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PubMedDate not supplied

Cytokine production in thromboangiitis obliterans patients: new evidence for an immune-mediated inflammatory disorder.

OBJECTIVE: To study IL-6, IL-10, IL-12 levels and circulating immune complexes (CIC) containing IgG, IgM or IgA in sera of 14 TAO patients and 12 healthy blood donors. To evaluates the ability of TAO PBMC to produce IL-6, IL-10, IL-12, as well as to detect PBMC apoptosis after stimulation with different stimuli. METHODS: In vitro stimulation of PBMC with lypopolysaccharide (LPS), phytohemagglutinin (PHA), C3 binding glycoprotein from uscuta europea (C3bgp), pokeweed mitogen (PWM), and dexamethasone (DM) were performed. The quantities of the secreted cytokines in sera and in culture supernatants, as well as CIC were detected by ELISA. The apoptosis was assessed according to nuclear morphology, after acridine orange staining, by fluorescence microscopy. RESULTS: Significantly higher IL-6 levels in the patients', than in the controls' sera was found. An increased production of IL-6 and IL-12 in TAO PBMC supernatants was detected, regardless of the stimuli used. A hyporeactivity of TAO PBMC toward IL-10 production was found after C3bgp, LPS, PHA and PWM stimulation, compared to the controls' PBMC. The spontaneous and induced apoptosis was significantly higher in TAO compared to the control group. Increased CIC quantities were detected in 75% of the patients tested. According to the CIC isotype, the IgG CIC positives (75%) prevailed over IgA CIC positives (50 %). CONCLUSION: The altered production of IL-6, IL-12 and IL-10, the increased apoptosis as well as the elevated levels of CIC could be a reason for the persisting immune inflammation in TAO.

Adult↗
PubMed2005

Gustatory stimulation influences the processing of intranasal stimuli.

OBJECTIVES: Taste and smell interact. The aim of this study was to examine this interaction using gustatory and olfactory stimuli applied at the same time, which exhibited perceptual compatibility and incompatibility. METHODS: Thirty-two, young, healthy normosmic subjects (16 men, 16 women) took part in two randomized sessions. Event-related potentials (ERP) were recorded in response to vanillin, or gaseous CO2. These two conditions were combined with three "taste conditions" including sweet taste, sour taste, and the intraoral presentation of an empty taste dispenser. RESULTS: Vanillin responses were largest for the "sweet" condition, while they were smaller for the "sour condition". In contrast, responses to CO2 were largest under the "sour" condition, and smallest under the "sweet" condition. Moreover, during the "sweet" condition the latencies of P1 and N1 were shorter than in the "sour" condition, which was the other way around for CO2. CONCLUSIONS: Results of the present investigation suggested that (1) the early processing of intranasal chemosensory stimuli is modulated through concomitant gustatory stimulation, and that (2) this modulation may depend, at least in part, on the contextual compatibility between intranasal and intraoral stimuli.

Adult↗
PubMedDate not supplied

Measurement of the activating function of magnetic stimulation using combined electrical and magnetic stimuli.

The technique of combined magnetic and electrical stimulation of a peripheral nerve was used to determine the effectiveness of the combined stimulus and its dependence on the relative positioning of electrodes and stimulator coil along the axis of the nerve. The results were used to determine the magnetic stimulation-activating function of a long, straight nerve in the arm, and are shown to be consistent with published theoretical models constructed under conditions of simplified tissue geometry. With appropriate positioning of the two stimulators and similar tissue current waveforms, both enhancement and inhibition of an electrical stimulus were demonstrated and the maximum amplitude of the combined stimulus approached the arithmetic sum of that produced by each stimulator individually.

Arm↗
PubMed2001

Synaptojanin 1 contributes to maintaining the stability of GABAergic transmission in primary cultures of cortical neurons.

Inhibitory synapses in the CNS can exhibit a considerable stability of neurotransmission over prolonged periods of high-frequency stimulation. Previously, we showed that synaptojanin 1 (SJ1), a presynaptic polyphosphoinositide phosphatase, is required for normal synaptic vesicle recycling (Cremona et al., 1999). We asked whether the stability of inhibitory synaptic responses was dependent on SJ1. Whole-cell patch-clamp recordings of unitary IPSCs were obtained in primary cortical cultures between cell pairs containing a presynaptic, fast-spiking inhibitory neuron (33.5-35 degrees C). Prolonged presynaptic stimulation (1000 stimuli, 2-20 Hz) evoked postsynaptic responses that decreased in size with a bi-exponential time course. A fast component developed within a few stimuli and was quantified with paired-pulse protocols. Paired-pulse depression (PPD) appeared to be independent of previous GABA release at intervals of >/=100 msec. The characteristics of PPD, and synaptic depression induced within the first approximately 80 stimuli in the trains, were unaltered in SJ1-deficient inhibitory synapses. A slow component of depression developed within hundreds of stimuli, and steady-state depression showed a sigmoidal dependence on stimulation frequency, with half-maximal depression at 6.0 +/- 0.5 Hz. Slow depression was increased when release probability was augmented, and there was a small negative correlation between consecutive synaptic amplitudes during steady-state depression, consistent with a presynaptic depletion process. Slow depression was increased in SJ1-deficient synapses, with half-maximal depression at 3.3 +/- 0.9 Hz, and the recovery was retarded approximately 3.6-fold. Our studies establish a link between a distinct kinetic component of physiologically monitored synaptic depression and a molecular modification known to affect synaptic vesicle reformation.

Action Potentials↗
PubMed1975

[RNA synthesis in the brains of rats with changes in the function of their central nervous systems].

A method of electrophoresis in polyacrylamide gel was applied to the study of the RNA synthesis in the phenol nuclei and the cytoplasm of the cells of the higher portions of the brain in rats under normal conditions, during training of these animals in the motor-defence habit in a complicated labyrinth, and in active control (irregular presentation of motor-defence stimuli). Behaviouristic stimulation and an irregular presentation to the animals of the same stimuli as in the elaboration of habits, but not leading to their formation, activated the RNA synthesis in the phenol nuclei with sedimentation characteristics of 18S, 28S and over. Thy cytoplasmic RNA displayed an increase in the labeled precursor incorporation in the 18S region.

Animals↗
PubMed1985

Cerebral somatosensory potentials evoked by muscle stretch, cutaneous taps and electrical stimulation of peripheral nerves in the lower limbs in man.

Somatosensory cerebral evoked potentials were recorded in man to natural forms of somatosensory stimulation of the lower extremity including stretching of the muscle tendons, tapping on muscle bellies and tapping on cutaneous surfaces. These potentials were compared with those evoked by electrical stimulation of peripheral nerves measuring the amplitudes and latencies of the evoked potential components and defining the effects of stimulus variables on these parameters. Spinal cord potentials could only be detected to electrical stimuli. Mechanical stimulation of tendons and muscle bellies evoked scalp potentials at latencies earlier than those evoked by electrical stimulation of the peripheral nerve and by cutaneous stimulation at the same level of the leg. Muscle receptors, most probably muscle spindles, are the source of the short latency components obtained by the stretching of tendons and tapping on muscle bellies. The proximal location of these receptors as well as very rapid spinal conduction account for the latency difference. The potentials were larger to electrical stimulation of nerve trunks than to mechanical stimulation of tendons or skin, suggesting the asynchronous activation of a smaller number of fibres by the latter. Individuals with the largest potentials to one form of stimulation usually had the largest potentials to the other modes of stimulation. The use of physiological stimuli such as muscle stretch to test the transmission in specific neural pathways might be useful in investigating the processing of relatively selective afferent volleys using noninvasive evoked potential recordings.

Adult↗
PubMed1991

Inhibition of lateral vestibular nucleus neurons by 5-hydroxytryptamine derived from the dorsal raphe nucleus.

Electrophysiological studies were performed to elucidate the effect of 5-hydroxytryptamine (5-HT) originating in the dorsal raphe nucleus (DR) on neuronal activity in the lateral vestibular nucleus (LVN) neurons, using cats anesthetized with alpha-chloralose. LVN neurons were classified into monosynaptic and polysynaptic neurons according to their responses to vestibular nerve stimulation. Conditioning stimuli applied to the DR inhibited orthodromic spikes elicited by vestibular nerve stimulation predominantly in polysynaptic neurons of the LVN. The iontophoretic application of 5-HT also inhibited orthodromic spikes of the LVN neurons. A close correlation was observed between the effects of DR conditioning stimulation and iontophoretically applied 5-HT in the same neurons. These inhibitions with both treatments were antagonized during the application of methysergide, a 5-HT antagonist. In the majority of LVN polysynaptic neurons that responded to antidromic stimulation of the ipsilateral or contralateral abducens nucleus, orthodromic spikes elicited by vestibular nerve stimulation were inhibited by DR conditioning stimulation and the iontophoretic application of 5-HT. In contrast, LVN neurons that responded to antidromic stimulation of the vestibulospinal tract were rarely affected by these treatments. These results indicate that 5-HT derived from the DR inhibits the synaptic transmission of LVN polysynaptic neurons ascending to the abducens nucleus, and suggest that 5-HT derived from the DR is involved in the regulation of the vestibulo-ocular reflex.

Abducens Nerve↗
PubMed1989

Arachidonic acid release in rabbit neutrophils.

[3H]Arachidonic acid is released after stimulation of rabbit neutrophils with fMet-Leu-Phe or platelet-activating factor (PAF). The release is rapid and dose-dependent, and is inhibited in phorbol 12-myristate 13-acetate (PMA)-treated rabbit neutrophils. The protein kinase C (PKC) inhibitor 1-(5-isoquinoline-sulphonyl)-2-methylpiperazine (H-7) prevents this inhibition. In addition, PMA increases arachidonic acid release in H-7-treated cells stimulated with fMet-Leu-Phe. [3H]Arachidonic acid release, but not the rise in the concentration of intracellular Ca2+, is inhibited in pertussis-toxin-treated neutrophils stimulated with PAF. The diacylglycerol kinase inhibitor R59022 increases the concentration of diacylglycerol and potentiates [3H]arachidonic acid release in neutrophils stimulated with fMet-Leu-Phe. This potentiation is not inhibited by H-7. These results suggest several points. (1) A rise in the intracellular concentration of free Ca2+ is not sufficient for arachidonic acid release in rabbit neutrophils stimulated by physiological stimuli. (2) A functional pertussis-toxin-sensitive guanine nucleotide regulatory protein and/or one or more of the changes produced by phospholipase C activation are necessary for arachidonic acid release produced by physiological stimuli. (3) Agents that stimulate PKC potentiate arachidonic acid release, and this potentiation is not inhibited by H-7. These agents produce their actions in part by direct membrane perturbation.

Animals↗
PubMed1990

[Ca2+], not diacylglycerol, is the primary regulator of sustained swine arterial smooth muscle contraction.

Sustained smooth muscle contraction has been proposed to be regulated by either 1) sustained increases in intracellular Ca2+ concentration [(Ca2+]i)-dependent myosin phosphorylation or 2) diacylglycerol-dependent protein kinase C activation. We measured diacylglycerol mass with the diacylglycerol kinase assay and myoplasmic [Ca2+] with aequorin in swine carotid medial smooth muscle. Sustained and significant increases in [Ca2+], myosin light chain phosphorylation, and isometric stress were observed with histamine or endothelin stimulation. Neither stimuli, however, induced significant increases in diacylglycerol mass. Relaxation of histamine-stimulated tissues was induced by removal of histamine or removal of extracellular CaCl2 in the continued presence of histamine. The rate of decline of both [Ca2+] and force was similar in both protocols, suggesting that removal of Ca2+ (without removing the stimulus) was equivalent to removal of the stimulus. These data suggest that [Ca2+]i is the primary regulator of sustained swine arterial smooth muscle contraction, whereas diacylglycerol has, at most, only a minor role.

Alkaloids↗
PubMed1977

Substantia nigra and somatosensory evoked responses in the caudate nucleus.

The nigro-caudate relationships were studied in fifteen adult anesthetized cats, paralyzed with Flaxedil. Single shocks applied to substantia nigra (SN) evoked biphasic field potentials in the ipsilateral caudate nucleus. Similar positive-negative waves were recorded in the caudate nucleus by sciatic stimulation, although with longer latencies. A triphasic field potential was also observed after cerebral peduncle stimulation. Conditioning stimuli applied to the SN at varying time intervals prior to sciatic stimulation did not modify the test response. In contrast, conditioning stimulation of the cerebral peduncle produced a marked inhibition between 25 and 100 msec. Recovery was complete after 200 msec. The present observations indicate that nigral stimulation does not influence the pool of neurons responding to sciatic nerve in the caudate nucleus. On the other hand, the cerebral peduncles exert an inhibitory action on such activity.

Animals↗
PubMed2001

A multi-channel whisker stimulator for producing spatiotemporally complex tactile stimuli.

A system is described that delivers complex, biologically realistic, tactile stimuli to the rat's facial whisker pad by independently stimulating up to 16 individual facial whiskers in a flexible yet highly controlled and repeatable manner. The system is technically simple and inexpensive to construct. The system consists of an array of 16 miniature-solenoid driven actuators that are attached to 16 individual facial whiskers via very small (130 microm dia.) Teflon-coated stainless steel wires. When individual solenoids are energized, the wire is rapidly retracted, resulting in a deflection of individual whiskers. The rise time of deflection is approx. 1 mm/ms. Repeatable stimulation of individual whiskers can be achieved without touching adjacent whiskers, thereby allowing a very high density of stimulators to be attached within the spatially restricted region of the facial whisker pad. Complex patterns of whisker stimulation (designed to mimic biologically realistic stimuli) are delivered to the whisker pad by activating individual solenoid actuators in precisely controlled temporal patterns. These stimulations can be combined with multi-electrode single-unit ensemble recordings at multiple sites within the rat trigeminal somatosensory system. Analysis of neuronal population responses to these complex stimuli is intended to examine how the trigeminal somatosensory system encodes and processes spatiotemporally complex stimuli.

Animals↗
PubMedDate not supplied

[Selective involvement of opioids in mechanisms of synapse-specific plasticity in Helix lucorum snail during sensitization acquisition].

Effects of met-enkephalin (opioid peptide) and naloxone (opioid antagonist) on nociceptive sensitization were studied in L-RP11 Helix neurons. In control snails sensitizing stimulation produced reversible membrane depolarization and depression of neural responses evoked by sensory stimuli during the short-term stage of sensitization and facilitation of these responses at the long-term stage. Met-enkephalin (10 but not 0.1 microM) suppressed the neural responses evoked by nociceptive stimuli. Sensitizing stimulation during metenkephalin application prevented the facilitation of neural responses evoked by tactile stimulation of snail head, whereas facilitation of neural responses evoked by chemical stimulation of head or tactile stimulation of foot were similar to that in control sensitized snails. Sensitizing stimulation during met-enkephalin and/or naloxone application prevented the facilitation of neural responses evoked by chemical stimulation of snail head, whereas responses evoked by tactile stimulation of snail head or foot were facilitated (as in neurons of control sensitized snails). Opioids are suggested to be involved in regulation of nociceptive mechanisms and selective induction of long-term plasticity in L-RP11 neural inputs activated by tactile of chemical stimulation of snail head.

Action Potentials↗
PubMed1998

The mechanics of vascular cell motility.

Alterations in vascular cell shape and motility occur during developmental processes and in response to injury. Similarly, during tumor vascularization and atherogenesis, endothelial and smooth muscle cells undergo motile and proliferative responses to extracellular cues. Recent inroads into our understanding of signal transduction have identified several candidate pathways by which the extracellular matrix- and growth factor-mediated stimulation of vascular cell motility may be mediated. The multiple and divergent extracellular stimuli that stimulate vascular motile responses may converge on the cytoskeleton via a family of ras-related GTPases. Biochemical analyses as well as examination of cytoskeletal dynamics in vivo indicate that actin polymerization at the forward aspects of spreading cytoplasm is capable of driving forward protrusion formation in the absence of a conventional actin motor. Actin polymerization at the plasma membrane of leading lamellae may be mediated both by de novo nucleation of actin filaments and the generation of free filament ends by uncapping the barbed ends of existing actin filaments. This review summarizes the most recent findings in extracellular-cytoskeletal-signal transduction, therein, providing a framework to explain the remarkable remodeling seen in the vasculature during developmental and disease-related processes.

Actin Cytoskeleton↗
PubMed1976

Opiate and stimulus-produced analgesia: functional anatomy of a medullospinal pathway.

Neurons in ventromedial medulla, including the nucleus raphe magnus, project to trigeminal nucleus caudalis and, via the dorsolateral funiculus, to spinal dorsal horn. The terminals of this descending system are in loci containing cells responsive to noxious stimuli. Electrical stimulation of nucleus raphe magnus selectively inhibits spinal dorsal horn neurons that respond to noxious stimuli. These neurons are located near the anatomically demonstrated terminals of this descending system. Dorsolateral funiculus lesions block this descending inhibition of spinal neurons as well as the analgesic action of morphine. This evidence supports the hypothesis that this neuron population mediates the analgesia produced by opiates and electrical stimulation of certain diencephalic and brainstem sites.

Analgesia↗
PubMed1993

[Control of oxytocin secretion in lactation].

The most established physiological function of oxytocin is to induce milk ejection from the mammary gland of lactating animals. It is now known that during lactation oxytocin is released pulsatively following brief periods of burst-like and synchronous activation of many thousands of oxytocin cells in the hypothalamus. The mechanism generating such activity in oxytocin cells has been extensively studied, but it has not been fully understood yet. To explain that suckling stimuli produce a recurrence of milk ejection bursts of oxytocin cells without any change in their background activity, a gating mechanism has been hypothesized. In the excitatory transmission of afferent signals of the milk ejection reflex, alpha adrenergic receptors are indicated to be involved. Among neuropeptides, oxytocin and CRF are potent facilitatory factors. As non-neurochemical factors that facilitate milk ejection bursts of oxytocin cells, there are osmotic stimuli, neurohypophyseal stimulation and vaginal distention. During the lactation period, responsiveness of oxytocin cells to various stimuli such as stress, osmotic stimuli and CCK is markedly reduced. The cause of the change has not been discovered, but it is assumed that the reduction in responsiveness may enable the animal to adapt to the large demands for the hormone during the lactation period.

Animals↗
PubMed1974

Pain reduction by focal electrical stimulation of the brain: an anatomical and behavioral analysis.

These experiments have examined several aspects of analgesia produced by focal electrical stimulation of the brain. (1) Anatomical locus of analgesic effects: only stimulation of the mesencephalic central gray matter and periventricular gray matter greatly reduced or totally abolished responsiveness to all noxious stimuli employed. Stimulation of other brain areas increased jump threshold to electric shock (septal nuclei, dorsomedial thalamic nucleus) and sometimes even abolished responsiveness to tissue destructive pinch (ventral tegmentum, dorsomedial thalamic nucleus), but never eliminated resonding to radiant heat applied to the tail. Stimulation of the ventrobasal complex of the thalamus and the lateral hypothalamus produced little or no analgesia at all. (2) Magnitude of analgesia: stimulation of the central and periventricular gray matter produced analgesia equal to or greater than 10 mg/kg morphine on all tests. (3) Relationship to reward: stimulation-produced analgesia was found not to be casually related to the rewarding properties of the stimulation. Analgesia was often produced by stimulation at electrode sites which did not support self-stimulation behavior; and many animals self-stimulated at high rates but were not analgesic. (4) Relationship to seizure activity: electrographic or overt motor seizure activity was not related to stimulation-produced analgesia. (5) By analogy with the site and mechanism of morphine action, it is proposed that focal electrical stimulation activates a pain suppressive system concentrated in periventricular and periaqueductal regions and its activation reduces responsiveness to noxious stimuli, at least in part, by blocking transmission of nociceptive information through the spinal cord.

Animals↗
PubMed1997

Chronic electrical stimulation of the auditory nerve at high stimulus rates: a physiological and histopathological study.

A major factor associated with recent improvements in the clinical performance of cochlear implant patients has been the development of speech-processing strategies based on high stimulation rates. While these processing strategies show clear clinical advantage, we know little of their long-term safety implications. The present study was designed to evaluate the physiological and histopathological effects of long-term intracochlear electrical stimulation using these high rates. Thirteen normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods of up to 2100 h using either two pairs of bipolar or three monopolar stimulating electrodes. Stimuli consisted of short duration (25-50 microseconds/phase) charge-balanced biphasic current pulses presented at 1000 pulses per second (pps) per channel for monopolar stimulation, and 2000 pps/channel for bipolar stimulation. The electrodes were shorted between current pulses to minimize any residual direct current, and the pulse trains were presented using a 50% duty cycle (500 ms on; 500 ms off) in order to simulate speech. Both acoustic (ABR) and electrical (EABR) auditory brainstem responses were recorded periodically during the chronic stimulation program. All cochleas showed an increase in the click-evoked ABR threshold following implant surgery; however, recovery to near-normal levels occurred in approximately half of the stimulated cochleas 1 month post-operatively. The use of frequency-specific stimuli indicated that the most extensive hearing loss generally occurred in the high-frequency basal region of the cochlea (12 and 24 kHz) adjacent to the stimulating electrode. However, thresholds at lower frequencies (2, 4 and 8 kHz), appeared at near-normal levels despite long-term electrode implantation and electrical stimulation. Our longitudinal EABR results showed a statistically significant increase in threshold in nearly 40% of the chronically stimulated electrodes evaluated; however, the gradient of the EABR input/output (I/O) function (evoked potential response amplitude versus stimulus current) generally remained quite stable throughout the chronic stimulation period. Histopathological examination of the cochleas showed no statistically significant difference in ganglion cell densities between cochleas using monopolar and bipolar electrode configurations (P = 0.67), and no evidence of cochlear damage caused by high-rate electrical stimulation when compared with control cochleas. Indeed, there was no statistically significant relationship between spiral ganglion cell density and electrical stimulation (P = 0.459), or between the extent of loss of inner (IHC, P = 0.86) or outer (OHC, P = 0.30) hair cells and electrical stimulation. Spiral ganglion cell loss was, however, influenced by the degree of inflammation (P = 0.016) and electrode insertion trauma. These histopathological findings were consistent with the physiological data. Finally, electrode impedance, measured at completion of the chronic stimulation program, showed close correlation with the degree of tissue response adjacent to the electrode array. These results indicated that chronic intracochlear electrical stimulation, using carefully controlled charge-balanced biphasic current pulses at stimulus rates of up to 2000 pps/channel, does not appear to adversely affect residual auditory nerve elements or the cochlea in general. This study provides an important basis for the safe application of improved speech-processing strategies based on high-rate electrical stimulation.

Action Potentials↗