Study of Anti-Ischemic Effect of Afobazole in Experimental Myocardial Infarction

Seven-day treatment of rats with experimental myocardial infarction with afobazole (5-ethoxy-2-[2-morpholino)-ethylthio] benzimidasole dihydrochloride) resulted in shrinkage of the ischemic damage area in the heart, stimulation of reparative processes in the myocardium, and prevention of postinfarction remodeling of the left ventricle. Anti-ischemic effect of afobazole in experimental myocardial infarction is presumably due to its interactions with σ₁ receptors.     

Model of electrical conductivity of skeletal muscle based on tissue structure

Recent experiments carried out in our laboratory with the four-electrode method showed that the electrical conductivity of skeletal muscle tissue depends on the frequency of the injected current and the distance between the current electrodes. A model is proposed in order to study these effects. The model takes into account the structure of the tissue on the scale of individual fibres. It discerns three main components with respect to electrical properties: (a) extracellular medium with electrical conductivity σ_e; (b) intracellular medium with electrical conductivity σ_i; (c) muscle fibre membrane with impedance Z_m. The model results show an apparent frequency dependence of the electrical conductivity of skeletal muscle tissue, as well as the way the conductivity is affected by the length the current is conducted.     

Wavelet-based statistical approach for speckle reduction in medical ultrasound images

A novel speckle-reduction method is introduced, based on soft thresholding of the wavelet coefficients of a logarithmically transformed medical ultrasound image. The method is based on the generalised Gaussian distributed (GGD) modelling of sub-band coefficients. The method used was a variant of the recently published BayesShrink method by Chang and Vetterli, derived in the Bayesian framework for denoising natural images. It was scale adaptive, because the parameters required for estimating the threshold depend on scale and sub-band data. The threshold was computed by Kσ/σ_x, where σ and σ_x were the standard deviation of the noise and the sub-band data of the noise-free image, respectively, and K was a scale parameter. Experimental results showed that the proposed method outperformed the median filter and the homomorphic Wiener filter by 29% in terms of the coefficient of correlation and 4% in terms of the edge preservation parameter. The numerical values of these quantitative parameters indicated the good feature preservation performance of the algorithm, as desired for better diagnosis in medical image processing.     

Effect of afobazole on teratogenic activity of cyclophosphamide in rats

A new anxiolytic afobazole (1–100 mg/kg perorally, Russia) dose-dependently abolished the embryotoxic and teratogenic effects of cyclophosphamide and reduced the range of induced malformations in outbred albino rats. Our results suggest that afobazole possesses antiteratogenic activity. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 4, pp. 414–417, April, 2008     

Real-time extraction of tissue impedance model parameters for electrical impedance spectrometer

This paper presents a new algorithm for real-time extraction of tissue electrical impedance model parameters from in vivo electrical impedance spectroscopic measurements. This algorithm was developed as a part of a system for muscle tissue ischemia measurements using electrical impedance spectroscopy. An iterative least square fitting method, biased with a priori knowledge of the impedance model was developed. It simultaneously uses both the real and imaginary impedance spectra to calculate tissue parameters R₀, R_∞, α and τ. The algorithm was tested with simulated data, and during real-time in vivo ischemia experiments. Experimental results were achieved with standard deviations of , σ_α=0.72%, and σ_τ=1.26%. On a Pentium II based PC, the algorithm converges to within 0.1% of the results in 17 ms. The results show that the algorithm possesses excellent parameter extraction capabilities, repeatability, speed and noise rejection.     

Neuroprotective effect of afobazole on rats with bilateral local photothrombosis of vessels in the prefrontal cortex

We studied the neuroprotective effect of a new selective anxiolytic afobazole on rats with bilateral focal ischemic stroke in the prefrontal cortex caused by photothrombosis. Intraperitoneal injection of 5 mg/kg afobazole 1 h after surgery and over the next 8 days (daily treatment) produced a neuroprotective effect. Afobazole was far superior to the reference cerebroprotective drug cavinton (4 mg/kg) by neuroprotective activity. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 2, pp. 167–169, February, 2008     

Effects of electrical stimulation of the tooth pulp and phrenic nerve fibers on C1 spinal neurons in the rat

 Effects of electrical stimulation of the ipsilateral tooth pulp (TP) on C₁ spinal neurons were determined in 33 anesthetized rats. One hundred and seven neurons responded to TP stimulation. In 10 rats, the activity of 18 C₁ spinal neurons and the amplitude of a digastric electromyogram (dEMG, n=10) increased proportionally during the TP stimulation at an intensity of 1–3 times the threshold for jaw-opening reflex (JOR). Excitatory receptive somatic fields were examined in 61 neurons. Somatic field locations of many neurons (67.2%) involved the ipsilateral face, neck, and jaw. The activity of 45 neurons was increased by both noxious pinch and brushing hair. Of the 107 C₁ spinal neurons responding to TP stimulation, 55 were tested to determine the effects of electrical stimulation of the ipsilateral phrenic nerve (PN) above the heart. Twenty-eight of 55 neurons tested were excited; no change in activity was seen for the remaining 27 neurons. The activity of six neurons increased as the intensity of PN stimulation was increased. Excitatory receptive somatic fields were determined in 28 neurons, and somatic field locations of 17 neurons (60.7%) included the ipsilateral face, neck, and jaw. Both noxious pinch and brushing hair excited all 28 neurons. These results suggest that there may be the convergence of face, neck, jaw, TP, and PN afferents on the same C₁ spinal neurons in the rat. Received: 23 June 1998 / Accepted: 11 December 1998     

Effect of befol on the electric threshold of ventricular fibrillation

Befol (20 mg/kg) rises electric threshold of ventricular fibrillation in cats. This effect is most pronounced in ischemized myocardium. It is shown that not only tricyclic but also monocyclic antidepressants exhibit antifibrillatory activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 3, pp. 305–307, March, 1997     

Ex vivo biomechanical behavior of abdominal aortic aneurysm: Assessment using a new mathematical model

Knowledge of the biomechanical behavior of abdominal aortic aneurysm (AAA) as compared to nonaneurysmal aorta may provide information on the natural history of this disease. We have performed uniaxial tensile testing of excised human aneurysmal and nonaneurysmal abdominal aortic specimens. A new mathematical model that conforms to the fibrous structure of the vascular tissue was used to quantify the measured elastic response. We determined for each specimen the yield σ_y and ultimate σ_u strengths, the separate contribution to total tissue stiffness by elastin (E _E) and collagen (E _C) fibers, and a collagen recruitment parameter (A), which is a measure of the tortuosity of the collagen fibers. There was no significant difference in any of these mechanical properties between longitudinal and circumferential AAA specimens, nor inE _E andE _C between longitudinally oriented aneurysmal and normal specimens.A, σ_y, and σ_u were all significantly higher for the normal than for the aneurysmal group:A=0.223±0.046versus A=0.091±0.009 (mean ± SEM;p<0.0005), σ_y versus σ_y (p<0.05), and σ_u versus σ_u (p<0.0005), respectively. Our findings suggest that the AAA tissue is isotropic with respect to these mechanical properties. The observed difference inA between aneurysmal and normal aorta may be due to the complete recruitment and loading of collagen fibers at lower extensions in the former. Our data indicate that AAA rupture may be related to a reduction in tensile strength and that the biomechanical properties of AAA should be considered in assessing the severity of an individual aneurysm.     

Effect of KLN-93 on ventricular fibrillation induced by reperfusion and electrical stimulation in cats

In experiments devoted to modeling of reperfusion ventricular fibrillation and determination of the electric threshold of fibrillation, a protective effect of KLN-93 (a para-aminobenzoic acid ester derivative) is compared with that of lidocaine. It is shown that KLN-93 in doses stopping reperfusion fibrillation is 2-4-fold less toxic than the isoeffective doses of lidocaine. In a dose of 0,4 mg/kg (2.5% LD₅₀) KLN-93 increases the fibrillation threshold 4.5-fold, while isotoxic dose of lidocaine increases this parameters apparoximately 2-fold. These data suggest that KLN-93 is an effective antifibrillatory agent. Translated fromByulleten' Eksperimental'noi i Meditsiny, Vol. 124, No. 8, pp. 135–137, August, 1997     

Opioid receptors and heart resistance to arrhythmogenic factors

We present detailed data on the role of central and peripheral opioid receptors in the regulation of heart resistance to arrhythmogenic factors. Stimulation of peripheral δ₂- and κ₁-receptors increases heart resistance to the arrhythmogenic effect of acute ischemia and reperfusion. Activation of peripheral μ- and δ₁-opioid receptors improves electrical stability of the heart in animals with postinfarction cardiosclerosis. Possible mechanisms for opioidergic regulation of heart resistance to arrhythmogenic factors are discussed. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 8, pp. 124–131, August, 2004 This work was supported by the Russian Foundation for Basic Research.     

Conductivity and geometrical factors affecting volume measurements with an impedancimetric catheter

With a model based on Poisson’s equation, computations employing published data and measurements made in glass cylinders filled with saline, the influence of conductivity and geometry on the determination of volume was analysed with an impedancimetric catheter. Two distal electrodes inject a constant current while a set of central electrodes sense by sections the potential along the cylindrical chamber. It was concluded that each section ought to be independently calibrated, the distribution of the electrodes along the catheter and its relationship to the chamber radius being of paramount importance for a linear calibration. The ratio σ _r , of the external medium conductivity σ _e to the internal conductivity σ _i influences drastically both the linearity and the calibration of each section. If a section volume is linearly related to the total chamber volume, that section admittance is a total volume estimator.     

Antimutagenic activity of afobazole in various regimens of treatment

The influence of a new 2-mercaptobenzimidazole derivative afobazole on cytogenetic effects of dioxidine and cyclophosphamide was studied by counting chromosome aberrations in bone marrow cells of C57B1/6 mice. Afobazole (1–100 mg/kg perorally) exhibited antimutagenic activity determined by its antioxidant properties. This activity depended on the dose and treatment shedule. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 11, pp. 539–542, November, 2000     

Regulation of pancreatic β-cell electrical activity and insulin release by physiological amino acid concentrations

 The mutual enhancement of insulin release by glucose and amino acids is not clearly understood. In this study, the effects on electrical activity and insulin release of a mixture of amino acids and glucose at concentrations found in fed (aa_FD) and fasted (aa_FT) animals were determined using freshly isolated mouse islets. Islets perifused with aa_FD mixture showed an oscillatory pattern of electrical activity at lower glucose concentrations (5 mmol/l) than in islets perifused with the aa_FT mixture and with glucose (G) alone (10 mmol/l). The concentration/response curve for the fraction of time spent by the membrane potential in the active phase in aa_FD-stimulated islets was found to be significantly shifted to the left and had a smaller slope than that for glucose-stimulated islets. Insulin release followed the same pattern. This resulted in a concentration/response curve for glucose that was closer to that recorded ”in vivo”. We have also found that four amino acids (leucine, isoleucine, alanine and arginine) are largely responsible for the observed effects and that there is a non-linear enhancement of insulin release as a consequence of the combined effect of amino acids and glucose. This effect was more pronounced in the second phase of insulin release and was dependent on intracellular Ca²⁺. These findings indicate that amino acids account for most of the leftward shift in the concentration/response curve for glucose and that a reduction in the threshold for the glucose-induced oscillatory electrical activity response and in the generation of Ca²⁺ spikes accounts for the triggering of insulin release at lower glucose concentrations. Nevertheless, the effects on insulin release at high glucose concentrations cannot be explained solely by the increase in glucose-induced electrical activity. Received: 4 November 1996 / Received after revision and accepted: 3 January 1997     

Excretion of afobazole and its metabolites with urine and feces in rats

The amount of afobazole and identified metabolites was measured in the urine and feces of rats after intraperitoneal and peroral administration of the drug in a dose of 25 mg/kg. Over 1 day after intraperitoneal or peroral treatment with afobazole, urine and feces contained 0.1% initial compound (from administered dose) and 42.1% metabolites. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 4, pp. 418–420, April, 2008     

Effect of suphan, lidocaine, and their combination on early occlusion and reperfusion arrhythmias in cats

It is shown that the nonglycoside cardiotonic drug suphan exhibits antiarrhythmic and antifibrillatory activity, although less pronounced than that of lidocaine. When lidocaine was administered after suphan, the antifibrillatory effects of both preparations increased. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 5, pp. 545–547, May, 1997     

Effect of intracellular anisotropy on electrical source determination in a muscle fibre

Expressions are available for describing, quantitatively, the source associated with an action potential propagating along an excitatble fibre. For a nerve fibre one such expression defines an equivalent volume dipole density function τ(x) = − ∂/∂x (σ_i φ_i(x) − σ_e φ_e(x))a_x (where x is the axial co-ordinate, i is the intracellular and e the extracellular region, σ_i and σ_e are isotropic conductivities, ϕ the potential at the membrane, while axial symmetry is assumed), and this source fills the intracellular region. This source, as distinct from transmembrane current formulations, lies in a uniform, isotropic, extracellular, medium. Consequently, for a fibre bundle a simple superposition of sources, all lying in a uniform, isotropic, extracellular space, can be accomplished. However, for muscle fibres the presence of non-conducting myofibrils causes the intracellular space to be anisotropic. The paper describes the modification in the aforementioned expressions for the case of longitudinal and transverse propagation and extrapolation to an arbitrary angle of propagation. The resultant source continues to be expressed relative to a uniform, isotropic, extracellular medium.     

Effects of Afobazole on Cognitive Behavior of the Offspring of Rats Exposed to Tobacco Smoke during Gestation Period

Experiments on the model of foraging behavior formation under conditions of free choice (T-maze) revealed learning failure against the background of reduced motor activity in the offspring of rats exposed to tobacco smoke on gestation days 1–20. Afobazole administered to pregnant rats orally in doses of 1 or 10 mg/kg daily during the whole gestation and/or entering rat pup body with breast milk from mothers receiving 200 mg/kg to day 20 of their life normalized their learning capacity. The formation of short-term and long-term memory in animals receiving afobazole did not differ from the control. Hence, afobazole corrects cognitive disorders in rats exposed to tobacco smoke during prenatal development.     

Estimation of the retainer height biomechanical contribution in posterior resin-bonded fixed partial dentures: a structural-thermal coupled finite element analysis

This study determines the RBFPD (resin-bonded fixed partial dentures) biomechanical aspects to retainer height using structural-thermal coupled finite element (FE) analysis under normal (37°C) and high (51°C) oral temperatures. Three RBFPD FE models with different retainer heights (100, 75, and 50% of the distance from 2 mm above the CE (cementum-enamel) junction to the occlusal surface) were created using image processing, contour stacking, and mapping mesh procedures. After FE model validation, the maximum first principal and von Mises stresses in the remaining tooth (σ_T) and prosthesis (σ_P), were recorded for all models under structural-thermal coupled analyses. The simulation results showed that the σ_T and σ_p values decreased with greater retainer height as a result of the increasing prosthesis stiffness and maximizing bonding area between the enamel and retainer at normal oral temperature (37°C). However, no significant stress differences were found according to the retainer height varying dimensions at high (51°C) temperatures. The RBFPD retainer height biomechanical response is dominated by the structural analysis result (at 37°C) and it is recommended that the prosthesis retainer have as great a height as possible to decrease the stress values.     

Cardiac assessment mechanics: 1 Left ventricular mechanomyocardiography,a new approach to the detection of diseased myocardial elements and states

The inadequacies of currently employed methods for assessment of cardiac mechanics are discussed, and the need for development of more intrinsic assessment parameters is emphasised. To this end, a new technique is presented to enable determination of regional mechanical constitutive properties of the myocardium during diastole; this technique has been originally named left-ventricular mechanomyocardiography (or l.v.-m.m.c.g.). The data required for implementation of the techniques consist of left-ventricular sequential dynamic geometry and associated recorded chamber pressure. The method entails matching of the inner-boundary deformations of the instantaneous finite-element model of the left ventricle (which is loaded by the recorded instantaneous incremental pressure) with the actual instantaneous endocardial deformations (as derived from either cineangiocardiography or 2-dimensional echocardiography), to determine the regional distribution of the Young's modulus E_ne and the incremental stresses Δσ_ne (and hence the total stress σ_ne=∑_nΔσ_ne) of the myocardial elements. The mechanical constitutive properties of the myocardial elements can be then characterised by the constitutive relation E_ne=a+bσ. The constitutive parameters a and b have typical ranges for normal and pathological (ischaemic and infarcted) myocardial elements and hence can be employed to distinguish diseased elements. The values of a and b are calculated for normal and pathological subjects and their normal and pathological ranges are presented.