Monophosphoryl lipid A prevents impairment of medullary thick ascending LIMB HCO3- absorption and improves plasma HCO3- concentration in septic mice.

Monophosphoryl lipid A prevents impairment of medullary thick ascending LIMB HCO3- absorption and improves plasma HCO3- concentration in septic mice. Am J Physiol Renal Physiol. 2018 May 09;: Authors: Watts BA, George T, Sherwood ER, Good DW Abstract Metabolic acidosis is the most common acid-base disorder in septic patients and is associated with increased mortality. Previously we demonstrated that sepsis induced by cecal ligation and puncture (CLP) impairs HCO3- absorption in the MTAL by: 1) decreasing the intrinsic HCO3- absorptive capacity, and 2) enhancing inhibition of HCO3- absorption by LPS through upregulation of TLR4 signaling. Both effects depend on ERK activation. Monophosphoryl lipid A (MPLA) is a detoxified TLR4 agonist that enhances innate antimicrobial immunity and improves survival following sepsis. Pretreatment of MTALs with MPLA in vitro prevents LPS inhibition of HCO3- absorption. Here we examined whether pretreatment with MPLA would protect the MTAL against sepsis. Mice were administered vehicle or MPLA 48 h before sham or CLP surgery. MTALs were studied in vitro 18 h post-surgery. Pretreatment with MPLA prevented both the effects of sepsis to decrease the basal HCO3- absorption rate and to enhance inhibition by LPS. These protective effects were mediated through MPLA stimulation of a TRIF-dependent PI3K-Akt pathway that prevents sepsis- and LPS-induced ERK activation. The effects of MPLA to improve MTAL HCO3- absorption were associa...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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CONCLUSION: Prevalence of antibiotic use was high not only versus other hospitals in the region but globally including Africa, coupled with significant evidence of sub-optimal prescribing. Swift action is needed to improve future prescribing to reduce AMR. One or two areas should initially be targeted for quality improvement including development of local guidelines, documentation of antibiotic indications and/or stop/review dates. PMID: 33034234 [PubMed - as supplied by publisher]
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
Authors: Rombauts A, Abelenda-Alonso G, Cuervo G, Gudiol C, Carratalà J Abstract INTRODUCTION: Despite adequate antibiotic coverage, community-acquired pneumonia (CAP) remains a leading cause of hospitalization and mortality worldwide. It induces both a local pulmonary and a systemic inflammatory response, particularly significant in severe cases. The intensity of the dysregulated host response varies from patient to patient and has a negative impact on survival and other outcomes. AREAS COVERED: This comprehensive review summarizes the pathophysiological aspects of the inflammatory response in CAP, brie...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
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Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
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Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
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