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Biomedical subjects

S I Alekseev

Publications and source records attributed to S I Alekseev.

At least 19 recordsLinked to original sources

Effect of cyclophosphamide and 61.22 GHz millimeter waves on T-cell, B-cell, and macrophage functions.

The present study was undertaken to investigate whether millimeter waves (MMWs) at 61.22 GHz can modulate the effect of cyclophosphamide (CPA), an anti-cancer drug, on the immune functions of mice. During the exposure each mouse's nose was placed in front of the center of the antenna aperture (1.5 x 1.5 cm) of MMW generator. The device produced 61.22 +/- 0.2 GHz wave radiation. Spatial peak Specific Absorption Rate (SAR) at the skin surface and spatial peak incident power density were measured as 885 +/- 100 W/kg and 31 +/- 5 mW/cm(2), respectively. Duration of the exposure was 30 min each day for 3 consecutive days. The maximum temperature elevation at the tip of the nose, measured at the end of 30 min, was 1 degrees C. CPA injection (100 mg/kg) was given intraperitoneally on the second day of exposure to MMWs. The animals were sacrificed 2, 5, and 7 days after CPA administration. MMW exposure caused upregulation in tumor necrosis factor-alpha (TNF-alpha) production in peritoneal macrophages suppressed by CPA administration. MMWs also caused a significant increase in interferon-gamma (IFN-gamma) production by splenocytes and enhanced proliferative activity of T-cells. Conversely, no changes were observed in interleukin-10 (IL-10) level and B-cell proliferation. These results suggest that MMWs accelerate the recovery process selectively through a T-cell-mediated immune response.

Animals↗

Local heating of human skin by millimeter waves: effect of blood flow.

We investigated the influence of blood perfusion on local heating of the forearm and middle finger skin following 42.25 GHz exposure with an open ended waveguide (WG) and with a YAV mm wave therapeutic device. Both sources had bell-shaped distributions of the incident power density (IPD) with peak intensities of 208 and 55 mW/cm(2), respectively. Blood perfusion was changed in two ways: by blood flow occlusion and by externally applied vasodilator (nonivamide/nicoboxil) cream to the skin. For thermal modeling, we used the bioheat transfer equation (BHTE) and the hybrid bioheat equation (HBHE) which combines the BHTE and the scalar effective thermal conductivity equation (ETCE). Under normal conditions with the 208 mW/cm(2) exposure, the cutaneous temperature elevation (DeltaT) in the finger (2.5 +/- 0.3 degrees C) having higher blood flow was notably smaller than the cutaneous DeltaT in the forearm (4.7 +/- 0.4 degrees C). However, heating of the forearm and finger skin with blood flow occluded was the same, indicating that the thermal conductivity of tissue in the absence of blood flow at both locations was also the same. The BHTE accurately predicted local hyperthermia in the forearm only at low blood flow. The HBHE made accurate predictions at both low and high perfusion rates. The relationship between blood flow and the effective thermal conductivity (k(eff)) was found to be linear. The heat dissipating effect of higher perfusion was mostly due to an apparent increase in k(eff). It was shown that mm wave exposure could result in steady state heating of tissue layers located much deeper than the penetration depth (0.56 mm). The surface DeltaT and heat penetration into tissue increased with enlarging the irradiating beam area and with increasing exposure duration. Thus, mm waves at sufficient intensities could thermally affect thermo-sensitive structures located in the skin and underlying tissue.

Capsaicin↗

Millimeter wave-induced suppression of B16 F10 melanoma growth in mice: involvement of endogenous opioids.

Millimeter wave treatment (MMWT) is widely used in Eastern European countries, but is virtually unknown in Western medicine. Among reported MMWT effects is suppression of tumor growth. The main aim of the present "blind" and dosimetrically controlled experiments was to evaluate quantitatively the ability of MMWT to influence tumor growth and to assess whether endogenous opioids are involved. The murine experimental model of B16 F10 melanoma subcutaneous growth was used. MMWT characteristics were: frequency, 61.22 GHz; average incident power density, 13.3 x 10(-3) W/cm2; single exposure duration, 15 min; and exposure area, nose. Naloxone (1 mg/kg, intraperitoneally, 30 min prior to MMWT) was used as a nonspecific blocker of opioid receptors. Five daily MMW exposures, if applied starting at the fifth day following B16 melanoma cell injection, suppressed subcutaneous tumor growth. Pretreatment with naloxone completely abolished the MMWT-induced suppression of melanoma growth. The same course of 5 MMW treatments, if started on day 1 or day 10 following tumor inoculations, was ineffective. We concluded that MMWT has an anticancer therapeutic potential and that endogenous opioids are involved in MMWT-induced suppression of melanoma growth in mice. However, appropriate indications and contraindications have to be developed experimentally before recommending MMWT for clinical usage.

Animals↗

Local heating of human skin by millimeter waves: a kinetics study.

Heating rates of human skin exposed locally to 42.25 GHz mm waves, coming from a waveguide (WG) opening or a YAV device designed for therapeutic application, were studied in vivo using infrared (IR) thermography. For both radiators, the power density distribution was described by a circularly symmetrical Gaussian type function on the exposed skin surface. Insertion of a small thermocouple (d = 0.1 mm) in the exposed area did not produce any significant artifact, either in the power density distribution or kinetics measurement, providing it was perpendicular to the E vector. The heating kinetics in the skin exposed with either the WG opening or the YAV device were well fitted to solutions of the 2-D bio-heat transfer equation for homogeneous tissue. Changes in irradiating beam size (1-8 mm) had no detectable effect on the initial (0.3-3.0 s) phase of the heating kinetics. However, the amplitude of the kinetics decreased substantially with decreasing the beam size. As the temperature rise in the time interval necessary for reliable measurement of the initial temperature rise rate was very small, an accurate experimental determination of specific absorption rate (SAR) becomes practically impossible at the low intensities normally used in our experiments. The correct SAR values may be found from fitting of the model to the heating kinetics. Bioelectromagnetics 24:571-581, 2003.

Body Temperature Regulation↗

Peripheral neural system involvement in hypoalgesic effect of electromagnetic millimeter waves.

In a series of blind experiments, using the cold water tail-flick test (cTFT) as a quantitative indicator of pain, the hypoalgesic effect of a single exposure of mice to low power electromagnetic millimeter waves (MW) was studied. The MW exposure characteristics were: frequency = 61.22 GHz; incident power density = 15 mW/cm2; and duration = 15 min. MW treatment was applied to the glabrous skin of the footpad. Exposure of an intact murine paw to the MW resulted in a statistically significant hypoalgesia as measured in the cTFT. These mice were able to resist cold noxious stimulation in the cTFF more than two times longer than animals from the sham-exposed group. A unilateral sciatic nerve transection was used to deafferent the area of exposure in animals from one of the experimental groups. This surgery, conducted six days before the MW treatment, completely abolished the hypoalgesic effect of the exposure to MW. The results obtained support the conclusion that the MW-skin nerve endings interaction is the essential step in the initiation of biological effects caused by MW. Based on our past and present results we recommend that in order to obtain a maximum therapeutic effect, densely innervated skin areas (head, hands) need to be used preferentially for exposure to MW in clinical practice.

Animals↗

Millimeter wave power density in aqueous biological samples.

Power density distribution inside a water sample placed between two parallel lossy dielectric plates (Polystyrene) was calculated using Fresnel equations for the frequency range of 42.25-53.57 GHz. Due to the multiple internal reflections from the sample boundaries, the distribution of the power density within the thin sample is more uniform than that within a semi-infinite medium. The power density in a sample depends on the thicknesses of the sample and the adjacent dielectric plates. For the given frequency range the sample thickness optimal for power density uniformity varies between 0.28 and 0.33 mm. The front plate has a significant effect on the magnitude of the power density within the sample but little effect on the power density distribution. The thicker the rear plate, the greater is the non uniformity of the power density distribution within the sample. Based on the calculated data, we determined the dimension of an exposure chamber providing the optimal power density distribution uniformity for mm-wave irradiation.

Air↗

Distortion of millimeter-wave absorption in biological media due to presence of thermocouples and other objects.

Specific absorption rate (SAR) distributions in the vicinity of a thermocouple or air bubble in water and in the presence of hair or sweat duct in skin were calculated using analytical and two-dimensional impedance methods. The objects were exposed to uniform 42.25 GHz plane electromagnetic fields. Insertion of a 0.1-mm thermocouple or similarly sized air bubble into water produced a strong localized disturbance of the otherwise uniform SAR distribution. However, the average of SAR values immediately surrounding the thermocouple was close to the undisturbed uniform average SAR. This allows measuring the average SAR during exposure of both unbounded and bounded media using calibrated small thermocouples (up to 0.1 mm). The SAR distribution in the vicinity of a hair was qualitatively similar to that produced by an air bubble. The maximal value of SAR was more than three times higher than the overall average SAR value in the skin. Sweat ducts produced a smaller disturbance of the millimeter-wave (mm-wave) field.

Absorption↗

Hypoalgesic effect of millimeter waves in mice: dependence on the site of exposure.

Based on a hypothesis of neural system involvement in the initial absorption and further processing of the millimeter electromagnetic waves (MW) signal, we reproduced, quantitatively assessed and compared the analgesic effect of a single MW treatment, exposing areas of skin possessing different innervation densities. The cold water tail flick test (cTFT) was used to assess experimental pain in mice. Three areas of exposure were used: the nose, the glabrous skin of the right footpad, and the hairy skin of the mid back at the level of T5-T10. The MW exposure characteristics were: frequency = 61.22 GHz; incident power density = 15mW/cm2; and duration = 15 min. The maximum hypoalgesic effect was achieved by exposing to MW the more densely innervated skin areas--the nose and the footpad. The hypoalgesic effect in the cTFT after MW exposure to the murine back, which is less densely innervated, was not statistically significant. These results support the hypothesis of neural system involvement in the systemic response to MW.

Analgesia↗

Reflection and absorption of millimeter waves by thin absorbing films.

Reflection, transmission, and absorption of mm-waves by thin absorbing films were determined at two therapeutic frequencies: 42. 25 and 53.57 GHz. Thin filter strips saturated with distilled water or an alcohol-water solution were used as absorbing samples of different thicknesses. The dependence of the power reflection coefficient R(d) on film thickness (d) was not monotonic. R(d) passed through a pronounced maximum before reaching its steady-state level [R(infinity)]. Similarly, absorption, A(d), passed two maximums with one minimum between them, before reaching its steady-state level [A(infinity)]. At 42.25 GHz, A(d) was compared with absorption in a semi-infinite water medium at a depth d. When d < 0.3 mm, absorption by the film increased: at d = 0.1 mm the absorption ratio for the thin layer sample and the semi-infinite medium was 3.2, while at d = 0.05 mm it increased up to 5.8. Calculations based on Fresnel equations for flat thin layers adequately described the dependence of the reflection, transmission, and absorption on d and allowed the determination of the refractive index (n), dielectric constant (epsilon), and penetration depth (delta) of the absorbing medium for various frequencies. For water samples, epsilon was found to be 12.4-19.3j, delta = 0.49 mm at 42.25 GHz, and epsilon = 9.0-19.5j, delta = 0.36 mm at 53.57 GHz. The calculated power density distribution within the film was strongly dependent on d. The measurements and calculations have shown that the reflection and absorption of mm-waves by thin absorbing layers can significantly differ from the reflection and absorption in similar semi-infinite media. The difference in reflection, absorption, and power density distribution in films, as compared to semi-infinite media, are caused by multiple internal reflections from the film boundaries. That is why, when using thin phantoms and thin biological samples, the specifics of the interaction of mm-waves with thin films should be taken into account.

Absorption↗

Effects of millimeter waves on ionic currents of Lymnaea neurons.

The effects of mm-waves 60.22-62.22 GHz and 75 GHz on A-type K+ currents and the effects of 61.22 GHz on Ca2+ currents of Lymnaea neurons were investigated using a whole-cell voltage-clamp technique. The open end of a rectangular waveguide covered with a thin Teflon film served as a radiator. Specific absorption rates at the waveguide outlet, inserted into physiological solution, were in the range of 0-2400 W/kg. Millimeter wave irradiation increased the peak amplitudes, activation rates, and inactivation rates of both ion currents. The changes in A-type K+ current were not dependent on the irradiation frequency. It was shown that the changes in the amplitudes and kinetics of both currents resulted from the temperature rise produced by irradiation. No additional effects of irradiation on A-type K+ current other than thermal were found when tested at the phase transition temperature or in the presence of ethanol. Ethanol reduced the thermal effect of irradiation. Millimeter waves had no effect on the steady-state activation and inactivation curves, suggesting that the membrane surface charge and binding of calcium ions to the membrane in the area of channel locations did not change.

Absorption↗

Millimeter waves thermally alter the firing rate of the Lymnaea pacemaker neuron.

The effects of millimeter waves (mm-waves, 75 GHz) and temperature elevation on the firing rate of the BP-4 pacemaker neuron of the pond snail Lymnaea stagnalis were studied by using microelectrode techniques. The open end to a rectangular waveguide covered with a thin Teflon film served as a radiator. Specific absorption rates (SARs), measured in physiological solution at the radiator outlet, ranged from 600 to 4,200 W/kg, causing temperatures rises from 0.3 to 2.2 degrees C, respectively. Irradiation at an SAR of 4200 W/kg caused a biphasic change in the firing rate, i.e., a transient decrease in the firing rate (69 +/- 22% below control) followed by a gradual increase to a new level that was 68 +/- 21% above control. The biphasic changes in the firing rate were reproduced by heating under the condition that the magnitude (2 degrees C) and the rate of temperature rise (0.96 degrees C/s) were equal to those produced by the irradiation (for an SAR of 4,030 W/kg). The addition of 0.05 mM of ouabain caused the disappearance of transient responses of the neuron to the irradiation. It was shown that the rate of temperature rise played an important role in the development of a transient neuronal response. The threshold stimulus for a transient response of the BP-4 neuron found in warming experiments was a temperature rise of 0.0025 degrees C/s.

Animals↗

Effects of alcohols on A-type K+ currents in Lymnaea neurons.

The effects of short-chain alcohols (methanol, ethanol and n-propanol) on the fast-inactivating, A-type, potassium current of Lymnaea neurons were examined using macroscopic recording techniques. Alcohols produced a blockade of the current and modified its inactivation mechanism. The extracellular concentrations of methanol, ethanol and n-propanol causing 50% suppression of the current were 2970, 830 and 230 mM, respectively. The main effects of alcohols on inactivation were a decrease in the amplitude of the fast component and a simultaneous increase in the amplitude of the slow component of inactivation. In a model, the suppression of the fast component could be reproduced by an increase of the backward rate constant related to the dissociation of the inactivation particle from its binding site. The blockade and modification of inactivation reveal similar dependences on ethanol concentration, indicating that the same type of interaction of ethanol with the channel underlies both of these events. Ethanol was effective only in extracellular applications. The data support an action of alcohols at a hydrophobic site near the extracellular portion of the channel.

Alcohols↗

Millimeter microwave effect on ion transport across lipid bilayer membranes.

The effects of millimeter microwaves in the frequency range of 54-76 GHz on capacitance and conductance of lipid bilayer membranes (BLM) were studied. Some of the membranes were modified by gramicidin A and amphotericin B or by tetraphenylboron anions (TPhB-). The millimeter microwaves were pulse-modulated (PW) at repetition rates ranging from 1 to 100 pps, PW at 1000 pps, or unmodulated continuous waves (CW). The maximum output power at the waveguide outlet was 20 mW. It was found that CW irradiation decreased the unmodified BLM capacitance by 1.2% +/- 0.5%. At the same time, membrane current induced by TPhB- transport increased by 5% +/- 1%. The changes in conductance of ionic channels formed by gramicidin A and amphotericin B were small (0.6% +/- 0.4%). No "resonance-like" effects of mm-wave irradiation on membrane capacitance, ionic channel currents, or TPhB- transport were detected. All changes in membrane capacitance and currents were independent of the modulation employed and were equivalent to heating by approximately 1.1 degrees C.

Amphotericin B↗

Two types of A-channels in Lymnaea neurons.

The gating mechanism of A-channels of Lymnaea neurons and the effect of tetraethylammonium (TEA) on these channels were studied using macroscopic recording techniques. Along with the fast-inactivating A-current (Iaf) described earlier we found a slow-inactivating A-current (Ias) in some neurons of the visceral ganglion. Both currents have revealed similar activation kinetics, but differ in the inactivation kinetics and mechanisms. The inactivation kinetics of Ias were satisfactorily described by a sum of two exponentials with rate constants (tau -1) of 28 s-1 and 4.5 s-1 at V = -20 mV. Intracellular TEA reduced the peak amplitudes of Iaf and Ias and slowed the rate of the fast phase of inactivation of Iaf. This resulted in a crossover of the current traces in the presence and absence of TEA, as though it competes with the binding of the inactivating particle. The mechanism of the fast phase of inactivation of Iaf is similar to that of fast inactivation of the Shaker K+ channels which appears to be due to a ball-and-chain mechanism. The slow phases of inactivation of Iaf and Ias reveal properties characteristic of C-type inactivation shown in Shaker K+ channels. A partially coupled model including three pathways for transition of a channel from the closed to open states accurately reproduces all of the experimental data. It has voltage-independent transitions to the inactivation states indicating that inactivation of A-current is not associated with charge movement through the membrane. The results suggest that Lymnaea A-channels seem to be heteromultimeric.

Action Potentials↗

Influence of microwaves on different types of receptors and the role of peroxidation of lipids on receptor-protein shedding.

The effects of a continuous wave or pulse-modulated, 900 MHz microwave field were studied by in vitro assays of rat chemoreceptors. The pulsed field was modulated as rectangular waves at rates of 1, 6, 16, 32, 75, or 100 pps. The pulse-period to pulse-duration ratio was 5 in all cases, and specific absorption rates (SARs) ranged from 0.5 to 18 W/kg. Binding of ligands to cell membranes was differentially affected by exposure to microwaves. For example, binding of H3-glutamic acid to hippocampal cells was not altered by a 15 min exposure to a continuous wave field at 1 W/kg, but binding of H3-dihydroalprenolol to liver-cell membranes of neonates underwent a fivefold decrease under the same field conditions. This effect was not dependent on modulation or on a change in the constant of stimulus-receptor binding but depended on a shedding of the membrane's receptor elements into solution. The magnitude of inhibition correlated with the oxygen concentration in the exposed suspension. Antioxidants (dithiothreitol and ionol) inhibited the shedding of receptor elements. The microwave exposure did not cause an accumulation of products from the peroxidation of lipids (POL). Ascorbate-dependent or non-enzymatic POL was not responsible for the inhibition, and POL was not found in other model systems. However, enzymatic POL mechanisms in localized areas of receptor binding remain a possibility.

Animals↗

Kinetic study of A-type current inactivation in Lymnaea neurons.

Macroscopic inactivation of A-current was studied in internally perfused Lymnaea neurons under voltage clamp conditions. Inactivation kinetics were satisfactorily described by the sum of two exponentials, suggesting the presence of two type inactivation. The kinetics of recovery from inactivation were exponential. The rate constants of the fast phase of inactivation gamma f(V) rose steeply with depolarization exposing the pronounced plateau in the range from -30 to 0 mV. The time course of inactivation in this potential range was more closely approximated with the sum of three exponentially decaying components. Calcium and hydrogen ions strongly affected the fast phase of inactivation. Calcium gave a positive shift of a part of the gamma f(V) curve on the left of the plateau. Raising the pH caused a negative shift of the right-hand branch of the gamma f(V) curve. It was shown that these effects are associated with Ca2+ and H+ binding to some specific sites of the channel protein. Two models give good fits with the experimental data. They include two pathways for fast inactivation. Calcium and hydrogen ions are assumed to selectively affect the voltage-dependent transitions related to these pathways of inactivation.

Animals↗

Interaction of sulfhydryl reagents with A-type channels of Lymnaea neurons.

The effect of sulfhydryl reagents on macroscopic inactivation of A-current in internally perfused Lymnaea neurons under voltage-clamp conditions was investigated. It was found that the binding of Hg2+ rather than PHMB with channel proteins resulted in a strong decrease of the peak current and the inactivation rate. Hg2+ markedly influenced the steady-state inactivation but did not change the rate of recovery from inactivation. It was found that both reagents reacted with the same groups of the channel protein and that those are most likely sulfhydryl groups. These groups seemed not to be involved in the gating charge movement. Hg2+ ions can immobilize some part of the gating charge thereby resulting in strong changes of the steady-state inactivation.

Animals↗