Temporal dichotomy of neutrophil function in acute liver injury and repair.

Background & Aims: Acetaminophen (APAP)-induced acute liver injury (APAP-ALI) is the leading cause of acute liver failure-induced death, with host innate immune responses driving outcomes. Neutrophils are activated and increased in APAP-ALI and reported to contribute to liver damage. However, neutrophil dysfunction in patients with acute liver failure is associated with non-survival, and recent reports highlight their importance in hepatic repair.

Semaphorin 7a is protective through immune modulation during acetaminophen-induced liver injury.

Background And Aim: Acetaminophen (APAP) induced acute liver injury (ALI), the leading cause acute liver failure in the western world, has limited treatment options. APAP toxicity results in massive hepatic necrosis and secondary infiltrating monocytes and neutrophils, which contribute to pathogenesis. Semaphorin 7a (Sema7a), a chemoattractant and modulator of monocytes and neutrophils, is a potential therapeutic target in other conditions, but its role in APAP-ALI is unexplored.

Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse.

Acute liver failure is a rapidly progressing, life-threatening condition most commonly caused by an overdose of acetaminophen (paracetamol). The antidote, N-acetylcysteine (NAC), has limited efficacy when liver injury is established. If acute liver damage is severe, liver failure can rapidly develop with associated high mortality rates.

Analysis of AT7519 as a pro-resolution compound in an acetaminophen-induced mouse model of acute inflammation by UPLC-MS/MS.

Background: Uncontrolled inflammation contributes to the progression of organ damage in acute conditions, such as acetaminophen-induced acute liver injury (APAP-ALI) and there are limited treatments for this condition. AT7519, a cyclic-dependent kinase inhibitor (CDKI), has been used successfully in several conditions, to resolve inflammation and return tissue homeostatic functions. AT7519 has not been assessed in APAP-ALI and its effect on APAP metabolism is unknown.

Inhibition of Cyclin-Dependent Kinase 9 Downregulates Cytokine Production Without Detrimentally Affecting Human Monocyte-Derived Macrophage Viability.

Cyclin-dependent kinase (CDK) inhibitor drugs (CDKi), such as R-roscovitine and AT7519, induce neutrophil apoptosis and enhance the resolution of inflammation in a number of models. This class of compounds are potential novel therapeutic agents that could promote the resolution of acute and chronic inflammatory conditions where neutrophil activation contributes to tissue damage and aberrant tissue repair. In this study we investigated CDKi effects on macrophage pro-inflammatory mediator production and viability.

Low vitamin D status is associated with anaemia in hospitalised cats.

Background: The major physiological role of vitamin D has traditionally been considered to be the regulation of calcium homeostasis and maintenance of skeletal health. However, there is increasing evidence that vitamin D influences a wider range of physiological processes including erythropoiesis. Vitamin D (25-hydroxyvitamin D, 25(OH)D) deficiency concentrations have been associated with anaemia in human beings.

Acute Ulcerative Enterocolitis With Severe Protein Loss Due to Mucosal Invasion With . in a Dog With Exocrine Pancreatic Insufficiency: A Case Report.

We describe an unusual case of severe acute protein-losing enteropathy in a dog, which presented with a systemic inflammatory response syndrome. This dog's condition could not be categorized as any well-known canine intestinal condition. Instead, components of several enteropathies like acute hemorrhagic diarrhea syndrome (AHDS), chronic inflammatory enteropathy (CIE), and ulcerative and granulomatous colitis were present.

Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation.

Eosinophils are key effector cells in allergic diseases. Here we investigated Mcl-1 (an anti-apoptotic protein) in experimental allergic airway inflammation using transgenic overexpressing human Mcl-1 mice (hMcl-1) and reducing Mcl-1 by a cyclin-dependent kinase inhibitor. Overexpression of Mcl-1 exacerbated allergic airway inflammation, with increased bronchoalveolar lavage fluid cellularity, eosinophil numbers and total protein, and an increase in airway mucus production.

Resolution of Inflammation and Gut Repair in IBD: Translational Steps Towards Complete Mucosal Healing.

Despite significant recent therapeutic advances, complete mucosal healing remains a difficult treatment target for many patients with inflammatory bowel diseases (IBD) to achieve. Our review focuses on the translational concept of promoting resolution of inflammation and repair as a necessary adjunctive step to reach this goal. We explore the roles of inflammatory cell apoptosis and efferocytosis to promote resolution, the new knowledge of gut monocyte-macrophage populations and their secreted prorepair mediators, and the processes of gut epithelial repair and regeneration to bridge this gap.

Alternatively activated macrophages promote resolution of necrosis following acute liver injury.

Background & Aim: Following acetaminophen (APAP) overdose, acute liver injury (ALI) can occur in patients that present too late for N-acetylcysteine treatment, potentially leading to acute liver failure, systemic inflammation, and death. Macrophages influence the progression and resolution of ALI due to their innate immunological function and paracrine activity. Syngeneic primary bone marrow-derived macrophages (BMDMs) were tested as a cell-based therapy in a mouse model of APAP-induced ALI (APAP-ALI).

Pilot study evaluating the monitoring of canine diabetes mellitus in primary care practice.

Objectives: This study aimed to describe how canine diabetes mellitus (CDM) is monitored in primary care practice (PCP) and to report outcomes.

Design: Retrospective case review.

Setting: PCP.

Inflammation Resolution and the Induction of Granulocyte Apoptosis by Cyclin-Dependent Kinase Inhibitor Drugs.

Inflammation is a necessary dynamic tissue response to injury or infection and it's resolution is essential to return tissue homeostasis and function. Defective or dysregulated inflammation resolution contributes significantly to the pathogenesis of many, often common and challenging to treat human conditions. The transition of inflammation to resolution is an active process, involving the clearance of inflammatory cells (granulocytes), a change of mediators and their receptors, and prevention of further inflammatory cell infiltration.

Relationship between vitamin D status and leukocytes in hospitalised cats.

Objectives Vitamin D deficiency, as assessed by serum 25-hydroxyvitamin D (25[OH]D) concentrations, has been linked to markers of systemic inflammation in human and canine medicine. However, the relationship between vitamin D status and inflammation has not been previously investigated in cats. The aim of this study was to examine the relationship between serum 25(OH)D concentrations and leukocyte counts in hospitalised sick cats.