Treatment of dementia with neurotransmission modulation

The prevalence of dementia is growing in developed countries where elderly patients are increasing in numbers. Neurotransmission modulation is one approach to the treatment of dementia. Cholinergic precursors, anticholinesterases, nicotine receptor agonists and muscarinic M-2 receptor antagonists are agents that enhance cholinergic neurotransmission and that depend on having some intact cholinergic innervation to be effective in the treatment of dementia. The cholinergic precursor choline alfoscerate may be emerging as a potential useful drug in the treatment of dementia, with few adverse effects. Of the anticholinesterases, donepezil, in addition to having a similar efficacy to tacrine in mild-to-moderate Alzheimer's disease (AD), appears to have major advantages; its use is associated with lower drop-out rates in clinical trials, a lower incidence of cholinergic-like side effects and no liver toxicity. Rivastigmine is efficacious in the treatment in dementia with Lewy bodies, a condition in which the other anticholinesterases have not been tested extensively to date. Galantamine is an anticholinesterase and also acts as an allosteric potentiating modulator at nicotinic receptors to increase the release of acetylcholine. Pooled data from clinical trials of patients with mild-to-moderate AD suggest that the benefits and safety profile of galantamine are similar to those of the anticholinesterases. Selective nicotine receptor agonists are being developed that enhance cognitive performance without influencing autonomic and skeletal muscle function, but these have not yet entered clinical trial for dementia. Unlike the cholinergic enhancers, the M, receptor agonists do not depend upon intact cholinergic nerves but on intact M, receptors for their action, which are mainly preserved in AD and dementia with Lewy bodies. The M, receptor-selective agonists developed to date have shown limited efficacy in clinical trials and have a high incidence of side effects. A major recent advancement in the treatment of dementia is memantine, a non-competitive antagonist at NMDA receptors. Memantine is beneficial in the treatment of severe and moderate to-severe AD and may also be of some benefit in the treatment of mild-to-moderate vascular dementia. Drugs that modulate 5-HT, somatostatin and noradrenergic neurotransmission are also being considered for the treatment of dementia.

Experiments and observations on the behaviour and brain of the aging female mouse with special reference to dementia of the Alzheimer type

The objective of this research was to investigate the effects of normal aging and the additional effects of chronic exposure to two experimental diets, one enriched in aluminium, the other enriched in lecithin, on aspects of the behaviour and brain histology of the female mouse. The aluminium diet was administered in an attempt to develop a rodent model of Dementia of the Alzheimer Type (DAT). With normal aging, almost all assessed aspects of behaviour were found to be impaired. As regards cognition, selective impairments of single-trial passive avoidance and Morris place learning were observed. While all aspects of open-field behaviour were impaired, the degree of impairment was directly related to the degree of motoric complexity. Deficits were also observed on non-visual sensorimotor coordination tasks and in olfactory discrimination. Histologically, neuron loss, gliosis, vacuolation and congophilic angiopathy were observed in several of the brain regions/fibre tracts believed to contribute to the control of some of the assessed behaviours. The aluminium treatment had very selective effects on both behaviour and brain histology, inducing several features observed in DAT. Behaviourally, the treatment induced impaired spatial reference memory; reduced ambulation; disturbed olfactory function and induced the premature development of the senile pattern of swimming. Histologically, significant neuron loss and gliosis were observed in the hippocampus, entorhinal cortex, amygdala, medial septum, pyriform and pr-frontal cortex. In addition, the brain distribution of congophilic angiopathy was significantly increased by the treatment. The lecithin treatment had effects on both non-cognitive and cognitive aspects of behaviour. The effects of aging on open-field ambulation and rearing were partially ameliorated by the treatment. A similar effect was observed for single-trial passive avoidance performance. Age-dependent improvements in acquisition/retention were observed in 17-23 month mice and Morris place task performance was improved in 11 and 17 month mice. Histologically, a partial sparing of neurons in the cerebellum, hippocampus, entorhinal cortex and subiculum was observed.

Characterization of the behavioural phenotype of calpain-knockout mice

Dissertação de Mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2016

Cuminum cyminum Linn (Apiaceae) extract attenuates MPTP-induced oxidative stress and behavioral impairments in mouse model of Parkinson’s disease

Purpose: To evaluate the protective effects of Cuminum cyminum Linn (Apiaceae, CCY) against 1- methyl-4 phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced oxidative stress and behavioral impairments in mouse model of Parkinson’s disease (PD). Methods: MPTP-intoxicated mice model of PD was used for evaluating the effect of CCY extract on behavioral deficits through rota rod, passive avoidance and open field tasks. The effect of CCY extract on oxidative stress levels were assessed by estimating enzyme status, including superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation(LPO) in brain tissues of MPTP-induced mice. Results: MPTP (25 mg/kg, i.p.)-treated mice resulted in a significant (p < 0.001) behavioral deficit in locomotor behavior (from 56.24 ± 1.21 to 27.64 ± 0.94) and cognitive functions (from 298 ± 3.68 s to 207.28 ± 4.12 s) compared with their respective control groups. Administration of CCY extract (100, 200 and 300 mg/kg, p.o.) for three weeks significantly and dose-dependently improved (p < 0.001 at 300 mg/kg) locomotor and cognitive deficits in MPTP-treated mice. CCY treatment also significantly (p < 0.001 at 300 mg/kg) inhibited MPTP-induced decrease in antioxidant enzyme levels (superoxide dismutase and catalase) and lipid peroxides in mice brain tissues. Conclusion: CCY extract exhibits strong protection against MPTP-induced behavioral deficit through enhancement of antioxidant defense mechanisms. Therefore, CCY may be developed as a therapeutic strategy in the treatment of neurodegeneration seen in PD.

Indigofera tinctoria Linn (Fabaceae) attenuates cognitive and behavioral deficits in scopolamine-induced amnesic mice

Purpose: To investigate the cognition-enhancing effects of aqueous extract of Indigofera tinctoria Linn (ITE, Fabaceae) in experimental amnesic mice. Methods: Scopolamine (2 mg/kg, i.p.) was used to induce amnesia in mice. The cognitive-enhancing activity of the ITE (5, 10 and 20 μg/mL) was studied by passive avoidance response, elevated plus maze and Y-maze behavioral paradigm in normal and scopolamine-induced amnesic mice. Antioxidant activities were also determined based on the ability of ITE to inhibit lipid peroxide, superoxide and hydroxyl radicals. Results: Scopolamine-induced cognitive deficits were significantly reversed by ITE (p < 0.001 at 20 mg/kg) in a dose-dependent fashion in all the behavioral paradigms tested. Furthermore, ITE dosedependently scavenged lipid peroxide, superoxide and hydroxyl free radicals with 50 % inhibition concentration (IC50) of 7.28 ± 0.37, 5.25 ± 0.28 and 7.62 ± 0.43 μg/mL, respectively. Conclusion: ITE possesses cognitive-enhancing properties in amnesic mice due to its potent antioxidant action.

Active and passive smoking and the risk of subarachnoid hemorrhage - An international population-based case-control study

Background and Purpose - This study was undertaken to better clarify the risks associated with cigarette smoking and subarachnoid hemorrhage (SAH). Methods - The study included 432 incident cases of SAH frequency matched to 473 community SAH-free controls to determine dose-dependent associations of active and passive smoking ( at home) and smoking cessation with SAH. Results - Compared with never smokers not exposed to passive smoking, the adjusted odds ratio for SAH among current smokers was 5.0 (95% confidence interval [CI], 3.1 to 8.1); for past smokers, 1.2 ( 95% CI, 0.8 to 2.0); and for passive smokers, 0.9 ( 95% CI, 0.6 to 1.5). Current and lifetime exposures showed a clear dose-dependent effect, and risks appeared more prominent in women and for aneurysmal SAH. Approximately 1 in 3 cases of SAH could be attributed to current smoking, but risks decline quickly after smoking cessation, even among heavy smokers. Conclusions - A strong positive association was found between cigarette smoking and SAH, especially for aneurysmal SAH and women, which is virtually eliminated within a few years of smoking cessation. Large opportunities exist for preventing SAH through smoking avoidance and cessation programs.

Potential evidence of parasite avoidance in an avian malarial vector

Epidemiological studies of malaria or other vector-transmitted diseases often consider vectors as passive actors in the complex life cycle of the parasites, assuming that vector populations are homogeneous and vertebrate hosts are equally susceptible to being infected during their lifetime. However, some studies based on both human and rodent malaria systems found that mosquito vectors preferentially selected infected vertebrate hosts. This subject has been scarcely investigated in avian malaria models and even less in wild animals using natural host-parasite associations. We investigated whether the malaria infection status of wild great tits, Parus major, played a role in host selection by the mosquito vector Culex pipiens. Pairs of infected and uninfected birds were tested in a dual-choice olfactometer to assess their attractiveness to the mosquitoes. Plasmodium-infected birds attracted significantly fewer mosquitoes than the uninfected ones, which suggest that avian malaria parasites alter hosts' odours involved in vector orientation. Reaction time of the mosquitoes, that is, the time taken to select a host, and activation of mosquitoes, defined as the proportion of individuals flying towards one of the hosts, were not affected by the bird's infection status. The importance of these behavioural responses for the vector is discussed in light of recent advances in related or similar model systems.

Comment On 'practical Advice For Avoidance Of Pain Associated With Insertion Of Intrauterine Contraceptives': Authors' Response.

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Tradução, adaptação transcultural e validação do "Body Image Avoidance Questionnaire (BIAQ)" e do "Body Checking Questionnaire (BCQ)" para lingua portuguesa no Brasil

Universidade Estadual de Campinas . Faculdade de Educação Física

Visual Feedforward Control in Human Locomotion During Avoidance of Obstacles that Change Size

The purpose of the current study was to understand how visual information about an ongoing change in obstacle size is used during obstacle avoidance for both lead and trail limbs. Participants were required to walk in a dark room and to step over an obstacle edged with a special tape visible in the dark. The obstacle's dimensions were manipulated one step before obstacle clearance by increasing or decreasing its size. Two increasing and two decreasing obstacle conditions were combined with seven control static conditions. Results showed that information about the obstacle's size was acquired and used to modulate trail limb trajectory, but had no effect on lead limb trajectory. The adaptive step was influenced by the time available to acquire and process visual information. In conclusion, visual information about obstacle size acquired during lead limb crossing was used in a feedforward manner to modulate trail limb trajectory.

Continental passive microwave-based rainfall estimation algorithm: Application to the Amazon Basin

This paper presents a new statistical algorithm to estimate rainfall over the Amazon Basin region using the Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI). The algorithm relies on empirical relationships derived for different raining-type systems between coincident measurements of surface rainfall rate and 85-GHz polarization-corrected brightness temperature as observed by the precipitation radar (PR) and TMI on board the TRMM satellite. The scheme includes rain/no-rain area delineation (screening) and system-type classification routines for rain retrieval. The algorithm is validated against independent measurements of the TRMM-PR and S-band dual-polarization Doppler radar (S-Pol) surface rainfall data for two different periods. Moreover, the performance of this rainfall estimation technique is evaluated against well-known methods, namely, the TRMM-2A12 [ the Goddard profiling algorithm (GPROF)], the Goddard scattering algorithm (GSCAT), and the National Environmental Satellite, Data, and Information Service (NESDIS) algorithms. The proposed algorithm shows a normalized bias of approximately 23% for both PR and S-Pol ground truth datasets and a mean error of 0.244 mm h(-1) ( PR) and -0.157 mm h(-1)(S-Pol). For rain volume estimates using PR as reference, a correlation coefficient of 0.939 and a normalized bias of 0.039 were found. With respect to rainfall distributions and rain area comparisons, the results showed that the formulation proposed is efficient and compatible with the physics and dynamics of the observed systems over the area of interest. The performance of the other algorithms showed that GSCAT presented low normalized bias for rain areas and rain volume [0.346 ( PR) and 0.361 (S-Pol)], and GPROF showed rainfall distribution similar to that of the PR and S-Pol but with a bimodal distribution. Last, the five algorithms were evaluated during the TRMM-Large-Scale Biosphere-Atmosphere Experiment in Amazonia (LBA) 1999 field campaign to verify the precipitation characteristics observed during the easterly and westerly Amazon wind flow regimes. The proposed algorithm presented a cumulative rainfall distribution similar to the observations during the easterly regime, but it underestimated for the westerly period for rainfall rates above 5 mm h(-1). NESDIS(1) overestimated for both wind regimes but presented the best westerly representation. NESDIS(2), GSCAT, and GPROF underestimated in both regimes, but GPROF was closer to the observations during the easterly flow.

Modeling and analysis of laminate composite plates with embedded active-passive piezoelectric networks

The objective of this work is to present the finite element modeling of laminate composite plates with embedded piezoelectric patches or layers that are then connected to active-passive resonant shunt circuits, composed of resistance, inductance and voltage source. Applications to passive vibration control and active control authority enhancement are also presented and discussed. The finite element model is based on an equivalent single layer theory combined with a third-order shear deformation theory. A stress-voltage electromechanical model is considered for the piezoelectric materials fully coupled to the electrical circuits. To this end, the electrical circuit equations are also included in the variational formulation. Hence, conservation of charge and full electromechanical coupling are guaranteed. The formulation results in a coupled finite element model with mechanical (displacements) and electrical (charges at electrodes) degrees of freedom. For a Graphite-Epoxy (Carbon-Fibre Reinforced) laminate composite plate, a parametric analysis is performed to evaluate optimal locations along the plate plane (xy) and thickness (z) that maximize the effective modal electromechanical coupling coefficient. Then, the passive vibration control performance is evaluated for a network of optimally located shunted piezoelectric patches embedded in the plate, through the design of resistance and inductance values of each circuit, to reduce the vibration amplitude of the first four vibration modes. A vibration amplitude reduction of at least 10 dB for all vibration modes was observed. Then, an analysis of the control authority enhancement due to the resonant shunt circuit, when the piezoelectric patches are used as actuators, is performed. It is shown that the control authority can indeed be improved near a selected resonance even with multiple pairs of piezoelectric patches and active-passive circuits acting simultaneously. (C) 2010 Elsevier Ltd. All rights reserved.

Experimental analysis of active-passive vibration control using viscoelastic materials and extension and shear piezoelectric actuators

Hybrid active-passive damping treatments combine the reliability, low cost and robustness of viscoelastic damping treatments and the high-performance, modal selective and adaptive piezoelectric active control. Numerous hybrid damping treatments have been reported in the literature. They differ mainly by the relative positions of viscoelastic treatments, sensors and piezoelectric actuators. In this work we present an experimental analysis of three active-passive damping design configurations applied to a cantilever beam. In particular, two design configurations based on the extension mode of piezoelectric actuators combined with viscoelastic constrained layer damping treatments and one design configuration with shear piezoelectric actuators embedded in a sandwich beam with viscoelastic core are analyzed. For comparison purposes, a purely active design configuration with an extension piezoelectric actuator bonded to an elastic beam is also analyzed. The active-passive damping performance of the four design configurations is compared. Results show that active-passive design configurations provide more reliable and wider-range damping performance than the purely active configuration.

Evaluation of passive confinement in CFT columns

This paper presents the experimental results of 32 axially loaded concrete-filled steel tubular columns (CFT). The load was introduced only on the concrete core by means of two high strength steel cylinders placed at the column ends to evaluate the passive confinement provided by the steel tube. The columns were filled with structural concretes with compressive strengths of 30, 60, 80 and 100 MPa. The outer diameter (D) of the column was 114.3 mm, and the length/diameter (L/D) ratios considered were 3, 5, 7 and 10. The wall thicknesses of the tubes (t) were 3.35 mm and 6.0 mm, resulting in diameter/thickness (D/t) ratios of 34 and 19, respectively. The force vs. axial strain curves obtained from the tests showed, in general, a good post-peak behavior of the CFT columns, even for those columns filled with high strength concrete. Three analytical models of confinement for short concrete-filled columns found in the literature were used to predict the axial capacity of the columns tested. To apply these models to slender columns, a correction factor was introduced to penalize the calculated results, giving good agreement with the experimental values. Additional results of 63 CFT columns tested by other researchers were also compared to the predictions of the modified analytical models and presented satisfactory results. (C) 2009 Elsevier Ltd. All rights reserved.

Influence of chloride ion concentration and temperature on the electrochemical properties of passive films formed on a superduplex stainless steel

Polarization measurements were conducted to monitor the corrosion behavior of superduplex stainless steel ASTM A995M-Gr.SA/EN 10283-Mat#1.4469(GX2CrNiMo26-7-4) when exposed to a) an electrolyte containing 22,700 parts per million (ppm) of chloride ions at seven different temperatures and b) an electrolyte at 25 GC and different chloride ion concentrations (5800, 22,700, 58,000 and 80,000 ppm of Cl(-)). The polarization curves indicate that the passive films formed are only slightly affected by NaCl concentration, but the pitting potential decreases drastically increasing the temperature, in particular >60 degrees C. The image analysis of the microstructure after potentiodynamic polarization showed that the pitting number and size vary in function of the temperature of the tested medium. Nyquist diagrams were determined by electrochemical impedance spectroscopy to characterize the resistance of the passive layer. According to Nyquist plots, the arc polarization resistance decreases increasing the temperature due to a catalytic degradation of the oxide passive films. (C) 2009 Elsevier Inc. All rights reserved.