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Cecal slurry

Kazumichi Fujioka, Flora Kalish, Hui Zhao, Ronald J Wong, David K Stevenson
BACKGROUND: Sepsis in preterm infants is associated with systemic inflammatory responses. The stress-response protein heme oxygenase-1 (HO-1) has protective anti-inflammatory properties. Recently, we reported a protective role of HO-1 using our non-surgical cecal slurry (CS) model in wild-type (WT) mouse pups. Here, we extend these findings to investigate the association of HO-1 deficiency with sepsis severity. METHODS: Adapting the Wynn model, we induced sepsis in 4-day-old HO-1-deficient (HO-1+/- , Het) pups to determine if HO-1 deficiency affected survival rates at the LD40 (2...
May 23, 2018: Pediatric Research
Alexandra C Bolognese, Weng-Lang Yang, Laura W Hansen, Archna Sharma, Jeffrey M Nicastro, Gene F Coppa, Ping Wang
Sepsis is the third leading cause of death in the neonatal population, due to susceptibility to infection conferred by immaturity of both the innate and adaptive components of the immune system. Invariant natural killer T (iNKT) cells are specialized adaptive immune cells that possess important innate-like characteristics and have not yet been well-studied in septic neonates. We hypothesized that iNKT cells would play an important role in mediating the neonatal immune response to sepsis. To study this, we subjected 5- to 7-day-old neonatal C57BL/6 mice to sepsis by intraperitoneal (i...
2018: Frontiers in Immunology
Alexandra C Bolognese, Weng-Lang Yang, Laura W Hansen, Naomi-Liza Denning, Jeffrey M Nicastro, Gene F Coppa, Ping Wang
BACKGROUND: Neonatal sepsis represents a unique therapeutic challenge owing to an immature immune system. Necroptosis is a form of programmed cell death that has been identified as an important mechanism of inflammation-induced cell death. Receptor-interacting protein kinase 1 plays a key role in mediating this process. We hypothesized that pharmacologic blockade of receptor-interacting protein kinase 1 activity would be protective in neonatal sepsis. METHODS: Sepsis was induced in C57BL/6 mouse pups (5-7 days old) by intraperitoneal injection of adult cecal slurry...
April 27, 2018: Surgery
Laura W Hansen, Asha Jacob, Weng Lang Yang, Alexandra C Bolognese, Jose Prince, Jeffrey M Nicastro, Gene F Coppa, Ping Wang
INTRODUCTION: Sepsis is the third leading cause of morbidity and mortality in neonates. Sepsis in neonates is characterized as the systemic inflammation owing to infection within the first 28days after birth. The molecular mechanism causing the exaggerated inflammation phenotype in neonates has not been completely elucidated. Receptor interacting protein kinase 3 (RIPK3) is a protein identified as a mediator in programmed necrosis or necroptosis. We hypothesize that RIPK3 could be responsible for the inflammatory response in neonates and that deficiency in the RIPK3 protein attenuates inflammation and organ injury in neonatal sepsis...
November 23, 2017: Journal of Pediatric Surgery
Eleanor A Fallon, Tristen T Chun, Whitney A Young, Chyna Gray, Alfred Ayala, Daithi S Heffernan
We have shown that invariant natural killer T ( i NKT) cells mediate sepsis-induced end-organ changes and immune responses, including macrophage bacterial phagocytosis, a finding regulated by the check point protein program cell death receptor-1 (PD-1). Furthermore, PD-1 mediates mortality in both adult and neonatal murine sepsis as well as in surgical patients. Given our previous findings, we hypothesize that i NKT cells will also modulate neonatal sepsis survival, and that this effect is regulated in part through PD-1...
2017: Frontiers in Immunology
Orlando Laitano, David Van Steenbergen, Alex J Mattingly, Christian K Garcia, Gerard P Robinson, Kevin O Murray, Thomas L Clanton, Elizabeth A Nunamaker
Sepsis continues to be a major challenge for modern medicine. Several preclinical models were developed to study sepsis and each has strengths and weaknesses. The cecal slurry (CS) method is a practical alternative because it does not require surgery, and the infection can be dosed. However, one disadvantage is that the dosage must be determined for each CS preparation using survival studies. Our aim was to refine a survival protocol for the CS model by determining a premonitory humane endpoint that would reduce animal suffering...
September 27, 2017: Shock
Phillip T Brooks, Kelsey A Brakel, Julia A Bell, Christopher E Bejcek, Trey Gilpin, Jean M Brudvig, Linda S Mansfield
BACKGROUND: Campylobacter jejuni is the leading antecedent infection to the autoimmune neuropathy Guillain-Barré syndrome (GBS), which is accompanied by an autoimmune anti-ganglioside antibody attack on peripheral nerves. Previously, we showed that contrasting immune responses mediate C. jejuni induced colitis and autoimmunity in interleukin-10 (IL-10)-deficient mice, dependent upon the infecting strain. Strains from colitis patients elicited T helper 1 (TH 1)-dependent inflammatory responses while strains from GBS patients elicited TH 2-dependent autoantibody production...
August 8, 2017: Microbiome
Si Hong Park, Sun Ae Kim, Sang In Lee, Peter M Rubinelli, Stephanie M Roto, Hilary O Pavlidis, Donald R McIntyre, Steven C Ricke
Feed supplements are utilized in the poultry industry as a means for improving growth performance and reducing pathogens. The aim of the present study was to evaluate the effects of Diamond V Original XPC(TM) (XPC, a fermented product generated from yeast cultures) on Salmonella Typhimurium ST 97 along with its potential for modulation of the cecal microbiota by using an anaerobic in vitro mixed culture assay. Cecal slurries obtained from three broiler chickens at each of three sampling ages (14, 28, and 42 days) were generated and exposed to a 24 h pre-incubation period with the various treatments: XPC (1% XPC, ceca, and feeds), CO (ceca only), and NC (negative control) group consisting of ceca and feeds...
2017: Frontiers in Microbiology
James F Colbert, Joshay A Ford, Sarah M Haeger, Yimu Yang, Kyrie L Dailey, Kristen C Allison, Viola Neudecker, Christopher M Evans, Vanessa L Richardson, Kelley S Brodsky, Sarah Faubel, Holger K Eltzschig, Eric P Schmidt, Adit A Ginde
Sepsis outcomes are heavily dependent on the development of septic organ injury, but no interventions exist to interrupt or reverse this process. microRNA-223 (miR-223) is known to be involved in both inflammatory gene regulation and host-pathogen interactions key to the pathogenesis of sepsis. The goal of this study was to determine the role of miR-223 as a mediator of septic kidney injury. Using miR-223 knockout mice and multiple models of experimental sepsis, we found that miR-223 differentially influences acute kidney injury (AKI) based on the model used...
August 1, 2017: American Journal of Physiology. Renal Physiology
Jessica R White, Huiyu Gong, Brock Pope, Patrick Schlievert, Steven J McElroy
Necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality in premature infants. Both human surgical specimens and animal models suggest a potential involvement of Paneth cells in NEC pathogenesis. Paneth cells play critical roles in epithelial homeostasis, innate immunity and host-microbial interactions. Yet, the complex interplay between Paneth cell disruption, epithelial barrier dysfunction and microbial-driven inflammation remains unclear in the immature intestine. In this study, mucosal intestinal injury consistent with human NEC was induced in postnatal day 14-16 (P14-P16) mice by disrupting Paneth cells, followed by gavage with Klebsiella pneumonia...
June 1, 2017: Disease Models & Mechanisms
Laura W Hansen, Weng Lang Yang, Alexandra C Bolognese, Asha Jacob, Tracy Chen, Jose M Prince, Jeffrey M Nicastro, Gene F Coppa, Ping Wang
BACKGROUND: Sepsis remains one of the leading causes of infant death worldwide. It is characterized by uncontrolled inflammatory responses due to proven bacterial infection. Despite improvement in supportive care and the availability of effective antibiotics, no specific therapy targeting the dysregulated inflammatory response is available for neonatal sepsis. Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is a secretory glycoprotein abundantly present in human milk. MFG-E8 suppresses the systemic inflammatory responses in adult murine injury models by improving the clearance of dying cells...
August 2017: Surgery
Whitney A Young, Eleanor A Fallon, Daithi S Heffernan, Philip A Efron, William G Cioffi, Alfred Ayala
BACKGROUND: Sepsis and the ensuing immune dysfunction continue to be major contributors to neonatal morbidity and mortality. Neonatal sepsis also is associated with profound immune dysfunction. We have recently identified a role for a family of coinhibitory molecules that are altered in murine sepsis and in critically ill adult patients, which may be a target for development of novel therapies. There is, however, a paucity of data pertaining to the role of coinhibitory checkpoint proteins in the control and modulation of neonatal sepsis...
May 2017: Surgery
Min Ji Lee, Kyuseok Kim, You Hwan Jo, Jae Hyuk Lee, Ji Eun Hwang
BACKGROUND: The cecal slurry model was introduced as an alternative method for creating an animal sepsis model. This study was performed to evaluate dose-dependent mortality and organ injury in a sepsis model of cecal slurry peritonitis. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into 5.0, 7.5, 10, or 15 mL/kg groups, according to the volume of cecal slurry administered into the peritoneal cavity. In the survival study, rats were observed for 14 d after sepsis induction...
December 2016: Journal of Surgical Research
Allison M Steele, Marlene E Starr, Hiroshi Saito
Current animal models of sepsis often incorporate antibiotics to be consistent with clinical standards for treatment of patients in the intensive care unit. However, such experimental intervention is commonly initiated very early after infectious insult, which likely blunts the progression of systemic inflammation and downstream pathology. The objective of this study was to establish an animal model of sepsis with delayed therapeutic intervention, allowing a longer disease course and downstream pathology, but still resulting in a high survival rate...
June 2017: Shock
Min Ji Lee, Kyuseok Kim, You Hwan Jo, Hoyoung Yune, Jae Hyuk Lee, Ji Eun Hwang
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
Hammad A Ganatra, Brian M Varisco, Kelli Harmon, Patrick Lahni, Amy Opoka, Hector R Wong
Children with severe sepsis are known to have altered zinc homeostasis and decreased circulating zinc levels, suggesting a role for zinc supplementation to improve outcomes. We tested the hypothesis that zinc supplementation would improve survival in a juvenile model of polymicrobial sepsis. Juvenile (13-14-d-old) C57BL/6 mice were treated with 10 mg/kg of zinc via i.p. injections (or vehicle) for 3 d prior to induction of polymicrobial sepsis via i.p. cecal slurry injections. Survival after sepsis was followed for 3 d, and bacterial clearance, ex vivo phagocytosis, systemic inflammatory markers and neutrophil extracellular trap (NET) formation were quantified...
January 2017: Innate Immunity
Sarah J Atkinson, Brian M Varisco, Mary Sandquist, Meghan N Daly, Lindsey Klingbeil, Joshua W Kuethe, Emily F Midura, Kelli Harmon, Amy Opaka, Patrick Lahni, Giovanna Piraino, Paul Hake, Basilia Zingarelli, Joel E Mortenson, James L Wynn, Hector R Wong
Genetic ablation or pharmacologic inhibition of matrix metalloproteinase-8 (MMP8) improves survival in an adult murine sepsis model. Because developmental age influences the host inflammatory response, we hypothesized that developmental age influences the role of MMP8 in sepsis. First, we compared sepsis survival between wild type (WT, C57BL/6) and MMP8 null juvenile-aged mice (12-14 days) after intraperitoneal injection of a standardized cecal slurry. Second, peritoneal lavages collected at 6 and 18 hours after cecal slurry injection were analyzed for bacterial burden, leukocyte subsets, and inflammatory cytokines...
August 8, 2016: Molecular Medicine
Kazumichi Fujioka, Flora Kalish, Hui Zhao, Sabrina Lu, Stephanie Wong, Ronald J Wong, David K Stevenson
Preterm sepsis is characterized by systemic bacterial invasion and inflammatory response. Its pathogenesis is unclear due to lack of proper animal models. Heme oxygenase-1 (HO-1) can affect physiologic and pathologic conditions through its anti-inflammatory, antioxidative, and anti-apoptotic properties. Since HO-1 is developmentally regulated, it may play a role in the pathogenesis of preterm sepsis. For this study, sepsis was induced using the non-surgical "cecal slurry" (CS) model. CS was given intraperitoneally at various doses to 4-day-old newborn mice to determine dose-dependent effects...
February 2017: Shock
Marlene E Starr, Allison M Steele, Donald A Cohen, Hiroshi Saito
OBJECTIVES: Visceral adipose tissue is a major site for expression of proinflammatory and procoagulant genes during acute systemic inflammation. In this study, we tested whether the loss of fat mass by dietary restriction would remove the major source of these factors resulting in improved tolerance to sepsis and endotoxemia. DESIGN: Prospective, laboratory controlled experiments. SETTING: Aging and critical care research laboratory in a university hospital...
July 2016: Critical Care Medicine
Sarah J Atkinson, Meghan Nolan, Lindsey Klingbeil, Kelli Harmon, Patrick Lahni, Basilia Zingarelli, Hector R Wong
OBJECTIVE: Inhibition of matrix metalloproteinase-8 improves survival following cecal ligation and puncture in mice, making it a potential therapeutic target. In the current study, we expand our understanding of the role of matrix metalloproteinase-8 in sepsis by using an adoptive transfer approach and alternative sepsis models. DESIGN: We used three different sepsis models: cecal ligation and puncture, cecal slurry, and intestinal implantation. In our first model, adoptive transfer experiments were followed by cecal ligation and puncture to test the hypothesis that matrix metalloproteinase-8-containing myeloid cells are a critical factor in sepsis following cecal ligation and puncture...
April 2016: Critical Care Medicine
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