A Bioengineered Cathepsin B-sensitive Gas Vesicle Nanosystem That Responds With Increased Gray-level Intensity of Ultrasound Biomicroscopic Images.

OBJECTIVE: This work aimed to promote the interaction of a modified gas vesicle (GV) with cathepsin B (CTSB) protease and analysed their backscattered signal by ultrasound (US). METHODS: We modified the sequence of the gene coding for GvpC to contain a CTSB cleavage and expressed the protein in an Escherichia coli recombinant system. The protein was purified and added to GVs preparations in which the original GvpC was removed (ΔGV), constituting the modified GV (GV*). Western blot testing was used to compare GVs with GvpC and engineered GvpC at starting (T0) and after 24 h (T24) reacting with CTSB. A 21 MHz US B-mode and non-linear contrast mode (5% total power) imaged US phantoms having samples of GVwt, ΔGV (stripped GV), GV* and CTSB + GV*. Also, a 21 MHz US B-mode imaged US phantoms having a tumour cell line extracellular fraction (TCEF) and the TCEF + GV* sample. A 100% total US power was applied to collapse the GV structure. RESULTS: On Western blotting, we detected a decrease in engineered GvpC levels 24 h after the incubation of GV* with CTSB, compared with the concentration at T0, suggesting that CTSB cleaved the engineered GvpC. Regions-of-interest over image of phantom cross-sections were determined and the B-mode image mean grey-level intensity resulted in a significant (p < 0.05) increase comparing CTSB + GV* with PBS (control), GVwt, ΔGV and GV*. Non-linear mode image grey-level intensity from CTSB + GV* increased by 11.79, 7.86 and 14.75 dB from samples containing GVwt, ΔGV and GV*, respectively. GV preparations incubated with TCEF and the TCEF + GV* sample showed an increase of 81% in signal compared with TCEF + GVwt. CONCLUSION: The increased US backscattered signal intensity suggests GVs as a potential biosensor for protease activity, possibly aiding the detection of protease-rich tissue regions.

The P2X7 Receptor Promotes Colorectal Inflammation and Tumorigenesis by Modulating Gut Microbiota and the Inflammasome.

Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). Methods: CA-CRC was induced in P2X7R+/+ and P2X7R-/- mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS). In a therapeutic protocol, P2X7R+/+ mice were treated with a P2X7R-selective inhibitor (A740003). Mice were evaluated with follow-up video endoscopy with endoluminal ultrasound biomicroscopy. Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. Results: The P2X7R+/+ mice displayed more ulcers, tumors, and greater wall thickness, than the P2X7R-/- and the P2X7R+/+ mice treated with A740003. The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. Microbial changes were observed in the P2X7R-/- and P2X7R+/+-induced mice, partially reversed by the A740003 treatment. Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development.

Shear Elastic Coefficient of Normal and Fibrinogen-Deficient Clotting Plasma Obtained with a Sphere-Motion-Based Acoustic-Radiation-Force Approach.

Blood coagulation is a process involving several chemical reactions governed by coagulation factors, during which the shear elastic coefficient, µ, varies as the medium transitions from liquid to gel phase. This work used ultrasound to measure µ during the clotting of human plasma samples by tracking the motion of a glass sphere located inside a cuvette filled with the plasma. A 2.03 MHz ultrasonic system generated an impulsive acoustic radiation force acting on the sphere, and a 4.89 MHz pulse-echo ultrasonic system tracked the sphere displacement induced by that force. Measurements of µ were determined by fitting a µ-dependent theoretical model to the motion waveform of the sphere immersed in clotting normal plasma and plasma samples with fibrinogen (FI) concentrations of 1.2 (FI-deficiency) and 3.6 (FI-normal) g/L. For normal plasma, µ started at 14.22 Pa and increased rapidly until 2 min, then slowly until it reached 210.23 Pa at 35 min after the clotting process started. A similar trend was exhibited in plasma samples with FI concentrations of 1.2 and 3.6 g/L, with µ reaching 120.55 and 679.42 Pa, respectively. A theoretical model, related to the kinetics of clot-structure formation, describes the time changes of µ for the clotting plasma samples. The sphere-motion-based acoustic-radiation-force approach allowed us to measure the shear elastic coefficient during the coagulation process of plasma samples with normal and deficient FI concentrations. Our results suggest that the method used in this study is capable of being used to detect bleeding disorders.

Dynamic assessment of plasma clotting in samples with distinct fibrinogen concentrations using impulsive acoustic radiation force.

While some diseases reduce fibrinogen concentration, others increase the amount of this clotting factor in the blood. Some studies have shown that the fibrinogen concentration in the blood is related to the stiffness of the formed clot. Hence, the aim of this study was to employ an ultrasonic method based on impulsive acoustic radiation force (IARF) to identify the fibrinogen concentration (coagulation factor I) in a plasma sample by means of peak-displacement (PD), time of peak-displacement (TPD), and shear modulus (µ) as well as to identify the change of plasma samples during the clot formation process. The IARF-based ultrasonic system transmitted bursts with a frequency of 2.03 MHz, duration of 246.31 µs, amplitude of 118 VPP, and pulse with 1.25 Hz repetition frequency to generate an IARF on a glass sphere (2.99 mm in diameter and 2500 kg/m3 in density) embedded in a plasma sample, causing a displacement that was monitored by a pulse-echo system with a center frequency of 4.89 MHz. The values of the shear moduli were 124.14 ± 3.02, 556.99 ± 11.76, and 670.39 ± 9.77 Pa, for fibrinogen concentrations of 1.2, 2.4, and 3.6 g/L 20 to 36 min after the beginning of the coagulation process. The TPD values obtained in the same period were 5.28 ± 0.09, 3.03 ± 0.02, and 2.83 ± 0.01 s. The results indicate that an IARF-based ultrasonic system can be used clinically because it uses small amounts of plasma and has the ability to detect differences in PD, TPD, and µ as a function of fibrinogen concentrations.

3-D Endoluminal Ultrasound Biomicroscopic Imaging and Volumetry of Mouse Colon Tumors.

Currently, colonoscopy is considered the gold standard procedure for diagnosis of colorectal cancer (CRC), the third most common cancer in the United States. However, this technique fails to detect flat adenomas, serrated polyps and advanced adenomas, with miss rates of 34%, 27% and 14%, respectively. These miss rates, more frequent than previously supposed, suggest the need for new CRC screening tools. In the work described here, the potential application of a 40-MHz ultrasound system to generate a sequence of 2-D endoluminal ultrasound biomicroscopy (eUBM-2-D) images of a mouse model of colon cancer was investigated, and this image sequence was used to render eUBM-3-D images and to measure tumor volume. The technique was validated with tissue-mimicking phantoms and used in vivo with mice bearing colon polypoid tumors. Estimated volumes ranged from 0.174-7.909 mm3 for targets in validation phantoms and from 0.066-6.082 mm3 for mouse colon tumors.

Detection of Mice Colorectal Tumors by Endoluminal Ultrasound Biomicroscopic Images and Quantification of Image Augmented Gray Values Following Injection of VEGFR-2 Targeted Contrast Agent.

RATIONALE AND OBJECTIVES: Ultrasound biomicroscopy (UBM) is a noninvasive imaging technique that can be applied in detecting colonic tumors and, once associated with an ultrasound contrast agent (UCA), can identify the molecular expression of cancer-related biomarkers, such as the vascular endothelial growth factor receptor 2 (VEGFR-2). The present work aimed to detect colonic tumors and quantify augmented gray values of endoluminal UBM (eUBM) images from colonic tumors following the injection of VEGFR-2 targeted UCA (VEGFR2-UCA) into a mouse model of colorectal cancer. MATERIAL AND METHODS: A 40 MHz miniprobe catheter inserted through the biopsy channel of a pediatric flexible bronchofiberscope was used to obtain colonoscopic and B-mode eUBM images simultaneously. Seventeen tumor-bearing mice had their colons inspected and six of them were subjected to a VEGFR2-UCA injection to predict VEGFR-2 expression. RESULTS: All animals developed distal colon tumors and eUBM was able to detect all of them and also to characterize the tumors, with 71.4% being in situ lesions and 28.6% being tumors invading the mucosa + muscularis mucosae + submucosa layers, as confirmed by histopathology. After VEGFR2-UCA injection, gray values from the eUBM tumoral images increased significantly (p < 0.01). Tumor sites with increased eUBM image gray values corresponded to areas with increased VEGFR-2 expression, as confirmed by immunohistochemistry. CONCLUSION: The results confirm eUBM as a powerful noninvasive and real-time tool for detecting colon tumor and its invasiveness and once associated with VEGFR2-UCA may become a tool for the detection of VEGFR-2 expression in colonic tumors.

Ultrasonic method of microvibration detection: part II - additional processing method and applications

Abstract Introduction In the last 28 years, the scientific community has been using elastography to evaluate the mechanical properties of biological tissue. The aim of this work was the optimization of the UDmV method, presented in Part I of the series, by means of modifying the technique employed to generate the reference sine and cosine functions, used for phase-quadrature demodulation, and determining how this modification improved the performance of the method. Additionally, the UDmV was employed to characterize the acoustic and mechanical properties of a 7% gelatin phantom. Methods A focused transducer, T F, with a nominal frequency of 2.25 MHz, was used to induce the shear waves, with frequency of 97.644 Hz. Then, the modified UDmV method was used to extract the phase and quadrature components from ultrasonic RF echo-signals collected from four positions along the propagation path of the shear wave, which allowed the investigation of the medium vibration caused by wave propagation. The phase velocity, c s, and attenuation, α s, of the phantom were measured and employed in the calculation of shear modulus, μ, and viscosity, η. Results The computational simulation demonstrated that the modification in UDmV method resulted in more accurate and precise estimates of the initial phases of the reference sinusoidal functions used for phase-quadrature demodulation. The values for c s and μ of 1.31 ± 0.01 m·s-1 and 1.66 ± 0.01 kPa, respectively, are very close to the values found in the literature (1.32 m·s-1 and 1.61 kPa) for the same material. Conclusion The UDmV method allowed estimating of the acoustic and viscoelastic parameters of phantom.

Ultrasound biomicroscopy and claudication test for in vivo follow-up of muscle repair enhancement based on platelet-rich plasma therapy in a rat model of gastrocnemius laceration

PURPOSE: To track the regeneration process of lateral gastrocnemius due to a muscle laceration in rats, and to treatment with plateletrich plasma (PRP). METHODS: Ultrasound (40 MHz) images were used for measuring pennation angle (PA), muscle thickness (MT) and mean pixel intensity, along with claudication scores, of treated (PRPG) and non-treated (NTG) groups of rats. RESULTS: NTG showed a PA increase for the non-injured leg (p<0.05) and a tendency of MT to increase, whereas for PRPG there were no differences. There was a progressive reduction of the claudication score for the PRPG group throughout the entire period, with an immediate difference after seven days (p<0.05), whereas the NTG had a significant reduction only at day 28 (p<0.05). CONCLUSION: It was observed a compensatory hypertrophic response due to the overload condition imposed to healthy leg for NTG that did not occur in PRPG, suggesting an accelerated repair process of the injured leg due to treatment, anticipating its use.

Generation of 3D ultrasound biomicroscopic images: technique validation and in vivo volumetric imaging of rat lateral gastrocnemius

Introduction Ultrasound biomicroscopy (UBM) is a technique for generating high-resolution images, with frequencies from 20 MHz to 100 MHz. For example, it has been used in animal research related to models of injury and diseases that mimic human conditions. With a three-dimensional ultrasound (3D) image system, an organ can be viewed at various angles and the volume estimated, contributing to an accurate diagnosis. This work refers to the generation of 3D-UBM images, employing a 35 MHz ultrasound system, from multiple two-dimensional (2D) images. Phantoms were used to validate the technique and to determine its reliability of volume measurements. Additionally, the technique was used to obtain 3D images of the rat gastrocnemius muscle. Methods Four different phantoms were used and ten acquisition sequences of 2D-images acquired for each one. Thereafter, 5 volume segmentations were performed for each acquisition sequence, resulting in 50 measured volumes for each phantom. The physical volumes of all phantoms were used to validate the technique based on the coefficient of variation (CV) and the intraclass correlation coefficient (ICC). Images of the gastrocnemius muscle were acquired and the partial volume quantified. Results The CV and ICC confirmed the reliability of volume measurements obtained by segmentation. Moreover, cross-sectional 2D images of rat hindlimb were obtained, allowing to identify the gastrocnemius muscle and to partially quantify the muscle volume from 3D images. Conclusion The results indicated that the technique is valid to generate 3D images and quantify the volume of a muscle compatible with the dimensions of a small animal.

Laceration in rat gastrocnemius. Following-up muscle repairing by ultrasound biomicroscopy (in vivo), contractility test (ex vivo) and histopathology.

PURPOSE: Implement a laceration protocol of the rat lateral gastrocnemius (LG) and following-up its repair with ultrasound biomicroscopy (UBM), contractility tests and histology. METHODS: Sixty-three male Wistar rats were distributed into two groups. One, with sub-groups GI, GII and GIII (n=12), each containing right LG lacerated (n=6), control and sham (n=3) animals. LG muscles in GI, GII and GIII were inspected by UBM (40 MHz) immediately after, 14 and 28 days post-surgery and thereafter excised with four (GI), 14 (GII) and 28 (GIII) days post-surgery for histology. Animals in second group were distributed into right LG lacerated and control sub-groups. LG muscles in lacerated sub-group were submitted to contractility tests at four (n=8), 14 (n=8) and 28 (n=8) days post-surgery, while in the control sub-group (n=5) were submitted to contractility tests along the course of the experiments. RESULTS: Descriptive findings agreed between the lesion model, muscle repair, UBM images and histology. Contractility results for right LG were different (p<0.05) between control and injured muscle with four and 14 days post-surgery, at tetanic stimulating frequencies (50 and 70 Hz). CONCLUSION: A laceration protocol of the lateral gastrocnemius was implemented and ultrasound biomicroscopy, contractility and histology findings agreed regarding the following-up of injured muscle repair.

Laceration in rat gastrocnemius. Following-up muscle repairing by ultrasound biomicroscopy (in vivo), contractility test (ex vivo) and histopathology

PURPOSE: Implement a laceration protocol of the rat lateral gastrocnemius (LG) and following-up its repair with ultrasound biomicroscopy (UBM), contractility tests and histology. METHODS: Sixty-three male Wistar rats were distributed into two groups. One, with sub-groups GI, GII and GIII (n=12), each containing right LG lacerated (n=6), control and sham (n=3) animals. LG muscles in GI, GII and GIII were inspected by UBM (40 MHz) immediately after, 14 and 28 days post-surgery and thereafter excised with four (GI), 14 (GII) and 28 (GIII) days post-surgery for histology. Animals in second group were distributed into right LG lacerated and control sub-groups. LG muscles in lacerated sub-group were submitted to contractility tests at four (n=8), 14 (n=8) and 28 (n=8) days post-surgery, while in the control sub-group (n=5) were submitted to contractility tests along the course of the experiments. RESULTS: Descriptive findings agreed between the lesion model, muscle repair, UBM images and histology. Contractility results for right LG were different (p<0.05) between control and injured muscle with four and 14 days post-surgery, at tetanic stimulating frequencies (50 and 70 Hz). CONCLUSION: A laceration protocol of the lateral gastrocnemius was implemented and ultrasound biomicroscopy, contractility and histology findings agreed regarding the following-up of injured muscle repair. .

Effects of galantamine and galantamine combined with nimodipine on cognitive speed and quality of life in mixed dementia: a 24-week, randomized, placebo-controlled exploratory trial (the REMIX study) / Efeitos da galantamina e da galantamina combinada à nimodipina sobre a velocidade de processamento cognitivo e qualidade de vida na demência mista: ensaio clínico exploratório, randomizado e controlado com placebo (estudo REMIX)

The effects of galantamine (GAL) on quality of life (QoL) and cognitive speed, as well its effects combined with nimodipine (NIM) in Alzheimer disease (AD) with cerebrovascular disease (mixed dementia), have not been explored. Method : Double-blind, placebo-controlled, multicenter Brazilian trial, studying the effects of GAL/NIM vs. GAL/placebo (PLA) in mild to moderate mixed dementia. Patients were randomized to receive GAL/NIM or GAL/PLA for 24 weeks. Primary efficacy measures were changes on a computerized neuropsychological battery (CNTB) and QoL Scale in Alzheimer's Disease (QoL-AD) from baseline to week 24. Results : Twenty-one patients received at least one drug dose (9 GAL/NIM and 12 GAL/PLA). Groups were matched for age, sex, education, cognitive and QoL scores at baseline. No significant differences were observed between groups on primary or secondary measures. QoL and cognitive performance showed significant improvement (p<0.05) from baseline when all GAL-treated patients were analyzed. Adverse events were predominantly mild to moderate. Conclusion : GAL treatment improved QoL in mixed dementia, in addition to its previously known cognitive benefits. The combination GAL/NIM was not advantageous. However, the small sample size precludes any definitive conclusions. Trial registered at ClinicalTrials.gov: NCT00814658 .

Os efeitos da galantamina (GAL) sobre qualidade de vida (QdV) e velocidade de processamento cognitivo, bem como da combinação com nimodipina (NIM) no tratamento da doença de Alzheimer (DA) com doença cerebrovascular (demência mista) ainda não foram investigados. Método : Estudo multicêntrico brasileiro, duplo-cego, controlado com placebo, avaliando os efeitos de GAL/NIM x GAL/placebo (PLA) na demência mista leve a moderada. Pacientes receberam tratamento com GAL/NIM ou GAL/PLA por 24 semanas. Medidas de eficácia primária foram as variações no desempenho em bateria de testes neuropsicológicos computadorizados e na escala QdV-DA ao final do estudo. Resultados : Vinte um pacientes receberam pelo menos uma dose da droga (9 GAL/NIM e 12 GAL/PLA). Os grupos foram emparelhados por idade, sexo, escolaridade, escores cognitivos e de QdV na linha de base. Não foram observadas diferenças significativas entre os dois grupos nas medidas de eficácia primária e secundária. Na avaliação de todos os pacientes que receberam GAL, houve melhora significativa (p<0,05) em QdV-DA e desempenho cognitivo. Os eventos adversos foram predominantemente leves a moderados. Conclusão : O tratamento com GAL proporcionou melhora da QdV na demência mista, além dos benefícios cognitivos previamente conhecidos. A combinação GAL/NIM não foi vantajosa. O reduzido tamanho amostral impede conclusões definitivas. .

Endoluminal ultrasound biomicroscopy as a reliable tool for in vivo assessment of colonic inflammation in rats.

PURPOSE: Endoscopic ultrasound (EUS) imaging of the colon is an important diagnostic tool for early neoplasia, although usually restricted to the rectum in inflammatory bowel disease (IBD). This study aimed to evaluate the ability of an endoluminal ultrasound biomicroscopic (eUBM) system to detect and characterize lesions simulating Crohn's disease in the colon of rats in vivo. METHODS: Colitis was induced with trinitrobenzene sulfonic acid instillated in the distal colon. Eighteen Wistar rats were submitted to eUBM in three time points: week 1 group (18 animals examined on day 3 after colitis induction), week 2 group (12 animals on days 3 and 10), and week 3 group (7 animals on days 3, 10, and 17). This design yielded distinct inflammation intensities. Three untreated rats were used for acquisition of control images. Scores were used for comparison with histology. RESULTS: Scores for eUBM and histology in the different moments of examination achieved a Spearman's rank correlation coefficient of 0.87 (p < 0.001). Findings of wall thickening presented positive predictive value (PPV) and sensitivity of 94 and of 100 %, respectively. Superficial and deep ulcers presented a PPV of 89 and 80 %, respectively, and negative predictive values of 100 and 85 %, respectively. CONCLUSION: Accurate detection and analysis of the lesions was achieved. The model is essential for the clinical development of the technique and a reproducible method for the evaluation of experimental colitis. eUBM might be applicable in different segments of the gut, developing into a novel adjunct method for IBD evaluation.

Statistical analysis of high frequency ultrasonic backscattered signals from basal cell carcinomas.

A statistical approach was implemented in the study of histologic characteristics from ex vivo basal cell carcinomas, based on the properties of backscattered acoustic waves, for the purpose of evaluating the method as a diagnostic tool. The study was developed using an ultrasound biomicroscope working at a frequency of 45 MHz. The parameters examined were signal-to-noise ratio (SNR), and shape parameters from the Weibull (b(W)) and generalized gamma (c(GG) and υ(GG)) probability density functions. Twenty-seven carcinomatous skin samples were obtained from volunteer patients and classified into two groups (BCC1 and BCC2) based on the distribution patterns of their tumor nests; also, seven non-tumoral samples were used for comparative purposes. Significant differences between groups were obtained for all studied parameters. The successful differentiation between some tissue groups suggests its potential use for carcinoma characterization.

Treatment of Alzheimers disease in Brazil: II. Behavioral and psychological symptoms of dementia / Tratamento da doença de Alzheimer no Brasil: II. Dos sintomas comportamentais e psicológicos da demência

This article reports the recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology for the treatment of Alzheimers disease (AD) in Brazil, with special focus on behavioral and psychological symptoms of dementia (BPSD). It constitutes a revision and broadening of the 2005 guidelines based on a consensus involving researchers (physicians and non-physicians) in the . The authors carried out a search of articles published since 2005 on the MEDLINE, LILACS and Cochrane Library databases. The search criteria were pharmacological and non-pharmacological treatment of the behavioral and psychological symptoms of AD. Studies retrieved were categorized into four classes, and evidence into four levels, based on the 2008 recommendations of the American Academy of Neurology. The recommendations on therapy are pertinent to the dementia phase of AD. Recommendations are proposed for the treatment of BPSD encompassing both pharmacological (including acetyl-cholinesterase inhibitors, memantine, neuroleptics, anti-depressives, benzodiazepines, anti-convulsants plus other drugs and substances) and non-pharmacological (including education-based interventions, physiotherapy, occupational therapy, music therapy, therapy using light, massage and art therapy) approaches. Recommendations for the treatment of cognitive disorders of AD symptoms are included in a separate article of this edition.

Esse texto apresenta as recomendações da Academia Brasileira de Neurologia, por intermédio do seu Departamento Científico de Neurologia Cognitiva e do Envelhecimento, para o tratamento da doença de Alzheimer (DA) no Brasil, enfocando os sintomas comportamentais e psicológicos da demência (SCPD). Trata-se de uma revisão ampliada das diretrizes publicadas em 2005, resultada de um consenso envolvendo pesquisadores da área, médicos e não médicos. Os autores realizaram uma busca de artigos publicados a partir de 2005 nas bases MEDLINE, LILACS e Cochrane Library. A busca foi direcionada para tratamento farmacológico e não farmacológico dos sintomas comportamentais e psicológicos da DA. Os estudos foram categorizados em quatro classes e as evidências em quatro níveis, com base nas recomendações da Academia Americana de Neurologia publicadas em 2008. As recomendações terapêuticas referem-se à fase demencial da DA. Apresentam-se recomendações para o tratamento dos SCPD, tanto farmacológico (incluindo inibidores da acetilcolinesterase, memantina, neurolépticos, antidepressivos, benzodiazepínicos, anticonvulsivantes e outros fármacos e substâncias), como não farmacológico (incluindo intervenções educacionais, fisioterapia, terapia ocupacional, musicoterapia, terapia com luz, massagem e arterapia). As recomendações para o tratamento dos transtornos cognitivos da DA são apresentadas em outro artigo desse fascículo.

Treatment of Alzheimers disease in Brazil: I. Cognitive disorders / Tratamento da doença de Alzheimer no Brasil: I. dos transtornos cognitivos

This article reports the recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology for the treatment of Alzheimers disease (AD) in Brazil, with special focus on cognitive disorders. It constitutes a revision and broadening of the 2005 guidelines based on a consensus involving researchers (physicians and non-physicians) in the . The authors carried out a search of articles published since 2005 on the MEDLINE, LILACS and Cochrane Library databases. The search criteria were pharmacological and non-pharmacological treatment of cognitive disorders in AD. Studies retrieved were categorized into four classes, and evidence into four levels, based on the 2008 recommendations of the American Academy of Neurology. The recommendations on therapy are pertinent to the dementia phase of AD. Recommendations are proposed for the treatment of cognitive disorders encompassing both pharmacological (including acetyl-cholinesterase inhibitors, memantine and other drugs and substances) and non-pharmacological (including cognitive rehabilitation, physical activity, occupational therapy, and music therapy) approaches. Recommendations for the treatment of behavioral and psychological symptoms of dementia due to Alzheimers disease are included in a separate article of this edition.

Esse texto apresenta as recomendações da Academia Brasileira de Neurologia, por intermédio do seu Departamento Científico de Neurologia Cognitiva e do Envelhecimento, para o tratamento da doença de Alzheimer (DA) no Brasil, enfocando os transtornos cognitivos. Trata-se de uma revisão ampliada das diretrizes publicadas em 2005, resultada de um consenso envolvendo pesquisadores da área, médicos e não médicos. Os autores realizaram uma busca de artigos publicados a partir de 2005 nas bases MEDLINE, LILACS e Cochrane Library. A busca foi direcionada para tratamento farmacológico e não farmacológico dos transtornos cognitivos da DA. Os estudos foram categorizados em quatro classes e as evidências em quatro níveis, com base nas recomendações da Academia Americana de Neurologia publicadas em 2008. As recomendações terapêuticas referem-se à fase demencial da DA. Apresentam-se recomendações para o tratamento dos transtornos cognitivos, tanto farmacológico (incluindo inibidores da acetilcolinesterase, memantina e outros fármacos e substâncias), como não farmacológico (incluindo reabilitação cognitiva, atividade física, terapia ocupacional e musicoterapia). As recomendações para o tratamento dos sintomas comportamentais e psicológicos da demência da DA são apresentadas em outro artigo desse fascículo.

The Pietà study: epidemiological investigation on successful brain aging in Caeté (MG), Brazil. Methods and baseline cohort characteristics / Estudo Pietà: investigação epidemiológica sobre envelhecimento cerebral bem sucedido em Caeté (MG), Brasil. Métodos e características de base da coorte

OBJECTIVES: To present the methods and baseline characteristics of the Pietà study, a population-based survey investigating successful brain aging in the oldest-old. METHOD: The study was conducted in Caeté (MG), Brazil. In 2007, 1,251 individuals aged 75+ years were living in the city and were invited to participate. Participants responded to a general health questionnaire and were submitted to clinical, neurological, cognitive, psychiatric and functional evaluations. A subgroup was submitted to neuropsychological testing, blood tests and magnetic resonance of the skull. Individuals were classified as having cognitive impairment-no dementia, dementia, parkinsonism, psychiatric disorders or successful brain aging. RESULTS: We evaluated 639 individuals (51.1 percent of the target population; 64 percent women), aged 81.4±5.2 years and with 2.7±2.6 years of schooling. Almost 30 percent of the elderly were illiterates and 82.1 percent belonged to middle/middle-low socioeconomic levels. Almost 50 percent were widows, but only 14.3 percent were living alone. CONCLUSION: The Pietà cohort is representative of the oldest-old Brazilian population. We believe the results of the study may contribute to increase our knowledge about healthy and pathological brain aging in the oldest-old.

OBJETIVOS: Apresentar os métodos e as características sociodemográficas do projeto Pietà, estudo de base populacional que investiga o envelhecimento cerebral bem sucedido em uma coorte de idosos muito idosos. MÉTODO: O estudo foi conduzido em Caeté (MG). Em 2007, 1.251 indivíduos com 75+ anos residiam no município e foram convidados a participar. Os idosos responderam a um questionário de saúde geral e foram submetidos à avaliação clínica, neurológica, cognitiva, psiquiátrica e funcional. Um subgrupo realizou avaliação neuropsicológica, exames laboratoriais e ressonância magnética de crânio. Os participantes foram classificados em grupos com comprometimento cognitivo-não demência, demência, parkinsonismo, transtornos psiquiátricos ou envelhecimento cerebral bem sucedido. RESULTADOS: Foram avaliados 639 idosos (51,1 por cento da população-alvo; 64 por cento mulheres), com idade 81,4±5,2 anos e escolaridade 2,7±2,6 anos. Quase 30 por cento eram analfabetos e 82,1 por cento pertenciam às classes sócio-econômicas média/média-baixa. Aproximadamente 50 por cento eram viúvos, mas somente 14,3 por cento viviam sozinhos. CONCLUSÃO: A coorte do estudo Pietà é representativa da população idosa muito idosa brasileira. Esperamos que os resultados do estudo contribuam para incrementar o conhecimento sobre envelhecimento cerebral normal e patológico em idosos muito idosos.

Tratamento da doença de Alzheimer / Alzheimer's disease Treatment

Esse texto apresenta as recomendações da Academia Brasileira de Neurologia (ABN), por intermédio do seu Departamento Científico de Neurologia Cognitiva e do Envelhecimento (DCNCE), para o tratamento da doença de Alzheimer no Brasil. Trata-se de uma revisão ampliada das recomendações publicadas em 2005. Os autores realizaram uma busca de artigos publicados a partir de 2005 nas bases MEDLINE (PubMed), LILACS e Cochrane Library. Os estudos foram categorizados em quatro classes e as evidências em quatro níveis, com base nas recomendações da Academia Americana de Neurologia publicadas em 2008. As recomendações terapêuticas referem-se à fase demencial da doença de Alzheimer. Apresentam-se recomendações para: farmacoterapia dos transtornos cognitivos, incluindo inibidores da acetilcolinesterase (IAChE), memantina e outros fármacos e substâncias; farmacoterapia dos sintomas comportamentais e psicológicos (SCPD), incluindo antipsicóticos, benzodiazepínicos, antidepressivos, anticonvulsivantes, IAChE, memantina e outros fármacos e substâncias; e tratamento não farmacológico dos transtornos cognitivos e dos SCPD.

Métodos de calibração de hidrofones / Hidrophone calibration methods

O presente trabalho consta de uma revisão minuciosa dos métodos de calibração de hodrofones, aplicáveis tanto aos do tipo agulha quanto aos de membrana. São revistos os métodos mais utilizados, absolutos e por comparação, associados às diversas técnicas de calibração e destinadas à determinação da sensibilidade do hidrofone. Os métodos descritos são: Reciprocidade, Varredura Plana, Interferometria a laser, TDS (Time Delay Spectrometry) e da Propagação Não Linear ou da Geração de Harmônicos. É apresentado um quadro comparativo descrevendo a incerteza típica e a máxima freqüência ultra-sônica inerentes a cada um dos métodos. A calibração de hidrofones com base no Método da Reciprocidade tem incerteza típica de cerca de mais ou menos 19 por cento (1,5dB) entre 0,5 e 15 MHz. Com o Método da Varredura Plana, a incerteza é de cerca de mais ou menos 6 por cento (0,5 dB) até 5 MHz, ou mais ou menos 15 por cento (1,2 dB) até 70 MHz. Para o Método TDS, as incertezas estão em torno de mais ou menos 7 por cento (0,7 dB) até 5 MHz e de mais ou menos 14 por cento (1,1 dB) até 30 MHz. Atualmente, o método interferométrico é considerado o melhor, mas não é de largo emprego devido ao seu alto custo de implementação.

Effects of galantamine on attention and memory in Alzheimer's disease measured by computerized neuropsychological tests: results of the Brazilian Multi-Center Galantamine Study (GAL-BRA-01)

OBJETIVO: Investigar os efeitos da galantamina no desempenho de pacientes portadores de doença de Alzheimer (DA) leve a moderada em uma bateria de testes neuropsicológicos computadorizados (BTNC). MÉTODO: Trinta e três pacientes com DA provável receberam tratamento com galantamina por três meses em ensaio clínico multicêntrico aberto e prospectivo. A escala BTNC e a ADAS-Cog foram administradas no início e ao final de 12 semanas. A BTNC incluiu testes de tempo de reação avaliando atenção, memória implícita e memória episódica para palavras e faces. Comparações estatísticas foram realizadas entre os resultados na 12ª semana versus a linha de base. Pacientes que não atingiram dose terapêutica foram excluídos da análise. RESULTADOS: Quatro pacientes (12,1%) foram excluídos por interrupção do tratamento (n=3) ou por não atingir dose terapêutica (n=1). Os 29 pacientes remanescentes foram tratados com doses de 24 mg/dia (n=22) e 16 mg/dia (n=7). Ao final de 12 semanas, reduções nos tempos de reação foram observadas nos testes de memória episódica para faces (p=0,023) e no teste de tempo de reação de dupla escoí lha (p=0,039) da BTNC. CONCLUSAO: O tratamento com galantamina melhorou o desempenho em testes de atenção e memória episódica, com redução estatisticamente significativa dos tempos de reação.