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BACKGROUND: Dipeptidyl peptidase 4 (DPP-4) plays a crucial role in breaking down various substrates. It also has effects on the insulin signaling pathway, contributing to insulin resistance, and involvement in inflammatory processes like obesity and type 2 diabetes mellitus. Emerging effects of DPP-4 on bone metabolism include an inverse relationship between DPP-4 activity levels and bone mineral density, along with an increased risk of fractures. MAIN BODY: The influence of DPP-4 on bone metabolism occurs through two axes. The entero-endocrine-osseous axis involves gastrointestinal substrates for DPP-4, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptides 1 (GLP-1) and 2 (GLP-2). Studies suggest that supraphysiological doses of exogenous GLP-2 has a significant inhibitory effect on bone resorption, however the specific mechanism by which GLP-2 influences bone metabolism remains unknown. Of these, GIP stands out for its role in bone formation. Other gastrointestinal DPP-4 substrates are pancreatic peptide YY and neuropeptide Y-both bind to the same receptors and appear to increase bone resorption and decrease bone formation. Adipokines (e.g., leptin and adiponectin) are regulated by DPP-4 and may influence bone remodeling and energy metabolism in a paracrine manner. The pancreatic-endocrine-osseous axis involves a potential link between DPP-4, bone, and energy metabolism through the receptor activator of nuclear factor kappa B ligand (RANKL), which induces DPP-4 expression in osteoclasts, leading to decreased GLP-1 levels and increased blood glucose levels. Inhibitors of DPP-4 participate in the pancreatic-endocrine-osseous axis by increasing endogenous GLP-1. In addition to their glycemic effects, DPP-4 inhibitors have the potential to decrease bone resorption, increase bone formation, and reduce the incidence of osteoporosis and fractures. Still, many questions on the interactions between DPP-4 and bone remain unanswered, particularly regarding the effects of DPP-4 inhibition on the skeleton of older individuals. CONCLUSION: The elucidation of the intricate interactions and impact of DPP-4 on bone is paramount for a proper understanding of the body's mechanisms in regulating bone homeostasis and responses to internal stimuli. This understanding bears significant implications in the investigation of conditions like osteoporosis, in which disruptions to these signaling pathways occur. Further research is essential to uncover the full extent of DPP-4's effects on bone metabolism and energy regulation, paving the way for novel therapeutic interventions targeting these pathways, particularly in older individuals.
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OBJECTIVE: To assess the association between residence place, socioeconomic conditions and oral health-related quality of life (OHRQoL) among schoolchildren from southern Brazil. METHODS: Participants were 9-14-year-old schoolchildren from rural and urban municipal schools from Rosário do Sul, Brazil. The Child Perceptions Questionnaire (CPQ11-14) was used to assess OHRQoL. A structured questionnaire collected data on sociodemographic condition (family income), residence place (urban or rural), use of dental services, and behavioral variables. Clinical oral examination recorded the presence of missing teeth and the gingival bleeding index. Multilevel Poisson regression analysis with a hierarchical approach assessed the association between predictors and CPQ11-14 scores. Rate ratios (RR) and 95% confidence intervals (CI) were estimated. RESULTS: A total of 373 schoolchildren were included (rural area=122; urban area=251), with a mean CPQ11-14 score of 11.83, ranging from 0 to 42. Low-income schoolchildren living in rural areas had 15% higher CPQ11-14 scores than high-income schoolchildren living in urban areas. In urban areas, family income predicted OHRQoL, with low-income schoolchildren having 9% higher CPQ11-14 scores than high-income children. In rural areas, schoolchildren with low household income had 19% higher CPQ11-14 scores than high-income children. CONCLUSION: Schoolchildren from low-income families had a poorer OHRQoL irrespective of their area of residence (rural or urban). The association between family income and OHRQoL was more pronounced among children living in rural areas.
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Cárie Dentária , Qualidade de Vida , Criança , Humanos , Adolescente , Saúde Bucal , Instituições Acadêmicas , Brasil , Inquéritos e QuestionáriosRESUMO
The Latin American Federation of Endocrinology position statement on osteoporosis was developed by endocrinologists from 9 countries. It encompasses the definition, diagnosis, treatment, and follow-up of the disease, the identification of barriers to healthcare, and proposals to improve the disease care in the region. INTRODUCTION: There is a gap in the understanding of osteoporosis in Latin America. The objective of this work is to state the position of the Latin American Federation of Endocrinology on osteoporosis care in postmenopausal women to better bridge this gap. METHODS: An experts' panel was formed comprising of 11 endocrinologists from 9 countries. A data search was conducted with a conceptual approach and data selection was based on the hierarchy of the EBHC pyramid. Unpublished data was considered for local epidemiological data and expert opinion for the identification of barriers to healthcare. An expert consensus based on the Delphi methodology was carried out. Experts were asked to respond on a 5-point Likert Scale to two provided answers to guiding questions. RESULTS: Consensus was agreed on the answer for the questions with the higher median on the Likert scale and synthetized on 16 statements covering the definition of osteoporosis, diagnostic approach, treatment options, and follow-up. Besides clinical topics, unmet needs in osteoporosis were identified in relation to local epidemiological data, barriers to treatment, and misclassification of programs within health systems. CONCLUSIONS: Through a process based on recognized methodological tools, FELAEN's position on osteoporosis was developed. This made it possible to state an optimum scenario for the care of the disease and helped to identify knowledge gaps. There is great variability in the approach to osteoporosis in Latin America and barriers in all the stages of healthcare persist.
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Osteoporose , Consenso , Feminino , Seguimentos , Humanos , América Latina/epidemiologia , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Osteoporose/terapiaRESUMO
AIM: The aim of the present study was to examine the vaccine immune response in ewes supplemented with Bacillus toyonensis BCT-7112T during a period of 5-day supplementation before vaccination against a recombinant Clostridium perfringens epsilon toxin (rETX). METHODS AND RESULTS: Ewes were vaccinated with 200 µg of rETX adjuvanted with 10% aluminium hydroxide. The treat group was orally supplemented with B. toyonensis BCT-7112T (3 × 108 viable spores) for 5 days prior to the first and second vaccination. Ewes supplemented with B. toyonensis BCT-7112T showed higher neutralizing antibody titres than the non-supplemented ewes (P < 0·05), with an increase in serum levels for total IgG anti-rETX by 3·2-fold (P < 0·0001), and for both IgG isotypes IgG1 and IgG2 by 2·1-fold and 2·3-fold (P < 0·01), respectively, compared with the control group. The peripheral blood mononuclear cells of ewes in the supplemented group had a higher (P < 0·05) cytokine mRNA transcription levels for IL-2 (6·4-fold increase), IFN-γ (2·9-fold increase) and transcription factor Bcl6 (2·3-fold increase) compared with the control group. CONCLUSION: We conclude that a 5 days of supplementation with B. toyonensis BCT-7112T prior vaccination is sufficient to significantly improve the humoral immune response of ewes against C. perfringens recombinant ETX vaccine. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings open a new perspective in the utilization of B. toyonensis BCT-7112T as an immunomodulator since a 5 days period of probiotic supplementation is sufficient to improve the vaccine immune response.
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Bacillus , Toxinas Bacterianas/imunologia , Vacinas Bacterianas/imunologia , Probióticos , Ovinos/imunologia , Animais , Toxinas Bacterianas/genética , Vacinas Bacterianas/genética , Feminino , Imunidade Humoral , Imunoglobulina G/sangue , Imunomodulação , Leucócitos Mononucleares/imunologia , Vacinação , Vacinas Sintéticas/imunologiaRESUMO
BACKGROUND: The aim of this study was to compare the prevalence of low muscle mass and sarcopenia in patients with type 2 diabetes mellitus (T2DM) versus paired controls (control group, CG) and the association between sarcopenia and chronic diabetes complications. METHODS: Men and women ≥50 years with T2DM (T2DM group, T2DMG) were recruited during routine outpatient visits. Total body densitometry and handgrip strength (HGS) were evaluated in the T2DMG and CG, while the T2DMG was also evaluated for the physical performance using the gait speed (GS) test. Sarcopenia was diagnosed according to the criteria of the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). RESULTS: The study included 177 individuals in the T2DMG and 146 in the CG. The mean HGS value was lower in the T2DMG (24.4 ± 10.3 kg) compared with the CG (30.9 ± 9.15 kg), p < 0.001, with low HGS in 46 (25.9%) and 10 (9%) in the T2DMG and CG, respectively (p < 0.001). The prevalence of sarcopenia defined according to the FNIH criteria was higher in the T2DMG 23 (12.9%) compared with the CG 8 (5.4%), p < 0.03. The presence of albuminuria increased the odds of sarcopenia (odds ratio (OR) 2.84, 95% confidence interval (CI) 1.07-7.68, p=0.04) and osteoporosis (OR 3.38, 95% CI 1.12-9.89, p=0.03), even in patients with mild to moderate nephropathy. The body composition analysis showed increased odds of sarcopenia with increased percentage of total fat (%TF) in women (OR 1.18, 95% CI, 1.03-1.43, p=0.03) and men (OR 1.31, 95% CI, 1.10-1.75, p=0.01). CONCLUSION: Patients with T2DM presenting with albuminuria, osteoporosis, and increased %TF were more likely to have sarcopenia. This finding emphasizes the need for patients with T2DM to be evaluated for sarcopenia to allow for early implementation of measures to prevent or treat this disorder.
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We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.
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Endotélio Vascular/patologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Trombofilia/patologia , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Endotélio Vascular/fisiopatologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Trombomodulina/sangue , Trombofilia/fisiopatologia , Tromboplastina/análise , Adulto JovemRESUMO
Many rural areas of Latin America and the Caribbean (LAC) region are economically depressed. Rural sewage treatment in most areas of LAC is deficient or non-existent. Consequently, the possibility of generating economic revenue from treated sewage is an attractive option for deprived areas of developing countries. Given its peculiar characteristics, rural sewage may be coupled with biological systems such as algae for nutrient cycling. Acceptable algae growth and nutrient elimination were obtained from rural sewage whose treatment may have fallen short of current disposal standards. In this study, aerobic systems working on an 8-month cycle at three different volumetric loading rates (Bv) were assessed in relation to the lifetime growth of three algae strains native to Ecuador. Results indicate Chlorella sp. M2 as the optimal algal strain, with the highest growth rate at Bv of 1 g COD L-1 d- 1 and a removal of organic-N (30%), PO4 3--P (87%) and NH4 +-N (95%). Concomitantly, the kinetic constants of the sewage resulted in a low biomass yield coefficient, making the proposed system highly suitable for developing countries. Finally, the proposed partial recovery stream method, combining nutrient recovery with economic resource generation, appears to contain great potential.
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Chlorella , Esgotos , Biomassa , Reatores Biológicos , Equador , Nitrogênio , Eliminação de Resíduos LíquidosRESUMO
Quinolinones and sulfonamides are moieties with biological potential that can be linked to form new hybrid compounds with improved potential. However, there are few hybrids of these molecules reported. In this sense, this work presents a structural description of a new sulfonamide-dihydroquinolinone (E)-2-(2-methoxyphenyl)-3-(3-nitrobenzylidene)-1-(phenylsulfonyl)-2,3 dihydroquinolin-4(1H)-one (DHQ). The molecular structure of DHQ was elucidated by X-ray diffraction, nuclear magnetic resonance and infrared spectroscopy, and both molecular packing and intermolecular interactions were analyzed by Hirshfeld surfaces and fingerprint maps. In addition, theoretical calculations on frontier orbitals, molecular electrostatic potential maps, and assignments were performed. The crystal packing of DHQ was found to be stabilized by a dimer through a weak C-Hâ¯O interaction along the c axis. Moreover, the structure is stabilized mainly by C-Hâ¯O and C-Hâ¯π interactions, since the interaction C25-H25â¯π contributes to a chain formation. The Hirshfeld normalized surface shows that the closest interactions are around the atoms linked to the dimer formation. The calculations indicate that DHQ possesses electrophilic sites near O atoms and depleted electrons around the H atoms. There is a band GAP of 3.29 eV between its frontier orbitals, which indicates that DHQ is more reactive than other analogues published.
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To evaluate bone mineral density (BMD) and morphometric vertebral fractures (MVF) in chronic obstructive pulmonary disease (COPD) patients in comparison with two control groups. BMD was lower in the disease group (DG) and was associated with the worst disease severity and prognosis. The prevalence of MVF was high and greater in the DG than in the control groups. INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is associated with osteoporosis and vertebral fractures. It is still unclear whether the presence of fractures and changes in bone mineral density (BMD) are associated with disease severity and prognosis. The aim of this study was to evaluate BMD and morphometric vertebral fractures (MVF) in COPD patients in comparison with two control groups and to correlate these parameters with indices of COPD severity (VEF1 and GOLD) and prognosis (BODE). METHODS: This was a cross-sectional study in COPD patients (disease group, DG) who underwent BMD and vertebral fracture assessment (VFA). Two control groups were used: smokers without COPD (smoker group, SG) and healthy never-smoker individuals (never-smoker group, NSG). RESULTS: The DG comprised 121 patients (65 women, mean age 67.9 ± 8.6 years). Altered BMD was observed in 88.4% of the patients in the DG, which was more prevalent when compared with the control groups (p < 0.001). The BMD values were lower in the DG than in the control groups (p < 0.05). BMD was associated with the worst disease severity and prognosis (p < 0.05). The prevalence of MVF was high (57.8%) and greater than that in the SG (23.8%) and the NSG (14.8%; p < 0.001). The prevalence of fractures was not associated with disease severity and prognosis. CONCLUSIONS: COPD patients have a higher prevalence of MVF and low BMD, and the latter was associated with the severity and poor prognosis of the disease.
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Densidade Óssea/fisiologia , Osteoporose/etiologia , Fraturas por Osteoporose/etiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Fraturas da Coluna Vertebral/etiologia , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Fêmur/fisiopatologia , Colo do Fêmur/fisiopatologia , Volume Expiratório Forçado/fisiologia , Humanos , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoporose/fisiopatologia , Fraturas por Osteoporose/fisiopatologia , Prognóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Índice de Gravidade de Doença , Fumar/efeitos adversos , Fumar/fisiopatologia , Fraturas da Coluna Vertebral/fisiopatologiaRESUMO
BACKGROUND: The 2015 International Panel for neuromyelitis optica (NMO) spectrum disorders (NMOSD) diagnosis (IPND) criteria was recently proposed. However, because there are no studies evaluating application of the IPND criteria in Latin American populations, we aimed to assess whether these new criteria improve the diagnostic rate and reduce the time taken to make the diagnosis in a cohort of Latin American patients. METHODS: We reviewed medical records and applied both the 2006 and 2015 diagnostic criteria to all patients seen in four centers in Argentina, Brazil and Venezuela. Patients with multiple sclerosis (MS, n = 915) or other well-established central nervous system (CNS) inflammatory diseases were excluded. AQP4-ab status was measured using indirect immunofluorescence (23%) and cell-based assay (CBA, 77%). In addition, data on gender, ethnicity, age and symptoms at onset, relapses, neuroimaging and immunosuppressive therapy were collected. RESULTS: A total of 104 patients were classified as presenting NMOSD (2015 IPND). Of these, 64 patients (61.5%) fulfilled the 2006 NMO criteria (32 AQP4-ab positive, 17 AQP4-ab negative and 15 unknown). Thus, 40 new patients (38.5%) were classified as presenting NMOSD using the 2015 IPND criteria (33 AQP4-ab positive, 5 AQP4-ab negative and 2 unknown AQP4-ab status), with a median time taken to fulfill the 2015 NMOSD criteria (n = 104) of 1 month (95% CI: 0.6-1.3) and a median time taken to fulfill the 2006 NMO criteria (n = 64) of 18 months (95% CI: 9-26) (log-rank test: p < 0.0001). Females, with median age of 37 years, white ethnicity and recurrent course, predominated in all samples. Ninety-nine patients (95.1%) had at least 1 of the 3 major core clinical characteristics, of which optic neuritis (56.7%) was the most frequent symptom at disease onset. CONCLUSION: This study showed that there was a 62.5% increase in the rate of diagnosing NMOSD through the 2015 IPND criteria, in comparison with the 2006 NMO criteria, with a shorter median time to diagnosis.
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Neuromielite Óptica/diagnóstico , Adulto , Argentina , Biomarcadores/metabolismo , Brasil , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Neuromielite Óptica/tratamento farmacológico , Estudos Retrospectivos , Fatores de Tempo , VenezuelaRESUMO
The limited efficacy of benznidazole (Bz) indicated by failures of current Phase II clinical trials emphasizes the urgent need to identify new drugs with improved safety and efficacy for treatment of Chagas disease (CD). Herein, we analyzed the efficacy of a series of 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones against different Trypanosoma cruzi discrete type units (DTUs) of relevant clinical forms of CD. Cytotoxic and trypanocidal effect of naphthoquinone derivatives were assessed in mammalian cells, trypomastigotes and intracellular amastigotes using, luminescent assays (CellTiter-Glo and T. cruzi Dm28c-luciferase) and/or counting with a light microscope. Reactive oxygen species (ROS) production and intracellular targets of promising compounds were assessed with 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) probe and ultrastructural analysis, respectively. ADMET properties were analyzed by in silico modeling. Most of the compounds showed low cytotoxic effect. Only two compounds (Compounds 2 and 11) had IC50 values lower than Bz, showing higher susceptibility of bloodstream trypomastigotes. Compound 2 exhibited greater efficacy against trypomastigotes from different T. cruzi DTUs, even better than Bz against Brazil and CL strains. Ultrastructural analysis revealed changes in intracellular compartments, suggesting autophagy as one possible mechanism of action. Oxidative stress, induced by Compound 2, resulted in elevated level of ROS, leading to parasite death. Compound 2 was also effective against intracellular amastigotes, showing high selectivity index. ADMET analysis predicted good oral bioavailability, reduced drug metabolism and no carcinogenic potential for Compound 2. The data highlight Compound 2 as a hit compound and stimulate further structural and pharmacological optimization to potentiate its trypanocidal activity and selectivity.
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Naftoquinonas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Linhagem Celular , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Macaca mulatta , Estrutura Molecular , Naftoquinonas/síntese química , Naftoquinonas/química , Testes de Sensibilidade Parasitária , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Trypanosoma cruzi/metabolismo , Células VeroRESUMO
The aim of this study was to investigate the effect of odontoplasty on apparent digestibility of diet for horses, consumption time, and particle size of feces. Nine horses were used, aged 14.5±3.3 years and weightng 531±38.7kg. The diet consisted of 1.5% of live weight (LW) in Tifton 85 hay and 0.75% of LW in concentrate for both assays. The experiment consisted of two tests of apparent digestibility using the method of total collection, before and after the odontoplasty, where the consumption time of hay and concentrate was also evaluated and the particle size of the feces was analyzed. An effect (P<0.05) of odontoplasty on the apparent digestibility coefficients of dry matter, organic matter, crude protein, neutral detergent fiber and acid detergent fiber was observed. Effect of the consumption time for the concentrate (P<0.05) was observed, but not for the forage (P<0.05). There was more retention (P<0.05) of the fecal particles in the sieves of bigger granulometry. The odontoplasty increases the digestibility of dietary nutrients and feces particle size, without changing feces quality. Animals after the procedure have shorter concentrate consumption time.(AU)
O objetivo deste estudo foi investigar o efeito da odontoplastia sobre a digestibilidade aparente de dieta para equinos, o tempo de consumo e o tamanho de partícula das fezes. Foram utilizados nove equinos, com idade de 14,5±3,3 anos e peso de 531±38,7kg. A dieta consistiu do oferecimento de 1,5% do peso vivo (PV) em feno de Tifton 85 e 0,75% do PV em concentrado para ambos os ensaios. O experimento compôs-se de dois ensaios de digestibilidade aparente pelo método de coleta total, antes e após a odontoplastia, em que também foi avaliado o tempo de consumo do feno e do concentrado e analisado o tamanho de partícula das fezes. Foi observado efeito (P<0,05) da odontoplastia sobre os coeficientes de digestibilidade aparente da matéria seca, matéria orgânica, proteína bruta, fibra em detergente neutro e fibra em detergente ácido. Verificou-se efeito do tempo de consumo para o concentrado (P<0,05), porém não se observou para o volumoso (P<0,05). Houve maior retenção (P<0,05) das partículas das fezes nas peneiras de maior granulometria. A odontoplastia aumenta a digestibilidade dos nutrientes da dieta e o tamanho de partículas nas fezes, sem alterar a qualidade destas. Animais após o procedimento apresentam menor tempo de consumo de concentrado.(AU)
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Animais , Cavalos/metabolismo , Odontologia/veterinária , Recomendações Nutricionais , Ração AnimalRESUMO
The aim of this study was to investigate the effect of odontoplasty on apparent digestibility of diet for horses, consumption time, and particle size of feces. Nine horses were used, aged 14.5±3.3 years and weightng 531±38.7kg. The diet consisted of 1.5% of live weight (LW) in Tifton 85 hay and 0.75% of LW in concentrate for both assays. The experiment consisted of two tests of apparent digestibility using the method of total collection, before and after the odontoplasty, where the consumption time of hay and concentrate was also evaluated and the particle size of the feces was analyzed. An effect (P<0.05) of odontoplasty on the apparent digestibility coefficients of dry matter, organic matter, crude protein, neutral detergent fiber and acid detergent fiber was observed. Effect of the consumption time for the concentrate (P<0.05) was observed, but not for the forage (P<0.05). There was more retention (P<0.05) of the fecal particles in the sieves of bigger granulometry. The odontoplasty increases the digestibility of dietary nutrients and feces particle size, without changing feces quality. Animals after the procedure have shorter concentrate consumption time.(AU)
O objetivo deste estudo foi investigar o efeito da odontoplastia sobre a digestibilidade aparente de dieta para equinos, o tempo de consumo e o tamanho de partícula das fezes. Foram utilizados nove equinos, com idade de 14,5±3,3 anos e peso de 531±38,7kg. A dieta consistiu do oferecimento de 1,5% do peso vivo (PV) em feno de Tifton 85 e 0,75% do PV em concentrado para ambos os ensaios. O experimento compôs-se de dois ensaios de digestibilidade aparente pelo método de coleta total, antes e após a odontoplastia, em que também foi avaliado o tempo de consumo do feno e do concentrado e analisado o tamanho de partícula das fezes. Foi observado efeito (P<0,05) da odontoplastia sobre os coeficientes de digestibilidade aparente da matéria seca, matéria orgânica, proteína bruta, fibra em detergente neutro e fibra em detergente ácido. Verificou-se efeito do tempo de consumo para o concentrado (P<0,05), porém não se observou para o volumoso (P<0,05). Houve maior retenção (P<0,05) das partículas das fezes nas peneiras de maior granulometria. A odontoplastia aumenta a digestibilidade dos nutrientes da dieta e o tamanho de partículas nas fezes, sem alterar a qualidade destas. Animais após o procedimento apresentam menor tempo de consumo de concentrado.(AU)
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Animais , Odontologia/veterinária , Cavalos/metabolismo , Recomendações Nutricionais , Ração AnimalRESUMO
This study determined the distribution of stx1 and stx2 genes in Escherichia coli isolated from dairy herds with regard to animal age, season, and farm production-scale, and analyzed the phylogenetic distribution of the groups A, B1, B2, and D of 276 isolates of bovine feces Shiga toxin-producing E. coli (STEC). The stx1 profile was the most common, detected in 20.4% (202/990) of the isolates, followed by stx2 (4.54%, 45/990) and stx1+stx2 (2.92%, 29/990). The stx1 gene was detected more frequently in calves than in adult animals. In the dry season (winter), the presence of stx1+stx2 profile in cattle feces was higher than in the rainy season (summer), while no significant changes were observed between seasons for the stx1 and stx2 profiles. The most predominant phylogenetic groups in adult animals were B1, A, and D, while groups A and B1 prevailed in calves. Our data highlight the importance of identifying STEC reservoirs, since 7.5% of the tested isolates were positive for stx2, the main profile responsible for the hemolytic-uremic syndrome (HUS). Moreover, these microorganisms are adapted to survive even in hostile environments and can contaminate the food production chain, posing a significant risk to consumers of animal products.(AU)
Esse estudo determinou a distribuição dos genes stx1 e stx2 em Escherichia coli isolados de rebanhos leiteiros em relação a idade, estação e produção, e analisaram a distribuição filogenética dos grupos A, B1, B2 e D de 276 E. coli produtoras de toxina Shiga (STEC). O perfil stx1 foi mais comum, detectado em 20,4% (202/990) dos isolados, seguido de stx2 (4,54%, 45/990) e stx1+stx2 (2,92%, 29/990). O gene stx1 foi detectado mais frequentemente em bezerros que animais adultos. No período de seca (inverno), a presença do perfil stx1+stx2 nas fezes dos bovinos foi mais prevalente que no período chuvoso (verão), apesar de não haver diferença significativa entre estações para os perfis stx1 e stx2. Os grupos filogenéticos mais predominantes em animais adultos foram B1, A e D, enquanto grupos A e B2 prevaleceram em bezerros. Nossos dados enfatizam a importância de se detectar reservatórios de STEC já que 7,5% dos isolados testados foram positivos para stx2, o perfil mais prevalente em casos de síndrome hemolítica-urêmica. Ademais, esses microorganismos são adaptados à sobreviver em ambientes hostis e contaminam a cadeia alimentar, levando a risco significativo para consumidores de alimentos de origem animal.(AU)
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Animais , Bovinos , Bovinos/genética , Toxina Shiga I/genética , Toxina Shiga II/genética , Escherichia coli/isolamento & purificação , Escherichia coli/genéticaRESUMO
This study determined the distribution of stx1 and stx2 genes in Escherichia coli isolated from dairy herds with regard to animal age, season, and farm production-scale, and analyzed the phylogenetic distribution of the groups A, B1, B2, and D of 276 isolates of bovine feces Shiga toxin-producing E. coli (STEC). The stx1 profile was the most common, detected in 20.4% (202/990) of the isolates, followed by stx2 (4.54%, 45/990) and stx1+stx2 (2.92%, 29/990). The stx1 gene was detected more frequently in calves than in adult animals. In the dry season (winter), the presence of stx1+stx2 profile in cattle feces was higher than in the rainy season (summer), while no significant changes were observed between seasons for the stx1 and stx2 profiles. The most predominant phylogenetic groups in adult animals were B1, A, and D, while groups A and B1 prevailed in calves. Our data highlight the importance of identifying STEC reservoirs, since 7.5% of the tested isolates were positive for stx2, the main profile responsible for the hemolytic-uremic syndrome (HUS). Moreover, these microorganisms are adapted to survive even in hostile environments and can contaminate the food production chain, posing a significant risk to consumers of animal products.(AU)
Esse estudo determinou a distribuição dos genes stx1 e stx2 em Escherichia coli isolados de rebanhos leiteiros em relação a idade, estação e produção, e analisaram a distribuição filogenética dos grupos A, B1, B2 e D de 276 E. coli produtoras de toxina Shiga (STEC). O perfil stx1 foi mais comum, detectado em 20,4% (202/990) dos isolados, seguido de stx2 (4,54%, 45/990) e stx1+stx2 (2,92%, 29/990). O gene stx1 foi detectado mais frequentemente em bezerros que animais adultos. No período de seca (inverno), a presença do perfil stx1+stx2 nas fezes dos bovinos foi mais prevalente que no período chuvoso (verão), apesar de não haver diferença significativa entre estações para os perfis stx1 e stx2. Os grupos filogenéticos mais predominantes em animais adultos foram B1, A e D, enquanto grupos A e B2 prevaleceram em bezerros. Nossos dados enfatizam a importância de se detectar reservatórios de STEC já que 7,5% dos isolados testados foram positivos para stx2, o perfil mais prevalente em casos de síndrome hemolítica-urêmica. Ademais, esses microorganismos são adaptados à sobreviver em ambientes hostis e contaminam a cadeia alimentar, levando a risco significativo para consumidores de alimentos de origem animal.(AU)
Assuntos
Animais , Bovinos , Bovinos/genética , Toxina Shiga I/genética , Toxina Shiga II/genética , Escherichia coli/isolamento & purificação , Escherichia coli/genéticaAssuntos
Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Osteoporose/tratamento farmacológico , Anabolizantes/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/ultraestrutura , Ensaios Clínicos como Assunto , Humanos , Osteoporose/patologia , Teriparatida/uso terapêutico , Tiofenos/uso terapêutico , Resultado do Tratamento , Ácido Zoledrônico/uso terapêuticoRESUMO
AIMS: The aims of this study were to design, synthesize and to evaluate 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones against Gram-negative and Gram-positive bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm, to probe for potential lead structures. METHODS AND RESULTS: Thirty-six new analogues were prepared with good yields using a simple, fast, operational three-procedure reaction and a thiol addition to an ο-quinone methide using microwave irradiation. All compounds were tested against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Proteus mirabilis ATCC 15290, Serratia marcescens ATCC 14756, Klebsiella pneumoniae ATCC 4352, Enterobacter cloacae ATCC 23355, Enterococcus faecalis ATCC 29212, S. aureus ATCC 25923, Staphylococcus simulans ATCC 27851, Staphylococcus epidermidis ATCC 12228 and a hospital strain of MRSA. Their antibacterial activity was determined using the disc diffusion method, revealing the activity of 19 compounds, mainly against Gram-positive strains. Interestingly, the minimal inhibitory concentration ranges detected for the hit molecules (32-128 µg ml-1 ) were within Clinical and Laboratory Standards Institute levels. Promisingly, compound 15 affected the MRSA strain, with a reduction of up to 50% in biofilm formation, which is better than vancomycin as biofilm forms a barrier against the antibiotic that avoids its action. CONCLUSIONS: After probing 36 naphthoquinones for a potential antibacterial lead structure against the bacterial biofilm, we found that compound 15 should be explored further and also should be structurally modified in the near future to test against Gram-negative strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Since vancomycin is one of the last treatment options currently available, and it is unable to inhibit biofilm, the research of new antimicrobials is urgent. In this context, 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones proved to be a promising lead structure against MRSA and bacterial biofilm.
Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Naftoquinonas/farmacologia , Enterobacter cloacae , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Naftoquinonas/química , Proteus mirabilis/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus/efeitos dos fármacos , VancomicinaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of Pyrostegia venusta are popularly used to treat vitiligo; however, none in vivo study showed its ability. AIM OF THE STUDY: The overall objective of the present study was to evaluate the antiinflammatory and hyperpigmentant activities of hydroethanolic (HE) extract of leaves from P. venusta in animal models of vitiligo induced by croton oil and monobenzone. MATERIALS AND METHODS: The antiinflamatory and antioxidative effects of topical and oral administration of HE extract of P. venusta were evaluated in Swiss mice on edema model induced by croton oil, and further the N-acetyl-b-d-glucosaminidase (NAG) activity, cell infiltration, and cytokine and reactive species oxygen (ROS) levels. The involvement on mice pigmentation, cell infiltration and cytokine levels were evaluated on vitiligo model induced by monobenzone in C56BL/6 mice. RESULTS: HE of P. venusta by gavage (300 mg/kg) reduced NAG activity in 32.5 ± 5% on mouse ear edema induced by croton oil. Similarly, cell infiltration was lower (42.3 ± 5.9%) when compared to control group, as well as interleukin-1ß (IL-1ß), interleukin (IL-6) and tumor necrosis factor-α (TNF-α) levels, in 44.1 ± 9.7%, 71.9 ± 22.2% and to basal levels, respectively. Topical treatment with HE of P. venusta (10%) diminished cell infiltration (67.7 ± 7.1%) and ROS levels (total reduction). P. venusta either by gavage (300 mg/Kg) or topically (10%) increased epidermal melanin level (116.5 ± 13% and 100 ± 16.9%, respectively), diminished dermal depigmentation (36.0 ± 6.7% and 38.2 ± 6.2%, respectively), as well as tissue TNF-α levels (68.2 ± 11.6% and 99.2 ± 12.1%, respectively) and cell infiltration (basal levels and 94.3 ± 9.17%, respectively). However, only topical treatment with HE of P. venusta altered melanin specific marker in hair follicles. CONCLUSIONS: For the first time these data show that topical and oral administrations of P. venusta have significant antiinflammatory and hyperpigmentant effects, demonstrating different topical and systemic effects through two animal models. Together these models are capable to mimic several features founded in vitiligo, and the results support the ethnopharmacological use of P. venusta.
Assuntos
Anti-Inflamatórios/uso terapêutico , Bignoniaceae , Edema/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Vitiligo/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Óleo de Cróton , Citocinas/metabolismo , Edema/induzido quimicamente , Edema/metabolismo , Feminino , Hidroquinonas , Masculino , Melaninas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fitoterapia , Extratos Vegetais/farmacologia , Folhas de Planta , Espécies Reativas de Oxigênio/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Vitiligo/induzido quimicamente , Vitiligo/metabolismoRESUMO
In this work, 25,806 potentially amplifiable microsatellite loci (PAL) were identified in pejerrey, (Odontesthes humensis), with 21% of dinucleotide, 22% trinucleotide, 37% tetranucleotide, 13% pentanucleotide and 7% hexanucleotide. Of the total loci, 167 were classified as "Best PAL", more likely to be variables in populations. The results show that with a small coverage of the genome it was possible to identify a large number of microsatellite loci...