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Biomedical subjects

A A Pilla

Publications and source records attributed to A A Pilla.

18 recordsLinked to original sources

Effects of permanent magnets on resting skin blood perfusion in healthy persons assessed by laser Doppler flowmetry and imaging.

Effects on skin blood perfusion of permanent ceramic magnets [0.1 T (1000 G) surface field], individually (disk shaped, 4 cm diameter x 1 cm thick) or in the form of a 11 x 7 in pad ( approximately 28 x 17.8 cm) with an array of 16 rectangular magnets (4.5 x 2.2 cm), were investigated in 16 female volunteers (27.4 +/- 1.7 years, range 21-48 years) using three separate protocols. In protocol A, a disk magnet was placed on the palmar surface of the hand in contact with the thenar eminence (n = 5). In protocol B, the magnet was placed on the hand dorsum overlying the thenar eminence (n = 5). In protocol C, the entire palm and fingers rested on the magnetic pad (n = 6). Magnets were in place for 36 min on one hand, and a sham was in place on the other hand. Blood perfusion was measured on the middle finger dorsum by laser Doppler flowmetry (LDF) and on the index finger by laser Doppler imaging (LDI). Perfusion measurements were simultaneously taken in sham and magnet exposed hands, before and during the entire magnet exposure interval. Magnetic field effects were tested by comparing skin blood perfusion sequences in magnet and sham exposed regions. Results showed no significant changes in either LDF or LDI perfusion at magnet or sham sites during exposure, nor were there any significant differences between sham and magnet sites for any protocol. Measurements of skin temperature at the LDF measurement sites also showed no significant change. It is concluded that in the healthy subjects studied with normal, unstressed circulation, magnets of the type and for the duration used, showed no detectible effect on skin blood perfusion in the anatomical area studied.

Adult↗

EMF signals and ion/ligand binding kinetics: prediction of bioeffective waveform parameters.

The kinetics of an electromagnetic field (EMF) target pathway are used to estimate frequency windows for EMF bioeffects. Ion/ligand binding is characterized via first order kinetics from which a specific electrical impedance can be derived. The resistance/capacitance properties of the binding pathway impedance, determined by the kinetics of the rate-determining step, define the frequency range over which the target pathway is most sensitive to external EMF. Applied signals may thus be configured such that their spectral content closely matches that of the target, using evaluation of the signal to thermal noise ratio to optimize waveform parameters. Using the approach proposed in this study, a pulsed radio frequency (PRF) waveform, currently employed clinically for soft tissue repair, was returned by modulation of burst duration, producing significant bioeffects at substantially reduced signal amplitude. Application is made to Ca2+/Calmodulin-dependent myosin phosphorylation, for which the binding time constants may be estimated from reported kinetics, neurite outgrowth from embryonic chick dorsal root explants and bone repair in a fracture model. The results showed that the retuned signal produced increased phosphorylation rates, neurite outgrowth and biomechanical strength that were indistinguishable from those produced by the clinical signal, but with a tenfold reduction in peak signal amplitude, approximately 800-fold reduction in average amplitude and approximately 10(6)-fold reduction in average power.

Algorithms↗

The sensitivity of cells and tissues to exogenous fields: effects of target system initial state.

The effect of the initial biochemical or metabolic state of a cell membrane target pathway on its sensitivity to exogenous electromagnetic (EMF) fields is considered. It is shown that the resting or initial transmembrane voltage can affect the frequency response of the membrane pathway and substantially alter the signal to thermal noise threshold (SNR) of the target. EMF sensitivity is examined using a model which describes the response to applied fields of both single cells and cells in gap junction contact via a distributed parameter electrical circuit analog, wherein a voltage-dependent membrane impedance, relating to the initial biochemical state of the target cell(s), is considered. Application of the Hodgkin-Huxley K(+)-conduction pathway membrane to this model results, at a given transmembrane voltage, in a preferential array response to applied field frequencies in the 1-100 Hz range, centered at approximately 16 Hz for 1-10 mm array lengths. Extension of the model to consider the voltage dependence of the Hodgkin-Huxley K+ pathway results in a significant modulation of array frequency response with changing membrane resting potential. The result is EMF sensitivity (SNR) depends upon the initial state of the target tissue, providing a possible explanation of why, e.g., repairing, rather than resting, bone exhibits a physiologically relevant response to certain weak EMF signals.

Algorithms↗

Lorentz approach to static magnetic field effects on bound-ion dynamics and binding kinetics: thermal noise considerations.

The present study characterizes an ion-binding site, a molecular cleft in a signalling molecule such as calmodulin or troponin C, as a damped linear isotropic oscillator potential for small displacements about the origin. Quantitative assessments of the effects of thermal noise and exogenous static magnetic fields are made through a statistical mechanical treatment of the Lorentz-Langevin equation for an ion bound in a molecular cleft. Thermal noise causes a bound ion to be ejected from the site after a bound lifetime dependent upon the thermal noise spectral density. It is shown that the Lorentz-Langevin model requires values of the viscous damping parameter many orders of magnitude below those for bulk water in order to characterize the binding site and to obtain realistic lifetimes for a bound ion. The model predicts that milliTesla-range magnetic fields are required for static field effects on dissociation kinetics. The Lorentz equation also yields a classic coherent solution describing precession of the bound-ion oscillator orientation at the Larmor frequency. The bound-ion dynamics described by this coherent solution are sensitive to microTesla-range static magnetic fields in the presence of thermal noise. Numerical integration of the contribution of thermal noise forces to these dynamics is in good agreement with the results of statistical mechanical analysis, also producing realistic bound lifetimes for only very low viscous damping values. The mechanisms by which modulation of precessional motion might enable a signalling molecule such as calmodulin to detect an exogenous magnetic field are presently unclear.

Animals↗

Non-invasive low-intensity pulsed ultrasound accelerates bone healing in the rabbit.

The effect of ultrasound (US) on the rate of fibula osteotomy healing in 139 mature New Zealand white rabbits was assessed in this study. Bilateral midshaft fibular osteotomies were made using a 1-mm Gigli saw. US was noninvasively applied to one limb for 20 minutes daily, while the contralateral limb served as a control. A 2.5-cm PZT transducer was applied to both limbs, with the treated limb receiving a 200-microseconds burst of 1.5-MHz sine waves repeated at 1.0 kHz. The incident intensity was approximately 30 mW/cm2. Animals were killed at intervals between 14 and 28 days. Maximum strength increases (significant to p less than or equal to 0.01) ranged from 40 to 85% from postoperative day 14 to 23. On day 28, no significant difference in ultimate strength was noted. From day 17 through day 28, all US-treated fractures were as strong as intact bones (p less than or equal to 0.005). On the other hand, the ultimate strength of the control osteotomies attained intact values only by day 28. These results indicate that biomechanical healing is accelerated by a factor of nearly 1.7. This occurs with an overall acceleration of the healing curve in this fresh fracture model. If noninvasive low-intensity pulsed sine wave ultrasound can significantly accelerate bone repair in clinical application with an in-home treatment of 20 minutes daily, then US may be a useful adjunct for fracture care with a concomitant impact on patient morbidity.

Animals↗

Electromagnetic modulation of biological processes: influence of culture media and significance of methodology in the Ca-uptake by embryonal chick tibia in vitro.

The present studies are aimed at establishing molecular correlations in the interaction of very low frequency electromagnetic fields with biological systems. Ca-uptake by chick embryo tibia rudiment in short-term culture was a useful model. Tibiae of 8- to 10-day-old chick embryos were incubated 60 min in simplified culture media in the presence of 45Ca at 37.5 +/- 0.5 degrees C either inside or outside pulsating electromagnetic fields. Radioactivity count in the medium was the most accurate method for determining Ca-uptake by the rudiment. The effect of the fields on the Ca-uptake depended markedly on the chemical composition of the culture medium: bicarbonate was indispensable; glucose or sucrose was important; phosphate was potentiating; ethanol, Mg2+, and NaF were stimulating. The field had no effect in (a) blank medium without tibia, (b) tibiae that had been altered by fixation with aqueous glutaraldehyde, (c) nonliving artificial systems endowed with great or small ion sorption capacity. The unique bicarbonate effect with living systems and the passive behavior of nonliving ion sorbing systems prompt the suggestion that the electromagnetic field probably couples with specific processes, such as a bicarbonate-dependent Ca2+ ATPase and the active ion transport, at the cell membrane level. The molecular mechanisms remain to be established.

Animals↗

Electromagnetic fields induced by Helmholtz aiding coils inside saline-filled boundaries.

The use of Helmholtz aiding coils to induce small electromagnetic (EM) fields in living tissue for both medical and research purposes has become quite common. While much progress has been made in showing that these induced EM signals can cause a variety of effects in tissues and individual cells, a satisfactory explanation of how the effects occur or how the EM signals couple to the tissue has not yet emerged. To address the latter problem adequately, it becomes necessary to know the spatial distribution of the induced fields inside a given set of boundaries. This paper examines the situation used for much in vitro research where a cylindrical culture dish is filled with a conducting solution and placed between the Helmholtz coils. Two cases are considered. The first assumes that the coils are above and below the culture dish (the planes of the coils are parallel with the top and bottom of the dish); the second assumes that the planes of the coils are parallel with the sides of the dish. A closed form solution is obtained for both cases, and it is shown that the induced EM field distribution is markedly different for the two cases.

Culture Techniques↗

Cytofluorometry of electromagnetically controlled cell dedifferentiation.

Cellular morphology changes, which appear related to dedifferentiation (despecialization), have been produced in vitro in the nucleated red blood cell of the frog. This has been achieved by controlled alterations in the electrochemical environment of these living cells, both by a selective modification of the ionic concentrations of an isotonic amphibian Ringer solution, and by the electromagnetic induction of pulsating current having specific waveform parameters. Laser flow microfluorometry shows that the modified Ringer solution is able, per se, to partially trigger the process in the same time interval that certain induced current waveforms can significantly affect the number of cells in the so-called dedifferentiated state. It has also been found that, for a given waveform, the repetition rate appears to have a significant effect on the rate of cell change. Preliminary automated image analysis of cell smears suggests that dedifferentiated and normal cells have the same integrated optical density but different nuclear areas. In conclusion, it appears that, after the initial electrochemical trigger, the early stage of the process, when the cells move from a state of specialized function to one of less specific activity, is the unfolding of their chromatin supercoil, not involving DNA synthesis. Then cytofluorometry allowed us to identify, for the first time, fundamental modifications which occur in the cell nucleus under electromagnetic exposure.

Acridine Orange↗

A non-operative salvage of surgically-resistant pseudarthroses and non-unions by pulsing electromagnetic fields. A preliminary report.

This report documents, for the first time, to the authors' knowledge, the therapeutic use in humans of low energy, electromagnetic fields pulsing in the extremely low frequency (E.L.F.) range. These fields, established outside the body, were used to treat congenital and acquired pseudarthroses and non-unions. Energy of this type appears to affect biological processes, not through heat production, but through electrically-induced changes in the environment of cells within the organism. Of the 29 patients included in the study, 17 had experienced at least one failure of surgical repair and, in each of these, amputation had been recommended. The overall success rate, including those patients treated with inadequate pulse characteristics and those who failed to follow the protocol, was in excess of 70 per cent. Improvements in the specificity of pulse characteristics hold promise for increasing the rate of success. The simple, clinical methodology, which is conducted on an out-patient basis, appears to be both safe and effective. It can be applied with or without surgery. This approach requires additional controlled investigations before it is ready for general use in the orthopaedic community. The indications for amputation of surgically-resistant pseudarthroses, however, should be reassessed. The principles and technology, which have been established during this endeavor, may have physiologic and practical significance for processes other than pseudarthrosis and non-union.

Adolescent↗

Augmentation of bone repair by inductively coupled electromagnetic fields.

Pulsing electromagnetic fields of low frequency and strength have been inductively coupled across skin, directly to bone, to enhance the repair of canine osteotomies. The induced voltage field in bone appears to increase the organization and strength of the repair process at 28 days after "fracture."

Animals↗

Bioeffects of weak electromagnetic fields.

Time varying magnetic fields are most often employed for therapeutic purposes and are present in environmental sources. In order for an electromagnetic field bioeffect to be possible, the signal parameters should not only satisfy the dielectric properties of the target, but also induce sufficient voltage to be detectable above thermal noise. The problem of the sensitivity of living cells and tissues is discussed in relation to signal/noise ratio at the target site. Some biophysical models for interactions of weak electromagnetic fields with biological systems are summarized. Cell studies and therapeutic application of electric and magnetic fields indicate that weak electromagnetic fields can have a profound effect on a large variety of biological systems.

Animals↗

Electromagnetic modulation of biological processes: bicarbonate effect and mechanistic considerations in the Ca-uptake by embryonal chick tibia in vitro.

Electromagnetically induced currents pulsating at very low frequency stimulated calcium uptake by chick embryo tibia rudiments only when bicarbonate was present in the culture medium. A bicarbonate-dependent Ca2+-ATPase might be implicated in coupling of the electromagnetic signal with processes that promote Ca-transport and storage in bone tissue.

Animals↗

Electromagnetic modulation of biological processes: ATPase function and DNA production by Raji cancer cells in vitro.

Addition of either ATP or ouabain to the culture medium markedly depressed thymidine incorporation into DNA in Raji cells. The electromagnetic field, pulsating at very low frequency, did not affect DNA synthesis in normal culture media nor did it alter its ouabain-inhibition, but it partially reversed the ATP-inhibition. In spite of the presence of ATP, ouabain prevented stimulation of ATPase and DNA synthesis by the field. Although no mechanism is known for the action of either ATP or the field, the results may be interpreted in light of existing speculations. In the absence of the field, external ATP may go into an ATP pool that either blocks ATPase or feeds adenyl cyclase, which hinders DNA synthesis. In contrast, the electromagnetic field may either turn off adenyl cyclase or simply stimulate the ATP-depressed ATPase.

Adenosine Triphosphatases↗