Modulating Expression of Endogenous Interleukin 1 Beta in the Acute Phase of the Pilocarpine Model of Epilepsy May Change Animal Survival.

The pilocarpine-induced (PILO) model has helped elucidate the electrophysiological and molecular aspects related to mesial temporal lobe epilepsy. It has been suggested that the extensive cell death and edema observed in the brains of these animals could be induced by increased inflammatory responses, such as the rapid release of the inflammatory cytokine interleukin 1 beta (Il1b). In this study, we investigate the role of endogenous Il1b in the acute phase of the PILO model. Our aim is twofold. First, we want to determine whether it is feasible to silence Il1b in the central nervous system using a non-invasive procedure. Second, we aim to investigate the effect of silencing endogenous Il1b and its antagonist, Il1rn.We used RNA interference applied non-invasively to knockdown Il1b and its endogenous antagonist Il1rn. We found that knocking down Il1b prior to pilocarpine injection increased the mortality rate of treated animals. Furthermore, we observed that, when exposing the animals to more Il1b by silencing its endogenous antagonist Il1rn, there was a better response to status epilepticus with decreased animal mortality in the acute phase of the PILO model. Thus, we show the feasibility of using a novel, less invasive approach to study genes involved in the inflammatory response in the central nervous system. Furthermore, our results provide suggestive evidence that modulating endogenous Il1b improves animal survival in the acute phase of the PILO model and may have effects that extend into the chronic phase.

Modeling epileptogenesis and temporal lobe epilepsy in a non-human primate.

Here we describe a new non-human primate model of temporal lobe epilepsy (TLE) to better investigate the cause/effect relationships of human TLE. Status epilepticus (SE) was induced in adult marmosets by pilocarpine injection (250mg/kg; i.p.). The animals were divided in 2 groups: acute (8h post-SE) and chronic (3 and 5 months post-SE). To manage the severity of SE, animals received diazepam 5min after the SE onset (acute group: 2.5 or 1.25mg/kg; i.p.; chronic group/; 1.25mg/kg; i.p). All animals were monitored by video and electrocorticography to assess SE and subsequent spontaneous recurrent seizures (SRS). To evaluate brain injury produced by SE or SRS we used argyrophil III, Nissl and neo-Timm staining techniques. Magnetic resonance image was also performed in the chronic group. We observed that pilocarpine was able to induce SE followed by SRS after a variable period of time. Prolonged SE episodes were associated with brain damage, mostly confined to the hippocampus and limbic structures. Similar to human TLE, anatomical disruption of dentate gyrus was observed after SRS. Our data suggest that pilocarpine marmoset model of epilepsy has great resemblance to human TLE, and could provide new tools to further evaluate the subtle changes associated with human epilepsy.

A Interleucina 1-beta mostra uma ação protetora na fase aguda do modelo de epilepsia induzido pela pilocarpina / The il1β have a protective action in the acute phase of the pilocarpine-induced epilepsy model

INTRODUÇÃO: Existem contradições na literatura quanto aos efeitos dos genes il1β e il1rn nas epilepsias. Nosso objetivo foi avaliar os efeitos do silenciamento desses dois genes na fase aguda do modelo de epilepsia induzido pela pilocarpina. MÉTODOS: Para alterar a expressão dos genes il1β e il1rn utilizamos a técnica de interferência por RNA. RESULTADOS: Obtivemos taxas de silenciamento significativas para os dois genes no sistema nervoso central. Observamos efeitos fenotípicos significativos, incluindo a alteração na taxa de mortalidade dos animais 5 dias após a indução do modelo. CONCLUSÕES: A il1β parece exercer um papel protetor na fase aguda do modelo de epilepsia induzido pela pilocarpina.

INTRODUCTION: There is contradictory information regarding the of effects il1β and il1rn in epilepsy. We aimed to evaluate the effect of silencing both genes in the acute phase of the pilocarpine-induced epilepsy model. METHODS: We used RNA interference in order to achieve gene silencing. RESULTS: We obtained significant gene silencing in the central nervous system. In addition, we observed phenotypic effects including differences in mortality rates of animals 5 days after pilocarpine injections. CONCLUSION: Our results indicate that il1β seems to have a protective effect in the acute phase of the pilocarpine-induced epilepsy model.

Analise do torque isometrico e da atividade elétrica apos lesão muscular induzida por exercício excentrico em humanos / Analysis of isometrci torque and of the electrical activity after induced muscle damage by eccentric exercise human

Este estudo avaliou e relacionou as alteracoes funcionais domusculo quadriceps femoral apos lesao induzida pelo exercicio excentrico. O torque isometrico maximo medio desse musculo e a eletromiografia de superficie (raiz quadrada da media dos quadrados, root meam square - RMS; frequencia mediana -FM) dos musculos vasto medial obliquo(VMO) e vasto lateral(VL) foram avaliados antes, imediatamente apos e durante os 7 dias apos o exercicio excentrico. As imagens de ressonancia magnetica nuclearRMN) de tres voluntarias foram usadas para evidenciar a presenca de lesao muscular. Nove mulheres (21,7+-1,48 anos), sedentarias e saudaveis, foram avaliadas. A lesao foi induzida por meio de contracoes isocineticas excentricas. O torque isometrico maximo medio e a atividade eletrica foram mensurados por meio da contracao isometrica maxima com o joelho a 90 graus de flexao. O torque isometrico maximo medio diminiu imediatamente apos o exercicio excentrico (p<0,01), com recuperacao gradual na primeira semana. O RMS do musculo VL diminuiu imediatamente apos o exercicio excentrico (p<0,05). Por outro lado, somente o musculo VMO ocorreu aumento na FM imediatamente apos o exercicio excentrico (p<0,01). Correlacao significativa foi observada entre o torque isometrico maximo medio e a FM do musculo VMO entre o 1o. e 7o. dia apos o exercicio (r=0,32, p<0,05). Extensas areas de lesao no musculo quadriceps femoral foram identificadas pela RMN. Em conclusao, o exercicio excentrico diminuiu o torque isometrico maximo medio e alterou o sinal eletromiografico, os quais se recuperaram gradualmente na primeira semana, apesar da presenca de lesao muscular

Effect of hypocaloric meals with different macronutrient compositions on energy metabolism and lung function in obese women.

OBJECTIVE: We investigated the effect of hypocaloric mixed diets with different proportions of carbohydrate, protein, and fat on resting metabolic rate and the thermic effect of food in obese women. METHODS: Three mixed hypocaloric diets were consumed in random order during separate periods lasting 7 d each. Between each dietary period there was a washout period of 10 d. Diet 1 had a higher proportion of energy from carbohydrate (72%), diet 2 had a higher proportion of energy from protein (43%), and diet 3 had a higher proportion of energy from fat (68%). Indirect calorimetry and lung function tests were done after the completion of each 7-d diet. Seven obese women, ages 22 to 45 y and with body mass indexes of 32 to 59 kg/m(2), participated in the study. Oxygen consumption, carbon dioxide production, resting metabolic rate, and the thermic effect of food by indirect calorimetry were measured. Lung function tests included spirometry in the seated and upright positions, arterial blood gas analysis, and maximal inspiratory and expiratory pressures. RESULTS: There were no statistically significant differences in the resting metabolic rate and the thermic effect of food resulting from the three diets. The mean resting metabolic rates (kJ/d) were 7453 +/- 1446 for diet 1, 7461 +/- 1965 for diet 2, and 7076 +/- 2048 for diet 3. The mean thermic effects of food (kcal/min) were -0.02 +/- 0.07 for diet 1, -0.01 +/- 0.25 for diet 2, and 0.05 +/- 0.13 for diet 3. Lung function tests were normal before and after the hypocaloic diets: partial pressure of oxygen (mmHg) values were 81 +/- 13, 77 +/- 8, and 78 +/- 11 for diets 1 to 3, respectively; and partial pressure of carbon dioxide (mmHg) were 37 +/- 4, 37 +/- 3, and 37 +/- 4 for diets 1 to 3, respectively. CONCLUSIONS: Obese women with normal lung function tests and consuming mixed hypocaloric diets showed no alteration in resting metabolic rate and a reduced or absent thermic effect of food independently of the macronutrient composition.

Functional changes of human quadriceps muscle injured by eccentric exercise.

The present study evaluated functional changes of quadriceps muscle after injury induced by eccentric exercise. Maximal isometric torque of quadriceps and the surface electromyography (root mean square, RMS, and median frequency, MDF) of the vastus medialis oblique (VMO) and vastus lateralis (VL) muscles were examined before, immediately after and during the first 7 days after injury. Serum creatine kinase (CK) levels and magnetic resonance imaging (MRI) were used to identify muscle injury. The subject was used as her own control and percent refers to pre-injury data. Experiments were carried out with a sedentary 23-year-old female. Injury was induced by 4 bouts of 15 maximal isokinetic eccentric contractions (angular velocity of 5 /s; range of motion from 40 to 110 of knee flexion). The isometric torque of the quadriceps (knee at 90 flexion) decreased 52% immediately after eccentric exercise and recovered on the 5th day. The highest reduction of RMS occurred on the 2nd day after injury in both VL (63%) and VMO (66%) and only VL recovered to the pre-injury level on the 7th day. Immediately after injury, the MDF decreased by 5 and 3% (VMO and VL, respectively) and recovered one day later. Serum CK levels increased by 109% on the 2nd day and were still increased by 32% on the 7th day. MRI showed large areas of injury especially in the deep region of quadriceps. In conclusion, eccentric exercise decreased the isometric torque and electromyographic signals of quadriceps muscle, which were recovered in one week, despite the muscle regeneration signals.

Functional changes of human quadriceps muscle injured by eccentric exercise

The present study evaluated functional changes of quadriceps muscle after injury induced by eccentric exercise. Maximal isometric torque of quadriceps and the surface electromyography (root mean square, RMS, and median frequency, MDF) of the vastus medialis oblique (VMO) and vastus lateralis (VL) muscles were examined before, immediately after and during the first 7 days after injury. Serum creatine kinase (CK) levels and magnetic resonance imaging (MRI) were used to identify muscle injury. The subject was used as her own control and percent refers to pre-injury data. Experiments were carried out with a sedentary 23-year-old female. Injury was induced by 4 bouts of 15 maximal isokinetic eccentric contractions (angular velocity of 5º/s; range of motion from 40º to 110º of knee flexion). The isometric torque of the quadriceps (knee at 90º flexion) decreased 52 percent immediately after eccentric exercise and recovered on the 5th day. The highest reduction of RMS occurred on the 2nd day after injury in both VL (63 percent) and VMO (66 percent) and only VL recovered to the pre-injury level on the 7th day. Immediately after injury, the MDF decreased by 5 and 3 percent (VMO and VL, respectively) and recovered one day later. Serum CK levels increased by 109 percent on the 2nd day and were still increased by 32 percent on the 7th day. MRI showed large areas of injury especially in the deep region of quadriceps. In conclusion, eccentric exercise decreased the isometric torque and electromyographic signals of quadriceps muscle, which were recovered in one week, despite the muscle regeneration signals

Asymmetrical gradient coil for head imaging.

This work presents a novel approach to develop dedicated transverse gradient coils for head imaging. The proposed coil design is based on the stochastic optimization of an asymmetrical stream function and improves the matching between the region-of-interest and the homogeneous gradient volume. Additionally, the electric field produced by these asymmetrical coils is 30% lower than that produced by standard symmetrical designs, which minimizes the risk of magnetostimulation of nerves in fast imaging techniques. A prototype of the asymmetrical gradient coil was built to test the method and magnetic field produced by the prototype was measured. Magnetic field measurements and electrical parameters of coils are in good agreement with theoretical calculations.

Energy expenditure after 2- to 3-hour elective surgical operations.

UNLABELLED: Energy expenditure was measured by indirect calorimetry in 17 adult patients (8 women and 9 men) before surgery, 4 hours immediately after surgery, and 24 hours late after surgery in patients undergoing elective surgery of small-to-medium scope. MATERIAL AND METHODS: The total duration of surgery ranged from 2 to 3 hours. Repeated measures were performed on the same patient, so that each patient was considered to be his/her own control. All patients received a 5% dextrose solution (2000 mL/day) throughout the postoperative period. RESULTS: Men showed a reduction in CO2 production during the immediately after surgery period (257+/-42 mL/min) compared to before surgery (306+/-48 mL/min) and late after surgery (301+/-45 mL/min); this reduction was not observed in women. Energy expenditure was also lower in men during immediately after surgery (6.6 kJ/min). None of the other measurements, including substrate oxidation, showed significant differences. CONCLUSION: Therefore, elective surgery itself cannot be considered an important trauma that would result in increased energy expenditure. According to this study, it is not necessary to prescribe an energy supply exceeding basal expenditure during the immediate after-surgery period. The present results suggest that the energy supply prescribed during the postoperative period after elective surgery of small-to-medium scope should not exceed 5-7 kJ/min, so the patient does not receive a carbohydrate overload from energy supplementation.

BISTRO: an outer-volume suppression method that tolerates RF field inhomogeneity.

A technique is described for performing frequency-selective signal suppression with a high degree of tolerance to RF field inhomogeneity. The method is called B1-insensitive train to obliterate signal (BISTRO). BISTRO consists of multiple amplitude- and frequency-modulated (FM) pulses interleaved with spoiler gradients. BISTRO was developed for the purpose of accomplishing band-selective signal removal, as in water suppression and outer-volume suppression (OVS), in applications requiring the use of an inhomogeneous RF transmitter, such as a surface coil. In the present work, Bloch simulations were used to illustrate the principles and theoretical performance of BISTRO. Its performance for OVS was evaluated experimentally using MRI and spectroscopic imaging of phantoms and in vivo animal and human brain. By using FM pulses featuring offset-independent adiabaticity, BISTRO permitted high-quality, broadband suppression with one (or two) discrete borders demarcating the edge(s) of the suppression band. Simulations and experiments demonstrated the ability to operate BISTRO with reasonably attainable peak RF power levels and with average RF energy deposition similar to other multipulse OVS techniques.

Adiabatic pulses.

Adiabatic pulses are sometimes considered to be mysterious and exotic entities which are difficult to understand, complex to generate and impractical to implement. This work is an attempt to bring familiarity and to fulfill the preliminary needs of anyone interested in learning more about this subject. The response of magnetization to stimuli produced by adiabatic pulses is analyzed using vector representations in a frequency modulated rotating frame. The first section deals with basic principles of amplitude and frequency modulated pulses and a vector representation in a second rotating frame is used to explain how the adiabatic condition can be satisfied. The subsequent section explains the principles of offset independent adiabaticity. These principles are then used to design optimal functions for the amplitude, frequency, and magnetic field gradient modulations for adiabatic inversion pulses. The last section considers some practical aspects for those who want to develop methodologies involving adiabatic pulses.