Motor neurone disease in South Estonia Diagnosis and incidence rate

The current study evaluated the diagnostic standards of MND and epidemiological markers of MND in Estonia. A total of 108 patients were referred to the University Hospital from 1986 to 1995 with the first suggested diagnosis or final diagnosis of amyotrophic syndrome, amyotrophic lateral sclerosis (ALS), progressive bulbar paralysis (PBP) or progressive muscular atrophy (PMA). In addition neurologists of the region and the National Society of Neuromuscular disorders were contacted. Some 94 patients satisfied the diagnostic criteria. The annual incidence rate in South Estonia and in the city of Tartu ranged from 0.5 to 2.8 per 100,000. The mean annual incidence rate in Tartu is 1.98 and in South Estonia in general 1.3. The highest incidence rate was 8.3 for men in the age group 60 to 64 years and 7.49 in the age group 70–74; among female patients the highest incidence rate -4.6 was in the age group from 65 to 69.     

Neuroprotective action of group I metabotropic glutamate receptor agonists against oxygen-glucose deprivation-induced neuronal death

The metabotropic glutamate receptor (mGluR) non-selective agonist (1S,3R)-1-aminocycloheptane-trans-1,3-dicarboxylic acid [(1S, 3R)ACPD] and group I selective receptor agonist 3, 5-dihydrophenylglycine (DHPG) effectively attenuated oxygen-glucose deprivation (OGD)-induced death of the cultured cerebellar granule cells. Furthermore, (1S,3R)ACPD (100 microM) reduced the number of apoptotic cells. Antiapoptotic action of (1S,3R)ACPD was prevented by the group I selective antagonist (RS)-1-aminoindan-1, 5-dicarboxylic acid (AIDA, 100 microM) and protein kinase C (PKC) inhibitor bisindolylmaleimide (BMI, 1 microM).     

Impaired oxidative phosphorylation in overtrained rat myocardium

The present study was undertaken to characterize and review the changes in energy metabolism in rat myocardium in response to chronic exhaustive exercise. It was shown that a treadmill exercise program applied for six weeks led the rats into a state characterized by decreased performance, loss of body weight and enhanced muscle catabolism, indicating development of overtraining syndrome. Electron microscopy revealed disintegration of the cardiomyocyte structure, cellular swelling and appearance of peroxisomes. Respirometric assessment of mitochondria in saponin-permeabilized cells in situ revealed a decreased rate of oxidative phosphorylation (OXPHOS) due to diminished control over it by ADP and impaired functional coupling of adenylate kinase to OXPHOS. In parallel, reduced tissue content of cytochrome c was observed, which could limit the maximal rate of OXPHOS. The results are discussed with respect to relationships between the volume of work and corresponding energy metabolism. It is concluded that overtraining syndrome is not restricted to skeletal muscle but can affect cardiac muscle as well.     

Unravelling genetic data by arrayed primer extension.

We have developed a method for arrayed primer extension (APEX) on an oligonucleotide microchip together with the 4-color fluoresence imaging equipment and supporting software, that allows analysis of the DNA sequence and changes in it. Mutation analysis of BRCA1 gene and single nucleotide polymorphism (SNP) chip for genotyping were used as a model system. Chip surface chemistry, template preparation and APEX reaction conditions were optimised and the assay is ready to be implemented in variety of DNA analysis from SNP testing to DNA resequencing.     

The risk of motor neurone disease and multiple sclerosis is different in Estonians and Russians. Data from South Estonia

Epidemiological studies were performed in South Estonia to establish the prevalence rate of multiple sclerosis (MS) and motor neurone disease (MND). The case finding method included information from the hospital records of the central hospital in the region-the University Hospital (for MS from 1942 to 1989), from all neurologists in the region, from the Estonian MS Society and Association of Muscular Disorders, and from nursing homes in the region. The prevalence day was 31 December 1989. MND incidence was established for the period of 1986-1995. The results demonstrated high prevalence rates of MS among native Estonians (55.3 per 100 000), somewhat lower prevalence among native-born representatives of other nationalities (43.6 per 100 000) and the lowest prevalence rate of MS among non-Estonian immigrants (26.6 per 100 000). The differences were not statistically significant. The results for MND demonstrated the opposite pattern. The mean annual incidence rate of MND for 10 years was statistically significantly higher among people of other nationalities (2.5 per 100 000) and Russians (2.6 per 100 000), and lower in native-born Estonians (1.1 per 100 000). No differences in health care or clinical picture were established. The reasons for the demonstrated differences in MND incidence remain unclear.     

Systemic resilience to cross‐border infectious disease threat events in Europe

Recurrent health emergencies threaten global health security. International Health Regulations (IHR) aim to prevent, detect and respond to such threats, through increase in national public health core capacities, but whether IHR core capacity implementation is necessary and sufficient has been contested. With a longitudinal study we relate changes in national IHR core capacities to changes in cross‐border infectious disease threat events (IDTE) between 2010 and 2016, collected through epidemic intelligence at the European Centre for Disease Prevention and Control (ECDC). By combining all IHR core capacities into one composite measure we found that a 10% increase in the mean of this composite IHR core capacity to be associated with a 19% decrease (p = 0.017) in the incidence of cross‐border IDTE in the EU. With respect to specific IHR core capacities, an individual increase in national legislation, policy & financing; coordination and communication with relevant sectors; surveillance; response; preparedness; risk communication; human resource capacity; or laboratory capacity was associated with a significant decrease in cross‐border IDTE incidence. In contrast, our analysis showed that IHR core capacities relating to point‐of‐entry, zoonotic events or food safety were not associated with IDTE in the EU. Due to high internal correlations between core capacities, we conducted a principal component analysis which confirmed a 20% decrease in risk of IDTE for every 10% increase in the core capacity score (95% CI: 0.73, 0.88). Globally (EU excluded), a 10% increase in the mean of all IHR core capacities combined was associated with a 14% decrease (p = 0.077) in cross‐border IDTE incidence. We provide quantitative evidence that improvements in IHR core capacities at country‐level are associated with fewer cross‐border IDTE in the EU, which may also hold true for other parts of the world.     

Neuroprotective action of group I metabotropic glutamate receptor agonists against oxygen–glucose deprivation-induced neuronal death

The metabotropic glutamate receptor (mGluR) non-selective agonist (1S,3R)-1-aminocycloheptane-trans-1,3-dicarboxylic acid [(1S,3R)ACPD] and group I selective receptor agonist 3,5-dihydrophenylglycine (DHPG) effectively attenuated oxygen–glucose deprivation (OGD)-induced death of the cultured cerebellar granule cells. Furthermore, (1S,3R)ACPD (100 μM) reduced the number of apoptotic cells. Antiapoptotic action of (1S,3R)ACPD was prevented by the group I selective antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA, 100 μM) and protein kinase C (PKC) inhibitor bisindolylmaleimide (BMI, 1 μM).     

Up-regulation of lysosomal cathepsin L and autophagy during neuronal death induced by reduced serum and potassium

Serum and potassium deprivation-induced neuronal death on the primary culture of rat cerebellar granule neurons is being widely used as an in vitro model of neurodegeneration and neuronal apoptosis. In our experiments, serum and potassium deprivation for 12 h induced neuronal death in approximately 20% of cerebellar granule neurons as demonstrated by Trypan Blue assay. Neuronal death was accompanied by a transient increase in the intralysosomal cathepsin L activity, which preceded neuronal death. During this time, the lysosomal membrane integrity remained preserved and no leakage of cathepsin L into the cytosol was seen. Ultrastructural analysis revealed the appearance of multiple vacuoles and autophagosomes in the cytoplasmatic compartment of serum- and potassium-deprived granule neurons. Addition of selective cathepsin L inhibitors or of the autophagy inhibitor 3-methyladenine provided partial protection against serum and potassium deprivation-induced death. Our data also show that combining cathepsin L inhibitors and caspase-3 inhibitors leads to a synergistic neuroprotective effect against serum and potassium deprivation. The results of the current study suggest that activation of the autophagosomal--lysosomal compartment plays an important role in neuronal death induced by serum and potassium deprivation in cultured cerebellar granule cells.     

Surgical treatment of patients with cranio-cerebral trauma and the role of neurological symptoms in the prognosis of its outcomes

Under examination there were 411 patients with cranio-cerebral traumas. A unified method was used at different medical institutions in order to study questions of prognosis of the outcomes. Surgical treatment was used in 117 of them. The investigations have shown that the state of trance-coma both before operation and in the postoperative period is absolutely unfavourable prognostically. The state of trance-coma and the value of 15 scores and less should be taken into consideration as a contraindication for the solution of the question of operation in patients with cranio-cerebral traumas.     

Seizure disorders in patients with brain tumors

The aim of this study was to analyze the clinical data of patients with epileptic seizures and diagnosed brain tumors. Analysis included 711 patients with primary and secondary brain tumors. 165 (23%) patients had experienced at least one seizure before tumor diagnosis. The mean time from the first epileptic seizure to tumor diagnosis was 16 months. The patient's age, location and pathology of tumor were associated with occurrence of seizures. Seizures were more common in patients aged 30-50 years. Tumors involving the frontal, frontoparietal, temporal and frontotemporal lobes were associated with occurrence of seizures. According to the histological diagnosis, patients with mixed gliomas (62%), oligodendrogliomas (53%) and astrocytomas (42%) experienced seizures most frequently.