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Biomedical subjects

M Bove

Publications and source records attributed to M Bove.

At least 19 recordsLinked to original sources
PubMed2006

The postural disorientation induced by neck muscle vibration subsides on lightly touching a stationary surface or aiming at it.

The aim of this study was to investigate whether the standing body spatial disorientation, induced by neck muscle vibration, and the related post-effects can be suppressed by light finger touch (LFT) of a stationary surface. Continuous (60 s) vibration of dorsal neck or sternocleidomastoid muscle was administered with eyes closed. The center of foot pressure (CFP) displacement, measured by a stabilometric platform, indicated the degree of vibration-induced body tilt. We also investigated whether sensory information from LFT itself was necessary or anticipation of a more secure posture was enough for reducing vibration effects. To this aim, we administered a vibration pulse (5 s) to dorsal neck or sternocleidomastoid muscle and during reaching to the stationary surface. CFP was recorded during both vibration and post-vibration condition and during the aiming task. Neck vibration induced significant CFP displacement in the direction opposite to vibration site. Post-vibration, CFP slowly returned to control values with ample oscillations. LFT during vibration reduced body tilt. LFT was more effective when fingertip contact was in the plane of the greatest tilt. LFT applied during either vibration or post-vibration period reduced post-vibration effects. Reaching toward the stationary surface was enough for reducing vibration-induced body tilt to values close to those observed during actual LFT. The novel conclusions of this study are: 1) LFT is able to relieve the effects of vibration-induced abnormal proprioceptive input from the neck, a segment central to postural control and orientation; 2) LFT during vibration also attenuates vibration post-effects, further suggesting that its action is not merely mechanical; 3) the intention to stabilize the body generates a new postural 'set' sufficient for diminishing body tilt.

Adult↗
PubMed2005

Evaluation of toxicity from high-dose systemic administration of recombinant adenovirus vector in vector-naive and pre-immunized mice.

Toxicity associated with in vivo administration of adenovirus (Ad) vectors has been linked to activation of both innate and adaptive immune responses. Pre-existing immunity to the prevalent Ad serotypes, acquired by the majority of the human population as a result of natural infections, has the potential to modulate vector efficacy and safety. Previously, we evaluated some aspects of toxicity from systemic Ad vector in vector-naive and pre-immunized rhesus monkeys. In this report, we summarize data from several studies analyzing toxic effects from systemically administered E1/E3-deleted Ad vector in vector-naive and pre-immunized C57BL/6 mice. Our results indicate that pre-immunization can be associated with increased mortality shortly after systemic administration of Ad. Transient leukopenia and thrombocytopenia were observed early post vector infusion in both vector-naive and pre-immunized animals. Pre-exposure to the vector did not prevent induction of pro-inflammatory cytokines; however, pre-immunized mice showed less tissue toxicity. Growth of bone marrow myeloid and erythroid progenitors was transiently inhibited in pre-immunized animals, but only the myeloid progenitors were affected in vector-naive animals. In summary, pre-existing immunity to Ad vector substantially modifies host immune responses to systemic Ad vector.

Adenoviridae↗
PubMed2005

Epithelial barrier integrity and intraluminal nitric oxide production in response to acid perfusion of the ferret oesophagus.

AIM: To evaluate the source and role of acid-induced intraluminal nitric oxide (NO) production in the oesophagus by studying how the exposure of the oesophagus to acid affects NO release, via the NO-producing enzyme NO synthase and its relation to changes in epithelial barrier integrity. METHODS: Ferrets were anaesthetized and their oesophagi were divided at both ends. The test subjects were pre-treated with the intravenous NO synthase inhibitors N(G)-nitro-L-arginine-methyl ester (L-NAME, 100 mg kg(-1)) and 1400W (12 mg kg(-1)). Untreated and N(G)-nitro-D-arginine-methyl ester pre-treated (D-NAME, 100 mg kg(-1)) animals served as controls. The oesophagus was then perfused with either HCl (0.1 m) or physiological saline for 20 min. The intraluminal NO concentration was determined before and after the acid/saline infusion while the transmucosal potential difference (PD) was monitored continuously. Oesophageal biopsies were examined for expression of inducible NO synthase using immunohistochemistry. RESULTS: The intraluminal NO concentration increased after acid exposure. This was blocked by L-NAME and 1400W, but not by D-NAME. The peak PD response was not affected by agents affecting NO synthesis, while the plateau response was attenuated by L-NAME, D-NAME and 1400W. Immunohistochemistry revealed inducible NO synthase expression in the epithelium. CONCLUSIONS: Exposing the ferret oesophageal mucosa to acid elicited an increase in juxtamucosal NO formation through the activation of inducible NO synthase. The corresponding electrophysiological observations suggested an association between mucosal NO production and epithelial integrity.

Amidines↗
PubMed2003

Effects of dietary nitrate on oesophageal motor function and gastro-oesophageal acid exposure in healthy volunteers and reflux patients.

BACKGROUND/AIMS: High concentrations of nitric oxide (NO), derived from dietary nitrite in an acid environment, have been demonstrated in the gastric fundus and in the oesophagus. The aim of this study was to investigate whether luminal NO can influence oesophageal smooth muscle performance, lower oesophageal sphincter (LOS) function or gastric and oesophageal acid exposure. METHODS: Eleven healthy volunteers and 9 patients with chronic gastro-oesophageal reflux disease (GORD) received a diet deprived of nitrate/nitrite but supplemented with placebo or potassium nitrate for 4 days in a randomised order. On day 4 in each trial period, manometry was performed including a sleeve sensor registration of the LOS followed by a simultaneous 24-hour intra-gastric and oesophageal pH registration. RESULTS: Nitrate supplementation increased the proportion of effective peristalsis when analysed for the entire study population. No other significant effects of dietary nitrate were found on oesophageal motor variables, on the sphincter resting tone or on the number or duration of transient sphincter relaxations. No effect was found on either gastric acidity or gastro-oesophageal reflux variables. Major reflux symptoms were not influenced by nitrate administration. CONCLUSION: Dietary nitrate did not significantly affect oesophageal motor or LOS function, gastro-oesophageal acid reflux or reflux symptomatology either in healthy volunteers or in GORD patients.

Adult↗
PubMed2002

Sources of intra-oesophageal nitric oxide production following intraluminal acid exposure.

BACKGROUND: The aim of the present study was to assess luminal nitric oxide (NO) levels in the oesophagus during baseline and acidic conditions and to clarify the sources of such oesophageal NO formation. METHODS: Healthy volunteers received an intra-oesophageal infusion of either HCl (100 mM) or NaCl (50 mM) on two separate study days. After a low nitrate diet, nitrate load or no dietary restrictions/pretreatment, direct intraluminal measurements of NO formation were performed using a tonometric technique. Endoscopy was performed and mucosal biopsies were taken and analysed by means of immunohistochemistry, Western blot and RT-PCR. RESULTS: No intra-oesophageal NO was detected during baseline conditions with pH neutrality. During the infusion of HCI the NO levels rose dramatically to around 12000 ppb. This high rate of NO formation fell by 95% following deviation of saliva. NO formation after an acute nitrate load was almost doubled during acid perfusion compared to control. Immunohistochemistry demonstrated distinct staining for iNOS in the oesophageal squamous epithelial cells, and Western blot and RT-PCR confirmed the presence of iNOS. CONCLUSION: Two sources exist for intra-oesophageal NO formation, both dependent on the luminal acidity: 1) chemical reduction of salivary nitrite, a mechanism related to dietary intake of nitrate, and 2) NO formation within the oesophageal mucosal epithelium by enzymatic degradation of L-arginine. In the latter case, the NO synthase has antigenic characteristics, indicating the inducible isoform, although a functional behaviour suggests an unconventional subtype.

Adolescent↗
PubMed2001

Neck muscle vibration disrupts steering of locomotion.

Neck muscle vibration was applied to human subjects to assess the influences of neck abnormal proprioceptive input on the organization and execution of gait. Subjects walked blindfolded to a previously seen target, located straight ahead at ~4 m. Vibration was applied on the right side of the neck, both during and before walking. The variables measured were length, duration, and velocity of trajectory; relative and absolute frontal errors at target; and width of walking support base. Vibration applied during locomotion produced an undershoot of target and deviation of gait trajectory toward the side opposite to vibration. Vibration applied before locomotion produced no effect on length of trajectory but slowing of velocity and nonsystematic deviation. When vibration frequency was increased, the amplitude of the nonsystematic deviation increased. Vibration applied during or before stance trials had minor effects on body sway. Vibration before stance had no effect on the position of mean center of foot pressure, whereas vibration during stance displaced it to the side opposite to the vibrated muscle. We suggest that vibration during locomotion reduces length and velocity of trajectory because of a direct action on the locomotor centers and produces trajectory deviation related to its effect on stance. Vibration before locomotion causes a major, nonsystematic deviation from the planned trajectory, possibly connected to a disorientation of the internal references.

Adult↗
PubMed2000

24-H pharyngeal pH monitoring in healthy volunteers: a normative study.

BACKGROUND: Gastropharyngeal reflux has been associated with disorders of the upper and lower airways. It may be shown by pharyngeal pH-metry, but reports on normality in healthy volunteers are scarce. No definite consensus has been reached considering the upper limit of normality (ULN). The aim of the present study was therefore to quantify the occurrence of pharyngeal acid exposure (pH < 4) in healthy volunteers and, further, to examine its relation to acid exposure of the oesophagus and oesophageal motility and its occurrence in relation to age, sex, and body position. METHODS: Forty healthy volunteers underwent ambulatory 24-h pH-metry, using antimony electrodes positioned 2 cm above the upper oesophageal sphincter and 5 cm above the lower oesophageal sphincter on the basis of manometry. Technical artefacts were excluded before calculation of all results. RESULTS: Gastropharyngeal reflux occurred in most healthy volunteers without any significant relation to age, sex, or body weight. Pharyngeal acid reflux occurred mainly in the upright position. The ULN for pharyngeal acid exposure time was assessed to 0.9% (0.2% after exclusion of mealtimes). The ULN for the number of acid events in the pharynx was 18 (6.1). The corresponding ULNs for the oesophagus were 7% and 84. CONCLUSION: Gastropharyngeal reflux may be effectively monitored by ambulatory pH-metry. The present study provides reference limits, a prerequisite for evaluating the pathophysiologic importance of the phenomenon.

Adult↗
PubMed2000

Insulin release at the molecular level: metabolic-electrophysiological modeling of the pancreatic beta-cells.

The role of pancreatic beta-cells is fundamental in the control endocrine system, maintaining the blood glucose homeostais in a physiological regime, via the glucose-induced release of insulin. An increasing amount of detailed experimental evidences at the cellular and molecular biology levels have been collected on the key factors determining the insulin release by the pancreatic beta-cells. The direct transposition of such experimental data into accurate mathematical descriptions might contribute to considerably clarify the impact of each cellular component on the global glucose metabolism. Under these perspectives, we model and computer-simulate the stimulus-secretion coupling in beta-cells by describing four interacting cellular subsystems, consisting in the glucose transport and metabolism, the excitable electrophysiological behavior, the dynamics of the intracellular calcium ions, and the exocytosis of granules containing insulin. We explicit the molecular nature of each subsystem, expressing the mutual relationships and the feedbacks that determine the metabolic-electrophysiological behavior of an isolated beta-cell. Finally, we discuss the simulation results of the behavior of isolated beta-cells as well as of population of electrically coupled beta-cells in Langerhans islets, under physiological and pathological conditions, including noninsulin-dependent diabetes mellitus (NIDDM) and hyperinsulinemic hypoglycaemia (PHHI).

Computer Simulation↗
PubMed1999

Fast calculation of short-term depressing synaptic conductances.

An efficient implementation of synaptic transmission models in realistic network simulations is an important theme of computational neuroscience. The amount of CPU time required to simulate synaptic interactions can increase as the square of the number of units of such networks, depending on the connectivity convergence. As a consequence, any realistic description of synaptic phenomena, incorporating biophysical details, is computationally highly demanding. We present a consolidating algorithm based on a biophysical extended model of ligand-gated postsynaptic channels, describing short-term plasticity such as synaptic depression. The considerable speed-up of simulation times makes this algorithm suitable for investigating emergent collective effects of short-term depression in large-scale networks of model neurons.

Algorithms↗
PubMed1999

A simple microfluidic system for patterning populations of neurons on silicon micromachined substrates.

The purpose of this paper is to describe a low-cost simple technique based on the hydraulically driven deposition of adhesion molecules for patterning populations of neurons on silicon micromachined substrates. First, the design and fabrication process of the silicon micromachined substrates and the design of a flow-through chamber for the localised deposition of adhesive proteins are described. The experimental protocol for the deposition of the adhesive proteins is then presented. Finally, the results of experiments of 'entrapment' of chick embryo spinal cord neurons in microstructures of the silicon substrates and of formation of patterned biological neural networks are shown.

Animals↗
PubMed1999

An array of Pt-tip microelectrodes for extracellular monitoring of activity of brain slices.

A microelectrode array (MEA) consisting of 34 silicon nitride passivated Pt-tip microelectrodes embedded on a perforated silicon substrate (porosity 35%) has been realized. The electrodes are 47 microns high, of which only the top 15 microns are exposed Pt-tips having a curvature of 0.5 micron. The MEA is intended for extracellular recordings of brain slices in vitro. Here we report the fabrication, characterization and initial electrophysiological evaluation of the first generation of Pt-tip MEAs.

Animals↗
PubMed1999

Coupling of organotypic brain slice cultures to silicon-based arrays of electrodes.

Fetal or early postnatal brain tissue can be cultured in viable and healthy condition for several weeks with development and preservation of the basic cellular and connective organization as so-called organotypic brain slice cultures. Here we demonstrate and describe how it is possible to establish such hippocampal rat brain slice cultures on biocompatible silicon-based chips with arrays of electrodes with a histological organization comparable to that of conventional brain slice cultures grown by the roller drum technique and on semiporous membranes. Intracellular and extracellular recordings from neurons in the slice cultures show that the electroresponsive properties of the neurons and synaptic circuitry are in accordance with those described for cells in acutely prepared slices of the adult rat hippocampus. Based on the recordings and the possibilities of stimulating the cultured cells through the electrode arrays it is anticipated that the setup eventually will allow long-term studies of defined neuronal networks and provide valuable information on both normal and neurotoxicological and neuropathological conditions.

Animals↗
PubMed1998

Analysis of the signals generated by networks of neurons coupled to planar arrays of microtransducers in simulated experiments.

Planar microelectrode arrays can be used to characterize the dynamics of networks of neurons reconstituted in vitro. In this paper simulations related to experiments of the electrical activity recording by means of planar arrays of microtransducers coupled to networks of neurons are described. First a detailed model of single and synaptically connected neurons is given, appropriate to computer simulate the action potentials of neuronal populations. Then 'realistic' signals are generated. These signals are intended to reproduce, both in shape and intensity, those recorded by a microelectrode array. Typical experimental conditions are considered, and a detailed analysis given, of the bioelectronic coupling and of its influence on the shape of the recorded signals. Finally, simulated experiments dealing with dorsal root ganglia neurons are described and analysed in comparison with experimental results reported in the literature and obtained in our own laboratory. The effectiveness of the planar microelectrode technique is briefly discussed.

Animals↗
PubMed1998

Thermal oral-pharyngeal stimulation and elicitation of swallowing.

The influence of thermal stimulation of the oral and pharyngeal mucosa on the elicitation of swallowing was studied in 14 healthy volunteers. The Repeated Dry Swallowing Test was used to study the ability to elicit swallows. The test consists of 11 manometrically recorded dry swallows performed at maximum speed. The time between swallows 1 and 11 (Swallowing Test Time) is considered a measure of the ease of eliciting the swallowing reflex. The study includes two controlled experiments, each consisting of an active test done immediately after a cold stimulus and a control done after a stimulus at body temperature. In one experiment the stimulus consisted of stimulation of the fauces with a laryngeal mirror and in the other of swallowing water. Each subject served as his or her own control. The order of the tests was randomized and the results read blindly. In the mirror experiment, the swallowing test times obtained after application of a cold laryngeal mirror did not differ significantly from those obtained after stimulation at body temperature. In the water experiment, swallowing test times were shorter after swallowing cold water compared to those after swallowing water at body temperature in 11 of the 14 volunteers (n.s.). The concept that swallowing is significantly facilitated by cold applied to the oral-pharyngeal mucosa was thus not supported by the present study. The importance of these findings is discussed.

Adult↗
PubMed1997

Experimental analysis of neuronal dynamics in cultured cortical networks and transitions between different patterns of activity.

Experimental investigation of the dynamics of biological networks is a fundamental step towards understanding how the nervous system works. Spontaneous activity in cultured networks of cortical neurons has been investigated by using a multisite recording technique with planar electrode arrays. In these networks, the spatiotemporal firing patterns were studied in the presence of different extracellular solutions. Transitions from asynchronous firing dynamics to synchronous firing dynamics were observed when the extracellular Ca2+ concentration was increased from 0.1 mM to 1 mM. Addition of extracellular Mg2+ reduced the spontaneous activity at any Ca2+ concentration, and an increase in the extracellular K+ concentration enhanced the frequency of periodical synchronous bursts. N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor antagonists inhibited synchronous activity. A spatiotemporal analysis of the data has been performed, and the properties of the network such as the synchronization and the periodicity have been quantified in order to clarify how variations of intrinsic parameters of the network can induce structural transitions in the neural dynamics. This experimental study is a possible approach to investigate the computational properties of a neuronal network.

Animals↗
PubMed1997

The effect of administered crystalloid fluid temperature on aural temperature of moderately and severely injured children.

OBJECTIVE: Warm intravenous fluid (W-IVF) administration is the standard of care to prevent hypothermia in injured adults. It is argued that such administration may not be helpful for treating injured children, because children often do not require as much intravenous fluid (i.v.f.) as adults. The purpose of this study was to compare the effects of W-i.v.f. to room temperature intravenous fluid (RT-i.v.f.) administration on aural temperature (Ta) in injured children during the first hour of trauma resuscitation. DESIGN: A randomized, controlled repeated-measures trial. SETTING: Emergency department, intensive care unit, and diagnostic areas in a level I pediatric trauma center. SAMPLE: Thirty moderately or severely injured children, ranging in age from 2 to 17 years (mean age = 8.9 years; SD = 4.4). METHODS: Eligible children were randomly assigned to receive either W-i.v.f. or RT-i.v.f. on ED arrival. Warmed IVF was administered with the Hotline fluid warmer (SIMS Level 1, Rockland, Mass). Aural temperatures were measured on arrival and every 10 minutes for 1 hour with a Core-Check Tympanic Thermometer (IVAC Medical Systems, San Diego, Calif). The level of significance for hypothesis testing was set at 0.05 (two-tailed). RESULTS: Groups were comparable in age, gender, weight, amount of infused i.v.f., Revised Trauma Score, room temperature, and baseline Ta. On average, Ta for the W-i.v.f. group increased by 0.25 degree C from baseline to final Ta, whereas Ta for the RT-i.v.f. group decreased by 0.32 degree C from baseline to final Ta. Repeated-measures analysis of covariance, treating baseline Ta as a covariate, demonstrated that Ta response profiles were similar (p = 0.06). CONCLUSIONS: When comparing the changes between baseline and final Ta for the W-i.v.f. and RT-i.v.f. groups, the standardized difference in temperature change was 0.62. Although results of the repeated measures analysis of covariance were not statistically significant, the standardized difference in temperature changes was large enough to warrant administration of W-i.v.f., even at slow flow rates, to prevent hypothermia in injured children.

Adolescent↗
PubMed1997

In vitro 2-D networks of neurons characterized by processing the signals recorded with a planar microtransducer array.

The purpose of this paper is to extensively analyze and utilize the key features that characterize the recently available electrophysiological technique of growing selected populations of neurons on planar substrate microelectrode arrays. This experimental configuration is first simulated by modeling the signal transduction operated by an array of microtransducers coupled to a network of Hodgkin-Huxley-like neurons, connected to each other with given levels of synaptic strength. Signal processing tools are then described and validated by identifying the various degrees of connectivity previously introduced into the simulated network. Finally, these software tools are utilized to characterize the activity and identify the synaptic connectivity of networks of cultured neurons extracted from dorsal root ganglia (DRG) of chick embryos and exposed to synapse inhibiting/reinforcing ions. As a result, correlations between various regimens of electrophysiological activity and synaptic strength are obtained.

Algorithms↗