Search results for "BOS"
showing 10 items of 3713 documents
Ticagrelor, but not clopidogrel, reduces arterial thrombosis via endothelial tissue factor suppression
2017
The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with focus on arterial thrombosis and its key trigger tissue factor have not been previously investigated.Methods and results: Human aortic endothelial cells were treated with ticagrelor or clopidogrel active metabolite (CAM) and stimulated with tumour necrosis factor-alpha (TNF-α); effects on procoagulant tissue factor (TF) expression and activity, its counter-player TF pathway inhibito…
Inter-individual differences in the susceptibility of primary human hepatocytes towards drug-induced cholestasis are compound and time dependent.
2018
Abstract Cholestasis represents a major subtype of drug-induced liver injury and novel preclinical models for its prediction are needed. Here we used primary human hepatocytes (PHH) from different donors in 2D-sandwich (2D-sw) and/or 3D-spheroid cultures to study inter-individual differences in the response towards cholestatic hepatotoxins after short-term (48–72 hours) and long-term repeated exposures (14 days). The cholestatic liabilities of drugs were determined by comparing cell viability upon exposure to the highest non-cytotoxic drug concentration in the presence and absence of a non-cytotoxic concentrated bile acid mixture. In 2D-sw culture, cyclosporine A and amiodarone presented cl…
Clinical Determinants of Thrombin Generation Measured in Presence and Absence of Platelets-Results from the Gutenberg Health Study.
2018
AbstractThe tendency of a plasma sample to generate thrombin, a central enzyme in blood coagulation, might be an important indicator of prothrombotic risk linked to cardiovascular disease (CVD), but the presence of platelets may be a critical determinant. Clinical data, laboratory markers and thrombin generation (TG), investigated in both platelet-rich plasma (PRP) and platelet-free plasma (PFP) at 1 pM TF, were available in 407 individuals from the Gutenberg Health Study. Given the well-known effect of anticoagulants on TG, subjects taking anticoagulants (n = 15) have been excluded resulting in 392 subjects for further analysis. Lag time, endogenous thrombin potential (ETP) and peak height…
Association of metformin administration with gut microbiome dysbiosis in healthy volunteers
2018
Background Metformin is a widely used first-line drug for treatment of type 2 diabetes. Despite its advantages, metformin has variable therapeutic effects, contraindications, and side effects. Here, for the very first time, we investigate the short-term effect of metformin on the composition of healthy human gut microbiota. Methods We used an exploratory longitudinal study design in which the first sample from an individual was the control for further samples. Eighteen healthy individuals were treated with metformin (2 × 850 mg) for 7 days. Stool samples were collected at three time points: prior to administration, 24 hours and 7 days after metformin administration. Taxonomic composition of…
Effects of an Antimutagenic 1,4-Dihydropyridine AV-153 on Expression of Nitric Oxide Synthases and DNA Repair-related Enzymes and Genes in Kidneys of…
2016
Development of complications of diabetes mellitus (DM), including diabetic nephropathy, is a complex multi-stage process, dependent on many factors including the modification of nitric oxide (NO) production and an impaired DNA repair. The goal of this work was to study in vivo effects of 1,4-dihydropyridine AV-153, known as antimutagen and DNA binder, on the expression of several genes and proteins involved in NO metabolism and DNA repair in the kidneys of rats with a streptozotocin (STZ)-induced model of DM. Transcription intensity was monitored by means of real-time RT-PCR and the expression of proteins by immunohistochemistry. Development of DM significantly induced PARP1 protein express…
Sex-specific differences in genetic and nongenetic determinants of mean platelet volume: results from the Gutenberg Health Study.
2016
Mean platelet volume (MPV), a measure of platelet size, is a potential biological marker of platelet function. To date, a comprehensive analysis including known genetic and nongenetic factors that determine MPV is still lacking. MPV has been evaluated in 15 010 individuals from the population-based Gutenberg Health Study. Genetic information was available for 4175 individuals. Our results showed that age (β, 0.0346; 95% confidence interval [CI], 0.0255 to 0.0436), cardiovascular risk factors (CVRFs) such as smoking (β, 0.178; 95% CI, 0.128 to 0.229), hypertension (β, 0.05; 95% CI, 0.00289 to .0981), and high glucose level (β, 0.00179; 95% CI, 0.0006 to 0.00299) were linked with higher MPV i…
Skin and gut microbiomes of a wild mammal respond to different environmental cues
2018
Background Animal skin and gut microbiomes are important components of host fitness. However, the processes that shape the microbiomes of wildlife are poorly understood, particularly with regard to exposure to environmental contaminants. We used 16S rRNA amplicon sequencing to quantify how exposure to radionuclides impacts the skin and gut microbiota of a small mammal, the bank vole Myodes glareolus, inhabiting areas within and outside the Chernobyl Exclusion Zone (CEZ), Ukraine. Results Skin microbiomes of male bank voles were more diverse than females. However, the most pronounced differences in skin microbiomes occurred at a larger spatial scale, with higher alpha diversity in the skin m…
In Vitro Antimicrobial Activity of Frankincense Oils from Boswellia sacra Grown in Different Locations of the Dhofar Region (Oman)
2020
Frankincense essential oils from Boswellia sacra have been commonly used to treat microbial infections from as early as the 11th century. The main feature of the plant is its gum resin, from which it is possible to obtain essential oils. In the present study, we focused on the comparative study of the oils extracted from the resins of three different Boswellia sacra cultivars (Najdi, Sahli and Houjri). From each of frankincense resin three successive essential oil samples (Grade 1, Grade 2, Grade 3) were obtained. Houjri gum resin gave the lowest percentage (5%) of total essential oil content but showed the maximum number of volatile components in all three grades. Najdi Grade 2 essential o…
The Gut Microbiota in Cardiovascular Disease and Arterial Thrombosis
2019
The gut microbiota has emerged as a contributing factor in the development of atherosclerosis and arterial thrombosis. Metabolites from the gut microbiota, such as trimethylamine N-oxide and short chain fatty acids, were identified as messengers that induce cell type-specific signaling mechanisms and immune reactions in the host vasculature, impacting the development of cardiovascular diseases. In addition, microbial-associated molecular patterns drive atherogenesis and the microbiota was recently demonstrated to promote arterial thrombosis through Toll-like receptor signaling. Furthermore, by the use of germ-free mouse models, the presence of a gut microbiota was shown to influence the syn…
Whole-genome characterization of Shewanella algae strain SYT3 isolated from seawater reveals insight into hemolysis.
2018
Aim: To describe the genomic characteristics of seawater-borne hemolytic Shewanella algae and its resistance genes. Materials & methods: Whole genome sequence of S. algae SYT3 was determined using llumina MiSeq platform. Multiple-database-based analysis was performed to identify the genetic background of its hemolytic activity and the antibiotic resistance genes. Results: S. algae SYT3 possesses a homolog of the hly operon involved in the synthesis of hemolysin. We also identified candidate genes associated with resistance to β-lactam antibiotics (bla OXA-55) and fluoroquinolone (qnrA3). Conclusion: The study provides an insight into the hemolytic activity of S. algae. Our findings als…