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1.
Biodivers Data J ; 12: e112217, 2024.
Article in English | MEDLINE | ID: mdl-38495307

ABSTRACT

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.

2.
Rev Soc Bras Med Trop ; 56: e0321, 2023.
Article in English | MEDLINE | ID: mdl-36820655

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.


Subject(s)
Leprosy , Humans , Mozambique/epidemiology , Cross-Sectional Studies , Leprosy/diagnosis , Leprosy/epidemiology , Mycobacterium leprae , Family Characteristics
3.
Rev. Soc. Bras. Med. Trop ; 56: e0321, 2023. tab
Article in English | LILACS-Express | LILACS, Sec. Est. Saúde SP, HANSEN, Hanseníase Leprosy, SESSP-ILSLPROD, Sec. Est. Saúde SP, SESSP-ILSLACERVO, Sec. Est. Saúde SP | ID: biblio-1422893

ABSTRACT

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.

4.
Rev Soc Bras Med Trop ; 55: e0657, 2022.
Article in English | MEDLINE | ID: mdl-35293550

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.


Subject(s)
Chagas Disease , Quality of Life , Health Status , Humans
5.
Rev. Soc. Bras. Med. Trop ; 55: e0657, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1365438

ABSTRACT

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.

6.
Mol Ther Nucleic Acids ; 16: 770-777, 2019 Jun 07.
Article in English | MEDLINE | ID: mdl-31150930

ABSTRACT

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.

7.
Rev Assoc Med Bras (1992) ; 65(3): 326-329, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30994827

ABSTRACT

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.


Subject(s)
Eosinophilia/pathology , Fasciitis/pathology , Adult , Biopsy , Edema/pathology , Eosinophilia/diagnostic imaging , Eosinophilia/drug therapy , Fasciitis/diagnostic imaging , Fasciitis/drug therapy , Female , Humans , Magnetic Resonance Imaging , Rare Diseases , Skin/pathology , Treatment Outcome
8.
Rev. Assoc. Med. Bras. (1992) ; 65(3): 326-329, Mar. 2019. graf
Article in English | LILACS | ID: biblio-1003043

ABSTRACT

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.


Subject(s)
Humans , Female , Adult , Eosinophilia/pathology , Fasciitis/pathology , Skin/pathology , Biopsy , Magnetic Resonance Imaging , Treatment Outcome , Rare Diseases , Edema/pathology , Eosinophilia/drug therapy , Eosinophilia/diagnostic imaging , Fasciitis/drug therapy , Fasciitis/diagnostic imaging
9.
Intern Emerg Med ; 12(5): 693-703, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27905006

ABSTRACT

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.


Subject(s)
Atrial Fibrillation/drug therapy , Disease Management , Guidelines as Topic/standards , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Atrial Fibrillation/physiopathology , Education, Medical, Continuing/methods , Electric Countershock/methods , Electric Countershock/standards , Emergency Service, Hospital/organization & administration , Emergency Service, Hospital/statistics & numerical data , Evidence-Based Medicine/methods , Heart Rate/drug effects , Hemodynamics/drug effects , Humans
12.
Fisioter. mov ; 28(1): 61-67, jan-mar/2015. tab
Article in English | LILACS | ID: lil-742844

ABSTRACT

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. .

13.
Gerais (Esc. Saúde Pública Minas Gerais) ; 2(2): 65-70, jul.-dez. 2014.
Article in Portuguese | Coleciona SUS, SES-MG | ID: biblio-945070

ABSTRACT

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.


Subject(s)
Humans , Resistance Training , Quality of Life
14.
Nucleic Acids Res ; 42(12): 8161-73, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24944197

ABSTRACT

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.


Subject(s)
G-Quadruplexes , Introns , Oligonucleotides, Antisense/chemistry , Proinsulin/genetics , RNA Splicing , 5' Untranslated Regions , Animals , COS Cells , Cell Line , Chlorocebus aethiops , DEAD-box RNA Helicases/antagonists & inhibitors , Humans , RNA/chemistry , RNA Precursors/metabolism , RNA Splice Sites , RNA, Messenger/metabolism , RNA-Binding Proteins/metabolism
15.
J Biol Chem ; 288(44): 31752-60, 2013 Nov 01.
Article in English | MEDLINE | ID: mdl-24030829

ABSTRACT

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.


Subject(s)
Apoptosis , Gene Expression Regulation , Human Umbilical Vein Endothelial Cells/metabolism , Mutation, Missense , Neovascularization, Physiologic , Prealbumin/metabolism , Allografts , Amino Acid Substitution , Amyloid Neuropathies, Familial/genetics , Amyloid Neuropathies, Familial/metabolism , Amyloid Neuropathies, Familial/pathology , Amyloid Neuropathies, Familial/surgery , Cell Survival , Cells, Cultured , Human Umbilical Vein Endothelial Cells/pathology , Humans , Liver/blood supply , Liver/metabolism , Liver/pathology , Liver Transplantation , Prealbumin/genetics , Thrombosis/genetics , Thrombosis/metabolism , Thrombosis/pathology
16.
Vasc Health Risk Manag ; 9: 29-35, 2013.
Article in English | MEDLINE | ID: mdl-23378770

ABSTRACT

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.


Subject(s)
Exercise Test , Muscle Contraction , Muscle, Skeletal/blood supply , Muscle, Skeletal/physiopathology , Peripheral Arterial Disease/diagnosis , Aged , Cross-Sectional Studies , Exercise Tolerance , Female , Humans , Lower Extremity , Male , Middle Aged , Muscle Fatigue , Peripheral Arterial Disease/physiopathology , Predictive Value of Tests , Reproducibility of Results , Surveys and Questionnaires , Time Factors , Walking
17.
Biochim Biophys Acta ; 1834(6): 1010-22, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23228929

ABSTRACT

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.


Subject(s)
Amyloid/metabolism , Cytochromes c/metabolism , Glycosylation , Pyruvaldehyde/metabolism , Amino Acid Sequence , Animals , Horses , Kinetics , Membrane Lipids/metabolism , Protein Conformation , Protein Folding , Thermodynamics
18.
BMC Biochem ; 12: 41, 2011 Aug 05.
Article in English | MEDLINE | ID: mdl-21819598

ABSTRACT

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.


Subject(s)
Insulin/chemistry , Insulin/metabolism , Protein Multimerization/drug effects , Pyruvaldehyde/pharmacology , Amino Acid Sequence , Dose-Response Relationship, Drug , Glycosylation/drug effects , Humans , Protein Stability/drug effects , Protein Structure, Secondary
19.
Rev. psiquiatr. Rio Gd. Sul ; 33(1): 55-62, 2011. tab
Article in Portuguese | LILACS-Express | LILACS | ID: lil-588238

ABSTRACT

INTRODUÇÃO: O transtorno de estresse pós-traumático (TEPT) tem sido associado à desregulação de diversos parâmetros psicofisiológicos e pode apresentar comorbidade com diversas psicopatologias, inclusive a dissociação, podendo dificultar o tratamento. O objetivo do presente trabalho foi investigar os efeitos da terapia cognitivo-comportamental em um paciente com TEPT e sintomas dissociativos com base em medidas psicofisiológicas e psicométricas em diferentes momentos do tratamento. DESCRIÇÃO DO CASO: O paciente é um homem de 38 anos, com diagnósticos de TEPT e transtorno depressivo maior recorrente com sintomas dissociativos e resistência ao tratamento farmacológico. O tratamento psicoterápico teve duração de 4 meses, sendo composto por uma sessão semanal de terapia e três sessões semanais de coterapia. Os parâmetros fisiológicos (frequência cardíaca, tônus vagal, balanço simpático e cortisol) e psicométricos (afeto negativo e positivo, resiliência e sintomas de estresse pós-traumático, depressão, ansiedade e dissociação) foram medidos antes, durante (uma vez ao mês) e após o tratamento. COMENTÁRIOS: Os resultados mostraram diminuição do balanço simpático e aumento do tônus vagal, da frequência cardíaca e dos níveis de cortisol ao longo do tratamento. O tratamento também promoveu redução no afeto negativo e nos sintomas de estresse pós-traumático, depressão, ansiedade e dissociação, além de um aumento nos escores de resiliência, apoio social e afeto positivo. Esses resultados sugerem que a terapia cognitivo-comportamental é um tratamento eficaz para o TEPT com sintomas dissociativos. Além disso, parece promover a normalização das alterações fisiológicas do sistema nervoso autônomo e neuroendócrino relacionadas ao TEPT.


INTRODUCTION: Post-traumatic stress disorder (PTSD) has been associated with dysregulation of many psychophysiological parameters and may present comorbidity with different psychopathologies, including dissociation, potentially affecting treatment outcome. The aim of this study was to evaluate the effects of cognitive behavioral therapy in a patient with PTSD and dissociative symptoms based on psychophysiological and psychometric measures at different time points throughout the course of treatment. CASE DESCRIPTION: Our patient is a 38-year old man diagnosed with PTSD, major depression, and dissociative symptoms, resistant to pharmacotherapy. Psychological treatment lasted for 4 months and consisted of one weekly therapy session and three weekly coaching sessions. Physiological (heart rate, vagal tone, sympathovagal balance, and cortisol) and psychometric measures (negative and positive affect, resilience, and post-traumatic stress, depression, anxiety, and dissociative symptoms) were obtained before, during (once a month) and after treatment. COMMENTS: Results showed a decrease in sympathovagal balance and an increase in heart rate, vagal tone and cortisol levels during the course of treatment. Treatment also lead to a decrease in negative affect and in post-traumatic stress, depression, anxiety, and dissociation symptoms, as well as to an increase in resilience, social support and positive affect scores. These results suggest that cognitive behavioral therapy is an effective treatment for PTSD patients with dissociative symptoms. Moreover, the treatment seems to be able to normalize PTSD-related physiological parameters in the neuroendocrine and autonomic nervous systems.

20.
Arch. Clin. Psychiatry (Impr.) ; 38(4): 155-160, 2011. tab
Article in Portuguese | LILACS | ID: lil-597111

ABSTRACT

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.


Subject(s)
Biomarkers , Cognitive Behavioral Therapy , Behavior Therapy , Stress Disorders, Post-Traumatic/psychology
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