Open-Label Interventional Study in Healthy Volunteers to Evaluate NO-Mediated Vasodilation by Dermal Allyl Isothiocyanate Challenge and Whole-Body Heat Stress.

Dermal allyl isothiocyanate (AITC) administration and whole-body heat stress (WBHS) are two challenge models that are used to evaluate physiological mechanisms of vasodilation and pharmacological activity in humans. Their exact vasodilatory mechanisms in humans are not fully elucidated but are likely to be nitric oxide (NO)-mediated. This study aimed to evaluate whether there is overlap in the vasodilatory pathways of dermal AITC application and WBHS by combining the challenges.

Microvascular effects of a mixed meal tolerance test: a model validation study.

Purpose: Endothelial dysfunction is a pathophysiological change preceding many cardiovascular events. Measuring improvements of endothelial function is challenging when function is already optimal, which may be remediated using a physiological challenge. This study aimed to determine whether imaging assessments can detect microvascular effects of a mixed meal tolerance test (MMTT).

Impact of fibre supplementation on microbiome and resilience in healthy participants: A randomized, placebo-controlled clinical trial.

Background And Aims: The gut microbiome exerts important roles in health, e.g., functions in metabolism and immunology.

A Phase 1 randomized, open-label clinical trial to evaluate the effect of a far-infrared emitting patch on local skin perfusion, microcirculation and oxygenation.

Far-infrared radiation (FIR) has been investigated for reduction of pain and improvement of dermal blood flow. The FIRTECH patch is a medical device designed to re-emit FIR radiated by the body. This phase 1 study was conducted to evaluate the local effects of the FIRTECH patch on local skin perfusion, microcirculation and oxygenation.

Randomized placebo-controlled crossover study to assess tolerability and pharmacodynamics of zagociguat, a soluble guanylyl cyclase stimulator, in healthy elderly.

Aims: Dysfunction of nitric oxide-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate signalling is implicated in the pathophysiology of cognitive impairment. Zagociguat is a central nervous system (CNS) penetrant sGC stimulator designed to amplify nitric oxide-cyclic guanosine monophosphate signalling in the CNS. This article describes a phase 1b study evaluating the safety and pharmacodynamic effects of zagociguat.

Identification of peripheral vascular function measures and circulating biomarkers of mitochondrial function in patients with mitochondrial disease.

The development of pharmacological therapies for mitochondrial diseases is hampered by the lack of tissue-level and circulating biomarkers reflecting effects of compounds on endothelial and mitochondrial function. This phase 0 study aimed to identify biomarkers differentiating between patients with mitochondrial disease and healthy volunteers (HVs). In this cross-sectional case-control study, eight participants with mitochondrial disease and eight HVs matched on age, sex, and body mass index underwent study assessments consisting of blood collection for evaluation of plasma and serum biomarkers, mitochondrial function in peripheral blood mononuclear cells (PBMCs), and an array of imaging methods for assessment of (micro)circulation.

First-in-human trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of zagociguat (CY6463), a CNS-penetrant soluble guanylyl cyclase stimulator.

Soluble guanylate cyclase (sGC) and its product, cyclic guanosine monophosphate, play a role in learning and memory formation. Zagociguat (CY6463) is a novel stimulator of sGC being developed for the treatment of neurodegenerative disease. Single zagociguat doses of 0.

Immunosuppression by hydroxychloroquine: mechanistic proof in in vitro experiments but limited systemic activity in a randomized placebo-controlled clinical pharmacology study.

Based on its wide range of immunosuppressive properties, hydroxychloroquine (HCQ) is used for the treatment of several autoimmune diseases. Limited literature is available on the relationship between HCQ concentration and its immunosuppressive effect. To gain insight in this relationship, we performed in vitro experiments in human PBMCs and explored the effect of HCQ on T and B cell proliferation and Toll-like receptor (TLR)3/TLR7/TLR9/RIG-I-induced cytokine production.

Safety of low-volume PEG-asc bowel cleansing preparation for colonoscopy: identifying patients at risk for hypokalemia in a prospective cohort study.

The aim of bowel cleansing preparation should be high-quality results and conformance with safety standards. Previously, we reported that hypokalemia occurred in 23.6 % of patients after bowel preparation in a high-risk population on diuretics or hospitalized and referred for colonoscopy.