Reactivity of neurons of the orbito-frontal cortex of the cat during exposure to the scent or sight of food

Reactivity of neurones in orbitofrontal cortex of the cat to the action of light or sound was studied in consecutive stages of alimentary behaviour conditioned by the smell and then the sight of food. Changes were found of the character of neuronal reactions to the light and sound stimuli at the change of smell to the sight of food. A conclusion is drown, that polysensory properties of the neurones of the orbitofrontal cortex provide integral organization of brain sensory function at separate stages of alimentary behaviour.     

In Vivo Quantitative Assessment of Myocardial Structure,Function, Perfusion and Viability Using Cardiac Micro-computed Tomography

The use of Micro-Computed Tomography (MicroCT) for in vivo studies of small animals as models of human disease has risen tremendously due to the fact that MicroCT provides quantitative high-resolution three-dimensional (3D) anatomical data non-destructively and longitudinally. Most importantly, with the development of a novel preclinical iodinated contrast agent called eXIA160, functional and metabolic assessment of the heart became possible. However, prior to the advent of commercial MicroCT scanners equipped with X-ray flat-panel detector technology and easy-to-use cardio-respiratory gating, preclinical studies of cardiovascular disease (CVD) in small animals required a MicroCT technologist with advanced skills, and thus were impractical for widespread implementation. The goal of this work is to provide a practical guide to the use of the high-speed Quantum FX MicroCT system for comprehensive determination of myocardial global and regional function along with assessment of myocardial perfusion, metabolism and viability in healthy mice and in a cardiac ischemia mouse model induced by permanent occlusion of the left anterior descending coronary artery (LAD).     

Direct coronary arterial stenting without predilatation in patients with coronary heart disease

The study was undertaken to evaluate the safety and efficiency of direct stenting versus routine stenting with predilation. It included 133 patients. By the decision of operators, direct stenting was conducted in 66 patients (71 stenoses) (Group 1). The remaining 67 patients (73 stenoses) underwent routine stenting with predilation (Group 2). The initial angiographic success of stenting was 100% in Group 1 and 98 in Group 2. Complications were absent. In the direct stenting group, technical problems occurred during a session in 9 (12%) cases. In this group the mean duration of fluoroscopy and the total duration of a session were much less than in the routine stenting group. The mean number of balloons used at dilation per stenosis and the number of dilation sessions per stenosis were much lower in Group 1 than in Group 2. The results of quantitative angiogram analysis before and after a session were similar in both patient groups. Six months following stenting, angiographic restenosis occurred in 7 (10%) patients in Group 1 and in 9 (12%) in Group 2. Direct stenting is a safe and effective treatment for non-occlusive coronary lesions without marked kinks and calcinosis. Direct stenting reduces the duration of fluoroscopy and the total duration of an operation by 50 and 22%, respectively, as compared to predilation stenting.     

Magnetic resonance tomography in the diagnosis of renovascular hypertension]

MR tomography was used for investigation of 38 patients with renovascular hypertension (RVH) and 26 healthy persons. A possibility of the use and practical value of the method in the diagnosis and evaluation of renal function and renal arteries (RA) were under study. Some quantitative MRT indices were calculated both for the patients and healthy persons. They included spin-spin relaxation time, proton density, and signal intensity. These data can provide important information on renal function in RVH with relation to kidney sizes and the state of the renal parenchyma (evaluation of the cortical substance and medulla and the border between them). In some cases MRT ensures noninvasive diagnosis of PA stenosis.     

Mechanisms of oxidative modification of low density lipoproteins under conditions of oxidative and carbonyl stress

Low-molecular-weight aldehydes (glyoxal, methylglyoxal, 3-deoxyglucosone) generated on autooxidation of glucose under conditions of carbonyl stress react much more actively with amino groups of L-lysine and epsilon-amino groups of lysine residues of apoprotein B-100 in human blood plasma low density lipoproteins (LDL) than their structural analogs (malonic dialdehyde (MDA), 4-hydroxynonenal) resulting on free radical oxidation of lipids under conditions of oxidative stress. Glyoxal-modified LDL aggregate in the incubation medium with a significantly higher rate than LDL modified by MDA, and MDA-modified LDL are markedly more poorly absorbed by cultured human macrophages and significantly more slowly eliminated from the rat bloodstream upon intravenous injection. Studies on kinetics of free radical oxidation of rat liver membrane phospholipids have shown that ubiquinol Q(10) is the most active lipid-soluble natural antioxidant, and suppression of ubiquinol Q(10) biosynthesis by beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors (statins) is accompanied by intensification of lipid peroxidation in rat liver biomembranes and in LDL of human blood plasma. Injection of ubiquinone Q(10) protects the human blood plasma LDL against oxidation and prevents oxidative stress-induced damages to rat myocardium. A unified molecular mechanism of atherogenic action of carbonyl-modified LDL in disorders of lipid and carbohydrate metabolism is discussed.     

Spatial-temporal synchronization of cerebral biopotentials and the problem of the brain's activity as a whole

The author compares the results of his own investigations into the influence of instantaneous and multiple reversible (cold) inactivation of the neocortex on the manifestation and elaboration of conditioned reflexes in cats with dynamic characteristics of spatial-temporal synchronization of biopotentials in the cortex and subcortical formations at different stages of formation and manifestation of the conditioned reflex in animals, and in different functional states (emotions and mental stress) in humans, as presented in the studies by M.N. Livanov and coworkers. It has been stressed that different experimental approaches reveal the one principle of brain functioning, its integral involvement in any purposeful activity.     

Probability analysis of elements of rat behavior after sudden and signalled interruption of food reinforcement

Probability analysis was carried out of the appearance of single elements of rats behaviour in the process of extinction of a conditioned alimentary motor reflex. The dynamics of effector behavioural components at a sudden cessation of reinforcement (usual schedule of extinction) was compared with cessation of reinforcement signalled by a previously differentiated signal and with reinforcement cessation preceded by a stimulus initially unknown to the animal. If the reinforcement cessation is signalled by a previously differentiated (negative) stimulus, in response to its action the animals "loose the aim", what is revealed in a rapid complete reduction of all elements of the goal-directed alimentary behaviour. Obviously differentiation signal actualises the memory trace of "nonreinforcement" which was formed in the previous negative experience of the animal; this is revealed in accelerated inhibition of the alimentary motor reflex under extinction.     

Abdominal Distension and Escherichia coli Peritonitis in Mice Lacking Myeloid Differentiation Factor 88

Here we describe the gross and microscopic findings of naturally occurring, β-hemolytic Escherichia coli peritonitis in B6.129-Myd88^tm1Aki male and female mice. Over approximately 5 mo, 10 homozygous mutant mice deficient in myeloid differentiation factor 88 (C57BL/6 strain; male and female) that had not been used in research protocols developed rapid-onset abdominal swelling associated with copious viscous ascites. Each mouse developed an anterior peritonitis, primarily involving the parietal peritoneum and the visceral surface of the spleen, liver, diaphragm, and stomach. Inflammation was confined to the organ surfaces, with no indication of septicemia or grossly apparent gastrointestinal perforation or other tissue compromise that would initiate peritonitis. Peritonitis was likely attributable to compromised antibacterial innate immunity; cohoused, similarly immunodeficient littermates did not develop similar clinical signs. An unusual finding in all cases was mesothelial cell hyperplasia and hypertrophy. Although the underlying innate immune deficiency accounts for much of the observed pathology, the remarkable mesothelial cell morphology and the episodic nature of the peritonitis in some littermates and not others remain unexplained.Abbreviations: MyD88, myeloid differentiation response 88; TLR, Toll-like receptorMice deficient in myeloid differentiation factor 88 (myD88) are commonly studied in immunologic research as models of various diseases, including inflammatory bowel disease and diabetes.^2,3 MyD88 is a key signal transduction molecule for most of the Toll-like receptors (TLR) and IL1 family receptors, initiating cytokine release essential for effective innate immunity.¹⁸ The loss of this adapter protein impairs production of IL1, IL6, IL18, macrophage inhibitory proteins 1 and 2, and various chemokines.^1,12,14 Knockout mutant mice are especially susceptible to gram-negative bacteria, because TLR4, which triggers signaling through MyD88, mediates responses to LPS.^7,17 These immunologic mutants are common in research animal colonies, but their development of clinical signs and lesions consistent with Escherichia coli peritonitis, which arose at different times and affected only some of the immunodeficient mice, was previously unknown.     

Antioxidants decreases the intensification of low density lipoprotein in vivo peroxidation during therapy with statins

The oxidative modification of low density lipoprotein (LDL) is thought to play an important role in atherogenesis. Drugs of -hydroxy--methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) family are usually used as a very effective lipid-lowering preparations but they simultaneously block biosynthesis of both cholesterol and ubiquinone Q₁₀ (coenzyme Q), which is an intermediate electron carrier in the mitochondrial respiratory chain. It is known that reduced form of ubiquinone Q₁₀ acts in the human LDL as very effective natural antioxidant. Daily per os administration of HMG-CoA reductase inhibitor simvastatin to rats for 30 day had no effect on high-energy phosphates (adenosin triphosphate, creatine phosphate) content in liver but decreased a level of these substances in myocardium. We study the Cu²⁺-mediated susceptibility of human LDL to oxidation and the levels of free radical products of LDL lipoperoxidation in LDL particles from patients with atherosclerosis after 3 months treatment with natural antioxidants vitamin E as well as during 6 months administration of HMG-CoA reductase inhibitors such as pravastatin and cerivastatin in monotherapy and in combination with natural antioxidant ubiquinone Q₁₀ or synthetic antioxidant probucol in a double-blind placebo-controlled trials. The 3 months of natural antioxidant vitamin E administration (400 mg daily) to patients did not increase the susceptibility of LDL to oxidation. On the other hand, synthetic antioxidant probucol during long-time period of treatment (3–6 months) in low-dose (250 mg daily) doesn't change the lipid metabolism parameters in the blood of patients but their high antioxidant activity was observed. Really, after oxidation of probucol-contained LDL by C-15 animal lipoxygenase in these particles we identified the electron spin resonance signal of probucol phenoxyl radical that suggests the interaction of LDL-associated probucol with lipid radicals in vivo. We observed that 6 months treatment of patients with pravastatine (40 mg daily) or cerivastatin (0.4 mg daily) was followed by sufficiently accumulation of LDL lipoperoxides in vivo. In contrast, the 6 months therapy with pravastatin in combination with ubiquinone Q₁₀ (60 mg daily) sharply decreased the LDL initial lipoperoxides level whereas during treatment with cerivastatin in combination with probucol (250 mg daily) the LDL lipoperoxides concentration was maintained on an invariable level. Therefore, antioxidants may be very effective in the prevention of atherogenic oxidative modification of LDL during HMG-CoA reductase inhibitors therapy.