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Injection of bicuculline elicits firing of luteinizing hormone releasing hormone pulse generator in muscimol-treated ovariectomized rats.

We have already demonstrated that, although exogenous gamma-aminobutyric acidA (GABAA) receptor agonist is capable of inhibiting the activity of luteinizing hormone releasing hormone (LHRH) pulse generator, the reduction in the endogenous GABAA receptor activity does not have a significant effect in ovariectomized rats, suggesting a minor role of inhibitory GABA neurons in the control of pulsatile release of LHRH. In this study, we further analyzed the role of the GABAA receptor system in the regulation of LHRH pulse generator activity observed by recording the multiunit activity (MUA) in the hypothalamus of ovariectomized rats. An abrupt increase (volley) in the MUA in the arcuate nucleus (ARC)-median eminence region (ME) was accompanied by the initiation of a luteinizing hormone (LH) pulse, determined by measuring LH concentrations in blood sampled simultaneously. The injection of 1-3 mg/kg muscimol (MUS), a GABAA receptor agonist, decreased the basal MUA and delayed the occurrence of the next MUA volley, but it did not change the LH pulse amplitude. I.v. injection of 5 mg/kg bicuculline (BIC), a GABAA receptor antagonist, during continuous infusion of MUS (5 mg/kg/h) which decreased the basal MUA and prevented the MUA volley from occurring, evoked MUA volleys and LH pulses whose amplitudes were similar to those found before the MUS infusion. Injection of the same dose of BIC during the infusion of saline increased the MUA transiently, but this increase was not accompanied by an LH pulse and afterwards there occurred MUA volleys at ordinary intervals accompanied by LH pulses with unchanged pulse amplitudes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Factors affecting paired-pulse facilitation in hippocampal CA1 neurons in vitro.

Factors underlying paired-pulse facilitation (PPF) were studied by intracellular and field recordings of CA1 neurons in the hippocampal slice in vitro, following stimulation of the Schaffer collaterals apical dendritic afferents. Similar magnitudes of PPF were found using the slopes or peaks of the excitatory postsynaptic potentials (EPSPs) recorded intracellularly or extracellularly at the soma or dendrites. The paired-pulse EPSP facilitation index (EPI), defined as the ratio of EPSP slope evoked by the second pulse (E2) to that evoked by the first pulse (E1), had a broad peak at 30-60 ms interpulse interval (IPI). EPI was largest at small E1 and decreased with an E1 increase. Spiking excitability was enhanced after the second as compared to the first pulse as evidenced by (1) a decreased latency to fire and (2) an increased tendency to fire double or multiple spikes. The PPF of spiking resulted partly from an increased E2 and partly from a diminished inhibition evoked by the second pulse. Whether the first pulse elicited a spike or not had no significant effect on the EPI. Multiple spiking evoked by the second pulse was partly blocked by the GABAB antagonist CGP35348 (1 mM). The PPF of the EPSP slopes, however, was not significantly affected by GABAB antagonists, GABAA antagonist bicuculline or NMDA antagonist 2-aminophosphonovalerate. In conclusion, PPF may serve as a means of amplification of synaptic transmission such that reliable spike output may result from a given set of synapses.

Action Potentials↗

Pulse duration and alpha 2-adrenoceptors modify noradrenaline release from field-stimulated atria.

In guinea-pig atria preloaded with 10 muCi [3H]noradrenaline, field stimulation during the refractory period increased the release of radioactivity and the force of contraction. Both effects were dependent on the extracellular Ca2+ concentration and were abolished by 3 x 10(-8) mol/l tetrodotoxin. When applied during each refractory period, two short (0.05 ms) pulses released significantly more radioactivity than one pulse of 0.1 ms duration applied during each refractory period. Similarly, a train of four pulses (0.05 ms each) was more effective than one pulse lasting 0.2 ms. The radioactivity released by single, long-lasting pulses in each refractory period was increased by phentolamine, idazoxan and N-ethylmaleimide. A small increase was also obtained with prazosin. The effect of phentolamine was antagonized by clonidine but not by phenylephrine. Clonidine did not prevent the effect of N-ethylmaleimide (all drugs 3 x 10(-5) mol/l; atropine 10(-7) mol/l and cocaine 3 x 10(-6) mol/l present in all experiments). It is concluded that activation of prejunctional alpha 2-adrenoceptors reduces the amount of noradrenaline release by one long field pulse in each refractory period. In most experiments, the inotropic effect of the two stimulation protocols was not significantly different. However, when atria were stimulated with four pulses immediately before stimulation with one pulse, the autoinhibition thus caused was strong enough to also reduce the inotropic effect of this stimulation protocol.

Adrenergic alpha-Agonists↗

Continuous monitoring of fetal oxygen saturation by pulse oximetry.

OBJECTIVE: To compare spectrophotometric saturation values of fetal blood sampling to the saturation readings by pulse oximetry. METHODS: During a clinical trial, fetal oxygen saturation was monitored during labor by a fetal oxisensor and a fetal pulse oximeter. Fifty-one fetal scalp blood samples were assessed because of abnormal fetal heart rate (FHR) patterns. The pulse oximeter displayed only signal quality readings. The investigator had to perform adjustments if signal quality fell below 50%. After delivery, the saturation at the moment of fetal blood analysis could be read from a printout and compared to the saturation values of scalp blood sampling. RESULTS: The share of usable signal time was 51% overall, but only 40% in the 20-minute period during fetal blood sampling. Comparison with the reference method resulted in a median deviation of 6% (tenth percentile -10%; 90th percentile 18%) for pulse oximetry. The correlation coefficient between saturation values by pulse oximetry and fetal scalp blood sampling was 0.67. The correlation coefficient with the partial pressure of oxygen and oxygen saturation by pulse oximetry was 0.61, whereas it was 0.88 between partial pressure and saturation from the spectrophotometric analysis of the scalp sample. CONCLUSIONS: Fetal pulse oximetry corresponds satisfactorily to results from fetal blood analysis. Low invasiveness and continuous monitoring are the advantages of this method. At present, the available sensor generates only a limited amount of signal time. However, in combination with FHR monitoring, pulse oximetry promises greatly improved detection of fetal hypoxia.

Female↗

Modification of acoustic and tactile startle by single microwave pulses.

Single microwave pulses at 1.25 GHz were delivered to the head and neck of male Long-Evans rats as a prestimulus to acoustic and tactile startle. For acoustic startle, pulses averaging 0.96 microsecond in duration were tested with two specific absorption rate (specific absorption) ranges, 15.0-30.0 kW/kg (16.0-44.2 mJ/kg) and 35.5-86.0 kW/kg (66.6-141.8 mJ/kg), delivered 201, 101, 51, 3, and 1 ms before and 1 ms after onset of a startling noise. The low-intensity pulse did not affect peak amplitude, integral, or latency of the whole-body startle response. The high-intensity pulse at 101 and 51 ms inhibited the startle response by decreasing peak amplitude and integral; at 201 and 51 ms latency was increased. The high-intensity pulse at 1 ms enhanced the startle response by increasing peak amplitude and at 3 ms by increasing integral. For tactile startle, either microwave pulses averaging 7.82 microseconds in duration and 55.9-113.3 kW/kg (525.0-1055.7 mJ/kg) or 94 dB SPL clicks were delivered 157, 107, 57, and 7 ms before and 43 ms after onset of a startling air burst. The microwave pulse at 57 ms inhibited the startle response by decreasing peak amplitude; at 157, 107, 57, and 7 ms it increased latency. The microwave pulse at 43 ms after onset enhanced the startle response by increasing peak amplitude. The acoustic click at 157 and 57 ms inhibited the startle response by decreasing peak amplitude; at 157,2 107, and 57 ms it increased latency.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

Corpus luteum regression induced by ultra-low pulses of prostaglandin F2 alpha.

In view of the pulsatile nature of PGF2 alpha secretion from the ovine uterus at the time of luteolysis, experiments were designed to examine the effect of pulsed infusions of PGF2 alpha on luteal function and to re-examine the minimal effective levels of PGF2 alpha required to induce luteolysis. To mimic physiological conditions, hour-long infusions of PGF2 alpha in increasing concentrations were given either 4 times in 19 h or 5 times in 25 h into the arterial supply of the autotransplanted ovary in conscious sheep on day 12 of an induced cycle. Blood flow and progesterone secretion rate from the ovary were used to monitor directly the luteolytic effect of administered PGF2 alpha. The concentration of LH in peripheral plasma was measured throughout each infusion experiment and the presence of a preovulatory peak of LH was used as an indicator of the permanence of luteal regression. Four pulses of PGF2 alpha in 19 h caused complete corpus luteum regression in only 1 of 4 animals whereas the addition of a fifth pulse (5 pulses in 25 h) caused permanent regression in 4 out of 4 animals. Infusion of 5 hour-long pulses of saline or PGF2 alpha at a rate less than 0.04 microgram/h did not induce permanent suppression of progesterone secretion. The average total effective dose of PGF2 alpha required to induce luteal regression when given as 5 pulses was 1/40th of the amount currently regarded as the minimal effective one when given by constant infusion into the ovarian artery. In another series of experiments the luteolytic effect of a single hour-long pulse of 0.1 microgram/h PGF2 alpha given daily for either 3 or 4 days was investigated. A significant fall (ANOVA, F0.01) in progesterone secretion rate, which reached a nadir at 5.3 +/- 2.2 h (means +/- S.D., n = 15), was followed by a recovery of progesterone secretion rate. Permanent luteal regression did not occur with this protracted regimen, suggesting that a relatively short pulse frequency of PGF2 alpha over a minimal period of 24 h is a necessary condition for physiological regression of the corpus luteum in sheep.

Animals↗

Randomized double pulse stimulation for assessing stimulus frequency-dependent conduction in injured spinal and peripheral axons.

Injury compromises the ability of axons to conduct action potentials at high frequencies. To study stimulus frequency-dependent conduction in injured spinal and peripheral axons, we developed a new stimulation paradigm which applies trains of double pulses at 5 Hz and randomly varied interpulse intervals of 3, 4, 5, 8, 10, 30, 50, and 80 msec. In each double pulse, the first pulse was used to condition the response activated by the second test pulse. Responses elicited by double pulses with 80 msec intervals served as controls. The L5 dorsal root was stimulated to activate dorsal column and dorsal root compound action potentials in pentobarbital anesthetized rats. To injure the spinal cord, we compressed the cord stepwise (0.25 mm every 5 min) until action potential conduction across the compression site was abolished and then decompressed the spinal cord 10 min later. Before injury, conditioning pulses applied 3-80 msec before the test pulses did not alter dorsal column responses except for a slight amplitude augmentation at 20 msec interpulse intervals (mean +/- S. E., + 4.2 +/- 0.8%, P less than 0.02) compared to controls. Injury had 3 effects on the responses. First, it significantly reduced response amplitudes and increased response latencies at 3-5 msec interpulse intervals, i.e., responses activated with 3 msec intervals were 26.0 +/- 7.4% (P less than 0.002, paired t test, n = 6) smaller and had 108 +/- 45 microseconds (P less than 0.04) longer latency than control responses. Second, response amplitude increases at 20 msec interpulse intervals (9.0 +/- 0.7%, P less than 0.0001) significantly exceeded those observed before injury (P less than 0.02, paired t test). Third, injury accentuated response amplitude declines during the stimulus train, most prominently at 80 msec intervals. Spinal cord injury did not affect the dorsal root responses. L5 root compression injury depressed dorsal root action potentials at 3-5 msec interpulse intervals (36.9 +/- 8.4%, n = 4, P less than 0.0001) but had no other effect on the responses. Our data indicate that randomized double pulse evoked potentials are sensitive detectors of acute axonal dysfunction and can be used to quantify stimulus frequency-dependent conduction deficits in injured central and peripheral axons.

Action Potentials↗

The propagation of Gaussian modulated pulses in dissipative and/or dispersive media such as tissue.

The interrogating pulse used in most conventional medical ultrasonic imaging systems can be approximated as a band-limited Gaussian modulated pulse. In this paper we analyze the propagation of such a pulse in an attenuating media such as tissue. We show that an initially Gaussian pulse retains its Gaussian shape during propagation provided that the medium has attenuation with a power-law dependence on frequency of between zero and two. That is, if the attenuation factor is e- alpha x, where alpha is the attenuation coefficient and x is the distance over which the pulse has traveled, then the pulse will remain Gaussian provided alpha = afp, where a is a constant, f is the frequency, and 0 less than p less than or equal to 2. This condition is certainly valid for soft tissue (p approximately 1) as well as for all other attenuating materials with which we are familiar. Although a Gaussian pulse retains its Gaussian shape in an attenuating media, it does suffer a shift in its mean frequency as well as a broadening in its shape. Here we also obtain analytical expressions relating the mean frequency shift and the pulse broadening to the attenuating properties of the medium. In contrast to other studies recently published in the literature, we consider propagation in a medium which has velocity dispersion as well as frequency dependent loss.

Animals↗

Numerically optimized RF-refocusing pulses in localized MR proton spectroscopy.

The slice selection properties of three different soft refocusing-pulses (sinc-pulse, Hanning filtered sinc-pulse, and the numerically optimized reburp-pulse) within a standard double spin-echo sequence for localized proton spectroscopy were examined and compared. The slice profiles were measured acquiring two-dimensional images of the selected volumes of interest (VOI) appending a gradient-echo imaging part at the end of the spectroscopic part of the sequence. A comparison of the reached signal strength with the different pulses using the same voxel size (same Full Width Half Maximum, FWHM) was performed by in vitro and in vivo measurements. Additionally theoretical calculations using the Schrödinger equation for spin 1/2 particles in combination with a phase averaging method that takes into account the magnetic field spoiling and selection gradients of the spectroscopy sequence were performed. Calculated and measured slice profiles did well correspond. The numerically optimized reburp-pulse showed significant better slice selection and phase behaviour properties compared to the sinc-pulses. Further, a signal gain of about 20% was measured using the reburp-pulse, which was in good agreement with the calculated signal gain of 23%.

Adolescent↗

Continuous intra-arterial oximetry, pulse oximetry, and co-oximetry during cardiac surgery.

This study evaluated arterial catheter oximetry versus pulse oximetry in eight patients (ASA III-IV) who underwent cardiac surgery. Co-oximeter saturation values served as the standard. Arterial oxygen saturation was determined simultaneously with these three methods at 162 prospectively defined points of measurement before, during, and after cardiopulmonary bypass (CPB). At the same times before and after CPB, arterial, pulmonary arterial, and central venous pressures, and cardiac output determinations were recorded. Saturation readings were obtained in more than 99% of measurements with catheter oximetry and in only 59% to 84% of measurements with pulse oximetry. Failure of pulse oximetry correlated with low mean arterial pressures and low cardiac outputs, but not with high systemic vascular resistance. The mean saturation values determined by catheter oximetry as well as by pulse oximetry differed from the mean values obtained by co-oximetry by less than 1% (= bias). The standard deviations of the individual differences between readings of catheter or pulse oximetry and readings of co-oximetry (= precision) were +/- 0.5% to +/- 1.0% for catheter oximetry and +/- 1.0% to +/- 1.2% for pulse oximetry. In summary, catheter oximetry was superior to pulse oximetry with regard to obtaining readings and to reliability of the obtained readings. Invasiveness and high costs influence the decision as to whether to use catheter oximetry, but if reliable and precise measurements of saturation are important at any time during surgery, pulse oximetry is an insufficient method and co-oximetry is a time-consuming method of analysis, whereas catheter oximetry is quick, reliable, and precise.

Adult↗

Use of fetal pulse oximetry among high-risk women in labor: a randomized clinical trial.

OBJECTIVE: The purpose of this study was to determine the clinical role of fetal pulse oximetry to reduce cesarean delivery for a nonreassuring fetal heart rate tracing. STUDY DESIGN: Singletons > or =28 weeks were randomized to fetal pulse oximetry plus electronic fetal heart rate monitoring (monitoring + fetal pulse oximetry) or monitoring alone. RESULTS: Overall, 360 women in labor were recruited: 150 cases with monitoring+fetal pulse oximetry and 177 cases with monitoring alone were analyzed. Most demographic, obstetric, and neonatal characteristics were similar. Specifically, the gestational age, cervical dilation, and station of the fetal head were not differential factors. In addition, cesarean delivery for nonreassuring fetal heart rate tracing was not different between the group with monitoring+fetal pulse oximetry (29%) and the group with monitoring alone (32%; relative risk, 0.95; 95% CI, 0.75, 1.22). Likewise, cesarean delivery for arrest disorder was similar between the group with monitoring+fetal pulse oximetry (22%) and the group with monitoring alone (23%; relative risk, 1.05; 95% CI, 0.79, 1.44). However, the decision-to-incision time was shorter for the group with monitoring+fetal pulse oximetry (17.8 +/- 8.2 min) than for the group with monitoring alone (27.7 +/- 13.9 min; P < .0001). CONCLUSION: The use of fetal pulse oximetry with electronic fetal heart rate monitoring does not decrease the rate of cesarean delivery, although it does alter the decision-to-incision time.

Adult↗

Calcium bursts induced by nanosecond electric pulses.

We report here real-time imaging of calcium bursts in human lymphocytes exposed to nanosecond, megavolt-per-meter pulsed electric fields. Ultra-short (less than 30 ns), high-field (greater than 1 MV/m), electric pulses induce increases in cytosolic calcium concentration and translocation of phosphatidylserine (PS) to the outer layer of the plasma membrane in Jurkat T lymphoblasts. Pulse-induced calcium bursts occur within milliseconds and PS externalization within minutes. Caspase activation and other indicators of apoptosis follow these initial symptoms of nanosecond pulse exposure. Pulse-induced PS translocation is observed even in the presence of caspase inhibitors. Ultra-short, high-field, electroperturbative pulse effects differ substantially from those associated with electroporation, where pulses of a few tens of kilovolts-per-meter lasting a few tens of microseconds open pores in the cytoplasmic membrane. Nanosecond pulsed electric fields, because their duration is less than the plasma membrane charging time, develop voltages across intracellular structures without porating the cell.

Calcium↗

Is urea pulsing in toadfish related to environmental O2 or CO2 levels?

The neurochemical, serotonin (5-hydroxytryptamine; 5-HT) is involved in the regulation of toadfish pulsatile urea excretion as well as the teleost hypoxia response. Thus, the goal of this study was to determine whether environmental conditions that activate branchial chemoreceptors also trigger pulsatile urea excretion in toadfish, since environmental dissolved oxygen levels in a typical toadfish habitat show significant diel fluctuations, often reaching hypoxic conditions at dawn. Toadfish were fitted with arterial, venous and/or buccal catheters and were exposed to various environmental conditions, and/or injected with the O(2) chemoreceptor agonist NaCN or the 5-HT(2) receptor agonist alpha-methyl-5HT. Arterial PO(2), as well as ammonia and urea excretion were monitored. Natural fluctuations in arterial PO(2) levels in toadfish did not correlate with the occurrence of a urea pulse. Chronic exposure (24 h) of toadfish to hyperoxia was without effect on nitrogen excretion, however, exposure to hypoxia caused a significant reduction in the frequency of urea pulses, and exposure to hypercapnia resulted in a reduction in the percentage of nitrogen waste excreted as urea. Of toadfish exposed acutely to hypoxia, 20% pulsed within 1 h, whereas none pulsed after normoxic or hypercapnic treatments. Furthermore, 20% of fish injected intravenously with NaCN pulsed within 1 h of injection, but no fish pulsed after injection of NaCN into the buccal cavity. To test whether environmental conditions affected 5-HT(2) receptors, toadfish were injected with alpha-methyl-5HT, which elicits urea pulses in toadfish. No significant differences in pulse size occurred among the various environmental treatments. Our findings suggest that neither the environmental conditions of hypoxia, hyperoxia or hypercapnia, nor direct branchial chemoreceptor activation by NaCN play a major role in the regulation of pulsatile urea excretion in toadfish.

Animals↗

Performance of pulsed plate bioreactor for biodegradation of phenol.

Biodegradation of phenol was carried out using Nocardia hydrocarbonoxydans immobilised on glass beads, in a pulsed plate bioreactor. The effect of operating parameters like frequency of pulsation and amplitude of pulsation on the performance of pulsed plate bioreactor for biodegradation of phenol in a synthetic wastewater containing 500ppm phenol was studied. Axial concentration profile measurements revealed that the pulsed plate bioreactor shows continuous stirred tank behaviour. As the amplitude was increased, percentage degradation increased, reaching 100% at amplitude of 4.7cm and higher. Introduction of pulsation is found to increase the percentage degradation. Percentage degradation has increased with increase in frequency and 100% degradation was achieved at 0.5s(-1) and above. Biofilms developed in a non-pulsed bioreactor were thicker than those in the pulsed plate bioreactor. But biofilm thickness remained almost constant with increasing frequency. Biofilm density was found to be influenced by pulsation. The time required to reach steady state was more for pulsed reactor than the non-pulsed reactor and this start-up time had increased with increase in frequency of pulsation. The performance studies reveal that the pulsed plate bioreactor with immobilized cells has the potential to be an efficient bioreactor for wastewater treatment.

Biodegradation, Environmental↗

Enhancing sonochemical activity in aqueous media using power-modulated pulsed ultrasound: an initial study.

Relatively little is known about the effects of pulsed ultrasound on the facilitation of chemical reactivity. Previous studies have indicated that sonochemistry using pulses is generally less effective than continuous ultrasonic irradiation. However, the pulse trains employed were such that the peak power of the pulses was the same as the maximum power used in continuous irradiation. As a result, less acoustic energy was transmitted to the solutions over the same period of time. The effectiveness of ultrasound when the pulse is adjusted so that the same amount of acoustic energy is input compared to continuous irradiation over a given time has not been previously explored. In this study we have embarked on an examination of the efficacy of power-modulated pulsed (PMP) sonochemistry. Specifically, we have explored the effects of pulse type and pulse frequency on the oxidation of potassium iodide and the degradation of acid orange, a common industrial colorant. A rate increase by a factor of three was observed compared with continuous irradiation under conditions of equivalent acoustic input power.

Journal Article↗

Characterization of electric-pulse-induced permeabilization of porcine skin using surface electrodes.

We measured the transient and long-term changes of permeability of full-thickness porcine skin after the application of a single or a train of electric pulses, as the basis for optimization of the electrical parameters for enhancing transdermal drug or gene delivery by electroporation. Two electrodes were attached to the stratum corneum of excised skin for transdermal electric pulse delivery and impedance measurement. Both transient and long-term permeabilization were found to be dependent on the electrical exposure dose, i.e., the product of pulse voltage and cumulative pulsing (exposure) time. Skin resistance dropped to about 20% of its prepulsing value when pulsed beyond a critical dosage of 0.4 V-s (with 20-40 V across each skin path), but recovered rapidly within seconds after the pulse. Long-term permeabilization of the skin required repeated pulsing with a minimum potential of 160 V (80 V across each skin path). The maximum long-term resistance drop, to 35% of the initial value, required a dose greater than 200 V-s, recovering slowly and seldom completely in tens of minutes to hours. The decrease and recovery of the resistance were dependent on the frequency and pulse length only for low-dose electrical exposure.

Administration, Cutaneous↗

Photoresponses of Halobacterium salinarum to repetitive pulse stimuli.

Halobacterium salinarum cells from 3-day-old cultures have been stimulated with different patterns of repetitive pulse stimuli. A short train of 0.6-s orange light pulses with a 4-s period resulted in reversal peaks of increasing intensity. The reverse occurred when blue light pulses were delivered as a finite train: with a 3-s period, the response declined in sequence from the first to the last pulse. To evaluate the response of the system under steady-state conditions of stimulation, continuous trains of pulses were also applied; whereas blue light always produced a sharply peaked response immediately after each pulse, orange pulses resulted in a declining peak of reversals that lasted until the subsequent pulse. An attempt to account for these results in terms of current excitation/adaptation models shows that additional mechanisms appear to be at work in this transduction chain.

Biophysical Phenomena↗

Time-dependent ultrastructural changes to porcine stratum corneum following an electric pulse.

The morphological changes to heat-stripped porcine stratum corneum following an electroporating pulse were studied by time-resolved freeze fracture electron microscopy. Pulses at a supra-electroporation threshold of 80 volts and 300 microseconds were applied across the stratum corneum with a pair of copper plate electrodes, which also served as cooling contacts. Multilamellar vesicles of 0.1-5.5 mm in diameter in the intercellular lipid bilayers of the stratum corneum appeared in less than milliseconds after pulsing. Pulsed samples exhibited aggregations of vesicles, whereas only occasional single vesicles were seen in the unpulsed samples. Aggregates form in less than a millisecond and disappear within minutes after the pulse. Their size ranged from 0.3 to 700 mm2. The size of individual vesicles, aggregate density, and size were analyzed as functions of postpulse time. These aggregate formations seem to be a secondary reaction to the pulse-induced skin permeabilization, determined by the resistance drop and recovery after the pulse. Heating the samples to 65 degrees C also caused vesicle aggregates of similar appearance to form, suggesting that these aggregations are related to the heating effect of the pulse. Hydration is thought to play an important role in aggregate formation.

Administration, Cutaneous↗