Sonda uretral flexível como método alternativo para aferição invasiva da pressão intracraniana em trauma cranioencefálico induzido em coelhos / Flexible urethral catheter as alternative method to invasive measurement of intracranial pressure in induced head trauma in rabbits

O objetivo deste estudo foi utilizar a sonda uretral flexível como método alternativo para aferição da pressão intracraniana em coelhos com trauma cranioencefálico induzido pelo cateter de Fogarty 4 Fr (balão epidural) e comparar os dados obtidos com o método convencional de cateter de ventriculostomia. Foram utilizados 12 coelhos, machos, adultos, distribuídos aleatoriamente em dois grupos, denominados de G1: mensuração da PIC com cateter de ventriculostomia (n=6) e G2: mensuração com sonda uretral (n=6). Foram realizadas duas craniotomias na região parietal direita e esquerda para a implantação do cateter de ventriculostomia ou sonda uretral flexível e o balão epidural, respectivamente. A PAM, a PPC, a FC, a FR e a TR foram mensurados antes e após a craniotomia. A PIC foi avaliada após a craniotomia e a cada 10 minutos depois do preenchimento do balonete com 0,3mL de NaCl 0,9%, durante 40 minutos, e com 0,6mL, pelo mesmo período de tempo, totalizando 80 minutos. A PIC aumentou em ambos os grupos, sendo menores os valores registrados com a sonda uretral flexível. Foi possível reproduzir o aumento da PIC com o modelo experimental de TCE utilizando o cateter de Fogarty 4 Fr na região epidural e, embora haja a necessidade de outros estudos, a sonda uretral flexível demonstra ser um método alternativo de mensuração da PIC em coelhos com trauma cranioencefálico.(AU)

The aim of this study was to evaluate the use of flexible urethral catheter as an alternative method for measuring intracranial pressure in rabbits with head trauma induced by 4 F Fogarty catheter (epidural balloon) and compare the data obtained with the conventional method of ventriculostomy catheter. In this study, New Zealand rabbits were randomly distributed into two groups, G1: measuring the ICP with ventriculostomy catheter (n=6) and G2: measuring the ICP with urethral catheter (n=6). Two craniotomies were performed in the right and left parietal region for the implantation of a ventriculostomy catheter and/or flexible urethral catheter and epidural 4 Fr Fogarty arterial embolectomy catheter, respectively. MAP, CPP, HR, RF and RT values were measured before and after of the craniotomy. The ICP value was measured after craniotomy, every five minutes during 40 minutes after the balloon was inflated with 0.3 ml with NaCl and further 40 minutes after the balloon was inflated with 0.6 ml. The ICP value increased in both groups; however, the ICP values were lower in the flexible urethral catheter. The flexible urethral catheter can be used as an alternative method to measure ICP values in rabbits with head injury.(AU)

Sonda uretral flexível como método alternativo para aferição invasiva da pressão intracraniana em trauma cranioencefálico induzido em coelhos / Flexible urethral catheter as alternative method to invasive measurement of intracranial pressure in induced head trauma in rabbits

O objetivo deste estudo foi utilizar a sonda uretral flexível como método alternativo para aferição da pressão intracraniana em coelhos com trauma cranioencefálico induzido pelo cateter de Fogarty 4 Fr (balão epidural) e comparar os dados obtidos com o método convencional de cateter de ventriculostomia. Foram utilizados 12 coelhos, machos, adultos, distribuídos aleatoriamente em dois grupos, denominados de G1: mensuração da PIC com cateter de ventriculostomia (n=6) e G2: mensuração com sonda uretral (n=6). Foram realizadas duas craniotomias na região parietal direita e esquerda para a implantação do cateter de ventriculostomia ou sonda uretral flexível e o balão epidural, respectivamente. A PAM, a PPC, a FC, a FR e a TR foram mensurados antes e após a craniotomia. A PIC foi avaliada após a craniotomia e a cada 10 minutos depois do preenchimento do balonete com 0,3mL de NaCl 0,9%, durante 40 minutos, e com 0,6mL, pelo mesmo período de tempo, totalizando 80 minutos. A PIC aumentou em ambos os grupos, sendo menores os valores registrados com a sonda uretral flexível. Foi possível reproduzir o aumento da PIC com o modelo experimental de TCE utilizando o cateter de Fogarty 4 Fr na região epidural e, embora haja a necessidade de outros estudos, a sonda uretral flexível demonstra ser um método alternativo de mensuração da PIC em coelhos com trauma cranioencefálico.(AU)

The aim of this study was to evaluate the use of flexible urethral catheter as an alternative method for measuring intracranial pressure in rabbits with head trauma induced by 4 F Fogarty catheter (epidural balloon) and compare the data obtained with the conventional method of ventriculostomy catheter. In this study, New Zealand rabbits were randomly distributed into two groups, G1: measuring the ICP with ventriculostomy catheter (n=6) and G2: measuring the ICP with urethral catheter (n=6). Two craniotomies were performed in the right and left parietal region for the implantation of a ventriculostomy catheter and/or flexible urethral catheter and epidural 4 Fr Fogarty arterial embolectomy catheter, respectively. MAP, CPP, HR, RF and RT values were measured before and after of the craniotomy. The ICP value was measured after craniotomy, every five minutes during 40 minutes after the balloon was inflated with 0.3 ml with NaCl and further 40 minutes after the balloon was inflated with 0.6 ml. The ICP value increased in both groups; however, the ICP values were lower in the flexible urethral catheter. The flexible urethral catheter can be used as an alternative method to measure ICP values in rabbits with head injury.(AU)

Sonda uretral flexível como método alternativo para aferição invasiva da pressão intracraniana em trauma cranioencefálico induzido em coelhos

ABSTRACT The aim of this study was to evaluate the use of flexible urethral catheter as an alternative method for measuring intracranial pressure in rabbits with head trauma induced by 4 F Fogarty catheter (epidural balloon) and compare the data obtained with the conventional method of ventriculostomy catheter. In this study, New Zealand rabbits were randomly distributed into two groups, G1: measuring the ICP with ventriculostomy catheter (n=6) and G2: measuring the ICP with urethral catheter (n=6). Two craniotomies were performed in the right and left parietal region for the implantation of a ventriculostomy catheter and/or flexible urethral catheter and epidural 4 Fr Fogarty arterial embolectomy catheter, respectively. MAP, CPP, HR, RF and RT values were measured before and after of the craniotomy. The ICP value was measured after craniotomy, every five minutes during 40 minutes after the balloon was inflated with 0.3 ml with NaCl and further 40 minutes after the balloon was inflated with 0.6 ml. The ICP value increased in both groups; however, the ICP values were lower in the flexible urethral catheter. The flexible urethral catheter can be used as an alternative method to measure ICP values in rabbits with head injury.

RESUMO O objetivo deste estudo foi utilizar a sonda uretral flexível como método alternativo para aferição da pressão intracraniana em coelhos com trauma cranioencefálico induzido pelo cateter de Fogarty 4 Fr (balão epidural) e comparar os dados obtidos com o método convencional de cateter de ventriculostomia. Foram utilizados 12 coelhos, machos, adultos, distribuídos aleatoriamente em dois grupos, denominados de G1: mensuração da PIC com cateter de ventriculostomia (n=6) e G2: mensuração com sonda uretral (n=6). Foram realizadas duas craniotomias na região parietal direita e esquerda para a implantação do cateter de ventriculostomia ou sonda uretral flexível e o balão epidural, respectivamente. A PAM, a PPC, a FC, a FR e a TR foram mensurados antes e após a craniotomia. A PIC foi avaliada após a craniotomia e a cada 10 minutos depois do preenchimento do balonete com 0,3mL de NaCl 0,9%, durante 40 minutos, e com 0,6mL, pelo mesmo período de tempo, totalizando 80 minutos. A PIC aumentou em ambos os grupos, sendo menores os valores registrados com a sonda uretral flexível. Foi possível reproduzir o aumento da PIC com o modelo experimental de TCE utilizando o cateter de Fogarty 4 Fr na região epidural e, embora haja a necessidade de outros estudos, a sonda uretral flexível demonstra ser um método alternativo de mensuração da PIC em coelhos com trauma cranioencefálico.

X-ray pelvimetry in common marmoset (Callithrix jacchus - LINNAEUS, 1758) / Pelvimetria radiográfica em sagui-de-tufo-branco (Callithrix jacchus - LINNAEUS, 1758)

The common marmoset is an important Neotropical primate for biomedical research. With the intention of providing pelvimetric values that allow the selection of animals with better characteristics for reproduction, we studied the X-ray of the pelvis, in ventro-dorsal projection of 12 adult animals, six males and six females, belonging to the National Center of Primates - CENP. The measurements were made to right diagonal diameters (RDD), left diagonal diameter (LDD), bi-iliac middle diameter (BIMD), bi-iliac upper diameter (BIUD), bi-iliac lower diameter (BILD), sacrum-pubic diameter (SPD), and the input area of the pelvis (IAP), which were compared in relation to sex and bodily correlated with the biometrics. The results of the means and standard deviations regarding pelvimetry (cm) were: for the RDD in males of 1.91±0.14 and in the females of 2.05±0.08; LDD in males of 1.85±0.16 and in females of 2.03± 0.08; BIMD in males of 1.46±0.12 and in the females of 1.5±0; BIUD showed in males 1.3±0.1 and in females of 1.3±0.06; BILD in males of 1.35±0.15 and in females of 1.25±0.08; SPD in males of 1.68±0.09 and in females of 1.93±0.13; IAP in males of 1.9±0.26 and in the females of 2.23±0.13. It was concluded that the pelvis of Callithrix jacchus could be classified as dolicopelvic type, there is sexual dimorphism in relation to the pelvis of adult animals and that the bodily measurements have low positive correlation with pelvic measurements.(AU)

O sagui-de-tufo-branco se destaca como um importante primata neotropical para as pesquisas biomédicas. Com o intuito de fornecer valores pelvimétricos que permitam a seleção de animais com melhores características para a reprodução, estudaram-se radiografias da pelve, em projeção ventrodorsal, de 12 animais, sendo seis machos e seis fêmeas, adultos, pertencentes ao Centro Nacional de Primatas - CENP. As mensurações realizadas foram referentes aos diâmetros diagonal direito (DDD), diagonal esquerdo (DDE), bi-ilíaco médio (DBIM), bi-ilíaco superior (DBIS), bi-ilíaco inferior (DBII), sacropúbico (DSP), além da área de entrada da pelve (AEP), os quais foram comparados em relação ao sexo e correlacionados com a biometria corpórea. Os resultados de médias e desvios-padrão com relação à pelvimetria (cm) foram: para o DDD nos machos de 1,91±0,14 e nas fêmeas de 2,05±0,08; DDE nos machos de 1,85±0,16 e nas fêmeas de 2,03±0,08; DBIM nos machos de 1,46±0,12 e nas fêmeas de 1,5±0; DBIS nos machos de 1,3±0,1 e nas fêmeas de 1,3±0,06; DBII nos machos de 1,35±0,15 e nas fêmeas de 1,25±0,08; DSP nos machos de 1,68±0,09 e nas fêmeas de 1,93±0,13; AEP nos machos de 1,9±0,26 e nas fêmeas de 2,23±0,13. Concluiu-se que a pelve de Callithrix jacchus pode ser classificada como do tipo dolicopélvica, existe dimorfismo sexual em relação às pelves de animais adultos e que as medidas corpóreas apresentam baixa correlação positiva com as medidas pélvicas.(AU)

GEINOFOTE: efficacy and safety of fotemustine in patients with high-grade recurrent gliomas and poor performance status.

PURPOSE: The treatment of recurrent high-grade gliomas (HGG) is controversial. There are different therapeutic schedules but without a clear orientation about which of them should be used in each clinical situation. In addition, when patients suffer a second recurrence or they have poor performance status, they are excluded from clinical trials, although second recurrences and poor performance status are indeed more and more real and common situations in the clinical setting. In this study, we assessed the efficacy and safety of fotemustine (FTM) in HGG [fundamentally, glioblastomas (GB)], independent of time of recurrence or performance status. METHODS/PATIENTS: Retrospective study in HGG patients treated with FTM in second or further line according to standard, the Addeo or any other scheme, starting treatment prior to 30 November 2012. Included patients reflect the regular situation in which the drug is used in terms of comorbidities and analytic situation (hematologic, renal and hepatic functions). Response assessment was performed by MRI and according to the clinical protocols of each center (every 8-12 weeks). Clinical situation and supportive care drugs were evaluated in each medical consultation. Clinical end-points analyzed, among others, were: PFS-6, PFS, OS, response rates, toxicity, quality of life and neurocognitive impact. RESULTS: In terms of activity, an overall response rate of 8 % was observed: partial response 6 % (7 patients) and complete response 2 % (2 patients). The median time to achieve the greater response with FTM was 73 days (4-841 days). Patients treated according to the Addeo schedule had a shorter time to greater response in comparison with other schedules (85.9 vs 114 days), although without statistical significance. There were no significant differences in progression-free survival (PFS) when comparing different FTM schedules or using FTM in first or second recurrence. Median PFS: 3 months. PFS-6: 30.3 %. Overall survival (OS): although without significant differences, a tendency to better survival when using the Addeo schedule versus other schedules was observed (at 6 months, 44.6 vs 34.5 %; at 12 months, 25 vs 23.6 %; at 18 months, 11.5 vs 7.9 %), as well as if earlier use (second vs third line) concerning OS-12 (33.7 vs 18.2 %). Median OS: 5.2 months. Grades 3-4 toxicity was 28 % (31 patients), being neutropenia (4 %) and thrombocytopenia (17 %) the most frequent adverse reactions. From quality of life and neuro-cognitive function perspectives, 11 patients (10 %) and 16 (14 %) improved the Karnofsky Index and neurological impairment, respectively, after FTM treatment. CONCLUSION: This study has shown that FTM is safe and has a comparable activity with other available therapeutic options of use in the treatment of recurrent HGG.

X-ray pelvimetry in common marmoset (Callithrix jacchus - LINNAEUS, 1758) / Pelvimetria radiográfica em sagui-de-tufo-branco (Callithrix jacchus - LINNAEUS, 1758)

The common marmoset is an important Neotropical primate for biomedical research. With the intention of providing pelvimetric values that allow the selection of animals with better characteristics for reproduction, we studied the X-ray of the pelvis, in ventro-dorsal projection of 12 adult animals, six males and six females, belonging to the National Center of Primates - CENP. The measurements were made to right diagonal diameters (RDD), left diagonal diameter (LDD), bi-iliac middle diameter (BIMD), bi-iliac upper diameter (BIUD), bi-iliac lower diameter (BILD), sacrum-pubic diameter (SPD), and the input area of the pelvis (IAP), which were compared in relation to sex and bodily correlated with the biometrics. The results of the means and standard deviations regarding pelvimetry (cm) were: for the RDD in males of 1.91±0.14 and in the females of 2.05±0.08; LDD in males of 1.85±0.16 and in females of 2.03± 0.08; BIMD in males of 1.46±0.12 and in the females of 1.5±0; BIUD showed in males 1.3±0.1 and in females of 1.3±0.06; BILD in males of 1.35±0.15 and in females of 1.25±0.08; SPD in males of 1.68±0.09 and in females of 1.93±0.13; IAP in males of 1.9±0.26 and in the females of 2.23±0.13. It was concluded that the pelvis of Callithrix jacchus could be classified as dolicopelvic type, there is sexual dimorphism in relation to the pelvis of adult animals and that the bodily measurements have low positive correlation with pelvic measurements.(AU)

O sagui-de-tufo-branco se destaca como um importante primata neotropical para as pesquisas biomédicas. Com o intuito de fornecer valores pelvimétricos que permitam a seleção de animais com melhores características para a reprodução, estudaram-se radiografias da pelve, em projeção ventrodorsal, de 12 animais, sendo seis machos e seis fêmeas, adultos, pertencentes ao Centro Nacional de Primatas - CENP. As mensurações realizadas foram referentes aos diâmetros diagonal direito (DDD), diagonal esquerdo (DDE), bi-ilíaco médio (DBIM), bi-ilíaco superior (DBIS), bi-ilíaco inferior (DBII), sacropúbico (DSP), além da área de entrada da pelve (AEP), os quais foram comparados em relação ao sexo e correlacionados com a biometria corpórea. Os resultados de médias e desvios-padrão com relação à pelvimetria (cm) foram: para o DDD nos machos de 1,91±0,14 e nas fêmeas de 2,05±0,08; DDE nos machos de 1,85±0,16 e nas fêmeas de 2,03±0,08; DBIM nos machos de 1,46±0,12 e nas fêmeas de 1,5±0; DBIS nos machos de 1,3±0,1 e nas fêmeas de 1,3±0,06; DBII nos machos de 1,35±0,15 e nas fêmeas de 1,25±0,08; DSP nos machos de 1,68±0,09 e nas fêmeas de 1,93±0,13; AEP nos machos de 1,9±0,26 e nas fêmeas de 2,23±0,13. Concluiu-se que a pelve de Callithrix jacchus pode ser classificada como do tipo dolicopélvica, existe dimorfismo sexual em relação às pelves de animais adultos e que as medidas corpóreas apresentam baixa correlação positiva com as medidas pélvicas.(AU)

Effects of intra-session exercise sequence during water-based concurrent training.

The aim was to investigate the effects of the intra-session exercise order during water-based concurrent training on the neuromuscular adaptations in young women. 26 women (25.1±2.9 years) were placed into 2 groups: resistance prior to (RA) or after (AR) aerobic training. Subjects performed resistance (sets at maximal effort) and aerobic training (exercises at heart rate corresponding to the second ventilatory threshold) twice a week over 12 weeks, performing both exercise types in the same training session. Upper (elbow flexion) and lower-body (knee extension) one-repetition maximum test (1RM) and peak torque (PT) were evaluated. The muscle thickness (MT) of upper (sum of MT of biceps brachii and brachialis) and lower-body (sum of MT of vastus lateralis, vastus medialis, vastus intermedius, and rectus femoris) was determined by ultrasonography. Moreover, the maximal electromyographic activity (EMG) of upper (biceps brachii) and lower-body (sum of EMG of vastus lateralis and rectus femoris) was measured. Both RA and AR groups increased the upper and lower-body 1RM and PT, while the lower-body 1RM increases observed in the RA was greater than AR (43.58±14.00 vs. 27.01±18.05%). RA and AR showed MT increases in all muscles evaluated, while the lower-body MT increases observed in the RA were also greater than AR (10.24±3.11 vs. 5.76±1.88%). There were increases in the maximal EMG of upper and lower-body in both RA and AR, with no differences between groups. Performing resistance prior to aerobic exercise during water-based concurrent training seems to optimize the lower-body strength and hypertrophy.

Should we continue temozolomide beyond six cycles in the adjuvant treatment of glioblastoma without an evidence of clinical benefit? A cost analysis based on prescribing patterns in Spain.

PURPOSE: The standard adjuvant treatment for glioblastoma is temozolomide concomitant with radiotherapy, followed by a further six cycles of temozolomide. However, due to the lack of empirical evidence and international consensus regarding the optimal duration of temozolomide treatment, it is often extended to 12 or more cycles, even in the absence of residual disease. No clinical trial has shown clear evidence of clinical benefit of this extended treatment. We have explored the economic impact of this practice in Spain. MATERIALS AND METHODS: Spanish neuro-oncologists completed a questionnaire on the clinical management of glioblastomas in their centers. Based on their responses and on available clinical and demographic data, we estimated the number of patients who receive more than six cycles of temozolomide and calculated the cost of this extended treatment. RESULTS: Temozolomide treatment is continued for more than six cycles by 80.5 % of neuro-oncologists: 44.4 % only if there is residual disease; 27.8 % for 12 cycles even in the absence of residual disease; and 8.3 % until progression. Thus, 292 patients annually will continue treatment beyond six cycles in spite of a lack of clear evidence of clinical benefit. Temozolomide is covered by the National Health Insurance System, and the additional economic burden to society of this extended treatment is nearly 1.5 million euros a year. CONCLUSIONS: The optimal duration of adjuvant temozolomide treatment merits investigation in a clinical trial due to the economic consequences of prolonged treatment without evidence of greater patient benefit.

Time course of neuromuscular adaptations to knee extensor eccentric training.

This study investigated the chronology of neural and morphological adaptations to knee extensor eccentric training and their contribution to strength gains in isometric, concentric and eccentric muscle actions. 20 male healthy subjects performed a 12-week eccentric training program on an isokinetic dynamometer, and neuromuscular evaluations of knee extensors were performed every 4 weeks. After 12 training weeks, significant increases were observed for: isometric (24%), concentric (15%) and eccentric (29%) torques; isometric (29%) and eccentric (33%) electromyographic activity; muscle thickness (10%) and anatomical cross-sectional area (19%). Eccentric and isometric torques increased progressively until the end of the program. Concentric torque and muscle mass parameters increased until the eighth training week, but did not change from this point to the twelfth training week. Eccentric and isometric activation increased at 4 and 8 training weeks, respectively, while no change was found in concentric activation. These results suggest that: 1) the relative increment in concentric strength was minor and does not relate to neural effects; 2) eccentric and isometric strength gains up to 8 training weeks are explained by the increased neural activation and muscle mass, whereas the increments in the last 4 training weeks seem to be associated with other mechanisms.

Relationships between dendritic morphology, spatial distribution and firing patterns in rat layer 1 neurons

The cortical layer 1 contains mainly small interneurons, which have traditionally been classified according to their axonal morphology. The dendritic morphology of these cells, however, has received little attention and remains ill defined. Very little is known about how the dendritic morphology and spatial distribution of these cells may relate to functional neuronal properties. We used biocytin labeling and whole cell patch clamp recordings, associated with digital reconstruction and quantitative morphological analysis, to assess correlations between dendritic morphology, spatial distribution and membrane properties of rat layer 1 neurons. A total of 106 cells were recorded, labeled and subjected to morphological analysis. Based on the quantitative patterns of their dendritic arbor, cells were divided into four major morphotypes: horizontal, radial, ascendant, and descendant cells. Descendant cells exhibited a highly distinct spatial distribution in relation to other morphotypes, suggesting that they may have a distinct function in these cortical circuits. A significant difference was also found in the distribution of firing patterns between each morphotype and between the neuronal populations of each sublayer. Passive membrane properties were, however, statistically homogeneous among all subgroups. We speculate that the differences observed in active membrane properties might be related to differences in the synaptic input of specific types of afferent fibers and to differences in the computational roles of each morphotype in layer 1 circuits. Our findings provide new insights into dendritic morphology and neuronal spatial distribution in layer 1 circuits, indicating that variations in these properties may be correlated with distinct physiological functions.

Non-ribosomal halogenated protease inhibitors from cyanobacterial isolates as attractive drug targets.

Cyanobacteria possess the ability to produce compounds with remarkable biological activity, and have thus attracted the attention of the pharmaceutical industry. Cyanopeptides acting as protease inhibitors have shown potential in the field of pharmacotherapy through regulation of abnormal physiological processes in the human body. Despite the already described cyanopeptide protease inhibitors, the search for new congeners is of considerable interest which may pave the way for more efficient molecules. In this study, the presence of the protease inhibitors aeruginosin and cyanopeptolin with non-, mono- and dichlorination and also genes coding for their synthetases was investigated in 90 cyanobacterial strains. Mass spectrometry analyses highlighted production of 91, 19 and 3 non-, mono- and dichlorinated congeners, respectively. The purified extract of Microcystis botrys SPC759 inhibited 61% of pepsin protease. PCR amplifications of aeruginosin and cyanopeptolin synthetase gene regions were observed in 41 and 28% of evaluated strains, respectively. The sequences obtained for the aerA-aerB (aeruginosin) and mcnC-mcnE (cyanopeptolin) gene regions grouped together with their homologues found in other cyanobacterial strains in the phylogenetic analyses with high bootstrap support. Antimicrobial activity assays performed using all intracellular extracts inhibited 31 and 26% of Gram-negative and Gram-positive pathogenic bacterial growth, respectively. The results of this study showed the production of aeruginosin and cyanopeptolin and the presence of their genes in several cyanobacterial genera for the first time besides the discovery of novel congeners.

Relationships between dendritic morphology, spatial distribution and firing patterns in rat layer 1 neurons.

The cortical layer 1 contains mainly small interneurons, which have traditionally been classified according to their axonal morphology. The dendritic morphology of these cells, however, has received little attention and remains ill defined. Very little is known about how the dendritic morphology and spatial distribution of these cells may relate to functional neuronal properties. We used biocytin labeling and whole cell patch clamp recordings, associated with digital reconstruction and quantitative morphological analysis, to assess correlations between dendritic morphology, spatial distribution and membrane properties of rat layer 1 neurons. A total of 106 cells were recorded, labeled and subjected to morphological analysis. Based on the quantitative patterns of their dendritic arbor, cells were divided into four major morphotypes: horizontal, radial, ascendant, and descendant cells. Descendant cells exhibited a highly distinct spatial distribution in relation to other morphotypes, suggesting that they may have a distinct function in these cortical circuits. A significant difference was also found in the distribution of firing patterns between each morphotype and between the neuronal populations of each sublayer. Passive membrane properties were, however, statistically homogeneous among all subgroups. We speculate that the differences observed in active membrane properties might be related to differences in the synaptic input of specific types of afferent fibers and to differences in the computational roles of each morphotype in layer 1 circuits. Our findings provide new insights into dendritic morphology and neuronal spatial distribution in layer 1 circuits, indicating that variations in these properties may be correlated with distinct physiological functions.

Determination of the relevant magnetic interactions in low-dimensional molecular materials: the fundamental role of single crystal high frequency EPR.

A new one-dimensional copper(II) complex with formula [Cu(hfac)(2)(N(3)TEMPO)](n) (hfac = hexafluoroacetylacetonate and N(3)TEMPO = 4-azido-2,2,6,6-tetramethylpiperidine-1-oxyl) has been synthesized and investigated by X-ray crystallography, magnetometry and multifrequency single crystal EPR. The system crystallizes in the P1 space group with two non equivalent copper(II) ions in the unit cell, the two nitroxide radicals being coordinated to Cu(1) in axial positions. The copper(II) ions are bridged by N(3)TEMPO radicals resulting in a zig-zag chain structure. The magnetic susceptibility data were at first satisfactorily modeled assuming an alternating spin chain along the monodimensional covalent skeleton, with a ferromagnetic interaction between Cu(1) and the nitroxide moieties and a weaker antiferromagnetic interaction between these and Cu(2) (J(1) = -13.8 cm(-1), J(2) = +2.4 cm(-1)). However, single crystal EPR studies performed at the X- and W-band clearly demonstrate that the observed magnetic monodimensional character of the complex is actually due to the intermolecular contacts involving N(3)TEMPO ligands. This prompted us to fit the magnetic data using a consistent model, pointing out the fundamental role of single crystal EPR data in defining a correct model to describe the magnetic properties of molecular low dimensional systems.

Effects of altering pedal frequency on the slow component of pulmonary VO2 kinetics and EMG activity.

This study investigated the effects of pedal frequency on the slow component of pulmonary oxygen uptake ( V O(2)) kinetics during heavy exercise at the same relative intensity. We hypothesized that higher pedal frequency (expected to enhance fast-twitch muscle fiber recruitment) would be associated with greater slow component amplitude (A' (s)), surface electromyography (normalized root mean square; RMS) and blood lactate concentration ([lactate]). Eight subjects performed square-wave transitions to heavy exercise at 35 and 115 rpm. Furthermore, alternated cadences square-wave transitions (35-115 rpm) were performed to examine the potential effects of additional fast-twitch muscle fiber recruitment on the slow component. Significance was accepted when P<0.05. The A' (s) was greater at higher cadences (0.58+/-0.08 and 0.70+/-0.09 L.min (-1) at 115 and 35-115 rpm, respectively) than at 35 rpm (0.35+/-0.04 L.min (-1)). Greater EMG increase over time (DeltaRMS ((10-3 min))) and [lactate] were observed at 115 and 35-115 rpm compared with 35 rpm. There was a significant correlation between A' (s) and overall DeltaRMS ((10-3 min)) for all pedal frequencies combined (r=0.63; P=0.001). Pedal frequency had no effect on time constants or time delays. These findings are consistent with the concept that progressive recruitment of muscle fibers is associated with the V O(2) slow component.

Low-frequency fatigue at maximal and submaximal muscle contractions

Skeletal muscle force production following repetitive contractions is preferentially reduced when muscle is evaluated with low-frequency stimulation. This selective impairment in force generation is called low-frequency fatigue (LFF) and could be dependent on the contraction type. The purpose of this study was to compare LFF after concentric and eccentric maximal and submaximal contractions of knee extensor muscles. Ten healthy male subjects (age: 23.6 ± 4.2 years; weight: 73.8 ± 7.7 kg; height: 1.79 ± 0.05 m) executed maximal voluntary contractions that were measured before a fatigue test (pre-exercise), immediately after (after-exercise) and after 1 h of recovery (after-recovery). The fatigue test consisted of 60 maximal (100 percent) or submaximal (40 percent) dynamic concentric or eccentric knee extensions at an angular velocity of 60°/s. The isometric torque produced by low- (20 Hz) and high- (100 Hz) frequency stimulation was also measured at these times and the 20:100 Hz ratio was calculated to assess LFF. One-way ANOVA for repeated measures followed by the Newman-Keuls post hoc test was used to determine significant (P < 0.05) differences. LFF was evident after-recovery in all trials except following submaximal eccentric contractions. LFF was not evident after-exercise, regardless of exercise intensity or contraction type. Our results suggest that low-frequency fatigue was evident after submaximal concentric but not submaximal eccentric contractions and was more pronounced after 1-h of recovery.

Low-frequency fatigue at maximal and submaximal muscle contractions.

Skeletal muscle force production following repetitive contractions is preferentially reduced when muscle is evaluated with low-frequency stimulation. This selective impairment in force generation is called low-frequency fatigue (LFF) and could be dependent on the contraction type. The purpose of this study was to compare LFF after concentric and eccentric maximal and submaximal contractions of knee extensor muscles. Ten healthy male subjects (age: 23.6 +/- 4.2 years; weight: 73.8 +/- 7.7 kg; height: 1.79 +/- 0.05 m) executed maximal voluntary contractions that were measured before a fatigue test (pre-exercise), immediately after (after-exercise) and after 1 h of recovery (after-recovery). The fatigue test consisted of 60 maximal (100%) or submaximal (40%) dynamic concentric or eccentric knee extensions at an angular velocity of 60 degrees /s. The isometric torque produced by low- (20 Hz) and high- (100 Hz) frequency stimulation was also measured at these times and the 20:100 Hz ratio was calculated to assess LFF. One-way ANOVA for repeated measures followed by the Newman-Keuls post hoc test was used to determine significant (P < 0.05) differences. LFF was evident after-recovery in all trials except following submaximal eccentric contractions. LFF was not evident after-exercise, regardless of exercise intensity or contraction type. Our results suggest that low-frequency fatigue was evident after submaximal concentric but not submaximal eccentric contractions and was more pronounced after 1-h of recovery.

Temporomandibular joint dysfunction and trapezius muscle fatigability

INTRODUCTION: It has been suggested that pain increases trapezius muscle activation in patients with temporomandibular joint dysfunction (TMD). Changes in muscle activation might change muscle resistance to fatigue. The purpose of this study was to evaluate the fatigability of the trapezius muscle in patients with TMD. METHOD: Fourteen patients with TMD (clinically diagnosed and referred by a dentist) and eleven healthy subjects performed a fatigue test consisting of shoulder elevation performed at 70 percent of the maximal voluntary isometric contraction, which was maintained for 30 seconds. Electromyographic signals were obtained from the upper portion of the trapezius muscle (sampling frequency: 2000 Hz/channel). Consecutive segments of three seconds in duration each were extracted from the electromyographic signal and analyzed in the frequency domain using a Fast Fourier Transform algorithm. Linear regression analysis was applied to the consecutive median frequencies for each subject. The slope of the regression line was used to describe muscle fatigability. RESULTS: No changes were observed in fatigability between the right and left trapezius of either group or between the left trapezius of the healthy and TMD groups. The linear regression for median frequencies in the right trapezius of the TMD group showed a slope of -0.15 ± 0.33 (mean ± SD), which was smaller than the slope for the healthy group (-0.44 ± 0.46; p= 0.049). These results suggested that the fatigability of the right trapezius was lower in the TMD group than in the healthy group.

INTRODUÇÃO: Tem sido sugerido que a dor aumenta a ativação do músculo trapézio em pacientes com disfunção temporomandibular (TMD). Mudanças na ativação do músculo podem alterar a resistência à fadiga. O objetivo do estudo foi investigar a fatigabilidade do músculo trapézio em pacientes com TMJ. MÉTODOS: Quatorze indivíduos com TMD (diagnosticados clinicamente e encaminhados pelo especialista odontólogo) e onze indivíduos saudáveis realizaram um protocolo de fadiga que consistiu em uma contração isométrica submáxima de elevação do ombro, em um nível de 70 por cento da contração voluntária máxima, mantida por um período de 30 segundos. O sinal eletromiográfico (EMG) foi obtido da porção superior do músculo trapézio, (taxa de amostragem de 2000Hz/canal). Três segundos consecutivos do sinal EMG foram analisados no domínio da freqüência usando a Transformada Rápida de Fourier (FFT). Uma análise de regressão linear foi aplicada para valores consecutivos da freqüência mediana (MF) de cada sujeito, e a inclinação da regressão linear foi utilizada para descrever a fatigabilidade muscular. RESULTADOS: Nenhuma diferença foi observada na fatigabilidade do músculo trapézio direito e esquerdo para ambos os grupos e entre o trapézio esquerdo do grupo saudável e com TMD. A MF do músculo trapézio direito do grupo com disfunção apresentou valores de inclinação da reta de regressão linear de -0,15 ± 0,33 (média ± SD), os quais foram menores que os valores do grupo saudável (-0,44 ± 0,46; média ± SD; p= 0,049). Esses resultados sugerem que a fatigabilidade do trapézio direito é menor no grupo com TMD do que no grupo saudável.

Long-term outcome of a phase II study of weekly docetaxel with a short course of estramustine and enoxaparine in hormone-resistant prostate cancer patients.

OBJECTIVE: The objective was to define the toxicity and activity of weekly docetaxel administered with a short course of estramustine and enoxaparine in patients with hormone-resistant prostate cancer (HRPC). PATIENTS AND METHODS: Twenty-four patients were treated with the next regimen: weekly docetaxel 36 mg/m(2) iv for three consecutive weeks every 28 days, and estramustine 280 mg three times a day for three consecutive days beginning the day before docetaxel (days 1-3, 8-10 and 15-17). In order to prevent thromboembolic events, 40 mg of subcutaneous enoxaparine was administered daily sc on the same days as estramustine. Primary endpoints were: toxicity, especially the presence of thromboembolic events, PSA response rate and response in measurable disease. Secondary endpoints were: time to PSA progression and overall survival. RESULTS: Nineteen of 24 patients (79.1%, 95% CI 71-87%) had a PSA response = or >50%. Four of the eleven patients with measurable disease had a partial response. The median time to PSA progression was 7 months (CI 95%: 6.5-9) and the median survival was 19 months (IC 95%: 11-24). Toxicity was manageable with no treatment- related mortality. Only two patients had grade 4 neutropenia. Two patients had thrombotic events, one deep venous thrombosis and one stroke. The main grade 3 non-haematologic toxicity was diarrhoea and asthenia, both in 25% of patients. CONCLUSIONS: Weekly docetaxel with a short course of estramustine and enoxaparine is active and tolerable in HRPC patients. The observed incidence of thrombosis was lower than previously reported but the association of enoxaparine was not enough to completely prevent the thromboembolic events.

Worse renal transplant outcomes observed among Afro-Brazilian patients on prospective registry data of 2461 renal transplants at least 1 year follow-up.

We present prospective registry data of 2461 (live donor = 1753 and deceased donor = 08) renal transplants performed between 1999 and 2003. All subjects were followed for more than 1 year after transplantation and most were treated with a calcineurin inhibitor and azathioprine. Afro-Brazilian, white, and mixed patients constituted 11% (272), 67.1% (1651), and 14.9% (367) of the population respectively. Mean dialysis time was 42.3 +/- 32.9 months and delayed graft function, occurred in more than 60%. Three-year patient survival rates were 96.3%, 92.8%, and 86.7% for living-related, living-unrelated, and deceased donors, respectively. Corresponding 3-year graft survival rates were 87.3%, 82.1%, and 71.3% and functional graft survival rates were 90.2%, 88.8%, and 81.5%. The poorer transplant outcome observed among Afro-Brazilian patients has been mainly attributed to differences in absorption of cyclosporine, tacrolimus, and mycophenolate mofetil.

Evaluation of the protective effects of quercetin in the hepatopulmonary syndrome.

The hepatopulmonary syndrome (HPS) occurs when intrapulmonary dilatation causes hypoxemia in cirrhosis. The free radicals may play a significant contributory role in the progression of HPS, and flavonoid agents could protect against deleterious effects of free radicals. The flavonoid quercetin was evaluated in an experimental model of biliary cirrhosis induced by bile duct ligation (BDL) in rats. Quercetin was administered at 50mg/kg for 14 days to cirrhotic and non-cirrhotic rats. Bone marrow was extracted from animals to analyze micronuclei. Lung, liver and blood were extracted to detect DNA damage using the comet assay. The results showed that the micronuclei and DNA damages to lung and liver were increased in BDL rats. Quercetin caused no damage to the DNA while decreasing the occurrence of micronucleated cells in bone marrow as well as DNA damage to lung and liver in cirrhotic rats. Quercetin showed antimutagenic activity against hydroperoxides as evaluated by the oxidative stress sensitive bacterial strains TA102 Salmonella typhimurium and IC203 Escherichia coli, suggesting protection by free radical scavenging. In Saccharomyces cerevisie yeast strains lacking mitochondrial or cytosolic superoxide dismutase, these results indicate that quercetin protects cells by induction of antioxidant enzymes. The present study is the first report of genotoxic/antigenotoxic effects of quercetin in a model of animal cirrhosis. In this model, quercetin was not able to induce genotoxicity and, conversely, it increased the genomic stability in the cirrhotic rats, suggesting beneficial effects, probably by its antioxidant properties.