Long-term application of adrenergic agonists modulates nociceptive ion channels.

Dorsal root ganglia (DRG) neurons transduce and convey somatosensory information from the periphery to the central nervous system. Adrenergic mediators are known to modulate nociceptive inputs in DRG neurons, acting as up- or down-regulators of neuronal excitability. They are also important in the development of sympathetic neuropathy. ATP-activated P2X channels and capsaicin-activated TRPV1 channels are directly involved in the transduction of nociceptive stimuli. In this work, we show that long-term (up to 3 days) in vitro stimulation of DRG neurons with selective α1-adrenergic agonist increased slow but not fast ATP-activated currents, with no effect on capsaicin currents. Selective agonists for α2, ß1 and ß3-adrenergic receptors decreased capsaicin activated currents and had no effect on ATP currents. Capsaicin currents were associated with increased neuronal excitability, while none of the adrenergic modulators produced change in rheobase. These results demonstrate that chronic adrenergic activation modulates two nociceptive transducer molecules, increasing or decreasing channel current depending on the adrenergic receptor subtype. These observations aid our understanding of nociceptive or antinociceptive effects of adrenergic agonists.

Characterization of resolution, sensitivity, and shielding of a gamma-probe for sentinel lymph node localization: an experimental study.

OBJECTIVE: The aim of this study was to evaluate angular, spatial, and energy resolution, sensitivity, and shielding of a gamma-probe. MATERIALS AND METHODS: The EUROPROBE II gamma-probe (EuroRad) with sources of technetium-99m was assessed according to NEMA NU-3-2004. Resolution tests were evaluated considering the full width at half maximum (FWHM). The following parameters were evaluated: angular resolution in air, spatial resolution with a scattering medium and in air, energy resolution, and sensitivity and shielding. The collimator was used to evaluate angular and spatial resolution, sensitivity, and shielding. Background radiation was considered and did not affect the counts. RESULTS: FWHM of angular resolution (at 3/30 cm) was 39.17°/33.13° with the collimator and 74.08°/71.51° without the collimator; FWHM of spatial resolution in air at 10 mm was 13.32 mm with the collimator and 21.23 mm without the collimator. Energy resolution (%FWHM) was 20.51%. Sensitivity at 10 mm was 4.642±5 cps/MBq without the collimator and 1.063±2 cps/MBq with the collimator; shielding effectiveness of the probe tip was 99.52%. Background was not relevant to the counts. CONCLUSION: We showed that the collimator improved angular and spatial resolution to the detriment of sensitivity. Feasible results of energy resolution, sensitivity, and shielding were achieved.

Evaluation of oesophageal transit velocity using the improved Demons technique.

PURPOSE: This paper presents a novel method to compute oesophageal transit velocity in a direct and automatized manner by the registration of scintigraphy images. METHODS: A total of 36 images from nine healthy volunteers were processed. Four dynamic image series per volunteer were acquired after a minimum 8 h fast. Each acquisition was made following the ingestion of 5 ml saline labelled with about 26 MBq (700 µCi) technetium-99m phytate in a single swallow. Between the acquisitions, another two swallows of 5 ml saline were performed to clear the oesophagus. The composite acquired files were made of 240 frames of anterior and posterior views. Each frame is the accumulate count for 250 ms.At the end of acquisitions, the images were corrected for radioactive decay, the geometric mean was computed between the anterior and posterior views and the registration of a set of subsequent images was performed. Utilizing the improved Demons technique, we obtained from the deformation field the regional resultant velocity, which is directly related to the oesophagus transit velocity. RESULTS: The mean regional resulting velocities decreases progressively from the proximal to the distal oesophageal portions and, at the proximal portion, is virtually identical to the primary peristaltic pump typical velocity. Comparison between this parameter and 'time-activity' curves reveals consistency in velocities obtained using both methods, for the proximal portion. CONCLUSION: Application of the improved Demons technique, as an easy and automated method to evaluate velocities of oesophageal bolus transit, is feasible and seems to yield consistent data, particularly for the proximal oesophagus.

Segmented independent component analysis for improved separation of fetal cardiac signals from nonstationary fetal magnetocardiograms.

Fetal magnetocardiograms (fMCGs) have been successfully processed with independent component analysis (ICA) to separate the fetal cardiac signals, but ICA effectiveness can be limited by signal nonstationarities due to fetal movements. We propose an ICA-based method to improve the quality of fetal signals separated from fMCG affected by fetal movements. This technique (SegICA) includes a procedure to detect signal nonstationarities, according to which the fMCG recordings are divided in stationary segments that are then processed with ICA. The first and second statistical moments and the signal polarity reversal were used at different threshold levels to detect signal transients. SegICA effectiveness was assessed in two fMCG datasets (with and without fetal movements) by comparing the signal-to-noise ratio (SNR) of the signals extracted with ICA and with SegICA. Results showed that the SNR of fetal signals affected by fetal movements improved with SegICA, whereas the SNR gain was negligible elsewhere. The best measure to detect signal nonstationarities of physiological origin was signal polarity reversal at threshold level 0.9. The first statistical moment also provided good results at threshold level 0.6. SegICA seems a promising method to separate fetal cardiac signals of improved quality from nonstationary fMCG recordings affected by fetal movements.

A novel dynamic scintigraphic technique for assessing duodenal contractions during gastric emptying in humans: a feasibility study.

Duodenal contractions are thought to play a role in the control of gastric emptying. Although noninvasive techniques, such as ultrasonography and MRI, have been proposed for studying duodenal contractile activity in humans, there are no reports on the use of scintigraphy for this purpose. This work aimed to describe a novel scintigraphic technique for assessing duodenal contractility during gastric emptying in humans, and to present preliminary data on the frequency and amplitude of contractions detected in three different duodenal segments. Fasted young healthy volunteers (N=12) were given either a liquid or a solid test meal of similar calorie content (400 kcal) labeled with 99mTc-phytate. Static images were collected to determine gastric emptying. Dynamic images of the anterior aspect of the abdomen (1 frame/s) were also acquired periodically in a standard position for 256 s at 15-30 min intervals. 'Activity versus time' curves were generated for regions of interest corresponding to the proximal, middle, and distal duodenal segments. Curves were digitally filtered and processed to estimate both dominant frequency (fast Fourier transform) and amplitude (mean ejection fraction) of postprandial duodenal contractions. There were no significant differences regarding dominant frequency among proximal, middle, and distal duodenal regions of interest. In addition, there were no significant differences between the liquid and the solid meal in terms of either frequency or amplitude of duodenal contractions. Characterization of duodenal contractions in humans using scintigraphy is feasible and yields consistent data for both the frequency and the amplitude of postprandial contractions, which seems to be rather independent of meal consistency.

Towards component-based validation of GATE: aspects of the coincidence processor.

GATE is public domain software widely used for Monte Carlo simulation in emission tomography. Validations of GATE have primarily been performed on a whole-system basis, leaving the possibility that errors in one sub-system may be offset by errors in others. We assess the accuracy of the GATE PET coincidence generation sub-system in isolation, focusing on the options most closely modeling the majority of commercially available scanners. Independent coincidence generators were coded by teams at Toshiba Medical Research Unit (TMRU) and UC Davis. A model similar to the Siemens mCT scanner was created in GATE. Annihilation photons interacting with the detectors were recorded. Coincidences were generated using GATE, TMRU and UC Davis code and results compared to "ground truth" obtained from the history of the photon interactions. GATE was tested twice, once with every qualified single event opening a time window and initiating a coincidence check (the "multiple window method"), and once where a time window is opened and a coincidence check initiated only by the first single event to occur after the end of the prior time window (the "single window method"). True, scattered and random coincidences were compared. Noise equivalent count rates were also computed and compared. The TMRU and UC Davis coincidence generators agree well with ground truth. With GATE, reasonable accuracy can be obtained if the single window method option is chosen and random coincidences are estimated without use of the delayed coincidence option. However in this GATE version, other parameter combinations can result in significant errors.

Verbal and visual stimulation effects on rectus femoris and biceps femoris muscles during isometric and concentric.

BACKGROUND: Coactivation may be both desirable (injury prevention) or undesirable (strength measurement). In this context, different styles of muscle strength stimulus have being investigated. In this study we evaluated the effects of verbal and visual stimulation on rectus femoris and biceps femoris muscles contraction during isometric and concentric. METHODS: We investigated 13 men (age =23.1 ± 3.8 years old; body mass =75.6 ± 9.1 kg; height =1.8 ± 0.07 m). We used the isokinetic dynamometer BIODEX device and an electromyographic (EMG) system. We evaluated the maximum isometric and isokinetic knee extension and flexion at 60°/s. The following conditions were evaluated: without visual nor verbal command (control); verbal command; visual command and; verbal and visual command. In relation to the concentric contraction, the volunteers performed five reciprocal and continuous contractions at 60°/s. With respect to isometric contractions it was made three contractions of five seconds for flexion and extension in a period of one minute. RESULTS: We found that the peak torque during isometric flexion was higher in the subjects in the VVC condition (p > 0.05). In relation to muscle coactivation, the subjects presented higher values at the control condition (p > 0.05). CONCLUSION: We suggest that this type of stimulus is effective for the lower limbs.

Angiotensin-(1-7) induces peripheral antinociception through mas receptor activation in an opioid-independent pathway.

The G protein-coupled receptor Mas was recently described as an angiotensin-(1-7) [Ang-(1-7)] receptor. In the present study, we demonstrate an antinociceptive effect of Ang-(1-7) for the first time. Additionally, we evaluated the anatomical localization of Mas in the dorsal root ganglia using immunofluorescence. This is the first evidence indicating that this receptor is present in sensitive neurons. The antinociceptive effect was demonstrated using the rat paw pressure test. For this test, sensitivity is increased by intraplantar injection of prostaglandin E(2). Ang-(1-7) administered locally into the right hind paw elicited a dose-dependent antinociceptive effect. Because the higher dose of Ang-(1-7) did not produce an effect when injected into the contralateral paw, this effect was considered local. The specific antagonist for the Mas receptor, A-779, inhibited the peripheral antinociception induced by exposure to 4 µg/paw Ang-(1-7) in a dose-dependent manner. The highest dose completely reversed the antinociceptive effect induced by Ang-(1-7), suggesting that the Mas receptor is an obligatory component in this process and that other angiotensin receptors may not be involved. When injected alone, the antagonist was unable to induce hyperalgesia or antinociception. Alternatively, naloxone was unable to inhibit the antinociceptive effect induced by Ang-(1-7), suggesting that endogenous opioid peptides may not be involved in this response. These data provide the first anatomical basis for the physiological role of Ang-(1-7) in the modulation of pain perception via Mas receptor activation in an opioid-independent pathway. Taken together, these results provide new perspectives for the development of a new class of analgesic drugs.

Differential effects of Tityus bahiensis scorpion venom on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium currents.

We examined modification of sodium channel gating by Tityus bahiensis scorpion venom (TbScV), and compared effects on native tetrodotoxin-sensitive and tetrodotoxin-resistant sodium currents from rat dorsal root ganglion neurons and cardiac myocytes. In neurons, TbScV dramatically reduced the rate of sodium current inactivation, increased current amplitude, and caused a negative shift in the voltage-dependence of activation and inactivation of tetrodotoxin-sensitive channels. Enhanced activation of modified sodium channels was independent of a depolarizing prepulse. We identified two components of neuronal tetrodotoxin-resistant current with biophysical properties similar to those described for NaV1.8 and NaV1.9. In contrast to its effects on neuronal tetrodotoxin-sensitive current, TbScV caused a small decrease in neuronal tetrodotoxin-resistant sodium current amplitude and the gating modifications described above were absent. A third tetrodotoxin-resistant current, NaV1.5 recorded in rat cardiac ventricular myocytes, was inhibited approximately 50% by TbScV, and the remaining current exhibited markedly slowed activation and inactivation. In conclusion, TbScV has very different effects on different sodium channel isoforms. Among the neuronal types, currents resistant to tetrodotoxin are also resistant to gating modification by TbScV. The cardiac tetrodotoxin-resistant current has complex sensitivity that includes both inhibition of current amplitude and slowing of activation and inactivation.

Comparison between manual and automated techniques for assessment of data from dynamic antral scintigraphy.

OBJECTIVE: This work aimed at determining whether data from dynamic antral scintigraphy (DAS) yielded by a simple, manual technique are as accurate as those generated by a conventional automated technique (fast Fourier transform) for assessing gastric contractility. METHODS: Seventy-one stretches (4 min) of "activity versus time" curves obtained by DAS from 10 healthy volunteers and 11 functional dyspepsia patients, after ingesting a liquid meal (320 ml, 437 kcal) labeled with technetium-99m (99mTc)-phytate, were independently analyzed by manual and automated techniques. RESULTS: Data obtained by both techniques for the frequency of antral contractions were similar. Contraction amplitude determined by the manual technique was significantly higher than that estimated by the automated method, in both patients and controls. The contraction frequency 30 min post-meal was significantly lower in patients than in controls, which was correctly shown by both techniques. CONCLUSIONS: A manual technique using ordinary resources of the gamma camera workstation, despite yielding higher figures for the amplitude of gastric contractions, is as accurate as the conventional automated technique of DAS analysis. These findings may favor a more intensive use of DAS coupled to gastric emptying studies, which would provide a more comprehensive assessment of gastric motor function in disease.

Assessment of the post-prandial distribution of intragastric contents using an automated technique.

The distribution of intragastric contents has been studied using operator-dependent methods. We devised an automated technique for determining post-prandial intragastric distribution of radiolabeled meals, based on the calculation of the 'center of activity' (CA) of the radioactivity contained in the stomach in any given scintigraphic image. Twelve healthy volunteers and eleven functional dyspepsia (FD) patients ingested a liquid meal (320 mL, 450 kcal) labeled with (99m)Technetium-phytate. Images of the stomach were acquired every 5-10 min for 2 h, and counted to determine the percentage of total activity retained in the upper half of the stomach, as visually delineated. Each image was then processed using an algorithm for calculating a CA value representing the average of image-forming points corrected by pixel number. The relative CA position along the main longitudinal axis of the stomach, as defined by a digital 'skeletonizing' process, was expressed in a '0 to 1' scale. In the FD patients, the average of all CA determinations was significantly higher than in the controls (0.56, 0.30-0.80 versus 0.48, 0.33-0.68, p < 0.05) and correlated significantly with proximal stomach retention values assessed by a visual method (R = -0.64, p < 0.001). Assessing post-prandial intragastric distribution by a novel automated method is feasible and yields reliable data, while being much less operator dependent.

Relationships between intragastric food maldistribution, disturbances of antral contractility, and symptoms in functional dyspepsia.

We investigated the relationships between intragastric food maldistribution and antral dysmotility in functional dyspepsia, and whether these abnormalities relate to meal-induced symptoms. Intragastric distribution of food throughout gastric emptying was determined in patients (n = 24) and controls (n = 38) after a liquid nutrient meal labeled with (99m)technetium phytate. Antral contractility was also periodically assessed by dynamic scintigraphy and postprandial symptoms were monitored with visual analog scales. Residence of food in the proximal stomach was decreased in 8 (33%) and antral contractility was increased in 9 (37.5%) and decreased in 2 (8%) patients. Proximal and distal stomach motor abnormalities were neither significantly correlated nor associated. Increased antral contractility was significantly correlated (Rs = 0.54; P < .01) with postprandial nausea. We conclude that diminished residence of food in the proximal stomach and disturbed antral contractility occur independently in different subsets of functional dyspepsia patients. Increased antral contractility seems to play a role in postprandial nausea in functional dyspepsia.

Diminished retention of food in the proximal stomach correlates with increased acidic reflux in patients with gastroesophageal reflux disease and dyspeptic symptoms.

This work aimed at evaluating the intragastric distribution of food in patients with GERD and dyspepsia and its relationship to acidic reflux episodes. Gastric emptying and food retention in the proximal stomach were evaluated by scintigraphy in 12 healthy subjects and 19 patients with GERD and dyspepsia after a liquid test meal. Patients also underwent 24-hr esophageal pH monitoring, which included a 2-hr postprandial period following a similar test meal. Total gastric emptying was similar in patients and controls, whereas proximal gastric retention (AUCprox/AUCtot) was significantly decreased in patients (mean +/- SD: 0.48 +/- 0.07 vs. 0.56 +/- 0.06; P = 0.02). Within the GERD-dyspepsia group, a significant negative correlation was found between proximal gastric retention and the number of acidic reflux episodes. We concluded that abnormally decreased retention of gastric contents in the proximal stomach after a liquid meal may contribute to the pathogenesis of acidic reflux episodes in patients with GERD and dyspepsia.

Adaptive, autoregressive spectral estimation for analysis of electrical signals of gastric origin.

The electrical activity of the human stomach, which normally shows a frequency of about 0.05 Hz, may be studied non-invasively by either cutaneous electrogastrography (EGG) or surface magnetogastrography (MGG). Detection of changes in frequency with time may be useful to characterize gastric disorders. The fast Fourier transform (FFT) has been the most commonly used method for the automated spectral analysis of the signals obtained from the EGG or the MGG. We have used an autoregressive (AR) parametric spectrum estimator to analyse simulated signals of gastric electrical activity, and to evaluate the results of human studies using EGG and MGG. In comparison with the FFT, our results showed that the AR spectrum estimator provided more detailed qualitative information about frequency variations of short duration simulated signals than the FFT. In the human studies, the AR estimator was as good as the conventional FFT methods in detecting physiological changes in frequency and in identifying abnormal recordings. We conclude that the AR spectral estimator may provide a better qualitative analysis of frequency variations in small portions of the signal, and is as useful as the FFT to analyse human EGG or MGG studies.

Estudos em magnetogastrografia / Study in magnetogastrography

O registro da atividade elétrica doo estômago, através da detecção do campo magnético associado foi detectado. A comparação desta atividade através do registro simultâneo do sinal elétrico e magnético foi feita através da função de correlação, análise de Fourier e testes estatísticos. A medida desta atividade pode auxiliar no diagnóstico de patologias do trato gastrointestinal. O método magnético apresenta a vantagem de ser completamente não invasivo.

Abstract - This work shows the study of the stomach electrical activity by the measurement of the magnetic field produced by the electrical currents generated at the stomach. A comparison between the electric and magnetic measurements was performed by the correlation function, Fourier analysis and statistical tests. These measurements can help on diagnostic of gastric-intestinal pathologies. This method has the advantage of the being non invasive