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PubMed2005

Double stimulation of tiny skin areas in human subjects increases the number of C- and Adelta-fiber responses.

The stimulation of tiny skin areas has been shown to be a useful method for the investigation of the central nervous processing of C-fiber stimulation. However, recent studies have also indicated that most subjects fail to recognize a large number of such stimulation. This fact renders this method to be rather time consuming, a fact that limits its applicability. To reduce the duration of examination, we here examined the effects of double stimulation of tiny skin areas as compared to the stimulation of tiny skin areas with a single stimulus. The comparison is based on subjects' number of recognized stimuli for single and double stimulation and ratings of stimulus intensity. Double stimulation of tiny skin areas resulted in a significant increase of the number of recognized stimuli as compared to single stimulation. This increase of the number of recognized stimuli is accompanied by an increase of the averaged subjects' experience of stimulus intensity. However, there was no significant increase of intensity rating for the different types of fibers stimulated. Data indicate that the double stimulation of tiny skin areas represents an alternative option to the application of single stimuli to tiny skin areas that significantly reduces the exposure time of subjects in order to evaluate behavioral consequences of the stimulation as well as central nervous processing of C- and Adelta-fiber input.

Action Potentials↗

PubMed2003

The magnocellular oxytocin system, the fount of maternity: adaptations in pregnancy.

Oxytocin secretion from the posterior pituitary gland is increased during parturition, stimulated by the uterine contractions that forcefully expel the fetuses. Since oxytocin stimulates further contractions of the uterus, which is exquisitely sensitive to oxytocin at the end of pregnancy, a positive feedback loop is activated. The neural pathway that drives oxytocin neurons via a brainstem relay has been partially characterised, and involves A2 noradrenergic cells in the brainstem. Until close to term the responsiveness of oxytocin neurons is restrained by neuroactive steroid metabolites of progesterone that potentiate GABA inhibitory mechanisms. As parturition approaches, and this inhibition fades as progesterone secretion collapses, a central opioid inhibitory mechanism is activated that restrains the excitation of oxytocin cells by brainstem inputs. This opioid restraint is the predominant damper of oxytocin cells before and during parturition, limiting stimulation by extraneous stimuli, and perhaps facilitating optimal spacing of births and economical use of the store of oxytocin accumulated during pregnancy. During parturition, oxytocin cells increase their basal activity, and hence oxytocin secretion increases. In addition, the oxytocin cells discharge a burst of action potentials as each fetus passes through the birth canal. Each burst causes the secretion of a pulse of oxytocin, which sharply increases uterine tone; these bursts depend upon auto-stimulation by oxytocin released from the dendrites of the magnocellular neurons in the supraoptic and paraventricular nuclei. With the exception of the opioid mechanism that emerges to restrain oxytocin cell responsiveness, the behavior of oxytocin cells and their inputs in pregnancy and parturition is explicable from the effects of hormones of pregnancy (relaxin, estrogen, progesterone) on pre-existing mechanisms, leading through relative quiescence at term inter alia to net increase in oxytocin storage, and reduced auto-inhibition by nitric oxide generation. Cyto-architectonic changes in parturition, involving evident retraction of glial processes between oxytocin cells so they get closer together, are probably a response to oxytocin neuron activation rather than being essential for their patterns of firing in parturition.

Action Potentials↗

PubMed1985

Psychophysics of vibrotactile stimulation.

The effects of a wide range of stimulus parameters upon the psychophysical responses of subjects are important to an understanding of the functional characteristics of neural systems that underlie responses to cutaneous mechanical stimulation and the interactions that may occur between these systems. This understanding may also be useful to design considerations in the development of devices for tactile communication. This paper begins with a brief description of the two major systems in terms of psychophysical measurements and then focuses on a more detailed examination of possible interactions between them. The effects of time and space variables, such as frequency, temporal and intensity relationships between stimuli, area of stimulation, and surface gradients on the skin, are considered.

Acoustic Stimulation↗

PubMed1980

[A common pool of adenylate cyclase for different types of afferent receptors].

The authors investigate whether adenylate cyclase, that is a component of different receptors, i.e. the beta-adrenergic and H2-Histaminic ones of the heart, either plays a specific role for the activation of each receptor of forms the same pool for two types of receptors. On the mechanogram of guinea pig ventricle, stimulated by electric stimuli, an analysis of interferences among isoprenaline, propranolol, histamine and noradrenaline shows that isoprenaline inhibits histamine; in presence of propranolol the isoprenaline doesn't block histamine. Therefore the AA. conclude that adenylate cyclase is common to both receptors.

Adenylyl Cyclases↗

PubMed1996

Differential effects of changes in local myocardial refractoriness on atrial and ventricular latency.

BACKGROUND: Assessment of myocardial refractoriness and conduction properties, critical to development and propagation of reentrant arrhythmias, is an integral part of the investigation of atrial and ventricular tachycardias through the use of programmed electrical stimulation. Local conduction itself, however, may be affected by myocardial refractoriness. METHODS AND RESULTS: We studied the effects of changes in myocardial refractoriness on local conduction in right atrial and ventricular myocardium in 19 patients. Changes in effective, functional, and relative refractoriness were accomplished with the use of four pacing protocols, including drive train pacing cycle lengths (PCLs) of 600 and 400 milliseconds (ms) and drive train durations (DTDs) of 8 and 50 stimuli. Unipolar cathodal stimulation was performed from the distal electrode, and unipolar electrograms were recorded from the proximal three poles of quadripolar catheters with 5-mm interelectrode spaces. Atrial and ventricular effective and relative refractory periods (ERPs and RRPs) were significantly shortened by both the reduction in PCL and the increase in DTD. The reduction in the PCL shortened atrial and ventricular refractory periods significantly more than did the increase in the DTD. Changes in ventricular refractory periods were significantly greater compared with atrial refractory periods. The ratio of RRP to ERP was reduced in the atrium but significantly increased in the ventricle with reduction in PCL and increase in DTD. For all premature intervals, the conduction interval from stimulus to the first recording electrode pole was significantly greater than conduction intervals measured between subsequent electrode poles. The greatest increase in conduction interval with closely coupled premature complexes occurred between the stimulus artifact and the first recording electrode pole. Reduction in ventricular but not atrial ERP was associated with significantly increased local conduction interval. CONCLUSIONS: First, most of the conduction delay after the stimulus artifact occurs within 5 mm from the pacing site. Second, closely coupled premature complexes delay conduction primarily by prolonging latency in the first 5 mm from the pacing site. Third, fundamental differences occur between the atrium and ventricle regarding changes in local conduction as a function of changes in ERP, suggesting that factors involved in sudden changes in refractoriness (eg, heart rate acceleration) could produce divergent effects on atrial and ventricular arrhythmogenesis.

Adult↗

PubMed1987

Purification of eosinophils from normal human blood, preparation of eosinoplasts and characterization of their functional response to various stimuli.

Eosinophils from the blood of normal individuals were purified by centrifugation over discontinuous Percoll gradients. Eosinophil suspensions were obtained with a mean purity of 96% and a mean recovery of 64% (n = 19). When incubated with phorbol-myristate acetate, eosinophils consumed twice as much oxygen as did neutrophils from the same donors. With serum-treated zymosan, 70% and 100% of the maximal oxidative response (i.e. the response to phorbol-myristate acetate) was obtained with eosinophils and neutrophils, respectively. The calcium ionophore A23187 is a weak stimulus that triggered only 2.5% of the eosinophil and 10% of the neutrophil oxidative capacity. The response of both cell types to formyl-methionyl-leucyl-phenylalanine (fMLP) was rapid, with a maximum after 3 min. The magnitude of this eosinophil reaction was half that of neutrophils. Although the activities of the granule enzymes beta-glucuronidase and arylsulphatase were 2.5 and 6 times higher in eosinophils than in neutrophils, respectively, the exocytosis of these enzymes in response to various stimuli was lower in eosinophils. The high yield of eosinophils from our separation method enabled us to prepare eosinoplasts by centrifugation of eosinophils over discontinuous Ficoll gradients that contained cytochalasin B. Eosinoplasts are plasma membrane vesicles derived from eosinophils, filled with cytoplasm but devoid of granules and nucleus. The eosinoplasts contained 30% of the cytoplasm and plasma membrane present in intact eosinophils. Eosinoplasts still possessed a functionally intact oxidase enzyme that could be stimulated with various stimuli. Therefore, eosinoplasts may provide a valuable tool to study separately the role of the oxidase products and that of the granule contents in eosinophil functions.

Arylsulfatases↗

PubMed2005

Contribution of natural products to the discovery of the transient receptor potential (TRP) channels family and their functions.

Members of the transient receptor potential (TRP) family of nonselective cation channels are involved in several pathological and physiological conditions. The search for the molecular targets for naturally occurring substances, especially from plants, allowed the characterization of many TRP channels. In fact, attempts to understand the hot and painful action of the vanillyl group containing compounds capsaicin (from Capsicum sp.) and its ultrapotent analogue resiniferatoxin (RTX, from Euphorbia sp.) led to the cloning of the vanilloid receptor (TRPV1) 7 years ago. TRPV1 is found in sensory fibers and functions as a molecular integrator of several painful stimuli, being especially stimulated during inflammation. Since TRPV1 is involved in several pathological conditions, selective ligands or modulators of this channel are substances of potential interest to treat such diseases. Once again, natural products seem to be also interesting sources of compounds that might be prototype TRPV1 ligands. The cloning of TRPV1 also enabled the discovery of other members of the TRPV family of channels. Similar to TRPV1, these receptors function as molecular detectors of physical and chemical stimuli, such as innocuous and noxious heat, as well as mechanical force. Recently, novel TRP channels sensitive to low temperatures also have been cloned, namely, TRPM8 and TRPA1. Such channels are also activated by naturally occurring substances but knowledge of their involvement in health and disease is in its infancy. In the present review, we focused on the contribution of natural products to the discovery of TRP channels and to the development of novel drugs to treat pathological conditions in which these channels are involved.

Animals↗

PubMed2004

Human leukocyte elastase and cathepsin G are specific inhibitors of C5a-dependent neutrophil enzyme release and chemotaxis.

Circulating human neutrophils from patients with severe inflammatory disorders such as erysipelas and sepsis are specifically desensitized to complement factor C5a stimulation but not to stimulation with other stimuli like N-formyl-methionyl-leucyl-phenylalanine (FMLP), interleukin-8 (IL-8), leukotriene B4 (LTB4), or platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine). In this study, we raised the question whether factors released from polymorphonuclear leukocytes (PMNs) can specifically down-regulate C5a-dependent neutrophil functions. When neutrophils were preincubated with either neutrophil lysates or neutrophil degranulation supernatants, a complete inhibition of C5a-stimulated beta-glucuronidase release and chemotaxis could be observed, whereas FMLP-, IL-8-, LTB4- or PAF-dependent functions were not affected. Serine protease inhibitors like phenylmethylsulfonyl fluoride, antileukoprotease, or elafin abolished this effect. High-performance liquid chromatography of neutrophil degranulation supernatants revealed pronounced inhibition of C5a-dependent neutrophil functions in fractions exerting elastase or cathepsin G activity, but not in fractions exerting proteinase 3 activity. Using purified human leukocyte elastase (HLE), C5a responses like intracellular calcium influx, beta-glucuronidase release, and chemotaxis were also specifically inhibited. Our experiments show that the release of HLE or cathepsin G from neutrophils specifically down-regulates the responsiveness of neutrophils to C5a. Elastase and cathepsin G may therefore play an important role in the down-regulation of acute inflammation.

Adult↗

PubMed1979

The NIH-ERG ganzfeld stimulator.

The design specifications of a NIH-ERG ganzfield stimulator is discussed. Based on a proposed standard for clinical electroretinography, the stimulator uses stroboscopic stimuli as a whole field flash. But by varying the parameters of wavelengths and background illumination, a complete isolation of the rods and cone systems of the retina is obtained. This information is invaluable at times in early detection and diagnosis of retinal dysfunctions.

Diagnosis, Differential↗

PubMed1991

[Visually evoked P300 waves].

The event-related potentials after a competitive visual stimulation are presented. The stimulation with target stimuli results in two pronounced positive potentials in the grand-average, the P2 and the P3 component of the ERP, and a long-lasting positivity following the P3 wave. Similar but smaller potential components are elicited by non-target stimuli. Some examples of individual ERP demonstrate the high degree of inter-individual variability, as in the positive components as in the restoration of the poststimulus baseline. Some aspects of a possibly fundamental difference between visually and acoustically elicited P300 waves are demonstrated.

Acoustic Stimulation↗

PubMed1975

[Micromotor recording of writing pressure during intracerevral stimulation at stereotactic operations (author's transl)].

Eight cases of spastic torticollis were examined during the course of stereotactic operations with the writing pressure apparatus of Steinwachs while the ventrolateral thalamus was stimulated. When 50 stimuli per sec are given, the significant changes of motor function in writing are the following: slowing of writing speed, an increase in writing pressure, greater changes of pressure amplitude with tendences to parallel course. With 25 stimuli per sec, simular results may appear, but smaller amplitude changes and lowering of writing pressure may also occur. When 8 stimuli per sec are given, no changes of pressure patterns in writing were found. Three typical cases are described. It is concluded that the recording of fine pressure changes in writing may indicate alterations of cerebral motor regulations although specific changes for certain thalamic stimulus locations were lacking.

Adult↗

PubMed1994

Changes in intrinsic optical signal of rat neocortical slices following afferent stimulation.

Changes in intrinsic optical signal of rat neocortical slices following afferent stimulation were recorded using darkfield infrared-videomicroscopy. Response amplitude was linearly related to stimulation intensity. The intensity of the optical signal reached its maximum 3 s after onset of stimulation and redecayed with a mean time constant of 23 +/- 7.1 s. The optical signal had a columnar shape. The size of the column was independent from stimulation intensity with stimuli of medium amplitudes. The extent of the optical signal corresponded to the extent of the electrical activation. Changes in intrinsic optical properties may be a useful tool for the study of spread of excitation in neuronal tissue in vitro.

Afferent Pathways↗

PubMed1993

Evaluation of ferric oxalate as an agent for use during surgery to prevent post-operative root hypersensitivity.

The aim of this study was to evaluate the effectiveness of a 6% ferric oxalate solution applied during periodontal surgery to prevent post-operative tooth hypersensitivity. Twenty-five adult patients with similar bilateral periodontal defects participated in this study. Data were collected at baseline (1 week prior to surgery) and 1, 2, 4, and 6 weeks following surgery. Sensitivity level was determined using the visual analog scale (VAS) with the following stimuli: 1) mechanical stimulation with a No. 23 dental explorer; 2) water at 50 degrees C; 3) ice; and 4) electric pulp tester (EPT). Teeth were randomly assigned to either test (6% ferric oxalate in 0.9% saline) or control (0.9% saline) groups. Solutions were applied to the exposed root surfaces for 1 minute during surgery. Data were analyzed by repeated measures ANOVA, paired t-test, and Pearson's correlation test. Results from this study demonstrated statistically significant reduction in the responses to thermal stimuli, especially cold, between groups treated with ferric oxalate as compared to those treated with saline. For the cold test the difference increased with time from baseline to 6 weeks. Statistically significant (P < 0.05) differences in sensitivity to heat between groups were also observed, but only at 2 and 4 weeks following surgery. There were no differences at any time period between the test and control groups when tactile or EPT techniques were used. In addition, there was no correlation between sensitivity and other clinical parameters. It was concluded from this study that 6% ferric oxalate was effective in reducing post-surgical cold sensitivity when applied during periodontal surgical procedures.

Adult↗

PubMed1999

Differences in human visual evoked potentials during the perception of colour as revealed by a bootstrap method to compare cortical activity. A prospective study.

The aim of this prospective study was to investigate the colour related information in cortical activity as it is recorded from the scalp, by comparing the shape of the potential fields. Six healthy volunteers and two volunteers with known protanopsia were used to record multichannel visual evoked potentials after stimulation with chromatic stimuli of equally perceived brightness. The scalp fields resulting from each of the four chromatic stimuli were compared in pairs, in every possible combination and for each time point, using Efron's bootstrap method. It was found that, in comparison to other stimuli responses, the long dominant wavelength stimulus results in significant differences of cortical activity. These are mainly identified in two time periods: (a) at mid-latency responses, usually during the onset and development of P100 component, and (b) after the peak (on the decline) of P100 component. Similar but less evident behaviour was identified when the responses from the short dominant wavelength stimulus were compared with those from the other stimuli. Colour effects were not significant in protanops. The proposed method can be used to locate in time and quantify the differences in cortical activity during colour perception.

Adult↗

PubMed1988

Physiological characterization of the renal-sympathetic reflex in rabbits.

In urethane-anesthetized and vagotomized rabbits, electrical stimulation of the afferent renal nerve (RN) elicited reflex changes in renal nerve activity (RNA) and arterial pressure (AP). The responses were attributable mostly to excitation of nonmyelinated afferent fibers, although, in about 30% of the animals, they were contributed slightly by myelinated afferents. In about 70% of rabbits, the peristimulus time histogram (PTH) of RNA following stimulation of the RN consisted of a long-lasting inhibitory (I) component occasionally accompanied, during its recovery phase, by a transient excitatory (E) component. In these animals, tetanic stimulation of the RN resulted in a depressor response, either alone or, if an E component was present in the PTH, followed by a slight pressor response. In the remaining rabbits, the PTH was composed exclusively of an E component and tetanic stimulation caused a pressor response. Stimulation of the RN evoked reflex changes in cardiac sympathetic discharges comparable to that of RNA, whereas the change in cervical sympathetic discharges was much smaller. The sympathetic response remained intact after a total transection of the rostral medulla near the ponto-medullary junction; the I component was even augmented. However, it usually disappeared following a transection at the high cervical cord. Bilateral lesions of the nucl. tractus solitarius (NTS) near the obex failed to appreciably affect the response. Among chemical and mechanical stimuli examined, nociceptive stimulation of the kidney elicited a sympathetic response comparable to that following nerve stimulation. In conclusion, the renal-sympathetic reflex in rabbits (1) originates predominantly from nonmyelinated afferent renal fibers activated effectively by nociceptive stimulation applied to the kidney; (2) depends critically on medullary structures other than the NTS; and (3) evokes changes of the same temporal pattern but of nonuniform magnitude in sympathetic discharges to different organs.

Animals↗

PubMed2004

Secretion of oncostatin M by neutrophils in rheumatoid arthritis.

OBJECTIVE: Neutrophils are known to express and release a large number of proinflammatory cytokines when they are stimulated by inflammatory stimuli. The objective of this study was to determine whether neutrophils express oncostatin M (OSM), a member of the interleukin-6 family of cytokines that has been implicated in the pathogenesis of inflammatory joint disease. METHODS: Neutrophils were isolated from the blood of healthy volunteer donors and from the blood and synovial fluid of patients with rheumatoid arthritis (RA). OSM levels were measured in cell extracts and in culture supernatants by Western blotting. Total RNA was isolated from control and granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated neutrophils, and OSM messenger RNA levels were quantified by hybridization of a radiolabeled probe. RESULTS: GM-CSF stimulated a rapid and transient expression and release of OSM from blood neutrophils, which was more rapid than the expression and release from blood monocytes. A 28-kd protein was identified in cell extracts, but an additional 25-kd isoform was detected in culture supernatants. Synovial fluid neutrophils could not be stimulated to express OSM, but this cytokine was detected in cell-free supernatants at various levels. CONCLUSION: Blood neutrophils can be stimulated to express and rapidly release large quantities of OSM. We propose that this important cytokine is released from neutrophils as they infiltrate rheumatoid joints and, thus, contribute to the complex cytokine network that characterizes RA.

Arthritis, Rheumatoid↗

PubMed2004

Effect of novel non-peptidic delta opioid receptor antagonists on human T and B cell activation.

The effects of the antagonist naltrindole (NTI) on cells of the immune system have been largely studied although the mechanisms of action are still unclear. The aim of this study is to evaluate, in vitro, the immunomodulatory activity of four new delta-selective opioid compounds structurally related to naltrindole. The effects at different concentrations of these opioid antagonists on proliferative response were studied on normal human peripheral blood mononuclear cells (PBMC) stimulated with different stimuli: mitogens, the antigen PPD, the anti-CD3 monoclonal antibodies (mAb), the superantigen Staphylococcus aureus Cowan strain 1 (SAC) and alloantigens in the mixed lymphocyte cultures (MLR). The immunomodulatory capacity of these compounds was evaluated by determining the interleukin-2 (IL-2) release in mitogen activated PBMC. The present study shows that all the new delta opioid antagonists at 10(-5) M concentration are immunosuppressive. The inhibitory action is also evident at lower concentrations when anti-CD3 mAb and SAC were used as stimulators. In addition, the production of IL-2 was inhibited by the opioid treatment, but this might not be the only mechanism of action.

B-Lymphocytes↗

PubMed1997

The genetic basis of primary, predominantly specific immunodeficiencies.

The presented review lists primary immunodeficiencies which essentially involve a mutation in genes coding for functionally important molecules, membrane antigens (e.g., MHC), chains of lymphokine receptors, protein kinases of the signal cascade, transcription factors, and some important regulators of cellular metabolism. Mutations are expressed as early as during embryogenesis (lymphopoiesis-I) as well as during induction of the immune response by antigen ligand binding to cell receptors, TCR, BCR (immunopoiesis-II). Immunodeficiencies are classified by the stage of development (I) or immune response induction (II) in which they occur most markedly, even in clinical terms. It has been pointed out that the same autoactivation stimuli and mechanisms, allowing differentiation-maturation of cells during embryogenesis (action of stem cell factor (SFC), IL-3, IL-7, and activation cascade), serve even later as a functional prerequisite for an adaptive immune response to antigen. As a result, this attempt to classify primary immunodeficiencies by differentiation periods (when they become evident most markedly in terms of their function) has an inherent logical limitation. Some early mutations turn immediately lethal, some express themselves by blocking embryonic lymphopoiesis while other mutations do not become demonstrable until after cell stimulation by antigens. This explains why the developmental differentiation scheme is bound to turn, in the future, into an immunodeficiency classification by localization of gene mutations and their incidence in time, e.g., increased mutation incidence during proliferation following cell stimulation by antigen stimuli.

Animals↗