Генератор для электротерапии и стимуляции нервных центров человека

IONOTROPIC adenosine 5′-triphosphate (ATP) (P2X) receptors are expressed in some primary afferent neurons, and activation of these receptors results in membrane depolarisation. 1Many studies indicate that one subtype, the P2X3receptor, may contribute to the transduction of nociceptive stimuli in somatosensory 2and visceral afferents. 3,4However, the function of this receptor in the peripheral human nervous system is poorly understood. Using sensory testing, pain was experienced on local application of ATP on a human blister base preparation 5or by iontophoresis of ATP to human skin. 6However, it was not possible to identify the subtype of purinergic receptor underlying this effect. In the current study, we have used a new human nerve preparation. We tested the sensitivity of isolated fascicles of human vagus nerve to agonists at P2X3receptors. It is known that persistent changes in membrane potential and axonal excitability occur during application of the P2X3receptor agonist α,β-methylene ATP (α,β-meATP) to rat nodose ganglion cells, 1to isolated rat vagus nerve 7,8and in single vagal afferents in the mouse. 9Our data indicate that isolated fascicles of human vagus nerve can be used to study the pharmacology of P2X3receptors in the peripheral human autonomic nervous system.The experiments on human vagus nerves were conducted using 12 isolated fascicles from four patients. Approval for this procedure was obtained from the Ethics Committee of the University of Munich, and the patients gave written informed consent. The patients (male, n = 4) were aged 49, 55, 66, and 69 yr when they underwent the procedure. All of them underwent complete surgical resection of the stomach because of cancer. A 2- to 3-cm part of the anterior vagal trunk at the distal abdominal esophagus (subdiaphragmatic) was removed from the area of gastrectomy.Experimental procedures were done as described previously. 10Briefly, isolated human nerve fascicles nerves were held at each end by suction electrodes in an organ bath. One suction electrode was used to elicit action potentials; the other was used as a recording electrode. The distance between stimulating and recording electrodes was approximately 3 mm. The organ bath (volume, 2 ml) was continuously perfused with solution at a flow rate of 6–8 ml/min (32°C). The perfusion solution contained (in mM) NaCl 118, KCl 3.0, CaCl21.5, MgCl21.0, D-glucose 5.0, NaHCO325, and NaH2PO41.2, and it was bubbled with 95% O2/5% CO2(pH 7.4).Isolated fascicles of human vagus nerve were stimulated with a linear stimulus isolator (A395, WPI, Sarasota, FL) with 1.0-ms current pulses (100–500 μA) at a frequency of 1 Hz. The stimulator was controlled by a computer via a data acquisition board (Data Translation DT2812, Marlboro MA). Compound action potentials were elicited and recorded, making use of the QTRAC program (copyright, Hugh Bostock, Ph.D., Professor, Institute of Neurology, London, United Kingdom). The peak amplitude of the C-fiber component was measured continuously from the negative to the positive maximum.Cells in the nerve fascicles were loaded with membrane-permeant esters of the fluorescent dyes Calcium Green-1 and Fura Red. The organ bath containing the nerve fascicles was mounted on an inverted fluorescence microscope (Zeiss Axiovert 35, Jena, Germany) with a custom-made photometric attachment and was illuminated at 0.33Hz with 10-ms light pulses at 485 nm. Intensity of the emitted fluorescent light was measured after filtering by two photodiodes at 530 nm (Calcium Green) and 660 nm (Fura Red). Emission intensities were recorded using the QTRAC program. The ratio of the two emission intensities was calculated off-line to give a measure of intracellular calcium concentration.α,β-meATP (α,β-methylene-adenosine 5′-triphosphate),Ap5A (diadenosine pentaphosphate), ATP (adenosine 5′-triphosphate), and ATPγS (adenosine 5′[γ-thio] triphosphate) were purchased from Sigma (St. Louis, MO). Trinitrophenyl (TNP)-ATP (2′ (or 3′)-O -adenosine 5′-triphosphate), Calcium Green-1, and Fura Red were purchased from Molecular Probes (Eugene, OR). MRS 2179 (2′-deoxy-N6-methyladenosine 3′,5′-bisphosphate) was purchased from Tocris (Bristol, UK). Agonists at purinergic receptors were administered for 2–4 min with application-free intervals of at least 10 min after recovery to baseline. TNP-ATP and MRS 2179 were usually given 10 min before application of the agonists.Data are given as deviation from the resting “peak amplitude” and the intracellular Ca2+baseline, both set as 100% (mean ± SD).Compound action potentials of unmyelinated axons (C-fiber component) were recorded from isolated fascicles of human vagus nerve during repetitive electrical stimulation at 1 Hz. Agonists and one antagonist at P2X receptors were applied via the bathing solution and tested on the peak amplitude of the C-fiber compound action potentials. A representative experiment is illustrated in figure 1. α,β-meATP was tested in concentrations from 1 to 30 μm, and a reduction in compound action potential amplitude was observed. Quantitatively (mean ± SD), α,β-meATP in a concentration of 1 μm did not change the peak amplitude, whereas a reduction in peak amplitude was observed in concentrations of 3 μm (−9.6 ± 4.8%, n = 3), 10 μm (−18.6 ± 10.3%, n = 3), 20 μm (−12.3 ± 3.3%, n = 9), and 30 μm (−20.1 ± 9.7%, n = 3).In further experiments, other agonists at P2X receptors were tested. Reduction in peak amplitude was also observed by using Ap5A (45 μm) and ATPγS (100 μm). These compounds reduced the amplitude of the C-fiber compound action potential by 8.4 ± 2.9% (n = 3) and 14.1% (n = 2), respectively. The effects of α,β-meATP (n = 4), Ap5A (n = 2), and ATPγS (n = 1) were completely blocked in the presence of 20 μm TNP-ATP (fig. 2).In additional experiments, application of ATP (100 μm) to the bathing solution induced a rapid and transient rise in intracellular Ca2+. Quantitatively, ATP (100 μm) increased the emission ratio of Calcium Green/Fura Red by 19.4 ± 10.8% (n = 7). MRS 2179 (20 μm), an antagonist at P2Y1receptors, blocked the ATP-induced intracellular Ca2+transient (fig. 3).The data indicate that recordings from isolated fascicles of human vagus nerve can be used for functional studies of P2Y and P2X receptors in the peripheral human nervous system. To our knowledge, this is the first optical and electrophysiologic study on an isolated human vagus nerve preparation. The presence of P2Y receptors in human peripheral nerve has already been demonstrated using ATP-induced Ca2+transients in isolated sural nerve. 10,11Schwann cells are most likely the cellular elements causing these intracellular Ca2+transients. 12In the current study, ATP-induced Ca2+transients were also found in isolated human vagus nerve (fig. 3). These Ca2+transients were blocked by MRS 2179, a potent antagonist at P2Y1receptors. 13This indicates that P2Y receptors are functional in both somatosensory and visceral human nerves.To our knowledge, electrophysiologic evidence for the activity of P2X receptors in the peripheral human nervous system has not been described, except for the observation that α,β-meATP induces contraction of muscle specimen from human bladder. 14In the current study, clear effects of agonists at P2X receptors were found on action potentials of unmyelinated axons in segments of human vagus nerve. The pharmacologic profile indicates the presence of P2X3and/or heteromeric P2X2/3receptors, because α,β-meATP is an agonist and TNP-ATP is an antagonist at these subtypes of P2X receptor. 15–17P2X receptors in human vagus nerve were also activated by the less specific P2X receptor agonists Ap5A 18and ATPγS. Recently, desensitization of P2X3receptors by low concentrations of Ap5A has been described. 19This effect was not tested in the current study. It is known that P2X receptors depolarize neurons. We therefore interpret the changes in compound action potentials as a consequence of axonal depolarization in the human vagus nerve (e.g. , due to inactivation of sodium channels).In previous studies, effects of ATP on afferent human nerve fibers have been observed using microneurography 20and sensory testing. In the latter case, pain was experienced on local application of ATP on a human blister base preparation 5or by iontophoresis of ATP to human skin. 6However, in intact nervous tissue, there is rapid enzymatic degradation of ATP to adenosine, 21and the effects of ATP seen in these studies might have been caused by activation of adenosine/P1 receptors. In fact, the effects of ATP on the excitability of unmyelinated axons in isolated segments of human sural nerve were blocked by adenosine receptor antagonists; evidence for activation of P2X receptors (using α,β-meATP) was not found. 10,22The effectiveness of α,β-meATP on human vagus nerve (current study) and its ineffectiveness on human sural nerve 10might be attributable to the expression of heteromultimeric P2X2/3receptors in human vagus nerve and homomeric P2X3receptors in human sural nerve. In this case, bath application of α,β-meATP is sufficient for activation of slowly desensitizing P2X2/3receptors 16and is probably too slow for the activation of rapidly desensitizing P2X3receptors.The function of P2X receptors on unmyelinated afferent nerve fibers in the vagus nerve is not well understood. There is evidence that 80–85% of the vagal nerve fibers are afferent. 23Mice lacking P2X3receptors have marked urinary bladder hyporeflexia, 24,25and it is plausible that a similar mechanosensory function may be found for P2X receptors in reflex control of distension of the esophagus and/or stomach. 4,9Models of visceral pain were not investigated in P2X3knock-out mice. However, TNP-ATP blocks acetic acid-induced abdominal constriction in mice, which indicates a contribution of P2X3and heteromeric P2X2/3receptors to inflammatory visceral pain. 3A possible function of P2X receptors in vomiting, emesis, and digestion should be explored. More selective, stable, and bioavailable P2X receptor antagonists might be helpful in such studies and in the treatment of visceral pain. 26Studies on isolated segments of human vagus nerve could be useful in such investigations.The authors thank Klaus Hallfeldt, M.D., Ph.D., and Thomas Mussack, M.D. (Staff Surgeons, Department of Surgery, University of Munich, Germany), for preparation of the vagus nerve; Christina Müller (Laboratory Technician, Department of Physiology, University of Munich) for technical assistance; and David J. Tracey, Ph.D. (Professor, Department of Anatomy, University of New South Wales, Sydney, Australia), for helpful discussions on the manuscript.

1. We measured the modulation of the background firing rate of cat spinal motoneurons produced by simulated, repetitive excitatory postsynaptic potentials (EPSPs) to test the accuracy of several proposed motoneuron input-output functions. Rhythmic discharge was elicited in the motoneurons by injecting suprathreshold current steps 1-1.5 s in duration. On alternate trials, trains of short (0.5-5 ms) current pulses were superimposed on the current steps to stimulate the effects of trains of individual EPSPs. The increase in firing rate (delta F) due to the addition of the pulses was calculated as the difference in motoneuron discharge rate between trials with and without the superimposed pulse trains. 2. In the same motoneurons, we were able to study the effects of changes in pulse frequency, duration, and amplitude, as well as changes in the background discharge rate. A sublinear relationship between pulse rate and delta F was observed, with delta F rising relatively steeply with increasing pulse frequency at low pulse rates and saturating at high pulse rates. A similarly shaped relation was observed between delta F and pulse duration. In contrast, delta F generally increased in a greater than linear fashion with increasing pulse amplitude. 3. In previous studies we demonstrated that when a relatively constant synaptic input is produced by high-frequency synaptic activity, delta F is approximately equal to the product of the net synaptic current reaching the soma and the slope of the motoneuron's steady-state frequency-current (f-I) relation. In the present study, this input-output function consistently underestimated the observed delta F, particularly for low input rates, indicating that the transient current pulses are more effective in modulating motoneuron discharge than an equivalent amount of constant current. 4. Other investigators have proposed input-output functions derived from the relation between synaptic potential amplitude and the magnitude of the peak of a cross correlogram compiled from the discharge of the pre- and postsynaptic neurons. These functions consistently overestimated the observed delta F, particularly for high pulse rates. This overestimation may result in part from the fact that the effects of a synaptic potential (or current pulse) on postsynaptic discharge probability also include a period of decreased firing probability. Moreover, the cross correlation function may depend on the arrival rate of synaptic potentials (or current pulses). 5. Another proposed input-output function based on a simple threshold-crossing model of the motoneuron with a fixed spike threshold predicts firing rates that were often close to the observed delta F. However, the model did not reproduce the observed relations between delta F and input pulse rate or pulse duration. 6. The deficiencies of the basic threshold-crossing model may arise from the fact that it does not incorporate variations in membrane conductance and firing threshold that occur in real motoneurons. A more complete motoneuron model that incorporates both of these features was able to replicate the observed delta Fs associated with changes in input pulse frequency and duration.

Tolerance level and rapid fatigue onset are limitations in the use of neuromuscular electrical stimulation (NMES) as an electrotherapeutic resource in rehabilitation and training protocols; however, it is unclear if pulsed current (PC) and alternating current (AC) produce different fatigue levels when applied at submaximal contraction level. The purpose of this study was to compare fatigue and discomfort levels between PC and AC during a submaximal contraction protocol in people who are healthy. In this double-blind, randomized crossover trial conducted in a laboratory setting, 30 male volunteers [23.23 years of age (SD=4.59)] performed 2 submaximal fatigue protocols (with a 7-day interval) in a randomized order: PC (pulse duration=2 milliseconds, pulse frequency=100Hz) and AC (2.5kHz, pulse duration=0.4 milliseconds, burst frequency=100Hz). NMES currents were applied to the knee extensor motor point of the dominant limb. The NMES protocol consisted of 80 evoked contractions (time on:off=5:10seconds) and lasted 20minutes. The current was maintained at a constant intensity throughout the NMES protocol. The primary outcome measures were maximal voluntary isometric contraction, fatigue index (evoked torque decline), fatigability (number of contractions for a 50% drop in evoked-torque from the protocol start), total evoked torque-time integral (TTI), decline in TTI, and discomfort level. AC at 2.5kHz demonstrated higher maximal voluntary isometric contraction decline post-fatigue, higher fatigue index, higher fatigability (ie, fewer contractions to reach the 50% evoked torque decline from the protocol start), smaller total TTI, and higher TTI decline compared with PC. No between-currents difference was observed in discomfort level. PC is less fatigable than AC at 2.5kHz. Based on this study, PC is the preferred current choice when the NMES goal is to generate higher muscle work, higher mechanical load, and smaller fatigability during training both for athletes who are healthy and for rehabilitation programs for people with disease or injury.

The present research work aims to optimize the process parameters in the Pulsed Current Gas Tungsten Arc Welding (PCGTAW) process by employing the Design of Experiment (DOE) technique on ASTM 106 Grade-B Steel pipes. Taguchi method-based orthogonal array, L9 for four factors Pulse current (PC), Background Current (BC), Pulse Frequency (PF), and Pulse on time (PO) with three levels are employed. The higher the better reaction is picked to decide the ideal conditions for maximum ultimate tensile strength. The optimum values are found to be 220 A pulse current, 100 A background current, 4 Hz pulse frequency, and pulse ontime 50 %. ANOVA is implemented to gauge each factor's % contribution. The outcomes indicate that background current and pulse current are the significant process parameters to yield maximum ultimate tensile strength. Regression equations are used to model ultimate tensile strength, microhardness, and impact strength. Confirmation experiments are conducted to validate the results.

Pulse-electrodeposited NiP–SiC composite coatings

Prediction and optimization of pulsed current tungsten inert gas welding parameters to attain maximum tensile strength in AZ61A magnesium alloy

The idea of using electrical pulse current at manual arc welding with coated electrode starts from the observation of frequency influence, unchanging in manual TIG welding with filler materials, on weld pool volume, by partial solidification of the weld pool in base time of the pulse current, thus being able to control its volume.This paper presents for the first time this new challenge of inverter modern sources: manual metal arc welding using pulsed current.Experimental research findings highlight the technological aspects when using pulsed current in manual metal arc welding, using STEL welding equipment that has this option. The application - concerns the establishment the lack of fusion welded joints in fillet positions. It highlights the beneficial effect of pulsed current, in particular by the joint penetration.Experiments have pursued highlighting of welding pulsed current and frequency of the pulses by the appearance of the joint and the influence by weld geometry for lack of fusion fillet joint. Also, the influence of frequency pulsed current by arc stability, sprays, etc. compared with standard welding was observed.

Microstructure and mechanical properties of Mg-Nd-Zn-Zr alloy fabricated by TIG-based wire – Arc directed energy deposition with pulsed current

Lithium-ion batteries are commonly charged following the constant current -constant voltage (CC-CV) protocol. Current flow during charging implies an equivalent ionic flow through the battery materials. Intercalation and de-intercalation of Li+ are accompanied by concentration gradients that are reflected by the rise in the cells’ potentials that is required to maintain the constant current during the CC regime. In this work, two new pulsed charging protocols were tested. Firstly, a square current pulse is applied to the cell until the cut-off voltage is reached, followed by a pulsed square voltage protocol (PV). The second methodology keeps the same current pulse, however, after the limiting voltage was reached, the pulsing regime consisted in alternating between a maximum voltage value and a minimum, non-zero, constant current value. Different voltage pulse widths and frequencies were tested, in order to study the maximum electrodes’ capacity, the time required to reach that capacity, the contribution of each individual step (i.e. PC and PV) to the total electrodes’ capacity, and the thermal variations for each. The second pulsing mode produced capacity values 7%–8% higher than in the classical CC–CV protocol, and in charging times periods from 5%–25% faster, without compromising the batteries’ cycle life.

This study investigates the Pulsed Current Gas Tungsten Arc Welding (PCGTAW) of ASME SA 106 low-carbon steel pipes, used in steam boiler membrane walls. Pipes of 50 mm diameter and 5 mm thickness are welded using a 1.5 mm root gap, 1 mm land and 30° chamfer. The root pass used 1.2-mm ER70S2 filler wire, and the final pass used 2.5-mm wire. The key parameters, namely pulse current, background current, frequency and pulse-on time, are optimized using a Taguchi L9 orthogonal array and ANOVA. Optimal settings are 200 A pulse current, 100 A background current, 4 Hz frequency and 50% pulse-on time. The resulting welds exhibited an ultimate tensile strength of 469.46 N/mm2 (14% higher than base metal) and an impact strength of 116 J (10% lower) than base metal. Microstructure reveals acicular and polygonal ferrite, carbides and pearlite. Microhardness is 205 HV. Fractography indicates ductile failure. XRD revealed Fe, Fe3 C and Fe4 C phases; EDAX showed Cr and Si, contributing to strength. Corrosion analysis reveals slight increase in weld area corrosion rate (0.026662 mm/year) compared to the base metal (0.022601 mm/year). Overall, optimized PCGTAW yields strong, reliable joints suitable for pressure vessel.

Oxide layers on Mg97Y2Zn1 magnesium alloy with strengthening LPSO-phase were formed by plasma electrolytic oxidation (PEO) in bipolar mode with frequency variation of forming current pulses (50 and 500 Hz) and addition of sodium aluminate or sodium silicate to alkali phosphate fluoride electrolyte. Microstructure, chemical and phase composition, corrosion and mechanical properties of the oxide layers formed were investigated. With increasing current frequency for both electrolytes, an increase in homogeneity of the oxide layers structure and a decrease in their porosity and fracturing at constant thickness were recorded. The oxide layers formed at 500 Hz even with some decrease in hardness have better adhesive strength and 2 orders of magnitude higher short-term corrosion resistance values. PEO of Mg-alloy with LPSO-phase in the electrolyte with addition of sodium aluminate in combination with increased pulse frequency (500 Hz) allows forming the best-quality uniform oxide layer with high hardness, adhesive strength and corrosion resistance properties. The use of electrolyte with addition of sodium silicate reduced the adhesive strength by 1.5 times and brought down the long-term corrosion resistance of oxide layers by an order of magnitude, as compared with the electrolyte with sodium aluminate. The reason for a significant improvement in the complex of protective properties of the oxide layers with an increase in the current pulse frequency is supposed to be a decrease in the power and duration of individual microarc discharges with simultaneous increase in their number per unit oxidized area.

Pulsatile secretion of prolactin in laying and incubating turkey hens

A study on the wear resistance characteristics of pulse electroforming Ni–P alloy coatings as plated

Lithium-ion batteries (LIBs) require to be preheated under cold weather to restore performance, while DC pulse discharging is often considered a promising approach. Applying a larger pulse current can shorten the heating time, but it may lead to battery decay and demand additional cost. To keep the current lower in preheating, it is necessary to explore the effects of pulse current on the cell temperature rise and make full use of the battery’s heat-generating potential. This paper experimentally compared the effects of DC pulse, average (AVG) current, root mean square (RMS) current, pulse frequency, and state of charge (SOC) of the LIBs on its temperature rise rate, respectively. It is found that within the frequency of 1 kHz~10 kHz, the heat generation is affected by all factors above, among which the frequency has less impact while AVG current has the highest impact. During DC pulse discharging, it is shown that there is more entropy heat produced than the Joule heat in some SOC ranges. Therefore, entropy heat cannot be overlooked in the heat generation model. Moreover, as the thermal coefficient of entropy varies greatly with the SOC, the battery temperature rise rate will be inconsistent during the DC pulse discharging, which might cause an inconsistent warm-up time.

Optimization of Process Parameters of Laser Cladding 304L Alloy Powder Based on Orthogonal Experiment