134 research outputs found

    Non-invasive Coronary Flow Velocity Reserve Assessment Predicts Adverse Outcome In Women With unstable angina Without Obstructive Coronary Artery Stenosis

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    Background: Evaluation of coronary flow velocity reserve (CFVR) is the physiological approach to assess the severity of coronary stenosis and microvascular dysfunction. Impaired CFVR occurs frequently in women with suspected or known coronary artery disease . The aim of this study was to assess the role of CFVR to predict long-term cardiovascular event rate in women with unstable angina (UA) without obstructive coronary artery stenosis. Methods: CFVR in left anterior descending coronary artery was assessed by adenosine transthoracic echocardiograhy in 161 women admitted at our Department with UA and without obstructive coronary artery disease. Results: During a mean FU of 32.5 ±19.6 months, 53 cardiac events occurred: 6 nonfatal acute myocardial infarction , 22 UA, 7 coronary revascularization by percutaneous transluminal coronary angioplasty, 1 coronary bypass surgery, 3 ischemic stroke and 8 episodes of congestive heart failure with preserved ejection fraction and 6 cardiac deaths. Using a ROC curve analysis, CFVR 2.14 was the best predictor of cardiac events and was considered as abnormal CFVR. Abnormal CFVR was associated with lower cardiac event-free survival (30% vs 80%, p<0.0001). During FU, 70% of women with reduced CFVR had cardiac events whereas only 20% with normal CFVR (p=0.0001). At multivariate Cox analysis, smoke habitus (p=0.003), metabolic syndrome (p=0.01), and CFVR (p<0.0001) were significantly associated with cardiac events at FU. Conclusion: Noninvasive CFVR provides an independent predictor of cardiovascular prognosis information in women with UA without obstructive coronary artery disease whereas, impaired CFVR seems to be associated with higher CV events at FU

    Chemical and antimicrobial profiling of propolis from different regions within Libya.

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    Extracts from twelve samples of propolis collected from different regions of Libya were tested for their activity against Trypanosoma brucei, Leishmania donovani, Plasmodium falciparum, Crithidia fasciculata and Mycobacterium marinum and the cytotoxicity of the extracts was tested against mammalian cells. All the extracts were active to some degree against all of the protozoa and the mycobacterium, exhibiting a range of EC50 values between 1.65 and 53.6 μg/ml. The toxicity against mammalian cell lines was only moderate; the most active extract against the protozoan species, P2, displayed an IC50 value of 53.2 μg/ml. The extracts were profiled by using liquid chromatography coupled to high resolution mass spectrometry. The data sets were extracted using m/z Mine and the accurate masses of the features extracted were searched against the Dictionary of Natural Products (DNP). A principal component analysis (PCA) model was constructed which, in combination with hierarchical cluster analysis (HCA), divided the samples into five groups. The outlying groups had different sets of dominant compounds in the extracts, which could be characterised by their elemental composition. Orthogonal partial least squares (OPLS) analysis was used to link the activity of each extract against the different micro-organisms to particular components in the extracts

    Plasmodium falciparum LipB mutants display altered redox and carbon metabolism in asexual stages and cannot complete sporogony in Anopheles mosquitoes

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    Malaria is still one of the most important global infectious diseases. Emergence of drug resistance and a shortage of new efficient antimalarials continue to hamper a malaria eradication agenda. Malaria parasites are highly sensitive to changes in the redox environment. Understanding the mechanisms regulating parasite redox could contribute to the design of new drugs. Malaria parasites have a complex network of redox regulatory systems housed in their cytosol, in their mitochondrion and in their plastid (apicoplast). While the roles of enzymes of the thioredoxin and glutathione pathways in parasite survival have been explored, the antioxidant role of α-lipoic acid (LA) produced in the apicoplast has not been tested. To take a first step in teasing a putative role of LA in redox regulation, we analysed a mutant Plasmodium falciparum (3D7 strain) lacking the apicoplast lipoic acid protein ligase B (lipB) known to be depleted of LA. Our results showed a change in expression of redox regulators in the apicoplast and the cytosol. We further detected a change in parasite central carbon metabolism, with lipB deletion resulting in changes to glycolysis and tricarboxylic acid cycle activity. Further, in another Plasmodium cell line (NF54), deletion of lipB impacted development in the mosquito, preventing the detection of infectious sporozoite stages. While it is not clear at this point if the observed phenotypes are linked, these findings flag LA biosynthesis as an important subject for further study in the context of redox regulation in asexual stages, and point to LipB as a potential target for the development of new transmission drugs
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