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1.
J Microsc ; 290(3): 161-167, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37038805

RESUMO

In the last years, microtomography has proved to be a powerful technique on insects' studies, allowing a detailed view of the structures' internal with a high resolution. One of the most important advantages about the use of microtomography in these studies is the fact that the dissection is not necessary, which decreases considerably the number of samples used on the insects' research. Some insects are used constantly in studies about morphology, metamorphosis, and reproduction, because they work as a model for others, and Rhodnius prolixus is one of the most studied in this group. This insect is also one of the main insect vectors of Chagas disease that kills around 12,000 people every year in Latin America. Some studies using laboratory microtomography conventional scanners combining with the correct staining methods have proved that it could be a powerful tool in biological research, allowing the visualisation of low-density tissues. The main goal of the present work was to use staining protocols to study Rhodnius prolixus with laboratory microtomography conventional scanners. The experiments were carried out at the imaging lab in the Theoretical Biology Department, University of Vienna, using an Xradia MicroXCT and at the University of Oslo, using a Skyscan 2211.


Assuntos
Doença de Chagas , Rhodnius , Animais , Humanos , Rhodnius/anatomia & histologia , Doença de Chagas/diagnóstico por imagem , Insetos Vetores , Coloração e Rotulagem
2.
J Dairy Sci ; 106(5): 3525-3536, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36894419

RESUMO

Objectives were to evaluate differences in the uterine and serum metabolomes associated with metritis in dairy cows. Vaginal discharge was evaluated using a Metricheck device (Simcro) at 5, 7, and 11 d in milk (DIM; herd 1) or 4, 6, 8, 10, and 12 DIM (herd 2). Cows with reddish or brownish, watery, and fetid discharge were diagnosed with metritis (n = 24). Cows with metritis were paired with herdmates without metritis (i.e., clear mucous vaginal discharge or clear lochia with ≤50% of pus) based on DIM and parity (n = 24). Day of metritis diagnosis was considered study d 0. All cows diagnosed with metritis received antimicrobial therapy. The metabolome of uterine lavage collected on d 0 and 5, and serum samples collected on d 0 were evaluated using untargeted gas chromatography time-of-flight mass spectrometry. Normalized data were subjected to multivariate canonical analysis of population using the MultBiplotR and MixOmics packages in R Studio. Univariate analyses including t-test, principal component analyses, partial least squares discriminant analyses, and pathway analyses were conducted using Metaboanalyst. The uterine metabolome differed between cows with and without metritis on d 0. Differences in the uterine metabolome associated with metritis on d 0 were related to the metabolism of butanoate, amino acids (i.e., glycine, serine, threonine, alanine, aspartate, and glutamate), glycolysis and gluconeogenesis, and the tricarboxylic acid cycle. No differences in the serum metabolome were observed between cows diagnosed with metritis and counterparts without metritis on d 0. Similarly, no differences in uterine metabolome were observed between cows with metritis and counterparts not diagnosed with metritis on d 5. These results indicate that the establishment of metritis in dairy cows is associated with local disturbances in amino acid, lipid, and carbohydrate metabolism in the uterus. The lack of differences in the uterine metabolome on d 5 indicates that processes implicated with the disease are reestablished by d 5 after diagnosis and treatment.


Assuntos
Doenças dos Bovinos , Endometrite , Doença Inflamatória Pélvica , Descarga Vaginal , Gravidez , Feminino , Bovinos , Animais , Lactação , Endometrite/veterinária , Endometrite/diagnóstico , Útero , Doença Inflamatória Pélvica/veterinária , Descarga Vaginal/veterinária , Metaboloma , Doenças dos Bovinos/diagnóstico , Período Pós-Parto
3.
Rev Neurol (Paris) ; 179(8): 812-830, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36906457

RESUMO

Alzheimer's disease (AD) is a multi-etiology disease. The biological system of AD is associated with multidomain genetic, molecular, cellular, and network brain dysfunctions, interacting with central and peripheral immunity. These dysfunctions have been primarily conceptualized according to the assumption that amyloid deposition in the brain, whether from a stochastic or a genetic accident, is the upstream pathological change. However, the arborescence of AD pathological changes suggests that a single amyloid pathway might be too restrictive or inconsistent with a cascading effect. In this review, we discuss the recent human studies of late-onset AD pathophysiology in an attempt to establish a general updated view focusing on the early stages. Several factors highlight heterogenous multi-cellular pathological changes in AD, which seem to work in a self-amplifying manner with amyloid and tau pathologies. Neuroinflammation has an increasing importance as a major pathological driver, and perhaps as a convergent biological basis of aging, genetic, lifestyle and environmental risk factors.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/etiologia , Encéfalo/patologia , Envelhecimento , Peptídeos beta-Amiloides/metabolismo , Proteínas tau/metabolismo
4.
Int Endod J ; 54(8): 1275-1288, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33829522

RESUMO

AIM: To introduce a methodology designed to simultaneously visualize dental ultrastructures, including cellular and soft tissue components, by utilizing phosphotungstic acid (PTA) as a contrast-enhancement agent. METHODOLOGY: Sound third molars were collected from healthy human adults and fixed in 4% buffered paraformaldehyde. To evaluate the impact of PTA in concentrations of 0.3%, 0.7% and 1% on dental soft and hard tissues for CT imaging, cementum and dentine-pulp sections were cut, dehydrated and stained with immersion periods of 12, 24 h, 2 days or 5 days. The samples were scanned in a high-resolution nano-CT device using pixel sizes down to 0.5 µm to examine both the cementum and pulpal regions. RESULTS: Dental cementum and periodontium as well as odontoblasts and predentine were made visible through PTA staining in high-resolution three-dimensional nano-CT scans. Different segments of the tooth required different staining protocols. The thickness of the cementum could be computed over the length of the tooth once it was made visible by the PTA-enhanced contrast, and the attached soft tissue components of the interior of the tooth could be shown on the dentine-pulp interface in greater detail. Three-dimensional illustrations allowed a histology-like visualization of the sections in all orientations with a single scan and easy sample preparation. The segmentation of the sigmoidal dentinal tubules and the surrounding dentine allowed a three-dimensional investigation and quantitative of the dentine composition, such as the tubular lumen or the ratio of the tubular lumen area to the dentinal surface. CONCLUSION: The staining protocol made it possible to visualize hard tissues along with cellular layers and soft tissues in teeth using a laboratory-based nano-CT technique. The protocol depended on both tissue type and size. This methodology offers enhanced possibilities for the concomitant visualization of soft and hard dental tissues.


Assuntos
Polpa Dentária , Dentina , Adulto , Dentina/diagnóstico por imagem , Humanos , Odontoblastos
5.
Osteoporos Int ; 29(10): 2261-2274, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29978256

RESUMO

The association of genetic polymorphisms with low bone mineral density in elite athletes have not been considered previously. The present study found that bone mass phenotypes in elite and pre-elite dancers are related to genetic variants at the Wnt/ß-catenin and ER pathways. INTRODUCTION: Some athletes (e.g. gymnasts, dancers, swimmers) are at increased risk for low bone mineral density (BMD) which, if untreated, can lead to osteoporosis. To investigate the association of genetic polymorphisms in the oestrogen receptor (ER) and the Wnt/ß-catenin signalling pathways with low BMD in elite and pre-elite dancers (impact sport athletes). METHODS: The study included three phases: (1) 151 elite and pre-elite dancers were screened for the presence of low BMD and traditional osteoporosis risk factors (low body weight, menstrual disturbances, low energy availability); (2) a genetic association study was conducted in 151 elite and pre-elite dancers and age- and sex- controls; (3) serum sclerostin was measured in 101 pre-elite dancers and age- and sex-matched controls within a 3-year period. RESULTS: Eighty dancers revealed low BMD: 56.3% had at least one traditional osteoporosis risk factor, whereas 28.6% did not display any risk factor (37.2% revealed traditional osteoporosis risk factors, but had normal BMD). Body weight, menstrual disturbances and energy availability did not fully predict bone mass acquisition. Instead, genetic polymorphisms in the ER and Wnt/ß-catenin pathways were found to be risk factors for low BMD in elite dancers. Sclerostin was significantly increased in dancers compared to controls during the 3-year follow-up (p < 0.05). CONCLUSIONS: Elite and pre-elite dancers demonstrate high prevalence of low BMD, which is likely related to genetic variants at the Wnt/ß-catenin and ER pathways and not to factors usually associated with BMD in athletes (body weight, menstrual disturbances, energy deficiency).


Assuntos
Densidade Óssea/genética , Dança/fisiologia , Osteoporose/genética , Polimorfismo de Nucleotídeo Único , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Antropometria/métodos , Densidade Óssea/fisiologia , Proteínas Morfogenéticas Ósseas/sangue , Estudos Transversais , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Variação Genética , Humanos , Estudos Longitudinais , Masculino , Doenças Profissionais/genética , Doenças Profissionais/fisiopatologia , Osteoporose/fisiopatologia , Receptores de Estrogênio/genética , Fatores de Risco , Transdução de Sinais/genética , Suporte de Carga/fisiologia , Via de Sinalização Wnt/genética , Adulto Jovem , beta Catenina/genética
6.
Osteoporos Int ; 28(10): 2903-2912, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28656365

RESUMO

According to existing literature, bone health in ballet dancers is controversial. We have verified that, compared to controls, young female and male vocational ballet dancers have lower bone mineral density (BMD) at both impact and non-impact sites, whereas female professional ballet dancers have lower BMD only at non-impact sites. INTRODUCTION: The aims of this study were to (a) assess bone mineral density (BMD) in vocational (VBD) and professional (PBD) ballet dancers and (b) investigate its association with body mass (BM), fat mass (FM), lean mass (LM), maturation and menarche. METHODS: The total of 152 VBD (13 ± 2.3 years; 112 girls, 40 boys) and 96 controls (14 ± 2.1 years; 56 girls, 40 boys) and 184 PBD (28 ± 8.5 years; 129 females, 55 males) and 160 controls (27 ± 9.5 years; 110 female, 50 males) were assessed at the lumbar spine (LS), femoral neck (FN), forearm and total body by dual-energy X-ray absorptiometry. Maturation and menarche were assessed via questionnaires. RESULTS: VBD revealed lower unadjusted BMD at all anatomical sites compared to controls (p < 0.001); following adjustments for Tanner stage and gynaecological age, female VBD showed similar BMD values at impact sites. However, no factors were found to explain the lower adjusted BMD values in VBD (female and male) at the forearm (non-impact site), nor for the lower adjusted BMD values in male VBD at the FN. Compared to controls, female PBD showed higher unadjusted and adjusted BMD for potential associated factors at the FN (impact site) (p < 0.001) and lower adjusted at the forearm (p < 0.001). Male PBD did not reveal lower BMD than controls at any site. CONCLUSIONS: Both females and males VBD have lower BMD at impact and non-impact sites compared to control, whereas this is only the case at non-impact site in female PBD. Maturation seems to explain the lower BMD at impact sites in female VBD.


Assuntos
Densidade Óssea/fisiologia , Dança/fisiologia , Saúde Ocupacional , Absorciometria de Fóton/métodos , Adolescente , Adulto , Antropometria/métodos , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Feminino , Colo do Fêmur/fisiologia , Antebraço/fisiologia , Humanos , Vértebras Lombares/fisiologia , Masculino , Menarca/fisiologia , Caracteres Sexuais , Suporte de Carga/fisiologia , Adulto Jovem
7.
Eur J Neurol ; 24(5): 748-750, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28251720

RESUMO

BACKGROUND AND PURPOSE: Portugal has been identified as one of the countries with a high prevalence of LRRK2-G2019S, considered to be the most frequent known cause of familial and sporadic Parkinson's disease (PD). The aim of this study was to evaluate the prevalence of PD in Portugal using a door-to-door methodology. METHODS: A cross-sectional study was conducted in the Portuguese community-dwelling population; that is, elderly people living in the community on their own, aged ≥50 years and resident in mainland Portugal, in two phases: (i) a questionnaire was applied to screen potential cases of PD; and (ii) screened cases were evaluated by an expert in PD to confirm diagnosis. RESULTS: The adjusted prevalence of PD for the Portuguese community-dwelling population aged ≥50 years was 0.24%. The estimated total number of cases of PD for the Portuguese population is 180/100 000 inhabitants. CONCLUSIONS: The results of this study show that a geographical region with a high frequency of a causal mutation for PD does not automatically imply a high prevalence of patients with PD.


Assuntos
Doença de Parkinson/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Portugal/epidemiologia , Prevalência
8.
Am J Transplant ; 16(10): 2986-2993, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27062091

RESUMO

US transplant centers are required to report cancers in transplant recipients to the transplant network. The accuracy and completeness of these data, collected in the Scientific Registry of Transplant Recipients (SRTR), are unknown. We compared diagnoses in the SRTR and 15 linked cancer registries for colorectal, liver, lung, breast, prostate and kidney cancers; melanoma; and non-Hodgkin lymphoma (NHL). Among 187 384 transplants, 9323 cancers were documented in the SRTR or cancer registries. Only 36.8% of cancers were in both, with 47.5% and 15.7% of cases additionally documented solely in cancer registries or the SRTR, respectively. Agreement between the SRTR and cancer registries varied (kappa = 0.28 for liver cancer and kappa = 0.52-0.66 for lung, prostate, kidney, colorectum, and breast cancers). Upon evaluation, some NHLs documented only in cancer registries were identified in the SRTR as another type of posttransplant lymphoproliferative disorder. Some SRTR-only cases were explained by miscoding (colorectal cancer instead of anal cancer, metastases as lung or liver cancers) or missed matches with cancer registries, partly due to recipients' outmigration from catchment areas. Estimated sensitivity for identifying cancer was 52.5% for the SRTR and 84.3% for cancer registries. In conclusion, SRTR cancer data are substantially incomplete, limiting their usefulness for surveillance and research.


Assuntos
Coleta de Dados/normas , Neoplasias/diagnóstico , Transplante de Órgãos , Sistema de Registros/normas , Adulto , Feminino , Humanos , Incidência , Masculino , Neoplasias/epidemiologia , Prognóstico , Estados Unidos/epidemiologia
9.
Oral Dis ; 22(7): 658-64, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27250598

RESUMO

OBJECTIVE: Interleukin-1 beta (IL1B) pathway is a key player in orthodontic-induced external apical root resorption (EARR). The aim of this work was to identify the genes related to the IL1 pathway as possible candidate genes for EARR, which might be included in an integrative predictive model of this complex phenotype. MATERIALS AND METHODS: Using a stepwise multiple linear regression model, 195 patients who had undergone orthodontic treatment were assessed for clinical and genetic factors associated with %EARRmax (maximum %EARR value obtained for each patient). The four maxillary incisors and the two maxillary canines were assessed. Three functional single nucleotide polymorphisms (SNPs) were genotyped: rs1143634 in IL1B gene, rs315952 in IL1RN gene, and rs1059703 in X-linked IRAK1 gene. RESULTS: The model showed that four of the nine clinical variables and one SNP explained 30% of the %EARRmax variability. The most significant unique contributions to the model were gender (P = 0.001), treatment duration (P < 0.001), premolar extractions (P = 0.003), Hyrax appliance (P < 0.001), and homozygosity/hemizygosity for variant C from IRAK1 gene (P = 0.018), which proved to be a protective factor. CONCLUSION: IRAK1 polymorphism is proposed as a protective variant for EARR.


Assuntos
Quinases Associadas a Receptores de Interleucina-1/genética , Interleucina-1beta/metabolismo , Ortodontia , Reabsorção da Raiz/genética , Adolescente , Feminino , Variação Genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
10.
Health Care Manag Sci ; 19(1): 31-42, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24744263

RESUMO

The demand for highly efficient and effective services and consumer goods is an essential prerequisite for modern organizations. In healthcare, efficiency and effectiveness mean reducing disabilities and maintaining human life. One challenge is guaranteeing rapid Emergency Medical Service (EMS) response. This study analyzes the EMS of Belo Horizonte, Brazil, using two modeling techniques: optimization and simulation. The optimization model locates ambulance bases and allocates ambulances to those bases. A simulation of this proposed configuration is run to analyze the dynamic behavior of the system. The main assumption is that optimizing the ambulance base locations can improve the system response time. Feasible solutions were found and the current system may be improved while considering economic and operational changes.


Assuntos
Eficiência Organizacional , Serviços Médicos de Emergência/organização & administração , Modelos Teóricos , Ambulâncias/organização & administração , Brasil , Simulação por Computador , Humanos , Fatores de Tempo
12.
J Dairy Sci ; 98(7): 4266-72, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25912870

RESUMO

The effect of the addition of galactooligosaccharide (GOS) on the physicochemical, optical, and sensory characteristics of ice cream was investigated. Vanilla ice cream was supplemented with 0, 1.5, and 3.0% (wt/wt) GOS and characterized for pH, firmness, color, melting, overrun, as well as subjected to a discriminative sensory test (triangle test). For comparison purposes, ice creams containing fructooligosaccharide were also manufactured. The GOS ice creams were characterized by increased firmness and lower melting rates. Different perceptions were reported in the sensory evaluation for the 3.0% GOS ice cream when compared with the control, which was not observed for the fructooligosaccharide ice cream. Overall, the findings suggest it is possible to produce GOS ice cream with improved stability in relation to the physicochemical parameters and sensory perception.


Assuntos
Manipulação de Alimentos , Sorvetes/análise , Oligossacarídeos/química , Aromatizantes/análise , Galactose/química , Paladar , Vanilla
13.
Genet Mol Res ; 14(4): 13519-31, 2015 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-26535666

RESUMO

We evaluated the expression of the PCA3 gene in urine from patients with nodular hyperplasia/benign prostatic hyperplasia (PNH) or adenocarcinoma type prostate cancer (PCa).The study included 59 men: 22 with PCa, 26 with PNH, and 11 with no alterations (controls). Patients' urine was collected following prostatic massage and quantified by quantitative real-time PCR for prostate cancer antigen 3 gene (PCA3) and prostate-specific antigen gene (PSA) expression with the ACTB gene for normalization. PCA3 gene expression was detected in 16 patients with PCa and 4 with PNH; in the control group, there was no expression of the gene. No significant difference was observed in the mean levels of PCA3 and PSA expression, the PCA3/PSA ratio, and the total PSA levels when the groups of patients with PCa and PNH were compared. The area under the receiver operating characteristic (ROC) curve was 0.625, 0.596, 0.559, and 0.503 for PCA3 and PSA expression, the PCA3/PSA ratio, and total PSA levels, respectively. The sensitivity and specificity of the PCA3 test were 73 and 85%, respectively. Considering the estimated cutoff values (0.2219 and 0.5007 for PCA3 and PCA3/PSA, respectively), we observed a significant difference between the frequency of individuals with values above in the PCa group compared with the PNH group (P < 0.001). We conclude that the qualitative PCA3 test could be applied to initial screening for differentiation between individuals with PCa or PNH and those without prostate changes.


Assuntos
Antígenos de Neoplasias/urina , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/diagnóstico , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/sangue , Hiperplasia Prostática/urina , Neoplasias da Próstata/sangue , Neoplasias da Próstata/urina , Sensibilidade e Especificidade
14.
Ann Rheum Dis ; 73(6): 1246-52, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23636655

RESUMO

OBJECTIVES: To evaluate the proportions of rheumatoid arthritis (RA) sera containing anticitrullinated proteins autoantibodies (ACPA) reactive to α36-50Cit38,42 and/or ß60-74Cit60,72,74, two peptides identified as bearing the immunodominant epitopes of their major target, citrullinated fibrin. To analyse the relationships of anti-α36-50Cit38,42 and anti-ß60-74Cit60,72,74 autoantibodies with autoantibodies reactive to the complete citrullinated human fibrinogen molecule (AhFibA) and with anti-CCP2 antibodies. METHODS: 617 sera from 181 patients with established RA and 436 with non-RA rheumatic diseases were tested by ELISA for AhFibA, anti-CCP2, anti-α36-50Cit38,42, anti-ß60-74Cit60,72,74 autoantibodies, and by nephelometry for rheumatoid factor (RF). Diagnostic indexes, correlations and concordances between tests were analysed. Crossreactivity of anti-α36-50Cit38,42 and anti-ß60-74Cit60,72,74 autoantibodies was assessed in competition experiments. RESULTS: At a diagnostic specificity of 95%, the diagnostic sensitivity of AhFibA (83%) was significantly higher than that of all other tests. The diagnostic sensitivity of anti-ß60-74Cit60,72,74 (71%) was significantly higher than that of anti-α36-50Cit38,42 autoantibodies (51%) but similar to that of anti-CCP2 (74%). Titres of RF, anti-α36-50Cit38,42 and anti-ß60-74Cit60,72,74 autoantibodies were weakly correlated with each other, whereas titres of anti-ß60-74Cit60,72,74 were strongly correlated with those of AhFibA (r=0.633) and anti-CCP2 (r=0.634). Anti-α36-50Cit38,42 and anti-ß60-74Cit60,72,74 mainly corresponded to two non-crossreactive subfamilies of ACPA. More than 90% of AhFibA-positive or anti-CCP2-positive sera recognised the α36-50Cit38,42 and/or the ß60-74Cit60,72,74 peptide. CONCLUSIONS: Autoantibodies reactive to α36-50Cit38,42 and ß60-74Cit60,72,74 form two distinct, non-overlapping subfamilies of ACPA that, together, cover practically all the ACPA reactivity to citrullinated fibrinogen and to CCP2 antigens. In established RA, anti-ß60-74Cit60,72,74 autoantibodies show diagnostic indexes similar to those of anti-CCP2.


Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Citrulina/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/imunologia , Peptídeos Cíclicos/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Epitopos , Feminino , Fibrina/imunologia , Fibrinogênio/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/imunologia , Doenças Reumáticas/imunologia , Fator Reumatoide/imunologia , Adulto Jovem
15.
J Autoimmun ; 50: 67-76, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24365380

RESUMO

B-cell depletion therapy (BCDT) based on rituximab (RTX) induces clinical remission in a majority of seropositive patients with Rheumatoid arthritis (RA). However, all patients eventually relapse. The aim of this study was to determine whether dynamic changes in combinations of serological measures of B-cell activation were associated over up to three cycles of BCDT. We included only RA patients who gave an adequate clinical response, as measured by DAS28. Twenty three patients were studied over 1 cycle, 21 over 2, and 15 over 3 cycles of BCDT. Serum analytes including isotypes of Rheumatoid factors (RhF) and anti-citrullinated protein/peptide antibodies (ACPA), B-cell activating factor (BAFF), serum free light chains (SFLC), soluble CD23 (sCD23), antibodies to tetanus toxoid (TT) and to pneumococcal capsular polysaccharide (PCP) were measured by ELISA at 4 key points in each cycle, namely: Baseline (pre-RTX in each cycle); when B-cell depleted (CD19+B-cells < 5/µl); at B-cell return (CD19+B-cells ≥ 5/µl); and at clinical relapse (ΔDAS28 > 1.2). SFLC were used as a measure of plasmablast activity. As sCD23 is cleaved from naïve B-cells coincident with attaining CD27 expression, levels were used as a novel measure of maturation of B-cells to CD27+. The most consistent changes between baseline and B-cell depletion within all 3 cycles were in SFLC, sCD23 and IgM-RhF which fell and in BAFF levels which rose. After 3 complete cycles of BCDT, both IgM autoantibodies and IgG-CCP had decreased, BAFF levels were higher (all p < 0.05); other analytes remained unchanged compared with baseline. Dynamic changes in λSFLC, sCD23, IgM-RhF and BAFF were also consistently associated with relapse in patients with longer clinical responses after B-cell return. Incremental rises in sCD23 levels in cycles 2 and 3 were correlated with time to relapse. Repopulation of the periphery after BCDT is initiated by naïve B-cells and precedes relapse. Our study showed that differentiation into plasmablasts, attended by sCD23 and SFLC production and IgM-RhF specificity may be required to precipitate relapse in patients experiencing longer responses after RTX. These studies also provide novel information related to the resumption of autoimmune responses and their association with B-cell kinetics following BCDT.


Assuntos
Artrite Reumatoide/terapia , Subpopulações de Linfócitos B/imunologia , Depleção Linfocítica , Plasmócitos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Autoanticorpos/sangue , Fator Ativador de Células B/genética , Fator Ativador de Células B/imunologia , Subpopulações de Linfócitos B/efeitos dos fármacos , Subpopulações de Linfócitos B/patologia , Biomarcadores/metabolismo , Diferenciação Celular , Expressão Gênica , Humanos , Imunoglobulina M/genética , Imunoglobulina M/imunologia , Ativação Linfocitária , Pessoa de Meia-Idade , Plasmócitos/efeitos dos fármacos , Plasmócitos/patologia , Receptores de IgE/genética , Receptores de IgE/imunologia , Recidiva , Indução de Remissão , Rituximab , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia
16.
Clin Radiol ; 69(4): 378-84, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24360516

RESUMO

AIM: To evaluate the performance of diffusion-weighted imaging (DWI) at 3 T for the detection and characterization of breast lesions. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) of the breast, including DWI single-shot spin-echo echo planar images (SS-SE-EPI; eight b-values, 50-3000 s/mm(2)), were acquired in women with a clinical indication for breast MRI. The exclusion criteria were as follows: (1) previous breast surgery, radiotherapy and/or chemotherapy within the prior 48 months (14 women); (2) only cystic lesions (one woman); (3) no detectable enhancing lesion at dynamic contrast-enhanced (DCE)-MRI (15 women); and (4) breast implants (four women). MRI results were corroborated by histopathology or imaging follow-up. Apparent diffusion coefficients (ADCs) were estimated for lesions and normal glandular tissue. Differences in the ADC between tissue types were evaluated and the sensitivity and specificity of the method calculated by receiver operating characteristics (ROC) curves. RESULTS: The final cohort comprised 53 patients with 59 lesions. Histopathology was obtained for 58 lesions. One lesion was validated as benign on imaging follow-up. Mean ADCs of 1.99 ± 0.27 × 10(-3) mm(2)/s, 1.08 ± 0.25 × 10(-3) mm(2)/s, and 1.74 ± 0.35 × 10(-3) mm(2)/s were obtained for normal tissue, malignant, and benign lesions, respectively. Mean ADCs of malignancies were significantly lower than those of benign lesions (p < 0.001) and normal tissue (p < 0.0001). The sensitivity and specificity for stratifying lesions, considering an ADC threshold of 1.41 × 10(-3) mm(2)/s, were 94.3% and 87.5%, respectively; accuracy was 91.5%. CONCLUSION: DWI proved useful for the detection and characterization of breast lesions in the present sample. ADC values provide a high diagnostic performance for differentiation between benign and malignant lesions.


Assuntos
Neoplasias da Mama/diagnóstico , Mama/patologia , Meios de Contraste , Imagem de Difusão por Ressonância Magnética , Detecção Precoce de Câncer , Gadolínio DTPA , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade
17.
Oral Dis ; 20(7): 659-67, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24118270

RESUMO

OBJECTIVE: Orthodontic-induced external apical root resorption (EARR) is a complex phenotype determined by poorly defined mechanical and patient intrinsic factors. The aim of this work was to construct a multifactorial integrative model, including clinical and genetic susceptibility factors, to analyze the risk of developing this common orthodontic complication. MATERIALS AND METHODS: This retrospective study included 195 orthodontic patients. Using a multiple-linear regression model, where the dependent variable was the maximum% of root resorption (%EARRmax) for each patient, we assessed the contribution of nine clinical variables and four polymorphisms of genes involved in bone and tooth root remodeling (rs1718119 from P2RX7, rs1143634 from IL1B, rs3102735 from TNFRSF11B, encoding OPG, and rs1805034 from TNFRSF11A, encoding RANK). RESULTS: Clinical and genetic variables explained 30% of%EARRmax variability. The variables with the most significant unique contribution to the model were: gender (P < 0.05), treatment duration (P < 0.001), premolar extractions (P < 0.01), Hyrax appliance (P < 0.001) and GG genotype of rs1718119 from P2RX7 gene (P < 0.01). Age, overjet, tongue thrust, skeletal class II and the other polymorphisms made minor contributions. CONCLUSION: This study highlights the P2RX7 gene as a possible factor of susceptibility to EARR. A more extensive genetic profile may improve this model.


Assuntos
Polimorfismo Genético , Reabsorção de Dente/genética , Adolescente , Feminino , Humanos , Interleucina-1beta/genética , Masculino , Ortodontia Corretiva , Ligante RANK/genética , Receptores Purinérgicos P2X7/genética , Estudos Retrospectivos
18.
Amino Acids ; 44(6): 1521-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23519707

RESUMO

Antimicrobial peptides (AMPs) are a promising solution to face the antibiotic-resistant problem because they display little or no resistance effects. Dimeric analogues of select AMPs have shown pharmacotechnical advantages, making these molecules promising candidates for the development of novel antibiotic agents. Here, we evaluate the effects of dimerization on the structure and biological activity of the AMP aurein 1.2 (AU). AU and the C- and N-terminal dimers, (AU)2K and E(AU)2, respectively, were synthesized by solid-phase peptide synthesis. Circular dichroism spectra indicated that E(AU)2 has a "coiled coil" structure in water while (AU)2K has an α-helix structure. In contrast, AU displayed typical spectra for disordered structures. In LPC micelles, all peptides acquired a high amount of α-helix structure. Hemolytic and vesicle permeabilization assays showed that AU has a concentration dependence activity, while this effect was less pronounced for dimeric versions, suggesting that dimerization may change the mechanism of action of AU. Notably, the antimicrobial activity against bacteria and yeast decreased with dimerization. However, dimeric peptides promoted the aggregation of C. albicans. The ability to aggregate yeast cells makes dimeric versions of AU attractive candidates to inhibit the adhesion of C. albicans to biological targets and medical devices, preventing disease caused by this fungus.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Candida albicans/efeitos dos fármacos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Dicroísmo Circular , Escherichia coli/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Permeabilidade , Conformação Proteica , Multimerização Proteica , Técnicas de Síntese em Fase Sólida , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade
19.
Appetite ; 66: 84-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23500416

RESUMO

The heightened intake of sodium from processed foods is of great public health concern throughout the world. This study evaluated the sodium contents of cheeses available in Brazil and the contribution of cheese to the daily intake of this micronutrient. The labels of 156 commercial samples of various types of Brazilian cheese (Minas, Prato, mozarella, and requeijão cheese, as well as padrão cheese) were evaluated with respect to the reported sodium content. A high variability in the sodium contents of cheeses within each category was observed, although no significant difference was observed in the sodium content present in one serving (30 g) of cheese versus that present in 100 g of product (p > 0.05). With the exception of Minas cheese, more than 70% of the other cheeses examined in this study could be classified as high-sodium cheeses, with sodium contents exceeding 400 mg Na/100 g of product. These results suggest that cheese manufacturers need to reformulate their products and that public health authorities need to take additional measures to curb sodium intake from cheese consumption, including demand-specific labeling and implementing educational campaigns to inform the public about the dangers associated with high sodium intake.


Assuntos
Queijo/análise , Rotulagem de Alimentos/métodos , Sódio na Dieta/análise , Análise de Variância , Brasil , Rotulagem de Alimentos/estatística & dados numéricos , Humanos
20.
Water Sci Technol ; 67(12): 2746-52, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23787313

RESUMO

The objective of the work is to evaluate the performance of an innovative design of a trickling filter for small population sizes, which has been implemented for the post-treatment of sanitary effluent from a UASB (upflow anaerobic sludge blanket) reactor. The unit, named open trickling filter (OTF), operates with no side walls, no perforated bottom slab and no secondary settler. The OTF packing was 3.5 m high, composed of crushed stone, with a fixed distribution system made of channels with V-notch weirs. The OTF was operated with mean surface hydraulic loading rates of 4.1 and 9.3 m³ m⁻² d⁻¹, corresponding to population equivalents of approximately 250 and 550 inhabitants, respectively. For the surface hydraulic loading rate of 4.1 m³ m⁻² d⁻¹, the median removal efficiencies obtained by the OTF and overall system (UASB + OTF) were, respectively, 24 and 83% for total suspended solids (TSS), 44 and 79% for chemical oxygen demand (COD), 42 and 82% for biochemical oxygen demand (BOD), 40 and 40% for N-ammonia. For the surface hydraulic loading rate of 9.3 m³ m⁻² d⁻¹, the median removal efficiencies obtained by the OTF and global system (UASB + OTF) were 14 and 76% for TSS, 28 and 76% for COD, 25 and 86% for BOD, 15 and 15% for N-ammonia. Considering the great simplicity, no mechanization and small footprint of the system, these results can be considered satisfactory, suggesting that the OTF is suitable for small communities, especially in developing countries.


Assuntos
Cidades , Filtração/instrumentação , Amônia , Anaerobiose , Filtração/métodos , Eliminação de Resíduos Líquidos/métodos
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