Atherosclerosis is an inflammatory process that develops in individuals with known risk factors that include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, inflammatory mechanisms and vascular risk factors requires further research. We hypothesised that interleukin-1 (IL-1) signaling in the vessel wall would raise arterial blood pressure and promote atheroma. Apoe^−/− and Apoe^−/−/IL-1R1^−/− mice were fed high fat diets for 8 weeks, and their blood pressure and atherosclerosis development measured. Apoe^−/−/IL-R1^−/− mice had a reduced blood pressure and significantly less atheroma than Apoe^−/− mice. Selective loss of IL-1 signaling in the vessel wall by bone marrow transplantation also reduced plaque burden (p<0.05). This was associated with an IL-1 mediated loss of endothelium-dependent relaxation and an increase in vessel wall Nox 4. Inhibition of IL-1 restored endothelium-dependent vasodilatation and reduced levels of arterial oxidative stress. The IL-1 cytokine system links atherogenic environmental stimuli with arterial inflammation, oxidative stress, increased blood pressure and atherosclerosis. This is the first demonstration that inhibition of a single cytokine can block the rise in blood pressure in response to an environmental stimulus. IL-1 inhibition may have profound beneficial effects on atherogenesis in man.

This narrative review describes the oral microbiome, and its role in oral health and disease, before considering the impact of commonly used over-the-counter (OTC) mouthwashes on oral bacteria, viruses, bacteriophages, and fungi that make up these microbial communities in different niches of the mouth. Whilst certain mouthwashes have proven antimicrobial actions and clinical effectiveness supported by robust evidence, this review reports more recent metagenomics evidence, suggesting that mouthwashes such as chlorhexidine may cause "dysbiosis," whereby certain species of bacteria are killed, leaving others, sometimes unwanted, to predominate. There is little known about the effects of mouthwashes on fungi and viruses in the context of the oral microbiome (virome) in vivo, despite evidence that they "kill" certain viral pathogens ex vivo. Evidence for mouthwashes, much like antibiotics, is also emerging with regards to antimicrobial resistance, and this should further be considered in the context of their widespread use by clinicians and patients. Therefore, considering the potential of currently available OTC mouthwashes to alter the oral microbiome, this article finally proposes that the ideal mouthwash, whilst combatting oral disease, should "balance" antimicrobial communities, especially those associated with health. Which antimicrobial mouthwash best fits this ideal remains uncertain.

This review describes the laboratory evidence and microvascular mechanisms responsible for the beneficial effects of statins in sepsis. During sepsis, changes occur within the microcirculation including alterations in arteriolar tone influencing blood pressure, adaptations to endothelial cell integrity causing leakage of proteins and macromolecules, and adhesion and migration of leucocytes through the vascular endothelium. Statins are widely used as cholesterol-lowering agents, but appear to have anti-inflammatory actions during sepsis. We have discussed the effects of statins on specific pathological processed within the microcirculation and focused on the role of nitric oxide (NO). The main mechanism by which statins appear to be an effective treatment for sepsis is increased expression of endothelial nitric oxide synthase (eNOS), in conjunction with down-regulation of inducible nitric oxide synthase. Combined, this results in an increase in physiological concentrations of NO, thus restoring endothelial function. Laboratory studies have therefore suggested that enhancement of eNOS activity during sepsis may lead to restoration of microvascular tone, maintenance of microvascular integrity, and inhibition of cell adhesion molecules. However, other mechanisms independent of lipid-lowering effects, including antioxidant activity and alterations in the development of vascular atherosclerosis, may also contribute to the beneficial effects of statins. We have also addressed the influence on the effects of statins of lipid solubility and pre- and pro-phylactic administration.

This narrative literature review is the first in a 6-section supplement on the role of mouthwashes in oral care. This introduction briefly summarises current knowledge on antimicrobial mechanisms, relating to some of the most common over-the-counter mouthwash products available worldwide: chlorhexidine, hydrogen peroxide, cetylpyridinium chloride, povidone iodine, and essential oils. The aim of this first article is to describe how mouthwashes "kill" pathogenic microbes when used adjunctively and thus provide a basis for their widespread use to manage key oral diseases, namely caries, gingivitis, and periodontal disease. This article therefore sets the scene for subsequent, more detailed exploration of mouthwashes regarding their clinical effectiveness, impact on the oral microbiome, and possible effects on systemic health as well as natural alternatives and future directions. Other than the clinical effectiveness (for certain agents) of mouthwashes, on many topics there remains insufficient evidence for systematic review or formulation of robust national guidelines. The supplement, therefore, compiled by an international task team, is aimed at general dental practitioners across the globe, as an easy-to-read guide for helping to advise patients on mouthwash use based on the current best available evidence.

Introduction: Severe sepsis is characterised by intravascular or extravascular infection with microbial agents, systemic inflammation and microcirculatory dysfunction, leading to tissue damage, organ failure and death. The growth factor angiopoietin (Ang-1) has therapeutic potential but recombinant Ang-1 tends to aggregate and has a short half-life in vivo. This study aimed to investigate the acute effects of the more stable Ang-1 variant matrilin-1-angiopoietin-1 (MAT.Ang-1) on the function of the microcirculation in an experimental model of sepsis, and whether any protection by MAT-Ang-1 was associated with modulation of inflammatory cytokines, angiogenic factors or the endothelial nitric oxide synthase (eNOS)-Akt and vascular endothelial (VE)-cadherin pathways. Methods: Aluminium window chambers were implanted into the dorsal skinfold of male C3H/HeN mice (7 to 10 weeks old) to expose the striated muscle microcirculation. Endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (LPS, 1 mg/kg at 0 and 19 hours). MAT.Ang-1 was administered intravenously 20 hours after the onset of sepsis. Microcirculatory function was evaluated by intravital microscopy and Doppler fluximetry. Results: Endotoxemia resulted in macromolecular leak, which was ameliorated by MAT.Ang-1 post-treatment. LPS induced a dramatic reduction in tissue perfusion, which was improved by MAT.Ang-1. Proteome profiler array analysis of skeletal muscle also demonstrated increased inflammatory and reduced angiogenic factors during endotoxemia. MAT.Ang-1 post-treatment reduced the level of IL-1β but did not significantly induce the expression of angiogenic factors. MAT.Ang-1 alone did not induce leak or increase angiogenic factors but did reduce vascular endothelial growth factor expression in controls. Conclusion: Administration of MAT.Ang-1 after the onset of sepsis protects the microcirculation from endotoxemia-induced vascular dysfunction through reducing inflammation but without pro-angiogenic actions, thus representing a novel, potential pharmacotherapeutic agent for the treatment of sepsis.