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1.
J Neuroimmunol ; 337: 577080, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31670062

RESUMO

Myasthenia Gravis (MG) - an autoimmune neuromuscular disease - is known by the production of autoantibodies against components of the neuromuscular junction mainly to the acetylcholine receptor, which cause the destruction and compromises the synaptic transmission. This disease is characterized by fluctuating and fatigable muscle weakness, becoming more intensive with activity, but with an improvement under resting. There are many therapeutic strategies used to alleviate MG symptoms, either by improving the transmission of the nerve impulse or by ameliorating autoimmune reactions with e.g. steroids, immunosuppressant drugs, or monoclonal antibodies (rituximab and eculizumab). Many breakthroughs in the discovery of new therapeutic targets have been reported, but MG remains to be a chronic disease where the symptoms are kept in the majority of patients. In this review, we discuss the different therapeutic strategies that have been used over the years to alleviate MG symptoms, as well as innovative therapeutic approaches currently under study.

2.
Platelets ; : 1-8, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31625437

RESUMO

Deep vein thrombosis (DVT) is a disease with high prevalence and morbidity. It can lead to pulmonary embolism with severe respiratory insufficiency and risk of death. Mechanisms behind all stages of DVT, such as thrombosis commencement, propagation, and resolution, remain incompletely understood. Animal models represent an invaluable tool to explore these problems and identify new targets for DVT prevention and treatment. In this review, we discuss existing models of venous thrombosis, their advantages and disadvantages, and applicability to studying different aspects of DVT pathophysiology. We also speculate about requirements for an "ideal model" that would best recapitulate features of human DVT and discuss readouts of various models.

3.
Curr Pharm Des ; 25(11): 1312-1334, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31465282

RESUMO

Nanotechnology refers to the control, manipulation, study and manufacture of structures and devices at the nanometer size range. The small size, customized surface, improved solubility and multi-functionality of nanoparticles will continue to create new biomedical applications, as nanoparticles allow to dominate stability, solubility and bioavailability, as well controlled release of drugs. The type of a nanoparticle, and its related chemical, physical and morphological properties influence its interaction with living cells, as well as determine the route of clearance and possible toxic effects. This field requires cross-disciplinary research and gives opportunities to design and develop multifunctional devices, which allow the diagnosis and treatment of devastating diseases. Over the past few decades, biodegradable polymers have been studied for the fabrication of drug delivery systems. There was extensive development of biodegradable polymeric nanoparticles for drug delivery and tissue engineering, in view of their applications in controlling the release of drugs, stabilizing labile molecules from degradation and site-specific drug targeting. The primary aim is to reduce dosing frequency and prolong the therapeutic outcomes. For this purpose, inert excipients should be selected, being biopolymers, e.g. sodium alginate, commonly used in controlled drug delivery. Nanoparticles composed of alginate (known as anionic polysaccharide widely distributed in the cell walls of brown algae which, when in contact with water, forms a viscous gum) have emerged as one of the most extensively characterized biomaterials used for drug delivery and targeting a set of administration routes. Their advantages include not only the versatile physicochemical properties, which allow chemical modifications for site-specific targeting but also their biocompatibility and biodegradation profiles, as well as mucoadhesiveness. Furthermore, mechanical strength, gelation, and cell affinity can be modulated by combining alginate nanoparticles with other polymers, surface tailoring using specific targeting moieties and by chemical or physical cross-linking. However, for every physicochemical modification in the macromolecule/ nanoparticles, a new toxicological profile may be obtained. In this paper, the different aspects related to the use of alginate nanoparticles for drug delivery and targeting have been revised, as well as how their toxicological profile will determine the therapeutic outcome of the drug delivery system.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31274159

RESUMO

OBJECTIVES: SS is an autoimmune condition characterized by systemic B-cell activation, autoantibody production and ectopic germinal centres' formation within the salivary gland (SG). The extent of SG infiltrate has been proposed as a biomarker of disease severity. Plasma levels of CXCL13 correlate with germinal centres' activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B-cell activation. The aim of this study was to evaluate the potential role of CXCL13 as a biomarker of SG pathology in two independent SS cohorts. METHODS: 109 patients with SS were recruited at Sapienza University of Rome (Italy) (n = 60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n = 49). Both sera and matched minor SG biopsy were available. Sicca (n = 57) and healthy subjects' (n = 19) sera were used as control. RESULTS: CXCL13 serum level was higher in SS patients compared with controls. Correlations between its serum levels and a series of histomorphological parameters, including size of the aggregates and the presence germinal centres', were observed. CONCLUSION: Our data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies.

5.
Proc Natl Acad Sci U S A ; 116(27): 13490-13497, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31213547

RESUMO

Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases.

6.
Nature ; 570(7760): 246-251, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31142839

RESUMO

The identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune-mediated inflammatory diseases (IMIDs)1,2. However, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue-driven processes observed in IMIDs, such as inflammation and damage3-5. Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of fibroblast activation protein-α (FAPα)+ fibroblasts suppressed both inflammation and bone erosions in mouse models of resolving and persistent arthritis. Single-cell transcriptional analysis identified two distinct fibroblast subsets within the FAPα+ population: FAPα+THY1+ immune effector fibroblasts located in the synovial sub-lining, and FAPα+THY1- destructive fibroblasts restricted to the synovial lining layer. When adoptively transferred into the joint, FAPα+THY1- fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation, whereas transfer of FAPα+ THY1+ fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell-based therapies aimed at modulating inflammation and tissue damage.

7.
Cell Stem Cell ; 25(1): 137-148.e6, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31031138

RESUMO

Acute myeloid leukemia (AML) is an aggressive clonal disorder of hematopoietic stem cells (HSCs) and primitive progenitors that blocks their myeloid differentiation, generating self-renewing leukemic stem cells (LSCs). Here, we show that the mRNA m6A reader YTHDF2 is overexpressed in a broad spectrum of human AML and is required for disease initiation as well as propagation in mouse and human AML. YTHDF2 decreases the half-life of diverse m6A transcripts that contribute to the overall integrity of LSC function, including the tumor necrosis factor receptor Tnfrsf2, whose upregulation in Ythdf2-deficient LSCs primes cells for apoptosis. Intriguingly, YTHDF2 is not essential for normal HSC function, with YTHDF2 deficiency actually enhancing HSC activity. Thus, we identify YTHDF2 as a unique therapeutic target whose inhibition selectively targets LSCs while promoting HSC expansion.

8.
Acta Med Port ; 32(2): 101-110, 2019 Feb 28.
Artigo em Português | MEDLINE | ID: mdl-30896390

RESUMO

INTRODUCTION: Respiratory tract infections represent the most frequent conditions in pediatric clinical practice that motivate antibiotic prescribing. The objective was to identify the frequency and pattern of antibacterial prescribing in respiratory diseases. MATERIAL AND METHODS: Over a period of two years (divided by the presentation of the clinical guideline standards) data was collected from clinical records of children with respiratory disease. Chi-square tests or Fisher's exact test were used to test associations between variables, statistical significance p < 0.05. RESULTS: There were 547 visits (mean age 6 years ± 5.3, 55% male gender). Analysis for Group A Streptococcus of the oropharynx was most frequently requested by pediatric residents (p = 0.005). Chest x-rays were more frequently requested by the Family Physician (p = 0.033). An antibiotic was prescribed in 87% of pneumonias, 84% acute otitis media, 68% acute tonsillitis, 25% laryngitis, 17% upper respiratory infections, 16% acute bronchiolitis. The Family Physician prescribed antibiotics more often than the Pediatrics resident in acute tonsillitis (p = 0.003) and in acute otitis media (p = 0.013). The most frequently prescribed antibiotic was amoxicillin (61%). There were no significant differences between the two periods studied regarding the number of prescriptions and antibiotic choice of the conditions studied. DISCUSSION: Antibiotic prescribing in pediatric acute respiratory infections was high and the choice of antibiotic therapy could be adjusted. We found no difference in antibiotic prescribing after the presentation of the clinical guideline standards. CONCLUSION: An improvement in the antibiotic prescription in children and adolescents in the outpatient clinic is considered necessary.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Antibacterianos/uso terapêutico , Padrões de Prática Médica , Infecções Respiratórias/tratamento farmacológico , Adolescente , Amoxicilina/uso terapêutico , Anticorpos Antibacterianos/análise , Bronquite/tratamento farmacológico , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/tratamento farmacológico , Feminino , Medicina Geral/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Internato e Residência/estatística & dados numéricos , Masculino , Otite Média/tratamento farmacológico , Pediatria/estatística & dados numéricos , Pneumonia/tratamento farmacológico , Estudos Prospectivos , Infecções Respiratórias/diagnóstico por imagem , Infecções Respiratórias/microbiologia , Estudos Retrospectivos , Streptococcus pyogenes/imunologia , Tonsilite/tratamento farmacológico
9.
Motriz (Online) ; 25(2): e101914, 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1012698

RESUMO

Abstract Aim: To assess the prevalence, quality of life (QoL), and the damages caused by PH, in the professional and personal scope of Physical Education academics with Primary Hyperhidrosis (PH). Methods: A descriptive, exploratory, qualitative and quantitative cross-sectional study was carried out. Twenty-five students from the physical education course at Tiradentes University, Aracaju-SE, were interviewed from August to November 2017. Validated questionnaires were used on PH's influence in academic activities and QoL. absolute and relative frequencies in the case of categorical variables and measures of trend and central variability in the case of numerical variables. Results: The prevalence of PH in students of Physical Education was 11.11%, mainly in combined sites, such as palmoplantar, and with no difference between the sexes. The symptoms started mostly during childhood and adolescence. Most of the interviewees (92%) reported difficulties with activities such as sports, use of personal protective equipment, handling of work equipment and instruments, and exacerbation in stress situations. They reported significant harm to QoL in situations of greeting people with handshakes, writing, wearing socks and dancing socially. Conclusion: Although PH is a disease that negatively impacts the QoL, it is still little known in the academic world with little demand for medical help. Therefore, it is necessary greater dissemination of the disease for its early diagnosis, related to the intensity of the sweating for a better therapeutic approach.

10.
Curr Med Chem ; 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30378485

RESUMO

Linseed - also known as flaxseed -, is known for its beneficial effects on animal health attributed to its composition, comprising omega-6 (linoleic) and omega-3 (α-linolenic) fatty acids, various dietary fibers and lignans, which have health benefits in reducing the risk of cancer and cardiovascular diseases, lowering the levels of LDL-cholesterol and relaxing the smooth muscle cells in arteries increasing the blood flow. Essential fatty acids from flax participate in several metabolic processes of the cell, not only as structuring components of the cell membrane, but also as storage lipids. Flax is consumed in the form of seeds (whole, milled or roasted), as an oil and as flour to provide basic nutrition. Flax can be considered a functional food. Several formulations containing flax are available on the market in the form of e.g. capsules and microencapsulated powders having potential as nutraceuticals for their beneficial effects on health. This paper revises the different lipid classes found in flaxseeds and their genomics. It also discusses the beneficial effects of flax and flaxseed oil and their biological advantages as ingredients in pharmaceuticals and in nutraceuticals products.

11.
Eur J Pharm Sci ; 128: 27-35, 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-30472221

RESUMO

CAB51, a compact antibody against human epithelial growth receptor 2 (HER2, ErbB2), has been linked to cationic Solid Lipid Nanoparticles (SLN) via streptavidin-biotin interaction and their targeting potential evaluated against breast cancer cells. The amount of streptavidin and biotinylated antibody was optimised by monitoring the mean complex size (intensity weighed average diameter), polydispersity index and immediate stability in phosphate buffer saline (PBS). The effect on MCF-7 and BT-474 cells was evaluated at concentrations of 0.01 mg/mL and 0.1 mg/mL (counted as solid lipid). Streptavidin adsorption onto SLN surface had no influence on cell viability. Linking the antibody showed a synergistic effect on cell viability at lowest concentration tested (0.01 mg/mL) which was lower than that observed after exposure to SLN alone or antibody alone. At the higher tested concentration (0.1 mg/mL), the observed toxicity was entirely governed by the inherent toxicity of the SLN themselves. Streptavidin adsorption had no effect on accumulation in cells, while the antibody-containing complexes showed clearly increased internalisation in both cell lines. In HER2/neu positive BT-474 higher internalisation was observed than in HER2/neu negative MCF-7.

12.
Ann Rheum Dis ; 2018 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-30472652

RESUMO

BACKGROUND: The phosphatidylinositol 3-kinase delta isoform (PI3Kδ) belongs to an intracellular lipid kinase family that regulate lymphocyte metabolism, survival, proliferation, apoptosis and migration and has been successfully targeted in B-cell malignancies. Primary Sjögren's syndrome (pSS) is a chronic immune-mediated inflammatory disease characterised by exocrine gland lymphocytic infiltration and B-cell hyperactivation which results in systemic manifestations, autoantibody production and loss of glandular function. Given the central role of B cells in pSS pathogenesis, we investigated PI3Kδ pathway activation in pSS and the functional consequences of blocking PI3Kδ in a murine model of focal sialoadenitis that mimics some features of pSS. METHODS AND RESULTS: Target validation assays showed significant expression of phosphorylated ribosomal protein S6 (pS6), a downstream mediator of the phosphatidylinositol 3-kinase delta (PI3Kδ) pathway, within pSS salivary glands. pS6 distribution was found to co-localise with T/B cell markers within pSS aggregates and the CD138+ plasma cells infiltrating the glands. In vivo blockade of PI3Kδ activity with seletalisib, a PI3Kδ-selective inhibitor, in a murine model of focal sialoadenitis decreased accumulation of lymphocytes and plasma cells within the glands of treated mice in the prophylactic and therapeutic regimes. Additionally, production of lymphoid chemokines and cytokines associated with ectopic lymphoneogenesis and, remarkably, saliva flow and autoantibody production, were significantly affected by treatment with seletalisib. CONCLUSION: These data demonstrate activation of PI3Kδ pathway within the glands of patients with pSS and its contribution to disease pathogenesis in a model of disease, supporting the exploration of the therapeutic potential of PI3Kδ pathway inhibition in this condition.

13.
Pharm Dev Technol ; : 1-25, 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30477410

RESUMO

The aim of this work has been the development of a non-toxic, long-term stable solid lipid nanoparticles (SLN) formulation for the loading of Nimsulide (NiM) by a 22 factorial design. The optimized formulation was composed of 10 wt% of glyceryl behenate and 2.5 wt% of poloxamer 188. Immediately after production, Z-Ave of NiM-SLN was 166.1 ± 0.114 nm, with a polydispersity index (PI) of 0.171 ± 0051 and zeta potential nearly neutral (-3.10 ± 0.166 mV). A slight increase of Z-Ave was recorded for NiM-SLN stored at 25 °C for a period of 15 days, whereas at 4 °C particles kept size within similar range. Long-term stability was monitored using TurbiscanLab®, showing a high stability of the nanoparticles with variations in the backscattering profiles below 10%. The release profile of NiM-SLN followed a sustained pattern with ca. 30% of drug released up to 24 h. Empty-SLN and NiM-SLN were non-toxic after exposing Caco-2 cells to the highest concentration (100 µg/mL) up to 48 hours (cell viability higher than 80%). NiM-SLN were lyophilized using different cryoprotectants, producing particles of 463.1 ± 36.63 nm (PI 0.491 ± 0.027) with 5% trehalose. Solid character of NiM-SLN was confirmed by DSC, recording a recrystallization index of 83% for NiM-SLN and of 74% for lyophilized SLN.

14.
Acta Med Port ; 31(9): 489-495, 2018 Sep 28.
Artigo em Português | MEDLINE | ID: mdl-30332373

RESUMO

INTRODUCTION: Pulmonary thromboembolism and deep venous thrombosis occur in pediatric age, with unknown incidence, morbidity and mortality. Our aim is to review the epidemiology, clinical presentation, complementary diagnostic tests and prognosis of patients with pulmonary thromboembolism and deep venous thrombosis. MATERIAL AND METHODS: Retrospective, descriptive and analytical study of pediatric patients admitted to a Level II hospital for pulmonary thromboembolism and deep venous thrombosis, between 2000 and 2014. Demographic characteristics, clinical history, comorbidities and risk factors were studied. RESULTS: Eleven patients (n = 7 pulmonary thromboembolism, n = 5 deep venous thrombosis, n = 1 both), 64% females and with 16 years old average, were admitted. All patients with pulmonary thromboembolism presented symptoms of chest pain and/or dyspnea, 25% syncope/palpitations and 25% fever. All patients with deep venous thrombosis reported localized pain at the site of obstruction, 83% edema/cyanosis of the affected limb and 17% fever. The study of positive thrombophilia was the most frequent risk factor in both entities. The mean value of D-dimers was 3252 ug/dL and 2660 ug/dL in pulmonary thromboembolism and deep venous thrombosis, respectively. All patients started anticoagulation, three required intensive care, two had sequelae and one died. DISCUSSION: All patients had at least one risk factor, and hereditary hypercoagulability was most commonly established. CONCLUSIONS: The increased incidence in the pediatric population described in some studies can be attributed to an increased awareness of this pathology, medical advances and increasing survival of chronic diseases. There is a lack of evidence-based recommendations identifying patients at risk of thrombosis so that decisions can be made carefully, balancing the risk and benefit in each case.

15.
Mol Ecol ; 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30276912

RESUMO

A thorough understanding of ecological networks relies on comprehensive information on trophic relationships among species. Since unpicking the diet of many organisms is unattainable using traditional morphology-based approaches, the application of high-throughput sequencing methods represents a rapid and powerful way forward. Here, we assessed the application of DNA metabarcoding with nearly universal primers for the mitochondrial marker cytochrome c oxidase I in defining the trophic ecology of adult brown shrimp, Crangon crangon, in six European estuaries. The exact trophic role of this abundant and widespread coastal benthic species is somewhat controversial, while information on geographical variation remains scant. Results revealed a highly opportunistic behaviour. Shrimp stomach contents contained hundreds of taxa (>1,000 molecular operational taxonomic units), of which 291 were identified as distinct species, belonging to 35 phyla. Only twenty ascertained species had a mean relative abundance of more than 0.5%. Predominant species included other abundant coastal and estuarine taxa, including the shore crab Carcinus maenas and the amphipod Corophium volutator. Jacobs' selectivity index estimates based on DNA extracted from both shrimp stomachs and sediment samples were used to assess the shrimp's trophic niche indicating a generalist diet, dominated by crustaceans, polychaetes and fish. Spatial variation in diet composition, at regional and local scales, confirmed the highly flexible nature of this trophic opportunist. Furthermore, the detection of a prevalent, possibly endoparasitic fungus (Purpureocillium lilacinum) in the shrimp's stomach demonstrates the wide range of questions that can be addressed using metabarcoding, towards a more robust reconstruction of ecological networks.

16.
Sci Total Environ ; 642: 1163-1171, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30045498

RESUMO

The impact of European aquaculture, namely trout farms, in the spread of antibiotic resistance and/or zoonotic pathogens has been scarcely addressed. Moreover, aquaculture contamination sources and bacterial dissemination routes have been barely explored. In this study, we assessed the contribution of Portuguese land-based intensive rainbow trout farms and retailed market trout to the spread of Salmonella and bacteria carrying clinically-relevant antibiotic resistance genes (ARGs) as well as inflow water and feed as possible sources of those contaminants. Cultural and molecular methods were used to analyse 53 fish farm samples (upstream/downstream water and sediments, tanks and trout) and 25 marketed trout. Plasmid-mediated quinolone resistance (PMQR) genes were found in 21% (n = 11/53) of samples (water/sediment/feed/trout), from all collection points (upstream/within/downstream tanks) and seasons, as well as in 12% (n = 3/25) of marketed trout (3 supermarkets). PMQR genes (qnrS1-S2-S3, qnrB7-B19, qnrD1, oqxAB) were detected in Enterobacteriaceae or Aeromonas hydrophila. An E. coli strain producing extended-spectrum-beta-lactamase SHV-12 was detected in all sampled points of a fish farm. Salmonella (4 serotypes, including S. Newport-ST118) was detected in 26% (n = 14/53) of the samples from both farms (water/sediment upstream/within tanks). The clinically-relevant plasmid-mediated colistin resistance mcr genes were not detected. However, colistin resistant S. Abony with new mutations in the chromosomal pmrA and pmrB genes was observed. Identical Salmonella and SHV-12-producing E. coli strains (by PFGE/MLST) in water upstream and within trout tanks points to inflow-water of trout farms as an important source of pathogenic bacteria and ARG contamination. These results highlight the need to define microbiological standards for water supplying fish farms in the EU and to establish surveillance and control strategies to limit bacterial transmission associated with this fastest growing food sector worldwide.

17.
Int J Food Microbiol ; 285: 34-41, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30015261

RESUMO

Simpler, quick and low-cost methods for routine Salmonella enterica typing are required for epidemiologic surveillance of this important zoonotic pathogen. In this study, using a comprehensive isolate collection, we investigated the potential of Fourier transform infrared spectroscopy (FTIRS) to discriminate the most clinically-relevant serogroups and serotypes of non-typhoid Salmonella. Moreover, the role of O-units composition on the FTIRS Salmonella discrimination was also explored. S. enterica isolates (n = 325; 2002-2015; different sources and countries), of 57 serotypes and 15 serogroups [including the most frequent ones, B-n = 122; C-n = 108; D-n = 43 and E-n = 33)] were analysed by FTIRS. Infrared spectra were analysed by Partial Least Square Discriminant Analysis (PLSDA) and/or Principal Component Analysis (PCA). The polysaccharides region provided the spectral sharpest differences being used in the subsequent Salmonella typing. Serogroups (B, C, D and E) discrimination was achieved with high accuracy (99.6% of correct assignments; PLSDA model). Differences in the O-unit structures composition of those serogroups are likely justifying the discrimination achieved. Other serogroups (G, H, K, L, M, N, O, T, U, Y, Z) were correctly predicted as not belonging to serogroups B, C, D nor E, except for 3 isolates of serogroups H (S. Sundsvall, n = 1) and K (S. Cerro, n = 2). In fact, O-unit structure of serogroup H and K shows some similarity with sub-serogroup C1 with the remaining serogroups presenting marked differences in this cellular component. The sub-serogroups discrimination was successfully achieved for C1, C2 and C3 (using PCA), and for E1-E2-E3 and E4 (by PLSDA). Appropriate serotype discrimination was obtained for most of S. Rissen from the remaining C1 serotypes (91.5%-PLSDA), and S. Enteritidis (D1) from the remaining D1/D2 serotypes (93.4%-PLSDA). The lack of available O-unit composition for particular serotypes prevents the elucidation of the role of this cellular component on the discrimination at serotype level obtained. FTIRS was able to discriminate relevant serogroups (B, C, D and E), sub-serogroups (C1, C2 and C3; E1-E2-E3 and E4) and particular important serotypes (S. Enteritidis, S. Rissen and S. Senftenberg). Further studies on O-antigen composition would clarify the fundaments of discrimination obtained by FTIRS.

18.
Sci Total Environ ; 625: 1102-1112, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29996407

RESUMO

The role of European fish farms in the spread of antimicrobial-resistance in the environment and food chain, as well as possible sources of their contamination by clinically relevant antimicrobial-resistance bacteria is scarcely known. This study aimed to assess the contribution of Portuguese rural trout farms on dispersion of Enterococcus with antimicrobial-resistance and putative virulence genes in the environment and food chain, as well as to identify farms contamination sources. We also assessed the presence of Enterococcus with low-levels of antimicrobial-resistance using epidemiological cut-offs (ECOFFs). Enterococcus spp. (n=391) from water/sediment recovered upstream, within and downstream trout tanks, feed, trout (2 aquacultures; no antibiotic use) and marketed trout (8 supermarkets) showed variable resistance to tetracycline, erythromycin, ciprofloxacin, chloramphenicol, quinupristin-dalfopristin, nitrofurantoin or aminoglycosides. Antimicrobial-resistance rates were similar among upstream, within and downstream trout tank samples (P>0.05), positioning water-supplying aquacultures as a source of multidrug-resistant (MDR) strains. Nevertheless, predominance of MDR E. faecium in feed, trout tanks and trout comparing to upstream samples, suggests feed as an additional aquaculture contamination source. The observation of E. faecium and E. faecalis susceptible to ampicillin and gentamicin by clinical breakpoints but with low-levels of resistance to those antimicrobials by ECOFFs breakpoints is of concern, as they might evolve throughout secondary genetic events to resistance levels with human clinical impact. Multiple MDR clones carrying copper tolerance (tcrB/cueO), putative virulence or other genes often associated with clinical strains (e.g. E. faecium with IS16/ptsD/sgrA) were observed, some in distinct samples (e.g. upstream and within trout tanks). They included major human and animal Enterococcus lineages, suggesting human and non-aquatic animal origins. The results highlight the need to define the maximum acceptance level of antimicrobial-resistance genes/bacteria to assess water quality and to monitor antimicrobial-resistance strains on feed, essential requirements to maintain a sustainable aquaculture production.


Assuntos
Aquicultura , Farmacorresistência Bacteriana Múltipla/genética , Oncorhynchus mykiss/crescimento & desenvolvimento , Poluição da Água/análise , Abastecimento de Água/estatística & dados numéricos , Animais , Portugal , Poluição da Água/estatística & dados numéricos
19.
Sci. med. (Porto Alegre, Online) ; 28(3): ID29642, jul-set 2018.
Artigo em Português | LILACS, RHS | ID: biblio-909969

RESUMO

OBJETIVOS: Caraterizar como os especialistas e residentes de Pediatria e de Medicina Geral e Familiar consideram que abordam os adolescentes, identificar as suas habilitações em Medicina do Adolescente, averiguar que tópicos dessa área os médicos gostariam de ver abordados em futuros treinamentos e comparar as percepções dos médicos das duas especialidades em relação à sua experiência na prática em saúde do adolescente. MÉTODOS: Estudo transversal com base em inquérito enviado via correio eletrônico a 241 médicos da área de influência de um hospital de nível II, tendo-se incluído especialistas e residentes de Pediatria e de Medicina Geral e Familiar de centros de saúde do concelho de Viseu, Portugal. Utilizaram-se os testes Qui-quadrado ou teste Exacto de Fisher para testar associações entre variáveis, assumindo-se significado estatístico quando p<0,05. RESULTADOS: Um total de 113 médicos completou o inquérito, sendo 74% do gênero feminino, com uma mediana de anos de prática de 12 anos (intervalo interquartil 5-30, mínimo 2 anos, máximo 38 anos). O grupo de Pediatria tinha mais formação em Medicina do Adolescente (57%) do que o grupo de Medicina Geral e Familiar (25%) (p=0,007). Mais médicos com formação específica em Medicina do Adolescente consideravam-se preparados para a entrevista ao adolescente (51%, vs. 28% dos que não tinham formação específica, p=0,03). Os médicos Gerais e de Família orientavam mais os adolescentes sobre consumo de substâncias, contracepção e doenças sexualmente transmissíveis, enquanto os médicos de Pediatria identificavam mais adolescentes com depressão. A maioria dos médicos avaliou-se como tendo conhecimentos insuficientes em Medicina do Adolescente, sendo o treino insuficiente a barreira mais frequentemente referida. Cinquenta e sete por cento dos médicos de Pediatria, 78% dos médicos Gerais e de Família e 84% dos que não tinham formação específica em Medicina do Adolescente, considerando as duas especialidades, gostariam de aprofundar os seus conhecimentos nessa área. CONCLUSÕES: Este estudo permitiu identificar que áreas de conhecimento sobre Medicina do Adolescente estão deficitárias na formação dos pediatras e dos médicos gerais e de família. A maioria dos médicos, principalmente os que não tiveram formação em Medicina do Adolescente, mostraram-se interessados em preencher essa lacuna.


AIMS: To characterize the way in which General and Family physicians and Pediatricians consider approaching adolescents, identify their qualifications in Adolescent Medicine, ascertain which topics of this specialty these physicians would like to see addressed in future training, and to compare the perceptions of physicians of both specialties with respect to their experience in adolescent health practice. METHODS: Cross-sectional study based on a survey sent by e-mail to 241 physicians in the area of influence of a level II hospital, including specific training interns or experts in Pediatrics and General and Family Medicine from health centers of the municipality of Viseu, Portugal. Chi-square tests or Fisher's exact test were used to test associations between variables, assuming statistical significance when p<0.05. RESULTS: A total of 113 physicians completed the survey, of them 74% female, with a median of 12 years of practice (interquartile range 5-30, minimum 2 years, maximum 38 years). The Pediatrics group had more training in Adolescent Medicine (57%) than the General and Family Medicine group (25%) (p=0.007). More physicians with specific training in Adolescent Medicine considered themselves prepared for the adolescent interview (51%, vs. 28% of those who did not have specific training, p=0.03). Family and General practitioners guided adolescents more about substance use, contraception, and sexually transmitted diseases, while Pediatrics doctors identified more adolescents with depression. Most physicians rated themselves as having insufficient knowledge in Adolescent Medicine, with insufficient training being the most frequently referred barrier. Fifty-seven percent of Pediatrics doctors, 78% of General practitioners and 84% of those with no specific training in Adolescent Medicine, considering the two specialties, would like to deepen their knowledge in this area. CONCLUSIONS: This study allowed identifying which areas of knowledge on Adolescent Medicine are deficient in the training of Pediatricians and General practitioners. Most physicians, especially those with no training in Adolescent Medicine, showed interest in filling this gap.


Assuntos
Medicina do Adolescente , Saúde do Adolescente , Educação Médica , Pediatria , Medicina de Família e Comunidade , Clínicos Gerais/educação
20.
Curr Pharm Des ; 24(21): 2508-2512, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29788879

RESUMO

Fats are essential nutrients that have a significant role in the human diet and are essential to provide energy. Fatty acids are present in several types of lipids, such as triglycerides and phospholipids. Fatty acids differ among them, depending on the number of double bonds and on the length of the hydrocarbon chains. If there are no double bonds, the fatty acids are considered saturated and show a linear structure. Compounds with double bonds are unsaturated and have bent structure. The saturated fatty acids are usually solid at room temperature and the unsaturated fatty acids are liquid at that very same temperature. These compounds are of recognized value as raw materials for drug delivery systems, such as lipid nanoparticles. The behaviour of the macroscopic aspects of fat polymorphisms is directly influenced by the melting point, the crystallization and their polymorphic transformations. In this work, we revise the most critical factors contributing for the long-term stability of lipid nanoparticles, as well as the influence of the polymorphism on the loading capacity for drug molecules.

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