298 research outputs found

    Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition

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    BACKGROUND: The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease. METHODS: We have examined microglial MHC class II expression, a widely used marker of microglial activation, the occurrence of CD68-positive phagocytes and alpha-synuclein immunoreactivity in post-mortem human substantia nigra affected by idiopathic Parkinson's disease (PD). Using semi-quantitative severity ratings, we have examined the relationship between microglial activation, alpha-synuclein deposition, classical neuropathological criteria for PD, subtype of the disease and clinical course. RESULTS: While we did not observe an association between microglial MHC class II expression and clinical parameters, we did find a correlation between disease duration and the macrophage marker CD68 which is expressed by phagocytic microglia. In addition, we observed a significant correlation between the degree of MHC class II expression and alpha-synuclein deposition in the substantia nigra in PD. CONCLUSION: While microglia appeared to respond to alpha-synuclein deposition, MHC class II antigen expression by microglia in the substantia nigra cannot be used as an indicator of clinical PD severity or disease progression. In addition, a contributory or even causative role for microglia in the neuronal loss associated with PD as suggested by some authors seems unlikely. Our data further suggest that an assessment of microglial activation in the aged brain on the basis of immunohistochemistry for MHC class II antigens alone should be done with caution

    Biocompatible polymeric microparticles produced by a simple biomimetic approach

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    The use of superhydrophobic surfaces to produce polymeric particles proves to be biologically friendly since it entails the pipetting and subsequent cross-linking of polymeric solutions under mild experimental conditions. Moreover, it renders encapsulation efficiencies of ∼100%. However, the obtained particles are 1 to 2 mm in size, hindering to a large extent their application in clinical trials. Improving on this technique, we propose the fabrication of polymeric microparticles by spraying a hydrogel precursor over superhydrophobic surfaces followed by photo-cross-linking. The particles were produced from methacrylamide chitosan (MA-CH) and characterized in terms of their size and morphology. As demonstrated by optical and fluorescence microscopy, spraying followed by photo-cross-linking led, for the first time, to the production of spherical particles with diameters on the order of micrometers, nominal sizes not attainable by pipetting. Particles such as these are suitable for medical applications such as drug delivery and tissue engineering.We thank Ivo Aroso and Ana Isabel Neto for their valuable support with FTIR and compression experiments, respectively. A.M.S.C. thanks FCT for financial support through grant BIM/PTDC/CTM-BPC/112774/2009_02. M.A.-M. thanks CONACyT (Mexico) for financial support through post-doc grant no. 203732. N.M.O. thanks FCT for financial support through Ph.D. scholarship no. SFRH/BD/73172/2010. This work was funded by the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. REGPOT-CT2012-316331-POLARIS, by FEDER through the Competitive Factors Operation Program-COMPETE, and by national funds through FCT - Fundacao para a Ciencia e a Tecnologia in the scope of project PTDC/CTM-BIO/1814/2012

    Supramolecular thermoplastics and thermoplastic elastomer materials with self-healing ability based on oligomeric charged triblock copolymers

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    Supramolecular polymeric materials constitute a unique class of materials held together by non-covalent interactions. These dynamic supramolecular interactions can provide unique properties such as a strong decrease in viscosity upon relatively mild heating, as well as self-healing ability. In this study we demonstrate the unique mechanical properties of phase-separated electrostatic supramolecular materials based on mixing of low molar mass, oligomeric, ABA-triblock copolyacrylates with oppositely charged outer blocks. In case of well-chosen mixtures and block lengths, the charged blocks are phase separated from the uncharged matrix in a hexagonally packed nanomorphology as observed by transmission electron microscopy. Thermal and mechanical analysis of the material shows that the charged sections have a T-g closely beyond room temperature, whereas the material shows an elastic response at temperatures far above this T-g ascribed to the electrostatic supramolecular interactions. A broad set of materials having systematic variations in triblock copolymer structures was used to provide insights in the mechanical properties and and self-healing ability in correlation with the nanomorphology of the materials

    Fitness efficacy of vibratory exercise compared to walking in postmenopausal women

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    In this study, we compared the efficacy of 8 months of low-frequency vibration and a walk-based program in health-related fitness. Twenty-seven postmenopausal women were randomly assigned into two groups: whole-body vibration (WBV) group (n = 18) performed three times/week a static exercise on a vibration platform (6 sets of 1-min with 1 min of rest, with a 12.6 Hz of frequency and an amplitude of 3 mm); walk-based program (WP) group (n = 18) performed three times/week a 60-min of walk activity at 70-75% of maximal heart rate. A health-related battery of tests was applied. Maximal unilateral concentric and eccentric isokinetic torque of the knee extensors was recorded by an isokinetic dynamometer. Physical fitness was measured using the following tests: vertical jump test, chair rise test and maximal walking speed test over 4 m. Maximal unilateral isokinetic strength was measured in the knee extensors in concentric actions at 60 and 300 degrees /s, and eccentric action at 60 degrees /s. After 8 months, the WP improved the time spent to walk 4 m (20%) and to perform the chair rise test (12%) compared to the WBV group (P = 0.006, 0.002, respectively). In contrast, the comparison of the changes in vertical jump showed the higher effectiveness of the vibratory exercise in 7% (P = 0.025). None of exercise programs showed change on isokinetic measurements. These results indicate that both programs differed in the main achievements and could be complementary to prevent lower limbs muscle strength decrease as we age [ISRCTN76235671]

    Bioactivity, biocompatibility and antimicrobial properties of a chitosan-mineral composite for periodontal tissue regeneration

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    A composite membrane of the polymer, chitosan, and the silver-exchanged mineral phase, tobermorite, was prepared by solvent casting and characterised by scanning electron microscopy and Fourier transform infrared spectroscopy. The in vitro bioactivity, cytocompatibility and antimicrobial activity of the composite were evaluated with respect to its potential application as a guided tissue regeneration (GTR) membrane. The in vitro bioactivity was verified by the formation of hydroxyapatite on the surface of the membrane in simulated body fluid and its cytocompatibility was established using MG63 human osteosarcoma cells. The presence of silver ions conferred significant antimicrobial activity against S. aureus, P. aeruginosa and E. coli. The findings of this investigation have indicated that the chitosansilver-tobermorite composite is a prospective candidate for GTR applications

    Activation of store-operated calcium entry in airway smooth muscle cells: insight from a mathematical model

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    Intracellular dynamics of airway smooth muscle cells (ASMC) mediate ASMC contraction and proliferation, and thus play a key role in airway hyper-responsiveness (AHR) and remodelling in asthma. We evaluate the importance of store-operated entry (SOCE) in these dynamics by constructing a mathematical model of ASMC signaling based on experimental data from lung slices. The model confirms that SOCE is elicited upon sufficient depletion of the sarcoplasmic reticulum (SR), while receptor-operated entry (ROCE) is inhibited in such conditions. It also shows that SOCE can sustain agonist-induced oscillations in the absence of other influx. SOCE up-regulation may thus contribute to AHR by increasing the oscillation frequency that in turn regulates ASMC contraction. The model also provides an explanation for the failure of the SERCA pump blocker CPA to clamp the cytosolic of ASMC in lung slices, by showing that CPA is unable to maintain the SR empty of . This prediction is confirmed by experimental data from mouse lung slices, and strongly suggests that CPA only partially inhibits SERCA in ASMC

    Fast-growing pancreatic neuroendocrine carcinoma in a patient with multiple endocrine neoplasia type 1: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Predictive genetic screening and regular screening programs in patients with multiple endocrine neoplasia type 1 are intended to detect and treat malignant tumors at the earliest stage possible. Malignant neuroendocrine pancreatic tumors are the most frequent cause of death in these patients. However, the extent and intervals of screening in patients with multiple endocrine neoplasia type 1 are controversial as neuroendocrine tumors are usually slow growing. Here we report the case of a patient who developed a fast-growing neuroendocrine carcinoma within 15 months of a laparoscopic distal pancreatic resection.</p> <p>Case presentation</p> <p>We followed a group of 45 patients with multiple endocrine neoplasia type 1 by an annual screening program in the Department of Visceral, Thoracic, and Vascular Surgery at the University Hospital Marburg in cooperation with the Department of Radiology and the Division of Endocrinology. A man with multiple endocrine neoplasia type 1 who was diagnosed with a recurrent primary hyperparathyroidism underwent a distal pancreatic resection for a non-functional neuroendocrine tumor. In the context of our regular screening program, a large non-functional neuroendocrine tumor was diagnosed in the pancreatic head 15 months after the first pancreatic surgery. Therefore, we performed an enucleation and regional lymph node resection. At histology, the diagnosis of a neuroendocrine carcinoma with one lymph node metastasis was established. There was no evidence of recurrence 9 months after re-operation.</p> <p>Conclusion</p> <p>Fast-growing neuroendocrine tumors are rare in patients with multiple endocrine neoplasia type 1. The intervals, both postoperative and in newly diagnosed pancreatic lesions, in patients with multiple endocrine neoplasia type 1 should be reduced to 6 months to establish the early diagnosis of rapidly progressive disease in a small subset of patients.</p

    Sex differences in shoulder performance fatiguability are affected by arm position, dominance and muscle group

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    Background: Injury prevalence data, muscle strength, and fatiguability differ between males and females. In addition, arm spatial orientation affects muscle activation and strength of the shoulder muscles. Nevertheless, little research has been conducted in relation to the shoulder rotator muscles comparing men and women. Therefore, the main aim of of this study was to perform a comparative investigation between two arm spatial orientations (45° and 90° of abduction in the frontal plane) during a fatigue assessment of the internal rotator (IR) and external rotator (ER) shoulder muscles. Secondly, the interaction between sex and dominance with muscular performance was assessed. Methods: Forty healthy sedentary participants, 20 males and 20 females took part in this study. Participants performed a fatigue resistance protocol consisting of 30 consecutive maximal concentric contractions of the IR and ER shoulder muscles in a supine position at a speed of 180°/s. The upper limb was abducted to an angle of 45° or 90° in the frontal plane and each participant was tested on the dominant and nom-dominant side, counterbalanced in order of administration. Performance measures of Induced Fatigue (IF; %), Cumulated Performance (C.Perf; J) and Best Repetition (BR; J) were calculated and used for analysis. IF represents the % difference between the amount of work done over the last 3 and first 3 repetitions, BR represents the largest amount of work done during a single contraction, and C.Perf represents the total amount of work done during all repetitions. Results: Muscle group was the only factor to display significant variation when not considering other factors, with higher values for C.Perf (mean difference = 353.59 J, P < 0.0005), BR (mean difference = 14.21 J, P < 0.0005) and IF (mean difference = 3.65%, P = 0.0046). There was a significant difference between both angles, with higher values observed at 90° compared to 45° of abduction for C.Perf by ~ 7.5% (mean difference = 75 to 152 J) and ~ 10.8% (mean difference = 5.1 to 9.4 J) for BR in the ER, in males and females respectively (P < 0.0005). The dominant arm was significantly stronger than the non-dominant arm for C.Perf by 11.7% (mean difference = 111.58 J) for males and by 18% (mean difference = 82.77 J) for females in the ER at 45° abduction. At 90° abduction, only females were stronger in the dominant arm by 18.8% (mean difference = 88.17 J). Values for BR ranged from 9.2 to 21.8% depending on the abduction angle and sex of the athlete (mean difference = 2.44 – 4.85 J). Males were significantly stronger than females by 48.8 to 50.7% for values of C.Perf and BR in both the IR and ER (P < 0.0005). There was a significant difference between the ER and IR muscles, with significantly higher values observed for the IR in C.Perf (mean difference = 331.74 J) by 30.0% and in BR (mean difference = 13.31 J) by 26.64%. Discussion: Differences in shoulder performance fatiguability between sexes are affected by arm position, arm dominance and muscle groups. In agreement with the literature, performance values in males were approximately 50% higher than in females. However, the amount of IF was no different between both sexes. Based on findings in literature, it could be suggested that this is due to differences between males and females in motor control and/or coordination strategies during repetitive tasks. In addition, we also observed the IR muscles to be significantly stronger than the ER muscles. It has long been established in literature that these observations are due to the muscle-size differences between both muscle groups, where the IR muscles can produce a larger amount of force due to the larger cross-sectional area. Results of our study found similar ER:IR ratios compared to previous reports. Conclusion: Therefore, these findings are useful for clinicians when monitoring rehabilitation programs in sedentary individuals following shoulder injuries
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