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Biomedical subjects

M C Ziskin

Publications and source records attributed to M C Ziskin.

At least 37 records · Page 2Linked to original sources

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↗

Antipruritic effect of millimeter waves in mice: evidence for opioid involvement.

In our previous studies, exposure of mice to millimeter waves (MW) increased the duration of anesthesia caused by either ketamine or chloral hydrate, and this effect was blocked by naloxone. To further characterize the biological effects of MW, we have chosen a new animal model of experimental itch. Male Swiss albino mice were injected s.c. in the rostral part of the back with the pruritogenic agent, compound 48/80, with or without naloxone pretreatment. After a 15-min exposure of mice to MW (frequency, 61.22 GHz; incident power density, 15 mW/cm2), the number of scratches of the injected site was counted for 90 min post-injection. MW inhibited the scratching activity of mice by more than 2 times in comparison with the sham-exposed controls (p<0.005). Pretreatment of animals with (-)-naloxone (0.1-1.0 mg/kg, i.p.) suppressed the antipruritic effect of MW in a dose-dependent manner, while the inactive enantiomer (+)-naloxone at 1 mg/kg did not alter the effect. These results suggest that MW trigger the release of opioids in exposed subjects.

Animals↗

Effects of two ultrasound devices and angles of application on the temperature of tissue phantom.

Ultrasound is a commonly used therapeutic modality for which there is little research on the effect of treatment dosage on the extent of tissue heating. The purpose of this study was to investigate the effect of two different ultrasound devices, angle of ultrasound application, and treatment time on the temperature of a tissue phantom. Four trials were performed at four ultrasound application angles (90 degrees, 80 degrees, 70 degrees, and 60 degrees) with both an Excel UltraMax and a Mettler Sonicator 720. A continuous 1-MHz frequency at 2.0 W/cm2 was administered for 5 minutes, with tissue phantom temperature recorded at 1-minute intervals. The analysis of the data revealed significant main effects between ultrasound devices, angle of application, and treatment times. Interactions were identified between ultrasound device and treatment times and angle of application and treatment times. Analysis of simple effects revealed significant differences between ultrasound devices after 2, 3, 4, and 5 minutes of treatment and between treatment times and 80 degrees and 60 degrees angles of application. Maximal temperature increase after a 5-minute treatment was 2.025 degrees C. This level of tissue heating falls below expected values and may not yield therapeutic results. The thermal effects were noted to be greatest at 80 degrees and 90 degrees angles of application. Despite appropriate calibration and identical treatment protocols, the two ultrasound devices yielded significantly different tissue phantom temperatures, which were notably lower than expected values. We concluded that direct monitoring of ultrasound device output and calculation of treatment dosage should occur on a routine basis, as treatment outcome will certainly be affected by the actual dosage of ultrasonic energy.

Evaluation Studies as Topic↗

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↗

The sensitivity of biological tissue to ultrasound.

Mammalian tissues have differing sensitivities to damage by physical agents such as ultrasound. This article evaluates the scientific data in terms of known physical mechanisms of interaction and the impact on pre- and postnatal tissues. Actively dividing cells of the embryonic and fetal central nervous system are most readily disturbed. As a diagnostic ultrasound beam envelopes a small volume of tissue, it is possible that the effects of mild disturbance may not be detected unless major neural pathways are involved. There is evidence that ultrasound can be detected by the central nervous system; however, this does not necessarily imply that the bioeffect is hazardous to the fetus. Biologically significant temperature increases can occur at or near to bone in the fetus from the second trimester, if the beam is held stationary for more than 30 s in some pulsed Doppler applications. In this way, sensory organs that are encased in bone may be susceptible to heating by conduction. Reports in animals and humans of retarded growth and development following frequent exposures to diagnostic ultrasound, in the absence of significant heating, are difficult to explain from the current knowledge of ultrasound mechanisms. There is no evidence of cavitation effects occurring in the soft tissues of the fetus when exposed to diagnostic ultrasound; however, the possibility exists that such effects may be enhanced by the introduction of echo-contrast agents.

Animals↗

Electromagnetic millimeter waves increase the duration of anaesthesia caused by ketamine and chloral hydrate in mice.

BALB/c mice were injected i.p. with either ketamine 80 mg/kg or chloral hydrate 450 mg/kg. Anaesthetized mice were exposed to unmodulated electromagnetic millimeter waves at the frequency of 61.22 GHz with a peak specific absorption rate of 420 W/kg and corresponding incident power density of 15 mW/cm2 for 15 min or sham-exposed. In combination with either of the anaesthetics used, mm waves increased the duration of anaesthesia by approximately 50% (p < 0.05) in a dose (power)-dependent manner. Sham exposure to mm waves did not affect the sleeping time of mice. Pretreatment of mice with naloxone, an opioid antagonist, did not change the duration of anaesthesia caused by the corresponding chemical agent, but completely blocked or decreased the additional effect of mm waves. The data in this study indicates that exposure of mice to mm waves in vivo releases endogenous opioids or enhances the activity of opioid signalling pathway.

Anesthesia↗

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↗

Temperature oscillations in liquid media caused by continuous (nonmodulated) millimeter wavelength electromagnetic irradiation.

Convection in liquids caused by 53-78 GHz millimeter wave irradiation with incident power density that ranged from 10 microW/cm2 to 1 W/cm2 was studied. Infrared thermography was used as an artifact-free method for recording surface-temperature dynamics during irradiation. It was found that continuous (nonmodulated) waves can produce a relaxation-type temperature oscillation in liquids with a relatively high stability of the period between temperature spikes. The temperature oscillation is due to the repetitive formation and dissipation of a torroidal type of convection vortex. When the vortex became stable during irradiation, we observed a temperature decrease following the initial temperature-rise phase, even though the irradiation was constantly maintained. This result constitutes a new process that can play a significant role in producing microwave bioeffects, including some so-called "nonthermal" effects and some effects that are inversely related to heating. Also, it can be considered as a newly discovered potential artifact in microwave bioeffects studies.

Biophysical Phenomena↗

Continuous millimeter-wave radiation has no effect on lipid peroxidation in liposomes.

The effect of millimeter waves on lipid peroxidation was studied in the presence and absence of melanin. Irradiation of liposomes with continuous millimeter electromagnetic waves at frequencies of 53.6, 61.2 and 78.2 GHz and incident power densities of 10, 1 and 500 mW/cm2, respectively, did not show an enhancement in the formation of lipid peroxides compared to unirradiated samples. Liposomes exposed to 254 nm UVC radiation at 0.32 mW/cm2 and 302 nm UVB radiation at 1.12 mW/cm2 served as positive controls. No increment in the formation of lipid peroxides was observed when irradiation of liposomes was carried out in the presence of ADP-Fe+3 and EDTA-Fe+3. Direct irradiation of melanin with millimeter waves did not exhibit an increased formation of superoxide or hydrogen peroxide. The present results indicate that millimeter waves of the above frequencies and intensities do not cause lipid peroxidation in liposomal membranes.

Hydrogen Peroxide↗

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↗

Effect of millimeter waves on survival of UVC-exposed Escherichia coli.

Bacterial cells of the strain Escherichia coli K12 were exposed to millimeter electromagnetic waves (mm waves) with and without additional exposure to ultraviolet light lambda = 254 nm (UVC). The mm waves were produced by a medical microwave generator emitting a 4-GHz-wide band around a 61 GHz center frequency and delivering an irradiation of 1 mW/cm2 and a standard absorption rate (SAR) of 84 W/kg to the bacteria. Exposure to the mm waves alone for up to 39 minutes did not change the survival rate of bacteria. Exposure to mm waves followed by UVC irradiation also did not alter the number of surviving E. coli cells in comparison to UVC-treated controls. When mm waves were applied after the UVC exposure, a dose-dependent increase of up to 30% in the survival of E. coli was observed compared to UVC + sham-irradiated bacteria. Because sham controls and experimental samples were maintained under the same thermal conditions, the effect is not likely to be due to heating, although the possibility of nonuniform distribution of microwave heating in different layers of irradiated bacterial suspension cannot be ruled out. The mechanism for this effect appears to involve certain DNA repair systems that act as cellular targets for mm waves.

Culture Media↗

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↗

Current status of research on biophysical effects of ultrasound.

This overview of bioeffects of ultrasound presents some key aspects of selected papers dealing with biophysical end-points. Its purpose is to establish a basis for exposure and dosimetric standards for medical ultrasonic equipment. It is intended to provide essential background resource material for the medical/scientific community, and more specifically for scientific working groups. This document was prepared by members of the Safety Committee of the World Federation for Ultrasound in Medicine and Biology. It was produced as a resource document in response to a request for information by Working Group 12 (Ultrasound exposure parameters) of the International Electrotechnical Commission Technical Committee 87, Ultrasonics. IEC TC 87, WG12 is the working group responsible for generating international standards for the classification of equipment by its acoustic fields based on safety thresholds. Our paper is intended to update and supplement information on the thermal mechanism provided in the publication, "WFUMB Symposium on Safety and Standardisation in Medical Ultrasound: Issues and Recommendations Regarding Thermal Mechanisms for Biological Effects of Ultrasound" (WFUMB 1992). It also provides an overview of trends in research into nonthermal mechanisms as a preliminary to the next WFUMB Symposium on Safety of Medical Ultrasound when this subject will be examined in detail by a select group of international experts. The WFUMB-sponsored workshop will take place in Utsunomiya, Japan during 11-15th July, 1994. The purpose of the meeting is to evaluate the scientific literature and to formulate internationally accepted recommendations on the safe use of diagnostic ultrasound that may be endorsed as official policy of the WFUMB. It should be noted that the current publication is not intended for review or endorsement as an official WFUMB document. It is produced as a scientific paper by individuals who are members of the WFUMB Safety Committee, and it therefore represents the opinions of the authors. Nevertheless, during the preparation of this document, contributions were received from members of the International Electrotechnical Commission Technical Committee 87 as well as many other individual experts, and the authors sincerely acknowledge their support.

Air↗

Heating patterns in biological tissue phantoms caused by millimeter wave electromagnetic irradiation.

Distribution of millimeter wavelength electromagnetic energy absorption in surface layers of biological tissue models was studied using methods of Infrared Thermography. 0.1 mm thin-layer phantoms were irradiated in the near field using different types of horn antennas in the 37-78 GHz frequency range. Heating patterns were recorded during microwave irradiation, and surface SAR distributions were calculated. The temperature resolution was better than 0.05 K. It was found that horn antennas produced nonuniform heating patterns in irradiated objects. These nonuniform patterns were due to a geometrical resonance resulting from a secondary wave-mode interaction between an irradiated object and the corresponding critical cross-section of the horn antenna. Local SAR values in hot spots exceeded the spatially averaged values by over 10 times, and the widths of these hot spots at 5 times the average SAR were often 1 mm or less. The location, quantity, number and size of the local field absorption maxima of irradiated objects strongly depended on the frequency of electromagnetic irradiation, with equivalent Q-factors of 500 or more. These findings provide an explanation for a number of frequency-dependent effects of millimeter wave electromagnetic irradiation.

Infrared Rays↗

Effect of ultrasound on the neonatal rat brain.

Six-day-old rat neonates were exposed to 2.25 MHz continuous wave (CW) ultrasound for 5 min at an intensity of 2.5 W/cm2 (SATA). The temperatures on the head surface and in the mouth were measured. There was a higher average temperature elevation in the mouth (9 degrees C) than on the head surface (7 degrees C). Survival differs between control and exposed groups at 30 days after exposure. Ninety percent of the control group lived to 30 days, versus 59.7% for the exposed group. At differing times following exposure, the brains of the pups were removed and tested for enzymatic activities. Changes in acetylcholine esterase and in 2',3'-cyclic nucleotide phosphohydrolase activities were not statistically significantly different from controls. There were no significant differences in brain weight and total protein between control and exposed pups.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗