Health impacts of particulate matter in five major Estonian towns: main sources of exposure and local differences

Particulate matter (PM) is the major air pollution problem with health impacts in Estonia. The prevailing sources of particles are traffic and local heating. In this study, we quantified the health effects of PM in neighbourhoods of five main cities with a health impact assessment (HIA) approach that uses information on exposure, baseline mortality/morbidity and exposure–response relationships from previous epidemiological studies. The exposure was defined as modelled PM_2.5 annual levels and daily averages of PM₁₀ (monitoring data in Tallinn and Kohtla-Järve and modelled levels in Tartu, Narva and Pärnu). The modelled results were validated with data from monitoring stations and additional measuring programmes. The annual average concentration of PM_2.5 in the neighbourhoods studied varied from 7.6 to 23.6 μg m^?3. The analysis indicated that the exposure above natural background corresponds to 462 [95% confidence interval (CI) 120–815] premature deaths, resulting in 6,034 (95% CI 1,583–10,309) years of life lost per year. The average decrease in life-expectancy at birth per resident of Tallinn was estimated to be 0.63 (95% CI 0.16–1.08) years. In the polluted city centres, this average decrease may reach >1 year and in Pärnu, it may reach 0.95 year. However, in the least polluted neighbourhood, the decrease of life expectancy was only 0.17 years. In addition, 231 (95% CI 145–306) respiratory and 338 (95% CI 205–454) cardiovascular hospitalisations per year could be expected. The majority of the external costs are related to the long-term effects on mortality and amount to ?70 (95% CI 190–350) million annually. In comparison, the costs of hospitalisations contribute just ?.1 (95% CI 0.6–1.6) million. The main differences in health impacts were mostly driven by differences in the pollution sources, the magnitude of such sources and distribution patterns in the atmosphere. The smallest health effects, with the exception of the green residential areas, were observed in the industrial cities Kohtla-Järve and Narva (due to the small share contributed by local residential heating and relatively little car traffic). However, it is questionable whether the mass of fine particles is the best indicator of air pollution risk in such areas.     

Changes in fast-twitch muscle oxidative capacity and myosin isoforms modulation during endurance training

AIM: The purpose of this study was to investigate the effect of endurance training on changes in myosin heavy (MyHC) and light (MyLC) chains expression, their turnover rate in fast-twitch (FT) skeletal muscles, and relations with changes in contractile proteins degradation rate and muscle oxidative capacity. METHODS: Wistar rats were run at 35 m/min for 6 weeks (from 10 min to 60 min per day, from 1.8 kJ to 7 kJ per training session and power of work was 1.5 W). The FT muscles were used for measurement of myosin isoforms and oxidative capacity. Double isotope method ((3)H/(14)C) was used. RESULTS: During endurance training in plantaris and extensor digitorum longus (EDL) muscles the relative content of MyHC IIb isoform decreased while there was an increase in the relative content of MyHC IIa and IId isoforms. MyLC 3(fast) isoform increased in FT muscles. Degradation rate of MyHC isoforms increased during endurance training simultaneously with the increase of contractile proteins degradation and increase of cytochrome aa3 content in FT muscles. Endurance training increased MyHC I, IIa and IId isoform turnover rate, whereas MyHC IIb and MyLC isoforms turnover rate did not change significantly. CONCLUSIONS: Adaptation of FT skeletal muscles to endurance training shows coordination between increase in oxidative capacity and faster turnover rate of MyHC isoforms in contractile apparatus. FT muscles show high potential of recruitment in endurance training.     

The effects of glutamate receptor antagonists on cerebellar granule cell survival and development

N-Methyl-d-aspartate (NMDA) receptor stimulation promotes neuronal survival and differentiation under both in vitro and in vivo conditions. We studied the effects of various NMDA receptor antagonists acting at different NMDA receptor binding sites and non-NMDA receptor antagonists on the development and survival of cerebellar granule cell (CGC) culture. Only three of the drugs tested induced neurotoxicity-MK-801 (non-competitive NMDA channel blocking antagonist), ifenprodil (an antagonist of the NR2B site and polyamine site of the NMDA receptor) and L-701.324 (full antagonist at glycine site), while CGP-37849 (a competitive NMDA antagonist), (+)-HA-966 (a partial agonist of the glycine site of the NMDA receptor), and NBQX (a competitively acting AMPA receptor antagonist) were not toxic at any concentration (1-100 microM) used. Among these drugs, only MK-801 was toxic for the immature CGC on second day in vitro (2DIV), and toxicity was diminished parallel to the neuronal maturation. In more mature neurons (7DIV), MK-801 demonstrated some neuroprotection, which diminished spontaneously occurring neuronal death in culture. Neither NMDA nor glutamate were able to prevent the neurotoxic effect of MK-801 at 2DIV. MK-801, ifenprodil and L-701.324 induced DNA fragmentation on 2DIV in CGC culture measured by the TUNEL method. The BOC-D-FMK, the universal caspase inhibitor, completely reversed MK-801-induced DNA fragmentation, suggesting an apoptotic pathway of MK-801-induced cell death. Neurite outgrowth as a characteristic feature of the development of CGC was diminished after treatment with MK-801, ifenprodil and L-701.324. In conclusion, the results of the present study demonstrate that only nonselective channel blocker MK-801 decreases cell viability, induces apoptosis and inhibits neurite outgrowth of CGC in a development-dependent manner.     

Do nuclear condensation or fragmentation and DNA fragmentation reflect the mode of neuronal death?

It is generally believed that nuclear condensation and fragmentation as well as DNA fragmentation reflect the events related to the neuronal apoptosis. Our report demonstrates that severe oxygen-glucose deprivation (OGD) induced condensation and fragmentation of nuclear chromatin of neurones in primary cultures of cerebellar granule cells without intemucleosomal DNA fragmentation. DNA fragmentation detected by TUNEL assay was seen only after mild OGD or after addition of colchicine but not after severe OGD. Thus, at least in primary cerebellar granule cell cultures, the chromatin condensation and fragmentation cannot be considered as a hallmark of apoptosis but rather reflect the neuronal death despite of its form.     

Clinical and laboratory-reconfirmed myasthenia gravis: a population-based study

The aim of this study was to compare the clinically based prevalence of myasthenia gravis (MG) with the prevalence of laboratory-confirmed cases. All patients with a diagnosis of MG living in Estonia as on 1 January 1997 were asked to participate in re-examination. The criteria for laboratory-supported MG were weakness and rapid fatigue and a positive outcome of at least one of three laboratory tests: (i) blinded acetylcholinesterase inhibitor test; (ii) determination of antibodies to acetylcholine receptor and (iii) neurophysiological examination using repetitive nerve stimulation and single-fibre EMG. Eighty-nine patients were re-examined and 70 patients (79%) fulfilled the criteria of laboratory-supported MG. The corrected prevalence ratio was 78 per million. In the non-confirmed MG group, there was more women (92%) than men (43%) whose diagnosis was established within 1 year from onset of symptoms ( P  = 0.016). In all women with non-confirmed MG the diagnosis was established within 1 year from referral to the physician, whereas 68% of women with confirmed MG was diagnosed within 1 year ( P  < 0.0001). Thus, we conclude that, in Estonia the prevalence of MG based on medical records seems overestimated by 21% and women are at higher risk of obtaining an uncertain diagnosis of MG.     

Numerical Buoyancy-Wave Model for Wave Stress and Drag Simulations in the Atmosphere

Orographic drag formation is investigated using a numerical wave model (NWM), based on the pressure-coordinate dynamics of non-hydrostatic HIRLAM. The surface drag, wave stress (vertical flux of horizontal momentum), and wave drag are split to the longitudinal and transverse components and presented as Fourier sums of their spectral amplitudes weighted with the power spectrum of relative orographic height. The NWM is accomplished, enabling a spectral investigation of the buoyancy wave stress, and drag generation by orography and is then applied to a cold front, characterised by low static stability of the upper troposphere, large vertical and directional wind variations, and intensive trapped wave generation downstream of obstacles. Resonances are discovered in the stress and drag spectra in the form of high narrow peaks. The stress conservation problem is revisited. Longitudinal stress conserves in unidirectional flow, 2D orography conditions, but becomes convergent for rotating wind or 3D orography. Even in the convergent case the vertical momentum flux from the troposphere to stratosphere remains substantial. The transverse stress never conserves. Disappearing at the surface and on the top, it realises the main momentum exchange between lower an upper parts of the troposphere. Existence of stationary stratospheric quasi-turbulence (SQT) is established above wind minimum in the stratosphere.     

Altered tryptophan metabolism in the brain of cystatin B-deficient mice: a model system for progressive myoclonus epilepsy

PURPOSE: Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is a rare neurologic disorder, associated with mutations in the Cystatin B (Cstb) gene. Mice lacking Cstb, a cysteine protease inhibitor of the cathepsine family of proteases, provide a mammalian model for EPM1 by displaying similarly progressive ataxia, myoclonic seizures, and neurodegeneration. However, the linkage of Cstb deficit on the molecular level to pathologic features like myoclonic jerks or tonic-clonic seizures has remained unclear. We examined the tryptophan (TRP) metabolism, along the serotonin (5HT) and kynurenine (KYN) pathway in the brain of Cstb-deficient mice, in relation to their possible involvement in the seizure phenotype. METHODS: TRP and its metabolites, along the 5HT and KYN pathways, were assayed in brain tissue by high-pressure liquid chromatography (HPLC) with electrochemical detection. The inverted wire grid and mild handling tests were used for evaluation of ataxia and myoclonic activity. RESULTS: The Cstb-deficient mice had constitutively increased TRP, 5HT, and 5-hydroxyindole acetic acid (5HIAA) levels in the cerebral cortex and cerebellum and increased levels of KYN in the cerebellum. These neurochemical changes were accompanied with ataxia and an apparent myoclonic phenotype among the Cstb-deficient mice. CONCLUSIONS: Our findings suggest that secondary processes (i.e., overstimulation of serotoninergic transmission) on the cellular level, initiated by Cstb deficiency in specific brain regions, may be responsible for the myoclonic/seizure phenotype in EPM1.     

The Effect of Asphyxia upon the Lactate,Pyruvate and Bicarbonate Concentrations of Brain Tissue and Cisternal CSF,and upon the Tissue Concentrations of Phosphocreatine and Adenine Nucleotides in Anesthetized Rats

Kaasik , A. E., L. Nilsson and B. K. Siesjö . The effect of asphyxia upon the lactate, pyruvate and bicarbonate concentrations of brain tissue and cisternal CSF, and upon the tissue concentrations of phosphocreatine and adenine nucleotides in anesthetized rats. Acta physiol. scand. 1970. 78. 433–447. The effect of asphyxia upon the lactate, pyruvate and bicarbonate concentrations of brain tissue and cisternal CSF, and upon the tissue concentrations of phosphocreatine, ATP, ADP and AMP was studied in anesthetized and curarized rats, both at various times during (1, 2, 3 and 4 min) respiratory arrest, and after (1, 2, 5, 10 and 60 min) an arrest of 3 min. After 3 min of asphyxia the intracellular lactate concentration had increased to about 22 mMol/kg of i.c. water, while the calculated pHi' had decreased about 0.6 units to 6.50. At the same time almost all phosphocreatine had disappeared, and AMP had increased about tenfold, while there were clearcut, although less drastic, changes in AIP and 4DP. When the asphyxia was prolonged to 4 min the pH reduction apparently inhibited further glucolysis, and asphyxiawasa further fall in pHi'. Upon resumption of ventilation, the ATP, ADP and AMP concentrations, and the calculated cytoplasmatic NADH/NAD+ ratio, normalized within 2 min, and the phosphocreatine concentration as well as the sum of the adenine nucleotides within 5 min, while almost all excess lactate and pyruvate had disappeared within 10 min. There was a gradual and slow normalization of the calculated intracellular pHi' and the tissue was still acid 10 min after restarting the respirator. The three min period of asphyxia was associated with a rapid and marked lactacidosis in arterial blood which was normalized at 60, but not at 10 min. In the CSF, the lactacidosis developed gradually during several min, and the lactate concentration had not normalized until in the 60 min group.     

The effect of mechanical loading on the MyHC synthesis rate and composition in rat plantaris muscle

The aim of this study was to investigate the response of protein synthesis rate, particularly myosin heavy chain (MyHC) isoforms synthesis and the magnitude of its isoform transformation in fast-twitch plantaris muscle, to different modes of prolonged mechanical loading. Different protocols of mechanical loading were used: resistance training (RT), compensatory hypertrophy (CH) of m. plantaris after tenotomy of m. gastrocnemius and a combination of the two previous loadings (RT + CH). During the different modes of loading, plantaris muscle hypertrophy in RT group was approximately 10 %, CH approximately 40 % and CH + RT approximately 44 %. MyHC I and IID isoform synthesis rate increased in all experimental groups, as well as their relative content. MyHC IIA relative content decreased during RT and RT + CH and increased during CH. MHC IIB isoform relative content decreased in all experimental groups, but compared with CH in CH + RT MyHC IIB isoform content increased in plantaris muscle. These results demonstrate that different modes of mechanical loading resulted in the selective up- and down-regulation of MyHC isoforms in fast-twitch skeletal muscle. The synthesis rate and relative content of the two fastest isoforms of MyHC IIB and IID are regulated to different directions during mechanical loading.     

A population based epidemiological study on myasthenia gravis in Estonia

OBJECTIVE: To describe the occurrence of myasthenia gravis in the Baltic area. METHODS: Data were obtained from hospital files recorded during the period 1942 to 1996 from neurologists and the patient organisation. Survival data were checked with the Estonian Citizenship and Migration Board. Prevalence was determined on 1 January 1997. A questionnaire on the course of myasthenia gravis was sent to all the prevalent patients. RESULTS: The size of the population surveyed was 1 462 130. The average annual incidence from 1970 to 1996 was 4.0 per million (women, 5.2; men, 2.6). The point prevalence was 99 per million (women, 133; men 59). The incidence in the younger age group (<50 years) was 3.4 per million (women, 4.8; men, 1.9) and in the older age group (>or=50 years), 5.5 (women, 5.9; men, 4.9). The prevalence ratio was twofold higher in the older age group (p<0.0001)-for men (p = 0.034) as well as for women (p<0.001). CONCLUSIONS: Prevalence and incidence values of myasthenia gravis from Estonia are similar to those reported in most studies from Europe and north America. However, there seems to be a higher frequency in the elderly (>or=50 years) in Estonia.