Energetic depression caused by mitochondrial dysfunction

Mitochondria not only provide most of the ATP needed for cell work and numerous specific anabolic and catabolic functions, they also contribute to Ca++ signalling and play a key role in the pathway to cell death. Impairment of mitochondrial functions caused by mutations of the mt-genome or by acute processes, is responsible for numerous diseases. Decreased concentrations of adenine nucleotides, leaky outer and inner mitochondrial membranes, and decreased activities of respiratory chain enzymes contribute to depression of cellular energy metabolism, one of the most important consequences of mitochondrial impairment as characterized by decreased cytosolic phosphorylation potentials.     

Energetic depression caused by mitochondrial dysfunction

Mitochondria, providing most of ATP needed for cell work, realizing numerous specific functions as biosyntheses or degradations, contributing to Ca2+ signalling also play a key role in the pathways to cell death. Impairment of mitochondrial functions caused by mutations of mt-genome and by acute processes are responsible for numerous diseases. The relations between changes on the level of molecules and the clinical state are rather complex, and the prediction of thresholds is difficult. Therefore investigations on different levels of an organismus (genome, metabolites, enzymes, mitochondrial function in vivo and in vitro) are necessary (multi level approach). Metabolic control theory is a valuable tool for understanding the different effects of mutations on the level of enzyme activities and mitochondrial function. Decreased concentrations of adenine nucleotides, leaky outer and inner mitochondrial membranes, decreased rates of mitochondrial linked pathways and decreased activities of respiratory chain enzymes contribute to depression of cellular energy metabolism characterized by decreased cytosolic phosphorylation potentials as one of the most important consequences of mitochondrial impairments. This review regards classical bioenergetic mechanisms of mitochondrial impairment which contribute to energetic depression.     

慢性温和应激抑郁模型大鼠5-羟色胺、色氨酸和应激激素的变化

目的：通过观察慢性温和应激对大鼠行为及5-羟色胺、色氨酸、应激激素的影响,进一步阐明应激致抑郁发生的机制。方法：利用慢性不可预计温和应激（CUMS）结合行为学指标建立大鼠抑郁动物模型;高效液相检测血浆和脑5-HT、儿荼酚胺;放免方法检测血浆皮质醇换算成皮质酮含量;氨基酸分析仪检测血清色氨酸的含量。结果：①CUMS诱导8周大鼠糖水偏爱性与对照组相比明显减低（P〈0．05）;体重和旷场实验评分下降（P〈0．05）。②CUMS诱导8周大鼠大脑和血浆5-HT含量显著下降（P〈0．05）;而血清色氨酸含量与对照组相比则明显升高（P〈0．05）。③CUMS诱导8周大鼠血浆去甲肾上腺素和肾上腺素含量与对照组相比明显升高（P〈0．05）：血浆皮质酮含量与对照组相比统计学上无显著性差异（P〉0．05）。结论：利用CUMS建立的抑郁模型大鼠存在着神经内分泌紊乱,CUMS大鼠抑郁样行为的发生可能与血浆去甲肾上腺素和肾上腺素升高对色氨酸代谢的影响有关。     

Time-dependent oxidative stress caused by benznidazole

Abstract

Benznidazole (BZN) is a nitroimidazole derivative which has a notable trypanocide activity, and it is the only drug used in Brazil and Argentina for the treatment of Chagas' disease. The drug in current use is thought to act, at least in part, by inducing oxidative stress within the parasite. Imidazolic compounds are involved in the production of reactive oxygen species (ROS). In order to evaluate the effect of BZN on ROS production and on the antioxidant status of the host, male rats were treated for different periods of time (2, 4, 6, 10 and 30 days) with 40 mg BZN/kg body weight. After treatment, biomarkers of oxidative stress such as the activities of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione reductase (GR), and also thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH), total glutathione (TG) and oxidized glutathione (GSSG) concentrations, were measured in crude hepatic homogenates. Our results revealed that BZN is able to cause tissue damage as shown by increased TBARS content, inhibition of some antioxidants and induction of other antioxidants in a concentration- and time-dependent manner. The tissue damage measured as TBARS increased up to the 10th day of treatment. GST activity was inhibited during the BZN treatment. On the other hand, CAT and GR showed similar increased activities at the beginning, followed by decreased activities at the end of the treatment. After 30 days of treatment, GR activity remained low while CAT activity was high, compared to controls. The SOD activities remained unchanged throughout the experimental period. GSH showed lower values at the beginning of BZN treatment but the hepatic concentrations were enhanced at the end of the experimental period. Total glutathione showed a similar profile, and oxidized glutathione showed higher values in rats treated with BZN. In conclusion, these results indicate that, at therapeutic doses, BZN treatment elicits an oxidative stress in rat hepatocytes.     

Time-dependent oxidative stress caused by benznidazole

Benznidazole (BZN) is a nitroimidazole derivative which has a notable trypanocide activity, and it is the only drug used in Brazil and Argentina for the treatment of Chagas' disease. The drug in current use is thought to act, at least in part, by inducing oxidative stress within the parasite. Imidazolic compounds are involved in the production of reactive oxygen species (ROS). In order to evaluate the effect of BZN on ROS production and on the antioxidant status of the host, male rats were treated for different periods of time (2, 4, 6, 10 and 30 days) with 40 mg BZN/kg body weight. After treatment, biomarkers of oxidative stress such as the activities of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione reductase (GR), and also thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH), total glutathione (TG) and oxidized glutathione (GSSG) concentrations, were measured in crude hepatic homogenates. Our results revealed that BZN is able to cause tissue damage as shown by increased TBARS content, inhibition of some antioxidants and induction of other antioxidants in a concentration- and time-dependent manner. The tissue damage measured as TBARS increased up to the 10th day of treatment. GST activity was inhibited during the BZN treatment. On the other hand, CAT and GR showed similar increased activities at the beginning, followed by decreased activities at the end of the treatment. After 30 days of treatment, GR activity remained low while CAT activity was high, compared to controls. The SOD activities remained unchanged throughout the experimental period. GSH showed lower values at the beginning of BZN treatment but the hepatic concentrations were enhanced at the end of the experimental period. Total glutathione showed a similar profile, and oxidized glutathione showed higher values in rats treated with BZN. In conclusion, these results indicate that, at therapeutic doses, BZN treatment elicits an oxidative stress in rat hepatocytes.     

应激诱发抑郁症机制的研究进展

慢性应激或长期使用外源性应激激素糖皮质类固醇,可以引起机体神经系统功能失调,诱导抑郁、学习和记忆障碍、衰老过程加速等。其中,应激激素对海马的选择性损伤是导致这些疾患发展的关键原因。其表现为海马出现糖皮质激素（GC）受体下调、神经元萎缩甚至缺失等退行性变化。其机制可能与GC及继发性释放的兴奋性氨基酸（EAAs)协同作用,最终使神经营养因子（如NGF）表达低下有关。本文就慢性应激诱发抑郁症机制的研究进展进行综述。     

Experimental infection caused by Issyk-Kul' arbovirus

Experimentally in green monkeys, Syrian hamsters and white mice the authors studied the pathogenic properties of a new virus Issyk-Kul. The virus was determined in all animals--in blood and organs (brain, lungs, liver, spleen, kidneys). During the histological investigation the inflammatory and dystrophic injuries were established: in CNS, lungs, liver and kidneys. There was a distinct immunomorphological reaction in the spleen. The virus has pantropic properties and causes a generalized infection in animals.     

Experimental study of microorganism disruption using shear stress

There has been a broad spectrum of theoretical and experimental works on microorganism disruption methods undertaken in the past. However, there is a lack of understanding regarding the actual reasons for microorganism disruption using ultrasound and whether it is caused by shock or shear. In the case of shear stress, which is the focus of this paper, analysis of the intense turbulent flow region of an in-house built shear apparatus combined with the experimental results demonstrated that when the energy dissipation rate in the turbulence region is high, and the size of the eddy is smaller than the size of the cell, the likelihood of yeast disruption is high. The mechanical properties of yeast cells combined with the calculated energy dissipation rate were used to evaluate the yeast disruption efficiency (log reduction). The results show that the shear apparatus can efficiently and effectively disrupt S. cerevisiae at different treatment times, suspension temperatures and rotor speeds. The experimental work suggests that maximum yeast log reduction was achieved when the maximum power dissipation of 2.095 kW was recorded at 10,000 RPM, while suspension temperature was controlled below 35 °C. The corresponding shear stress at 10,000 RPM was 2586.2 Pa.     

A new model of depression induced by psychogenenic stress

A new depression model has been obtained, based on use of stressors of the psychogenic nature. The laboratory rats in a special stress-camera turned out to be unable to induce the bilateral reaction of active avoidance, with subsequently led to formation of depression in the animals. Analysis of the tests sensitive to depression--a forceful swimming and a hanging by tail as well as of dynamics of the animals' body mass and of the behavior on the whole confirms development of their depression. This model has turned out to be sensitive to a selective inhibitor of the serotonin reuptake--fluoxetine; this also indicates our obtained model to be a model of depression.     

A new model of depression induced by psychogenic stress

A new model of depression based on use of stressors of the psychogenic nature has been created. It turned out that laboratory rats in a special stress-camera were unable to elaborate bilateral reaction of active avoidance, which later on led to formation of their depression-like state. Development of such their state was confirmed by analysis of tests sensitive to depression: forced swimming and tail suspension, dynamics of the animal body mass and their behavior on the whole. This model has turned out to be sensitive to a selective inhibitor of the serotonin uptake??fluoxetine, which also confirms that our obtained model is the model of depression.     

Anxiety in females caused by long-term psycho-emotional stress

Behaviour of female mice was studied under long-lasting psychoemotional influence. Daily presence of females during inter-male confrontations through a perforated transparent partition in the same cage and the next female placing on the male territory (sawdust) after the confrontations, were included as the influencing factors. Under these conditions, the increased level of anxiety in the females was revealed in the elevated plus-maze test. At the same time, the females demonstrated a more passive behaviour in the Porsol test. The psycho-emotional influence also affected the females' behaviour in the partition test. The females spent a significantly longer time near the partition both 5 minutes prior to and during the inter-male confrontations.