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1.
Quality of life in stroke survivor–caregiver dyads: a new conceptual framework and longitudinal study protocol
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2.
N. S. Hari Narayana Moorthy Sergio F. Sousa Maria J. Ramos Pedro A. Fernandes 《Medicinal chemistry research》2016,25(7):1340-1357
Farnesyltransferase (FTase) is one of the prenyltransferase family enzymes that catalyse the transfer of 15-membered isoprenoid (farnesyl) moiety to the cysteine of CAAX motif-containing proteins including Rho and Ras family of G proteins. Inhibitors of FTase act as drugs for cancer, malaria, progeria and other diseases. In the present investigation, we have developed two structure-based pharmacophore models from protein–ligand complex (3E33 and 3E37) obtained from the protein data bank. Molecular dynamics (MD) simulations were performed on the complexes, and different conformers of the same complex were generated. These conformers were undergone protein–ligand interaction fingerprint (PLIF) analysis, and the fingerprint bits have been used for structure-based pharmacophore model development. The PLIF results showed that Lys164, Tyr166, TrpB106 and TyrB361 are the major interacting residues in both the complexes. The RMSD and RMSF analyses on the MD-simulated systems showed that the absence of FPP in the complex 3E37 has significant effect in the conformational changes of the ligands. During this conformational change, some interactions between the protein and the ligands are lost, but regained after some simulations (after 2 ns). The structure-based pharmacophore models showed that the hydrophobic and acceptor contours are predominantly present in the models. The pharmacophore models were validated using reference compounds, which significantly identified as HITs with smaller RMSD values. The developed structure-based pharmacophore models are significant, and the methodology used in this study is novel from the existing methods (the original X-ray crystallographic coordination of the ligands is used for the model building). In our study, along with the original coordination of the ligand, different conformers of the same complex (protein–ligand) are used. It concluded that the developed methodology is significant for the virtual screening of novel molecules on different targets. 相似文献
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Leonardo Jönck Staub Roberta Rodolfo Mazzali Biscaro Erikson Kaszubowski Rosemeri Maurici 《The Journal of emergency medicine》2019,56(1):53-69
Background
Lung ultrasound can accelerate the diagnosis of life-threatening diseases in adults with respiratory symptoms.Objective
Systematically review the accuracy of lung ultrasonography (LUS) for emergency diagnosis of pneumonia, acute heart failure, and exacerbation of chronic obstructive pulmonary disease (COPD)/asthma in adults.Methods
PubMed, Embase, Scopus, Web of Science, and LILACS (Literatura Latino Americana e do Caribe em Ciências da Saúde; until 2016) were searched for prospective diagnostic accuracy studies. Rutter-Gatsonis hierarchical summary receiver operating characteristic method was used to measure the overall accuracy of LUS and Reitsma bivariate model to measure the accuracy of the different sonographic signs. This review was previously registered in PROSPERO (Centre for Reviews and Dissemination, University of York, York, UK; CRD42016048085).Results
Twenty-five studies were included: 14 assessing pneumonia, 14 assessing acute heart failure, and four assessing exacerbations of COPD/asthma. The area under the summary receiver operating characteristic curve of LUS was 0.948 for pneumonia, 0.914 for acute heart failure, and 0.906 for exacerbations of COPD/asthma. In patients suspected to have pneumonia, consolidation had sensitivity of 0.82 (95% confidence interval [CI] 0.74–0.88) and specificity of 0.94 (95% CI 0.85–0.98) for this disease. In acutely dyspneic patients, modified diffuse interstitial syndrome had sensitivity of 0.90 (95% CI 0.87–0.93) and specificity of 0.93 (95% CI 0.91–0.95) for acute heart failure, whereas B-profile had sensitivity of 0.93 (95% CI 0.72–0.98) and specificity of 0.92 (95% CI 0.79–0.97) for this disease in patients with respiratory failure. In patients with acute dyspnea or respiratory failure, the A-profile without PLAPS (posterior-lateral alveolar pleural syndrome) had sensitivity of 0.78 (95% CI 0.67–0.86) and specificity of 0.94 (95% CI 0.89–0.97) for exacerbations of COPD/asthma.Conclusion
Lung ultrasound is an accurate tool for the emergency diagnosis of pneumonia, acute heart failure, and exacerbations of COPD/asthma. 相似文献5.
6.
Milena Soares Santos Guilherme de Sousa Ribeiro Tainara Queiroz Oliveira Renan Cardoso Nery Santos Edilane Gouveia Kátia Salgado Daniele Takahashi Cleuber Fontes Leila Carvalho Campos Mitermayer Galvão Reis Albert Icksang Ko Joice Neves Reis 《International journal of infectious diseases》2009,13(4):456-461
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8.
Khalil Fattouch Giuseppe Bianco Giuseppe Speziale Roberta Sampognaro Carlo Lavalle Francesco Guccione Pietro Dioguardi Giovanni Ruvolo 《European journal of cardio-thoracic surgery》2007,32(2):326-332
BACKGROUND: The inflammatory cascade has been hypothesized to be an important mechanism of post-ischaemic myocardial reperfusion injury and several studies demonstrated that C1 esterase inhibitor (C1-INH) is effective in post-ischaemia myocardial protection. Therefore, we aimed to investigate prospectively in a randomised double-blind study the cardioprotective effects of C1-INH in ST segment elevation myocardial infarction (STEMI) in patients who underwent emergent reperfusion with coronary artery bypass grafting (CABG). METHODS: In this study, we enrolled 80 patients affected with STEMI who underwent emergent CABG. Patients were assigned in two groups (C1-INH group: receive 1000 UI of C1-INH; and placebo group: receive a saline solution). The effects of C1-INH on complement inhibition, myocardial cell injury extension and clinical outcome were studied. Haemodynamic data and myocardial function were monitored. C1-INH, C3a, C4a complement activation fragments and cardiac troponin I (cTnI) serum levels were measured before, during and after surgery. RESULTS: Patient characteristics were not different between the two groups. The overall in-hospital mortality rate was 6.2%. No statistical significant difference was observed between the two groups with regard to early mortality (p=0.36). Statistical significant difference between the two groups was showed for cardiopulmonary bypass support (p=0.04), administration of high dose of inotropes drugs (p=0.001), time of intubation (p=0.03), intensive care unit (ICU) stay (p=0.04) and in-hospital stay (p=0.03). A significant improvement in mean arterial pressure (p=0.03), cardiac index (p=0.02) and stroke volume (p=0.03) was showed in C1-INH group versus placebo group. The serum cTnI levels were significantly low in the C1-INH group versus placebo group after reperfusion, during the observation period. Plasma levels of C3a and C4a complement fragments were reduced significantly in C1-INH group. No drugs-related adverse effects were observed. CONCLUSIONS: The inhibition of the classic complement pathway by C1-INH appears to be an effective mean of preserving ischaemic myocardium from reperfusion injury as demonstrated by low serum cTnI levels in C1-INH group. Therefore, the use of C1-INH during CABG as a rescue therapy in STEMI patients is probably an effective treatment to inhibit complement activity and to improve cardiac function and haemodynamic performance without impacting early mortality. Large randomised study should be performed to support our results. 相似文献
9.
A. B. Soares P. R. Faria L. A. Magna M. E. P. Correa C. A. de Sousa O. P. Almeida M. L. Cintra 《Journal of oral pathology & medicine》2005,34(6):368-373
BACKGROUND: Graft-vs.-host disease (GVHD) is the major cause of morbidity and mortality in patients undergoing allogeneic Bone Marrow Transplantation (BMT). The aim of our study was to identify the most relevant histological features for diagnosis of chronic Graft-vs.-Host Disease (cGVHD) in oral mucosa and minor salivary glands of 25 patients, as well as to evaluate the immunophenotype of the inflammatory cells. METHODS: Sixteen patients that were submitted to allogeneic BMT but did not present cGVHD were selected as a control group. The sections were studied on H & E and CD68, CD45, CD4, CD8, CD20 staining. RESULTS: The most frequent histologic findings in oral mucosa at the day of diagnosis of cGVHD were: hydropic degeneration of the basal layer of the epithelium, apoptotic bodies, lymphocytic infiltration, and focal or total cleavage between the epithelial and connective tissue. In the labial salivary glands (LSG), lymphocytic infiltration, acinar loss and fibrosis were the main alterations. Cytotoxic CD8-T cells and macrophages were predominant both in the epithelium and connective tissue, as well as in minor salivary glands. CONCLUSIONS: Histological features were useful in the diagnosis of oral cGVHD. It is suggested that CD8-T cells and macrophages play important role in the pathogenesis of the disease. 相似文献
10.
Intestinal intraepithelial lymphocytes (iIEL) are primarily CD8 cells and most of them have a CD28? phenotype, the phenotype of effector cytotoxic T cells. We asked whether the predominance of CD8+ CD28? T cells in the gut may result from peripheral blood T cells preferentially migrating to the iIEL compartment and adhering to iEC. Compared with CD4 cells, adhesion of resting CD8+ T cells to iEC cell lines was significantly higher. Adhesion could be blocked with a MoAb to gp180, a molecule expressed on iEC which is known to interact with CD8/lck. No significant difference in the level of adhesion was observed between CD8+ CD28+ and CD8+ CD28? T cells. Thus CD8 cells may preferentially migrate to the iIEL compartment, but loss of CD28 expression could occur in situ after migration. Consistent with this hypothesis, the CD8+ CD28? cells became enriched after co-culturing T cells with iEC cell lines and primary iEC. Induction of the CD8+ CD28? phenotype in cord blood and adult T cells was observed in co-cultures with iEC and also with mitogens and superantigens. In the latter case, CD28 down-modulation was seen specifically in the Vβ subset targeted by the superantigen, indicating that loss of CD28 expression is a direct result of T cell receptor (TCR)-mediated stimulation. The combined results suggest that CD8+ CD28? T cells are antigen experienced T cells, and that they may have a survival advantage in the presence of gut epithelial cells in vitro. This may contribute to the predominance of CD8+ CD28? T cells in the iIEL compartment. 相似文献