Biomedical subjects

A E Villa

Publications and source records attributed to A E Villa.

At least 19 recordsLinked to original sources

PubMed1999

Pharmaceutical fingerprinting in phase space. 1. Construction of phase fingerprints.

The present study proposes a general method for constructing pharmaceutical fingerprints in the analysis of HPLC trace organic impurity patterns. The approach considers signals in phase space and accounts for two different types of noise: additive and perturbative. The first type, additive noise, contributes to distortion of the absolute values of signal peaks. The second type, perturbative noise, contributes to variations of the retention times of signal peaks and distorts the time scale of the trace organic impurity patterns. The ability of the proposed approach to consider both types of noise significantly distinguishes it from existing methods of data analysis that are usually designed to treat only the additive noise. Analysis of the HPLC signals in phase space eliminates the problem of perturbation noise and enables detection and comparison of similar signal segments recorded at different retention times. The current study analyzes the chromatographic trace organic impurity patterns collected from six different manufacturers of L-tryptophan using three HPLC columns. For five manufacturers the variability of data recorded with the same column are in perfect agreement with the proposed model. A significant variance of parameters is detected for one manufacturer, thus indicating a possible change in its product consistency. The analysis in phase space is also used to explain the previously detected variability of HPLC signals across columns. The accompanying paper reports an application of the proposed approach for the pattern recognition of HPLC data.

Algorithms↗

PubMed1999

Pharmaceutical fingerprinting in phase space. 2. Pattern recognition.

The current study introduces an approach for pattern recognition of drug manufacturers according to their HPLC trace impurity data. This method considers signals in phase space and accounts for two different types of noise: additive and perturbative. The pharmaceutical fingerprints are estimated as mean trajectories of HPLC trace impurity data and are used as reference models for recognition of new data by the minimal length classifier. The chromatographic trace organic impurity patterns collected from six different manufacturers of L-tryptophan are analyzed as an example. The prediction ability of the new method tested using three different cross-validation procedures remains about 95% even if the number of available data in the training sets decreases by 5 times. The accuracy of prediction in phase space is superior compared to results calculated using a Window Preprocessing method and artificial neural networks. The difference in performance between new and previous methods becomes more significant under particular conditions that are more adequate for practical application of the method. In addition, the current approach enables simple and comprehensive interpretation of the calculated results.

Artificial Intelligence↗

PubMed1999

Spatiotemporal activity patterns of rat cortical neurons predict responses in a conditioned task.

Precise and repeated spike-train timings within and across neurons define spatiotemporal patterns of activity. Although the existence of these patterns in the brain is well established in several species, there has been no direct evidence of their influence on behavioral output. To address this question, up to 15 neurons were recorded simultaneously in the auditory cortex of freely moving rats while animals waited for acoustic cues in a Go/NoGo task. A total of 235 significant patterns were detected during this interval from an analysis of 13 hr of recording involving over 1 million spikes. Of particular interest were 129 (55%) patterns that were significantly associated with the type of response the animal made later, independent of whether the response was that prompted by the cue because the response occurred later and the cue was chosen randomly. Of these behavior-predicting patterns, half (59/129) were associated with an enhanced tendency to go in response to the stimulus, and for 11 patterns of this subset, trials including the pattern were followed by significantly faster reaction time than those lacking the pattern. The remaining behavior-predicting patterns were associated with an enhanced NoGo tendency. Overall mean discharge rates did not vary across trials. Hence, these data demonstrate that particular spatiotemporal patterns predict future behavioral responses. Such presignal activity could form templates for extracting specific sensory information, motor programs prespecifying preference for a particular act, and/or some intermediate, associative brain process.

Acoustic Stimulation↗

PubMed1999

Preferential induction of fos-like immunoreactivity in granule cells of the cochlear nucleus by acoustic stimulation in behaving rats.

Neuronal activity in the cochlear nucleus was mapped in relation to acoustic stimuli that signalled a sensory-motor response, using Fos-like immunoreactivity. Rats were trained to associate an acoustic stimulus with a reward and then to discriminate between two sounds ('learning' rats; n = 18). The same stimuli carrying no behavioural significance were pseudo-randomly presented to 'control' rats (n = 4) to differentiate stimulus related- from learning related-activity. To establish a baseline, Fos-like immunoreactivity was determined in rats (n = 2) unexposed to acoustic stimulation. The number of Fos-positive cells was significantly increased in the rats exposed to sounds ('learning' and 'control') as compared to the non-stimulated animals. This stimulus related increase of Fos-like activity in the cochlear nucleus was most prominent in a subpopulation of small neurons, whose spatial distribution corresponds to that of the granule cells. There was also an increase in the number of Fos-positive neurons of larger size, but less prominent than for the small cells. Brief exposure to sounds (30 s) was sufficient to induce Fos-like activity.

Acoustic Stimulation↗

PubMed1999

Corticofugal modulation of functional connectivity within the auditory thalamus of rat, guinea pig and cat revealed by cooling deactivation.

Microelectrode recordings were simultaneously performed at multiple sites in the medial geniculate body (MGB) of anesthetized cats, rats and guinea pigs. We studied the effect of cortical deactivation on the association of neural activity within the thalamus during spontaneous activity. The corticofugal influence was suppressed by temporary cooling of the auditory cortex. Pairs of spike trains recorded from the same electrode were distinguished from cases where units were in MGB but recorded with different electrodes. Time domain analyses included crosscorrelations and search for precise repetition of complex spatiotemporal firing patterns of reverberating thalamic circuits. As a complementary approach we performed bispectral analyses of simultaneously recorded local field potentials in order to uncover the frequency components of their power spectra which are non linearly coupled. All results suggest that new functional neuronal circuits might appear at the thalamic level in the absence of input from the cortex. The newly active intrathalamic connections would provide the necessary input to sustain the reverberating activity of thalamic cell assemblies and generate low frequency non-linear interactions. The dynamic control exerted by the cortex over the functional segregation of information processing carried out in the thalamus conforms with theoretical neural network studies and with the functional selectivity-adaptive filtering theory of thalamic neuronal assemblies. Although this general conclusion remains valid across species, specific differences are discussed in the frame of known differences of the microcircuitry elements.

Animals↗

PubMed1999

Prediction of partition coefficient based on atom-type electrotopological state indices.

The aim of this study was to determine the efficacy of atom-type electrotopological state indices for estimation of the octanol-water partition coefficient (log P) values in a set of 345 drug compounds or related complex chemical structures. Multilinear regression analysis and artificial neural networks were used to construct models based on molecular weights and atom-type electrotopological state indices. Both multilinear regression and artificial neural networks provide reliable log P estimations. For the same set of parameters, application of neural networks provided better prediction ability for training and test sets. The present study indicates that atom-type electrotopological state indices offer valuable parameters for fast evaluation of octanol-water partition coefficients that can be applied to screen large databases of chemical compounds, such as combinatorial libraries.

Chemical Phenomena↗

PubMed1999

Estimation of the fraction of an ingested dose of fluoride excreted through urine in pre-school children.

OBJECTIVE: To determine the fraction of an ingested fluoride dose of 1 mg in 50 mL orange juice that is excreted through the urine (FUEF) of children aged 3-5 years. METHODS: Eighty-eight controlled determinations involving 24-hour urinary collections from a total of 48 children were carried out during consecutive control and test days. Net fluoride urinary excretion due to the ingested dose was calculated as the difference between the total amount of fluoride excreted by each child on test and control days. RESULTS: Excretion of the fluoride ingested from the single fluoride dose presented an average value of 30.7% (95% CI: 28.9-32.5%). No significant associations were found between individual FUEF values with either anthropometrical variables or urinary pH values. The average FUEF value found in the present study lies between previously reported values for infants and young adults. The epidemiological usefulness of the FUEF values in estimating daily fluoride dose in pre-school children is discussed.

Administration, Oral↗

PubMed1998

Computer assisted neurophysiology by a distributed Java program.

We have developed a distributed software package which allows neurophysiologists to have at hand a set of network and graphic tools in order to perform the analysis of data collected from the electrical activity of neurons, studied in the experimental laboratory. This system is built around three major components. First, the experimental data are processed in order to select specific data files from the networked computer and display the spike trains as raster dots. The second part selects one type of analysis (e.g., cross-correlation, out of a set of possible choices) after configuration of some specific parameters. Finally, the third component deals with the results of data analyses, which are selected and displayed on a multi-parameter graphic "ring binder." We have used the Java programming language to implement this application. This recent object-oriented language offers platform-independent software tools including graphic package and standard network protocols.

Algorithms↗

PubMed1998

Discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus of the rat.

The aim of the present study was to characterize the discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the rat. In the absence of acoustic stimulation, two types of spontaneous discharge patterns were observed: units tended to fire in a bursting or in a nonbursting mode. The distribution of units in the DNLL based on spontaneous firing rate followed a rostrocaudal gradient: units with high spontaneous rates were most commonly located in the rostral part of the DNLL, whereas in the caudal part units had lower spontaneous discharge rates. The most common response pattern of DNLL units to 200 ms binaural noise bursts contained a prominent onset response followed by a lower but steady-state response and an inhibitory response in the early-off period. Thresholds of response to noise bursts were on average higher for DNLL units than for units recorded in the inferior colliculus under the same experimental conditions. The DNLL units were arranged according to a mediolateral sensitivity gradient with the lowest threshold units in the most lateral part of the nucleus. In the rat, as in other mammals, the most common DNLL binaural input type was an excitatory response to contralateral ear stimulation and inhibitory response to ipsilateral ear stimulation (EI type). Pure tone bursts were in general a more effective stimulus compared to noise bursts. Best frequency (BF) was established for 97 DNLL units and plotted according to their spatial location. The DNLL exhibits a loose tonotopic organization, where there is a concentric pattern with high BF units located in the most dorsal and ventral parts of the DNLL and lower BF units in the middle part of the nucleus.

Acoustic Stimulation↗

PubMed1998

Estimation of optimal concentration of fluoride in drinking water under conditions prevailing in Chile.

The purpose of this comparative study of caries and dental fluorosis experience in Chilean children was to estimate the optimal range of fluoride concentration in tap water under conditions currently prevailing in Chile. The sample included 2431 schoolchildren 7, 12 and 15 years old, life-long residents of five communities with fluoride concentrations in their tap water in the range 0.07-1.1 mg/L. The study population received an oral clinical examination including caries experience and an enamel fluorosis evaluation of the permanent dentition (Dean's scoring system). For 15-year-old children, the DMFT index changed from 5.06 to 2.60, and for 12-year-olds it changed from 3.10 to 1.36 when fluoride water concentration changed from 0.07 to 1.10 mg/L. For 7-year-old children the dmft index correspondingly changed from 3.67 to 1.59. The relationship between DMFT for 12-year-olds and water fluoride concentration was best fitted by a logarithmic function (r2=0.98). The Community Fluorosis Index (CFI) was used to assess enamel fluorosis in the study population, and it showed a linear relationship (r2=0.983) with increasing fluoride concentration of water for the 12-year-old group. Results obtained suggest that under current Chilean conditions, the optimal range of fluoride concentration in potable water should lie in the 0.5-0.6 mg/L range.

Adolescent↗

PubMed1998

Dental fluorosis in Chilean children: evaluation of risk factors.

The purpose of this case-control study was to determine the association between very-mild-to-moderate enamel fluorosis and exposure during early childhood to fluoridated water, mainly through ingestion of powdered milk. Analysis was performed on 136 residents of the optimally fluoridated community of San Felipe in the Chilean Fifth Region, who were categorised into one of three groups according to their age when water fluoridation was introduced in 1986: Group I was born after 1986; Group II was 16-24 months old in 1986; and Group III was >24 months of age. The case and control subjects were selected on the basis of a clinical examination given in July 1996. Dean's scoring system was used to determine fluorosis status. Risk factor exposure was ascertained by a questionnaire used in interviews with mothers of participating children. Logistic regression analysis, after adjustment for confounding variables, revealed that very-mild-to-moderate enamel fluorosis of permanent central maxillary incisors (CMI) was strongly associated both with the age of the subjects when water fluoridation began and with breast-feeding duration for children belonging to Group I. Subjects in Group I were 20.44 times more likely (95% CI: 5.00-93.48) to develop CMI fluorosis than children who were older than 24 months (Group III) when fluoridation began. Subjects who were between 16 and 24 months old when water fluoridation began were 4.15 times more likely (95% CI: 1.05-16.43) to have CMI fluorosis than children older than 24 months. An inverse association was found with breastfeeding duration (OR=0.86, 95% CI: 0.75-0.98) among Group I subjects but not in Groups II and III. Results obtained suggest that the current fluoride concentration in drinking water may be contributing to fluorosis. Further studies will be necessary to determine the relative competing risks of dental fluorosis and dental caries in Chilean children in order to establish the most appropriate water fluoridation level in Chile.

Analysis of Variance↗

PubMed1997

Ketamine modulation of the temporal pattern of discharges and spike train interactions in the rat substantia nigra pars reticulata.

This study compares the temporal pattern of discharges of extracellularly recorded substantia nigra pars reticulata (SNr) single units in two experimental conditions: Equithesin- and ketamine-induced anesthesia. The analysis of the statistical properties of the spike trains recorded in the Equithesin group of animals showed that this experimental condition could be considered as a control condition with respect to previous data reported in the literature. We investigated the glutamatergic modulation of SNr activity at spike train level in a steady-state condition by using the anesthetic agent ketamine, which is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) glutamatergic receptors. The most relevant effect of ketamine at single unit level was to induce burst discharges, with an intraburst frequency rate near 50 Hz, specifically in units characterized by an initial long refractoriness in the Equithesin condition. The other classes of single units tended to discharge at a higher rate without any significant change in their temporal pattern of firing. Simultaneous recording of the spike trains of 108 SNr pairs (46 and 62 during Equithesin and ketamine condition, respectively) were equally distributed between pairs of units simultaneously recorded from the same electrode and from distinct electrodes at a distance up to 400 microm in the same hemisphere. Ketamine induced a significant increase in the number of pairs with synchronous firing (from 4 to 49%), which was strongly, but not exclusively, associated with an increased tendency to fire in bursts. Neighboring cells tended to fire with a similar pattern in either condition of recording, whereas synchronous firing between distant cells was observed only during ketamine condition.

Action Potentials↗

PubMed1996

Low-dimensional chaotic attractors in the rat brain.

The existence of chaotic attractors for discrete time series, derived from the occurrences of spikes during electrophysiological recordings, was investigated. The time series included between 800 and 5200 points per analyzed record. The spike trains were recorded in the substantia nigra pars reticulata (n = 13) and in the auditory thalamus (n = 14). The experiments were performed on anesthetized rats during spontaneous activity and during auditory stimulation. According to standard methods of dynamical systems theory, an embedding space was constructed using delay coordinates. The embedding and correlation dimensions were computed by means of the correlation integrals. For 7 of 27 samples, a deterministic structure with a low embedding dimension (ranging between 2 and 6) and a correlation dimension between 0.14 and 3.3 could be determined. Evidence was found that the sensory stimulation may affect the chaotic behavior. Single units recorded simultaneously from the same electrode tip may display different chaotic dynamics, even with a similar time-locked response to the stimulus onset.

Acoustic Stimulation↗

PubMed1996

Nerve growth factor modulates information processing in the auditory thalamus.

The spatio-temporal organization of spike discharges was studied in rat auditory thalamus (i.e., medial geniculate body and auditory sector of thalamic reticular nucleus) following a 2-week continuous intracerebroventricular administration of nerve growth factor (NGF). Recording of extracellular single-unit activity indicated that, in medial geniculate body, NGF induced a significant increase of the mean firing rate. In thalamic reticular nucleus, where units tend to discharge in bursts, NGF increased the average burst size (number of spikes) and the intraburst frequency without affecting the firing rate. Following white noise acoustical stimulation, in medial geniculate body, more onset excitation and a lower signal-to-noise ratio were observed in NGF-treated rats than in controls. Conversely, in thalamic reticular nucleus, NGF-treated animals showed more inhibitory responses than controls. In addition, within the medial geniculate body, functional interactions between pairs of units simultaneously recorded from different electrodes were greatly increased by the nerve growth factor treatment. These data indicate that modifications of temporal pattern of discharges in selected brain regions are among the effects induced by the intracerebroventricular administration of nerve growth factor.

Animals↗

PubMed1996

Reversible deactivation of cerebral network components.

Reversible deactivation techniques have shown that the cerebral network: (1) is dynamic, its functions depending on contemporaneous processing elsewhere in the network; (2) is composed of single nodes that contribute to several behaviors; (3) possesses an inherent plasticity that tends to minimize lesion-induced deficits; and (4) comprises feedforward and lateral connections that contribute in different ways to network operations. The next major advances in understanding network operations will probably be made by applying a combination of behavioral, neuron-recording and deactivation techniques. The greatest near-term gains are likely to be made in understanding the contributions that feedback projections make to cerebral network function.

Animals↗

PubMed1996

Caries experience and fluorosis prevalence in Chilean children from different socio-economic status.

Caries experience and enamel fluorosis prevalence in 8-year-old children belonging to different socio-economic classes were determined in two Chilean twin cities that are served by optimally fluoridated community water from the same waterworks facility. Low socio-economic status (LSES) children had a higher mean dmft and DMFT indices (P < 0.001) than high socioeconomic status (HSES) children. Prevalence of enamel fluorosis in the permanent teeth of LSES children was 0.79, significantly higher (chi 2 = 9.0; P < 0.003) than the value 0.59 found in HSES children. The proportion of Dean's scores 2, 3, 4 and 5 in first molars, mandibular and maxillary incisors in LSES children was higher than in HSES children (P < 0.001). Differences in prevalence and severity of enamel fluorosis between both groups are tentatively attributed to a different pattern of tap water and tea consumption at pre-school ages. Suggestions are advanced to minimize the undesirable prevalence and severity of enamel fluorosis.

Child↗

PubMed1995

Evidence for a repetitive (burst) firing pattern in a sub-population of 5-hydroxytryptamine neurons in the dorsal and median raphe nuclei of the rat.

Previous electrophysiological studies have shown that spontaneously active mesencephalic 5-hydroxytryptaminergic neurons of anaesthetized or freely moving animals fire solitary spikes in a slow, regular pattern. In the present study, using extracellular single unit recordings from dorsal and median raphe neurons of the anaesthetized rat, an additional electrophysiological property of a sub-population of presumed 5-hydroxytryptaminergic neurons was observed. These neurons, during their otherwise regular firing pattern, repeatedly fired two (or occasionally three or even four) spikes where only one was expected. Spikes in this burst-like repetitive firing mode (spikes in doublets or triplets) occurred in a short time interval (range: 2.4-11.5 ms), and with a diminishing spike amplitude. Cross-correlation analysis of spikes in doublets revealed a very high interdependency between them. The proportion of spikes in doublets to solitary spikes showed great variation between different neurons, ranging from 5 to 95% of the total spikes displayed. However, for each neuron the proportion of spikes in doublets to solitary spikes, and the time interval between the spikes in doublets, remained constant during control recordings. All these features are characteristic of single neurons firing in a repetitive firing pattern rather than simultaneous recordings of two separate 5-hydroxytryptaminergic neurons. Repetitive firing neurons were recorded with a similar frequency in both chloral hydrate and Saffan anaesthetized rats, and were detected using both glass and metal electrodes. Furthermore, neurons with a repetitive firing pattern were inhibited by intravenous administration of a selective 5-hydroxytryptamine1A receptor agonist and a 5-hydroxytryptamine reuptake inhibitor, thus displaying responses typical of 5-hydroxytryptaminergic neurons. Repetitive firing neurons occurred in both the dorsal and median raphe nuclei, although they were much more frequent in the dorsal raphe nucleus (91 of 332 neurons). The occurrence of repetitive firing neurons in the midbrain raphe nuclei is a newly described phenomenon which may indicate unique properties of a sub-population of 5-hydroxytryptaminergic neurons. In functional terms, it could modify both axonal and dendritic 5-hydroxytryptamine release, and provide an additional option for neuronal information signalling.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1995

Morphology and spatial distribution of corticothalamic terminals originating from the cat auditory cortex.

In this paper we studied the morphology and spatial distribution of corticothalamic axons and terminals originating from the auditory cortical fields of the cat. The anterograde tracer biocytin was injected at electrophysiologically characterized loci in the primary (AI) (N = 2), anterior (AAF) (N = 1), posterior (PAF) (N = 1) and secondary (AII) (N = 2) auditory fields. In all cases, two different types of labeled terminals were found in the auditory thalamus: small spherical endings (1-2 microns) and giant, finger-like endings (5-10 microns). After biocytin injections in AI and AAF, the majority of anterogradely labeled axons terminated in the rostral half of the pars lateralis (LV) of the ventral division of the medial geniculate body (vMGB). In LV, the corticothalamic axons ramified profusely, giving rise to dense terminal fields forming well delineated curved stripes, with small spherical endings. Additional terminal fields formed by small endings were observed in the medial division of the medial geniculate body (mMGB). Giant endings were observed in a small area in the dorsal nucleus (D) of the dorsal division of the medial geniculate body (dMGB), near its border with the vMGB. PAF projections were located in the caudal half of vMGB and in mMGB, where only small terminals were found. Giant endings were seen in the superficial part of dMGB emerging from labeled corticothalamic axons oriented in parallel to the dorsal surface of the MGB. Projections from AII gave rise to a main terminal field of small endings in D; a second terminal field consisting of giant endings intermingled with small endings was found in the deep dorsal nucleus (DD) of dMGB. We conclude that small terminals serve the feedback projection to the thalamic nucleus from which the injected cortical field receives its main input, whereas giant terminals cross the borders between the parallel ascending auditory pathways.

Acoustic Stimulation↗