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Sepsis nonhuman primate

Bryce Wolfe, Gregory J Wiepz, Michele Schotzko, Gennadiy I Bondarenko, Maureen Durning, Heather A Simmons, Andres Mejia, Nancy G Faith, Emmanuel Sampene, Marulasiddappa Suresh, Sophia Kathariou, Charles J Czuprynski, Thaddeus G Golos
Infection with Listeria monocytogenes during pregnancy is associated with miscarriage, preterm birth, and neonatal complications, including sepsis and meningitis. While the risk of these conditions is thought to be greatest during the third trimester of pregnancy, the determinants of fetoplacental susceptibility to infection, the contribution of gestational age, and the in vivo progression of disease at the maternal-fetal interface are poorly understood. We developed a nonhuman primate model of listeriosis to better understand antecedents of adverse pregnancy outcomes in early pregnancy...
February 21, 2017: MBio
Erica Boldenow, Claire Gendrin, Lisa Ngo, Craig Bierle, Jay Vornhagen, Michelle Coleman, Sean Merillat, Blair Armistead, Christopher Whidbey, Varchita Alishetti, Veronica Santana-Ufret, Jason Ogle, Michael Gough, Sengkeo Srinouanprachanh, James W MacDonald, Theo K Bammler, Aasthaa Bansal, H Denny Liggitt, Lakshmi Rajagopal, Kristina M Adams Waldorf
Preterm birth is a leading cause of neonatal morbidity and mortality. Although microbial invasion of the amniotic cavity (MIAC) is associated with the majority of early preterm births, the temporal events that occur during MIAC and preterm labor are not known. Group B Streptococci (GBS) are β-hemolytic, gram-positive bacteria, which commonly colonize the vagina but have been recovered from the amniotic fluid in preterm birth cases. To understand temporal events that occur during MIAC, we utilized a unique chronically catheterized nonhuman primate model that closely emulates human pregnancy...
October 2016: Science Immunology
Li Ang Zhang, Robert S Parker, David Swigon, Ipsita Banerjee, Soheyl Bahrami, Heinz Redl, Gilles Clermont
OBJECTIVES: Sepsis therapies have proven to be elusive because of the difficulty of translating biologically sound and effective interventions in animal models to humans. A part of this problem originates from the fact that septic patients present at various times after the onset of sepsis, whereas the exact time of infection is controlled in animal models. We sought to determine whether data mining longitudinal physiologic data in a nonhuman primate model of Escherichia coli-induced sepsis could help inform the time of onset of infection...
June 2016: Critical Care Medicine
Laura E Fredenburgh, Bryan D Kraft, Dean R Hess, R Scott Harris, Monroe A Wolf, Hagir B Suliman, Victor L Roggli, John D Davies, Tilo Winkler, Alex Stenzler, Rebecca M Baron, B Taylor Thompson, Augustine M Choi, Karen E Welty-Wolf, Claude A Piantadosi
Inhaled carbon monoxide (CO) gas has therapeutic potential for patients with acute respiratory distress syndrome if a safe, evidence-based dosing strategy and a ventilator-compatible CO delivery system can be developed. In this study, we used a clinically relevant baboon model of Streptococcus pneumoniae pneumonia to 1) test a novel, ventilator-compatible CO delivery system; 2) establish a safe and effective CO dosing regimen; and 3) investigate the local and systemic effects of CO therapy on inflammation and acute lung injury (ALI)...
October 15, 2015: American Journal of Physiology. Lung Cellular and Molecular Physiology
Shahabuddin Alam, Kei Amemiya, Robert C Bernhards, Robert G Ulrich, David M Waag, Kamal U Saikh
Burkholderia pseudomallei infection causes melioidosis and is often characterized by severe sepsis. Although rare in humans, Burkholderia mallei has caused infections in laboratory workers, and the early innate cellular response to B. mallei in human and nonhuman primates has not been characterized. In this study, we examined the primary cellular immune response to B. mallei in PBMC cultures of non-human primates (NHPs), Chlorocebus aethiops (African Green Monkeys), Macaca fascicularis (Cynomolgus macaque), and Macaca mulatta (Rhesus macaque) and humans...
January 2015: Microbial Pathogenesis
Tolga Sursal, Deborah J Stearns-Kurosawa, Kiyoshi Itagaki, Sun-Young Oh, Shiqin Sun, Shinichiro Kurosawa, Carl J Hauser
Systemic inflammatory response syndrome (SIRS) is a fundamental host response common to bacterial infection and sterile tissue injury. Systemic inflammatory response syndrome can cause organ dysfunction and death, but its mechanisms are incompletely understood. Moreover, SIRS can progress to organ failure or death despite being sterile or after control of the inciting infection. Biomarkers discriminating between sepsis, sterile SIRS, and postinfective SIRS would therefore help direct care. Circulating mitochondrial DNA (mtDNA) is a damage-associated molecular pattern reflecting cellular injury...
January 2013: Shock
Jacqueline J Fremont, Robert P Marini, James G Fox, Arlin B Rogers
Acute respiratory distress syndrome (ARDS) is an important and potentially life-threatening complication in humans that arises subsequent to a variety of primary insults including noxious fume inhalation, infection, and trauma. Here we describe the first two cases of ARDS reported in association with postoperative complications in rhesus macaques. In agreement with the multifactorial nature of the human syndrome, ARDS in one monkey was attributed to sepsis, whereas in the other it was ascribed to neurogenic trauma...
September 2008: Journal of the American Association for Laboratory Animal Science: JAALAS
Luiz F Poli-de-Figueiredo, Alejandra G Garrido, Naomi Nakagawa, Paulina Sannomiya
Sepsis remains a major cause of morbidity and mortality mainly because of sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have failed to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors...
October 2008: Shock
Deborah J Stearns-Kurosawa, Florea Lupu, Fletcher B Taylor, Gary Kinasewitz, Shinichiro Kurosawa
Studies that define natural responses to bacterial sepsis assumed new relevance after the lethal bioterrorist attacks with Bacillus anthracis (anthrax), a spore-forming, toxigenic gram-positive bacillus. Considerable effort has focused on identifying adjunctive therapeutics and vaccines to prevent future deaths, but translation of promising compounds into the clinical setting necessitates an animal model that recapitulates responses observed in humans. Here we describe a nonhuman primate (Papio c. cynocephalus) model of B...
August 2006: American Journal of Pathology
Mansour Mohamadzadeh, Sadie S Coberley, Gene G Olinger, Warren V Kalina, Gordon Ruthel, Claudette L Fuller, Dana L Swenson, William D Pratt, Douglas B Kuhns, Alan L Schmaljohn
Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family Filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. High viral burden is coincident with inadequate adaptive immune responses and robust inflammatory responses, and virus-mediated dysregulation of early host defenses has been proposed. Recently, a novel class of innate receptors called the triggering receptors expressed in myeloid cells (TREM) has been discovered and shown to play an important role in innate inflammatory responses and sepsis...
July 2006: Journal of Virology
Patricia E Losco, Ellen W Evans, Stephen A Barat, Pamela E Blackshear, Larisa Reyderman, Jay S Fine, Loretta A Bober, John C Anthes, Elmer J Mirro, Francis M Cuss
SCH351591, a novel phosphodiesterase-4 inhibitor under investigation as a potential therapeutic for asthma and chronic obstructive pulmonary disease (COPD), was evaluated in a 3-month rising-dose study in Cynomolgus monkeys. Four groups, containing four monkeys/sex, received vehicle control or rising doses up to 12, 24, or 48 mg/kg of SCH351591 daily. Although initial exposure produced clinical signs of emesis, reduced food intake, and reduced body weight, tachyphylaxis to the emesis allowed dose escalation up to 48 mg/kg/day...
May 2004: Toxicologic Pathology
Toshihiro Kaneko, D J Stearns-Kurosawa, Fletcher Taylor, Michaele Twigg, Koichi Osaki, Gary T Kinasewitz, Glenn Peer, Shinichiro Kurosawa
CD10, also known as neutral endopeptidase or CALLA, is a major metalloproteinase that regulates levels of biologically active peptides that initiate inflammatory, cardiovascular, and neurogenic responses. Relative tissue expression levels of CD10, its peptide substrates, and their receptors constitute the basic regulatory mechanism. Neutrophils contain abundant CD10 and are rapid responders to an inflammatory septic challenge. Expression of neutrophil surface antigens in response to inflammation was studied in the primate model of Escherichia coli-mediated sepsis and in human volunteers injected with lipopolysaccharide (LPS)...
August 2003: Shock
Rita E Landman, Jardena J Puder, Ennian Xiao, Pamela U Freda, Michel Ferin, Sharon L Wardlaw
Leptin, which plays a key role in regulating energy homeostasis, may also modulate the inflammatory response. An inflammatory challenge with endotoxin has been shown to stimulate leptin release in the rodent. This finding has not been reproduced in humans or in nonhuman primates, although leptin levels have been reported to increase in septic patients. We have therefore examined the effects of endotoxin injection on plasma leptin levels in nine ovariectomized monkeys and four postmenopausal women. In an initial study in five monkeys, mean leptin levels did not increase during the first 5 h after endotoxin treatment, but did increase significantly from 6...
March 2003: Journal of Clinical Endocrinology and Metabolism
P Ramirez, R Chavez, M Majado, V Munitiz, A Muñoz, Q Hernandez, C G Palenciano, G Pino-Chavez, M Loba, A Minguela, J Yelamos, M R Gago, A S Vizcaino, H Asensi, M G Cayuela, B Segura, F Marin, A Rubio, T Fuente, R Robles, F S Bueno, T Sansano, F Acosta, J M Rodriguez, F Navarro, J Cabezuelo, E Cozzi, D J White, R Y Calne, P Parrilla
BACKGROUND: It is not known whether the pig liver is capable of functioning efficiently when transplanted into a primate, neither is there experience in transplanting a liver from a transgenic pigs expressing the human complement regulator human complement regulator decay accelerating factor (h-DAF) into a baboon. The objective of this study was to determine whether the porcine liver would support the metabolic functions of non-human primates and to establish the effect of hDAF expression in the prevention of hyperacute rejection of porcine livers transplanted into primates...
October 15, 2000: Transplantation
P M Jansen, B Eisele, I W de Jong, A Chang, U Delvos, F B Taylor, C E Hack
We evaluated the effect of C1 inhibitor (C1-inh), an inhibitor of the classical pathway of complement and the contact system, on the physiologic and inflammatory response in baboons suffering from lethal Escherichia coli sepsis. Five animals pretreated with 500 U/kg C1-inh (treatment group; n = 5), followed by a 9-h continuous infusion of 200 U/kg C1-inh subsequent to bacterial challenge, were compared with five controls receiving E. coli alone. Of the treatment group, one animal survived and another lived beyond 48 h, whereas all control animals died within 27 h...
January 1, 1998: Journal of Immunology: Official Journal of the American Association of Immunologists
D H Munn, A G Bree, A C Beall, M D Kaviani, H Sabio, R G Schaub, R K Alpaugh, L M Weiner, S J Goldman
The CD16 receptor (Fc gamma R-III) is found on many tissue macrophages (M phi s), but its expression on circulating monocytes is restricted to a small, phenotypically distinct subset. The number of these CD16+ monocytes may be markedly increased in response to sepsis, human immunodeficiency virus infection, or metastatic malignancy. We have recently shown that the CD16+ monocyte population is selectively expanded by administration of recombinant human macrophage colony-stimulating factor (rhM-CSF). In the current study, we used the highly rhM-CSF-responsive cynomolgus primate model to further characterize this novel monocyte population...
August 15, 1996: Blood
P M Jansen, T C van der Pouw Kraan, I W de Jong, G van Mierlo, J Wijdenes, A A Chang, L A Aarden, F B Taylor, C E Hack
Interleukin (IL)-12 is thought to be a key factor for the induction of interferon gamma (IFN-gamma), a cytokine essential for the lethal effects of endotoxin. We report here on the release of the nonfunctional subunit of IL-12, p40, as well as biologically active heterodimeric IL-12, p70, after administration of a lethal (n = 5) or sublethal (n = 8) dose of live Escherichia coli to baboons. Remarkably, on lethal challenge, peak levels of p40 were observed at 3 hours that were about twofold lower than those elicited after sublethal challenge (2,813 +/- 515 pg/mL v 4,972 +/- 732 pg/mL, P < ...
June 15, 1996: Blood
P M Jansen, R A Pixley, M Brouwer, I W de Jong, A C Chang, C E Hack, F B Taylor, R W Colman
In previous studies, we have shown that administration of monoclonal antibody (MoAb) C6B7 against human factor XII to baboons challenged with a lethal dose of Escherichia coli abrogates activation of the contact system and modulates secondary hypotension. To evaluate the contribution of activated contact proteases to the appearance of other inflammatory mediators in this experimental model of sepsis, we studied the effect of administration of MoAb C6B7 on activation of complement and fibrinolytic cascades, stimulation of neutrophil degranulation, and release of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)...
March 15, 1996: Blood
P M Jansen, M A Boermeester, E Fischer, I W de Jong, T van der Poll, L L Moldawer, C E Hack, S F Lowry
Although studies with interleukin-1 receptor antagonist (IL-1ra) in animal models have shown that IL-1 contributes to mortality in sepsis, the mechanisms whereby IL-1 mediates lethal effects are not well established. A possible mechanism is that IL-1 enhances the activation and release of other inflammatory mediator systems such as coagulation, fibrinolysis, neutrophils, and secretory-type phospholipase A2 (sPLA2). We investigated this possibility by assessing the effect of intravenously injected recombinant human IL-1 alpha (rhIL-1 alpha) on these plasma parameters in baboons...
August 1, 1995: Blood
L Mieles, Y Ye, Y Luo, T Kobayashi, S F Li, M Niekrasz, S Kosanke, D Smith, D K Cooper
Auxiliary liver transplantation has been performed in the baboon using allografts (n = 8) and concordant xenografts from donor African green monkeys (n = 8). The native portal vein was ligated in all cases and the native common bile duct was ligated in 5 cases. The immunosuppressive therapy used was identical in both the allografts and xenografts and consisted of triple drug therapy (cyclosporine, cyclophosphamide, and methylprednisolone), all at dosages consistent with clinical use. During the determination of the surgical technique to be applied, there were 5 early failures (3 allografts, 2 xenografts), and 2 deaths at 10 and 20 days from multiorgan failure and sepsis, respectively (xenografts)...
June 27, 1995: Transplantation
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