RESUMO
Dexamethasone is a potent and widely used anti-inflammatory and immunosuppressive drug. However, recent evidences suggest that dexamethasone cause pathologic cardiac remodeling, which later impairs cardiac function. The mechanism behind the cardiotoxic effect of dexamethasone is elusive. The present study aimed to verify if dexamethasone-induced cardiotoxicity would be associated with changes in the cardiac net balance of calcium handling protein and calcineurin signaling pathway activation. Wistar rats (~400 g) were treated with dexamethasone (35 µg/g) in drinking water for 15 days. After dexamethasone treatment, we analyzed cardiac function, cardiomyocyte diameter, cardiac fibrosis, and the expression of proteins involved in calcium handling and calcineurin signaling pathway. Dexamethasone-treated rats showed several cardiovascular abnormalities, including elevated blood pressure, diastolic dysfunction, cardiac fibrosis, and cardiomyocyte apoptosis. Regarding the expression of proteins involved in calcium handling, dexamethasone increased phosphorylation of phospholamban at threonine 17, reduced protein levels of Na+/Ca2+ exchanger, and had no effect on protein expression of Serca2a. Protein levels of NFAT and GATA-4 were increased in both cytoplasmic and nuclear faction. In addition, dexamethasone increased nuclear protein levels of calcineurin. Altogether our findings suggest that dexamethasone causes pathologic cardiac remodeling and diastolic dysfunction, which is associated with impaired calcium handling and calcineurin signaling pathway activation.
Assuntos
Calcineurina/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Cardiomegalia/metabolismo , Dexametasona/efeitos adversos , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Dexametasona/farmacologia , Masculino , Miocárdio/patologia , Miócitos Cardíacos/patologia , Ratos , Ratos WistarRESUMO
Leucine supplementation potentiates the effects of aerobic exercise training (AET) on skeletal muscle; however, its potential effects associated with AET on cardiac muscle have not been clarified yet. We tested whether leucine supplementation would potentiate the anti-cardiac remodeling effect of AET in a genetic model of sympathetic hyperactivity-induced heart failure in mice (α2A/α2CARKO). Mice were assigned to five groups: wild type mice treated with placebo and sedentary (WT, n = 11), α2A/α2CARKO treated with placebo and sedentary (KO, n = 9), α2A/α2CARKO treated with leucine and sedentary (KOL, n = 11), α2A/α2CARKO treated with placebo and AET (KOT, n = 12) or α2A/α2CARKO treated with leucine and AET (KOLT, n = 12). AET consisted of four weeks on a treadmill with 60 min sessions (six days/week, 60% of maximal speed) and administration by gavage of leucine (1.35 g/kg/day) or placebo (distilled water). The AET significantly improved exercise capacity, fractional shortening and re-established cardiomyocytes' diameter and collagen fraction in KOT. Additionally, AET significantly prevented the proteasome hyperactivity, increased misfolded proteins and HSP27 expression. Isolated leucine supplementation displayed no effect on cardiac function and structure (KOL), however, when associated with AET (KOLT), it increased exercise tolerance to a higher degree than isolated AET (KOT) despite no additional effects on AET induced anti-cardiac remodeling. Our results provide evidence for the modest impact of leucine supplementation on cardiac structure and function in exercised heart failure mice. Leucine supplementation potentiated AET effects on exercise tolerance, which might be related to its recognized impact on skeletal muscle.
Assuntos
Suplementos Nutricionais , Tolerância ao Exercício/efeitos dos fármacos , Insuficiência Cardíaca/patologia , Coração/efeitos dos fármacos , Leucina/farmacologia , Miocárdio/patologia , Condicionamento Físico Animal/fisiologia , Animais , Colágeno/metabolismo , Teste de Esforço , Proteínas de Choque Térmico HSP27/metabolismo , Coração/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Leucina/uso terapêutico , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/efeitos dos fármacos , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Dobramento de Proteína/efeitos dos fármacos , Sistema Nervoso SimpáticoRESUMO
In addition to hypertension, dyslipidemia, atherosclerosis, and diabetes, a sedentary lifestyle plays a pivotal role in cerebro- and cardiovascular disease and progressive cognitive decline, including vascular dementia and Alzheimer's disease. The present study investigated whether controlling the key risks and participating in physical activity have a beneficial impact on these disorders. Elderly volunteers were enrolled in a 3-month program that consisted of structured exercise three times per week. The daily routine, medical treatment, and vital parameters were evaluated and correlated with the subjects' neuropsychiatric status. High blood pressure was found in 40% of the participants, with no significant differences between the sexes. A higher proportion of females (55%) than males (18%) forgot to take their medication during the observation period. Significant negative correlations were found between Mini-Mental State Examination (MMSE) scores and age, lack of a caregiver, and increased pulse rate before or after exercise. These results suggest that the presence of home assistance and subsequent improvement in medication compliance, vital parameter optimization, and regular physical activity may yield better MMSE results and a lower risk for cerebro- and cardiovascular disease.
Assuntos
Anti-Hipertensivos/uso terapêutico , Exercício Físico/fisiologia , Hipertensão/fisiopatologia , Hipertensão/terapia , Adesão à Medicação/psicologia , Idoso , Envelhecimento , Estudos Transversais , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Pulso Arterial , Medição de Risco , Fatores de Risco , Comportamento Sedentário , Inquéritos e Questionários , Resultado do TratamentoRESUMO
INTRODUÇÃO: Recentes evidências indicam que a suplementação de creatina (Cr) é capaz de aumentar a densidade mineral óssea (DMO) no fêmur de ratos saudáveis em crescimento. Entretanto, há poucos estudos que testam a efetividade da suplementação desse nutriente em condições de perda óssea. OBJETIVO: Investigar o efeito da suplementação de Cr na DMO e no conteúdo mineral ósseo (CMO) de ratos espontaneamente hipertensos (SHR), um modelo experimental de baixa massa óssea. MATERIAIS E MÉTODOS: Dezesseis ratos SHR machos com 8 meses de idade foram randomizados em dois grupos experimentais pareados pelo peso corporal, a saber: 1) Pl: SHR tratados com placebo (água destilada; n = 8); e 2) Cr: SHR tratados com Cr (n = 8). Após nove semanas de suplementação os animais foram eutanasiados e o fêmur e a coluna vertebral (L1-L4) foram analisados por densitometria óssea (Dual Energy X-Ray Absorptiometry). RESULTADOS: Não houve diferença significativa na DMO (Pl = 0,249 ± 0,003 g/cm² vs. Cr = 0,249 ± 0,004 g/cm²; P = 0,95) e no CMO (Pl = 0,509 ± 0,150 g vs. Cr = 0,509 ± 0,017 g; P = 0,99) da coluna vertebral e na DMO (Pl = 0,210 ± 0,004 g/cm² vs. Cr = 0,206 ± 0,004 g/cm2;P = 0,49) e no CMO (Pl = 0,407 ± 0,021 g vs. Cr = 0,385 ± 0,021 g; P = 0,46) do fêmur total entre os grupos experimentais. CONCLUSÃO: Neste estudo, usando um modelo experimental de baixa massa óssea, a suplementação de Cr não afetou a massa óssea.
INTRODUCTION: Recent evidence has suggested that creatine supplementation (Cr) can increase the bone mineral density (BMD) of the femur in healthy growing rats. Nevertheless, studies assessing the efficacy of the Cr supplementation in conditions characterized by bone mass loss are scarce. OBJECTIVE: To investigate the effect of Cr supplementation on BMD and bone mineral content (BMC) in spontaneously hypertensive rats (SHRs), an experimental model of osteoporosis. MATERIALS AND METHODS: Sixteen 8-month-old male SHRs were randomly allocated into two groups matched by body weight: 1) Pl group: SHRs treated with placebo (distilled water; n = 8); and 2) Cr group: SHRs treated with Cr (n = 8). After nine weeks of supplementation, the animals were euthanized and their femur and spine (L1-L4) were analyzed by use of densitometry (Dual Energy X-Ray Absorptiometry). RESULTS: No significant difference was observed between the groups regarding either the spine or the total femur measures as follows: spine - BMD (Pl = 0.249 ± 0.003 g/cm² vs. Cr = 0.249 ± 0.004 g/cm²; P = 0.95) and BMC (Pl = 0.509 ± 0.150 g vs. Cr = 0.509 ± 0.017 g; P > 0.99); and total femur - BMD (Pl = 0.210 ± 0.004 g/cm² vs. Cr = 0.206 ± 0.004 g/cm²; P > 0.49) and BMC (Pl = 0.407 ± 0.021 g vs. Cr = 0.385 ± 0.021 g; P > 0.46). CONCLUSION: In this study, using the experimental model of osteoporosis, Cr supplementation had no effect on bone mass.
Assuntos
Animais , Masculino , Ratos , Densidade Óssea/efeitos dos fármacos , Creatina/farmacologia , Ratos Endogâmicos SHRRESUMO
INTRODUCTION: Recent evidence has suggested that creatine supplementation (Cr) can increase the bone mineral density (BMD) of the femur in healthy growing rats. Nevertheless, studies assessing the efficacy of the Cr supplementation in conditions characterized by bone mass loss are scarce. OBJECTIVE: To investigate the effect of Cr supplementation on BMD and bone mineral content (BMC) in spontaneously hypertensive rats (SHRs), an experimental model of osteoporosis. MATERIALS AND METHODS: Sixteen 8-month-old male SHRs were randomly allocated into two groups matched by body weight: 1) Pl group: SHRs treated with placebo (distilled water; n = 8); and 2) Cr group: SHRs treated with Cr (n = 8). After nine weeks of supplementation, the animals were euthanized and their femur and spine (L1-L4) were analyzed by use of densitometry (Dual Energy X-Ray Absorptiometry). RESULTS: No significant difference was observed between the groups regarding either the spine or the total femur measures as follows: spine - BMD (Pl = 0.249 ± 0.003 g/cm² vs. Cr = 0.249 ± 0.004 g/cm²; P = 0.95) and BMC (Pl = 0.509 ± 0.150 g vs. Cr = 0.509 ± 0.017 g; P > 0.99); and total femur - BMD (Pl = 0.210 ± 0.004 g/cm² vs. Cr = 0.206 ± 0.004 g/cm²; P > 0.49) and BMC (Pl = 0.407 ± 0.021 g vs. Cr = 0.385 ± 0.021 g; P > 0.46). CONCLUSION: In this study, using the experimental model of osteoporosis, Cr supplementation had no effect on bone mass.
Assuntos
Densidade Óssea/efeitos dos fármacos , Creatina/farmacologia , Animais , Masculino , Ratos , Ratos Endogâmicos SHRRESUMO
We aimed to investigate the possible role of creatine (CR) supplementation in counteracting dexamethasone-induced muscle wasting and insulin resistance in rats. Also, we examined whether CR intake would modulate molecular pathways involved in muscle remodeling and insulin signaling. Animals were randomly divided into four groups: (1) dexamethasone (DEX); (2) control pair-fed (CON-PF); (3) dexamethasone plus CR (DEX-CR); and (4) CR pair-fed (CR-PF). Dexamethasone (5 mg/kg/day) and CR (5 g/kg/day) were given via drinking water for 7 days. Plantaris and extensor digitorum longus (EDL) muscles were removed for analysis. Plantaris and EDL muscle mass were significantly reduced in the DEX-CR and DEX groups when compared with the CON-PF and CR-PF groups (P<0.05). Dexamethasone significantly decreased phospho-Ser473-Akt protein levels compared to the CON-PF group (P<0.05) and CR supplementation aggravated this response (P<0.001). Serum glucose was significantly increased in the DEX group when compared with the CON-PF group (DEX 7.8±0.6 vs. CON-PF 5.2±0.5 mmol/l; P<0.05). CR supplementation significantly exacerbated hyperglycemia in the dexamethasone-treated animals (DEX-CR 15.1±2.4 mmol/l; P<0.05 vs. others). Dexamethasone reduced GLUT-4 translocation when compared with the CON-PF and CR-PF (P<0.05) groups and this response was aggravated by CR supplementation (P<0.05 vs. others). In conclusion, supplementation with CR resulted in increased insulin resistance and did not attenuate muscle wasting in rats treated with dexamethasone. Given the contrast with the results of human studies that have shown benefits of CR supplementation on muscle atrophy and insulin sensitivity, we suggest caution when extrapolating this animal data to human subjects.
Assuntos
Creatina/administração & dosagem , Dexametasona/administração & dosagem , Resistência à Insulina , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/metabolismo , Animais , Glicemia/efeitos dos fármacos , Água Potável , Transportador de Glucose Tipo 4/metabolismo , Humanos , Masculino , Músculo Esquelético/metabolismo , Atrofia Muscular/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , RatosRESUMO
Considerando a importância do procedimento de cimentação adesiva para as restaurações indiretas, o propósito desse estudo foi analisar o tipo de falha ocorrida sob diferentes tratamentos de superfície e após ensaio de microtração entre dois substratos (zircônia Y-TZP e resina composta). Assim, 16 blocos (12mm X 12mm X 4mm) de uma zircônia completamente sinterizada foram polidos e divididos em 04 grupos de acordo com o tratamento de superfície a ser realizado sobre a zircônia: jateamento (G1), jateamento + primer universal (G2), primer universal (G3), e NaOH + primer universal (G4), previamente ao procedimento de cimentação. Os blocos de zircô-nia foram cimentados aos blocos de resina composta (12mm X 12mm X 4mm) previamente confeccionados e fotopolimerizados para em seguida serem cortados sob abundante refrigeração a fim de produzir secções de 0,8mm X 0,8mm X 8mm. Os palitos obtidos foram ensaiados em máquina universal de ensaios para detectar o tipo de falha ocorrida, que foi classificada em adesiva, coesiva ou mista. Os resultados evidenciaram uma maior percentagem de falhas mistas para os grupos G2 e G4 (65,2% e 67,3%, respectivamente), enquanto que o G3 apresentou maior percentagem de falhas adesivas (75,6%). Concluiu-se que o tratamento de superfície com jateamento com óxido de alumínio sobre a superfície da zircônia (G1) não é recomendado para a zircônia do tipo Y-TZP
Considering the importance of the adhesive cementation procedure for indirect restoration, the aim of this study was to analyze the failure kind met under different surface treatment and after microtensile test between two substrates (zirconia Y-TZP and resin composite). In this way, 16 blocks (12mm X 12mm X 4mm) of a zirconia completely sintering were polished and divided into 04 groups according to the surface treatment to be executed over the zirconia: sandblast (G1); sandblast + universal primer (G2); universal primer (G3); NaOH + universal primer (G4), previously to the cementation procedure. The zirconia blocks were cemented into the resin composite blocks (12mm X 12mm X 4mm) previously done and photopolimerized, to be in the sequence cut under copious refrigeration to produce sections of approximately 0.8mm x 0.8mm X 0.8mm. These obtained sticks were tested in a universal machine to detect the kind of failure, which was classified in adhesive, cohesive or mix. The results showed a higher percentage of mix failure to the group G2 and G4 (65.2% e 67.3%, respectively), while the group G3 showed a higher percentage of adhesive failure (75.6%). It was concluded that the sandblast treatment surface with aluminum oxide over the zirconia surface wasnt recommended to the Y-TZP zirconia
Assuntos
Adesivos Dentinários/efeitos adversos , Cerâmica , Cimentação/métodos , Colagem Dentária , Adesivos Dentinários , Teste de Materiais , Resinas Compostas/químicaRESUMO
Abstract: Alzheimers disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline, including memory loss, behavioral and psychological symptoms and personality changes. The neuropathological hallmarks of AD are the presence of neuritic (senile) plaques (NP) and neurofibrillary tangles (NFT), along with neuronal loss, dystrophic neurites, and gliosis. Neuritic plaques are extracellular lesions and their main constituent is the amyloid-beta42 peptide (A- beta42). Neurofibrillary tangles are intracellular lesions that are mainly composed of hyperphosphorylated ta u protein. In this article, we review the major hypotheses concerning the physiopathology of AD, focusing on the beta-amyloid cascade as primary events (supported by the "beta-aptists") and cytoskeletal abnormalities secondary to the hyperphosphorylation of protein Tau (as advocated by the "Tauists"). We further provide an integrative view of the physiopathology of AD.
Resumo: A doença de Alzheimer (DA) é uma desordem neurodegenerativa progressiva que cursa comprometimento da memória e outras funções cognitivas, alterações comportamentais, psíquicas e da personalidade. Os achados neuropatológicos característicos da DA são as placas neuríticas (senis) e os emaranhados neurofibrilares, também ocorrendo distrofia de neuritos, gliose e perda neuronal. As placas neuríticas são lesões extracelulares que têm no peptídeo beta-amilóide (A beta42) seu principal constituinte. Os emaranhados neurofibrilares são lesões intraneuronais compostas por agregados de proteína TAU em estado hiperfosforilado. Neste artigo de revisão, apresentamos as principais hipóteses relacionadas à fisiopatologia da DA, com foco na cascata do amilóide como evento inicial (hipótese preconizada pelos "beta-aptistas") e nas alterações do citoesqueleto neuronal, decorrentes da fosforilação anormal da TAU (conforme proposto pelos "beta-tauístas"). Os achados são discutidos numa leitura integrada desses dois mecanismos fisiopatológicos.
Assuntos
Humanos , Peptídeos beta-Amiloides , Proteínas tau , Secretases da Proteína Precursora do Amiloide , Doença de AlzheimerRESUMO
Phyllanthus niruri L., commonly known in Brazil as 'quebra-pedra', has long been used in the treatment of diverse diseases and especially urolithiasis. The therapeutic effects of P. niruri are attributed to various compounds present in the plant, including the hydrolysable tannin corilagin. In the present study, high-performance liquid chromatography (HPLC-/PAD) profiles of leaves and commercial extracts of P. niruri were examined and three compounds, found to be present in all of the samples studied, were isolated by open column chromatography over C18)silica gel followed by preparative HPLC. These compounds were identified by nuclear magnetic resonance as corilagin, rutin and ethyl 3,4,5-trihydroxybenzoate. Corilagin, which has been proposed as a phytochemical marker for P. niruri, was employed as an external standard in the development and validation of a rapid and efficient qualitative and quantitative HPLC assay for the analyte. The method may be applied in the standardization of herbs and phytomedicines commercialized in Brazil as quebra-pedra.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ácido Gálico/análogos & derivados , Glucosídeos/análise , Phyllanthus/química , Extratos Vegetais/análise , Rutina/análise , Cromatografia Líquida de Alta Pressão/economia , Cromatografia Líquida de Alta Pressão/instrumentação , Ácido Gálico/análise , Ácido Gálico/isolamento & purificação , Taninos Hidrolisáveis , Espectroscopia de Ressonância Magnética , Folhas de Planta/química , Reprodutibilidade dos Testes , Rutina/isolamento & purificação , Sensibilidade e Especificidade , Fatores de TempoRESUMO
BACKGROUND: Individual randomized clinical trials (RCTs) with cholinesterase inhibitors (ChEIs) aiming to delay the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) have not found significant benefit of their use for this purpose. The objective of this study is to meta-analyze the RCTs conducted with ChEIs in order to assess whether pooled analysis could show the benefit of these drugs in delaying the progression from MCI to AD. METHODS: We searched for references of published and unpublished studies on electronic databases (Medline, Embase, Web of Science, and Clinical Trial Database Registry, particularly the Clinicaltrials.gov--http://www.clinicaltrials.gov ). We retrieved 173 references, which yielded three references for data extraction. A total of 3.574 subjects from four RCTs were included in the meta-analysis. Among 1,784 subjects allocated in the ChEI-treatment group, 275 (15.4%) progressed to AD/dementia, as opposed to 366 (20.4%) out of 1,790 subjects in the placebo group. The relative risk (RR) for progression to AD/dementia in the ChEI-treated group was 0.75 [CI(95%) 0.66-0.87], z = -3.89, P < 0.001. The patients on the ChEI group had a significantly higher all-cause dropout risk than the patients on the placebo group (RR = 1.36 CI(95%) [1.24-1.49]; z = 6.59, P < 0.001). The RR for serious adverse events (SAE) in the ChEI-treated group showed no significantly statistical difference from the placebo group (RR = 0.95 [CI(95%) 0.83-1.09], z = -0.72, P = 0.47). The subjects in the ChEI-treated group had a marginally, non-significant, higher risk of death due to any cause than those in the placebo-treated group (RR = 1.04, CI(95%) 0.63-1.70, z = 0.16, P = 0.86). CONCLUSION: The long-term use of ChEIs in subjects with MCI may attenuate the risk of progression to AD/dementia. This finding may have a significant impact on public health and pharmaco-economic policies.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/prevenção & controle , Inibidores da Colinesterase/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Doença de Alzheimer/psicologia , Transtornos Cognitivos/psicologia , Progressão da Doença , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Resultado do TratamentoRESUMO
Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline, including memory loss, behavioral and psychological symptoms and personality changes. The neuropathological hallmarks of AD are the presence of neuritic (senile) plaques (NP) and neurofibrillary tangles (NFT), along with neuronal loss, dystrophic neurites, and gliosis. Neuritic plaques are extracellular lesions and their main constituent is the amyloid-ß42 peptide (Aß42). Neurofibrillary tangles are intracellular lesions that are mainly composed of hyperphosphorylated Tau protein. In this article, we review the major hypotheses concerning the physiopathology of AD, focusing on the ß-amyloid cascade as primary events (supported by the "ßaptists") and cytoskeletal abnormalities secondary to the hyperphosphorylation of protein Tau (as advocated by the "Tauists"). We further provide an integrative view of the physiopathology of AD.
A doença de Alzheimer (DA) é uma desordem neurodegenerativa progressiva que cursa comprometimento da memória e outras funções cognitivas, alterações comportamentais, psíquicas e da personalidade. Os achados neuropatológicos característicos da DA são as placas neuríticas (senis) e os emaranhados neurofibrilares, também ocorrendo distrofia de neuritos, gliose e perda neuronal. As placas neuríticas são lesões extracelulares que têm no peptídeo beta-amilóide (Aß42) seu principal constituinte. Os emaranhados neurofibrilares são lesões intraneuronais compostas por agregados de proteína TAU em estado hiperfosforilado. Neste artigo de revisão, apresentamos as principais hipóteses relacionadas à fisiopatologia da DA, com foco na cascata do amilóide como evento inicial (hipótese preconizada pelos "ßaptistas") e nas alterações do citoesqueleto neuronal, decorrentes da fosforilação anormal da TAU (conforme proposto pelos "tauístas"). Os achados são discutidos numa leitura integrada desses dois mecanismos fisiopatológicos.
RESUMO
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 por cento 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 percent 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.
Assuntos
Demência , Fosforilação , Proteínas tau/biossínteseRESUMO
Hypercalcemia can result from excessive bone resorption, renal calcium retention, excessive intestinal calcium absorption, or a combination of these conditions. Hypercalcemia may also provoke acute renal failure (ARF) or hypertension, or aggravate the tubular necrosis that is frequently found in cases of ARF. The association of ARF and hypercalcemia was studied retrospectively in eight patients based in the data in their charts. Data are expressed as median and percentile (25th; 75th). Our results show that ARF associated with hypercalcemia was related with comorbidity in all cases (cancer, multiple myeloma, hyperparathyroidism, sarcoidosis, vitamin D intoxication, and leprosy). Maximum median serum creatinine levels were 3.3 mg/dL (2.7, 3.8 mg/dL) before treatment and 1.1 mg/dL (0.9, 1.3 mg/dL) after treatment. Maximum total median serum calcium was 15.9 mg/dL (13.5, 19.8 mg/dL) before treatment and 9.1 mg/dL (8.4, 9.7 mg/dL) after treatment. Maximum median ionized serum calcium was 2.1 mmol/L (1.8, 2.2 mmol/L) before treatment and 1.1 mmol/L (1.0, 1.2 mmol/L) after treatment. Different kinds of treatment induced a rapid fall in serum calcium concentration. All patients were treated with hydration and diuretics, and three patients also received calcitonin. Serum creatinine concentration always fell simultaneously with the decrease in serum calcium in all cases. All patients progressed with nonoliguric renal failure. In conclusion, in ARF, patients are frequently hypocalcemic. Usually, the presence of hypercalcemia associated with ARF is indicative of the presence of comorbidity, as observed in all eight patients studied here. There was an improvement of renal function in all cases as serum calcium levels decreased.
Assuntos
Injúria Renal Aguda/complicações , Hipercalcemia/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Objetivo: O Segundo Consenso Brasileiro de Fator Antinuclear (FAN) em Células HEp-2 ratificou os algoritmos de decisão para leitura dos padrões do FAN na imunofluorescência indireta vistos na primeira edição do Consenso Brasileiro, adicionando ainda um novo algoritmo relacionado com os padrões mistos. Métodos: Tendo em vista a habilidade do teste em detectar auto-antígenos nos distintos compartimentos celulares, e não apenas no núcleo, propõe-se novas denominações para este exame laboratorial. Resultados e Conclusões: Como novas denominações algumas sugestões foram igualmente aceitas, dentro do tema "pesquisa de aut-anticorpos contra constituintes do núcleo (FAN HEp-2), nucléolo, citoplasma e aparelho mitótico". Foram abordadas as principais relevâncias clínicas com os padrões de FAN descritos, facilitando o melhor uso do ensaio pelo médico
Assuntos
Autoanticorpos , Autoantígenos , ImunofluorescênciaRESUMO
A análise da presença de auto-anticorpos feita por imunofluorescência indireta em células HEp-2 constitui-se em um método de triagem escolhido na maioria dos laboratórios clínicos. A ausência de uma nomenclatura definida para a descrição dos laudos tem trazido problemas na utilização clínica do teste, pelas dificuldades no controle de qualidade e na padronização dos resultados, que, por sua vez, embora similares, recebiam denominações diferentes. O I Consenso Brasileiro para Padronização dos Laudos de FAN HEp-2 reuniu em agosto de 2000, em Goiânia, diversos especialistas de todo o Brasil. Esses emitiram pareceres em consenso para os distintos padrões: nucleares, nucleolares, citoplasmáticos e aparelho mitótico. Foram feitas recomendações sobre os critérios para a leitura de uma lâmina, bem como para relação entre a diluição de triagem e o sistema óptico utilizado