A comparative perspective on longevity: the effect of body size dominates over ecology in moths.

Both physiologically and ecologically based explanations have been proposed to account for among-species differences in lifespan, but they remain poorly tested. Phylogenetically explicit comparative analyses are still scarce and those that exist are biased towards homoeothermic vertebrates. Insect studies can significantly contribute as lifespan can feasibly be measured in a high number of species, and the selective forces that have shaped it may differ largely between species and from those acting on larger animals. We recorded adult lifespan in 98 species of geometrid moths. Phylogenetic comparative analyses were applied to study variation in species-specific values of lifespan and to reveal its ecological and life-history correlates. Among-species and between-gender differences in lifespan were found to be notably limited; there was also no evidence of phylogenetic signal in this trait. Larger moth species were found to live longer, with this result supporting a physiological rather than ecological explanation of this relationship. Species-specific lifespan values could not be explained by traits such as reproductive season and larval diet breadth, strengthening the evidence for the dominance of physiological determinants of longevity over ecological ones.

Elevated atmospheric humidity shapes the carbon cycle of a silver birch forest ecosystem: A FAHM study.

Processes determining the carbon (C) balance of a forest ecosystem are influenced by a number of climatic and environmental factors. In Northern Europe, a rise in atmospheric humidity and precipitation is predicted. The study aims to ascertain the effect of elevated atmospheric humidity on the components of the C budget and on the C-sequestration capacity of a young birch forest. Biomass production, soil respiration, and other C fluxes were measured in young silver birch (Betula pendula Roth) stands growing on the Free Air Humidity Manipulation (FAHM) experimental site, located in South-East Estonia. The C input fluxes: C sequestration in trees and understory, litter input into soil, and methane oxidation, as well as C output fluxes: soil heterotrophic respiration and C leaching were estimated. Humidified birch stands stored C from the atmosphere, but control stands can be considered as C neutral. Two years of elevated air humidity increased C sequestration in the understory but decreased it in trees. Humidification treatment increased remarkably the C input to the soil. The main reason for such an increase was the higher root litter input into the soil, brought about by the more than two-fold increase of belowground biomass production of the understory in the humidification treatment. Elevated atmospheric humidity increased C sequestration in young silver birch stands, mitigating increasing CO2 concentration in the atmosphere. However, the effect of elevated atmospheric humidity is expected to decrease over time, as plants and soil organisms acclimate, and new communities emerge.

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.

Energetic crosstalk between organelles: architectural integration of energy production and utilization.

Cells with high and fluctuating energy demands such as cardiomyocytes need efficient systems to link energy production to energy utilization. This is achieved in part by compartmentalized energy transfer enzymes such as creatine kinase (CK). However, hearts from CK-deficient mice develop normal cardiac function under conditions of moderate workload. We have therefore investigated whether a direct functional interplay exists between mitochondria and sarcoplasmic reticulum or between mitochondria and myofilaments in cardiac cells that catalyzes direct energy and signal channeling between organelles. We used the selective permeabilization of sarcolemmal membranes with saponin to study the functional interactions between organelles within the cellular architecture. We measured contractile kinetics, oxygen consumption, and caffeine-induced tension transients. The results show that in hearts of normal mice, ATP produced by mitochondria (supplied with substrates, oxygen, and adenine nucleotides) was able to sustain calcium uptake and contractile speed. Moreover, direct mitochondrially supplied ATP was nearly as effective as CK-supplied ATP and much more effective than externally supplied ATP, suggesting that a direct ATP/ADP channeling exists between the sites of energy production (mitochondria) and energy utilization (sarcoplasmic reticulum and myofilaments). On the other hand, in cardiac cells of mice deficient in mitochondrial and cytosolic CK, marked cytoarchitectural modifications were observed, and direct adenine nucleotide channeling between mitochondria and organelles was still effective for sarcoplasmic reticulum and myofilaments. Such direct crosstalk between organelles may explain the preserved cardiac function of CK-deficient mice under moderate workloads.

Subcellular creatine kinase alterations. Implications in heart failure.

We have tested the hypothesis that decreased functioning of creatine kinase (CK) at sites of energy production and utilization may contribute to alterations in energy fluxes and calcium homeostasis in congestive heart failure (CHF). Heart failure was induced by aortic banding in 3-week-old rats. Myofilaments, sarcoplasmic reticulum (SR), mitochondrial functions, and CK compartmentation were studied in situ using selective membrane permeabilization of left ventricular fibers with detergents (saponin for mitochondria and SR and Triton X-100 for myofibrils). Seven months after surgery, animals were in CHF. A decrease in total CK activity could be accounted for by a 4-fold decrease in activity and content (Western blots) of mitochondrial CK and a 30% decrease in M isoform of CK (MM-CK) activity. In myofibrils, maximal force, crossbridge kinetics, and alpha-myosin heavy-chain expression decreased, whereas calcium sensitivity of tension development remained unaltered. Myofibrillar CK efficacy was unchanged. Calcium uptake capacities of SR were estimated from the surface of caffeine-induced tension transient (SCa) after loading with different substrates. In CHF, SCa decreased by 23%, and phosphocreatine was 2 times less efficient in enhancing calcium uptake. Oxidative capacities of the failing myocardium measured as oxygen consumption per gram of fiber dry weight decreased by 28%. Moreover, the control of respiration by creatine, ADP, and AMP was severely impaired. Our observations provide evidence that alterations in CK compartmentation may contribute to alterations of energy fluxes and calcium homeostasis in CHF.

Thyroid hormones increase the contractility but suppress the effects of beta-adrenergic agonist by decreasing phospholamban expression in rat atria.

OBJECTIVE: The aim of the present study was to characterize the relationships between the thyroid-hormone-dependent changes in sarcoplasmic reticulum (SR) Ca2+ handling and contractile performance in atria. METHODS: Hypothyroidism in rats was induced by adding 0.05% 6-n-propyl-2-thiouracil to their drinking water for 6 weeks. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (1 microgram/g body weight) to euthyroid rats for 1 week. Left atria from the hearts with different thyroid states were examined by means of contractile measurements, SR oxalate-supported Ca(2+)-uptake, and Western blot of SR proteins. RESULTS: The tissue level of SR Ca(2+)-pump protein decreased in hypothyroid (46 +/- 6%) atria, but remained unchanged in hyperthyroid (110 +/- 8%) atria as compared with euthyroid atria. Hypothyroidism was associated with increased phospholamban expression (141 +/- 25%), whereas it was drastically downregulated under hyperthyroidism (21 +/- 4%). The rate of SR Ca(2+)-uptake, measured in the presence of the protein kinase A inhibitor, H-89, was higher in hyperthyroid atria and lower in hypothyroid atria than in euthyroid atria (397 +/- 40, 55 +/- 6 and 194 +/- 17 nmol Ca2+/g protein/min, respectively). However, the stimulation of SR Ca(2+)-uptake by the catalytic subunit of protein kinase A was relatively weaker in hyperthyroid (130 +/- 20% over control level without catalytic subunit) and stronger in hypothyroid (640 +/- 60%) than in euthyroid atria (280 +/- 40%). The rates of inotropic contraction (+dT/dt) were higher in the hyperthyroid atria (133 +/- 10 mN/s), but lower in hypothyroid atria (15 +/- 3 mN/s) than in their euthyroid counterparts (95 +/- 13 mN/s). Inversely, hypothyroid atria responded to isoproterenol with much larger increases in contractility (883 +/- 164% over the control values for the same muscle before addition of isoproterenol) and hyperthyroid with smaller increases (25 +/- 9%) than euthyroid preparations (207 +/- 17%) CONCLUSIONS: Thyroid hormones increase the contractility, but decrease the inotropic response to isoproterenol through decreasing the phospholamban/SR Ca(2+)-pump ratio in rat atria.

Nitric oxide inhibits cardiac energy production via inhibition of mitochondrial creatine kinase.

Nitric oxide biosynthesis in cardiac muscle leads to a decreased oxygen consumption and lower ATP synthesis. It is suggested that this effect of nitric oxide is mainly due to the inhibition of the mitochondrial respiratory chain enzyme, cytochrome c oxidase. However, this work demonstrates that nitric oxide is able to inhibit soluble mitochondrial creatine kinase (CK), mitochondrial CK bound in purified mitochondria, CK in situ in skinned fibres as well as the functional activity of mitochondrial CK in situ in skinned fibres. Since mitochondrial isoenzyme is functionally coupled to oxidative phosphorylation, its inhibition also leads to decreased sensitivity of mitochondrial respiration to ADP and thus decreases ATP synthesis and oxygen consumption under physiological ADP concentrations.

Survival of patients with primary CNS tumours in Estonia.

We studied a population-based survey that included 1417 patients with a primary central nervous system (CNS) tumour diagnosed in Estonia between 1986 and 1996. Survival rates at 1 and 5 years and median survival by histology and patient's age at diagnosis were estimated. Median survival time for all tumours was 33.2 months and 1- and 5-year survival rates were 59.3 and 46.0%, respectively. In multivariate analysis, younger age, better clinical condition (i.e. a Karnofsky Performance Status (KPS) score of 60 and more) and tumour histology were all dependent prognostic factors for better survival. Risk of death was more than 8 times greater for glioblastoma (Risk Ratio (RR) 8.31) and approximately seven times greater for anaplastic astrocytoma (RR 7.22) and other gliomas (RR 5.74) compared with meningiomas. Comparing the first (1986-1989) and the third (1994-1996) time periods, statistically significant improvements in survival occurred for all tumours and astrocytomas. Declines in survival during the second period (1990-1993) were statistically significant for all the tumour groups, but the most striking decrease took place in patients with glioblastoma. Age-specific rates showed that the increase in survival was more evident for patients aged between 45 and 64 years.

Dehydroepiandrosterone sulphate prevents oxygen-glucose deprivation-induced injury in cerebellar granule cell culture.

Decreased levels of dehydroepiandrosterone sulphate have been hypothesized to contribute to increased vulnerability of the ageing or stressed human brain to ischemia. To help to address the question of whether of dehydroepiandrosterone sulphate has a possible neuroprotective effect against ischemic neuronal injury, we tested its effect on the neurodegeneration induced by oxygen-glucose deprivation in rat cultured cerebellar granule cells. Dehydroepiandrosterone sulphate added to the medium after injury demonstrated a neuroprotective effect with a median inhibitory concentration of 0.5 microM. At 10 microM concentration almost full neuroprotection was observed. Even more pronounced neuroprotective effect was found when dehydroepiandrosterone sulphate was added for 48h before injury. Furthermore, partial neuroprotection of dehydroepiandrosterone sulphate was also found against 1-methyl-4-phenylpyridinium, colchicine, glutamate and N-methyl-D-aspartate-induced toxicity. Further analysis demonstrated that dehydroepiandrosterone sulphate eliminated the apoptotic features of the oxygen-glucose deprivation-induced neuronal death: DNA fragmentation and nuclear condensation/fragmentation.Thus, our data suggest that dehydroepiandrosterone sulphate may have therapeutic potential in the prevention and treatment of ischemic/hypoxic neuronal damage. The neuroprotective action of dehydroepiandrosterone sulphate was inhibited by both a GABA(A) receptor-linked chloride channel agonist and an antagonist, pentobarbital and picrotoxin, respectively. It seems that GABA(A) receptor-mediated neuronal inhibition as well as neuronal excitation can reduce the neuroprotective action of dehydroepiandrosterone sulphate.

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.

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).

A catecholamine-mediated increase in cerebral oxygen uptake during immobilisation stress in rats.

Anxiety and grave apprehension have been supposed to increase cerebral metabolism, and it has earlier been suggested that intravenous infusion of adrenaline may increase cerebral blood flow (CBF) and cerebral oxygen consumption (CMR02). In an experimental model on rats, it could be shown that immobilisation stress increased CBF and CMR02 after 5 min (about 150% of control values) and 30 min (about 190% of control values). By previous adrenalectomy or by administration of a beta-receptor blocker (propranolol, 1.4 mg/kg) the changes in CBF and CMR02 could be prevented. It is concluded that the excessive increase in CBF and CMR02 was mediated via release of catecholamines from the adrenal glands.

Membrane-bound phosphodiesterases in rat myocardium.

Isoenzyme-specific phosphodiesterase (PDE) inhibitors are potential positive inotropic drugs. For evaluating such drugs in experimental models and to understand the physiological roles of the different isoenzymes, it is necessary to know what isoenzymes are present in the tissues studied. Rat myocardium has been reported to be devoid of the particulate cGMP-inhibited cAMP-PDE (type III isoenzyme). Here we re-evaluate the isoenzyme profile of rat myocardium. The cAMP-PDE isoenzyme patterns were studied by ion-exchange chromatography using siguazodan and rolipram, specific inhibitors of type III and IV isoenzymes, respectively. In contrast to earlier reports, type III isoenzyme was abundant in the particulate fraction. PDE III-specific antibodies depressed PDE activity and stained bands in Western blot with molecular masses 64 and 71 kDa. Type III isoenzyme of myocardial membranes was found to be unstable at 37 degrees C which may explain why earlier investigators have failed to demonstrate its presence. The data presented in this paper show that rat heart particulate fraction contains two low Km PDE isoenzymes, type III and type IV, in equal activities. Thus, in contrast to previous reports, this paper clearly shows the presence of considerable amounts of membrane-bound type III PDE isoenzyme in rat myocardium.

Felt stigma and impact of epilepsy on employment status among Estonian people: exploratory study.

This article examines the impact of epilepsy and its treatment on employment status and the extent of stigma among patients with epilepsy. Clinical and demographic data concerning patients examined during a recent epidemiological survey were obtained from medical notes and postal self-completed questionnaires. Information was collected from 90 patients aged 16-70 years. A third of the respondents had been seizure-free during the last year. Thirty-nine percent were working full-time, 24% were working part-time and 11% were unemployed. Sixty-three percent from those working part-time or unemployed considered their epilepsy to be a significant reason for this. Overall, 55.4% believed they had been treated unfairly at work or when trying to get a job. Fifty-one percent of respondents felt stigmatized by epilepsy, 14% of them highly so. The level of employment among epileptic people was not lower than in the general population. The percentage of stigmatization in general and the percentage of the severely stigmatized was as high or even higher than in other studies. Occurrence of stigma and its severity depended first and foremost on the type of seizures. The frequency of seizures was not clearly related to this.

Local blood flow in the thalamus and frontal cortex in alert and narcotized dogs.

The magnitude of the local blood flow in the thalamus and cerebral cortex is studied on 22 sexually mature nonpedigree dogs. Mean values of local blood flow are obtained in alert animals, and the effect of narcosis (nitrous oxide) on the local cerebral blood flow is studied. The mean local blood flow in alert dogs is found to be 84.8 +/- 2.9 ml/100 g/min in the cerebral cortex and 68.7 +/- 1.6 ml/100 g/min in the thalamus. Insignificant fluctuations are found during a dynamic recording of the local blood flow during 7 days. Under narcosis (70% nitrous oxide) the local blood flow decreases 3-12%. According to the findings, nitrous oxide narcosis does not significantly affect the brain circulation, so that it is suitable for an experimental study of the latter.

[Enzymatic activity of the cerebrospinal fluid in patients with cerebral infarct]. / Aktivnost' énzimov likvora u bol'nykh s infarktom golovnogo mozga.

Dynamic measurements in the cerebrospinal fluid (CSF) of the activities of lactate dehydrogenase (LDH), its first isoenzyme (LDH1), aspartate amino transferase (AsAT), alanine amino transferase (AlAT), creatine phosphokinase (CPK), gamma-glutamyl transpeptidase (GGT) and alkaline phosphatases (ALP) were performed in 99 patients with ischemic stroke. The mean activities of LDH, LDH1, AsAT, CPC and GGT in the CSF of the patients significantly exceeded those in the control group during the first and second weeks of the disease. The increased activities of LDH, LDH1, CPK and AsAT in patients with ischemic stroke indicate the severity of cerebral lesion and resultant hypoxia of the cerebral tissue. High levels of enzymic activity, particularly over a long period of time, always predict a poor outcome.

[Non-invasive method of measuring central hemodynamics in cerebral infarct patients]. / Neinvazivnyi metod izmereniia tsentral'noi gemodinamiki u bol'nykh s infarktom golovnogo mozga.

Changes in parameters of the central hemodynamics (CH) determined by integral rheography of the body (IRB) were analyzed in 39 patients with cerebral stroke (CS). It was found that despite a stable neurological and somatic status, parameters of cardiac contractivity diminished while the vascular tonus increased within the first 2 weeks of the disease. These alterations were more pronounced in obese patients. The authors believe that their data on an increased vascular tone indicate a compensatory function of the CH after the development of CS and suggest that the use of hypotensive drugs in such cases is inadvisable. A conclusion is drawn that IRB is an informative method of the dynamic examination of the CH in cerebral stroke patients.

[Hyperbaric oxygenation in the treatment of patients with ischemic stroke]. / Giperbaricheskaia oksigenatsiia v lechenii bol'nykh s ishemicheskim insul'tom.

Biochemical parameters (the gaseous composition and acid-base balance of the blood and cerebrospinal fluid (CSF) were investigated in patients with ischemic stroke in the process of hyperbaric oxygenation treatment. A characteristic peculiarity observed was the presence of compensated metabolic acidosis in the CSF which was most expressed in patients with an extensive focus of cerebral infarction. A characteristic change in the venous blood of the brain was the presence of compensated metabolic acidosis. Metabolic acidosis of the cerebral venous blood in patients treated with hyperbaric oxygenation significantly diminished as compared with the control group.

[Cerebral creatine kinase isoenzyme in the cerebrospinal fluid: importance of its measuring for prognosis of the disease outcome in cerebral ischemic disorders]. / Mozgovoi izoénzim kreatinkinazy v spinnomozgovoi zhidkosti: vazhnost' opredeleniia soderzhaniia dlia prognozirovaniia iskhoda bolezni pri ishemicheskikh narusheniiakh golovnogo mozga.

The concentration of cerebral isoenzyme of creatine kinase was measured repeatedly in the cerebrospinal fluid (CSF) in 84 patients with ischemic disorders of brain circulation. Of these, 14 patients presented with transitory ischemic attacks, 20 patients with regressing deficit, and 50 with brain infarction. The patients' health status and functional capacities were estimated on discharge from the hospital. It was discovered that in each patient, the maximum level of cerebral isoenzyme in the CSF was in a good agreement with the clinical course of the disease and neurological status in the survived patients. It may be concluded that measurements of the concentration of the enzyme in the CSF makes it possible to draw more valid prognostic conclusions in patients with ischemic disorders of brain circulation.