The Neurotoxic Effect of ß-Amyloid Is Accompanied by Changes in the Mitochondrial Dynamics and Autophagy in Neurons and Brain Endothelial Cells in the Experimental Model of Alzheimer's Disease.

A comparative assessment of the expression of the mitochondrial fission marker Drp1 and the autophagy marker LC3 in neurons and endothelial cells in the hippocampus and entorhinal cortex during progression of cognitive deficit was performed in animals with intrahippocampal administration of ß-amyloid. In both brain regions, the expression of Drp1 and LC3 in neuronal and endothelial cells was enhanced. The peak of cognitive impairment corresponded to the maximum expression of Drp1 and LC3 in hippocampal neurons and was preceded by an increase in the number of Drp1+ and LC3+ endothelial cells in this brain region. These data attests to a possible role of aberrant mitochondrial dynamics and autophagy of endothelial cells in the impairment of brain plasticity in the Alzheimer's type neurodegeneration.

SkQR1 Reduces Neurologic Deficit Caused by Rat Brain Compression Ischemia.

The protective effect of antioxidant SkQR1 was examined on the model of left-sided compression ischemia in rat sensorimotor cortex. The special tests aimed to determine the neurologic deficit in the limbs and assess performance of the forelimbs showed that a 2.5-min ischemia produced no disturbance in the limb functions on postsurgery days 1, 3, and 7. Elevation of compression time resulted in neurologic deficit in animals, and its severity depended on this time. A single intravenous injection of SkQR1 (250 nmol/kg body weight) performed 30 min after ischemia significantly reduced the degree of neurologic deficit. In vitro model of ischemia in surviving rat hippocampal slices showed that a 15-min-long ischemia significantly inhibited the population excitatory postsynaptic potentials, which did not restore during reperfusion. Preincubation of the slices with SkQR1 did not significantly affect recovery of these potentials.

GK-2 Reduces Death of Cultured Granule Neurons in Cerebellum Induced by the Toxic Effects of Zinc Ions.

Peptide mimetic of nerve growth factor GK-2 in a dose of 1-2 mg/liter improves survival of cultured rat cerebellar granule neurons exposed to the cytotoxic effect of zinc ions, but has no protective effect against copper ion cytotoxicity. Experiments on cultured rat hippocampal slices demonstrated that GK-2 did not affect reactivity of pyramidal neurons and long-term potentiation in the hippocampal field CA1 and the probability of glutamate release from presynaptic terminals in the synapses of the CA3-CA1 fields. The results suggest that GK-2 does not affect the functional properties of synaptic transmission under normal conditions, but protects neurons from the toxic effects of zinc, which creates prerequisites for GK-12 use in the treatment of neurodegenerative diseases.

[Why Is It So Important to Invest into Breast-Feeding and How to Ameliorate Its Practice?]

Nowadays, the breast-feeding, despite the approved advantages, is not a standard in many communities. The multi-factorial determinants determining its prevalence need to be supported at various levels - from legal and legislative one to views and values of society, conditions of women's labor and also health care system that can develop a favorable environment for breast-feeding. The breast-feeding effects positively on health, economic development and ecology and therefor it is a benefit for children, women and whole society in short-term and long-term perspective. The defense, propaganda and support of breast-feeding need a political will, and financial investments to implement its advantages.

Acidosis and 5-(N-ethyl-N-isopropyl)amiloride (EIPA) Attenuate Zinc/Kainate Toxicity in Cultured Cerebellar Granule Neurons.

Cultured cerebellar granule neurons (CGNs) are resistant to the toxic effect of ZnCl2 (0.005 mM, 3 h) and slightly sensitive to the effect of kainate (0.1 mM, 3 h). Simultaneous treatment of CGNs with kainate and ZnCl2 caused intensive neuronal death, which was attenuated by external acidosis (pH 6.5) or 5-(N-ethyl-N-isopropyl)amiloride (EIPA, Na+/H+ exchange blocker, 0.03 mM). Intracellular zinc and calcium ion concentrations ([Zn2+]i and [Ca2+]i) were increased under the toxic action of kainate + ZnCl2, this effect being significantly decreased on external acidosis and increased in case of EIPA addition. Neuronal Zn2+ imaging demonstrated that EIPA increases the cytosolic concentration of free Zn2+ on incubation in Zn2+-containing solution. These data imply that acidosis reduces ZnCl2/kainate toxic effects by decreasing Zn2+ entry into neurons, and EIPA prevents zinc stores from being overloaded with zinc.

[The effect of viral infections on the cytokine profile in pregnant women with obstetric complications and immunotherapy with human alpha2b interferon].

The goal of this work was to examine the effects of infections caused by HSV1/2, CMV, and HPV on the cytokine profile in pregnant women with obstetric complications (OC) and to evaluate the efficacy of the therapy with recombinant human alpha2b interferon. Direct markers of the viruses were identified using PCR and rapid culture method in 85 pregnant women divided into 3 groups: group 1 (n = 21), women with visual HPV-related clinical manifestations; group 2 (n = 48), with detectable markers of viral infections and no clinical manifestations, and group 3 consisting of pregnant women with OC without markers and clinical manifestations of viral infections (n = 16). The rate of HPV DNA detection in pregnant women was higher than that of herpesviruses (HV) CMV and/ or HSV: 37.6% vs. 11.8%. The frequency of mixed HV/HPV infection in group 1 was 2.3-fold higher than in group 2. The cytokine levels of IFNalpha, IFNgamma, IL-4, IL-6, IL-8, and TNFalpha in blood plasma and vaginal washings were studied. Statistically significant differences in infected women (groups 1 and 2) in comparison with uninfected women (group 3) were detected: a) blood plasma concentration of IFNgamma increased in clinically manifested HPV infection; b) blood plasma IL-8 concentration increased in clinically manifested HPV and in mixed HV+HPV infections without clinical symptoms of HPV infection; c) blood plasma concentration of TNFalpha increased in women with asymptomatic HPV-infection; d) IL-6 concentration in vaginal washings increased in mixed infection in group 1. The effect of IFN-alpha2b was assessed by analyzing cytokine levels in women on basic therapy with and without Viferon. In infected women, Viferon caused a 2-3-fold decrease in the concentrations of IFNgamma and IL-8 in blood plasma, thus bringing them near those of uninfected women with OC. The analysis of the state of newborns health has shown that for women with OC the risk of giving birth to a child in critical condition is 4.3-fold higher when CMV is detected in the third trimester of pregnancy.

Mitochondria-targeted plastoquinone antioxidant SkQR1 decreases trauma-induced neurological deficit in rat.

A protective effect of a mitochondria-targeted antioxidant, a cationic rhodamine derivative linked to a plastoquinone molecule (10-(6'-plastoquinonyl)decylrhodamine-19, SkQR1) was studied in the model of open focal trauma of rat brain sensorimotor cortex. It was found that daily intraperitoneal injections of SkQR1 (100 nmol/kg) for 4 days after the trauma improved performance in a test characterizing neurological deficit and decreased the volume of the damaged cortical area. Our results suggest that SkQR1 exhibits profound neuroprotective effect, which may be explained by its antioxidative activity.

[Neuroprotective effect of recombinant human erythropoietin-loaded poly(lactic-co-glycolic) acid nanoparticles in rats with intracerebral posttraumatic hematoma].

The neuroprotective activity of recombinant human erythropoietin (rhEPO) loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been observed in rats with model intracerebral post-traumatic hematoma (hemorrhagic stroke). It is established that rhEPO-loaded PLGA nanoparticles produce a neuroprotective effect in rats with hemorrhagic stroke, which is manifested by reduced number of lethal outcomes and animals with neurological disorders. Treatment with rhEPO-loaded PLGA prevented amnesia of passive avoidance reflex (PAR), which was produced by the hemorrhagic stroke, and reduced the area of brain damage caused by the intracerebral hematoma. These effects were recorded during one-week observation period. Native rhEPO exhibited a similar, but much less pronounced effect on the major disorders caused by the model hemorrhagic stroke in rats.

Glutamine effect on cultured granule neuron death induced by glucose deprivation and chemical hypoxia.

Using a specific fluorescent probe of mitochondrial membrane potential (tetramethylrhodamine ethyl ester), we have shown that glucose deprivation (GD) of cultured cerebellar granule neurons (CGN) for 3 h lowers mitochondrial membrane potential in these cells. Longer glucose starvation (24 h) causes CGN death that is not prevented by blockers of ionotropic glutamate receptors (MK-801 (10 µM) and NBQX (10 µM)). Glutamine or pyruvate (2 mM) maintain membrane potential of mitochondria and decrease CGN death under GD conditions. In the presence of glucose the mitochondrial respiratory chain blocker rotenone induces neuron death potentiated by glutamine. The potentiation effect is completely prevented by blockers of ionotropic glutamate receptors. These results show that glutamine under conditions of GD can be utilized by mitochondria as substrate, but at the same time, in the case of mitochondrial function deterioration, metabolism of this amino acid results in glutamate accumulation to toxic level.

Glutamine-mediated protection from neuronal cell death depends on mitochondrial activity.

The specific aim of this study was to elucidate the role of mitochondria in a neuronal death caused by different metabolic effectors and possible role of intracellular calcium ions ([Ca(2+)](i)) and glutamine in mitochondria- and non-mitochondria-mediated cell death. Inhibition of mitochondrial complex I by rotenone was found to cause intensive death of cultured cerebellar granule neurons (CGNs) that was preceded by an increase in intracellular calcium concentration ([Ca(2+)](i)). The neuronal death induced by rotenone was significantly potentiated by glutamine. In addition, inhibition of Na/K-ATPase by ouabain also caused [Ca(2+)](i) increase, but it induced neuronal cell death only in the absence of glucose. Treatment with glutamine prevented the toxic effect of ouabain and decreased [Ca(2+)](i). Blockade of ionotropic glutamate receptors prevented neuronal death and significantly decreased [Ca(2+)](i), demonstrating that toxicity of rotenone and ouabain was at least partially mediated by activation of these receptors. Activation of glutamate receptors by NMDA increased [Ca(2+)](i) and decreased mitochondrial membrane potential leading to markedly decreased neuronal survival under glucose deprivation. Glutamine treatment under these conditions prevented cell death and significantly decreased the disturbances of [Ca(2+)](i) and changes in mitochondrial membrane potential caused by NMDA during hypoglycemia. Our results indicate that glutamine stimulates glutamate-dependent neuronal damage when mitochondrial respiration is impaired. However, when mitochondria are functionally active, glutamine can be used by mitochondria as an alternative substrate to maintain cellular energy levels and promote cell survival.

[Vibrophoresis of mud lipid extract in the rehabilitation of patients with osteoarthrosis]. / Vibroforez ékstrakta lipidov griazi v vosstanovitel'nom lechenii bol'nykh osteoartrozom.

Experimental and clinical evidence (76 patients with osteoarthrosis) justifies combined use of thermovibration massage and lipid extract from therapeutic mud eplir. This combination produces analgetic, antiedematic, antiinflammatory actions and promotes normalization of systemic immunity and peripheral hemodynamics.

[Results of peripheral densitometry in a population of postmenopausal women]. / Rezul'taty perifericheskoi densitometrii pri populiatsionnom obsledovanii zhenshchin v postmenopauze.

Osteodensity was compared in 582 postmenopausal patients with such pathologies as urogenital atrophy, osteoporosis, vulvar craurosis, breast carcinoma, hyperplasia and endometrial carcinoma. A double-photon Z-ray densitometer with a computer program designed for postmenopausal women examination was employed. It was shown that osteodensity measurements can distinguish two opposite patterns of homeostasis in postmenopause: involute-atrophic vs. hyperplastic processes in target tissues characterized by high oncological susceptibility. However, if strict and clear distinctions are applied, many patterns of pathology combination so typical of postmenopause will stay outside the classification. Much in further studies of the problem will depend on progress made in investigation of estrogen receptors in target tissues.

[Experimental validation of the administration into the body of the lipids from therapeutic muds by means of vibration]. / Eksperimental'noe obosnovanie vvedeniia lipidov lechebnykh griazei v organizm s pomoshch'iu vibratsii.

Infrared and ultraviolet spectroscopy were used to study the ability of therapeutic mud lipids to penetrate through the animal skin when compress or vibration were used. Vibrophoresis appeared to be 1.5-fold more effective compared to compress in improving skin permeability. It promotes entering the body for biologically active compounds containing heteroatoms: oxygen, nitrogen, sulfur, phosphorus, high-molecular acids, spirits, ethers, chlorophils, sulpho- and phospholipids.

[Possibility of predicting intrauterine fetal growth retardation by a single ultrasonic examination (using varying standards)]. / Vozmozhnost' prognozirovaniia zaderzhki vnutriutrobnogo razvitiia ploda po odnokratnomu ul'trazvukovomu issledovaniiu (s ispol'zovaniem skol'ziashchikh normativov).

The paper deals with early prediction of fetal growth retardation and its severity in a newborn from single ultrasound fetal biometric findings (biparietal head size, chest and belly diameters) at week 20 of pregnancy. The prediction was made by employing the developed varying standards for these parameters as percentile curves and tables. A stepwise prediction of fetal growth retardation was proposed for obstetric in- and outpatient settings, which was presented as an IBM personal computer dialogue program. The positive diagnostic value of fetal growth retardation prediction was found to be 69.7%, its negative value was 86.9%. The paper discusses whether therapeutic measures and pregnancy length affect the efficiency of its prediction and stresses that the prediction is valuable for individual well-grounded tactics for pregnancy management.