Use of spot measurements for assessing residential ELF magnetic field exposure: a validity study

The purpose of this study was to evaluate residential short term "spot" measurements as surrogates for long term personal magnetic field (MF) exposure. In an epidemiological study on birth weight and pregnancy delay, MF exposure was assessed by taking five spot measurements in each room. For a subsample of 30 subjects 24 h personal MF measurements were made, and the following exposure metrics were calculated: 24 h arithmetic mean, 24 h median, percentage of time above 0.15 microT, and percentage of time above 0.29 microT. The 24 h exposure metrics were used as gold standards, when evaluating the validity of various summary measures calculated from spot measurements for assessing personal exposure. Based on Spearman correlation coefficient (r), specificity and sensitivity, the average of the spot measurements of a residence resulted in least exposure measurement error (misclassification). Also the above bed spot value correlated better with the 24 h metrics than any room average. Spot measurements performed about equally well in predicting different types of exposure metrics.     

Melatonin and the wintering strategy of the tundra vole,Microtus oeconomus

Short photoperiod induces physiological changes connected to the wintering of the tundra vole, Microtus oeconomus. The aim of the present study was to investigate the effects of continuous melatonin treatment on selected hormones and enzyme activities associated with energy metabolism in the species. Liver, kidney, and muscle glycogen concentrations and glycogen phosphorylase activities, as well as liver and kidney glucose-6-phosphatase and lipase esterase activities were determined. Plasma leptin, ghrelin, thyroxine, testosterone, cortisol, and melatonin concentrations were also measured. Exogenous melatonin stimulated gluconeogenesis, increased glycogen stores, and reduced fat mobilization in kidneys. Melatonin treatment also increased the food intake of the voles. This may have been mediated via elevated ghrelin levels of the melatonin-treated animals, as ghrelin is known to increase appetite of rodents. Winter metabolism of the species does not seem to require accumulation of fat or extra stores of liver or muscle glycogen. On the contrary, successful wintering of the tundra vole presumably depends on continuous food availability.     

p53-independent apoptosis in UV-irradiated mouse skin: possible inhibition by 50 Hz magnetic fields

Our recent results suggest that 50 Hz magnetic fields (MF) enhance ultraviolet (UV)-induced tumorigenesis in mouse skin. The aim of the present experiment was to study suppression of apoptosis as a possible mechanism for MF effects on skin tumorigenesis. Another aim was to test the importance of a UV and MF exposure schedule, particularly the role of MF exposure prior to UV irradiation. Female mice were exposed to a UV dose of 2 human MED and to 100 microT MF of 50 Hz, using the following exposure schedules: group 1 sham MF 24 h, UV 1 h, sham MF 24 h; group 2 sham MF 24 h, UV 1 h, MF 24 h; group 3 MF 24 h, UV 1 h, MF 24 h. Lamps emitting simulated solar radiation (SSR) were used for UV irradiation. Skin samples were analysed for apoptosis, expression of the p53 gene, activity of the enzyme ornithine decarboxylase (ODC) and polyamine concentrations. A significantly (p = 0.017) lower number of apoptotic cells was measured in group 2 compared to group 1. A similar but not statistically significant (p = 0.064) decrease was also detected in group 3. No p53 expression was detected in any sample. The levels of ODC and putrescine did not differ significantly between the UV-only and UV and MF-exposed groups. Spermidine and spermine levels were significantly (p = 0.014 and 0.014, respectively) lower in group 3 than in group 1, but no decrease was observed in group 2. Our findings suggest that SSR induces p53-independent apoptosis in mouse skin and that the apoptotic response may be inhibited by exposure to MF. The exposure schedule did not alter the MF effect. The results do not support a causal role for polyamines in MF effects on apoptosis.     

Seasonal weight regulation of the raccoon dog (Nyctereutes procyonoides): interactions between melatonin,leptin, ghrelin,and growth hormone

The raccoon dog (Nyctereutes procyonoides, Canidae, Carnivora) is a middle-sized omnivore with excessive autumnal fattening and winter sleep. We studied seasonal weight regulation of the species by following the plasma leptin, ghrelin, and growth hormone (GH) levels of farm-bred raccoon dogs (n = 32) for 6 months. In August, half of the raccoon dogs received continuous-release melatonin implants, and in November, half of the animals of both the sham-operated and melatonin-treated groups were fasted for 2 months. In the autumn, the plasma leptin and GH levels were low, but the ghrelin levels were relatively high and correlated positively with energy intake. This represents the period of energy storage. Leptin and GH levels peaked simultaneously in late October, and melatonin advanced the peaks by 1 week. Thereafter, the levels rapidly declined, representing the transition period from autumnal anabolism to wintertime catabolism. In the winter, the leptin and GH levels rose to high levels, but the ghrelin-leptin ratio was very low. This is the period of winter sleep, with fat accumulated in the autumn as the principal metabolic fuel. In the winter, leptin, ghrelin, and GH may work in synergy to increase lipolysis. GH may also induce winter sleep to the raccoon dog. Fasting had no effect on the hormone levels, unlike in humans and rodents. Instead of the amount of fat in the body, the main regulators of the levels of these hormones in the raccoon dog are presumably seasonal rhythms entrained by melatonin.     

Hereditary minisatellite mutations among the offspring of Estonian Chernobyl cleanup workers

A single accidental event such as the fallout released from the Chernobyl reactor in 1986 can expose millions of people to non-natural environmental radiation. Ionizing radiation increases the frequency of germline mutations in experimental studies, but the genetic effects of radiation in humans remain largely undefined. To evaluate the hereditary effects of low radiation doses, we compared the minisatellite mutation rates of 155 children born to Estonian Chernobyl cleanup workers after the accident with those of their siblings born prior to it. All together, 94 de novo paternal minisatellite mutations were found at eight tested loci (52 and 42 mutants among children born after and before the accident, respectively). The minisatellite mutation rate was nonsignificantly increased among children born after the accident (0.042 compared to 0.036, OR 1.33, 95% CI 0.80-2.20). Furthermore, there was some indication of an increased mutation rate among offspring born after the accident to workers who had received doses of 20 cSv or above compared with their siblings born before the accident (OR 3.0, 95% CI 0.97-9.30). The mutation rate was not associated with the father's age (OR 1.04, 95% CI 0.94-1.15) or the sex of the child (OR 0.95, 95% CI 0.50-1.79). Our results are consistent with both no effect of radiation on minisatellite mutations and a slight increase at dose levels exceeding 20 cSv.     

Seasonal reproductive endocrine profile of the raccoon dog (Nyctereutes procyonoides)-effects of melatonin and food deprivation

The raccoon dog (Nyctereutes procyonoides, Canidae, Carnivora) is a middle-sized omnivore with excessive autumnal fattening and winter sleep. We studied adaptations of the species to boreal climate and photoperiod by following the plasma reproductive and thyroid hormone concentrations of farm-bred raccoon dogs (n=32) for 12 months. On August 16, 2000, and February 8, 2001, half of the raccoon dogs received continuous-release melatonin implants (the MEL group). The other half was sham-operated (the SHAM group). Between November 27, 2000, and January 25, 2001, half of the animals of both groups were fasted. The plasma testosterone concentrations of the MEL males peaked in February, a month earlier than in the SHAM males. Autumnal melatonin treatment also advanced the gestation period reflected by the plasma progesterone concentrations by seven weeks. Food deprivation in winter seems to accentuate the sex steroid response during the mating as the fasted males had higher testosterone concentrations than the fed males in February and March.     

Mechanisms of pattern formation in development and evolution

We present a classification of developmental mechanisms that have been shown experimentally to generate pattern and form in metazoan organisms. We propose that all such mechanisms can be organized into three basic categories and that two of these may act as composite mechanisms in two different ways. The simple categories are cell autonomous mechanisms in which cells enter into specific arrangements ('patterns') without interacting, inductive mechanisms in which cell communication leads to changes in pattern by reciprocal or hierarchical alteration of cell phenotypes ('states') and morphogenetic mechanisms in which pattern changes by means of cell interactions that do not change cell states. The latter two types of mechanism can be combined either morphostatically, in which case inductive mechanisms act first, followed by the morphogenetic mechanism, or morphodynamically, in which case both types of mechanisms interact continuously to modify each other's dynamics. We propose that this previously unexplored distinction in the operation of composite developmental mechanisms provides insight into the dynamics of many developmental processes. In particular, morphostatic and morphodynamic mechanisms respond to small changes in their genetic and microenvironmental components in dramatically different ways. We suggest that these differences in 'variational properties' lead to morphostatic and morphodynamic mechanisms being represented to different extents in early and late stages of development and to their contributing in distinct ways to morphological transitions in evolution.     

Nitric oxide donors retard wound healing in cultured rabbit gastric epithelial cell monolayers

Effects of nitric oxide (NO) on gastric wound healing were investigated in primary rabbit gastric epithelial cell cultures. We analyzed the speed of cell migration, proliferation, and apoptosis after creating a round wound on the cell cultures. The monolayers were incubated with or without the NO donor sodium nitroprusside, oxatriazolimine 1,2,3,4-oxatriazolium, 5amino-3-(3,4-dichlorophenylchloride), or the peroxynitrite generator 3-morpholinosydnomine-N-ethylcarbamide. The possible role of cGMP as a second messenger of NO was investigated with 8-bromo-cGMP. The role of O2(-*) was evaluated using diethyldithiocarbamate and pyrogallol. The effects of superoxide dismutase and allopurinol were also investigated. NO inhibited the speed of cell migration and proliferation and induced cell apoptosis in a dose- and time-dependent manner. The effects were augmented with O2(-*) generators and ameliorated by O2-(8) scavengers, whereas cGMP had no significant effect on wound healing. NO donors retard gastric wound healing by inhibiting migration and proliferation and inducing cell apoptosis. These effects do not seem to be mediated via cGMP, but O2(-*). or peroxynitrites may be involved.     

Rho‐kinase inhibitor Y‐27632 increases cellular proliferation and migration in human foreskin fibroblast cells

The idea of direct differentiation of somatic cells into other differentiated cell types has attracted a great interest recently. Rho‐kinase inhibitor Y‐27632 (ROCKi) is a potential drug molecule, which has been reported to support the gene expressions typical for the chondrocytes, thus restricting their phenotypic conversion to fibroblastic cells upon the cellular expansion. In this study, we have investigated the short‐term biological responses of ROCKi to human primary foreskin fibroblasts. The fibroblast cells were exposed to 1 and 10 μM ROCKi treatments. A proteomics analysis revealed expression changes of 56 proteins, and a further protein pathway analysis suggested their association with the cell morphology, the organization, and the increased cellular movement and the proliferation. These functional responses were confirmed by a Cell‐IQ time‐lapse imaging analysis. Rho‐kinase inhibitor treatment increased the cellular proliferation up to twofold during the first 12 h, and a wound model based migration assay showed 50% faster filling of the mechanically generated wound area. Additionally, significantly less vinculin‐associated focal adhesions were present in the ROCKi‐treated cells. Despite the marked changes in the cell behavior, ROCKi was not able to induce the expression of the chondrocyte‐specific genes, such as procollagen α₁(II) and aggrecan.     

Increased Visceral Adipose Tissue as a Potential Risk Factor in Patients with Embolic Stroke of Undetermined Source (ESUS)

Purpose

The etiology of an ischemic stroke remains undetermined in 20–35% of cases and many patients do not have any of the conventional risk factors. Increased visceral adipose tissue (VAT) is a suggested new risk factor for both carotid artery atherosclerosis (CAA) and atrial fibrillation (AF), but its role in the remaining stroke population is unknown. We assessed the amount of VAT in patients with embolic stroke of undetermined source (ESUS) after excluding major-risk cardioembolic sources, occlusive atherosclerosis, and lacunar stroke.

Methods

Altogether 58 patients (mean age 57.7±10.2 years, 44 men) with ischemic stroke of unknown etiology but without CAA, known AF or small vessel disease underwent computed tomography angiography and assessment of VAT. For comparison VAT values from three different reference populations were used. Conventional risk factors (smoking, hypertension, diabetes, increased total and LDL-cholesterol, decreased HDL-cholesterol) were also registered.

Results

Mean VAT area was significantly higher in stroke patients (205±103 cm² for men and 168±99 cm² for women) compared to all reference populations (P<0.01). 50% of male and 57% of female patients had an increased VAT area. In male patients, VAT was significantly higher despite similar body mass index (BMI). Increased VAT was more common than any of the conventional risk factors.

Conclusion

Increased VAT was found in over half of our patients with ESUS suggesting it may have a role in the pathogenesis of thromboembolism in this selected group of patients.