Influência de um programa de exercício na aptidão física pós-transplante hepático: o caso da polineuropatia amiloidótica familiar nas suas componentes composição corporal, capacidade funcional e função neuromuscular

Portugal é o país que mais transplantes hepáticos efectuou a nível mundial e o segundo com maior número de dadores por milhão de habitantes, com a região centro do país a liderar a doação de órgãos. Esta liderança na área da transplantação hepática contribui também para as elevadas taxas de sobrevivência destes doentes, suportada pela excelência técnica de uma equipa multidisciplinar diferenciada, complementada por recentes avanços terapêuticos. Portugal é, também a nível mundial, o país com maior número de casos de polineuropatia amiloidótica familiar (PAF), variante TTRmet30 (proteína transtirretina mutada) tipo português, diagnosticados, sendo em algumas regiões considerada como uma doença endémica. Apesar de novas terapêuticas em estudo (exemplo: Tafamidis), até à data o transplante hepático parece ser a única terapêutica com eficácia ao retardar ou mesmo na estabilização da evolução desta doença hereditária e degenerativa, progressiva e fatal no prazo de 10-15 anos após o início da sintomatologia.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

(-)-Hinokinin-loaded poly(d,l-lactide-co-glycolide) microparticles for Chagas disease

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Depressive symptoms and level of physical activity in patients with Alzheimer's disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Functional dependence and caregiver burden in Alzheimer's disease: a controlled trial on the benefits of motor intervention

Background: Cognitive decline has a negative impact on functional activities in Alzheimer's disease. Investigating the effects of motor intervention with the intent to reduce the decline in functionality is an expected target for patients and caregivers. The aim of this study was to verify if a 6-month motor intervention programme promoted functionality in Alzheimer's patients and attenuated caregivers' burden. Methods: The sample comprised 32 community patients with Alzheimer's disease and their 32 respective caregivers. Patients were divided into two groups: 16 participated in the motor intervention programme and 16 controls. Subjects performed 60 minutes of exercises, three times per week during the 6-month period, to improve flexibility, strength, agility and balance. Caregivers followed the procedures with their patients during this period. Functionality was evaluated by the Berg Functional Balance Scale and the Functional Independence Measure. Caregivers completed the Neuropsychiatric Inventory Caregiver Distress Scale and the Zarit Carer Burden Scale. Two-way ANOVA was used to verify the interaction between time (pre- and post-intervention) and the motor intervention program. Results: While patients in the motor programme preserved their functionality, as assessed by the Functional Independence Measure, the controls suffered a relative decline (motor intervention group: from 109.6 to 108.4 vs controls: from 99.5 to 71.6; P= 0.01). Patients from motor intervention also had better scores than the controls on functional balance assessed by Berg scale (F: 22.2; P= 0.001). As assessed by the Neuropsychiatric Inventory and Zarit scale, burden was reduced among caregivers whose patients participated in the motor intervention programme compared with caregivers whose patients did not participate in this programme (Neuropsychiatric Inventory, caregiver's part: F: 9.37; P= 0.01; Zarit: F: 11.28; P= 0.01). Conclusion: Patients from the motor intervention group showed reduced functional decline compared to the controls, and there was an associated decrease in caregivers' burden.

Gait and risk of falls associated with frontal cognitive functions at different stages of Alzheimer's disease

The decline in frontal cognitive functions contributes to alterations of gait and increases the risk of falls in patients with dementia, a category which included Alzheimer's disease (AD). The objective of the present study was to compare the gait parameters and the risk of falls among patients at different stages of AD, and to relate these variables with cognitive functions. This is a cross-sectional study with 23 patients with mild and moderate AD. The Clinical Dementia Rating was used to classify the dementia severity. The kinematic parameters of gait (cadence, stride length, and stride speed) were analyzed under two conditions: (a) single task (free gait) and (b) dual task (walking and counting down). The risk of falls was evaluated using the Timed Up-and-Go test. The frontal cognitive functions were evaluated using the Frontal Assessment Battery (FAB), the Clock Drawing Test (CDT) and the Symbol Search Subtest. The patients who were at the moderate stage suffered reduced performance in their stride length and stride speed in the single task and had made more counting errors in the dual task and still had a higher fall risk. Both the mild and the moderate patients exhibited significant decreases in stride length, stride speed and cadence in the dual task. Was detected a significant correlation between CDT, FAB, and stride speed in the dual task condition. We also found a significant correlation between subtest Similarities, FAB and cadence in the dual task condition. The dual task produced changes in the kinematic parameters of gait for the mild and moderate AD patients and the gait alterations are related to frontal cognitive functions, particularly executive functions.

Gastrointestinal cytomegalovirus disease in renal transplant recipients: A case series

The purpose of this article was to report a series of 23 renal transplant recipients with histologically proven and immunohistochemically confirmed cytomegalovirus (CMV) lesions in the gastrointestinal tract (GIT) and to assess the risk factors associated with severe disease/mortality. CMV patients (n=23) were allocated into two groups: those who died (n=6) and those considered cured (n=17). Overall mortality rate was 26% (6/23). Initial symptoms suggestive of lower GIT involvement were observed in all death cases and in 35.3% of those cured (p=0.01). Enterorrhagia was seen in 83.3% of the patients who died. Death risk increased twofold (RR 2 [1.13-3.52], p=0.01) when symptoms of lower GIT involvement were initially observed and sixfold when enterrohagia was present (RR 6 [1.1-35.9], p=0.001). Among death cases, mean time at diagnosis was significantly more distant (2002±2.9×2008±1.6, p=0.04). The difference in mortality rates seen as service practices changed along the years demonstrates the importance of early diagnosis. © 2011 John Wiley & Sons A/S.

Multimodal exercise intervention improves frontal cognitive functions and gait in Alzheimer's disease: A controlled trial

Aim: The objective of the present study was to investigate the effect of a multimodal exercise intervention on frontal cognitive functions and kinematic gait parameters in patients with Alzheimer's disease. Methods: A sample of elderly patients with Alzheimer's disease (n=27) were assigned to a training group (n=14; aged 78.0±7.3years) and a control group (n=13; aged 77.1±7.4years). Multimodal exercise intervention includes motor activities and cognitive tasks simultaneously. The participants attended a 1-h session three times a week for 16weeks, and the control participants maintained their regular daily activities during the same period. The frontal cognitive functions were evaluated using the Frontal Assessment Battery, the Clock Drawing Test and the Symbol Search Subtest. The kinematic parameters of gait-cadence, stride length and stride speed were analyzed under two conditions: (i) free gait (single task); and (ii) gait with frontal cognitive task (walking and counting down from 20 - dual task). Results and discussion: The patients in the intervention group significantly increased the scores in frontal cognitive variables, Frontal Assessment Battery (P<0.001) and Symbol Search Subtest (P<0.001) after the 16-week period. The control group decreased the scores in the Clock Drawing Test (P=0.001) and increased the number of counting errors during the dual task (P=0.008) after the same period. Conclusion: The multimodal exercise intervention improved the frontal cognitive functions in patients with Alzheimer's disease. © 2012 Japan Geriatrics Society.

Epidemiological Report on the Treatment of Patients with Gestational Trophoblastic Disease in 10 Brazilian Referral Centers Results After 12 Years Since International FIGO 2000 Consensus

OBJECTIVE: To evaluate treatment of Brazilian patients with gestational trophoblastic disease (GTD).STUDY DESIGN: A retrospective cohort study with analysis of medical reports performed in 10 Brazilian referral centers from January 2000 to December 2011.RESULTS: Of 5,250 patients 3 died (0.06%) at the time of uterine evacuation. Spontaneous remission of GTD (group G1) was observed in 4,103 cases, and 1,144 (21.8%) progressed to gestational trophoblastic neoplasia (GTN) (G2). In G1 2,716 (66.2%) had complete hydatidiform mole (HM) and 1,210, partial HM (29.5%); 3,772 patients (92.7%) recovered as noted in December 2012. In G2, of 1,118 patients treated, initial histopathological results of previous gestation were complete HM (77.5% [n = 886]), partial HM (8.8% [n = 100]), and choriocarcinoma (8.0% [n = 92]); 930 (81.3%) were low-risk, 200 (17.5%) were high-risk GTN, and 14 had placental site trophoblastic tumor (PSTT) (1.2%); cure was achieved in 1,078 cases (96.4%), but 26 patients (2.3%) died (4 low-risk [0.4%], 19 high-risk [9.5%], and 3 PSTT [21.4%]).CONCLUSION: The highest death rates were due to high-risk GTN and PSTT. Patients with molar pregnancy should be referred to a referral center for an early diagnosis and prompt treatment of GTN in order to reduce the morbidity and mortality found in advanced stages.

Evaluation of the Host Response in Various Models of Induced Periodontal Disease in Mice

Background: The aim of this study is to characterize and evaluate the host response caused by three different models of experimental periodontitis in mice.Methods: C57BL/6 wild-type female mice were distributed into six experimental groups and sacrificed at 7, 15, and 30 days after the induction of periodontal disease: 1) group C: no treatment control group; 2) group L: periodontal disease induced by ligature; 3) group G-Pg: oral gavage with Porphyromonas gingivalis (Pg); 4) group G-PgFn: oral gavage with Fusobacterium nucleatum + Pg; 5) group I-Pg: heat-killed Pg injected into the palatal mucosa between the molars; and 6) group I-V: phosphatebuffered saline injected into the palatal mucosa. The samples were used to analyze the immune-inflammatory process in the gingival tissue via descriptive histologic and real-time polymerase chain reaction analyses. The alveolar bone loss was evaluated using microcomputed tomography. The data were analyzed using the Kruskal-Wallis test, followed by a post hoc Dunn test and analysis of variance, followed by a Tukey test using a 5% significance level.Results: Only the ligature model displayed significant alveolar bone loss in the initial period (7 days), which was maintained with time. The group injected with heat-killed Pg displayed significant alveolar bone loss starting from day 15, which continued to progress with time (P < 0.05). A significant increase (P < 0.05) in the gene expression of proinflammatory cytokines (interleukin-6 and -1b) and proteins involved in osteoclastogenesis (receptor activator of nuclear factor-kB ligand and osteoprotegerin) was observed in the ligature group on day 7.Conclusion: The ligature and injection of heat-killed Pg models were the most representative of periodontal disease in humans, whereas the oral gavage models were not effective at inducing the disease under the experimental conditions.

The influence of citrus rootstocks on the relationship between the mite Brevipalpus phoenicis and citrus leprosis disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Benefits of Multimodal Exercise Intervention for Postural Control and Frontal Cognitive Functions in Individuals with Alzheimer's Disease: A Controlled Trial

Objective To verify the effects of a systematized multimodal exercise intervention program on frontal cognitive function, postural control, and functional capacity components of individuals with Alzheimer's disease (AD).DesignNonrandomized controlled trial with pre- and posttraining tests in a training group and a control group.SettingKinesiotherapy program for seniors with AD, SAo Paulo State University.ParticipantsConvenience sample of older adults with AD (n=30) were assigned to a training (n=14; aged 78.67.1) and a control (n=16; aged 77.06.3) group.InterventionThe intervention program was structured with the aim of simultaneously promoting better balance and frontal cognitive capacity. The participants attended a 1-hour session three times a week for 16weeks, whereas the control group did not participate in any activity during the same period.MeasurementsFrontal cognitive function was evaluated using the Montreal Cognitive Assessment, the Clock Drawing Test, the Frontal Assessment Battery, and the Symbol Search Subtest. Postural control (center of pressure area) was analyzed under four dual-task conditions. Functional capacity components were analyzed using the Timed Up and Go Test, the 30-second sit-to-stand test, the sit-and-reach test, and the Berg Functional Balance Scale.ResultsIntervention group participants showed a significant increase in frontal cognitive function (P<.001, partial (2)=0.838), with less body sway (P=.04, partial (2)=0.04) during the dual tasks, and greater functional capacity (P=.001, partial (2)=0.676) after the 16-week period.ConclusionIntervention participants performed better on dual-task activities and had better postural balance and greater functional capacity than controls.

Neurobiological Correlates of Apathy in Alzheimer's Disease and Mild Cognitive Impairment: A Critical Review

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Frequency and clinical predictors of coronary artery disease in chronic renal failure renal transplant candidates

Background/aims: Cardiovascular diseases are major causes of mortality in chronic renal failure patients before and after renal transplantation. Among them, coronary disease presents a particular risk; however, risk predictors have been used to diagnose coronary heart disease. This study evaluated the frequency and importance of clinical predictors of coronary artery disease in chronic renal failure patients undergoing dialysis who were renal transplant candidates, and assessed a previously developed scoring system. Methods: Coronary angiographies conducted between March 2008 and April 2013 from 99 candidates for renal transplantation from two transplant centers in Sao Paulo state were analyzed for associations between significant coronary artery diseases (>= 70% stenosis in one or more epicardial coronary arteries or >= 50% in the left main coronary artery) and clinical parameters. Results: Univariate logistic regression analysis identified diabetes, angina, and/or previous infarction, clinical peripheral arterial disease and dyslipidemia as predictors of coronary artery disease. Multiple logistic regression analysis identified only diabetes and angina and/or previous infarction as independent predictors. Conclusion: The results corroborate previous studies demonstrating the importance of these factors when selecting patients for coronary angiography in clinical pretransplant evaluation.