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PubMed1990

Three-generation reproductive study of cocoa powder in rats.

Male and female Sprague-Dawley rats were continuously exposed to dietary cocoa powder at levels of 0.0, 1.5, 3.5 or 5.0% for three generations. During the initial 12-wk growth periods for the F0-, F1b- and F2b-generation rats, mean methylxanthine exposures (mg/kg/day) for males/females were 30/36, 72/86 and 104/126 for the 1.5, 3.5 and 5.0% cocoa powder groups, respectively. No consistent dose-related effects on any of the monitored reproductive indices (mating, fertility, conception, gestation, viability or lactation) were noted over three generations. Minor reductions in mean body weight relative to controls at wk 12 were observed in male rats exposed to 3.5 or 5.0% cocoa powder and female rats exposed to 5.0% cocoa powder in the F1b and F2b generations. Renal tubular mineralization in the F0-generation male rats in the 5.0% cocoa powder group was the only statistically elevated histomorphological lesion observed. Plasma cholesterol concentrations in F1b-generation rats were elevated, but cocoa powder did not affect this parameter consistently across multiple generations. Thus, continuous cocoa powder consumption by rats at levels as high as 5.0% of the diet was without effect on reproductive capacity under the conditions of a standard three-generation evaluation.

Animals↗

PubMed1991

Afferent control of central pattern generators: experimental analysis of scratching in the decerebrate cat.

Systematic quantitative analysis of changes in the spinal scratching generator motor activity evoked by tonic and phasic peripheral afferent signals during "fictitious" scratching was carried out in the cat. Correlations between the kinematics of hindlimb scratching movement, sensory inflow, and primary afferent depolarization were investigated. Reliable correlations between the parameters of generator motor activity during fictitious scratching were revealed: they depended on tonic peripheral afferent inflow. The functional role of these dependencies consists of providing stability for aiming the hindlimb to the itch site. It was shown that scratching generator reaction to a phasic sensory signal depended significantly on afferent input, signal intensity, and its arrival phase in the cycle of motor activity. Phase correction of "scratching" rhythm was performed by inhibition of the current stage of "scratching" cycle, the inhibition magnitude depending on the intensity of a sensory signal run along high threshold afferent fibers. The moments in the scratching cycle, in which the afferent signal caused no rearrangement in scratching generator activity, were discovered for all investigated afferent inputs. These moments corresponded to the transitions from one scratching cycle phase to another. Integral afferent activity was distributed unevenly in the cycle during real scratching. The main part of it was observed just in that scratching cycle part which included the above mentioned no rearrangement phase points. The data obtained allowed us to conclude that the scratching generator should be considered as a working program for the motor optimal control system containing the intrinsic model of the controlled object dynamics (e.g. hindlimb scratching movement dynamics), which produces an inner analog of peripheral flow. This inner flow interacts with peripheral afferent inflow just as one of the latter components. Centrally originated modulation of primary afferent depolarization is a result of affecting the depolarization generating system by this inner "sensory" activity. It is the model, with the aid of which the generator can work after deafferentation. The functional organization of a central pattern generator is considered.

Afferent Pathways↗

PubMed1996

Fast Na+ spike generation in dendrites of guinea-pig substantia nigra pars compacta neurons.

Electric fields were applied to study the regenerative properties of substantia nigra pars compacta neurons in guinea-pig brain slices. Two types of spikes, of high or low amplitude, were generated in both the soma-hyperpolarizing and the soma-depolarizing directions of the field. The different sensitivity of the spikes to somatic polarization suggested that the high-amplitude spikes were generated near the cell body, whereas the low-amplitude spikes were generated at a distance from the soma. Application of tetrodotoxin or intracellular injection of QX 314 abolished both types of spike. The spikes were not inhibited in the presence of glutamate receptor antagonists or during Ca2+ channel blockade. Blockers of gap junctional conductance (sodium propionate, octanol and halothane) did not affect the field-induced spikes. The spike generation was highly sensitive to changes in membrane conductance induced by current injection in the soma or by external field application. The ability of a conditioning field stimulation to affect the spike generation in different neuronal compartments suggested that a transient outward current was generated in the dendrites. The field-induced spikes were facilitated by synaptic stimulation and, in some neurons, low-amplitude spikes were generated by synaptic potentials in the absence of field application. These results suggest that channels responsible for Na+ spike generation reside in the dendrites, and are influenced by spatially distributed voltage-dependent K+ currents and by synaptic input.

Anesthetics, Local↗

PubMed1996

Generators of the brainstem auditory evoked potential in cat. II. Correlating lesion sites with waveform changes.

Brainstem regions involved in generating the brainstem auditory evoked potential (BAEP) were identified by examining the effects of lesions on the click-evoked BAEP in cats. An excitotoxin, kainic acid, was injected into various parts of the cochlear nucleus (CN) or into the superior olivary complex (SOC). The locations of the resulting lesions were correlated with the changes produced in the various extrema of the BAEP waveforms. The results indicate that: (1) the earliest BAEP extrema (P1, N1 (recorded between vertex and the earbar ipsilateral to the stimulus) and P1a, P1b, (vertex to contralateral earbar)) are generated by cells with somata peripheral to the CN; (2) P2 is primarily generated by posterior anteroventral CN (AVCNp) and anterior posteroventral CN (PVCNa) cells; (3) SOC, anterior anteroventral CN (AVCNa), AVCNp, and PVCNa cells are involved in generating P3; (4) AVCNa cells are the main CN cells involved in P4, N4, and P5 generation; (5) both ipsilateral and contralateral SOC cells have a role in generating monaurally evoked P4 and P5; and (6) P5 is generated by cells with characteristic frequencies below 10 kHz. From (2) and (4), it is clear that P2 and P4-P5 are generated by cells in distinct, parallel pathways.

Acoustic Stimulation↗

PubMed1996

Generators of the brainstem auditory evoked potential in cat. III: Identified cell populations.

This paper examines the relationship between different brainstem cell populations and the brainstem auditory evoked potential (BAEP). First, we present a mathematical model relating the BAEP to underlying cellular activity. Then, we identify specific cellular generators of the click-evoked BAEP in cats by combining model-derived insights with key experimental data. These data include (a) a correspondence between particular brainstem regions and specific extrema in the BAEP waveform, determined from lesion experiments, and (b) values for model parameters derived from published physiological and anatomical information. Ultimately, we conclude (with varying degrees of confidence) that: (1) the earliest extrema in the BAEP are generated by spiral ganglion cells, (2) P2 is mainly generated by cochlear nucleus (CN) globular cells, (3) P3 is partly generated by CN spherical cells and partly by cells receiving inputs from globular cells, (4) P4 is predominantly generated by medial superior olive (MSO) principal cells, which are driven by spherical cells, (5) the generators of P5 are driven by MSO principal cells, and (6) the BAEP, as a whole, is generated mainly by cells with characteristic frequencies above 2 kHz. Thus, the BAEP in cats mainly reflects cellular activity in two parallel pathways, one originating with globular cells and the other with spherical cells. Since the globular cell pathway is poorly represented in humans, we suggest that the human BAEP is largely generated by brainstem cells in the spherical cell pathway. Given our conclusions, it should now be possible to relate activity in specific cell populations to psychophysical performance since the BAEP can be recorded in behaving humans and animals.

Acoustic Stimulation↗

PubMed1995

Hydroxyl radical generation by coal mine dust: possible implication to coal workers' pneumoconiosis (CWP).

Occupational exposure to coal mine dust causes coal workers' pneumoconiosis (CWP) and other pulmonary diseases by mechanisms that remain unclear. Because the hydroxyl radicals (.OH) may play an important role in the pathogenesis of CWP, we studied the potential role of bituminous coal mine dust samples for catalyzing the generation of .OH from hydrogen peroxide (H2O2). These coal mine dusts evaluated represented two geographic areas with diversity in CWP prevalence. Electron spin resonance (ESR), with the aid of spin trapping techniques, was used to measure the .OH radical generation. Bituminous coal mine dusts representing the Pittsburgh seam in the eastern United States and Blind Canyon seam in the mid-western United States were used together with a standard coal dust obtained from the National Institute of Standards and Technology, Gaithersburg, MD. All the coal mine dust samples generated varying levels of .OH radicals from H2O2 in the presence of a .OH spin trap 5,5-dimethyl-l-pyrroline-N-oxide (DMPO). .OH radical generation by the coal from H2O2 was effectively inhibited by deferoxamine and catalase, but only partially inhibited by superoxide dismutase. Metal chelators DETAPAC and EDTA enhanced the radical generation. These results indicated that the Fenton reaction is predominantly involved in the generation of .OH radicals from H2O2. The .OH-generating potential of all the coal dusts showed a positive correlation with the surface iron content of coal mine dusts. In addition, the potential to induce lipid peroxidation by the coal samples exhibited a good correlation with the available surface iron. Based on the results presented here, we propose that higher concentrations of surface iron in coal mine dust may be involved in the generation of increased levels of .OH radicals and may play an important role in the development of CWP in different coal mining areas.

Chelating Agents↗

PubMed1990

A comparison of multivariable mathematical methods for predicting survival--III. Accuracy of predictions in generating and challenge sets.

This paper concludes a study of "performance variability" when four methods of multivariable analysis--multiple linear regression, discriminant function analysis, multiple logistic regression, and two arrangements of Cox's proportional hazards regression--were applied to the same stratified random samples of "generating sets" containing seven different statistical distributions of cogent biologic attributes in a composite staging system for a large cohort of patients with lung cancer. Each model developed from the generating sets was also applied for predictions in a previously sequestered "challenge set". Across the different generating sets, the multivariable methods showed good agreement with one another in the stepwise choice of first two powerful predictor variables, but not in the sequence of subsequent choices or in the standardized coefficients assigned to the same collection of "forced" variables. In concordance of predictions for individual patients in the generating sets, the overall proportions of disagreement for pairs of methods ranged from 0 to 28%, and kappa values ranged from 0.49 to 1.00. The accuracy of individual predictions showed relatively similar results when the different methods were applied to the same generating set. Across the generating sets, the different methods showed similar total results but substantial variations in predictions for alive and dead patients. When the models from the generating sets were applied for predictions in the challenge set, the results showed an analogous pattern: similar accuracy within models for overall and live/dead predictions, but substantial variations in live/dead predictions across models derived from different generating sources. The results showed that the multivariable methods often had good agreement with one another in predictions for groups but not for individual persons; and that no single method was superior to the others or to the composite staging system. We conclude that multivariable analytic methods may be most effective and consistent if used to find the few most powerful predictor variables, omitting the many other variables that may be "statistically significant" but less cogent. The powerful predictors may sometimes be best constructed, before the analysis begins, as composite variables containing appropriate unions or ordinal arrangements of elemental candidate variables.

Cohort Studies↗

PubMed2005

Carbon monoxide poisoning from portable electric generators.

BACKGROUND: While the overall death rate from unintentional carbon monoxide (CO) poisoning has decreased in the United States due to improved automobile emissions controls and a decline in CO poisonings from motor vehicles, exposures have not changed from some sources of CO. One of these is the operation of portable electrical generators in poorly ventilated spaces. This study sought to describe the population poisoned from CO produced by portable electric generators, and to determine the reasons that generators are operated in a hazardous fashion. METHODS: Cases of CO poisoning referred for treatment with hyperbaric oxygen at Virginia Mason Medical Center in Seattle from November 1978 to March 2004 were reviewed. Those cases that resulted from portable generator use were selected for analysis. RESULTS: Sixty-three patients aged 2 to 85 years were treated for CO poisoning from portable electric generators. They included 34 males and 29 females who were poisoned in 37 separate incidents. Thirty-four lost consciousness with the exposure. Of the 63 total patients, 60 spoke English. Generators were typically used when normal electrical service was disrupted by a storm or in remote locations. In 29 of 37 incidents, the generator was operated in the home environment, most commonly in the garage. Lack of awareness of the dangers of CO poisoning or lack of knowledge of ventilation requirements were the most commonly identified reasons. CONCLUSIONS: CO poisoning from portable electric generators occurs in a characteristic population, in a few typical locations and for a limited number of reasons. This information may help target prevention efforts for this form of poisoning, such as warning labels or educational programs.

Accidents, Home↗

PubMed2005

Effect of sulfur amino acids on stimulus-induced superoxide generation and translocation of p47phox and p67phox to cell membrane in human neutrophils and the scavenging of free radical.

BACKGROUND: Various cystathionine metabolites are in the urine of the patients with cystathioninuria. Among these metabolites, cystathionine ketimine significantly enhanced N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide generation in parallel with tyrosyl phosphorylation of 45 kDa protein in human neutrophils. METHODS: We investigated the effect of various sulfur amino acids on fMLP-, phorbol-12-myristate-13-acetate (PMA)- and arachidonic acid (AA)-induced superoxide generation in human neutrophils. In addition, the effects of these sulfur amino acids on the membrane translocation of cytosolic compounds p47(phox) and p67(phox) and on the scavenging of superoxide anions were investigated. RESULTS: When the cells were preincubated with various sulfur amino acids, fMLP-induced superoxide generation was enhanced by D,L-homocysteine and D,L-homocysteine-thiolactone but was inhibited by other sulfur amino acids in a concentration-dependent manner. The AA-induced superoxide was enhanced by L-cysteine, N-acetyl-L-cysteine and D,L-homocysteine. The strength of enhancing effect was: L-cysteine>>N-acetyl-L-cysteine>D,L-homocysteine. On the other hand, the superoxide generation was weakly inhibited by L-cystathionine. The superoxide generation induced by PMA was weakly inhibited by L-cysteine, N-acetyl-L-cysteine and L-cystathionine. Homocysteine and D,L-homocysteine-thiolactone had no effect. In addition, D,L-homocysteine also enhanced translocation to the cell membrane of cytosolic compounds p47(phox) and p67(phox). Conversely, L-cystathionine and N-acetyl-L-cysteine inhibited the translocation to membrane of p47(phox) and p67(phox) in a concentration-dependent manner. N-acetyl-L-cysteine and L-cysteine revealed scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. The sulfur amino acids tested also indicated radical scavenging activity on superoxide anion generated by phenazine methoxysulfate (PMS)-NADH system. CONCLUSION: D,L-homocysteine and D,L-homocysteine-thiolactone enhanced fMLP-induced superoxide generation by the increment of translocation to membrane of p47(phox) and p67(phox). L-cystathionine and N-acetyl-L-cysteine suppressed fMLP- and PMA-induced superoxide generation by the inhibition of translocation to membrane of p47(phox) and p67(phox). N-acetyl-L-cysteine also had scavenging activity against DPPH radicals and superoxide anion.

Amino Acids, Sulfur↗

PubMed2006

Effect of sublethal concentrations of chlorpyrifos on three successive generations of Daphnia carinata.

Effects of sublethal concentrations of chlorpyrifos (ranging from 0.005 (0.01 LC(50)) to 0.500 microg/L (1 LC(50))) on population characteristics of individual cultures of Daphnia carinata were investigated over 21 days with subsequent testing of the two next generations. The endpoints for the first and second generations observed were survival, fecundity, time to first brood, and number of offspring per female. The results were incorporated into the computation of the intrinsic rate of natural increase for daphnids in each of the treatments. Exposure to chlorpyrifos affected survival and fecundity of animals in the first generation. In the second generation, the most affected endpoint was time to the first brood with an indication of hormesis. The LC(50) tests were then conducted using animals of the third generation from each of the exposures in individual tests. Despite the absence of a negative effect of chlorpyrifos in the second generation, results of testing the third generation showed constant significant decline in LC(50) from control daphnids through to 0.1 LC(50) preexposed daphnids (0.1 LC(50), 0.05 microg/L, being the highest concentration in which animals survived exposure to the toxicant in the second generation).

Animals↗

PubMed2003

Proliferation and wound healing of vascular cells trigger the generation of extracellular reactive oxygen species and LDL oxidation.

Cell proliferation of vascular cells is a key feature in vascular biology, wound healing, and pathophysiological processes such as atherosclerosis and restenosis. In atherosclerotic intima, cell proliferation colocalizes with oxidized LDL that indicate a local oxidative stress. This study aims to investigate whether cell proliferation is causally related with extracellular ROS generation and subsequent LDL oxidation. Sparse proliferating endothelial and smooth muscle cells generate higher levels of extracellular ROS (O2*- and H2O2) and LDL oxidation than confluent contact-inhibited cells. During wound healing of confluent cell layer, cell proliferation associated with healing also induced enhanced extracellular ROS generation and LDL oxidation. Proliferation-associated extracellular ROS generation is mediated through mitogenic signaling pathways, involving ERK1/2 and PKC, but is independent of de novo DNA synthesis, gene expression and protein synthesis. Data obtained with inhibitors of oxidases suggest that proliferation-associated extracellular ROS are not generated by a single ROS-generating system and are not essential for cell proliferation. In conclusion, our data show that proliferating vascular cells (in sparse culture or during wound healing) generate high levels of extracellular ROS and LDL oxidation through regulation of ROS-generating systems by mitogenic signaling. This constitutes a link between proliferative events and oxidative stress/LDL oxidation in atherosclerotic lesions and restenosis.

Animals↗

PubMed2004

Existence of infective juveniles in the offspring of first- and second-generation adults of Steinernema rarum (OLI strain): evaluation of their virulence.

Descriptions of the life cycle of the genus Steinernema do not consider the production of infective juveniles (IJs) by the first-generation developed within the insect host when more than one generation develops. We demonstrated IJ production by first- and second-generation adults of Steinernema rarum (OLI strain), evaluated their virulence and compared virulence and morphometric characters between the two IJ forms. Our results demonstrated not only the presence of IJs in the offspring of first- and second-generation adults but also a greater virulence of first-generation IJs. Both types of IJs also differed in five morphometric characters. According to our results, a population of IJs emerging from a host cadaver has individuals of two generations with different characteristics; hence, they should not be considered the same. These generational differences may be exploited, for example, for biocontrol purposes, by using a specific generation of IJs for inoculative release.

Animals↗

PubMed2004

The modulation of action potential generation by calcium-induced calcium release is enhanced by mitochondrial inhibitors in mudpuppy parasympathetic neurons.

Previously, we demonstrated that outward currents activated by calcium-induced calcium release (CICR) opposed depolarization-induced action potential (AP) generation in dissociated mudpuppy parasympathetic neurons [J Neurophysiol 88 (2002) 1119]. In the present study, we tested whether AP generation by depolarizing current ramps could be altered by dissipating the mitochondrial membrane potential and thus interrupting mitochondrial Ca2+ buffering. Exposure to the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP; 2 microM) alone or in combination with the mitochondrial ATP synthase inhibitor oligomycin (8 microg/ml), increased the latency to AP generation. Exposure to the electron transport chain inhibitor rotenone (10 microM) alone or in combination with oligomycin (8 microg/ml) similarly increased the latency to AP generation. CCCP and oligomycin or rotenone and oligomycin treatment caused rhodamine 123 loss from mitochondria within a few minutes, confirming that the mitochondrial membrane potential was dissipated during drug exposure. Oligomycin alone had no effect on the latency to AP generation and did not cause loss of rhodamine 123 from mitochondria. The increase in latency induced by CCCP and oligomycin was similar when recordings were made with either the perforated patch or standard whole cell patch recording configuration. Exposure to the endoplasmic reticulum Ca-ATPase inhibitor thapsigargin (1 microM), decreased the latency to AP generation. In cells pretreated with thapsigargin to eliminate CICR, CCCP and oligomycin had no effect on AP latency. Pretreatment with iberiotoxin (IBX; 100 nM), an inhibitor of large conductance, calcium- and voltage-activated potassium channels, reduced the extent of the CCCP- and oligomycin-induced increase in latency to AP generation. These results indicate that treatment with CCCP or rotenone to dissipate the mitochondrial membrane potential, a condition which should minimize sequestration of Ca2+ by mitochondria, facilitated the Ca(2+)-induced Ca2+ release activation of IBX-sensitive and IBX-insensitive conductances that regulate AP generation.

Action Potentials↗

PubMed2005

Development of respiratory rhythm generation in ectothermic vertebrates.

Compared with birds and mammals, very little is known about the development and regulation of respiratory rhythm generation in ectothermic vertebrates. The development and regulation of respiratory rhythm generation in ectothermic vertebrates (fish, amphibians and reptiles) should provide insight into the evolution of these mechanisms. One useful model for examining the development of respiratory rhythm generation in ectothermic vertebrates has emerged from studies with the North American bullfrog (Rana catesbeiana). A major advantage of bullfrogs as a comparative model for respiratory rhythm generation is that respiratory output may be measured at all stages of development, both in vivo and in vitro. An emerging view of recent studies in developing bullfrogs is that many of the mechanisms of respiratory rhythm generation are very similar to those seen in birds and mammals. The overall conclusion from these studies is that respiratory rhythm generation during development may be highly conserved during evolution. The development of respiratory rhythm generation in mammals may, therefore, reflect the antecedent mechanisms seen in ectothermic vertebrates. The main focus of this brief review is to discuss recent data on the development of respiratory rhythm generation in ectothermic vertebrates, with particular emphasis on the North American bullfrog (R. catesbeiana) as a model.

Amphibians↗

PubMed2004

The nitric oxide synthase inhibitor N(G)-nitro-L-arginine decreases defibrillation-induced free radical generation.

OBJECTIVES: to demonstrate that nitric oxide (NO) contributes to free radical generation after epicardial shocks and to determinethe effect of a nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine (L-NNA), on free radical generation. BACKGROUND: Free radicals are generated by direct current shocks for defibrillation. NO reacts with the superoxide (O2*-) radical to for peroxynitrite (O = NOO-), which is toxic and initiates additional free radical generation. The contribution of NO to free radical generation after defibrillation is not fully defined. METHODS AND RESULTS: Fourteen open chest dogs were studied. In the initial eight dogs, 40 J damped sinusoidal monophasic epicardial shocks was administered. Using electron paramagnetic resonance, we monitored the coronary sinus concentration of ascorbate free radical (Asc*-), a measure of free radical generation (total oxidative flux). Epicardial shocks were repeated after L-NNA, 5 mg/kg IV. In six additional dogs, immunohistochemical staining was done to identify nitrotyrosine, a marker of reactive nitrogen species-mediated injury, in post-shock myocardial tissue. Three of these dogs received L-NNA pre-shock. After the initial 40 J shock, Asc*- rose 39 +/- 2.5% from baseline. After L-NNA infusion, a similar 40 J shock caused Asc*- to increase only 2 +/- 3% form baseline (P < 0.05, post-L-NNA shock versus initial shock). Nitrotyrosine staining was more prominent in control animals than dogs receiving L-NNA, suggesting prevention of O = NOO- formation. CONCLUSION: NO contributes to free radical generation and nitrosative injury after epicardial shocks; NOS inhibitors decrease radical generation by inhibiting the production of O = NOO-.

Animals↗

PubMed2005

Generator replacement in epilepsy patients treated with vagus nerve stimulation.

PURPOSE: In epilepsy patients treated with vagus nerve stimulation (VNS), the occurrence of end of battery life (EOBL), when the generator will no longer deliver any stimulation, was investigated with regard to seizure control. EOBL is preceeded by end of effective stimulation (EOES) when irregular stimulation may occur. METHODS: In 14/78 patients, treated with VNS at Ghent University Hospital, generators were replaced at different times following EOES or EOBL. We retrospectively analysed the time of occurrence of EOES and EOBL and seizure control before and after generator replacement. RESULTS: EOES or EOBL was indicated by loss of seizure control, decreased perception of stimulation and recurrence of depression in 3, 3 and 1/14 patient(s), respectively. In 2 and 1/14 patient(s), EOBL and premature generator failure, respectively, were detected during routine check-up at the epilepsy clinic. In 4/14 patients, generator replacement was performed before estimated EOES. Pre-replacement seizure control could not be regained in 2/14 patients in whom replacement had been postponed for several months. Estimation of EOES and EOBL occurrence proved difficult in individual patients. CONCLUSION: EOES or EOBL may be indicated by loss of seizure control, decreased or irregular perception of stimulation by the patient and loss of other VNS-induced effects. Postponing generator replacement may result into permanent loss of seizure control. In responders we suggest generator replacement before EOBL. Our results call for performance of prospective studies in larger patient groups that may eventually lead to general guidelines on the indication and timing of generator replacement.

Adult↗

PubMed2004

Development of a compact self-focusing piezoelectric generator using electrical pre-strain piezocomposite material.

New clinical concepts in lithotripsy demand small shock heads. Reducing the size of piezoelectric shock heads will only be possible if the pressure generated at the surface of each transducer can be increased so that, the total pressure at the focus remains very high. So, we propose a new method allowing the generation of large surface pressures. It is well known that the piezoelectric rods in piezocomposite material are more fragile in the extension mode than in the compression mode. For this reason, actuators are mechanically pre-stressed between two flasks. This method cannot be used for transducers working at high frequencies, about 0.5 MHz. For this reason, we proposed to electrically pre-strain the piezoelectric material by applying high electric field in the opposite direction of the polarisation. In a first mode we proposed to pre-strain in continuous mode the transducer. Unfortunately we noticed a rapid de-poling and re-poling in the inverse direction. In a second mode to reduce depolarisation, this field was applied only during a short time just before the generation of the pulse which generate the compressive wave and in a third mode, the transducer was re-poled between two successive electrical pulses. Using this last method, it was possible to increase the maximum pressure at the surface of a 20 mm diameter plane piston to 20% and reach 4 MPa. According to this idea a very compact shock wave generator was designed. The generator made of a 1-3 piezocomposite material has a diameter of 120 mm and focused at 120 mm. The maximum pressure and the width of the compressive wave at the focus were, respectively, 60 MPa and 1.5 micros. The focal zone measured at -3 dB is an ellipsoid 6 mm high in the propagating axis and 3 mm width in the perpendicular direction. The efficacy of this generator was measured as the number of shocks necessary to totally disintegrate plaster balls 15 mm in diameter mimicking the kidney stones. At full power the number of shocks was only 150 which is rather the same number as the one obtained using electrohydraulic machine generally considered as the gold standard. This results show that piezoelectric material may be advantageously used for the manufacturing of shock wave generators.

Journal Article↗

PubMed2002

Generation of C5a by phagocytic cells.

The complement activation product, C5a, is a powerful phlogistic factor. Using antibodies to detect human or rat C5a, incubation at pH 7.4 of human blood neutrophils or rat alveolar macrophages (AMs) with C5 in the presence of phorbol 12-myristate 13-acetate (PMA) led to generation of C5a. Rat AMs activated with lipopolysaccharide also generated C5a from C5. With activated neutrophils, extensive cleavage of C5 occurred, whereas activated macrophages had much more selective proteolytic activity for C5. Peripheral blood human or rat mononuclear cells and rat alveolar epithelial cells when stimulated with phorbol ester all failed to demonstrate an ability to cleave C5, suggesting a specificity of C5 cleavage by phagocytic cells. With rat AMs, C5a generation was time-dependent and was blocked if AMs were pretreated with inhibitors of transcription or protein synthesis (actinomycin D or cycloheximide). Similar treatment of activated human polymorphonuclear leukocytes only partially reduced C5a generation after addition of C5. C5a generated by activated AMs was biologically (chemotactically) active. This generation was sensitive to serine protease inhibitors but not to other classes of inhibitors. These data indicate that phagocytic cells, especially lung macrophages, can generate C5a from C5. In the context of the lung, this may represent an important C5a-generating pathway that is independent of the plasma complement system.

Animals↗