Effects of increased nitrate intake from beetroot juice on blood markers of oxidative stress and inflammation in older adults with hypertension.

Background: Vascular oxidative stress and low-grade inflammation are important in the pathology of cardiovascular disorders, including hypertension. Cell culture and animal studies suggest that inorganic dietary nitrate may attenuate oxidative stress and inflammation through nitric oxide (NO), and there is a need to investigate whether this translates to humans.

Aim: In this randomised, placebo-controlled crossover study, by measuring a combination of multiple blood biomarkers, we evaluated whether previously reported benefits of dietary nitrate translate to a reduced oxidative stress and an improved inflammation status in 15 men and women (age range: 56-71 years) with treated hypertension.

The substitute ENSO 16 has low impact on glucose metabolism in healthy humans: a randomized, double-blind, active-controlled, cross-over trial.

High sugar consumption is associated with cardiovascular diseases and diabetes. Current sugar substitutes may cause taste sensations and gastrointestinal symptoms. ENSO 16 is a combination of 16 different sugar substitutes and plant fibers and has been designed as a sugar alternative.

Increased nitrate intake from beetroot juice over 4 weeks affects nitrate metabolism, but not vascular function or blood pressure in older adults with hypertension.

The decline in vascular function and increase in blood pressure with aging contribute to an increased cardiovascular disease risk. In this randomized placebo-controlled crossover study, we evaluated whether previously reported cardiovascular benefits of plant-derived inorganic nitrate nitric oxide (NO) translate into improved vascular function and blood pressure-lowering in 15 men and women (age range: 56-71 years) with treated hypertension. We investigated the effects of a single ∼400 mg-dose at 3 hours post-ingestion (3H POST) and the daily consumption of 2 × ∼400 mg of nitrate through nitrate-rich compared with nitrate-depleted (placebo) beetroot juice over 4 weeks (4WK POST).

Cardiovascular risk and mortality in patients with hyperuricemia treated with febuxostat or allopurinol: a retrospective nation-wide cohort study in Austria 2014-2017.

Patients with hyperuricemia and gout are at an increased risk for cardiovascular (CV) disease. Inhibition of the xanthine oxidase with allopurinol or febuxostat have become the mainstay for urate lowering therapy. However, it has been suggested that febuxostat increases the risk for CV mortality as compared to allopurinol.

Dose-dependent naloxone-induced morphine withdrawal symptoms in opioid-dependent males-a double-blinded, randomized study.

Aims: Oral opioid preparations combined with naloxone are intended to induce a transient acute withdrawal syndrome to avoid intravenous misuse. This trial aimed to establish an appropriate morphine-naloxone dose ratio for an abuse-deterrent oral opioid formulation.

Methods: In a randomized, double-blinded, 2 × 2 cross-over trial, 43 patients with opioid use disorder were challenged with intravenous morphine HCl Ph.

ADMA and NT pro-BNP are associated with overall mortality in elderly.

Background: Increased asymmetrical dimethylarginine (ADMA) and NT pro-BNP concentrations have been associated with mortality in patients with cardiovascular (CV) disease and the general population. The use of these prognostic markers in an older population is not established yet. The aim of the present study was to investigate the prognostic value of age, sex, BMI, co-medication and CV laboratory risk markers in geriatric care patients.

Vaccines Targeting PCSK9: A Promising Alternative to Passive Immunization with Monoclonal Antibodies in the Management of Hyperlipidaemia?

Hypercholesterolaemia is frequently observed in patients with cardiovascular diseases (CVD) and is associated with increased mortality. Statin treatment has been the standard of care for reducing low-density lipoprotein cholesterol (LDL-C) to improve cardiovascular outcomes. However, statins have limited effects in some patients and may be discontinued due to adverse effects resulting in LDL-C above target levels.

Atorvastatin combined with ticagrelor prevent ischemia-reperfusion induced vascular endothelial dysfunction in healthy young males - A randomized, placebo-controlled, double-blinded study.

Background: Atorvastatin and ticagrelor have been shown to prevent against tissue injury in animals. It is unclear if these beneficial effects are also detectable in humans. We studied the effect of high-dose atorvastatin combined with ticagrelor loading on endothelial dysfunction in a model of forearm vascular ischemia-reperfusion (IR) injury.

Ticagrelor mitigates ischaemia-reperfusion induced vascular endothelial dysfunction in healthy young males - a randomized, single-blinded study.

Aims: Animal data suggest that ticagrelor but not clopidogrel protects against tissue injury. It is unclear if this effect of ticagrelor is also detectable in humans. We studied the effect of ticagrelor and clopidogrel at standard clinical doses on endothelial dysfunction in an experimental model of forearm vascular ischaemia-reperfusion (IR) injury.

The effect of a dual or a triple antithrombotic therapy with apixaban on thrombus formation in vivo and in an ex vivo perfusion chamber model: An open-label, controlled, sequential study.

Background: There is a need to optimize pharmacological treatment in patients with acute coronary syndrome and concomitant atrial fibrillation, in particular with newer antithrombotic medicines. We have therefore studied if dual or triple combination of antithrombotic agents exert similar effects on coagulation activation in an in vivo model in the skin microvasculature and in an ex vivo perfusion chamber.

Methods And Results: Shed blood platelet activation (β-thromboglobulin [β-TG]), thrombin generation (thrombin-antithrombin complex [TAT]) and volume as well as markers of thrombus size (D-dimer) and its platelet content (P-selectin) in a perfusion chamber were studied in a sequential, open-label, parallel group trial in 40 healthy male volunteers (n = 20 per group).

Safety, tolerability and pharmacokinetics of liposomal curcumin in healthy humans.

Introduction: Experimental studies have shown that liposomal curcumin can exert a reduction in tumor growth in pancreatic and colorectal cancer. In this phase I clinical trial we investigated the pharmacokinetics, safety, and tolerability of intravenously administered liposomal curcumin in healthy subjects.

Material And Methods: 50 male and female participants were included in this randomized, placebo-controlled double-blind phase I dose escalation study.

Antithrombotic triple therapy and coagulation activation at the site of thrombus formation: a randomized trial in healthy subjects.

Background: Patients with acute coronary syndrome and concomitant atrial fibrillation may require antithrombotic triple therapy but clinical evidence of safety and efficacy is poor. We have therefore studied the combination of different antithrombotic medicines for coagulation activation in an in vivo model in the skin microvasculature.

Methods And Results: Platelet activation (β-thromboglobulin [β-TG]) and thrombin generation (prothrombin fragment 1 + 2 [F1+2 ], thrombin-antithrombin complex [TAT]) were studied in an open-label, randomized, parallel group trial in 60 healthy male subjects (n = 20 per group) who received ticagrelor and acetylsalicylic acid (ASA) in combination with dabigatran (150 mg bid), rivaroxaban (20 mg od) or phenprocoumon (INR 2.

Human pharmacokinetics of high dose oral curcumin and its effect on heme oxygenase-1 expression in healthy male subjects.

Purpose: Heme oxygenase-1 (HO-1) has been proposed to exert pharmacological benefits by its antioxidative and anti-inflammatory effects. HO-1 expression may be affected by the GT length polymorphism in the promoter region of the HO-1 gene. We investigated the inducibility of HO-1 by orally administered curcumin in healthy male subjects and its correlation with the GT length polymorphism.

Effect of systemic high dose vitamin C therapy on forearm blood flow reactivity during endotoxemia in healthy human subjects.

Objective: Acute inflammation induced by administration of Escherichia coli lipopolysaccharide endotoxin (LPS) reduces plasma concentrations of vitamin C and impairs vascular endothelium-derived nitric oxide (NO) bioactivity. We tested the hypothesis that systemically administered high dose vitamin C restores the endogenous anti-oxidant potential and improves NO-dependent vasodilatation in the forearm vasculature.

Design & Setting: 36 male subjects were enrolled in this balanced, placebo controlled cross-over study.

Effect of liposomal curcumin on red blood cells in vitro.

Background: The anti-inflammatory and antiproliferative agent curcumin has poor oral bioavailability and solubility in plasma. Liposomal formulations have therefore been developed, but the toxicity of these preparations is not yet established. We investigated the influence of free and liposomally formulated curcumin on human red blood cell (RBC) morphology in vitro.

The LPS-induced increase in circulating microparticles is not affected by vitamin C in humans.

Objective: Microparticles (MP) are considered to promote coagulation. This study aimed to characterize the time course of MP levels and the effect of high-dose vitamin C on MP formation during inflammation in an in vivo Escherichia coli endotoxin (LPS) model.

Methods: Microparticle formation was studied in 14 male subjects in a cross-over trial who received either intravenous vitamin C at 320 mg/kg body weight (BW) or 480 mg/kg BW or saline solution in a random order on alternate trial days 3 h after intravenous exposure to LPS (2 ng/kg BW).

Heme arginate improves reperfusion patterns after ischemia: a randomized, placebo-controlled trial in healthy male subjects.

Background: Heme arginate can induce heme oxygenase-1 to protect tissue against ischemia-reperfusion injury. Blood oxygen level dependent (BOLD) functional magnetic resonance imaging measures changes in tissue oxygenation with a high spatial and temporal resolution. BOLD imaging was applied to test the effect of heme arginate on experimental ischemia reperfusion injury in the calf muscles.

Analysis of cellular SUMO and SUMO-ubiquitin hybrid conjugates.

Posttranslational modification of proteins with the small ubiquitin-related modifier (SUMO) has been implicated in many important physiological functions, including the regulation of transcription and DNA repair. In most cases, only a small fraction of the total cellular amounts of a given protein is sumoylated at a certain point in time. Sensitive detection of sumoylated forms of proteins by western blotting is, therefore, an important step in the identification and/or characterization of a protein control by sumoylation.

Transcriptome mining, functional characterization, and phylogeny of a large terpene synthase gene family in spruce (Picea spp.).

Background: In conifers, terpene synthases (TPSs) of the gymnosperm-specific TPS-d subfamily form a diverse array of mono-, sesqui-, and diterpenoid compounds, which are components of the oleoresin secretions and volatile emissions. These compounds contribute to defence against herbivores and pathogens and perhaps also protect against abiotic stress.

Results: The availability of extensive transcriptome resources in the form of expressed sequence tags (ESTs) and full-length cDNAs in several spruce (Picea) species allowed us to estimate that a conifer genome contains at least 69 unique and transcriptionally active TPS genes.

Improved HIV-1 RNA quantitation by COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0 using a novel dual-target approach.

Background: HIV-1 RNA viral load is a key parameter for reliable treatment monitoring of HIV-1 infection. Accurate HIV-1 RNA quantitation can be impaired by primer and probe sequence polymorphisms as a result of tremendous genetic diversity and ongoing evolution of HIV-1. A novel dual HIV-1 target amplification approach was realized in the quantitative COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.

Hepatitis B virus (HBV) genotype determination by the COBAS AmpliPrep/COBAS TaqMan HBV Test, v2.0 in serum and plasma matrices.

Background: Viral load quantification is established in the clinical management of chronic Hepatitis B virus (HBV) infection for assessing efficacies and resistance developments in anti-viral drug treatment.

Objectives: The fully automated COBAS AmpliPrep/COBAS TaqMan HBV Test, v2.0 was evaluated for the linear measuring range and the inclusivity of HBV genotype determination in EDTA plasma and serum samples.

Arsenic trioxide stimulates SUMO-2/3 modification leading to RNF4-dependent proteolytic targeting of PML.

We have recently reported that poly-SUMO-2/3 conjugates are subject to a ubiquitin-dependent proteolytic control in human cells. Here we show that arsenic trioxide (ATO) increases SUMO-2/3 modification of promyelocytic leukemia (PML) leading to its subsequent ubiquitylation in vivo. The SUMO-binding ubiquitin ligase RNF4 mediates this modification and causes disruption of PML nuclear bodies upon treatment with ATO.

Functional plasticity of paralogous diterpene synthases involved in conifer defense.

The diversity of terpenoid compounds produced by plants plays an important role in mediating various plant-herbivore, plant-pollinator, and plant-pathogen interactions. This diversity has resulted from gene duplication and neofunctionalization of the enzymes that synthesize and subsequently modify terpenes. Two diterpene synthases in Norway spruce (Picea abies), isopimaradiene synthase and levopimaradiene/abietadiene synthase, provide the hydrocarbon precursors for most of the diterpene resin acids found in the defensive oleoresin of conifers.

Ubiquitin-dependent proteolytic control of SUMO conjugates.

Posttranslational protein modification with small ubiquitin-related modifier (SUMO) is an important regulatory mechanism implicated in many cellular processes, including several of biomedical relevance. We report that inhibition of the proteasome leads to accumulation of proteins that are simultaneously conjugated to both SUMO and ubiquitin in yeast and in human cells. A similar accumulation of such conjugates was detected in Saccharomyces cerevisiae ubc4 ubc5 cells as well as in mutants lacking two RING finger proteins, Ris1 and Hex3/Slx5-Slx8, that bind to SUMO as well as to the ubiquitin-conjugating enzyme Ubc4.