Participation of kinin receptors on memory impairment after chronic infusion of human amyloid-beta 1-40 peptide in mice

Chronic infusion of human amyloid-beta 1-40 (A beta) in the lateral ventricle (LV) of rats is associated with memory impairment and increase of kinin receptors in cortical and hippocampal areas. Deletion of kinin B1 or B2 receptors abolished memory impairment caused by an acute single injection of A beta in the LV. As brain tissue and kinin receptors could unlikely react to acute or chronic administration of a similar quantity of A beta, we evaluated the participation of B1 or B2 receptors in memory impairment after chronic infusion of A beta. Male C57BI/6 J (wt), knock-out B1 (koB1) or B2 (koB2) mice (12 weeks of age) previously trained in a two-way shuttle-box and achieving conditioned avoidance responses (CAR, % of 50 trials) were infused with AB (550 pmol, 0.12 mu L/h, 28 days) or vehicle in the LV using a mini-osmotic pump. They were tested before the surgery (TO), 7 and 35 days after the infusion started (T7; T35). In T0, no difference was observed between CAR of the control (Cwt = 59.7 +/- 6.7%; CkoB1 = 46.7 +/- 4.0%; CkoB2 = 64.4 +/- 5.8%) and A beta (A beta wt = 66.0 +/- 3.0%; A beta koB1 = 66.8 +/- 8.2%; A beta koB2 = 58.7 +/- 5.9%) groups. In T7, A beta koB2 showed a significant decrease in CAR (41.0 +/- 8.6%) compared to the control-koB2 (72.8 +/- 2.2%, P <0.05). In T35, a significant decrease (P <0.05) was observed in A beta wt (40.7 +/- 3.3%) and A beta koB2 (41.2 +/- 10.7%) but not in the A beta koB1 (64.0 +/- 14.0%) compared to their control groups. No changes were observed in the controls at T35. We suggest that in chronic infusion of BA, B1 receptors could playan important role in the neurodegenerative process. Conversely, the premature memory impairment of koB2 suggests that it may be a protective factor. (C) 2009 Elsevier Ltd. All rights reserved.

The accuracy of the Clock Drawing Test compared to that of standard screening tests for Alzheimer`s disease: results from a study of Brazilian elderly with heterogeneous educational backgrounds

Background: Although the Clock Drawing Test (CDT) is the second most used test in the world for the screening of dementia, there is still debate over its sensitivity specificity, application and interpretation in dementia diagnosis. This study has three main aims: to evaluate the sensitivity and specificity of the CDT in a sample composed of older adults with Alzheimer`s disease (AD) and normal controls; to compare CDT accuracy to the that of the Mini-mental State Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG), and to test whether the association of the MMSE with the CDT leads to higher or comparable accuracy as that reported for the CAMCOG. Methods: Cross-sectional assessment was carried out for 121 AD and 99 elderly controls with heterogeneous educational levels from a geriatric outpatient clinic who completed the Cambridge Examination for Mental Disorder of the Elderly (CAMDEX). The CDT was evaluated according to the Shulman, Mendez and Sunderland scales. Results: The CDT showed high sensitivity and specificity. There were significant correlations between the CDT and the MMSE (0.700-0.730; p < 0.001) and between the CDT and the CAMCOG (0.753-0.779; p < 0.001). The combination of the CDT with the MMSE improved sensitivity and specificity (SE = 89.2-90%; SP = 71.7-79.8%). Subgroup analysis indicated that for elderly people with lower education, sensitivity and specificity were both adequate and high. Conclusions: The CDT is a robust screening test when compared with the MMSE or the CAMCOG, independent of the scale used for its interpretation. The combination with the MMSE improves its performance significantly, becoming equivalent to the CAMCOG.

ABNORMAL EXPRESSION OF VOLTAGE-GATED SODIUM CHANNELS Nav1.7, Nav1.3 AND Nav1.8 IN TRIGEMINAL NEURALGIA

Voltage-gated sodium channels have been implicated in acute and chronic neuropathic pain. Among subtypes, Nav1.7 single mutations can cause congenital indifference to pain or chronic neuropathic pain syndromes, including paroxysmal ones. This channel is co-expressed with Nav1.8, which sustains the initial action potential; Nav1.3 is an embrionary channel which is expressed in neurons after injury, as in neuropathic conditions. Few studies are focused on the expression of these molecules in human tissues having chronic pain. Trigeminal neuralgia (TN) is an idiopathic paroxysmal pain treated with sodium channel blockers. The aim of this study was to investigate the expression of Nav1.3, Nav1.7 and Nav1.8 by RT-PCR in patients with TN, compared to controls. The gingival tissue was removed from the correspondent trigeminal area affected. We found that Nav1.7 was downregulated in TN (P=0.017) and Nav1.3 was upregulated in these patients (P=0.043). We propose a physiopathological mechanism for these findings. Besides vascular compression of TN, this disease might be also a channelopathy. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

Short Cognitive Performance Test: Diagnostic Accuracy and Education Bias in Older Brazilian Adults

The ""Short Cognitive Performance Test"" (Syndrom Kurztest, SKT) is a cognitive screening battery designed to detect memory and attention deficits. The aim of this study was to evaluate the diagnostic accuracy of the SKT as a screening tool for mild cognitive impairment (MCI) and dementia. A total of 46 patients with Alzheimer`s disease (AD), 82 with MCI, and 56 healthy controls were included in the study. Patients and controls were allocated into two groups according to educational level (< 8 years or > 8 years). ROC analyses suggested that the SKT adequately discriminates AD from non-demented subjects (MCI and controls), irrespective of the education group. The test had good sensitivity to discriminate MCI from unimpaired controls in the sub-sample of individuals with more than 8 years of schooling. Our findings suggest that the SKT is a good screening test for cognitive impairment and dementia. However, test results must be interpreted with caution when administered to less-educated individuals.

Change in central kinin B2 receptor density after exercise training in rats

Cardiovascular responses elicited by the stimulation of kinin B2 receptors in the IV cerebral ventricle paratrigeminal nucleus or in the thoracic spinal cord are similar to those observed during an exercise bout Considering that the kalikrein-kinin system (KKS) could act on the cardiovascular modulation during behavioral responses as physical exercise or stress this study evaluated the central B2 receptor densities of Wistar (W) and spontani ously hypertensive rats (SHR) after chronic moderate exercise Animals we re exercise-trained for ten weeks on a treadmill Afterwards systolic blood pressure decreased in both trained strains Animals were killed and the medulla and spinal cord extracted for B2 receptor autoradiography Trained animals were compared to their sedentary controls Sedentary groups showed specific binding sites for Hoe-140 (fmol/mg of tissue) in laminas 1 and 2 of the spinal cord nucleus of the solitary tract (NTS) area postrema (AP) spinal trigeminal tract (sp5) and paratrigeminal nucleus (Pa5) In trained W a significant increase (p<0 05) in specific binding was observed in the Pa5 (31 3%) and NTS (28 2%) Trained SHR showed a significant decrease in n ceptor density in lamina 2 (21 9%) of the thoracic spinal cord and an increase in specific binding in Pa5 (36 1%) We suggest that in the medulla chronic exercise could hyper stimulate the KKS enhancing their efficiency through the increase of B2 receptor density involving this receptor in central cardiovascular control during exercise or stress In the lamina 2 B2 receptor might be involved in the exercise-induced hypotension (C) 2010 Elsevier BV All rights reserved

Aging and calorie restriction modulate yeast redox state, oxidized protein removal, and the ubiquitin-proteasome system

The ubiquitin-proteasome system governs the half-life of most cellular proteins. Calorie restriction (CR) extends the maximum life span of a variety of species and prevents oxidized protein accumulation. We studied the effects of CR on the ubiquitin-proteasome system and protein turnover in aging Saccharomyces cerevisiae. CR increased chronological life span as well as proteasome activity compared to control cells. The levels of protein carbonyls, a marker of protein oxidation, and those of polyubiquitinated proteins were modulated by CR. Controls, but not CR cells, exhibited a significant increase in oxidized proteins. In keeping with decreased proteasome activity, polyubiquitinated proteins were increased in young control cells compared to time-matched CR cells, but were profoundly decreased in aged control cells despite decreased proteasomal activity. This finding is related to a decreased polyubiquitination ability due to the impairment of the ubiquitin-activating enzyme in aged control cells, probably related to a more oxidative microenvironment. CR preserves the ubiquitin-proteasome system activity. Overall, we found that aging and CR modulate many aspects of protein modification and turnover. (C) 2011 Elsevier Inc. All rights reserved.

Risk factors for neonatal transfers from the Sapopemba free-standing birth centre to a hospital in Sao Paulo, Brazil

Objective: to identify risk factors associated with neonatal transfers from a free-standing birth centre to a hospital. Design: epidemiological case-control study. Setting: midwifery-led free-standing birth centre in Sao Paulo, Brazil. Participants: 96 newborns were selected from 2840 births between September 1998 and August 2005. Cases were defined as all new borns transferred from the birth centre to a hospital (n = 32), and controls were defined as new borns delivered at the same birth centre, during the same time period, and who had not been transferred to a hospital (n = 64). Measurements and findings: data were collected from medical records available at the birth centre. Univariate and multivariate analyses were performed using logistic regression. The multivariate analysis included outcomes with p<0.25, specifically: smoking during pregnancy, prenatal care appointments, labour complications, weight in relation to gestational age, and one-minute Apgar score. Of the foregoing outcomes, those that remained in the full regression model as a risk factor associated with neonatal transfer were: smoking during pregnancy [p = 0.009, odds ratio (OR) = 4.1,95% confidence interval (CI) 1.03-16.33], labour complications (p<0.001, OR = 5.5, 95% CI 1.06-28.26) and one-minute Apgar score <= 7 (p<0.001, OR = 7.8,95% CI 1.62-37.03). Key conclusions and implications for practice: smoking during pregnancy, labour complications and one-minute Apgar score <= 7 were confirmed as risk factors for neonatal transfer from the birth centre to a hospital. The identified risk factors can help to improve institutional protocols and formulate hypotheses for other studies. (C) 2009 Elsevier Ltd. All rights reserved.

Effect of Oxalate Desensitizer on the Durability of Resin-Bonded Interfaces

Potassium oxalate desensitizers were previously shown to effectively reduce the immediate permeability of resin-bonded dentin. The current study evaluated whether the effect of the combined application of oxalate with etch-and-rinse adhesives interferes with the durability of resin-dentin bonds when using etch-and-rinse adhesives. The bond strength of resin-bonded dentin specimens composed of two-step or three-step etch-and-rinse adhesives (Single Bond, One-Step and Scotchbond Multi-Purpose, respectively) was tested immediately (24 hours) and after 12 months of water storage. The adhesives were used either according to the manufacturers` instructions (control groups) or after treating acid-etched dentin with a potassium oxalate gel (BisBlock, BISCO, Inc). The treatment of dentin with potassium oxalate was shown to negatively affect the baseline bond strength of resin-bonded dentin specimens, regardless of the adhesive used (p<0.05). After storage, the bond strength of the resin-bonded interfaces was significantly reduced for all the tested groups (p<0.001). Nevertheless, the rate of decreasing bond strength was significantly lower for oxalate-treated specimens than for the controls (p<0.05).

Acute and chronic effects of exercise on inflammatory markers and B-type natriuretic peptide in patients with coronary artery disease

Few studies have prospectively addressed the effects of exercise in the inflammatory activity of patients with coronary artery disease (CAD). We sought to evaluate the consequences of an acute bout of exercise on inflammatory markers and BNP in untrained CAD patients before and after randomization to a training program. 34 CAD patients underwent a 50-min acute exercise session on a cycle-ergometer at 65% peak oxygen uptake before and after blood sampling. They were then randomized to a 4-month chronic exercise program (15 patients) or general lifestyle recommendations (19 patients), undergoing a new acute session of exercise after that. In the overall population, acute exercise caused a significant increase in C-reactive protein [CRP; 1.79 (4.49) vs. 1.94 (4.89) mg/L, P < 0.001], monokine induced by interferon-gamma [Mig; 351 (324) vs. 373 (330) pg/mL, P = 0.027] and vascular adhesion molecule-1 [VCAM-1; 226 (82) vs. 252 (110) pg/mL, P = 0.02]. After 4-months, in exercise-trained patients, there was a significant decrease in the inflammatory response provoked by the acute exercise compared to patients in the control group reflected by a significant decrease in the differences between rest and post-exercise levels of CRP [-0.29 (0.84) mg/L vs. -0.11 (0.21) mg/L, P = 0.05]. Resting BNP was also significantly lower in exercise-trained patients when compared to untrained controls [15.6 (16.2) vs. 9.7 (11.4) pg/mL, P = 0.04 and 19.2 (27.8) vs. 23.2 (27.5) pg/mL, P = 0.76; respectively]. Chronic exercise training might partially reverse the inflammatory response caused by acute exercise in CAD patients. These results suggest that regular exercise is an important nonpharmacological strategy to the improvement in inflammation in CAD patients.

Effects of different levels of protein intake and physical training on growth and nutritional status of young rats

This study aimed to investigate the effects of physical training, and different levels of protein intake in the diet, on the growth and nutritional status of growing rats. Newly-weaned Wistar rats (n=48) were distributed into six experimental groups: three of them were subjected to physical swim training (1 h per day. 5 d per week, for 4 wk, after 2 wk of familiarization) and the other three were considered as controls (non-trained). Each pair of groups, trained and non-trained, received diets with a different level of protein in their composition: 14%. 21% or 28%. The animals were euthanized at the end of the training period and the following analyses were performed: proteoglycan synthesis as a biomarker of bone and cartilage growth, IGF-I (insulin-like growth factor-I) assay as a biomarker of growth and nutritional status. total RNA and protein concentration and protein synthesis measured in vivo using a large-dose phenylalanine method. As a main finding, increased dietary protein, combined with physical training, was able to improve neither tissue protein synthesis nor muscle growth. In addition, cartilage and bone growth seem to be deteriorated by the lower and the higher levels of protein intake. Our data allow us to conclude that protein enhancement in the diet, combined with physical exercise, does not stimulate tissue protein synthesis or muscle mass growth. Furthermore, physical training, combined with low protein intake, was not favorable to bone development in growing animals.

Weight loss associated with exercise training restores ventilatory efficiency in obese children

The purpose of this study was to test the hypothesis that in obese children: 1) Ventilatory efficiency (VentE) is decreased during graded exercise; and 2) Weight loss through diet alone (D) improves VentE, and 3) diet associated with exercise training (DET) leads to greater improvement in VentE than by D. Thirty-eight obese children (10 +/- 0.2 years; BMI > 95(th) percentile) were randomly divided into two Study groups: D (n=17; BMI = 30 +/- 1 kg/m(2)) and DET (n = 21; 28 +/- 1 kg/m(2)). Ten lean children were included in a control group (10 +/- 0.3 years; 17 +/- 0.5 kg/m(2)). All children performed maximal treadmill testing with respiratory gas analysis (breath-by-breath) to determine the ventilatory anaerobic threshold (VAT) and peak oxygen consumption (VO(2) peak). VentE was determined by the VE/VCO(2) method at VAT. Obese children showed lower VO(2) peak and lower VentE than controls (p < 0.05). After interventions, all obese children reduced body weight (p < 0.05). D group did not improve in terms of VO(2) peak or VentE (p > 0.05). In contrast, the DET group showed increased VO(2) peak (p = 0.01) and improved VentE(Delta VE/VCO(2) = -6.1 +/- 0.9; p = 0.01). VentE is decreased in obese children, where weight loss by means of DET, but not D alone, improves VentE and cardiorespiratory fitness during graded exercise.

Postural control during prolonged standing in persons with chronic low back pain

Prolonged standing has been associated with the onset of low back pain symptoms in working populations. So far, it is unknown how individuals with chronic low back pain (CLBP) behave during prolonged unconstrained standing (PS). The aim of the present study was to analyze the control of posture by subjects with CLBP during PS in comparison to matched healthy adults. The center of pressure (COP) position of 12 CLBP subjects and 12 matched healthy controls was recorded in prolonged standing (30 min) and quiet stance tasks (60 s) on a force plate. The number and amplitude of COP patterns, the root mean square (RMS), speed, and frequency of COP sway were analyzed. Statistical analyses showed that CLBP subjects produced less Postural changes in the antero-posterior direction with decreased postural sway during the prolonged standing task in comparison to the healthy group. Only CLBP subjects were influenced by the prolonged standing task, as demonstrated by their increased COP RMS, COP speed and COP frequency in the quiet standing trial after the prolonged standing task in comparison to the pre-PS trial. The present study provides additional evidence that individuals with CLBP might have altered sensory-motor function. Their inability to generate responses similar to those of healthy subjects during prolonged standing may contribute to CLBP persistence or an increase risk of recurrent back pain episodes. Moreover, quantification of postural changes during prolonged standing could be useful to identify CLBP subjects prone to postural control deficits. (C) 2008 Elsevier B.V. All rights reserved.

Intracellular mechanisms of specific beta-adrenoceptor antagonists involved in improved cardiac function and survival in a genetic model of heart failure

beta-blockers, as class, improve cardiac function and survival in heart failure (HF). However, the molecular mechanisms underlying these beneficial effects remain elusive. In the present study, metoprolol and carvedilol were used in doses that display comparable heart rate reduction to assess their beneficial effects in a genetic model of sympathetic hyperactivity-induced HF (alpha(2A)/alpha(2C)-ARKO mice). Five month-old HF mice were randomly assigned to receive either saline, metoprolol or carvedilol for 8 weeks and age-matched wild-type mice (WT) were used as controls. HF mice displayed baseline tachycardia, systolic dysfunction evaluated by echocardiography, 50% mortality rate, increased cardiac myocyte width (50%) and ventricular fibrosis (3-fold) compared with WT. All these responses were significantly improved by both treatments. Cardiomyocytes from HF mice showed reduced peak [Ca(2+)](i) transient (13%) using confocal microscopy imaging. Interestingly, while metoprolol improved [Ca(2+)](i) transient, carvedilol had no effect on peak [Ca(2+)](i) transient but also increased [Ca(2+)] transient decay dynamics. We then examined the influence of carvedilol in cardiac oxidative stress as an alternative target to explain its beneficial effects. Indeed, HF mice showed 10-fold decrease in cardiac reduced/oxidized glutathione ratio compared with WT, which was significantly improved only by carvedilol treatment. Taken together, we provide direct evidence that the beneficial effects of metoprolol were mainly associated with improved cardiac Ca(2+) transients and the net balance of cardiac Ca(2+) handling proteins while carvedilol preferentially improved cardiac redox state. (C) 2008 Elsevier Inc. All rights reserved.

Adaptations in autonomic function during exercise training in heart failure

Although neurohumoral excitation is the hallmark of heart failure (HF), the mechanisms underlying this alteration are not entirely known. Abnormalities in several systems contribute to neurohumoral excitation in HF, including arterial and cardiopulmonary baroreceptors, central and peripheral chemoreceptors, cardiac chemoreceptors, and central nervous system abnormalities. Exercise intolerance is characteristic of chronic HF, and growing evidence strongly suggests that exercise limitation in patients with chronic HF is not due to elevated filling pressures or inadequate cardiac output during exercise, but instead due to skeletal myopathy. Several lines of evidence suggest that sympathetic excitation contributes to the skeletal myopathy of HF, since sympathetic activity mediates vasoconstriction at rest and during exercise likely restrains muscle blood flow, arteriolar dilatation, and capillary recruitment, leading to underperfused areas of working muscle, and areas of muscle ischemia, release of reactive oxygen species (ROS), and inflammation. Although controversial, either unmyelinated, metabolite-sensitive afferent fibers, and/or myelinated, mechanosensitive afferent fibers in skeletal muscle underlie the exaggerated sympathetic activity in HF. Exercise training has emerged as a unique non-pharmacological strategy for the treatment of HF. Regular exercise improves functional capacity and quality of life, and perhaps prognosis in chronic HF patients. Recent studies have provided convincing evidence that these benefits in chronic HF patients are mediated by significant reduction in central sympathetic outflow as a consequence of improvement in arterial and chemoreflex controls, and correction of central nervous system abnormalities, and increase in peripheral blood flow with reduction in cytokines and increase in mass muscle.

Aerobic exercise is safe and effective in systemic sclerosis

Several studies have established that systemic sclerosis patients have a reduced exercise capacity when compared to healthy individuals. It is relevant to evaluate whether aerobic exercise in systemic sclerosis patients is a safe and effective intervention to improve aerobic capacity. Seven patients without pulmonary impairment and seven healthy controls were enrolled in an 8-week program consisting of moderate intensity aerobic exercise. Patients and controls had a significant improvement in peak oxygen consumption (19.72 +/- 3.51 vs. 22.27 +/- 2.53 and 22.94 +/- 4.70 vs. 24.55 +/- 3.00, respectively, p = 0.006), but difference between groups was not statistically significant (p = 0.149). This finding was reinforced by the fact that at the end of the study both groups were able to perform a significantly higher exercise intensity when compared to baseline, as measured by peak blood lactate (1.43 +/- 0.51 vs. 1.84 +/- 0.33 and 1.11 +/- 0.45 vs. 1.59 +/- 0.25, respectively, p = 0.01). Patients improved the peak exercise oxygen saturation comparing to the baseline (84.14 +/- 9.86 vs. 90.29 +/- 5.09, p = 0.048). Rodnan score was similar before and after the intervention(15.84 +/- 7.84 vs. 12.71 +/- 4.31, p = 0.0855). Digital ulcers and Raynaud`s phenomenon remained stable. Our data support the notion that improving aerobic capacity is a feasible goal in systemic sclerosis management. The long term benefit of this intervention needs to be determined in large prospective studies.