20 research outputs found

    Phenylbutyrate Counteracts Shigella Mediated Downregulation of Cathelicidin in Rabbit Lung and Intestinal Epithelia: A Potential Therapeutic Strategy

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    BACKGROUND: Cathelicidins and defensins are endogenous antimicrobial peptides (AMPs) that are downregulated in the mucosal epithelia of the large intestine in shigellosis. Oral treatment of Shigella infected rabbits with sodium butyrate (NaB) reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. AIMS: To develop novel regimen for treating infectious diseases by inducing innate immunity, we selected sodium 4-phenylbutyrate (PB), a registered drug for a metabolic disorder as a potential therapeutic candidate in a rabbit model of shigellosis. Since acute respiratory infections often cause secondary complications during shigellosis, the systemic effect of PB and NaB on CAP-18 expression in respiratory epithelia was also evaluated. METHODS: The readouts were clinical outcomes, CAP-18 expression in mucosa of colon, rectum, lung and trachea (immunohistochemistry and real-time PCR) and release of the CAP-18 peptide/protein in stool (Western blot). PRINCIPAL FINDINGS: Significant downregulation of CAP-18 expression in the epithelia of rectum and colon, the site of Shigella infection was confirmed. Interestingly, reduced expression of CAP-18 was also noticed in the epithelia of lung and trachea, indicating a systemic effect of the infection. This suggests a causative link to acute respiratory infections during shigellosis. Oral treatment with PB resulted in reduced clinical illness and upregulation of CAP-18 in the epithelium of rectum. Both PB and NaB counteracted the downregulation of CAP-18 in lung epithelium. The drug effect is suggested to be systemic as intravenous administration of NaB could also upregulate CAP-18 in the epithelia of lung, rectum and colon. CONCLUSION: Our results suggest that PB has treatment potential in human shigellosis. Enhancement of CAP-18 in the mucosal epithelia of the respiratory tract by PB or NaB is a novel discovery. This could mediate protection from secondary respiratory infections that frequently are the lethal causes in dysentery

    Impaired Release of Antimicrobial Peptides into Nasal Fluid of Hyper-IgE and CVID Patients

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    Patients with primary immunodeficiency (PID) often suffer from frequent respiratory tract infections. Despite standard treatment with IgG-substitution and antibiotics many patients do not improve significantly. Therefore, we hypothesized that additional immune deficits may be present among these patients.To investigate if PID patients exhibit impaired production of antimicrobial peptides (AMPs) in nasal fluid and a possible link between AMP-expression and Th17-cells.Nasal fluid, nasopharyngeal swabs and peripheral blood mononuclear cells (PBMCs) were collected from patients and healthy controls. AMP levels were measured in nasal fluid by Western blotting. Nasal swabs were cultured for bacteria. PBMCs were stimulated with antigen and the supernatants were assessed for IL-17A release by ELISA.In healthy controls and most patients, AMP levels in nasal fluid were increased in response to pathogenic bacteria. However, this increase was absent in patients with common variable immunodeficiency (CVID) and Hyper-IgE syndrome (HIES), despite the presence of pathogenic bacteria. Furthermore, stimulation of PBMCs revealed that both HIES and CVID patients exhibited an impaired production of IL-17A.CVID and HIES patients appear to have a dysregulated AMP response to pathogenic bacteria in the upper respiratory tract, which could be linked to an aberrant Th17 cell response

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    ANTIHYPERGLYCEMIC EFFECT OF BRIDELIA NDELLENSIS ETHANOL EXTRACT AND FRACTIONS IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

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    The effects of the ethanol extract (1.25 g/kg) and fractions (1 g/kg) of Bridelia ndellensis stem bark on the blood glucose levels in streptozotocin-induced types 1 and 2 diabetic rats at different prandial states were studied. The ethanol extract of B. ndellensis had no hypoglycemic effect in type 1 diabetic rats in fasting and postprandial glucose load conditions and, in type 2 diabetic rats in fasting condition. However, the extract, and its ethyl acetate and dichloromethane fractions significantly lowered blood glucose levels in type 2 diabetic rats when fed simultaneously with glucose. The active principles responsible for the antihyperglycaemic effect are concentrated in the ethyl acetate and dichloromethane fractions of the extract

    Antihyperglycemic effect of Bridelia ndellensis ethanol extract and fractions in streptozotocin-induced diabetic rats

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    The effects of the ethanol extract (1.25 g/kg) and fractions (1 g/kg) of Bridelia ndellensis stem bark on the blood glucose levels in streptozotocin-induced types 1 and 2 diabetic rats at different prandial states were studied. The ethanol extract of B. ndellensis had no hypoglycemic effect in type 1 diabetic rats in fasting and postprandial glucose load conditions and, in type 2 diabetic rats in fasting condition. However, the extract, and its ethyl acetate and dichloromethane fractions significantly lowered blood glucose levels in type 2 diabetic rats when fed simultaneously with glucose. The active principles responsible for the antihyperglycaemic effect are concentrated in the ethyl acetate and dichloromethane fractions of the extract

    Diabetic foot ulcer, antimicrobial remedies and emerging strategies for the treatment: An overview

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    According to the International Diabetes Federation's 2015 study, diabetes affects over 415 million people globally (5 million of whom die each year), and the incidence of diabetes is expected to climb to over 640 million (1 in 10) by 2040. (IDF 2015). Diabetes foot ulcers (DFU) are one of the most significant diabetic health consequences. Antimicrobial treatments, such as dressings, topical therapies, medicines, drugs, debridement procedures, molecular, cellular, and gene therapies, plant extracts, antimicrobial peptides, growth factors, devices, ozone, and energy-based therapies, would be the focus of this study. Scopus, Web of Science, Bentham Science, Science Direct, and Google Scholar were among the sources used to compile the English-language publications on DFU. DFU treatment requires a multidisciplinary approach that includes the use of proper diagnostic tools, competence, and experience. To prevent amputations, this starts with patient education and the use of new categories to steer treatment. New diagnostic methods, such as the 16S ribosomal DNA sequence in bacteria, should become available to acquire a better knowledge of the microbiota in DFUs.&nbsp
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