Dietary plasma proteins attenuate the innate immunity response in a mouse model of acute lung injury

We examined whether oral plasma protein supplements affect the innate immune response in a model of acute lung inflammation. Mice were fed diets supplemented with 8% spray-dried plasma (SDP) or 2% plasma Ig concentrate (IC) from day 19 (weaning) until day 34. The mice were challenged with intranasal lipopolysaccharide (LPS) at day 33 (and killed 24 h later for cytokine and leucocyte analyses) or at day 34 (and killed 6 h later for cytokine determinations). In bronchoalveolar lavage fluid (BALF), LPS increased the number of leucocytes by twenty-sevenfold, an effect that was partly prevented by both SDP and IC, and by twentyfold the percentage of activated monocytes, which was partly prevented by SDP. In the lung tissue, LPS increased the infiltrated leucocytes, and this effect was prevented in part by SDP. In unchallenged mice, both SDP and IC diets reduced the percentage of resident neutrophils and monocytes (P,0·05). In the blood, both SDP and IC completely prevented LPS-dependent monocyte activation (CD14þ; P,0·05). LPS dramatically increased the concentration of cytokines (TNF-a, IL-1a, IL-6, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor) and chemokines (CXCL1, CCL2, CCL3 and CCL4) in BALF. The acute response of cytokine production was reduced by 20-80% by both SDP and IC. For chemokines, plasma supplements had no effect on LPS-induced CXCL1 expression but significantly reduced CCL2, CCL3 and CCL4 production (P,0·05). The results support the view that dietary plasma proteins can be used to attenuate endotoxin-associated lung inflammation

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Oral Serum-Derived Bovine Immunoglobulin/Protein Isolate Has Immunomodulatory Effects on the Colon of Mice that Spontaneously Develop Colitis

Dietary immunoglobulin concentrates prepared from animal plasma can modulate the immune response of gut-associated lymphoid tissue (GALT). Previous studies have revealed that supplementation with serum-derived bovine immunoglobulin/protein isolate (SBI) ameliorates colonic barrier alterations in the mdr1a-/- genetic mouse model of IBD. Here, we examine the effects of SBI on mucosal inflammation in mdr1a-/- mice that spontaneously develop colitis. Wild type (WT) mice and mice lacking the mdr1a gene (KO) were fed diets supplemented with either SBI (2% w/w) or milk proteins (Control diet), from day 21 (weaning) until day 56. Leucocytes in mesenteric lymph nodes (MLN) and in lamina propria were determined, as was mucosal cytokine production. Neutrophil recruitment and activation in MLN and lamina propria of KO mice were increased, but were significantly reduced in both by SBI supplementation (p < 0.05). The increased neutrophil recruitment and activation observed in KO mice correlated with increased colon oxidative stress (p < 0.05) and SBI supplementation reduced this variable (p < 0.05). The Tact/Treg lymphocyte ratios in MLN and lamina propria were also increased in KO animals, but SBI prevented these changes (both p < 0.05). In the colon of KO mice, there was an increased production of mucosal proinflammatory cytokines such as IL-2 (2-fold), IL-6 (26-fold) and IL-17 (19-fold), and of chemokines MIP-1β (4.5-fold) and MCP-1 (7.2-fold). These effects were significantly prevented by SBI (p < 0.05). SBI also significantly increased TGF-β secretion in the colon mucosa, suggesting a role of this anti-inflammatory cytokine in the modulation of GALT and the reduction of the severity of the inflammatory response during the onset of colitis

Dietary spray-dried plasma improves intestinal morphology of mated female mice under stress condition

Abstract Background Stress causes inflammation that impairs intestinal barrier function. Dietary spray-dried plasma (SDP) has recognized anti-inflammatory effects and improvement of gut barrier function. Therefore, the purpose of this study was to investigate the effects of dietary SDP on intestinal morphology of mated female mice under stress condition. Results Villus height, width, and area of small intestines were low on gestation day (GD) 3 or 4 under stress conditions, and higher later (Time, P < 0.05). Crypt depth of colon was low on GD 4 and higher later (Time, P < 0.05). Meanwhile, the SDP treatments improved (P < 0.05) intestinal morphology, indicated by increased villus height, villus width, villus area, and ratio between villus height and crypt depth of small intestines and crypt depth of colon, and by decreased crypt depth of small intestines, compared with the control diet. The SDP treatments also increased (P < 0.05) the number of goblet cells in intestines compared with the control diet. There were no differences between different levels of SDP. Conclusion Dietary SDP improves intestinal morphology of mated female mice under stress condition

Spray-dried plasma attenuates inflammation and lethargic behaviors of pregnant mice caused by lipopolysaccharide.

This study evaluated whether dietary spray-dried plasma (SDP) can ameliorate inflammation, lethargic behaviors, and impairment of reproduction caused by lipopolysaccharide (LPS) challenge during late pregnancy. Two experiments were conducted with 125 mated female mice (C57BL/6 strain) in each experiment. All mice were shipped from a vendor on the gestation day (GD) 1 and arrived at the laboratory on GD 3. Mice were randomly assigned to dietary treatments with or without 8% SDP in the diet. On GD 17, mice determined pregnant by BW and abdomen shape were randomly assigned to intraperitoneal injections with or without 2 μg LPS. In experiment 1, 17 mice (26.7 ± 1.7 g BW) were identified pregnant and euthanized 6 h after the LPS challenge to measure inflammatory responses in uterus and placenta. In experiment 2, 44 mice (26.0 ± 1.6 g BW) were identified pregnant and euthanized 24 h after the LPS challenge to assess behavior and late-term pregnancy loss. Growth performance and reproductive responses, such as loss of pregnancy, percentage of fetal death, and etc., were measured in all pregnant mice. The LPS challenge increased (P < 0.05) uterine and placental tumor necrosis factor-α and interferon-γ, late-term pregnancy loss, and lethargy score, and decreased (P < 0.05) uterine transforming growth factor-β1, moving time and number of rearing, and growth and feed intake. The SDP decreased (P < 0.05) concentrations of both pro-inflammatory and anti-inflammatory cytokines in one or both tissues, and the lethargy score, and increased (P < 0.05) moving time and number of rearing, growth of pregnant mice, and fetal weight. However, the SDP did not affect late-term pregnancy loss caused by the LPS challenge. Consequently, dietary SDP attenuated acute inflammation and lethargic behaviors of pregnant mice caused by the LPS challenge, but did not affect late-term pregnancy loss after the acute inflammation