Brain functional and effective connectivity underlying the information processing speed assessed by the Symbol Digit Modalities Test.

Delayed Information Processing Speed (IPS) often underlies attention deficits and is particularly evident in patients with traumatic brain injury, Parkinson's disease, depression, dementia, and multiple sclerosis. Therefore, it is of interest to determine the brain network that is responsible for such essential cognitive function to understand IPS deficits and to develop effective rehabilitation programs. We assessed brain functional connectivity and effective connectivity during the performance of an adapted version of the Symbol Digit Modalities Test. Using dynamic causal modeling, we focused on obtaining a network model for IPS function in healthy subjects. Sixteen right-handed volunteers (seven women, age: 29.7 ±â€¯5.0 years) were included in the study after giving written consent for participating. Functional magnetic resonance images were acquired in a 3T scanner. According to our results, two systems interact during the IPS task performance. One is formed by frontoparietal and fronto-occipital networks, related to the control of goal-directed (top-down) selection for stimuli and response, while the second is composed of the temporoparietal and inferior frontal cortices, which are associated with stimulus-driven attention in the brain. Additionally, the default-mode network showed a significant correlation with networks positively associated with the task, mainly those related to visual detection and processing, indicating its relevant role in functional integration involving IPS. Therefore, an IPS-related network was proposed through a methodology that may be useful for future studies considering other cognitive functions and tasks, clinical groups, and longitudinal assessments.

Performance of electroencephalogram-derived parameters in prediction of depth of anaesthesia in a rabbit model.

BACKGROUND: The index of consciousness (IoC), the permutation entropy (PE), and the approximate entropy are recent EEG-derived indices of anaesthetic depth. In this study, a rabbit model under fentanyl and isoflurane anaesthesia was used to compare the performance of these indices and also the classic median and spectral edge frequency 95%. METHODS: EEG recordings were obtained from six rabbits. Animals received fentanyl for premedication, followed by induction with propofol and maintenance with isoflurane. Anaesthetic depth was evaluated according to a clinical scale from 1 (awake) to 4 (surgical anaesthesia). Animals were submitted to surgical implantation of a small device in the lumbar muscles. A correction factor for the EEG suppression ratio was applied to the spectral parameters and to the PE. The correlation of the indices with the clinical scale of anaesthesia was analysed using prediction probability. Repeated-measures analysis of variance or its non-parametric equivalent was used to analyse the indices values at the study times and to compare their variability. RESULTS: The IoC showed the best mean prediction probability value [0.94 (0.01)] followed by burst suppression-corrected PE [0.91(0.03)]. Both parameters also showed less variability than the others. CONCLUSIONS: The IoC and PE are promising indices for anaesthetic depth monitoring. The PE might benefit from the application of a burst suppression correction at deeper stages of anaesthesia. The rabbit is useful as a translational research animal model for the validation of clinical indices.

A step towards effect-site target-controlled infusion with propofol in dogs: a k(e0) for propofol.

Target-controlled infusion (TCI) anesthesia using target effect-site concentration rather than plasma concentration provides less drug consumption, safer anesthesia, less undesired side effects and improved animal welfare. The aim of this study was to calculate the constant that converts propofol plasma into effect-site concentration (k(e0)) in dogs, and to implement it in a TCI system and compare it with the effect on the central nervous system (CNS). All dogs were subjected to general anesthesia using propofol. Fourteen dogs were used as the pilot group to calculate k(e0), using the t(peak) method. Fourteen dogs were used as the test group to test and validate the model. RUGLOOP II software was used to drive the propofol syringe pump and to collect data from S/5 Datex monitor and cerebral state monitor. The calculated k(e0) was incorporated in an existing pharmacokinetic model (Beths Model). The relationship between propofol effect site concentrations and anesthetic planes, and propofol plasma and effect-site concentrations was compared using Pearson's correlation analysis. Average t(peak) was 3.1 min resulting in a k(e0) of 0.7230 min(-1). The test group showed a positive correlation between anesthetic planes and propofol effect-site concentration (R = 0.69; P < 0.0001). This study proposes a k(e0) for propofol with results that demonstrated a good adequacy for the pharmacokinetic model and the measured effect. The use of this k(e0) will allow an easier propofol titration according to the anesthetic depth, which may lead to a reduction in propofol consumption and less undesired side effects usually associated to high propofol concentrations in dogs.

Antibody responses in hyperthyroid rats.

This study evaluated antibody production against sheep red blood cells (SRBC) in hyperthyroid rats during treatment with triiodothyronine (T(3)). The immune response was evaluated by measuring plaque forming cells (PFC) in the spleen and by enzyme-linked immunosorbent assay (ELISA) in serum of male Wistar rats (180+/-10 g) treated with 25 mug/day of triiodotironine (T(3)) during 7-12 days and immunized with SRBC at the 8th day of treatment. The results showed that anti-SRBC antibody production was significantly decreased in animals treated for 12 days when compared to normal rats immunized with the same antigen, as evaluated by the two assays. These results show that in this experimental model hyperthyroidism decreases antibody response. We previously observed the opposite effect, that is, an increase in this response in hypothyroid rats resulting from the treatment with propylthyouracil, a blocker of thyroid hormone biosynthesis. It is suggested that antibody production is affected by thyroid hormone levels.

Practical aspects of the use of target controlled infusion with remifentanil in neurosurgical patients: predicted cerebral concentrations at intubation, incision and extubation.

Remifentanil has important side effects and it is not easy to know what remifentanil concentrations should be used during different endpoints of anaesthesia. We analyzed the remifentanil predicted effect-site concentrations (RemiCe) at different events during neurosurgical procedures and assessed if the concentrations used were clinically adequate. BIS and haemodynamic parameters were collected every 5 seconds. Predicted cerebral concentration of propofol (PropCe) and RemiCe were analyzed immediately prior to respective stimulus, and 30, 60 and 90 seconds after. RemiCe were 2.2 +/- 0.3, 6 +/- 2.6 and 2.2 +/- 0.9 ng ml(-1) at intubation, incision and extubation, respectively. PropCe observed in the same periods were 5 +/- 1, 2.6 +/- 0.9 and 1 +/- 0.3 microg ml(-1), also respectively. The remifentanil concentrations used in our patients were lower than reported concentrations, while being clinically adequate to minimize the haemodynamic response to stimulation.

[Hydroxyethyl starch 130/0.4 can be useful to prevent a hemodynamic response to a single dose of remifentanil]. / E1 hidroxietilalmidón (HES) 130/0.4 puede ser úitil en la prevención de la respuesta hemodinámica a un bolus de remifentanilo.

Intravenous propofol and remifentanil are often used in anesthesia. The combined use of these drugs tends to cause hemodynamic depression. We describe the absence of hemodynamic effects in response to infusion of propofol and remifentanil when hydroxyethyl starch (HES) 130/0.4 was also administered. During induction, because blood volume needed to be replaced, two patients aged 62 and 65 years received intravenous HES 130/0.4. They then received a single dose of 2 microg x kg(-1) of remifentanil during total intravenous anesthesia (TIVA) with propofol and remifentanil before placement of a Mayfield head holder. No changes in mean blood pressure or heart rate were observed in either patient after the remifentanil bolus when they have received HES 130/0.4 during TIVA with propofol and remifentanil HES 130/0.4 may play an active role in preventing a hemodynamic response to remifentanil bolus. This hypothesis should be tested in a randomized controlled trial.

Electroencephalogram-based indices applied to dogs' depth of anaesthesia monitoring.

Hypnotic drug administration causes alterations in the electroencephalogram (EEG) in a dose-dependent manner. These changes cannot be identified easily in the raw EEG, therefore EEG based indices were adopted for assessing depth of anaesthesia (DoA). This study examines several indices for estimating dogs' DoA. Data (EEG, clinical end-points) were collected from 8 dogs anaesthetized with propofol. EEG was initially collected without propofol. Then, 100 ml h⁻¹ (1000 mg h⁻¹) of propofol 1% infusion rate was administered until a deep anaesthetic stage was reached. The infusion rate was temporarily increased to 200 ml h⁻¹ (2000 mg h⁻¹) to achieve 80% of burst suppression. The index performance was accessed by correlation coefficient with the propofol concentrations, and prediction probability with the anaesthetic clinical end-points. The temporal entropy and the averaged instantaneous frequency were the best indices because they exhibit: (a) strong correlations with propofol concentrations, (b) high probabilities of predicting anaesthesia clinical end-points.

Fuzzy logic model to describe anesthetic effect and muscular influence on EEG Cerebral State Index.

The well-known Cerebral State Index (CSI) quantifies depth of anesthesia and is traditionally modeled with Hill equation and propofol effect-site concentration (Ce). This work brings out two novelties: introduction of electromyogram (EMG) and use of fuzzy logic models with ANFIS optimized parameters. The data were collected from dogs (n=27) during routine surgery considering two propofol administration protocols: constant infusion (G1, n=14) and bolus (G2, n=13). The median modeling error of the fuzzy logic model with Ce and EMG was lower or similar than that of the Hill with Ce (p=0.012-G1, p=0.522-G2). Furthermore, there was no significant performance impact due to model structure alteration (p=0.288-G1, p=0.330-G2) and EMG introduction increased or maintained the performance (p=0.036-G1, p=0.798-G2). Therefore, the new model can achieve higher performance than Hill model, mostly due to EMG information and not due to changes in the model structure. In conclusion, the fuzzy models adequately describe CSI data with advantages over traditional Hill models.

Caffeic acid phenethyl ester protects against the dopaminergic neuronal loss induced by 6-hydroxydopamine in rats.

Caffeic acid phenethyl ester (CAPE) is a botanical compound abundant in honeybees' propolis. It has anti-inflammatory, antiviral, antioxidant, immunomodulatory and antitumor properties. Its beneficial effects against neurodegenerative diseases, including Parkinson's disease, have also been suggested and some mechanisms have been proposed. Mitochondrial damage and oxidative stress are critical events in neurodegeneration. Release of cytochrome c from mitochondria to cytosol and the downstream activation of caspase-3 have been suggested as targets of the protective mechanism of CAPE. Most of the studies addressing the protective effect of CAPE have been performed in cell culture. This is the first study to demonstrate the protective effect of CAPE against the dopaminergic neuronal loss induced by 6-hydroxydopamine (6-OHDA) in rats. It also demonstrates, for the first time, the inhibitory effect of CAPE on mitochondrial permeability transition (MPT), a mediator of neuronal death that triggers cytochrome c release and caspase-3 activation. Scavenging of reactive oxygen species (ROS) and metal chelation was demonstrated in the brain-affected areas of the rats treated with 6-OHDA and CAPE. Additionally, we demonstrated that CAPE does not affect brain mitochondrial function. Based on these findings and on its ability to cross the blood-brain barrier, CAPE is a promising compound to treat Parkinson's and other neurodegenerative diseases.

Low-molecular-mass peptides from the venom of the Amazonian viper Bothrops atrox protect against brain mitochondrial swelling in rat: potential for neuroprotection.

The neurodegenerative diseases are important causes of morbidity and mortality in Western countries. Common mechanisms of toxicity involving mitochondrial damage have been suggested; however, a definitive treatment has not yet been found. Therefore, there has been great interest in the development of mitochondria-targeted protective compounds for the treatment of neuropathies. Animal toxins represent a promising source of new molecules with neuroprotective activity and potential to originate new drugs. We present here the effects of a low-molecular-mass peptides fraction (Ba-V) from Bothrops atrox snake venom, on rat brain mitochondrial function. Ba-V did not induce the mitochondrial swelling and moreover, was as effective as cyclosporin A (CsA) to inhibit the calcium/phosphate-induced swelling, which indicates its potential to prevent the mitochondrial permeability transition (MPT). The membrane electrochemical potential, the oxygen consumption during states-3 and -4 respirations as well as the respiratory control ratio (RCR) were not affected by Ba-V. Additionally, Ba-V did not induce reactive oxygen species (ROS) generation. Interestingly, Ba-V did not protect against the generation of ROS induced by t-BOH, which suggests a protection mechanism other than ROS scavenging. Given the important role of the mitochondrial damage and, more specifically, of MPT, in the development of neuropathies, Ba-V might be useful in the future strategies for the treatment of these diseases.

Correlation between clinical signs of depth of anaesthesia and cerebral state index responses in dogs during induction of anaesthesia with propofol.

The cerebral state index (CSI) is used for monitoring EEG and depth of anaesthesia. The objective of this study was to analyse the correlation between ocular reflexes, CSI and estimated propofol plasma concentrations (PropCP) in dogs during induction of anaesthesia with propofol. Fourteen dogs were premedicated with acepromazine 0.05 mg kg(-1) IM. Anaesthesia was induced with a 200 ml h(-1) propofol 1% constant infusion rate until loss of corneal reflex using RugLoop II software with Beths' pharmacokinetic model to estimate PropCp. Palpebral reflex (PR) and the corneal reflex (CR) were tested every 30s and classified as present (+) or absent (-), and eyeball position was registered as rotated ventromedialy (ERV) or centred (EC). Heart rate (HR), mean arterial pressure (MAP) and CSI values were analyzed from baseline before the beginning of propofol infusion (T0) until loss of CR; CSI and PropCp, CSI and anaesthetic planes, and PropCp and anaesthetic planes were compared using correlation analysis. PropCp reached 7.65+/-2.1 microg ml(-1) at the end of the study. CSI values at T0 were 89.2+/-3.8. Based on the observation of ocular reflexes and eyeball position, it was possible to define five anaesthetic planes: A (superficial) to E (deep), being A (PR+/CR+/EC), B (PR+/ERV/CR+), C (PR-/ERV/CR+), D (PR-/EC/CR+) and E (PR-/EC/CR-). There was a significant correlation between PropCp and the anaesthetic planes (R=0,861; P<0.01). No significant correlation was observed between CSI and the anaesthetic planes or between CSI and PropCp. MAP decreased significantly from T0 until loss of corneal reflex (from 98+/-14 mm Hg to 82+/-12 mm Hg); HR did not change significantly (from 101+/-30 bpm to 113+/-16 bpm). The CSI monitoring was not consistent with the clinical observations observed in the different stages of depth anaesthesia. This could limit the use of CSI for monitoring depth of anaesthesia with propofol.

The effect of a remifentanil bolus on the bispectral index of the EEG (BIS) in anaesthetized patients independently from intubation and surgical stimuli.

BACKGROUND AND OBJECTIVE: Remifentanil boluses are used in different clinical situations and the effects on bispectral index monitoring are unclear. We analysed the effect of a remifentanil bolus on the bispectral index of the electroencephalogram (bispectral index) under total intravenous anaesthesia with propofol and remifentanil. METHODS: ASA I-III patients were included in this study. All patients received a 2 microg k g-1 remifentanil bolus in a period free from stimuli. Bispectral index and haemodynamic data were collected from an A-2000XP bispectral index monitor (every second) and an AS/3 Datex monitor (every 5 s). Bispectral index data were analysed using the area under the curve. Mean arterial pressure and heart rate were averaged at each 30-s period and analysed using analysis of variance. RESULTS: A total of 240 bispectral index values were obtained per patient. The area under the curve between 90 and 120 s after the bolus was significantly lower than the basal area under the curve (average of all areas before the bolus, P < 0.05). Mean arterial pressure and heart rate were significantly reduced from 96.4 +/- 19.9 mmHg at the time of the bolus to 74.2 +/- 16.6 mmHg 120 s after, and from 70 +/- 16.4 bpm at the time of the bolus to 61 +/- 13.6 bpm after (P < 0.001), respectively. CONCLUSIONS: There was a significant reduction in the areas under the curve between 90-120 s following the bolus. Heart rate and blood pressure also showed significant reductions. Thus, remifentanil bolus given under total intravenous anaesthesia with propofol and remifentanil decreases bispectral index, an effect independent of intubation and surgical stimuli.

Radial basis function neural networks versus fuzzy models to predict return of consciousness after general anesthesia.

This work presents two modelling techniques to predict return of consciousness (ROC) after general anaesthesia, considering the effect concentration of the anaesthetic drug at awakening. First, several clinical variables were statistically analysed to determine their correlation with the awakening concentration. The anaesthetic and the analgesic mean dose during surgery, and the age of the patient, proved to have significantly high correlation coefficients. Variables like the mean bispectral index value during surgery, duration of surgery did not present a statistical relation with ROC. Radial basis function (RBF) neural networks were trained relating different sets of clinical values with the anaesthetic drug effect concentration at awakening. Secondly, fuzzy models were built using an adaptive network-based fuzzy inference system (ANFIS) also relating different sets of variables. Clinical data was used to train and test the models. The fuzzy models and RBF neural networks proved to have good prediction properties and balanced results.

Características de fermentação da silagem de cana-de-açúcar tratada com uréia, zeólita, inoculante bacteriano e inoculante bacteriano/enzimático / Fermentation of sugarcane silage treated with urea, zeolita, bacteria inoculant and bacteria/enzymatic inoculant

Estudaram-se as características de fermentação da cana-de-açúcar (RB72454) submetida aos tratamentos: controle; 0,5 por cento uréia; 0,5 por cento zeólita; 0,5 por cento uréia e 0,5 por cento zeólita; inoculante bacteriano comercial; inoculante bacteriano/enzimático comercial. O material ensilado foi aberto com um, três, cinco, sete, 14, 28 e 56 dias de fermentação e analisado quanto aos teores de MS, carboidratos solúveis, PB, NNH3/NT, pH, FDN, FDA, celulose, hemicelulose, lignina e DIVMS. Observou-se redução do conteúdo de MS em todas as silagens, com média de 21,1 por cento, em relação ao material original (28,7 por cento). A concentração média de carboidratos solúveis no material original foi de 19,7 por cento e, após 56 dias de fermentação, foi de 0,92 por cento. A concentração de PB das silagens testemunha e tratadas com zeólita, inoculante comercial bacteriano e inoculante comercial bacteriano/enzimático variou entre 2,1 por cento e 3,1 por cento e naquelas que receberam uréia e uréia+zeólita foi de 8,4 por cento. Os teores de NNH3/NT foram inferiores a 10 por cento nas silagens testemunha e tratadas com zeólita, inoculante bacteriano comercial e inoculante bacteriano/enzimático comercial, entretanto foi de 30,4 por cento e 31,1 por cento nas silagens com uréia e uréia+zeólita, respectivamente. No primeiro dia de fermentação, o pH apresentou média de 3,75. Após 56 dias de fermentação, as concentrações de FDN, FDA, celulose e hemicelulose aumentaram, apresentando média entre os tratamentos de 68,6 por cento, 39,6 por cento, 34,5 por cento e 29,1 por cento, respectivamente. O coeficiente de DIVMS reduziu-se com a ensilagem, em todos os tratamentos avaliados, sendo de 57,6 por cento no material original e média de 47,6 por cento nas silagens.

The characteristics of fermentation of sugarcane (RB72454) submitted to the treatments control; 0.5 percent urea; 0.5 percent zeolita; 0.5 percent urea and 0.5 percent zeolita; commercial bacterial inoculant and commercial bacterial/enzymatic inoculant were studied. The material stored in silos was opened on 1, 3, 5, 7, 14, 28 and 56 days of fermentation and was analysed for grades of MS, soluble carbohydrates, PB, NNH3/NT, pH, FDN, FDA, cellulosis, hemicellulosis, lignin and DIVMS. The reduction of the MS content of the silos was observed, with average of 21.1 percent compared to the original material (28.7 percent). The concentration of carbohydrates soluble on the original material was 19.7 percent and, after 56 days of fermentation, it was 0.92 percent. The concentration of PB in the control silage and treated with zeolita, commercial bacterial inoculant and commercial bacterial/enzymatic inoculant varied between 2.1 percent and 3.1 percent and in thoses that received urea and urea+zeolita was 8.4 percent. The grades of NNH3/NT were lower than 10 percent in the control silage and treated with zeolita, commercial bacterial inoculant and commercial bacterial/enzymatic inoculant. However, they were 30.4 percent and 31.1 percent in the silage with urea and urea+zeolita, respectively. On the first day of fermentation, the pH presented average of 3.75. After 56 days of fermentation, the concentration of FDN, FDA, cellulosis and hemicellulosis increased, presenting averages considering the treatments of 68.6 percent, 39.6 percent, 34.5 percent and 29.1 percent, respectively. The coefficient of DIVMS reduced with the fermentation, in all the evaluated treatments, being of 57.6 percent in the original material and averaging 47.6 percent in the silages.