577 research outputs found
The role of TAU protein in the pathophysiology of frontotemporal dementia
CONTEXTO: Sob a denominação demência frontotemporal (DFT) enquadram-se importantes síndromes demenciais de natureza degenerativa progressiva que acometem os lobos frontais e temporais em ambos os hemisférios. As DFTs podem ser agrupadas, segundo seus aspectos clínicos dominantes, em variante frontal, afasia progressiva não fluente e demência semântica. A proteína Tau tem papel importante na patogenia desses transtornos, e anormalidades conformacionais estão presentes em até 50% dos casos de DFT esporádica. Do ponto de vista neuropatológico, as DFTs podem ser classificadas em Tau negativas e Tau positivas, estas últimas também classificadas entre as tauopatias. OBJETIVO: Neste trabalho será revisto o papel da proteína Tau na patogenia das DFTs. MÉTODOS: Busca simples no Scielo e na Pubmed por meio das palavras-chave: "tauopatias", "demência frontotemporal" e "proteína Tau". Foram revisados os artigos publicados a partir de 2000, e artigos anteriores de maior relevância, identificados a partir das referências estudadas. RESULTADOS: Dentre os trabalhos incluídos nesta análise, 12 abordam as tauopatias, sendo dez originais e sete de revisão. Foram identificados 20 artigos sobre DFT, sendo 16 artigos originais e quatro de revisão. CONCLUSÃO: A proteína Tau tem papel fundamental na patogenia das DFTs e outras doenças neurodegenerativas. O conhecimento desses mecanismos fisiopatológicos é o passo inicial para o desenvolvimento de estratégias terapêuticas.BACKGROUND: Frontotemporal dementia (FTD) represents an important group of neurodegenerative diseases, affecting temporal and frontal lobes of both hemispheres. FTD can be divided into three clinical subsyndromes: frontal variant, non-fluent progressive aphasia, and semantic dementia. Abnormalities of the metabolism of Tau protein are present in the physiopathology of FTD, and is found in approximately 50% of sporadic cases, supporting the classification of the FTDs into Tau-negative and Tau-positive subtypes, the latter also called "Tauopathies". OBJECTIVE: To review the role of Tau in the pathophysiology of FTD. METHODS: Review of the literature on FTD published in the Pubmed and Scielo databases since the year 2000, using the keywords: Tau, Tauopathies, frontotemporal dementia. Relevant references previously published, as indicated in the reference list of selected articles, were also included. RESULTS: Through electronic search we identified 12 articles addressing Tauopathies (ten containing original data and seven reviews), and 20 articles (16 with original data and four reviews) on FTDs. CONCLUSIONS: There is consistent evidence in the literature to support the notion that Tau protein plays a crucial role in the pathogenesis of FTDs and other neurodegenerative dementias, and the knowledge on these mechanisms is necessary for the development of more specific therapies
Papel da proteína Tau na fisiopatologia da demência frontotemporal
BACKGROUND: Frontotemporal dementia (FTD) represents an important group of neurodegenerative diseases, affecting temporal and frontal lobes of both hemispheres. FTD can be divided into three clinical subsyndromes: frontal variant, non-fluent progressive aphasia, and semantic dementia. Abnormalities of the metabolism of Tau protein are present in the physiopathology of FTD, and is found in approximately 50% of sporadic cases, supporting the classification of the FTDs into Tau-negative and Tau-positive subtypes, the latter also called "Tauopathies". OBJECTIVE: To review the role of Tau in the pathophysiology of FTD. METHODS: Review of the literature on FTD published in the Pubmed and Scielo databases since the year 2000, using the keywords: Tau, Tauopathies, frontotemporal dementia. Relevant references previously published, as indicated in the reference list of selected articles, were also included. RESULTS: Through electronic search we identified 12 articles addressing Tauopathies (ten containing original data and seven reviews), and 20 articles (16 with original data and four reviews) on FTDs. CONCLUSIONS: There is consistent evidence in the literature to support the notion that Tau protein plays a crucial role in the pathogenesis of FTDs and other neurodegenerative dementias, and the knowledge on these mechanisms is necessary for the development of more specific therapies.CONTEXTO: Sob a denominação demência frontotemporal (DFT) enquadram-se importantes síndromes demenciais de natureza degenerativa progressiva que acometem os lobos frontais e temporais em ambos os hemisférios. As DFTs podem ser agrupadas, segundo seus aspectos clínicos dominantes, em variante frontal, afasia progressiva não fluente e demência semântica. A proteína Tau tem papel importante na patogenia desses transtornos, e anormalidades conformacionais estão presentes em até 50% dos casos de DFT esporádica. Do ponto de vista neuropatológico, as DFTs podem ser classificadas em Tau negativas e Tau positivas, estas últimas também classificadas entre as tauopatias. OBJETIVO: Neste trabalho será revisto o papel da proteína Tau na patogenia das DFTs. MÉTODOS: Busca simples no Scielo e na Pubmed por meio das palavras-chave: "tauopatias", "demência frontotemporal" e "proteína Tau". Foram revisados os artigos publicados a partir de 2000, e artigos anteriores de maior relevância, identificados a partir das referências estudadas. RESULTADOS: Dentre os trabalhos incluídos nesta análise, 12 abordam as tauopatias, sendo dez originais e sete de revisão. Foram identificados 20 artigos sobre DFT, sendo 16 artigos originais e quatro de revisão. CONCLUSÃO: A proteína Tau tem papel fundamental na patogenia das DFTs e outras doenças neurodegenerativas. O conhecimento desses mecanismos fisiopatológicos é o passo inicial para o desenvolvimento de estratégias terapêuticas
Novel spectrophotometric method for the determination of azithromycin in pharmaceutical formulations based on its charge transfer reaction with quinalizarin
This paper proposes a new method for simple and fast spectrophotometric determination of azithromycin in pharmaceutical formulations. The method is based on the charge transfer reaction between the azithromycin and quinalizarin in methanol medium. In order to achieve maximum sensitivity the effect of some chemical variables such as the type of solvent, reagent concentration and reaction time were evaluated. The reaction was characterized in terms of stability of the product formed and its stoichiometry, and the apparent molar absorptivity and association constant were derived. Best conditions for the analytical determination of azithromycin were observed in methanol medium with a quinalizarin concentration of 50 mg L-1. At these conditions, the radical anion (absorbing specie) was formed in the medium immediately after mixing of the reagents and showed maximum absorption at 564 nm. The method presented a limit of detection of 0.35 mg L-1 and a limit of quantification of 1.2 mg L-1. It was successfully applied in the determination of azithromycin in three commercial pharmaceutical formulations of azithromycin and no matrix interferences were observed
Caracterização química e avaliação das atividades antibacteriana, antifúngica, antimicobacteriana e citotóxica de Talinum paniculatum
In this study, the bioactivity of Talinum paniculatum was evaluated, a plant widely used in folk medicine. The extract from the T. paniculatum leaves (LE) was obtained by percolation with ethanol-water and then subjecting it to liquid-liquid partitions, yielding hexane (HX), ethyl acetate (EtOAc), butanol (BuOH), and aqueous (Aq) fractions. Screening for antimicrobial activity of the LE and its fractions was evaluated in vitro through broth microdilution method, against thirteen pathogenic and non-pathogenic microorganisms, and the antimycobacterial activity was performed through agar diffusion assay. The cytotoxic concentrations (CC90) for LE, HX, and EtOAc were obtained on BHK-21 cells by using MTT reduction assay. The LE showed activity against Serratia marcescens and Staphylococcus aureus, with Minimum Inhibitory Concentration (MIC) values of 250 and 500 µg/mL, respectively. Furthermore, HX demonstrated outstanding activity against Micrococcus luteus and Candida albicans with a MIC of 31.2 µg/mL in both cases. The MIC for EtOAc also was 31.2 µg/mL against Escherichia coli. Conversely, BuOH and Aq were inactive against all tested microorganisms and LE proved inactive against Mycobacterium tuberculosisand Mycobacterium bovisas well. Campesterol, stigmasterol, and sitosterol were the proposed structures as main compounds present in the EF and HX/EtOAc fractions, evidenced by mass spectrometry. Therefore, LE, HX, and EtOAc from T. paniculatumshowed potential as possible sources of antimicrobial compounds, mainly HX, for presenting low toxicity on BHK-21 cells with excellent Selectivity Index (SI = CC90/MIC) of 17.72 against C. albicans.Neste estudo foi avaliada a bioatividade de Talinum paniculatum, planta amplamente utilizada na medicina popular. O extrato das folhas (EF) de T. paniculatum foi obtido por percolação com etanol-água e, em seguida, submetido à partição líquido-líquido, obtendo-se as frações hexânica (HX), acetato-etílica (AcOEt), butanólica (BuOH) e aquosa (Aq). A triagem para a atividade antimicrobiana do EF e de suas frações foram avaliadas in vitro através do método de microdiluição em caldo contra treze micro-organismos patogênicos e não-patogênicos e, a atividade antimicobacteriana, foi avaliada através do teste de difusão em ágar. As concentrações citotóxicas (CC90) do EF e das frações HX e AcOEt foram obtidas sobre células da linhagem BHK-21 através do ensaio de redução do MTT. O EF mostrou atividade contra Serratia marcescens e Staphylococcus aureus, com valores de concentração inibitória mínima (CIM) de 250 e 500 µg/mL, respectivamente. Além disso, HX demonstrou excelente atividade contra Micrococcus luteus e Candida albicans com uma CIM de 31,2 µg/mL, em ambos os casos. Contra Escherichia coli, a CIM para AcOEt foi também de 31,2 µg/mL. Por outro lado, as frações BuOH e Aq foram inativas contra todos os micro-organismos testados, assim como o EF contra Mycobacterium tuberculosis e Mycobacterium bovis. Campesterol, estigmasterol e sitosterol foram as estruturas propostas como principais compostos presentes no EF e nas frações HX e AcOEt, evidenciadas através de espectrometria de massas. Portanto, o extrato da folha e as frações HX e AcOEt provenientes de T. paniculatum apresentaram potencial como possíveis fontes de compostos antimicrobianos, HX principalmente, por ter apresentado uma baixa toxicidade sobre células BHK-21 com um bom índice de seletividade (IS = CC90/MIC) de 17,72 contra C. albicans
Effects of a multidisciplinar cognitive rehabilitation program for patients with mild Alzheimer's disease
OBJECTIVE: To evaluate the effects of a multidisciplinary rehabilitation program on cognition, quality of life, and neuropsychiatry symptoms in patients with mild Alzheimer's disease. METHOD: The present study was a single-blind, controlled study that was conducted at a university-based day-hospital memory facility. The study included 25 Alzheimer's patients and their caregivers and involved a 12-week stimulation and psychoeducational program. The comparison group consisted of 16 Alzheimer's patients in waiting lists for future intervention. INTERVENTION: Group sessions were provided by a multiprofessional team and included memory training, computer-assisted cognitive stimulation, expressive activities (painting, verbal expression, writing), physiotherapy, and physical training. Treatment was administered twice a week during 6.5-h gatherings. MEASUREMENTS: The assessment battery comprised the following tests: Mini-Mental State Examination, Short Cognitive Test, Quality of Life in Alzheimer's disease, Neuropsychiatric Inventory, and Geriatric Depression Scale. Test scores were evaluated at baseline and the end of the study by raters who were blinded to the group assignments. RESULTS: Measurements of global cognitive function and performance on attention tasks indicated that patients in the experimental group remained stable, whereas controls displayed mild but significant worsening. The intervention was associated with reduced depression symptoms for patients and caregivers and decreased neuropsychiatric symptoms in Alzheimer's subjects. The treatment was also beneficial for the patients' quality of life. CONCLUSION: This multimodal rehabilitation program was associated with cognitive stability and significant improvements in the quality of life for Alzheimer's patients. We also observed a significant decrease in depressive symptoms and caregiver burden. These results support the notion that structured nonpharmacological interventions can yield adjunct and clinically relevant benefits in dementia treatment
Prime Focus Spectrograph - Subaru's future -
The Prime Focus Spectrograph (PFS) of the Subaru Measurement of Images and
Redshifts (SuMIRe) project has been endorsed by Japanese community as one of
the main future instruments of the Subaru 8.2-meter telescope at Mauna Kea,
Hawaii. This optical/near-infrared multi-fiber spectrograph targets cosmology
with galaxy surveys, Galactic archaeology, and studies of galaxy/AGN evolution.
Taking advantage of Subaru's wide field of view, which is further extended with
the recently completed Wide Field Corrector, PFS will enable us to carry out
multi-fiber spectroscopy of 2400 targets within 1.3 degree diameter. A
microlens is attached at each fiber entrance for F-ratio transformation into a
larger one so that difficulties of spectrograph design are eased. Fibers are
accurately placed onto target positions by positioners, each of which consists
of two stages of piezo-electric rotary motors, through iterations by using
back-illuminated fiber position measurements with a wide-field metrology
camera. Fibers then carry light to a set of four identical fast-Schmidt
spectrographs with three color arms each: the wavelength ranges from 0.38
{\mu}m to 1.3 {\mu}m will be simultaneously observed with an average resolving
power of 3000. Before and during the era of extremely large telescopes, PFS
will provide the unique capability of obtaining spectra of 2400
cosmological/astrophysical targets simultaneously with an 8-10 meter class
telescope. The PFS collaboration, led by IPMU, consists of USP/LNA in Brazil,
Caltech/JPL, Princeton, & JHU in USA, LAM in France, ASIAA in Taiwan, and
NAOJ/Subaru.Comment: 13 pages, 11 figures, submitted to "Ground-based and Airborne
Instrumentation for Astronomy IV, Ian S. McLean, Suzanne K. Ramsay, Hideki
Takami, Editors, Proc. SPIE 8446 (2012)
Design of a Skipper CCD Focal Plane for the SOAR Integral Field Spectrograph
We present the development of a Skipper Charge-Coupled Device (CCD) focal
plane prototype for the SOAR Telescope Integral Field Spectrograph (SIFS). This
mosaic focal plane consists of four 6k 1k, 15 m pixel Skipper
CCDs mounted inside a vacuum dewar. We describe the process of packaging the
CCDs so that they can be easily tested, transported, and installed in a mosaic
focal plane. We characterize the performance of m thick,
fully-depleted engineering-grade Skipper CCDs in preparation for performing
similar characterization tests on science-grade Skipper CCDs which will be
thinned to 250m and backside processed with an antireflective coating. We
achieve a single-sample readout noise of for the best
performing amplifiers and sub-electron resolution (photon counting
capabilities) with readout noise from 800
measurements of the charge in each pixel. We describe the design and
construction of the Skipper CCD focal plane and provide details about the
synchronized readout electronics system that will be implemented to
simultaneously read 16 amplifiers from the four Skipper CCDs (4-amplifiers per
detector). Finally, we outline future plans for laboratory testing,
installation, commissioning, and science verification of our Skipper CCD focal
plane
Collybistin and gephyrin are novel components of the eukaryotic translation initiation factor 3 complex
<p>Abstract</p> <p>Background</p> <p>Collybistin (CB), a neuron-specific guanine nucleotide exchange factor, has been implicated in targeting gephyrin-GABA<sub>A </sub>receptors clusters to inhibitory postsynaptic sites. However, little is known about additional CB partners and functions.</p> <p>Findings</p> <p>Here, we identified the p40 subunit of the eukaryotic translation initiation factor 3 (eIF3H) as a novel binding partner of CB, documenting the interaction in yeast, non-neuronal cell lines, and the brain. In addition, we demonstrated that gephyrin also interacts with eIF3H in non-neuronal cells and forms a complex with eIF3 in the brain.</p> <p>Conclusions</p> <p>Together, our results suggest, for the first time, that CB and gephyrin associate with the translation initiation machinery, and lend further support to the previous evidence that gephyrin may act as a regulator of synaptic protein synthesis.</p
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