[Morphological characteristic of a motor unit afferent limb in hypokinesia].

Neuromuscular spindles (NMS) of soleus muscle and their vascular bed was studied in 250 mature male Wistar rats following long-term (30, 60, 120 and 240 days) hypokinesia. Material was studied using Kulchitsky, Mason and Ranson histological staining, electron microscopic and histochemical methods (demonstration of succinate dehydrogenase). It was found that initial changes involved the decrease of the lumen of precapillary arterioles (by 25.4%) and blood capillaries (by 29.1%). These changes closely correlated with the increase of the subcapsular space width (by 34.7%), the decrease of NMS capsule thickness (by 48.7%) and equatorial zone diameter (by 17.9%). Activity of succinate dehydrogenase in the intrafusal muscle fibers was also decreased. As a result of disintegration of the majority of gamma-axon terminals, NMS cross sectional area was decreases by 75.6%. Thus, during hypokinesia initial changes were detected in the sources of NMS blood supply, while their structural remodelling involved destructive alterations.

Gene disruption of caspase-3 prevents MPTP-induced Parkinson's disease in mice.

The development of Parkinson's disease is accompanied by concurrent activation of caspase-3 and apoptosis of dopaminergic neurons of human patients and rodent models. The role of caspase-3, a final executioner of apoptosis, in the pathogenesis of Parkinson's disease, however, remains to be determined. Here, we show that gene disruption of caspase-3 protects mice from 1-methyle-4-phenyl-1,2,3,6-tetrahmydropyridine (MPTP)-induced Parkinsonian syndrome, as reflected by reversal of MPTP-induced bradykinesia and decreased tyrosine hydroxylase expression in the nigra-striatum. MPTP treatment resulted in increased caspase-3 activation and apoptosis in the substantia nigra of wild-type mice at 24 h after the inception of MPTP treatment, as compared with vehicle-treated control animals. Gene disruption of caspase-3 prevented MPTP-induced apoptosis in the substantia nigra. At 7 days after MPTP treatment, tyrosine hydroxylase expression was suppressed and infiltration of activated microglia and astrocytes was markedly increased in the nigra-striatum of wild-type mice. All of these alterations following MPTP treatment were blocked by disruption of caspase-3 in mice. These results clearly indicate that caspase-3 activation is required for the development of MPTP-induced Parkinson's disease in mice. These findings suggest that activation of caspase-3-mediated apoptosis of dopaminergic neurons in the early stage may play an important role in the pathogenesis of Parkinson's disease.

[Effect of melatonin on activity of superoxide dismutase (CuZn-SOD) in erythrocytes of patients during short- and long-term hypokinesis]. / Wplyw melatoniny na aktywnosc dysmutazy ponadtlenkowej (CuZn-SOD) w krwinkach czerwonych chorych w okresie hipokinezji krótko- i dlugoterminowej.

INTRODUCTION: Short- or long-lasting hypokinesis is to a large degree the consequence of negative habits of human beings towards a comfortable and more sedentary lifestyle. The period of decreased physical activity can cause disturbance in the balance between systemic processes of the oxidation and reduction, which leads to an increase in reactive oxygen species (ROS) and oxidative stress generation. The aim of the study was to determine the effect of melatonin administration on the cellular superoxide dismutase (CuZn-SOD) activity in red blood cells of patients with short- and long-term hypokinesis as compared to the group of subjects with normal physical activity. MATERIAL AND METHODS: The study included 33 subjects with immobilization. The study group was divided into two subgroups (depending on hypokinesis duration): group A: 15 subjects classified for total hip alloplasty (a short-lasting decrease in physical activity); group B: 18 subjects suffering from multiple sclerosis or the stroke of brain (the long-term hypokinesis). The control group (group C) comprised 17 subjects with normal physical activity. Melatonin was applied at a dose of 5 mg daily, one hour before sleep. The CuZn-SOD activity in red blood cells was determined, according to the Misra and Fridovich method, in two periods: 1) on the first day, 2) on the 10th day (group A), and 30 days (group B) after melatonin administration. RESULTS: A slight increase in CuZn-SOD activity (+3.1%) was observed in group A 10 days after alloplasty and melatonin administration as compared to group B, where a considerable rise in the enzyme activity (+23.3%) was found 30 days after rehabilitation and melatonin supplementation. The average CuZn-SOD activity in both investigative groups was lower than that in the controls (group C). CONCLUSIONS: It was estimated that the short- and long-lasting hypokinesis leads to an increase in ROS generation, what is confirmed by the increase in CuZn-SOD activity. The results of the study on superoxide dismutase activity indicate that oral administration of melatonin for the period of 30 days has a more favorable influence on antioxidative processes than 10-day's melatonin intake.

Monoacylglycerol lipase inhibition by organophosphorus compounds leads to elevation of brain 2-arachidonoylglycerol and the associated hypomotility in mice.

Three components of the cannabinoid system are sensitive to selected organophosphorus (OP) compounds: monoacylglycerol (MAG) lipase that hydrolyzes the major endogenous agonist 2-arachidonoylglycerol (2-AG); fatty acid amide hydrolase (FAAH) that cleaves the agonist anandamide present in smaller amounts; the CB1 receptor itself. This investigation considers which component of the cannabinoid system is the most likely contributor to OP-induced hypomotility in mice. Structure-activity studies by our laboratory and others rule against major involvement of a direct toxicant-CB1 receptor interaction for selected OPs. Attention was therefore focused on the OP sensitivities of MAG lipase and FAAH, assaying 19 structurally diverse OP chemicals (pesticides, their metabolites and designer compounds) for in vitro inhibition of both enzymes. Remarkably high potency and low selectivity is observed with three O-alkyl (C1, C2, C3) alkylphosphonofluoridates (C8, C12) (IC50 0.60-3.0 nM), five S-alkyl (C5, C7, C9) and alkyl (C10, C12) benzodioxaphosphorin oxides (IC50 0.15-5.7 nM) and one OP insecticide metabolite (chlorpyrifos oxon, IC50 34-40 nM). In ip-treated mice, the OPs at 1-30 mg/kg more potently inhibit brain FAAH than MAG lipase, but FAAH inhibition is not correlated with hypomotility. However, the alkylphosphonofluoridate-treated mice show dose-dependent increases in severity of hypomotility, inhibition of MAG lipase activity and elevation of 2-AG. Moderate to severe hypomotility is accompanied by 64 to 86% MAG lipase inhibition and about 6-fold elevation of brain 2-AG level. It therefore appears that OP-induced MAG lipase inhibition leads to elevated 2-AG and the associated hypomotility.

Erythrocyte superoxide dismutase activity differs in clinical subgroups of Parkinson's disease patients.

There is controversy as to whether there are clinical subgroups in Parkinson's disease (PD). Six tremor-dominant and six bradykinesia-dominant patients identified among 29 cases with PD were compared in terms of erythrocyte superoxide dismutase (SOD) activity and several clinical variables. Erythrocyte SOD activity in tremor-dominant patients was higher than in bradykinesia-dominant patients. According to our preliminary results obtained from small number of patients, the difference of SOD activity in clinically distinct subgroups suggests there may be separate clinical subgroups of PD which can be differentiated by a biological marker.

[Lipid peroxidation and activity of diagnostically important blood enzymes in rats during 35 days head-down suspension]. / Perekisnoe okislenie lipidov i aktivnost' diagnosticheski znachimykh fermentov krovi u krys pri 35-sutochnom vyveshivanii v antiortostaticheskom polozhenii.

In the experiment with 35-d head-down suspension of rats concentrations of lipid peroxidation (LPO) products and values of antioxidant defense (AOD) parameters were determined in the lever, skeletal muscles, myocardium, and blood plasma. In addition, activity of 11 plasma enzymes characteristics of these tissues was evaluated. LPO was found to be activated in the lever, myocardium and skeletal muscles in the first and 4-5 weeks of suspension. The period between weeks 2 and 4 marked phase variation of LPO intensity which could have baseline or increased values. Plasma LPO was inhibited due to AOD activation pointing to compensatory processes on the level of organism and absence of pathologies in the organs and tissues under study. As a rule, activity of the plasma enzymes directly or indirectly participating in energy metabolism was reduced. Enzymes-catalysts of other types of metabolism predominantly elevated activity during LPO intensification. Canonic analysis established a significant correlation of LPO, AOD and activity of plasma enzymes, and LPO and AOD in the rat's lever and plasma enzymes. These correlations between LPO, AOD and activity of diagnostically important enzymes can be used to diagnose and predict changes in the state of organism caused by simulated factors of space flight.

[The aspects of adenylate cyclase activity regulation in myocardium cell membranes during hypokinesia]. / Osobennosti reguliatsii aktivnosti adenilatsiklasy membran kletok miokarda pri gipokinezii.

Nonstimulated and isoproterenol, GTF, GITF, NaF stimulated activities of the adenylate cyclase in sarcolemma in white rats' myocardium was studied after two weeks of hypokinesia. As was established, in restrained animals the sensitivity of adenylate cyclase to the specified agents was increased and transition to the bimodal GTF regulation took place. It is hypothesised that involvement of membrane-bound Gi-proteins in the adrenergic effects on cardiomyocytes is one of mechanisms of the cardiotropic effects of restraint and heart distresses.

[Compensatory changes in the acid-base balance under the influence of excess ammonium chloride, hypodynamia and stress]. / Kompensovani zminy kyslotno-luzhnoï rivnovahy pid vplyvom nadlyshku amoniiu khlorydu, hipodynami]i ta stresu.

Two variants of alternative integrative compensatory mechanisms of metabolic reactions in organism developing at the compensated shifts of acid-base balance under the influence of different risk factors have been discovered by the authors. Compensated metabolic acidosis appears with the excess of salt ammonia in the animals ration, at the immobilization stress, hypodynamia, deafferentation and surgical stress. The start reaction of acidosis is lipolysis activation and nonacidified products accumulation at the reactions of tricarboxylic acid cycle are (TAC) inhibited. The compensatory mechanism directed to bind hydrogen ions and prevent pH shifts is activity of glyconeogenesis reactions, transamination, increase the contents ammonia, as well as by increases of restored combinations. Carbohydrates excess in the ration, emotional stress (anxiety expectation) lead to the metabolic alkalosis development at which low hydrogen ion formation and their rapid use in the activated process of peroxide lipids oxidation is compensated with the increase of organic acids formation in glycolysis and TAC as well as by the increase of oxidation properties in tissues. Besides adaptive physiological meaning, the described mechanisms may be the reason for a number of pathological state appearance. The discovery in population and prevention of endogenic risk factors prevention is principle new basis of modern integrated system of human and animals common diseases prevention.

[Effect of GABA and piracetam on on ATPase activity in brain and liver mitochondria in experimental hypokinesis]. / Vliianie GAMK i piratsetama na ATF-aznuiu aktivnost' mitokhondrii mozga i pecheni v usloviiakh éksperimental'noi gipokinezii.

Long-term hypokinesia is accompanied by changes in the activity of Mg(2+) and 2,4-dinitrophenol (DNP)-stimulated ATPases of rat brain and liver mitochondria. These changes are phasic and especially pronounced at periods characterised by most pronounced metabolic alterations Treatment of animals with GABA and piracetam tends to normalise the enzyme activities.

Protein kinase a activity is increased in rat heart during late hypodynamic phase of sepsis.

Changes in the activities of protein kinase A (PKA, or cAMP-dependent protein kinase) in rat heart during different cardiodynamic phases of sepsis were investigated. Sepsis was induced by cecal ligation and puncture. Experiments were divided into three groups: control, early sepsis, and late sepsis. Early and late sepsis refers to those animals killed at 9 and 18 h, respectively, after cecal ligation and puncture. Cardiac PKA was extracted and partially purified by acid precipitation, ammonium sulfate fractionation, and DEAE-cellulose chromatography. PKA was eluted from DEAE-cellulose column with a linear NaCl gradient. Two peaks of PKA, type I (eluted at low ionic strength) and type II (eluted at high ionic strength), were collected and their activities were determined based on the rate of incorporation of [gamma-32P]ATP into histone. Results obtained show that during early sepsis, both type I and type II PKA activities were unaffected. During late sepsis, type I PKA activities were stimulated by 66.7-97.7%, while type II PKA activities remained constant. Kinetic analysis of the data on type I PKA during late sepsis reveals that the Vmax values for ATP, cAMP, and histone were increased by 84.7, 66.7, and 97.7%, respectively; while the Km values for ATP, cAMP, and histone were unaltered. These data indicate that type I PKA is activated in rat heart during late hypodynamic phase of sepsis. Since kinase-mediated phosphorylation plays an important role in regulating myocardial function and metabolism, an activation of type I PKA during late sepsis may contribute to the development of altered myocardial function during hypodynamic phase of sepsis.

[Changes in the enzyme-active region of the neuromuscular synapse of the gastrocnemius muscle in rats during hypokinesis]. / Izmeneniia fermentoaktivnoi zony neiromyshechnogo sinapsa ikronozhnoi myshtsy u krys pri gipokinezii.

Restraint of white rats in fight cages leads to diminution of the area of neuromuscular synapse with an intricate structure of the enzyme-active region and reduction of the number of neuromuscular synapses per one fiber in the gastrocnemius muscle. Signs of dystrophy of neuromuscular synapses with the intricate enzyme-active region are observed. These changes arise by day 14 of hypokinesia and become more pronounced by day 28.

[Ontogenetic transformations in the energy metabolism system of the skeletal muscles under different conditions of animal development]. / Ontogeneticheskie preobrazovaniia sistemy énergeticheskogo metabolizma skeletnykh myshts pri razlichnykh usloviiakh razvitiia zhivotnykh.

Age-related changes in the general activity of creatin kinase (CrK), mitochondrial fraction of this enzyme (CrKmit), general activity of lactate dehydrogenase (LDH) and its anaerobic fractions (LDHan), content and ratio of cytochromes of the mitochondrial respiration chain, respiration rate of isolated mitochondria on various substrates in the 3rd state have been studied in the skeletal muscle of Wistar rats developing under the conditions of normo- (NK) and hypokinesia (HK). General patterns of changes in these indices have been shown, that do not depend on the conditions of animal development: the minimal CrK and CrKmit activity and increased saturation of the respiration chain with cytochrome b562 during the playing period, days 30 to 40 of postnatal period. The highest level of cytochrome aa3 was observed in the peak of sexual maturation (Day 45). However the conditions of development affect the timing of extreme indices and their level in adult animals. For example, in the animals developing under the NK conditions the highest saturation of the respiration chain with cytochrome b562 was observed on Day 30, while in those developing under the HK conditions by five days later. In 30-day old rats from the NK group the cytochrome aa3 content of skeletal muscle was almost maximal, while in the HK group the maximum was observed only at the peak of sexual maturation. In the adult animals of the HK group the activity of CrKmit, LDH and LDHan was higher, while the content of cytochrome aa3 and saturation of the respiration chain with cytochrome b562 was lower. A lesser b562/aa3 ratio is related to the predominance of NADH2-dependent electron transport pathways of oxidation in the mitochondria from the rat skeletal muscle. Thus, the conditions of development in the early postnatal period, especially during the playing period, determine the state of energy metabolism in the adult skeletal muscle.