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1.
Trop Med Int Health ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38961761

RESUMO

OBJECTIVE: This study aims to develop and validate predictive models that assess the risk of leprosy development among contacts, contributing to an enhanced understanding of disease occurrence in this population. METHODS: A cohort of 600 contacts of people with leprosy treated at the National Reference Center for Leprosy and Health Dermatology at the Federal University of Uberlândia (CREDESH/HC-UFU) was followed up between 2002 and 2022. The database was divided into two parts: two-third to construct the disease risk score and one-third to validate this score. Multivariate logistic regression models were used to construct the disease score. RESULTS: Of the four models constructed, model 3, which included the variables anti-phenolic glycolipid I immunoglobulin M positive, absence of Bacillus Calmette-Guérin vaccine scar and age ≥60 years, was considered the best for identifying a higher risk of illness, with a specificity of 89.2%, a positive predictive value of 60% and an accuracy of 78%. CONCLUSIONS: Risk prediction models can contribute to the management of leprosy contacts and the systematisation of contact surveillance protocols.

2.
Biodivers Data J ; 12: e112217, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495307

RESUMO

Background: The paper presents an extensive fish sampling dataset spanning a long-term period from 2010 to 2019. The data were collected in Lenta Marina, an upstream area in the Minho Estuary of the NW Iberian Peninsula, which belongs to a LTSER (Long-Term Socio-Ecological Research) platform. To capture fish, fyke nets were utilised as the sampling method and deployed at Lenta Marina. This dataset offers valuable insights into the abundance of each collected taxa recorded over time. New information: The dataset reports a comprehensive compilation of data on the abundance of fish species observed in the area during the sampling period (includes zeroes when a given taxonomic entity was absent in a given sampling event). It provides a detailed record of the abundances of the fish community through time in a frequent sampling regime (on average, sampling was done every 6 days). The dataset shows that the amount of fish from invasive taxa exceeds the count of fish from native taxa in the Minho Estuary.

3.
Rev Soc Bras Med Trop ; 56: e0321, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36820655

RESUMO

BACKGROUND: Leprosy is a neglected chronic infection caused by Mycobacterium leprae, that is curable. The magnitude of the disease and severity of the debilitation it causes renders leprosy a public health problem. This study aimed to analyze the endemic profile of leprosy in the Murrupula district and evaluate the socioeconomic, clinical, and serological profiles of leprosy contacts. METHODS: A cross-sectional study of patients with leprosy diagnosed between 2013 and 2017 and their household and community contacts was conducted in Murrupula District, Nampula Province, Mozambique. Interviews, simplified dermatoneurological examinations, Mycobacterium leprae flow (ML Flow) tests, and Mitsuda tests were performed. RESULTS: Most of the leprosy cases were multibacillary. The patients had some degree of physical disability. ML Flow positivity was more common in household contacts of the patients diagnosed with leprosy and in community individuals who spontaneously presented for testing. In total, 17 patients were diagnosed with leprosy. CONCLUSIONS: This study revealed an active chain of transmission, hidden prevalence, and operational deficiencies in leprosy surveillance and care. The results suggest that the implementation of a public health policy for leprosy prevention and control in Nampula Province is necessary. In future, the possibility of expanding the policy to the entire country should be considered.


Assuntos
Hanseníase , Humanos , Moçambique/epidemiologia , Estudos Transversais , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Mycobacterium leprae , Características da Família
4.
Rev. Soc. Bras. Med. Trop ; 56: e0321, 2023. tab
Artigo em Inglês | LILACS-Express | LILACS, Sec. Est. Saúde SP, HANSEN, Hanseníase, SESSP-ILSLPROD, Sec. Est. Saúde SP, SESSP-ILSLACERVO, Sec. Est. Saúde SP | ID: biblio-1422893

RESUMO

ABSTRACT Background: Leprosy is a neglected chronic infection caused by Mycobacterium leprae, that is curable. The magnitude of the disease and severity of the debilitation it causes renders leprosy a public health problem. This study aimed to analyze the endemic profile of leprosy in the Murrupula district and evaluate the socioeconomic, clinical, and serological profiles of leprosy contacts. Methods: A cross-sectional study of patients with leprosy diagnosed between 2013 and 2017 and their household and community contacts was conducted in Murrupula District, Nampula Province, Mozambique. Interviews, simplified dermatoneurological examinations, Mycobacterium leprae flow (ML Flow) tests, and Mitsuda tests were performed. Results: Most of the leprosy cases were multibacillary. The patients had some degree of physical disability. ML Flow positivity was more common in household contacts of the patients diagnosed with leprosy and in community individuals who spontaneously presented for testing. In total, 17 patients were diagnosed with leprosy. Conclusions: This study revealed an active chain of transmission, hidden prevalence, and operational deficiencies in leprosy surveillance and care. The results suggest that the implementation of a public health policy for leprosy prevention and control in Nampula Province is necessary. In future, the possibility of expanding the policy to the entire country should be considered.

5.
Rev Soc Bras Med Trop ; 55: e0657, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35293550

RESUMO

Chagas disease (CD) is a neglected tropical disease associated with poverty in which patients are surrounded by stigma. These factors can contribute to reducing health-related quality of life (HRQoL). Therefore, a broad discussion of HRQoL in the CD population is required. This study aimed to discuss the main findings of HRQoL in patients with CD, focusing on the association between sociodemographic and lifestyle factors, echocardiographic and functional determinants, and the effect of non-invasive interventions on HRQoL. A literature search of the MEDLINE, Web of Science, CINAHL, Scopus, and LILACS databases was performed with no data or language restrictions. Twenty-two articles were included in this meta-analysis. In general, HRQoL is worse in patients with CD than in healthy individuals, particularly in the presence of cardiovascular and/or gastrointestinal symptoms. Sex, age, functional class, level of physical activity, healthy habits, and medications received could affect HRQoL. Among the echocardiographic and functional determinants, decreased systolic function seems to negatively affect HRQoL. No association with the peak oxygen uptake was observed in the maximal tests. By contrast, well-tolerated field tests with submaximal intensities were associated with HRQoL. Both pharmaceutical care and exercise training have a positive effect on the HRQoL of patients with Chagas cardiomyopathy, and the mental component can be a prognostic marker in this population. In conclusion, assessment of HRQoL can provide important information about the health status of patients with CD, and its use in clinical practice is warranted.


Assuntos
Doença de Chagas , Qualidade de Vida , Nível de Saúde , Humanos
6.
Rev. Soc. Bras. Med. Trop ; 55: e0657, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1365438

RESUMO

ABSTRACT Chagas disease (CD) is a neglected tropical disease associated with poverty in which patients are surrounded by stigma. These factors can contribute to reducing health-related quality of life (HRQoL). Therefore, a broad discussion of HRQoL in the CD population is required. This study aimed to discuss the main findings of HRQoL in patients with CD, focusing on the association between sociodemographic and lifestyle factors, echocardiographic and functional determinants, and the effect of non-invasive interventions on HRQoL. A literature search of the MEDLINE, Web of Science, CINAHL, Scopus, and LILACS databases was performed with no data or language restrictions. Twenty-two articles were included in this meta-analysis. In general, HRQoL is worse in patients with CD than in healthy individuals, particularly in the presence of cardiovascular and/or gastrointestinal symptoms. Sex, age, functional class, level of physical activity, healthy habits, and medications received could affect HRQoL. Among the echocardiographic and functional determinants, decreased systolic function seems to negatively affect HRQoL. No association with the peak oxygen uptake was observed in the maximal tests. By contrast, well-tolerated field tests with submaximal intensities were associated with HRQoL. Both pharmaceutical care and exercise training have a positive effect on the HRQoL of patients with Chagas cardiomyopathy, and the mental component can be a prognostic marker in this population. In conclusion, assessment of HRQoL can provide important information about the health status of patients with CD, and its use in clinical practice is warranted.

7.
Mol Ther Nucleic Acids ; 16: 770-777, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31150930

RESUMO

The human proinsulin gene (INS) contains a thymine-to-adenine variant (rs689) located in the 3' splice site (3' ss) recognition motif of the first intron. The adenine at rs689 is strongly associated with type 1 diabetes. By weakening the polypyrimidine tract, the adenine allele reduces the efficiency of intron 1 splicing, which can be ameliorated by antisense oligonucleotides blocking a splicing silencer located upstream of the 3' ss. The silencer is surrounded by guanine-rich tracts that may form guanine quadruplexes (G4s) and modulate the accessibility of the silencer. Here, we employed thioflavin T (ThT) to monitor G4 formation in synthetic DNAs and RNAs derived from INS intron 1. We show that the antisense target is surrounded by ThT-positive segments in each direction, with oligoribonucleotides exhibiting consistently higher fluorescence than their DNA counterparts. The signal was reduced for ThT-positive oligonucleotides that were extended into the silencer, indicating that flanking G4s have a potential to mask target accessibility. Real-time monitoring of ThT fluorescence during INS transcription in vitro revealed a negative correlation with ex vivo splicing activities of corresponding INS constructs. Together, these results provide a better characterization of antisense targets in INS primary transcripts for restorative strategies designed to improve the INS splicing defect associated with type 1 diabetes.

8.
Rev Assoc Med Bras (1992) ; 65(3): 326-329, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30994827

RESUMO

Eosinophilic fasciitis, or Shulman's disease, is a rare disease of unknown etiology. It is characterized by peripheral eosinophilia, hypergammaglobulinemia, and high erythrocyte sedimentation rate. The diagnosis is confirmed by a deep biopsy of the skin. The first line of treatment is corticotherapy. We present a rare case of eosinophilic fasciitis in a 27-year-old woman with an atypical presentation with symmetrical peripheral edema and a Groove sign. The patient responded well to treatment with corticosteroids at high doses and, in this context, was associated with hydroxychloroquine and azathioprine. After two and a half years, peripheral eosinophilia had increased, and more of her skin had hardened. At that time, the therapy was modified to include corticoids, methotrexate, and penicillamine. It is of great importance to publicize these cases that allow us to gather experience and better treat our patients.


Assuntos
Eosinofilia/patologia , Fasciite/patologia , Adulto , Biópsia , Edema/patologia , Eosinofilia/diagnóstico por imagem , Eosinofilia/tratamento farmacológico , Fasciite/diagnóstico por imagem , Fasciite/tratamento farmacológico , Feminino , Humanos , Imageamento por Ressonância Magnética , Doenças Raras , Pele/patologia , Resultado do Tratamento
9.
Rev. Assoc. Med. Bras. (1992) ; 65(3): 326-329, Mar. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1003043

RESUMO

SUMMARY Eosinophilic fasciitis, or Shulman's disease, is a rare disease of unknown etiology. It is characterized by peripheral eosinophilia, hypergammaglobulinemia, and high erythrocyte sedimentation rate. The diagnosis is confirmed by a deep biopsy of the skin. The first line of treatment is corticotherapy. We present a rare case of eosinophilic fasciitis in a 27-year-old woman with an atypical presentation with symmetrical peripheral edema and a Groove sign. The patient responded well to treatment with corticosteroids at high doses and, in this context, was associated with hydroxychloroquine and azathioprine. After two and a half years, peripheral eosinophilia had increased, and more of her skin had hardened. At that time, the therapy was modified to include corticoids, methotrexate, and penicillamine. It is of great importance to publicize these cases that allow us to gather experience and better treat our patients.


RESUMO A fasciite eosinofílica ou doença de Shulman é uma doença rara de etiologia desconhecida. É caracterizada por eosinofilia periférica, hipergamaglobulinemia e velocidade de sedimentação eritrocitária elevada. O diagnóstico é confirmado por biópsia profunda da pele. O tratamento de primeira linha é a corticoterapia. Apresentamos um caso raro de fasciite eosinofílica numa mulher de 27 anos com uma apresentação atípica com edema periférico simétrico e sinal de Groove. A paciente respondeu bem ao tratamento com corticoides, mas em doses elevadas, e, nesse contexto, associou-se hidroxicloroquina e azatioprina. Ao fim de dois anos e meio verificou-se aumento de eosinofilia e novamente pele mais endurecida. Nessa altura alterou-se a terapêutica para corticoides, metrotexato e penicilamina. É de grande importância a divulgação desses casos que nos permitem reunir experiência e assim melhor tratar os nossos doentes.


Assuntos
Humanos , Feminino , Adulto , Eosinofilia/patologia , Fasciite/patologia , Pele/patologia , Biópsia , Imageamento por Ressonância Magnética , Resultado do Tratamento , Doenças Raras , Edema/patologia , Eosinofilia/tratamento farmacológico , Eosinofilia/diagnóstico por imagem , Fasciite/tratamento farmacológico , Fasciite/diagnóstico por imagem
10.
Intern Emerg Med ; 12(5): 693-703, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27905006

RESUMO

Several guidelines often exist on the same topic, sometimes offering divergent recommendations. For the clinician, it can be difficult to understand the reasons for this divergence and how to select the right recommendations. The aim of this study is to compare different guidelines on the management of atrial fibrillation (AF), and provide practical and affordable advice on its management in the acute setting. A PubMed search was performed in May 2014 to identify the three most recent and cited published guidelines on AF. During the 1-week school of the European School of Internal Medicine, the attending residents were divided in five working groups. The three selected guidelines were compared with five specific questions. The guidelines identified were: the European Society of Cardiology guidelines on AF, the Canadian guidelines on emergency department management of AF, and the American Heart Association guidelines on AF. Twenty-one relevant sub-questions were identified. For five of these, there was no agreement between guidelines; for three, there was partial agreement; for three data were not available (issue not covered by one of the guidelines), while for ten, there was complete agreement. Evidence on the management of AF in the acute setting is largely based on expert opinion rather than clinical trials. While there is broad agreement on the management of the haemodynamically unstable patient and the use of drugs for rate-control strategy, there is less agreement on drug therapy for rhythm control and no agreement on several other topics.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Gerenciamento Clínico , Guias como Assunto/normas , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Fibrilação Atrial/fisiopatologia , Educação Médica Continuada/métodos , Cardioversão Elétrica/métodos , Cardioversão Elétrica/normas , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Medicina Baseada em Evidências/métodos , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos
13.
Fisioter. mov ; 28(1): 61-67, jan-mar/2015. tab
Artigo em Inglês | LILACS | ID: lil-742844

RESUMO

Introduction Individuals with chronic venous insufficiency (CVI) have muscle pump dysfunction and reduced functionality. However, studies are inconsistent in proving whether a particular test can assess muscle functional capacity. Therefore, the aim of this study was to evaluate whether the heel-rise test (HRT) is able to explain functional capacity in patients with CVI. Materials and methods Subjects with CVI aged between 20 and 59 years old were selected for this study. All participants were classified by means of the Clinical Anatomy Etiology Pathophysiology Classification of Chronic Venous Disease (CEAP). The HRT and the shuttle walk test (SWT) were performed. Descriptive statistics, Spearman correlation, linear models and regression variance analysis (one-way ANOVA) were used for data analysis. Significance was set at alpha ≤ 5%. Results 79 subjects were included in the study (38.79 ± 1.34 years). The HRT was able to explain functional capacity only in individuals aged between 50-59 years (R2 = 0.60, p = 0.0001). The heel-rise test was not sensitive to detect differences between the CEAP classes analyzed (p > 0.05). Conclusion The HRT was able to explain functional capacity in individuals aged between 50-59 years, and it can be applied in clinical practice for the functional evaluation of patients with CVI with mild severity in this age range. .


Introdução Indivíduos com insuficiência venosa crônica (IVC) podem apresentar disfunção da bomba muscular e redução de sua funcionalidade. Porém, estudos são inconsistentes em afirmar se um teste específico muscular pode avaliar a capacidade funcional. Sendo assim, o objetivo do presente estudo é avaliar se o teste da ponta do pé (TPP) é capaz de predizer a capacidade funcional em indivíduos com IVC. Materiais e métodos Foram selecionados para o estudo indivíduos com IVC com idade entre 20 e 59 anos. Os participantes foram classificados por meio da CEAP (Clinical Etiology Anatomy Pathophysiology Classification of Chronic Venous Desease). Foram realizados o TPP e o teste do deslocamento bidirecional progressivo (TDBP). Estatísticas descritivas, correlação de Spearman, modelos de regressão linear e análise de variância (ANOVA one-way) foram utilizados para a análise dos dados. Para significância estatística, foi usado alfa de 5%. Resultados Foram incluídos 79 indivíduos (38,79 ± 1,34 anos) no estudo. O TPP foi capaz de predizer a capacidade funcional somente em indivíduos de 50 a 59 anos (R2 = 0,60; p = 0,0001). O TPP não foi sensível em detectar diferenças entre as classes CEAP analisadas (p > 0,05). Conclusão O TPP foi capaz de explicar a capacidade funcional em indivíduos de 50 a 59 anos, podendo ser aplicado na prática clínica de forma válida para a avaliação funcional de pacientes com IVC de gravidade leve nessa faixa etária. .

14.
Gerais (Esc. Saúde Pública Minas Gerais) ; 2(2): 65-70, jul.-dez. 2014.
Artigo em Português | Coleciona SUS, SES-MG | ID: biblio-945070

RESUMO

As complicações da insuficiência venosa crônica (IVC) estão relacionadas com a ineficiência da bomba muscular da panturrilha.Permanece incerto, porém, se pacientes que apresentam IVC sintomática, mas função de panturrilha pouco comprometida, poderiam se beneficiar do treino muscular. Apresentarum relato de caso, no qual foi realizado umtreinamento de resistência da musculaturada panturrilha em uma mulher com apresentação não usual da IVC. Mulher, 55 anos,com histórico de cirurgia de varizes, sintomas de queimação e peso na perna esquerda,foi avaliada pelo shuttle walking test (SWT),pelo heel rise test (HRT), pelo questionário SF-36 e pela pletismografia a ar, antes e após 15 semanas de treinamento físico.O treinamento consistiu em exercícios de resistência muscular da panturrilha; treino aeróbio de moderada intensidade (70% a 75%da FC pico do teste ergométrico), exercícios de resistência muscular com os membrosinferiores elevados e exercícios de alongamento estático envolvendo a musculatura treinada. Houve diminuição da fração de volume residual de 31,2% para 24,5%. Houve melhora da distância no SWT, desempenhono HRT e da qualidade de vida relacionada à saúde. A reabilitação pode ser benéfica mesmo em pacientes com apresentação não usual da IVC .


The complications of chronic venous insuficiency (CVI) are related to ineficiencyof the calf muscle pump. However it stillremains uncertain whether patients withCVI but with slightly impaired calf musclefunction could benefit from the calf muscletraining. to present the results of a resistancetraining of the calf muscle in a woman withan unusual presentation of CVI. Woman, 55years, submitted to a varicose vein surgery,with complaints of burning and weight in the left leg was evaluated by shuttle walkingtest (SWT), heel rise test (HRT), SF-36 questionnaire and air plethysmography, beforeand after 15 weeks of training: muscular resistance of the calf; aerobic training at moderate intensity (70-75% HR peak treadmill test) and static stretching exercises. Therewas a decrease in residual volume fractionfrom 31.2% to 24.5%. There was improvement of distance on SWT, performance onHRT and quality of life related to health.The physical therapy rehabilitation may bebeneficial even in patients with an unusualpresentation of CVI.


Assuntos
Humanos , Treinamento Resistido , Qualidade de Vida
15.
Nucleic Acids Res ; 42(12): 8161-73, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24944197

RESUMO

Splice-switching oligonucleotides (SSOs) have been widely used to inhibit exon usage but antisense strategies that promote removal of entire introns to increase splicing-mediated gene expression have not been developed. Here we show reduction of INS intron 1 retention by SSOs that bind transcripts derived from a human haplotype expressing low levels of proinsulin. This haplotype is tagged by a polypyrimidine tract variant rs689 that decreases the efficiency of intron 1 splicing and increases the relative abundance of mRNAs with extended 5' untranslated region (5' UTR), which curtails translation. Co-expression of haplotype-specific reporter constructs with SSOs bound to splicing regulatory motifs and decoy splice sites in primary transcripts revealed a motif that significantly reduced intron 1-containing mRNAs. Using an antisense microwalk at a single nucleotide resolution, the optimal target was mapped to a splicing silencer containing two pseudoacceptor sites sandwiched between predicted RNA guanine (G) quadruplex structures. Circular dichroism spectroscopy and nuclear magnetic resonance of synthetic G-rich oligoribonucleotide tracts derived from this region showed formation of a stable parallel 2-quartet G-quadruplex on the 3' side of the antisense retention target and an equilibrium between quadruplexes and stable hairpin-loop structures bound by optimal SSOs. This region interacts with heterogeneous nuclear ribonucleoproteins F and H that may interfere with conformational transitions involving the antisense target. The SSO-assisted promotion of weak intron removal from the 5' UTR through competing noncanonical and canonical RNA structures may facilitate development of novel strategies to enhance gene expression.


Assuntos
Quadruplex G , Íntrons , Oligonucleotídeos Antissenso/química , Proinsulina/genética , Splicing de RNA , Regiões 5' não Traduzidas , Animais , Células COS , Linhagem Celular , Chlorocebus aethiops , RNA Helicases DEAD-box/antagonistas & inibidores , Humanos , RNA/química , Precursores de RNA/metabolismo , Sítios de Splice de RNA , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo
16.
J Biol Chem ; 288(44): 31752-60, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24030829

RESUMO

Familial amyloidotic polyneuropathy (FAP) has a high prevalence in Portugal, and the most common form of hereditary amyloidosis is caused by an amyloidogenic variant of transthyretin (TTR) with a substitution of methionine for valine at position 30 (V30M). Until now, the available efficient therapy is liver transplantation, when performed in an early phase of the onset of the disease symptoms. However, transplanted FAP patients have a significantly higher incidence of early hepatic artery thrombosis compared with non-FAP transplanted patients. Because FAP was described as an independent risk factor for early hepatic artery thrombosis, more studies to understand the underlying mechanisms involved in this outcome are of the utmost importance. Knowing that the liver is the major site for TTR production, we investigated the biological effects of TTR proteins in the vasculature and on angiogenesis. In this study, we identified genes differentially expressed in endothelial cells exposed to the WT or V30M tetramer. We found that endothelial cells may acquire different molecular identities when exposed to these proteins, and consequently TTR could regulate angiogenesis. Moreover, we show that V30M decreases endothelial survival by inducing apoptosis, and it inhibits migration. These findings provide new knowledge that may have critical implications in the prevention of early hepatic artery thrombosis in FAP patients after liver transplantation.


Assuntos
Apoptose , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Mutação de Sentido Incorreto , Neovascularização Fisiológica , Pré-Albumina/metabolismo , Aloenxertos , Substituição de Aminoácidos , Neuropatias Amiloides Familiares/genética , Neuropatias Amiloides Familiares/metabolismo , Neuropatias Amiloides Familiares/patologia , Neuropatias Amiloides Familiares/cirurgia , Sobrevivência Celular , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Fígado/irrigação sanguínea , Fígado/metabolismo , Fígado/patologia , Transplante de Fígado , Pré-Albumina/genética , Trombose/genética , Trombose/metabolismo , Trombose/patologia
17.
Vasc Health Risk Manag ; 9: 29-35, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23378770

RESUMO

INTRODUCTION: The heel-rise test (HRT) is a clinical instrument relevant to vascular rehabilitation that has been proposed to assess the function of the triceps surae muscle. To use HRT in the assessment of individuals with peripheral arterial occlusive disease (PAOD), its ability to detect differences in the functional performance of patients with PAOD must be verified. AIM: To verify whether the test is sensitive in differentiating between individuals with PAOD with distinct functional capacities. MATERIALS AND METHODS: A transversal study in which individuals with PAOD were assessed using the HRT, the Walking Impairment Questionnaire (WIQ), and the Shuttle Walk Test. The following variables were analyzed: number of plantar flexions performed in the HRT (time in seconds) and velocity (plantar flexions per second) when performing plantar flexions up to the point of volunteer fatigue, maximum distance walked in the Shuttle Walk Test, and scores obtained in each WIQ domain. RESULTS: Twenty-five individuals (14 male) were included in the study, with a mean age of 63.36 ± 9.83 years. The variables number of plantar flexions and time to perform the HRT were sensitive enough to differentiate between distinct functional capacities in individuals with PAOD (P = 0.003 and P = 0.009, respectively). However, this result was not found for the variable of velocity in the HRT. The number of plantar flexions in the HRT was sensitive enough to differentiate individuals of extreme classes on the WIQ domain, stairs (P = 0.008). CONCLUSION: The HRT can be applied in clinical practice as a valid assessment of the distinct function capacities of individuals with PAOD.


Assuntos
Teste de Esforço , Contração Muscular , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/fisiopatologia , Doença Arterial Periférica/diagnóstico , Idoso , Estudos Transversais , Tolerância ao Exercício , Feminino , Humanos , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Fadiga Muscular , Doença Arterial Periférica/fisiopatologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Inquéritos e Questionários , Fatores de Tempo , Caminhada
18.
Biochim Biophys Acta ; 1834(6): 1010-22, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23228929

RESUMO

Several human neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Familial Amyloidotic Polyneuropathy, have long been associated with, structural and functional changes in disease related proteins leading to aggregation into amyloid fibrils. Such changes can be triggered by post-translational modifications. Methylglyoxal modifications have been shown to induce the formation of small and stable native-like aggregates in the case of the amyloidogenic proteins insulin and α-synuclein. However, the fundamental biophysical mechanism underlying such methylglyoxal-induced protein aggregation is not yet fully understood. In this work cytochrome c (Cyt c) was used as a model protein for the characterization of specific glycation targets and to study their impact on protein structure, stability, and ability to form native-like aggregates. Our results show that methylglyoxal covalently modifies Cyt c at a single residue and induces early conformational changes that lead to the formation of native-like aggregates. Furthermore, partially unfolded species are formed, but do not seem to be implicated in the aggregation process. This shows a clear difference from the amyloid fibril mechanisms which involve partially or totally unfolded intermediates. Equilibrium-unfolding experiments show that glycation strongly decreases Cyt c conformational stability, which is balanced with an increase of conformational stability upon aggregation. Data collected from analytical and spectroscopic techniques, along with kinetic analysis based on least-squares parameter fitting and statistical model discrimination are used to help to understand the driving force underlying glycation-induced native-like aggregation, and enable the proposal of a comprehensive thermodynamic and kinetic model for native-like aggregation of methylglyoxal glycated Cyt c.


Assuntos
Amiloide/metabolismo , Citocromos c/metabolismo , Glicosilação , Aldeído Pirúvico/metabolismo , Sequência de Aminoácidos , Animais , Cavalos , Cinética , Lipídeos de Membrana/metabolismo , Conformação Proteica , Dobramento de Proteína , Termodinâmica
19.
BMC Biochem ; 12: 41, 2011 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-21819598

RESUMO

BACKGROUND: Insulin is a hormone that regulates blood glucose homeostasis and is a central protein in a medical condition termed insulin injection amyloidosis. It is intimately associated with glycaemia and is vulnerable to glycation by glucose and other highly reactive carbonyls like methylglyoxal, especially in diabetic conditions. Protein glycation is involved in structure and stability changes that impair protein functionality, and is associated with several human diseases, such as diabetes and neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and Familiar Amyloidotic Polyneuropathy. In the present work, methylglyoxal was investigated for their effects on the structure, stability and fibril formation of insulin. RESULTS: Methylglyoxal was found to induce the formation of insulin native-like aggregates and reduce protein fibrillation by blocking the formation of the seeding nuclei. Equilibrium-unfolding experiments using chaotropic agents showed that glycated insulin has a small conformational stability and a weaker dependence on denaturant concentration (smaller m-value). Our observations suggest that methylglyoxal modification of insulin leads to a less compact and less stable structure that may be associated to an increased protein dynamics. CONCLUSIONS: We propose that higher dynamics in glycated insulin could prevent the formation of the rigid cross-ß core structure found in amyloid fibrils, thereby contributing to the reduction in the ability to form fibrils and to the population of different aggregation pathways like the formation of native-like aggregates.


Assuntos
Insulina/química , Insulina/metabolismo , Multimerização Proteica/efeitos dos fármacos , Aldeído Pirúvico/farmacologia , Sequência de Aminoácidos , Relação Dose-Resposta a Droga , Glicosilação/efeitos dos fármacos , Humanos , Estabilidade Proteica/efeitos dos fármacos , Estrutura Secundária de Proteína
20.
Arch. Clin. Psychiatry (Impr.) ; 38(4): 155-160, 2011. tab
Artigo em Português | LILACS | ID: lil-597111

RESUMO

CONTEXTO: O estabelecimento de biomarcadores relacionados à terapia cognitivo-comportamental (TCC) é uma maneira de consolidar a eficácia do tratamento de forma mais objetiva, sendo crítico para o avanço desse campo de pesquisa. OBJETIVOS: Foi realizada uma revisão sistemática de estudos que: 1) utilizaram parâmetros biológicos para verificar a eficácia da TCC no tratamento do transtorno de estresse pós-traumático (TEPT); e 2) utilizaram esses parâmetros como preditores de resposta à CBT. MÉTODOS: Foram conduzidas buscas eletrônicas nas bases PubMed/Medline, ISI/Thompson Reuters e Pilot. RESULTADOS: Doze artigos foram selecionados para esta revisão, sendo quatro deles estudos sobre predição de resposta ao tratamento. Foi observada relação entre a eficácia da TCC e modificações nesses parâmetros, sendo a resposta da frequência cardíaca à evocação de sintomas o parâmetro mais utilizado até o presente momento. Sua redução está associada à melhora nos sintomas de TEPT. Potenciais biomarcadores de predição de resposta encontrados incluem 5α-redutase, ativação da amígdala, ativação e volume do córtex cingulado anterior e frequência cardíaca. CONCLUSÃO: Apesar da escassez de estudos e das limitações metodológicas neles observadas, investigações iniciais sugerem que os biomarcadores da TCC em pacientes com TEPT poderão ser úteis para o monitoramento mais objetivo dos efeitos do tratamento, identificação de predição de resposta e para o desenvolvimento de estratégias mais eficazes de tratamento e prevenção do desenvolvimento de TEPT.


BACKGROUND: The establishment of biomarkers related to cognitive-behavior therapy (CBT) is a method to objectively consolidate treatment efficacy, which is critical to advancing the field. OBJECTIVES: We systematically reviewed studies that used biological parameters to assess the efficacy of CBT for the treatment of post-traumatic stress disorder (PTSD) and studies that used these parameters as predictors of response to CBT. METHODS: Computerized literature searches were conducted in PubMed/Medline, ISI/Thompson Reuters, and Pilot databases using both thesaurus and free-word search terms. RESULTS: 12 articles met the selection criteria. 4 of them were response predictors studies. A relationship was found between CBT efficacy and changes in the measured parameters, with heart rate responses to symptom provocation being the parameter most often studied. The reduction in heart rate was associated with an improvement in PTSD symptoms. The potential biomarkers of response predictions found included 5α-reductase, amygdala activation, activation and volume of the anterior cingulate cortex, and heart rate. DISCUSSION: Despite the scarcity of studies and their methodological shortcomings, initial investigations indicate that biomarkers of CBT in PTSD patients hold promise for more objective treatment outcome monitoring, identification of response predictors, and for developing novel treatment and prevention strategies.


Assuntos
Biomarcadores , Terapia Cognitivo-Comportamental , Terapia Comportamental , Transtornos de Estresse Pós-Traumáticos/psicologia
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