Gut Microbiota and Liver Dysfunction in Sepsis: The Role of Inflammatory Mediators and Therapeutic Approaches.

Sepsis is a life-threatening complication caused by an uncontrolled immune response to infection that can lead to multi-organ dysfunction, including liver injury. Recent research has shown the critical role of gut microbiota in sepsis pathogenesis, with the gut-liver axis playing a crucial role in disease progression. Mechanisms such as the disruption of the gut barrier and liver injury pathways mediated by cytokines, chemokines, adhesion molecules, hydrogen sulfide (HS).

Novel Monoclonal Antibodies 1D2 and 4E4 Against Glycoprotein Antigens Detect Early Invasive Aspergillosis in Mice.

Due to the high morbidity and mortality rates of invasive aspergillosis (IA) and the importance of early IA detection for successful treatment and subsequent outcome, this study aimed to determine a time course of detectable antigen in a mouse model of IA and correlate it with tissue invasion by using two novel monoclonal antibodies, 1D2 and 4E4, that can be used to detect the -derived glycoproteins. Immunocompromised mice were randomly divided into five groups: uninfected control, and inoculation with conidia from , , and . Conidia (2 × 10 cells/mL) were administered intravenously via tail vein injection.

The inhibitory effect of copper, zinc, and manganese on Legionella longbeachae in potting mix leachate.

Legionella longbeachae is the leading cause of Legionnaires' disease (LD) in Australasia and has been linked to exposure to compost and potting soils. Adding antimicrobial metal ions such as copper (Cu2+), zinc (Zn2+), and manganese (Mn2+) to potting soils may reduce the load of L. longbeachae bacteria and infection risk.

Low Vitamin C Concentrations in Patients with Community-Acquired Pneumonia Resolved with Pragmatic Administration of Intravenous and Oral Vitamin C.

Community-acquired pneumonia (CAP) is characterized by elevated markers of inflammation and oxidative stress and depleted circulating concentrations of the antioxidant nutrient vitamin C. A feasibility trial of intravenous and oral vitamin C supplementation, matched to the timing of intravenous and oral antibiotic formulations, was carried out and changes in vitamin C status were monitored to determine whether saturating status could be achieved throughout the administration period. Patients with moderate and severe CAP (CURB-65 ≥ 2; = 75) who were receiving intravenous antimicrobial therapy were randomized to placebo ( = 39) or intravenous vitamin C (2.

Adjunctive intravenous then oral vitamin C for moderate and severe community-acquired pneumonia in hospitalized adults: feasibility of randomized controlled trial.

Patients hospitalised with community acquired pneumonia (CAP) have low peripheral blood vitamin C concentrations and limited antioxidant capacity. The feasibility of a trial of vitamin C supplementation to improve patient outcomes was assessed. Participants with moderate and severe CAP (CURB-65 ≥ 2) on intravenous antimicrobial treatment were randomised to either intravenous vitamin C (2.

The inhibitory effect of copper, zinc, and manganese on Legionella longbeachae and other Legionella spp. in vitro.

Legionella longbeachae is an important cause of Legionnaires' disease in Australasia and is associated with exposure to potting soils. Our aim was to identify ways to reduce the load of L. longbeachae in potting soils.

A Novel Monoclonal Antibody 1D2 That Broadly Inhibits Clinically Important Species.

Aspergillus fumigatus is a ubiquitous airborne fungus, is the predominant cause (>90%) of invasive aspergillosis (IA) in immunosuppressed patients and has a high mortality. New approaches to prevention and treatment are needed because of the poor efficacy, toxicity and side effects of the current anti-Aspergillus drugs on patients. Thus, we aim to explore a new avenue to combat Aspergillus infection by using a novel monoclonal antibody (mAb) 1D2 against a glycoprotein on the cell wall of Aspergillus.

Hydrogen Sulfide and Substance P Levels in Patients with and Bacteraemia.

Hydrogen sulfide (HS) and substance P (SP) are known from animal models and in vitro studies as proinflammatory mediators. In this study, peripheral blood concentrations of HS and SP were measured in patients with or bacteraemia. Fifty patients were recruited from general wards at Christchurch Hospital, during 2020-2021.

Monoclonal Antibodies and Invasive Aspergillosis: Diagnostic and Therapeutic Perspectives.

Invasive aspergillosis (IA) is a life-threatening fungal disease that causes high morbidity and mortality in immunosuppressed patients. Early and accurate diagnosis and treatment of IA remain challenging. Given the broad range of non-specific clinical symptoms and the shortcomings of current diagnostic techniques, most patients are either diagnosed as "possible" or "probable" cases but not "proven".

Two Monoclonal Antibodies That Specifically Recognize Cell Wall Antigens and Can Detect Circulating Antigens in Infected Mice.

Invasive aspergillosis (IA) is a life-threatening disease mainly caused by and . Early diagnosis of this condition is crucial for patient treatment and survival. As current diagnostic techniques for IA lack sufficient accuracy, we have raised two monoclonal antibodies (1D2 and 4E4) against cell wall fragments that may provide a platform for a new diagnostic approach.

Legionellosis Caused by Non- Species, with a Focus on .

Although known as causes of community-acquired pneumonia and Pontiac fever, the global burden of infection caused by species other than is under-recognised. Non- legionellae have a worldwide distribution, although common testing strategies for legionellosis favour detection of over other species, leading to an inherent diagnostic bias and under-detection of cases. When systematically tested for in Australia and New Zealand, was shown to be a leading cause of community-acquired pneumonia.

Enhancement of Culture of Legionella longbeachae from Respiratory Samples by Use of Immunomagnetic Separation and Antimicrobial Decontamination.

is the commonest species identified in patients with community-acquired pneumonia in New Zealand. Isolation of the organism on culture is the gold standard for the diagnosis of Legionnaires disease, but it has poor sensitivity (40%) compared with quantitative PCR (qPCR). We have developed a selective decontamination process using glycine, vancomycin, polymyxin, and cycloheximide (GVPC) with immunomagnetic separation (IMS) for culturing A polyclonal antibody specific for was produced from New Zealand White rabbits and coupled to tosyl-activated magnetic beads.

Validating a breath collection and analysis system for the new tuberculosis breath test.

Mycobacterium tuberculosis releases four volatile compounds, methyl phenyl-acetate, methyl nicotinate, methyl p-anisate and o-phenylanisole, some of which we have previously been reported to be detected in the breath of tuberculosis patients (Syhre et al 2009 Tuberculosis 89 263-6). These volatiles have the potential to offer a non-invasive and sensitive breath test for the detection of tuberculosis infection. To determine the best sample collection and pre-concentration system a number of variables were examined.

Assessment of potential causes of falsely positive Mycobacterium tuberculosis breath test.

A suite of volatiles have previously been identified as specific markers of Mycobacterium tuberculosis metabolism in vitro. These markers - methyl phenylacetate, methyl p-anisate, methyl nicotinate, o-phenylanisole with the addition of methyl salicylate, may also be derived from other sources and confound development of a breath test for tuberculosis. To identify potential sources of these potential biomarkers food products, cosmetics, TB medication, environmental air and cigarette smoke were analysed for these markers using solid phase microextraction coupled with Gas Chromatography/Mass Spectrometry.

Quantification of hydrogen cyanide (HCN) in breath using selected ion flow tube mass spectrometry--HCN is not a biomarker of Pseudomonas in chronic suppurative lung disease.

Hydrogen cyanide (HCN) in exhaled breath has been proposed as a biomarker for airway inflammation, and also a marker of the presence in the airways of specific organisms, especially Pseudomonas aeruginosa. However the production of HCN by salivary peroxidase in the oral cavity increases orally exhaled concentrations, and may not reflect the condition of the lower airways. Using SIFT-MS we aimed to determine an appropriate single-exhalation breathing maneuver which avoids the interference of HCN produced in the oral cavity.

Developments in novel breath tests for bacterial and fungal pulmonary infection.

Purpose Of Review: Breath testing has developed over the last 20 years. New techniques that can identify fingerprints for specific diseases and specific markers of respiratory pathogens have been applied to breath analysis. This review discusses the recent advances in breath analysis for the diagnosis of bacterial and fungal lower respiratory tract infections.

Determining the limits and confounders for the 2-pentyl furan breath test by gas chromatography/mass spectrometry.

Aspergillus fumigatus produces 2-pentyl furan (2-PF), a volatile compound not produced by many other pathogens or normal human metabolism. 2-Pentyl furan has been detected in the breath of patients with invasive aspergillosis (IA) by SPME pre-concentration coupled with CG/MS providing the possibility of an attractive diagnostic test. The limit of detection (LOD) and quantification (LOQ) for peak integration were assessed both statistically and empirically respectively.

Potential sources of 2-aminoacetophenone to confound the Pseudomonas aeruginosa breath test, including analysis of a food challenge study.

2-Aminoacetophenone can be detected in the breath of Pseudomonas aeruginosa colonized cystic fibrosis patients; however, low levels were also detected in a small proportion of healthy subjects. It was hypothesized that food, beverages, cosmetics or medications could be a source of contamination of 2-aminoacetophenone in breath. To determine the potential confounding of these products on 2-aminoacetophenone breath analysis, screening for this volatile was performed in the laboratory by gas chromatography/mass spectrometry and a food challenge study carried out.

2-Aminoacetophenone as a potential breath biomarker for Pseudomonas aeruginosa in the cystic fibrosis lung.

Background: Pseudomonas aeruginosa infections are associated with progressive life threatening decline of lung function in cystic fibrosis sufferers. Growth of Ps. aeruginosa releases a "grape-like" odour that has been identified as the microbial volatile organic compound 2-aminoacetophenone (2-AA).

Novel diagnostics: progress toward a breath test for invasive Aspergillus fumigatus.

In this paper we will briefly review some of the possible techniques for the development of a breath test for aspergillosis and describe progress made toward validating 2-Pentyl furan (2PF) as a marker of Aspergillus infection. Breath testing to diagnose pulmonary aspergillosis is attractive because of the proximity of the lesion to the sample and the simplicity of obtaining diagnostic specimens. Techniques to detect volatile organic compounds (VOCs) in breath discussed include the electronic nose, selective ion flow mass spectrometry (SIFT), ion mobility spectrometry (IMS) and gas chromatography with mass spectrometry (GC/MS).

Hypothiocyanous acid is a potent inhibitor of apoptosis and caspase 3 activation in endothelial cells.

Hypothiocyanous acid (HOSCN) is a common, thiol-specific oxidant with strong antibacterial activity. It is thought to be nontoxic to mammalian cells, although its ability to specifically target intracellular thiols may potentially cause cellular dysfunction. In this study we demonstrate specific effects of HOSCN on human endothelial cells, with exposure to high concentrations resulting in morphology changes unlike those seen with other oxidants.