.05), with the corresponding odds ratio being 1.47 (95% CI 0.84-2.58) for the men and women not liable to anxiety. The effects of total or specific life events on sleep after 6 months were not dependent on liability to anxiety.

Conclusion: This study provides prospective evidence that individuals liable to anxiety may be at particularly high risk of post-event sleep disturbances at least during the first months after the event.

Cholesterol efflux from macrophage foam cells is enhanced by active phospholipid transfer protein through generation of two types of acceptor particles

Vikstedt, R., Metso, J., Hakala, J., Olkkonen, V. M., Ehnholm, C. and Jauhiainen, M.

Biochemistry. 2007; 46(42): 11979-86. IF 3.633

Phospholipid transfer protein (PLTP) is expressed by macrophage-derived foam cells in human atherosclerotic lesions, suggesting a regulatory role for PLTP in cellular cholesterol homeostasis. However, the exact role of PLTP in the reverse cholesterol transport pathway is not known. PLTP is present in plasma as two forms, a highly active (HA-PLTP) and a lowly active (LA-PLTP) form.

In this study we clarify the role of the two forms of PLTP in cholesterol efflux from [3H]cholesterol oleate-acetyl-LDL-loaded THP-1 macrophages. Incubation of HDL in the presence of HA-PLTP resulted in the formation of two types of acceptor particles, prebeta-HDL and large fused HDL. HA-PLTP increased prebeta-HDL formation and caused a 42% increase in [3H]cholesterol efflux to HDL, while LA-PLTP neither formed prebeta-HDL nor increased cholesterol efflux. Removal of the formed prebeta-HDL by immunoprecipitation decreased cholesterol efflux by 47%. Neither HA- nor LA-PLTP enhanced cholesterol efflux to lipid-free apoA-I. Importantly, also the large fused HDL particles formed during incubation of HDL with HA-PLTP acted as efficient cholesterol acceptors.

These observations demonstrate that only HA-PLTP increases macrophage cholesterol efflux, via formation of efficient cholesterol acceptors, prebeta-HDL and large fused HDL particles.

Birth size, adult body composition and muscle strength in later life

Yliharsila, H., Kajantie, E., Osmond, C., Forsen, T., Barker, D. J. and Eriksson, J. G.

Int J Obes (Lond). 2007; 31(9): 1392-9. IF 4.055

OBJECTIVE: Low birth weight has been linked to lower lean body mass and abdominal obesity later in life, whereas high birth weight has been suggested to predict later obesity as indicated by high body mass index (BMI). We examined how birth weight was related to adult body size, body composition and grip strength.

DESIGN/SUBJECTS: Cross-sectional study on 928 men and 1075 women born in 1934-1944, with measurements at birth recorded.

MEASUREMENTS: Height, weight, waist and hip circumference and isometric grip strength were measured. Lean and fat body mass were estimated by bioelectrical impedance with an eight-polar tactile electrode system.

RESULTS: A 1 kg increase in birth weight corresponded in men to a 4.1 kg (95% CI: 3.1, 5.1) and in women to a 2.9 kg (2.1, 3.6) increase in adult lean mass. This association remained significant after adjustment for age, adult body size, physical activity, smoking status, social class and maternal size. Grip strength was positively related to birth weight through its association with lean mass. The positive association of birth weight with adult BMI was explained by its association with lean mass. Low birth weight was related to higher body fat percentage only after adjustment for adult BMI. Abdominal obesity was not predicted by low birth weight.

CONCLUSIONS: Low birth weight is associated with lower lean mass in adult life and thus contributes to the risk of relative sarcopenia and the related functional inability at the other end of the lifespan. At a given level of adult BMI, low birth weight predicts higher body fat percentage.