IL-33/ST2 Axis in Organ Fibrosis

Interleukin 33 (IL-33) is highly expressed in barrier sites, acting via the suppression of tumorigenicity 2 receptor (ST2). IL-33/ST2 axis has long been known to play a pivotal role in immunity and cell homeostasis by promoting wound healing and tissue repair. However, it is also involved in the loss of balance between extensive inflammation and tissue regeneration lead to remodeling, the hallmark of fibrosis. The aim of the current review is to critically evaluate the available evidence regarding the role of the IL-33/ST2 axis in organ fibrosis. The role of the axis in tissue remodeling is better understood considering its crucial role reported in organ development and regeneration. Generally, the IL-33/ST2 signaling pathway has mainly anti-inflammatory/anti-proliferative effects; however, chronic tissue injury is responsible for pro-fibrogenetic responses. Regarding pulmonary fibrosis mature IL-33 enhances pro-fibrogenic type 2 cytokine production in an ST2- and macrophage-dependent manner, while full-length IL-33 is also implicated in the pulmonary fibrotic process in an ST2-independent, Th2-independent fashion. In liver fibrosis, evidence indicate that when acute and massive liver damage occurs, the release of IL-33 might act as an activator of tissue-protective mechanisms, while in cases of chronic injury IL-33 plays the role of a hepatic fibrotic factor. IL-33 signaling has also been involved in the pathogenesis of acute and chronic pancreatitis. Moreover, IL-33 could be used as an early marker for ulcer-associated activated fibroblasts and myofibroblast trans-differentiation; thus one cannot rule out its potential role in inflammatory bowel disease-associated fibrosis. Similarly, the upregulation of the IL-33/ST2 axismay contribute to tubular cell injury and fibrosis via epithelial to mesenchymal transition (EMT) of various cell types in the kidneys. Of note, IL-33 exerts a cardioprotective role via ST2 signaling, while soluble ST2 has been demonstrated as a marker of myocardial fibrosis. Finally, IL-33 is a crucial cytokine in skin pathology responsible for abnormal fibroblast proliferation, leukocyte infiltration and morphologic differentiation of human endothelial cells. Overall, emerging data support a novel contribution of the IL-33/ST2 pathway in tissue fibrosis and highlight the significant role of the Th2 pattern of immune response in the pathophysiology of organ fibrosis

Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a study protocol for a randomised controlled trial

© 2016 Lee et al. Background: Urinary tract infections [UTIs] are very common in people with Spinal Cord Injury [SCI]. UTIs are increasingly difficult and expensive to treat as the organisms that cause them become more antibiotic resistant. Among the SCI population, there is a high rate of multi-resistant organism [MRO] colonisation. Non-antibiotic prevention strategies are needed to prevent UTI without increasing resistance. Probiotics have been reported to be beneficial in preventing UTIs in post-menopausal women in several in vivo and in vitro studies. The main aim of this study is to determine whether probiotic therapy with combinations of Lactobacillus reuteri RC-14 + Lactobacillus rhamnosus GR-1 [RC14-GR1] and/or Lactobacillus rhamnosus GG + Bifidobacterium BB-12 [LGG-BB12] are effective in preventing UTI in people with SCI compared to placebo. Method: This is a multi-site randomised double-blind double-dummy placebo-controlled factorial design study conducted in New South Wales, Australia. All participants have a neurogenic bladder as a result of spinal injury. Recruitment started in April 2011. Participants are randomised to one of four arms, designed for factorial analysis of LGG-BB12 and/or RC14-GR1 v Placebo. This involves 24 weeks of daily oral treatment with RC14-GR1 + LGG-BB12, RC14-GR1 + placebo, LGG-BB12 + placebo or two placebo capsules. Randomisation is stratified by bladder management type and inpatient status. Participants are assessed at baseline, three months and six months for Short Form Health Survey [SF-36], microbiological swabs of rectum, nose and groin; urine culture and urinary catheters for subjects with indwelling catheters. A bowel questionnaire is administered at baseline and three months to assess effect of probiotics on bowel function. The primary outcome is time from randomisation to occurrence of symptomatic UTI. The secondary outcomes are change of MRO status and bowel function, quality of life and cost-effectiveness of probiotics in persons with SCI. The primary outcome will be analysed using survival analysis of factorial groups, with Cox regression modelling to test the effect of each treatment while allowing for the other, assuming no interaction effect. Hazard ratios and Kaplan-Meier survival curves will be used to summarise results. Discussion: If these probiotics are shown to be effective in preventing UTI and MRO colonisation, they would be a very attractive alternative for UTI prophylaxis and for combating the increasing rate of antibiotic resistance after SCI. Trial registration: Australian New Zealand Clinical Trials Registry [ ACTRN 12610000512022 ]. Date of registration: 21 June 2010

Emergence and spread of predominantly community-onset Clostridium difficile PCR ribotype 244 infection in Australia, 2010 to 2012

We describe an Australia-wide Clostridium difficile outbreak in 2011 and 2012 involving the previously uncommon ribotype 244. In Western Australia, 14 of 25 cases were community-associated, 11 were detected in patients younger than 65 years, 14 presented to emergency/outpatient departments, and 14 to non-tertiary/community hospitals. Using whole genome sequencing, we confirm ribotype 244 is from the same C. difficile clade as the epidemic ribotype 027. Like ribotype 027, it produces toxins A, B, and binary toxin, however it is fluoroquinolone-susceptible and thousands of single nucleotide variants distinct from ribotype 027. Fifteen outbreak isolates from across Australia were sequenced. Despite their geographic separation, all were genetically highly related without evidence of geographic clustering, consistent with a point source, for example affecting the national food chain. Comparison with reference laboratory strains revealed the outbreak clone shared a common ancestor with isolates from the United States and United Kingdom (UK). A strain obtained in the UK was phylogenetically related to our outbreak. Follow-up of that case revealed the patient had recently returned from Australia. Our data demonstrate new C. difficile strains are an on-going threat, with potential for rapid spread. Active surveillance is needed to identify and control emerging lineages

Venous thromboembolic disease in chronic inflammatory lung diseases: Knowns and unknowns

Persistent inflammation within the respiratory tract underlies the pathogenesis of numerous chronic pulmonary diseases. There is evidence supporting that chronic lung diseases are associated with a higher risk of venous thromboembolism (VTE). However, the relationship between lung diseases and/or lung function with VTE is unclear. Understanding the role of chronic lung inflammation as a predisposing factor for VTE may help determine the optimal management and aid in the development of future preventative strategies. We aimed to provide an overview of the relationship between the most common chronic inflammatory lung diseases and VTE. Asthma, chronic obstructive pulmonary disease, interstitial lung diseases, or tuberculosis increase the VTE risk, especially pulmonary embolism (PE), compared to the general population. However, high suspicion is needed to diagnose a thrombotic event early as the clinical presentation inevitably overlaps with respiratory disorders. PE risk increases with disease severity and exacerbations. Hence, hospitalized patients should be considered for thromboprophylaxis administration. Conversely, all VTE patients should be asked for lung comorbidities before determining anticoagulant therapy duration, as those patients are at increased risk of recurrent PE episodes rather than DVT. Further research is needed to understand the underlying pathophysiology of in-situ thrombosis in those patients. © 2021 by the author. Licensee MDPI, Basel, Switzerland

When the brain hurts the lung: neurogenic pulmonary edema following a first epileptic seizure

[No abstract available

Flaxseed and sprouted lentil seeds as functional ingredients in the development of nutritionally fortified “clean-label” gluten-free breads

A “clean-label” gluten-free bread (GFB) was developed by replacing the commonly used hydrocolloid additive, methylcellulose, with an aqueous flaxseed slurry (FSS), known for its structure-forming properties, at 3 or 4.5 % levels into GFB formulations; for further nutritional improvement of GFB, the inclusion of 5 or 10 % roasted-sprouted lentil flour (SLF) was also investigated. FSS and SLF addition increased hardness, consistency, storage and loss moduli, and viscosity of the composite batters. The specific volumes of fortified breads were reduced, compared to control bread containing methylcellulose; however, they were greatly improved compared to bread made without any added hydrocolloid. Fresh breads containing solely FSS (3, 4.5 %) and that made with 3 % FSS-5 % SLF exhibited crumb textural characteristics similar to the control; the 3 % FSS-5 % SLF fortified sample showed similar textural changes upon storage (48 h, 25 °C) and slightly lower amylopectin retrogradation, compared to control bread. Further to increasing the contents of protein and total dietary fiber, FSS incorporation into GFB decreased the glucose release upon in vitro starch digestion, whereas inclusion of both FSS and SLF weakened this effect. Moreover, the “nutty” and “roasted legume” flavor-aroma notes, introduced by FSS and SLF, reduced the typical flat “rice” flavor-aroma of GFB, thus contributing to the higher overall consumer acceptability scores received for breads containing solely FSS as well as those fortified with 3 %FSS-5 % SLF. Overall, both FSS and SLF appear to be promising functional ingredients for production of “clean-label” GFB, having higher contents of macronutrients, improved sensorial characteristics, and acceptable textural attributes

The impact of the lockdown caused by the covid-19 pandemic on the fine particulate matter (Pm2.5) air pollution: The greek paradigm

Introduction: Responding to the coronavirus pandemic, Greece implemented the largest quarantine in its history. No data exist regarding its impact on PM2.5 pollution. We aimed to assess PM2.5 levels before, during, and after lockdown (7 March 2020–16 May 2020) in Volos, one of Greece’s most polluted industrialized cities, and compare PM2.5 levels with those obtained during the same period last year. Meteorological conditions were examined as confounders. Methods: The study period was discriminated into three phases (pre-lockdown: 7 March–9 March, lockdown: 10 March–4 May, and post-lockdown period: 5 May–16 May). A wireless sensors network was used to collect PM2.5, temperature, relative humidity, rainfall, and wind speed data every 2 s. Results: The lockdown resulted in a significant drop of PM2.5 by 37.4% in 2020, compared to 2019 levels. The mean daily concentrations of PM2.5 exceeded the WHO’s guideline value for 24-h mean levels of PM2.5 35% of the study period. During the strictest lockdown (23 March to 4 May), the mean daily PM2.5 levels exceeded the standard 41% of the time. The transition from the pre-lockdown period into lockdown or post-lockdown periods was associated with lower PM2.5 concentrations. Conclusions: A reduction in the mean daily PM2.5 concentration was found compared to 2019. Lockdown was not enough to avoid severe exceedances of air pollution in Volos. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Clonidine changes lidocaine free concentrations in rat myocardium without affecting heart function measured by echocardiography

Lidocaine is a local anaesthetic widely used in regional and epidural anaesthesia. Clonidine a α2-adrenergic agonist is an antihypertensive agent, regulating the production of catecholamines (epinephrine and norepinephrine) and added to local anesthetic infusions in order to improve postoperative analgesia. The aim of the study was to investigate the influence of clonidine co-administration on the binding of 14C lidocaine to rat serum and heart tissue protein as well as its pharmacodynamic effects in the heart. Four groups of Wistar rats (n=7) were used; Groups I and II received 4 mg/kg lidocaine I.M. Groups III and IV received lidocaine and 1 μg/kg clonidine I.M. In group I and III fifteen minutes and in groups II and IV thirty minutes after the initial treatment, ultrasound examination of heart function (heart rate, diameter of left ventricle in systole and diastole, ejection fraction) was performed. The animals were then sacrificed in all groups. Lidocaine free fraction in serum and heart was evaluated via ultrafiltration. The kinetics of lidocaine was altered by clonidine co-administration probably by mechanisms related to protein binding alterations. However, the pharmacokinetic interactions were not accompanied by changes of pharmacodynamic parameters including those of heart function as measured by echocardiography