| 1. |
- Pöllänen, E., et al.
(författare)
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Differential influence of peripheral and systemic sex steroids on skeletal muscle quality in pre- and postmenopausal women
- 2011
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Ingår i: Aging Cell. - : Wiley. - 1474-9718. ; 10:4, s. 650-660
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Tidskriftsartikel (refereegranskat)abstract
- Aging is associated with gradual decline of skeletal muscle strength and mass often leading to diminished muscle quality. This phenomenon is known as sarcopenia and affects about 30% of the over 60-year-old population. Androgens act as anabolic agents regulating muscle mass and improving muscle performance. The role of female sex steroids as well as the ability of skeletal muscle tissue to locally produce sex steroids has been less extensively studied. We show that despite the extensive systemic deficit of sex steroid hormones in postmenopausal compared to premenopausal women, the hormone content of skeletal muscle does not follow the same trend. In contrast to the systemic levels, muscle tissue of post- and premenopausal women had similar concentrations of dehydroepiandrosterone and androstenedione, while the concentrations of estradiol and testosterone were significantly higher in muscle of the postmenopausal women. The presence of steroidogenetic enzymes in muscle tissue indicates that the elevated postmenopausal steroid levels in skeletal muscle are because of local steroidogenesis. The circulating sex steroids were associated with better muscle quality while the muscle concentrations reflected the amount of infiltrated fat within muscle tissue. We conclude that systemically delivered and peripherally produced sex steroids have distinct roles in the regulation of neuromuscular characteristics during aging.
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| 2. |
- Bradley, E. L., et al.
(författare)
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The BIOSAFEPAPER project for in vitro toxicity assessments : Preparation, detailed chemical characterisation and testing of extracts from paper and board samples
- 2008
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 46:7, s. 2498-2509
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Tidskriftsartikel (refereegranskat)abstract
- Nineteen food contact papers and boards and one non-food contact board were extracted following test protocols developed within European Union funded project BIOSAFEPAPER. The extraction media were either hot or cold water, 95% ethanol or Tenax, according to the end use of the sample. The extractable dry matter content of the samples varied from 1200 to 11,800 mg/kg (0.8-35.5 mg/dm2). According to GC-MS the main substances extracted into water were pulp-derived natural products such as fatty acids, resin acids, natural wood sterols and alkanols. Substances extracted into ethanol particularly, were diisopropylnaphthalenes, alkanes and phthalic acid esters. The non-food contact board showed the greatest number and highest concentrations of GC-MS detectable compounds. The extracts were subjected to a battery of in vitro toxicity tests measuring both acute and sublethal cytotoxicity and genotoxic effects. None of the water or Tenax extracts was positive in cytotoxicity or genotoxicity assays. The ethanol extract of the non-food contact board gave a positive response in the genotoxicity assays, and all four ethanol extracts gave positive response(s) in the cytotoxicity assays to some extent. These responses could not be pinpointed to any specific compound, although there appeared a correlation between the total amount of extractables and toxicity.
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| 3. |
- Flinkman, Ella, et al.
(författare)
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Association Between Blood Eosinophils and Neutrophils With Clinical Features in Adult-Onset Asthma.
- 2023
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Ingår i: The journal of allergy and clinical immunology. In practice. - : Elsevier BV. - 2213-2198 .- 2213-2201. ; 11:3, s. 811-821
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is a disease that can be separated into different phenotypes and endotypes based on the clinical characteristics and the molecular mechanisms of the condition, respectively.To assess the association between blood eosinophil and neutrophil counts with clinical and molecular features in patients with adult-onset asthma.Blood eosinophil and neutrophil counts were measured from 203 patients who took part in the Seinäjoki Adult Asthma Study and attended the 12-year follow-up visit. The patients were then divided into four groups (paucigranulocytic [n= 108], neutrophilic [n= 60], eosinophilic [n= 21], and mixed granulocytic [n= 14]), according to eosinophil and neutrophil levels. The cutoff values used to define the groups were 0.30× 109 · L-1 for blood eosinophils and 4.4× 109 · L-1 for blood neutrophils.The neutrophilic group had highest body mass index. It was dispensed the highest doses of inhaled corticosteroids during the 12-year follow-up and made the most unplanned respiratory visits. The neutrophilic, eosinophilic, and mixed granulocytic groups had more severe asthma compared with the paucigranulocytic group. The neutrophilic and eosinophilic groups were associated with higher dispensed antibiotics. The eosinophilic group had more nasal polyps, more suspected sinusitis, a greater decline in lung function, and increased levels of periostin, FeNO, and IgE. The neutrophilic group had increased high-sensitivity C-reactive protein, matrix metalloproteinase-9, IL-6, leptin, and soluble urokinase plasminogen activator receptor levels. The mixed granulocytic group showed increased resistin levels together with the neutrophilic group.In addition to blood eosinophils, the blood neutrophil count reflects underlying inflammatory patterns and indicates important differences in asthma clinical features and outcomes.
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| 4. |
- Honkalampi-Hämäläinen, U., et al.
(författare)
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Safety evaluation of food contact paper and board using chemical tests and in vitro bioassays : Role of known and unknown substances
- 2010
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Ingår i: Food Additives and Contaminants. - : Informa UK Limited. - 0265-203X .- 1464-5122. ; 27:3, s. 406-115
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Tidskriftsartikel (refereegranskat)abstract
- In vitro toxicological tests have been proposed as an approach to complement the chemical safety assessment of food contact materials, particularly those with a complex or unknown chemical composition such as paper and board. Among the concerns raised regarding the applicability of in vitro tests are the effects of interference of the extractables on the outcome of the cytotoxicity and genotoxicity tests applied and the role of known compounds present in chemically complex materials, such as paper and board, either as constituents or contaminants. To answer these questions, a series of experiments were performed to assess the role of natural substances (wood extracts, resin acids), some additives (diisopropylnaphthalene, phthalates, acrylamide, fluorescent whitening agents) and contaminants (2,4-diaminotoluene, benzo[a]pyrene) in the toxicological profile of paper and board. These substances were individually tested or used to spike actual paper and board extracts. The toxic concentrations of diisopropylnaphthalenes and phthalates were compared with those actually detected in paper and board extracts showing conspicuous toxicity. According to the results of the spiking experiments, the extracts did not affect the toxicity of tested chemicals nor was there any significant metabolic interference in the cases where two compounds were used in tests involving xenobiotic metabolism by the target cells. While the identified substances apparently have a role in the cytotoxicity of some of the project samples, their presence does not explain the total toxicological profile of the extracts. In conclusion, in vitro toxicological testing can have a role in the safety assessment of chemically complex materials in detecting potentially harmful activities not predictable by chemical analysis alone.
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| 5. |
- Hämäläinen, Jari, et al.
(författare)
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Multiobjective Decision Making for Papermaking
- 2004
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Ingår i: CD-Proceedings of MCDM2004, the 17th International Conference on Multiple Criteria Decision Making.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Knuuttila, M., et al.
(författare)
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Applying mass spectrometric methods to study androgen biosynthesis and metabolism in prostate cancer
- 2019
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Ingår i: Journal of molecular endocrinology. - 1479-6813. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- Recent development of gas chromatography and liquid chromatography-tandem mass spectrometry (GC-MS/MS, LC-MS/MS) has provided novel tools to define sex steroid concentrations. These new methods overcome several of the problems associated with immunoassays for sex steroids. With the novel MS-based applications we are now able to measure small concentrations of the steroid hormones reliably and with high accuracy in both body fluids and tissue homogenates. The sensitivity of the tandem mass spectrometry assays allows us also for the first time to reliably measure picomolar or even femtomolar concentrations of estrogens and androgens. Furthermore, due to a high sensitivity and specificity of MS technology, we are also able to measure low concentrations of steroid hormones of interest in the presence of pharmacological concentration of other steroids and structurally closely related compounds. Both of these features are essential for multiple preclinical models for prostate cancer. The MS assays are also valuable for the simultaneous measurement of multiple steroids and their metabolites in small sample volumes in serum and tissue biopsies of prostate cancer patients before and after drug interventions. As a result, novel information about steroid hormone synthesis and metabolic pathways in prostate cancer has been obtained. In our recent studies, we have extensively applied a GC-MS/MS method to study androgen biosynthesis and metabolism in VCaP prostate cancer xenografts in mice. In the present review, we shortly summarize some of the benefits of the GC-MS/MS and novel LC-MS/MS assays, and provide examples of their use in defining novel mechanisms of androgen action in prostate cancer.
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| 7. |
- Mannerkoski, Minna K., et al.
(författare)
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Subjects with intellectual disability and familial need for full-time special education show regional brain alterations : a voxel-based morphometry study
- 2009
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Ingår i: Pediatric Research. - 0031-3998 .- 1530-0447. ; 66:3, s. 306-311
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Tidskriftsartikel (refereegranskat)abstract
- Subjects attending full-time special education (SE) often have multifactorial background for their cognitive impairment, and brain MRI may show nonspecific changes. As voxel-based morphometry reveals regional volume differences, we applied this method to 119 subjects with cognitive impairments and familial need for full-time SE--graded into three levels from specific disorders of cognitive processes (level 1) to intellectual disability (IQ <70; level 3)--and to 43 age-matched controls attending mainstream education (level 0). Subjects in SE groups had smaller global brain white matter (WM), cerebrospinal fluid, and total brain volume than controls. Compared with controls, subjects with intellectual disabilities in SE level 3 showed greater regional gray matter volumes bilaterally in the ventral and dorsal anterior cingulate cortex and smaller regional gray matter volumes in the left thalamus and cerebellar hemisphere. Further, they had greater WM volume in the left frontoparietal region and smaller WM volumes in the posterior limbs of the internal capsules. Subjects in SE level 1 and 2 groups showed the same tendency, but the results were nonsignificant. In conclusion, compared with controls, subjects with intellectual disabilities showed in voxel-based morphometry analysis several regional brain alterations.
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| 8. |
- Rämö, JT, et al.
(författare)
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Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure
- 2023
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 157-
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Tidskriftsartikel (refereegranskat)abstract
- Otosclerosis is one of the most common causes of conductive hearing loss, affecting 0.3% of the population. It typically presents in adulthood and half of the patients have a positive family history. The pathophysiology of otosclerosis is poorly understood. A previous genome-wide association study (GWAS) identified a single association locus in an intronic region of RELN. Here, we report a meta-analysis of GWAS studies of otosclerosis in three population-based biobanks comprising 3504 cases and 861,198 controls. We identify 23 novel risk loci (p < 5 × 10−8) and report an association in RELN and three previously reported candidate gene or linkage regions (TGFB1, MEPE, and OTSC7). We demonstrate developmental stage-dependent immunostaining patterns of MEPE and RUNX2 in mouse otic capsules. In most association loci, the nearest protein-coding genes are implicated in bone remodelling, mineralization or severe skeletal disorders. We highlight multiple genes involved in transforming growth factor beta signalling for follow-up studies.
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