30.6.2008

Huttunen, K., Rintala, H., Hirvonen, M. R., Vepsäläinen, A., Hyvärinen, A., Meklin, T., Toivola, M. and Nevalainen, A.

Environ Res. 2008; 107(3): 291-8. IF 2.962

Many building-related health problems coincide with moisture damage and mold growth within a building. Their elimination is assumed to improve indoor air quality.

The aim of this study was to follow the success of remediation in two individual buildings by analyzing the microbial flora and immunotoxicological activity of filter samples. We compare results from samples collected from indoor air in the moisture-damaged buildings before and after renovation and results from matched reference buildings and outdoor air. The microbial characteristics of the samples were studied by analyzing ergosterol content and determining the composition of fungal flora with quantitative polymerase chain reaction (QPCR). In addition, the concentrations of particles were monitored with optical particle counter (OPC). The immunotoxicological activity of collected particle samples was tested by exposing mouse macrophages (RAW264.7) for 24 h to particle suspension extracted from the filters, and measuring the viability of the exposed cells (MTT-test) and production of inflammatory mediators (nitric oxide, IL-6 and TNF*) in cell culture medium by enzyme-linked immunoassay (ELISA).

The results show that for Location 1 the renovation decreased the immunotoxicological activity of the particles collected from damaged building, whereas no difference was detected in the corresponding samples collected from the reference building. Interestingly, only slight differences were seen in the concentration of fungi. In the Location 2, a decrease was seen in the concentration of fungi after the renovation, whereas no effect on the immunotoxicological responses was detected. In this case, the immunotoxicological responses to the indoor air samples were almost identical to those caused by the samples from outdoor air.

This indicates that the effects of remediation on the indoor air quality may not necessarily be readily measurable either with microbial or toxicological parameters. This may be associated with different spectrum of harmful agents in different mold and moisture-damaged buildings.

Deficiency of the INCL protein Ppt1 results in changes in ectopic F1-ATP synthase and altered cholesterol metabolism

Lyly, A., Marjavaara, S. K., Kyttälä, A., Uusi-Rauva, K., Luiro, K., Kopra, O., Martinez, L. O., Tanhuanpaa, K., Kalkkinen, N., Suomalainen, A., Jauhiainen, M. and Jalanko, A.

Hum Mol Genet. 2008; 17(10): 1406-17. IF 7.806

Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative disease caused by deficiency of palmitoyl protein thioesterase 1 (PPT1). INCL results in dramatic loss of thalamocortical neurons, but the disease mechanism has remained elusive. In the present work we describe the first interaction partner of PPT1, the F(1)-complex of the mitochondrial ATP synthase, by co-purification and in vitro-binding assays. In addition to mitochondria, subunits of F(1)-complex have been reported to localize in the plasma membrane, and to be capable of acting as receptors for various ligands such as apolipoprotein A-1. We verified here the plasma membrane localization of F(1)-subunits on mouse primary neurons and fibroblasts by cell surface biotinylation and TIRF-microscopy. To gain further insight into the Ppt1-mediated properties of the F(1)-complex, we utilized the Ppt1-deficient Ppt1(Delta ex4) mice. While no changes in the mitochondrial function could be detected in the brain of the Ppt1(Delta ex4) mice, the levels of F(1)-subunits alpha and beta on the plasma membrane were specifically increased in the Ppt1(Delta ex4) neurons. Significant changes were also detected in the apolipoprotein A-I uptake by the Ppt1(Delta ex4) neurons and the serum lipid composition in the Ppt1(Delta ex4) mice. These data indicate neuron-specific changes for F(1)-complex in the Ppt1-deficient cells and give clues for a possible link between lipid metabolism and neurodegeneration in INCL.

Assessment of the genotoxicity of the rat carcinogen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in rat liver epithelial cells in vitro

Mäki-Paakkanen, J. and Hakulinen, P.

Toxicol In Vitro. 2008; 22(2): 535-40. IF 2.193

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a disinfection by-product in chlorinated drinking water, is a multisite carcinogen in rats. One main target organ is the liver. The mechanism of the tumorigenicity was evaluated by testing the genotoxicity of MX in rat liver epithelial cell line cells. In the studies, the single cell gel/Comet assay and the hypoxanthine phosphoribosyl transferase locus assay to 6-thioguanine resistance were used. MX induced a dose-related genotoxic response in the comet assay. The lowest effective concentration was 120 microM when the exposure was in medium plus supplements and 3.75 microM when the exposure was in phosphate-buffered salt solution. MX also increased the frequency of TG(r) mutants, when the cells were treated in phosphate-buffered salt solution, at a concentration range of 2.3-9.2 microM. The present results show for the first time that MX causes DNA damage and gene mutations in rat liver epithelial cells, the target cells of MX's tumorigenicity in rats. We have earlier shown that MX also inhibits gap junctional intercellular communication in the same cells.

The genotoxic effects were induced starting at about 60 times higher concentration, in identical exposure conditions, compared with the lowest concentration of MX causing the tumor promoter effect.

Psychological distress and attitudes of emergency personnel towards suicide attempters

Suokas, J., Suominen, K. and Lönnqvist, J.

Nord J Psychiatry. 2008; 62(2): 144-6. IF 0.752

Emergency personnel attitudes towards suicide attempters are important because they have a key role in the management of these patients. We examined the association between staff members' psychological distress and the attitudes towards suicide attempters. We also compared the attitudes towards suicide attempters among emergency personnel between a general and a psychiatric hospital. The Understanding Suicidal Patients (USP) Questionnaire and the 12-item version of General Health Questionnaire were given to all staff in the emergency rooms of a general hospital and a psychiatric hospital (n=151). There was a general tendency among emergency room staff to view attempted suicide patients positively and sympathetically. However, there were clear differences in staff attitudes between the two hospitals: those working in the general hospital expressed more negative attitudes than those in the psychiatric hospital. No evidence emerged of association between staff members' psychological distress and negative attitudes towards suicide attempters.

There was no association between psychological distress and negative attitudes towards suicide attempters.

The genetic variation of the tenomodulin gene (TNMD) is associated with serum levels of systemic immune mediators-the Finnish Diabetes Prevention Study

Tolppanen, A. M., Pulkkinen, L., Herder, C., Koenig, W., Kolehmainen, M., Lindström, J., Tuomilehto, J. and Uusitupa, M.

Genet Med. 2008. IF 3.318

PURPOSE:: We have reported that the genetic variation of the tenomodulin gene (TNMD) is associated with the risk of type 2 diabetes (T2DM), central obesity, and impaired glucose metabolism and the TNMD mRNA levels correlate with serum and mRNA levels of inflammatory markers. Our objective was to investigate the genetic associations of the single nucleotide polymorphisms of the TNMD gene with the serum levels of systemic immune mediators.

METHODS:: Seven single nucleotide polymorphisms were genotyped from 507 participants of the Finnish Diabetes Prevention Study. All subjects had body mass index >25 and impaired glucose tolerance.

RESULTS:: The sequence variation of tenomodulin was consistently associated with the serum concentrations of acute phase reactants, macrophage migration inhibitory factor, and CCR5 receptor ligands. The genotype effects were modified by status of glucose metabolism and central obesity. Markers associated with increased risk of T2DM in our previous study were associated with serum concentrations of acute phase proteins in men so that the subjects possessing the genotypes associated with increased risk of T2DM had higher serum concentrations of acute phase reactants.

CONCLUSIONS:: These results indicate that the genetic variation of TNMD is associated with low-grade inflammation. The putative link between TNMD and T2DM could be mediated through the effects on systemic immune mediators.

Mortality in a cohort with high fish consumption

Turunen, A. W., Verkasalo, P. K., Kiviranta, H., Pukkala, E., Jula, A., Mannisto, S., Rasanen, R., Marniemi, J. and Vartiainen, T.

Int J Epidemiol. 2008. IF 5.151

BACKGROUND: Our aim was to assess the mortality of fishermen and fishermen's wives in Finland, presuming that the mortality reflects their high consumption of contaminated fish.

METHODS: All Finnish fishermen, registered since 1980, were identified from the Professional Fishermen Register (N = 6410), and the fishermen's wives from the national population register (N = 4260). The cohorts were individually linked with cause-of-death data until 2005 at Statistics Finland. The follow-up started in the year after the first registration as a fisherman and at marriage (if later) for the wives. The standardized mortality ratios (SMRs) were calculated based on the national mortality rates. In addition, blood samples and food frequency questionnaire data were collected from a volunteer sample.

RESULTS: The average fish consumption and serum concentrations of fish-derived fatty acids and environmental contaminants were higher among the fishermen and their wives than among the general population from the same region. The fishermen and their wives had lower mortality from all causes (SMR 0.78, 95% confidence interval (CI) 0.73-0.82, and 0.84, 0.76-0.93, respectively), and ischaemic heart diseases (0.73, 0.65-0.81, and 0.65, 0.50-0.83) than the general population. Mortality from cerebrovascular diseases and malignant neoplasms was decreased among the fishermen (0.67, 0.52-0.85, and 0.90, 0.80-1.01), but not among the wives. In addition, the fishermen's mortality from water transport accidents was extremely high (8.31, 5.65-11.79).

CONCLUSIONS: The fishermen and their wives had lower mortality from many natural causes. The high intakes of environmental contaminants in fish were not seen as excess mortality.