The human gastrointestinal (GI) tract is home to trillions of commensal organisms. Some of these microbes have the capacity to become pathogenic following changes in the microenvironment and/or host physiology. Candida albicans is one such organism, usually inhabiting the GI tract as a harmless commensal in most individuals but with the potential to cause serious infection.
View Article and Find Full Text PDFImportance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.
Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.
Design, Setting, And Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin.
Although it is known that medial temporal lobe (MTL) structures support declarative memory, the fact these structures have different architectonics and circuitry suggests they may also play different functional roles. Selective lesions of MTL structures offer an opportunity to understand these roles. We report, in this study, on JMG, a patient who presents highly unusual lesions that completely affected all MTL structures except for the right hippocampus and parts of neighbouring medial parahippocampal cortex.
View Article and Find Full Text PDFDectin-1 is an innate antifungal C-type lectin receptor necessary for protective antifungal immunity. We recently discovered that Dectin-1 is involved in controlling fungal infections of the gastrointestinal (GI) tract, but how this C-type lectin receptor mediates these activities is unknown. Here, we show that Dectin-1 is essential for driving fungal-specific CD4(+) T-cell responses in the GI tract.
View Article and Find Full Text PDFBackground: Myeloid inhibitory C-type lectin-like receptor (MICL, Clec12A) is a C-type lectin receptor (CLR) expressed predominantly by myeloid cells. Previous studies have suggested that MICL is involved in controlling inflammation.
Objective: To determine the role of this CLR in inflammatory pathology using Clec12A(-/-) mice.
Asthma is a heterogeneous disease whose etiology is poorly understood but is likely to involve innate responses to inhaled microbial components that are found in allergens. The influence of these components on pulmonary inflammation has been largely studied in the context of individual agonists, despite knowledge that they can have synergistic effects when used in combination. Here we have explored the effects of LPS and β-glucan, two commonly-encountered microbial agonists, on the pathogenesis of allergic and non-allergic respiratory responses to house dust mite allergen.
View Article and Find Full Text PDFThe ability of Candida albicans to cause disease is associated with its capacity to undergo morphological transition between yeast and filamentous forms, but the role of morphology in colonization and dissemination from the gastrointestinal (GI) tract remains poorly defined. To explore this, we made use of wild-type and morphological mutants of C. albicans in an established model of GI tract colonization, induced following antibiotic treatment of mice.
View Article and Find Full Text PDFNoroviruses (NoVs), currently recognised as the most common human food-borne pathogens, are ubiquitous in the environment and can be transmitted to humans through multiple foodstuffs. In this study, we evaluated the prevalence of human NoV genogroups I (GI) and II (GII) in 493 food samples including soft red fruits (n = 200), salad vegetables (n = 210) and bivalve mollusc shellfish (n = 83), using the Bovine Enterovirus type 1 as process extraction control for the first time. Viral extractions were performed by elution concentration and genome detection by TaqMan Real-Time RT-PCR (RT-qPCR).
View Article and Find Full Text PDFChitin is an essential structural polysaccharide of fungal pathogens and parasites, but its role in human immune responses remains largely unknown. It is the second most abundant polysaccharide in nature after cellulose and its derivatives today are widely used for medical and industrial purposes. We analysed the immunological properties of purified chitin particles derived from the opportunistic human fungal pathogen Candida albicans, which led to the selective secretion of the anti-inflammatory cytokine IL-10.
View Article and Find Full Text PDFThe β-glucan receptor Dectin-1 is a member of the C-type lectin family and functions as an innate pattern recognition receptor in antifungal immunity. In both mouse and man, Dectin-1 has been found to play an essential role in controlling infections with Candida albicans, a normally commensal fungus in man which can cause superficial mucocutaneous infections as well as life-threatening invasive diseases. Here, using in vivo models of infection, we show that the requirement for Dectin-1 in the control of systemic Candida albicans infections is fungal strain-specific; a phenotype that only becomes apparent during infection and cannot be recapitulated in vitro.
View Article and Find Full Text PDFCandida albicans is normally found as a commensal microbe, commonly colonizing the gastrointestinal tract in humans. However, this fungus can also cause mucosal and systemic infections once immune function is compromised. Dectin-1 is an innate pattern recognition receptor essential for the control of fungal infections in both mice and humans; however, its role in the control of C.
View Article and Find Full Text PDFFungi are the cause of opportunistic infections, predominantly in immunocompromised individuals although, primary fungal infections can occur in apparently healthy individuals. Successful host defence requires an effective innate and adaptive immune response. Central to host immune responses are the induction of cytokines; the signals which help to activate the innate immune system and which play a central role in directing the development of pathogen-specific immunity.
View Article and Find Full Text PDFThe present study examined individual latent changes in posttraumatic stress disorder (PTSD) symptoms over a 60-month period after an industrial disaster. Participants were recruited from survivors of a factory explosion. Participants were assessed retrospectively for peritraumatic reactions and acute stress symptoms.
View Article and Find Full Text PDFTh17 cells are a recently discovered subset of T helper cells characterised by the release of IL-17, and are thought to be important for mobilization of immune responses against microbial pathogens, but which also contribute to the development of autoimmune diseases. The identification of C-type lectin receptors which are capable of regulating the balance between Th1 and Th17 responses has been of particular recent interest, which they control, in part, though the release of Th17 inducing cytokines. Many of these receptors recognise fungi, and other pathogens, and play key roles in driving the development of protective anti-microbial immunity.
View Article and Find Full Text PDFPurpose: MPTP-induced dopaminergic degeneration is an experimental model commonly used to explore Parkinson's disease. Cerebral drug transport by ABC transporters in MPTP models has never been reported.
Methods: We have investigated the transport of bromocriptine through the blood-brain barrier (BBB) in a MPTP model to understand the influence of the dopaminergic degeneration on ABCB1 and ABCG2.
Expert Opin Drug Metab Toxicol
November 2009
ABCB1/P-glycoprotein (P-gp) is an ATP-dependant transmembrane efflux protein widely expressed in human organs and plays a protective role against endogenous and exogenous substances. It is involved in drug pharmacokinetics affecting drug absorption, disposition and elimination. At the BBB level, due to its luminal localisation, ABCB1 limits drug transport and is important in central detoxification.
View Article and Find Full Text PDFBalanced scales, that is, scales based on items whose content is either negatively or positively polarized, are often used in the hope of measuring a bipolar construct. Research has shown that usually balanced scales do not yield 1-dimensional measurements. This threatens their construct validity.
View Article and Find Full Text PDFAmyotrophic lateral sclerosis (ALS) is a neurodegenerative fatal disease. Drugs used in this disease need to cross the blood-brain barrier (BBB). Only riluzole is approved for ALS treatment.
View Article and Find Full Text PDFParkinson's disease is a neurodegenerative disorder that requires treatment by dopaminergic agonists, which may be responsible for central side effects. We hypothesized that the efflux transporter ABCB1/P-glycoprotein played a role in brain disposition of antiparkinsonian drugs and could control central toxicity. We aimed to evaluate antiparkinsonian drugs as ABCB1 substrates and/or inhibitors in rat brain endothelial cells GPNT, in order to predict potential clinical drug-drug interactions.
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