Science.gov

Sample records for acutely infected mice

  1. Interleukin-3 protects mice from acute herpes simplex virus infection.

    PubMed Central

    Chan, W L; Ziltener, H J; Liew, F Y

    1990-01-01

    Evidence presented here from kinetic studies of interleukin-3 (IL-3) production by spleen cells from adult mice infected subcutaneously with HSV-1 and stimulated with virus antigen in vitro shows that high levels of IL-3 were produced at the onset of the animal's recovery from the disease state. Injections of anti-IL-3 antibody into HSV-1-infected mice resulted in exacerbation of the disease. Primary mouse embryonic head cells grown in the presence of murine IL-3, when infected with HSV-1, showed a 1000-fold decrease in virus titre compared with untreated control cells. This inhibiting effect was reversed by anti-IL-3 and anti-IFN-alpha, beta and gamma antibodies. These data suggest that IL-3 plays a host-protective role against HSV infection and it does so probably by inducing brain cells to produce interferons which then inhibit virus replication. PMID:2176641

  2. Hippocampal protection in mice with an attenuated inflammatory monocyte response to acute CNS picornavirus infection

    PubMed Central

    Howe, Charles L.; LaFrance-Corey, Reghann G.; Sundsbak, Rhianna S.; Sauer, Brian M.; LaFrance, Stephanie J.; Buenz, Eric J.; Schmalstieg, William F.

    2012-01-01

    Neuronal injury during acute viral infection of the brain is associated with the development of persistent cognitive deficits and seizures in humans. In C57BL/6 mice acutely infected with the Theiler's murine encephalomyelitis virus, hippocampal CA1 neurons are injured by a rapid innate immune response, resulting in profound memory deficits. In contrast, infected SJL and B6xSJL F1 hybrid mice exhibit essentially complete hippocampal and memory preservation. Analysis of brain-infiltrating leukocytes revealed that SJL mice mount a sharply attenuated inflammatory monocyte response as compared to B6 mice. Bone marrow transplantation experiments isolated the attenuation to the SJL immune system. Adoptive transfer of B6 inflammatory monocytes into acutely infected B6xSJL hosts converted these mice to a hippocampal damage phenotype and induced a cognitive deficit marked by failure to recognize a novel object. These findings show that inflammatory monocytes are the critical cellular mediator of hippocampal injury during acute picornavirus infection of the brain. PMID:22848791

  3. Enhanced resistance to acute infection with Trypanosoma cruzi in mice treated with an interferon inducer.

    PubMed Central

    James, S L; Kipnis, T L; Sher, A; Hoff, R

    1982-01-01

    For an exploration of the effects of interferon-inducible resistance mechanisms in acute American trypanosomiasis, the synthetic interferon inducer tilerone hydrochloride was administered to mice of the C57BL/6J strain, which is highly resistant to Trypanosoma cruzi, 18 to 24 h before infection with a potentially lethal dose of bloodstream trypomastigotes. Although all of the control mice died within 30 days of the acute infection, approximately 50% of the tilerone-treated animals were able to survive indefinitely (P less than 0.05). The tilerone-treated mice demonstrated significant levels of serum interferon and splenic natural killer cells at the time of infection. Macrophages isolated from the peritoneal cavities of tilerone-treated C57BL/6J mice appeared to kill significant numbers of trypanosomes during 2 to 3 days of in vitro culture, indicating that activated macrophages may contribute to the enhanced resistance to T. cruzi infection in these mice. Beige mice treated with tilerone did not survive T. cruzi infection as well as tilerone-treated heterozygotes did, suggesting a role for natural killer cells in interferon-induced resistance. These results suggest that interferon or effector mechanisms enhanced by interferon induction can play a significant role in influencing resistance to T. cruzi infection. PMID:6173326

  4. [Detection of Trypanosoma cruzi DNA in the placenta and fetuses of mice with Chagasic acute infection].

    PubMed

    Alarcón, Maritza; Pérez, Mary Carmen; Villarreal, Juana; Araujo, Sonia; Goncalves, Loredana; González, Anajulia; Moreno, Elio; Lugo-Yarbuh, Ana

    2009-09-01

    The objective of the present study was to detect the presence of Trypanosoma cruzi DNA in the placenta and fetal tissues of NMRI mice (Mus musculus) inoculated with 22 x 10(3) trypomastigotes metacyclic of the M/HOM/BRA/53/Y strain by intraperitoneal route. Mice were pregnant in the acute phase of the infection. The course of patent parasitemia by T. cruzi was evaluated before mating and during pregnancy. At day twenty of gestation, animals were sacrificed and the fetuses and their placentas were removed to evaluate T. cruzi infection. Samples of fetal placenta, heart and skeletal muscle were fixed in 10%, formalin, included in paraffin and stained with hematoxilin and eosin (HE). The histopathological study of sections of fetal tissues revealed inflammatory infiltrates with mononuclear and polymorphonuclear cells and without parasitism in these tissues. The amplification of T. cruzi DNA by Polymerase Chain Reaction (PCR) showed a positive reaction in 18% of placental tissue of pregnant infected mice. The samples of heart and skeletal muscle of the fetuses of mothers infected with T. cruzi did not show the presence T. cruzi DNA. The placenta and skeletal muscle of the fetuses analyzed by Peroxidase anti Peroxidase inmunostaining showed T. cruzi antigens in those tissues. Negative results by PCR in fetal tissues might be related with the virulence and tropism associated with the biological and genetic characteristic Of the T. cruzi strain used in the experimental infection of female mice. PMID:19961056

  5. Influence of Parasite Load on Renal Function in Mice Acutely Infected with Trypanosoma cruzi

    PubMed Central

    Parreira, Ricardo Cambraia; Miguel, Renata Botelho; de Paula Rogerio, Alexandre; Oliveira, Carlo Jose Freire; Chica, Javier Emilio Lazo

    2013-01-01

    Background Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. Despite the vast number of studies evaluating the pathophysiological mechanisms of the disease, the influence of parasite burden on kidney lesions remains unclear. Thus, the main goal of this work was to evaluate the effect of T. cruzi infection on renal function and determine whether there was a correlation between parasite load and renal injury using an acute experimental model of the disease. Methodology/Principal Findings Low, medium and high parasite loads were generated by infecting C57BL/6 mice with 300 (low), 3,000 (medium) or 30,000 (high) numbers of “Y” strain trypomastigotes. We found that mice infected with T. cruzi trypomastigotes show increased renal injury. The infection resulted in reduced urinary excretion and creatinine clearance. We also observed a marked elevation in the ratio of urine volume to kidney and body weight, blood urea nitrogen, chloride ion, nitric oxide, pro- and anti-inflammatory cytokines and the number of leukocytes in the blood and/or renal tissues of infected mice. Additionally, we observed the presence of the parasite in the cortical/medullary and peri-renal region, an increase of inflammatory infiltrate and of vascular permeability of the kidney. Overall, most renal changes occurred mainly in animals infected with high parasitic loads. Conclusions/Significance These data demonstrate that T. cruzi impairs kidney function, and this impairment is more evident in mice infected with high parasitic loads. Moreover, these data suggest that, in addition to the extensively studied cardiovascular effects, renal injury should be regarded as an important indicator for better understanding the pan-infectivity of the parasite and consequently for understanding the disease in experimental models. PMID:23951243

  6. Use of Noninvasive Parameters to Evaluate Swiss Webster Mice During Trypanosoma cruzi Experimental Acute Infection.

    PubMed

    Campos, Jerônimo D S; Hoppe, Luanda Y; Duque, Thabata L A; de Castro, Solange Lisboa; Oliveira, Gabriel M

    2016-04-01

    Until now, there has been neither an agreed-upon experimental model nor descriptors of the clinical symptoms that occur over the course of acute murine infection. The aim of this work is to use noninvasive methods to evaluate clinical signs in Swiss Webster mice that were experimentally infected with the Y strain of Trypanosoma cruzi during acute phase (Inf group). Infected mice showed evident clinical changes beginning in the second week of infection (wpi) when compared to the noninfected group (NI): (1) animals in hunched postures, closed eyes, lowered ears, peeling skin, increased piloerection, prostration, and social isolation; (2) significant decrease in body weight (Inf: 26.2 ± 2.6 g vs. NI: 34.2 ± 2.5 g) and in chow (1.5 ± 0.3 vs. 6.3 ± 0.5 mg) and water (2.4 ± 0.5 vs. 5.8 ± 0.7 ml) intake; (3) significant decrease of spontaneous activity as locomotor parameters: distance (0.64 ± 0.06 vs. 1.8 ± 0.13 m), velocity (1.9 ± 0.3 vs. 6.7 ± 1.5 cm/sec), and exploratory behavior by frequency (1.0 ± 0.5 vs. 5.7 ± 1.0 events) and duration (1.4 ± 0.3 vs. 5.1 ± 0.5 sec in central arena region); (4) significant increase in the PR (41.7 ± 8.7 vs. 27.6 ± 1.9 msec) and QT intervals (39.7 ± 2.0 vs. 27.5 ± 4.0 msec), and a decreased cardiac frequency (505 ± 52.8 vs. 774 ± 17.8 msec), showing a marked sinus bradycardia and an atrioventricular block. At 3 and 4 wpi, the surviving animals showed a tendency of recovery in body weight, food intake, locomotor activity, and exploratory interest. Through the use of noninvasive parameters, we were able to monitor the severity of the infection in individuals prior to death. Our perspective is the application of noninvasive methods to describe clinical signs over the course of acute infection complementing the preclinical evaluation of new agents, alone or in combination with benznidazole. PMID:26741817

  7. Role of acute-phase proteins in interleukin-1-induced nonspecific resistance to bacterial infections in mice.

    PubMed Central

    Vogels, M T; Cantoni, L; Carelli, M; Sironi, M; Ghezzi, P; van der Meer, J W

    1993-01-01

    Treatment with a single low dose (80 to 800 ng) of interleukin-1 (IL-1) 24 h before a lethal bacterial challenge of granulocytopenic and normal mice enhances nonspecific resistance. Since IL-1 induces secretion of acute-phase proteins, liver proteins which possess several detoxifying effects, we investigated the role of these proteins in the IL-1-induced protection. Inhibition of liver protein synthesis with D-galactosamine (GALN) completely inhibited the IL-1-induced synthesis of acute-phase proteins. GALN pretreatment abolished the protective effect of IL-1 on survival completely (neutropenic mice infected with Pseudomonas aeruginosa) or partially (nonneutropenic mice infected with Klebsiella pneumoniae). Pretreatment with IL-6, a cytokine induced by IL-1, did not reproduce the protection offered after IL-1 pretreatment, nor did it enhance or deteriorate the IL-1-enhanced resistance to infection. A protective effect of IL-1 via effects on glucose homeostasis during the acute-phase response was investigated by comparing plasma glucose levels in IL-1-treated mice and control mice before and during infection. Although glucose levels in IL-1-pretreated mice were somewhat higher in the later stages of infection, no significant differences from levels in control mice were present, and the glucose levels in control-treated animals never fell to hypoglycemic values. We conclude that the IL-1-induced nonspecific resistance is mediated neither by the induction of IL-6 nor by the effects of IL-1 on glucose homeostasis. Acute-phase proteins generated after IL-1 pretreatment, however, seem to play a critical role in the IL-1-induced protection to infection. PMID:7509141

  8. Lethal Infection of K18-hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus▿

    PubMed Central

    McCray, Paul B.; Pewe, Lecia; Wohlford-Lenane, Christine; Hickey, Melissa; Manzel, Lori; Shi, Lei; Netland, Jason; Jia, Hong Peng; Halabi, Carmen; Sigmund, Curt D.; Meyerholz, David K.; Kirby, Patricia; Look, Dwight C.; Perlman, Stanley

    2007-01-01

    The severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV), resulted in substantial morbidity, mortality, and economic losses during the 2003 epidemic. While SARS-CoV infection has not recurred to a significant extent since 2003, it still remains a potential threat. Understanding of SARS and development of therapeutic approaches have been hampered by the absence of an animal model that mimics the human disease and is reproducible. Here we show that transgenic mice that express the SARS-CoV receptor (human angiotensin-converting enzyme 2 [hACE2]) in airway and other epithelia develop a rapidly lethal infection after intranasal inoculation with a human strain of the virus. Infection begins in airway epithelia, with subsequent alveolar involvement and extrapulmonary virus spread to the brain. Infection results in macrophage and lymphocyte infiltration in the lungs and upregulation of proinflammatory cytokines and chemokines in both the lung and the brain. This model of lethal infection with SARS-CoV should be useful for studies of pathogenesis and for the development of antiviral therapies. PMID:17079315

  9. Early Life Arsenic Exposure and Acute and Long-term Responses to Influenza A Infection in Mice

    PubMed Central

    Foong, Rachel E.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.

    2013-01-01

    Background: Arsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood. Objective: We aimed to determine if early life exposure to arsenic exacerbates the response to early life influenza infection in mice. Methods: C57BL/6 mice were exposed to arsenic in utero and throughout postnatal life. At 1 week of age, a subgroup of mice were infected with influenza A. We then assessed the acute and long-term effects of arsenic exposure on viral clearance, inflammation, lung structure, and lung function. Results: Early life arsenic exposure reduced the clearance of and exacerbated the inflammatory response to influenza A, and resulted in acute and long-term changes in lung mechanics and airway structure. Conclusions: Increased susceptibility to respiratory infections combined with exaggerated inflammatory responses throughout early life may contribute to the development of bronchiectasis in arsenic-exposed populations. Citation: Ramsey KA, Foong RE, Sly PD, Larcombe AN, Zosky GR. 2013. Early life arsenic exposure and acute and long-term responses to influenza A infection in mice. Environ Health Perspect 121:1187–1193; http://dx.doi.org/10.1289/ehp.1306748 PMID:23968752

  10. Inhibition of catecholamine degradation ameliorates while chemical sympathectomy aggravates the severity of acute Friend retrovirus infection in mice.

    PubMed

    Bloemker, Dominique; Mollerus, Sina; Gibbert, Kathrin; Dittmer, Ulf; del Rey, Adriana; Schedlowski, Manfred; Engler, Harald

    2016-05-01

    Several lines of evidence indicate that the sympathetic nervous system (SNS) might be involved in the pathogenesis and progression of retroviral infections. However, experimental data are scarce and findings inconsistent. Here, we investigated the role of the SNS during acute infection with Friend virus (FV), a pathogenic murine retrovirus that causes polyclonal proliferation of erythroid precursor cells and splenomegaly in adult mice. Experimental animals were infected with FV complex, and viral load, spleen weight, and splenic noradrenaline (NA) concentration was analyzed until 25 days post infection. Results show that FV infection caused a massive but transient depletion in splenic NA during the acute phase of the disease. At the peak of the virus-induced splenomegaly, splenic NA concentration was reduced by about 90% compared to naïve uninfected mice. Concurrently, expression of the catecholamine degrading enzymes monoamine oxidase A (MAO-A) and catechol-O-methyltransferase (COMT) was significantly upregulated in immune cells of the spleen. Pharmacological inhibition of MAO-A and COMT by the selective inhibitors clorgyline and 3,5-dinitrocatechol, respectively, efficiently blocked NA degradation and significantly reduced viral load and virus-induced splenomegaly. In contrast, chemical sympathectomy prior to FV inoculation aggravated the acute infection and extended the duration of the disease. Together these findings demonstrate that catecholamine availability at the site of viral replication is an important factor affecting the course of retroviral infections. PMID:26880342

  11. Depletion of Phagocytic Cells during Nonlethal Plasmodium yoelii Infection Causes Severe Malaria Characterized by Acute Renal Failure in Mice.

    PubMed

    Terkawi, Mohamad Alaa; Nishimura, Maki; Furuoka, Hidefumi; Nishikawa, Yoshifumi

    2016-03-01

    In the current study, we examined the effects of depletion of phagocytes on the progression of Plasmodium yoelii 17XNL infection in mice. Strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. Moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. The severity of infection was coincident with the increased sequestration of parasitized erythrocytes, the systematic upregulation of inflammation and coagulation, and the disruption of endothelial integrity in the liver and kidney. Aspirin was administered to the mice to minimize the risk of excessive activation of the coagulation response and fibrin deposition in the renal tissue. Interestingly, treatment with aspirin reduced the parasite burden and pathological lesions in the renal tissue and improved survival of phagocyte-depleted mice. Our data imply that the depletion of phagocytic cells, including macrophages, in the acute phase of infection increases the severity of malarial infection, typified by multiorgan failure and high mortality. PMID:26755155

  12. Mechanisms of vascular dysfunction in acute phase of Trypanosoma cruzi infection in mice.

    PubMed

    Silva, Josiane F; Capettini, Luciano S A; da Silva, José F P; Sales-Junior, Policarpo; Cruz, Jader Santos; Cortes, Steyner F; Lemos, Virginia S

    2016-07-01

    Vascular disorders have a direct link to mortality in the acute phase of Trypanosoma cruzi infection. However, the underlying mechanisms of vascular dysfunction in this phase are largely unknown. We hypothesize that T. cruzi invades endothelial cells causing dysfunction in contractility and relaxation of the mouse aorta. Immunodetection of T. cruzi antigen TcRBP28 was observed in endothelial cells. There was a decreased endothelial nitric oxide synthase (eNOS)-derived NO-dependent vascular relaxation, and increased vascular contractility accompanied by augmented superoxide anions production. Endothelial removal, inhibition of cyclooxygenase 2 (COX-2), blockade of thromboxane A2 (TXA2) TP receptors, and scavenger of superoxide normalized the contractile response. COX-2, thromboxane synthase, inducible nitric oxide synthase (iNOS), p65 NFκB subunit and p22(phox) of NAD(P)H oxidase (NOX) subunit expressions were increased in vessels of chagasic animals. Serum TNF-α was augmented. Basal NO production, and nitrotyrosine residue expression were increased. It is concluded that T. cruzi invades mice aorta endothelial cells and increases TXA2/TP receptor/NOX-derived superoxide formation. Alongside, T. cruzi promotes systemic TNF-α increase, which stimulates iNOS expression in vessels and nitrosative stress. In light of the heart failure that develops in the chronic phase of the disease, to understand the mechanism involved in the increased contractility of the aorta is crucial. PMID:26988253

  13. Trypanosoma cruzi Entrance through Systemic or Mucosal Infection Sites Differentially Modulates Regional Immune Response Following Acute Infection in Mice

    PubMed Central

    de Meis, Juliana; Barreto de Albuquerque, Juliana; Silva dos Santos, Danielle; Farias-de-Oliveira, Désio Aurélio; Berbert, Luiz Ricardo; Cotta-de-Almeida, Vinícius; Savino, Wilson

    2013-01-01

    Acute Chagas disease is characterized by a systemic infection that leads to the strong activation of the adaptive immune response. Outbreaks of oral contamination by the infective protozoan Trypanosoma cruzi are frequent in Brazil and other Latin American countries, and an increased severity of clinical manifestations and mortality is observed in infected patients. These findings have elicited questions about the specific responses triggered after T. cruzi entry via mucosal sites, possibly modulating local immune mechanisms, and further impacting regional and systemic immunity. Here, we provide evidence for the existence of differential lymphoid organ responses in experimental models of acute T. cruzi infection. PMID:23898334

  14. Ear infection - acute

    MedlinePlus

    Otitis media - acute; Infection - inner ear; Middle ear infection - acute ... Casselbrandt ML, Mandel EM. Acute otitis media and otitis media with effusion. In: Flint PW, Haughey BH, Lund V, et al, eds. Cummings Otolaryngology: Head & Neck Surgery . 6th ed. ...

  15. In the Absence of Endogenous Gamma Interferon, Mice Acutely Infected with Neospora caninum Succumb to a Lethal Immune Response Characterized by Inactivation of Peritoneal Macrophages

    PubMed Central

    Nishikawa, Yoshifumi; Tragoolpua, Khajornsak; Inoue, Noboru; Makala, Levi; Nagasawa, Hideyuki; Otsuka, Haruki; Mikami, Takeshi

    2001-01-01

    Following infection with Neospora caninum, BALB/c mice were shown to be resistant to an acute infection but developed a latent chronic infection. However, BALB/c background gamma interferon (IFN-γ)-deficient mice were sensitive to the acute infection. Since the immune response in IFN-γ-deficient mice is scantly known, we examined the function of macrophages, major histocompatibility complex (MHC) class II expression, T-cell responses, and serum cytokine levels in the mice. All IFN-γ-deficient mice died within 9 days of infection with N. caninum, whereas those treated with exogenous IFN-γ lived longer. Although N. caninum invaded various organs in both types of mice at the early stage of infection, the parasite was not detected in the brains of resistant hosts until 21 days postinfection (dpi). Peritoneal macrophages from IFN-γ-deficient mice were activated by exogenous IFN-γ associated with inhibition of parasite growth and nitric oxide production as were those from BALB/c mice. IFN-γ-deficient mice failed to increase MHC class II expression on macrophages. Moreover, BALB/c mice induced T-cell proliferation while IFN-γ-deficient mice did not. However, in vivo treatment with exogenous IFN-γ induced up-regulated MHC class II expression in IFN-γ-deficient mice. BALB/c mice treated with an antibody to CD4 showed an increase in morbidity and mortality after parasite infection. In serum, significant levels of IFN-γ and interleukin-4 (IL-4) were detected in resistant hosts, whereas IL-10 was detected in IFN-γ-deficient mice. The levels of IL-12 in IFN-γ-deficient mice were higher than those in BALB/c mice at 7 dpi. The present study indicates that early IFN-γ production has a crucial role in the activation of peritoneal macrophages for the induction of protective immune responses against N. caninum. PMID:11427432

  16. Herpes Simplex Virus 1 Infection of Tree Shrews Differs from That of Mice in the Severity of Acute Infection and Viral Transcription in the Peripheral Nervous System

    PubMed Central

    Li, Lihong; Li, Zhuoran; Wang, Erlin; Yang, Rui; Xiao, Yu; Han, Hongbo; Lang, Fengchao; Li, Xin; Xia, Yujie; Gao, Feng; Li, Qihan; Fraser, Nigel W.

    2015-01-01

    ABSTRACT Studies of herpes simplex virus (HSV) infections of humans are limited by the use of rodent models such as mice, rabbits, and guinea pigs. Tree shrews (Tupaia belangeri chinensis) are small mammals indigenous to southwest Asia. At behavioral, anatomical, genomic, and evolutionary levels, tree shrews are much closer to primates than rodents are, and tree shrews are susceptible to HSV infection. Thus, we have studied herpes simplex virus 1 (HSV-1) infection in the tree shrew trigeminal ganglion (TG) following ocular inoculation. In situ hybridization, PCR, and quantitative reverse transcription-PCR (qRT-PCR) analyses confirm that HSV-1 latently infects neurons of the TG. When explant cocultivation of trigeminal ganglia was performed, the virus was recovered after 5 days of cocultivation with high efficiency. Swabbing the corneas of latently infected tree shrews revealed that tree shrews shed virus spontaneously at low frequencies. However, tree shrews differ significantly from mice in the expression of key HSV-1 genes, including ICP0, ICP4, and latency-associated transcript (LAT). In acutely infected tree shrew TGs, no level of ICP4 was observed, suggesting the absence of infection or a very weak, acute infection compared to that of the mouse. Immunofluorescence staining with ICP4 monoclonal antibody, and immunohistochemistry detection by HSV-1 polyclonal antibodies, showed a lack of viral proteins in tree shrew TGs during both acute and latent phases of infection. Cultivation of supernatant from homogenized, acutely infected TGs with RS1 cells also exhibited an absence of infectious HSV-1 from tree shrew TGs. We conclude that the tree shrew has an undetectable, or a much weaker, acute infection in the TGs. Interestingly, compared to mice, tree shrew TGs express high levels of ICP0 transcript in addition to LAT during latency. However, the ICP0 transcript remained nuclear, and no ICP0 protein could be seen during the course of mouse and tree shrew TG

  17. Removal of regulatory T cells prevents secondary chronic infection but increases the mortality of subsequent sub-acute infection in sepsis mice

    PubMed Central

    Wang, Xiaoya; Zhao, Yong; Wang, Yi; Zhao, Xiaomin; Chang, Lingling; Liu, Shan-lu; Tong, Dewen; Zhang, Hai; Huang, Yong

    2016-01-01

    The immunosuppression following initial septic insult impairs resistance to secondary infection. Modulation of lymphocytes population may help to develop an effective therapeutic strategy. In this study, lipopolysaccharide (LPS)-induced endotoxemia was employed as the initial septic insult. 24 hours later, mice underwent cecal ligation and puncture to induce chronic or sub-acute peritonitis. Potential usefulness of T regs deletion antibody (anti-CD25) in improving LPS-induced immunosuppression and the survival of subsequent different infections were evaluated. LPS injection induced lymphocyte loss and led to decreased IL-6, TNF-α and IFN-γ, and weakened bacteria clearance upon chronic peritonitis at 24 h post-LPS, whereas reconstitution with lymphocytes reversed these changes. LPS-induced T regs expansion contributed to T and NK cells decrease in number and activity during sepsis. Depletion of T regs using anti-CD25 antibodies partly prevented lymphocyte loss and increased the responses of T and NK cells to subsequent stimulation, resulting in significantly increased bacterial clearance and survival in a 2-hit model of chronic peritonitis, but which significantly increased early mortality upon subsequently sub-acute infection. Yet, using lower dosage of anti-CD25 antibodies to moderate down-regulate T regs levels could partly improve bacterial clearance and survival in either chronic or sub-acute infection. These results demonstrate that using anti-CD25 antibodies to deplete T regs can ameliorate immunosuppression through increasing T cells and NK cells responses in sepsis, which is beneficial for preventing subsequently chronic infection, but will probably bring some deleterious effects for subsequent sub-acute infection. PMID:26918357

  18. Identification and Sequencing of a Novel Rodent Gammaherpesvirus That Establishes Acute and Latent Infection in Laboratory Mice

    PubMed Central

    Loh, Joy; Zhao, Guoyan; Nelson, Christopher A.; Coder, Penny; Droit, Lindsay; Handley, Scott A.; Johnson, L. Steven; Vachharajani, Punit; Guzman, Hilda; Tesh, Robert B.; Wang, David; Fremont, Daved H.; Virgin, Herbert W.

    2011-01-01

    Gammaherpesviruses encode numerous immunomodulatory molecules that contribute to their ability to evade the host immune response and establish persistent, lifelong infections. As the human gammaherpesviruses are strictly species specific, small animal models of gammaherpesvirus infection, such as murine gammaherpesvirus 68 (γHV68) infection, are important for studying the roles of gammaherpesvirus immune evasion genes in in vivo infection and pathogenesis. We report here the genome sequence and characterization of a novel rodent gammaherpesvirus, designated rodent herpesvirus Peru (RHVP), that shares conserved genes and genome organization with γHV68 and the primate gammaherpesviruses but is phylogenetically distinct from γHV68. RHVP establishes acute and latent infection in laboratory mice. Additionally, RHVP contains multiple open reading frames (ORFs) not present in γHV68 that have sequence similarity to primate gammaherpesvirus immunomodulatory genes or cellular genes. These include ORFs with similarity to major histocompatibility complex class I (MHC-I), C-type lectins, and the mouse mammary tumor virus and herpesvirus saimiri superantigens. As these ORFs may function as immunomodulatory or virulence factors, RHVP presents new opportunities for the study of mechanisms of immune evasion by gammaherpesviruses. PMID:21209105

  19. An Fc gamma RII-, Fc gamma RIII-specific monoclonal antibody (2.4G2) decreases acute Trypanosoma cruzi infection in mice.

    PubMed Central

    Araujo-Jorge, T; Rivera, M T; el Bouhdidi, A; Daëron, M; Carlier, Y

    1993-01-01

    In order to study the role of Fc gamma Rs in Trypanosoma cruzi infection in mice, the 2.4G2 monoclonal antibody (MAb), specific to the extracellular domains of Fc gamma RII and Fc gamma RIII, was injected intraperitoneally into mice. Flow cytometry studies of uninfected mice showed that 2.4G2 MAb bound to peritoneal and lymph node cells, respectively, on days 2 and 6 after injection. Repeating 2.4G2 injections every 3 to 4 days decreased the availability of Fc gamma Rs on peritoneal, lymph node, and spleen cells. Injections of 2.4G2 MAb into T. cruzi-infected mice, at days -1, 3, 7, 11, 16, 20, and 24 relative to infection, reduced mortality in comparison with that in infected animals injected with an unrelated MAb (50 versus 93.3% mortality; P < 0.01). Parasitemia in 2.4G2-treated mice was significantly (three times) lower than in control animals on days 21 and 24 postinfection (P < 0.05), before parasite-specific antibodies were detectable at significant levels. Immunoglobulin and T. cruzi-specific antibody levels were similar in all groups of mice. These results indicate that repeated injections of 2.4G2 MAb administered to acutely infected mice reduce the in vivo infection level, suggesting that Fc gamma Rs play a role in the early host invasion by T. cruzi parasites. Images PMID:8406898

  20. Inhibition of Acute in vivo Human Immunodeficiency Virus Infection by Human Interleukin 10 Treatment of SCID Mice Implanted with Human Fetal Thymus and Liver

    NASA Astrophysics Data System (ADS)

    Kollmann, Tobias R.; Pettoello-Mantovani, Massimo; Katopodis, Nikos F.; Hachamovitch, Moshe; Rubinstein, Arye; Kim, Ana; Goldstein, Harris

    1996-04-01

    To improve the usefulness of in vivo models for the investigation of the pathophysiology of human immunodeficiency virus (HIV) infection, we modified the construction of SCID mice implanted with human fetal thymus and liver (thy/liv-SCID-hu mice) so that the peripheral blood of the mice contained significant numbers of human monocytes and T cells. After inoculation with HIV-159, a primary patient isolate capable of infecting monocytes and T cells, the modified thy/liv-SCID-hu mice developed disseminated HIV infection that was associated with plasma viremia. The development of plasma viremia and HIV infection in thy/liv-SCID-hu mice inoculated with HIV-159 was inhibited by acute treatment with human interleukin (IL) 10 but not with human IL-12. The human peripheral blood mononuclear cells in these modified thy/liv-SCID-hu mice were responsive in vivo to treatment with exogenous cytokines. Human interferon γ expression in the circulating human peripheral blood mononuclear cells was induced by treatment with IL-12 and inhibited by treatment with IL-10. Thus, these modified thy/liv-SCID-hu mice should prove to be a valuable in vivo model for examining the role of immunomodulatory therapy in modifying HIV infection. Furthermore, our demonstration of the in vivo inhibitory effect of IL-10 on acute HIV infection suggests that further studies may be warranted to evaluate whether there is a role for IL-10 therapy in preventing HIV infection in individuals soon after exposure to HIV such as for children born to HIV-infected mothers.

  1. Comparison of the early host immune response to two widely diverse virulent strains of Burkholderia pseudomallei that cause acute or chronic infections in BALB/c mice.

    PubMed

    Amemiya, Kei; Dankmeyer, Jennifer L; Fetterer, David P; Worsham, Patricia L; Welkos, Susan L; Cote, Christopher K

    2015-09-01

    Burkholderia pseudomallei is the etiologic agent of melioidosis, which is endemic in Southeast Asia and Northern Australia. We previously found by the intraperitoneal (IP) route that we could discern differences in virulence in mice amongst different strains of B. pseudomallei. We report an early immune response study comparing two strains in our collection which represent the least, B. pseudomallei 1106a, and one of the most, HBPUB10134a, virulent strains in BALB/c mice. B. pseudomallei HBPUB10134a infected mouse spleens contained a 2-3 log higher bacterial burden than mice infected with B. pseudomallei 1106a 3 days post-infection (PI). More and higher amounts of inflammatory cytokines/chemokines were detected in sera and spleen extracts from B. pseudomallei HBPUB10134a than B. pseudomallei 1106a infected mice. The most prominent were IFNγ, IL-1α, IL-1β, IL-6, IL-10, IP-10, and MIG. After 7 days PI, there was a decrease in bacterial burden in spleens from 1106a infected mice and a decrease in cytokines/chemokines in sera and spleen extracts from both sets of mice. By day 14 PI we saw an increase in monocytes/macrophages, NK cells, and granulocytes in spleens from both sets of mice. No B. pseudomallei HBPUB10134a infected mice survived after this time. In summary, B. pseudomallei HBPUB10134a was more virulent and induced host innate immune responses typical of a more acute-type infection than did B. pseudomallei 1106a which produced a more chronic infection in mice. PMID:26162294

  2. Effect of elevated environmental temperature on the antibody response of mice to Trypanosoma cruzi during the acute phase of infection.

    PubMed Central

    Dimock, K A; Davis, C D; Kuhn, R E

    1991-01-01

    When held at 36 degrees C, Trypanosoma cruzi-infected C3H mice survive an otherwise lethal infection with significantly decreased parasitemia levels and enhanced immune responsiveness. Treatment of T. cruzi-infected mice with the immunosuppressive agent cyclophosphamide indicated that the positive effects of increased environmental temperature were primarily due to enhancement of immunity. A parasite-specific, enzyme-linked immunosorbent assay and immunoblot analysis were used to examine the effect of elevated environmental temperature on the production of anti-T. cruzi antibodies. Both the reactivity and diversity of anti-T. cruzi antibodies were found to be lower in infected mice held at 36 degrees C than in infected mice held at room temperature. However, reactivity and diversity could be enhanced by vaccination with culture forms of the parasite. Images PMID:1937796

  3. Protective efficacy of pVAX-RON5p against acute and chronic infections of Toxoplasma gondii in BALB/c mice.

    PubMed

    Zhao, Yu; Li, Zhong-Yuan; Chen, Jia; Sun, Xiao-Lin; Liu, Shan-Shan; Zhu, Xing-Quan; Zhou, Dong-Hui

    2016-04-01

    Toxoplasma gondii can infect all the warm-blooded animals and humans and causes serious diseases especially in immuno-compromised patients and pregnant women. Rhoptry neck proteins (RONs) play an important role in the formation of moving junction, which mediates the invasion of this parasite. A recombinant plasmid pVAX-RON5p, which can express part of RON5 protein in the eukaryocyte, was generated and used to immune BALB/c mice for evaluating the protective efficacy against the acute and chronic infections of T. gondii. Both humoral and cellular immune responses were evoked in mice by pVAX-RON5p immunization, and a slightly prolonged survival period was detected in the immunized group (7.6 ± 3.31 days) compared to the blank control (4.9 ± 0.32 days) after acute T. gondii infection (P < 0.05). For chronic infection of T. gondii, the number of cysts in the brain of pVAX-RON5p-immunized mice decreased 25.8% compared to blank control (P < 0.05). Our data suggested that RON5p DNA vaccine can induce partial protective immunity against acute and chronic T. gondii infections. PMID:26821295

  4. Differential Expression of microRNAs in Thymic Epithelial Cells from Trypanosoma cruzi Acutely Infected Mice: Putative Role in Thymic Atrophy

    PubMed Central

    Linhares-Lacerda, Leandra; Palu, Cintia Cristina; Ribeiro-Alves, Marcelo; Paredes, Bruno Diaz; Morrot, Alexandre; Garcia-Silva, Maria Rosa; Cayota, Alfonso; Savino, Wilson

    2015-01-01

    A common feature seen in acute infections is a severe atrophy of the thymus. This occurs in the murine model of acute Chagas disease. Moreover, in thymuses from Trypanosoma cruzi acutely infected mice, thymocytes exhibit an increase in the density of fibronectin and laminin integrin-type receptors, with an increase in migratory response ex vivo. Thymic epithelial cells (TEC) play a major role in the intrathymic T cell differentiation. To date, the consequences of molecular changes promoted by parasite infection upon thymus have not been elucidated. Considering the importance of microRNA for gene expression regulation, 85 microRNAs (mRNAs) were analyzed in TEC from T. cruzi acutely infected mice. The infection significantly modulated 29 miRNAs and modulation of 9 was also dependent whether TEC sorted out from the thymus exhibited cortical or medullary phenotype. In silico analysis revealed that these miRNAs may control target mRNAs known to be responsible for chemotaxis, cell adhesion, and cell death. Considering that we sorted TEC in the initial phase of thymocyte loss, it is conceivable that changes in TEC miRNA expression profile are functionally related to thymic atrophy, providing new clues to better understanding the mechanisms of the thymic involution seen in experimental Chagas disease. PMID:26347748

  5. Ear infection - acute

    MedlinePlus

    ... Risk factors for acute ear infections include: Attending day care (especially centers with more than 6 children) Changes ... hands and toys often. If possible, choose a day care that has 6 or fewer children. This can ...

  6. Impaired acquired resistance of mice to Klebsiella pneumoniae infection induced by acute NO/sub 2/ exposure

    SciTech Connect

    Bouley, G.; Azoulay-Dupuis, E.; Gaudebout, C.

    1985-12-01

    The natural resistance of nonimmunized C57B1/6 mice to an intraperitoneal Klebsiella pneumoniae challenge was not significantly affected by prior continuous exposure to 20 ppm NO/sub 2/ for 4 days. In contrast, the acquired resistance of mice immunized just before and infected just after NO/sub 2/ exposure was seriously impaired. This could not be explained by the loss of appetite (about 30%) observed in NO/sub 2/ treated mice, for neither the natural nor acquired resistance of control air exposure mice given approximately 70% ad libitum food and water were significantly modified.

  7. Splenic Leukocytes Traffic to the Thyroid and Produce a Novel TSHβ Isoform during Acute Listeria monocytogenes Infection in Mice.

    PubMed

    Montufar-Solis, Dina; Klein, John R

    2016-01-01

    The thyroid stimulating hormone beta-subunit (TSHβ) with TSHα form a glycoprotein hormone that is produced by the anterior pituitary in the hypothalamus-pituitary-thyroid (HPT) axis. Although TSHβ has been known for many years to be made by cells of the immune system, the role of immune system TSH has remained unclear. Recent studies demonstrated that cells of the immune system produce a novel splice variant isoform of TSHβ (TSHβv), but little if any native TSHβ. Here, we show that within three days of systemic infection of mice with Listeria monocytogenes, splenic leukocytes synthesized elevated levels of TSHβv. This was accompanied by an influx of CD14+, Ly6C+, Ly6G+ cells into the thyroid of infected mice, and increased levels of intrathyroidal TSHβv gene expression. Adoptive transfer of carboxyfluorescein succinimidyl ester (CFSE)-labeled splenic leukocytes from infected mice into non-infected mice migrated into the thyroid as early as forty-eight hours post-cell transfer, whereas CFSE-labeled cells from non-infected mice failed to traffic to the thyroid. These findings demonstrate for the first time that during bacterial infection peripheral leukocytes produce elevated levels of TSHβv, and that spleen cells traffic to the thyroid where they produce TSHβv intrathyroidally. PMID:26771831

  8. Splenic Leukocytes Traffic to the Thyroid and Produce a Novel TSHβ Isoform during Acute Listeria monocytogenes Infection in Mice

    PubMed Central

    Montufar-Solis, Dina; Klein, John R.

    2016-01-01

    The thyroid stimulating hormone beta-subunit (TSHβ) with TSHα form a glycoprotein hormone that is produced by the anterior pituitary in the hypothalamus-pituitary-thyroid (HPT) axis. Although TSHβ has been known for many years to be made by cells of the immune system, the role of immune system TSH has remained unclear. Recent studies demonstrated that cells of the immune system produce a novel splice variant isoform of TSHβ (TSHβv), but little if any native TSHβ. Here, we show that within three days of systemic infection of mice with Listeria monocytogenes, splenic leukocytes synthesized elevated levels of TSHβv. This was accompanied by an influx of CD14+, Ly6C+, Ly6G+ cells into the thyroid of infected mice, and increased levels of intrathyroidal TSHβv gene expression. Adoptive transfer of carboxyfluorescein succinimidyl ester (CFSE)-labeled splenic leukocytes from infected mice into non-infected mice migrated into the thyroid as early as forty-eight hours post-cell transfer, whereas CFSE-labeled cells from non-infected mice failed to traffic to the thyroid. These findings demonstrate for the first time that during bacterial infection peripheral leukocytes produce elevated levels of TSHβv, and that spleen cells traffic to the thyroid where they produce TSHβv intrathyroidally. PMID:26771831

  9. In vivo evaluation of adeno-associated virus gene transfer in airways of mice with acute or chronic respiratory infection.

    PubMed

    Myint, Melissa; Limberis, Maria P; Bell, Peter; Somanathan, Suryanarayan; Haczku, Angela; Wilson, James M; Diamond, Scott L

    2014-11-01

    Patients with cystic fibrosis (CF) often suffer chronic lung infection with concomitant inflammation, a setting that may reduce the efficacy of gene transfer. While gene therapy development for CF often involves viral-based vectors, little is known about gene transfer in the context of an infected airway. In this study, three mouse models were established to evaluate adeno-associated virus (AAV) gene transfer in such an environment. Bordetella bronchiseptica RB50 was used in a chronic, nonlethal respiratory infection in C57BL/6 mice. An inoculum of ∼10(5) CFU allowed B. bronchiseptica RB50 to persist in the upper and lower respiratory tracts for at least 21 days. In this infection model, administration of an AAV vector on day 2 resulted in 2.8-fold reduction of reporter gene expression compared with that observed in uninfected controls. Postponement of AAV administration to day 14 resulted in an even greater (eightfold) reduction of reporter gene expression, when compared with uninfected controls. In another infection model, Pseudomonas aeruginosa PAO1 was used to infect surfactant protein D (SP-D) or surfactant protein A (SP-A) knockout (KO) mice. With an inoculum of ∼10(5) CFU, infection persisted for 2 days in the nasal cavity of either mouse model. Reporter gene expression was approximately ∼2.5-fold lower compared with uninfected mice. In the SP-D KO model, postponement of AAV administration to day 9 postinfection resulted in only a two fold reduction in reporter gene expression, when compared with expression seen in uninfected controls. These results confirm that respiratory infections, both ongoing and recently resolved, decrease the efficacy of AAV-mediated gene transfer. PMID:25144316

  10. Brain Invasion by CD4(+) T Cells Infected with a Transmitted/Founder HIV-1BJZS7 During Acute Stage in Humanized Mice.

    PubMed

    Wu, Xilin; Liu, Li; Cheung, Ka-Wai; Wang, Hui; Lu, Xiaofan; Cheung, Allen Ka Loon; Liu, Wan; Huang, Xiuyan; Li, Yanlei; Chen, Zhiwei W; Chen, Samantha M Y; Zhang, Tong; Wu, Hao; Chen, Zhiwei

    2016-09-01

    Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is one of the common causes of cognitive dysfunction and morbidity among infected patients. However, to date, it remains unknown if a transmitted/founder (T/F) HIV-1 leads to neurological disorders during acute phase of infection. Since it is impossible to answer this question in humans, we studied NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ mice (NSG) reconstituted with human PBMC (NSG-HuPBL), followed by the peritoneal challenge with the chronic HIV-1JR-FL and the T/F HIV-1BJZS7, respectively. By measuring viral load, P24 antigenemia and P24(+) cells in peripheral blood and various tissue compartments, we found that systemic infections were rapidly established in NSG-HuPBL mice by both HIV-1 strains. Although comparable peripheral viral loads were detected during acute infection, the T/F virus appeared to cause less CD4(+) T cell loss and less numbers of infected cells in different organs and tissue compartments. Both viruses, however, invaded brains with P24(+)/CD3(+) T cells detected primarily in meninges, cerebral cortex and perivascular areas. Critically, brain infections with HIV-1JR-FL but not with HIV-1BJZS7 resulted in damaged neurons together with activated microgliosis and astrocytosis as determined by significantly increased numbers of Iba1(+) microglial cells and GFAP(+) astrocytes, respectively. The increased Iba1(+) microglia was correlated positively with levels of P24 antigenemia and negatively with numbers of NeuN(+) neurons in brains of infected animals. Our findings, therefore, indicate the establishment of two useful NSG-HuPBL models, which may facilitate future investigation of mechanisms underlying HIV-1-induced microgliosis and astrocytosis. PMID:26838362

  11. The Burkholderia pseudomallei Δasd Mutant Exhibits Attenuated Intracellular Infectivity and Imparts Protection against Acute Inhalation Melioidosis in Mice

    PubMed Central

    Norris, Michael H.; Propst, Katie L.; Kang, Yun; Dow, Steven W.; Schweizer, Herbert P.; Hoang, Tung T.

    2011-01-01

    Burkholderia pseudomallei, the cause of serious and life-threatening diseases in humans, is of national biodefense concern because of its potential use as a bioterrorism agent. This microbe is listed as a select agent by the CDC; therefore, development of vaccines is of significant importance. Here, we further investigated the growth characteristics of a recently created B. pseudomallei 1026b Δasd mutant in vitro, in a cell model, and in an animal model of infection. The mutant was typified by an inability to grow in the absence of exogenous diaminopimelate (DAP); upon single-copy complementation with a wild-type copy of the asd gene, growth was restored to wild-type levels. Further characterization of the B. pseudomallei Δasd mutant revealed a marked decrease in RAW264.7 murine macrophage cytotoxicity compared to the wild type and the complemented Δasd mutant. RAW264.7 cells infected by the Δasd mutant did not exhibit signs of cytopathology or multinucleated giant cell (MNGC) formation, which were observed in wild-type B. pseudomallei cell infections. The Δasd mutant was found to be avirulent in BALB/c mice, and mice vaccinated with the mutant were protected against acute inhalation melioidosis. Thus, the B. pseudomallei Δasd mutant may be a promising live attenuated vaccine strain and a biosafe strain for consideration of exclusion from the select agent list. PMID:21807903

  12. Recombinant BCG prime and PPE protein boost provides potent protection against acute Mycobacterium tuberculosis infection in mice.

    PubMed

    Yang, Enzhuo; Gu, Jin; Wang, Feifei; Wang, Honghai; Shen, Hongbo; Chen, Zheng W

    2016-04-01

    Since BCG, the only vaccine widely used against tuberculosis (TB) in the world, provides varied protective efficacy and may not be effective for inducing long-term cellular immunity, it is in an urgent need to develop more effective vaccines and more potent immune strategies against TB. Prime-boost is proven to be a good strategy by inducing long-term protection. In this study, we tested the protective effect against Mycobacterium tuberculosis (Mtb) challenge of prime-boost strategy by recombinant BCG (rBCG) expressing PPE protein Rv3425 fused with Ag85B and Rv3425. Results showed that the prime-boost strategy could significantly increase the protective efficiency against Mtb infection, characterized by reduction of bacterial load in lung and spleen, attenuation of tuberculosis lesions in lung tissues. Importantly, we found that Rv3425 boost, superior to Ag85B boost, provided better protection against Mtb infection. Further research proved that rBCG prime-Rv3425 boost could obviously increase the expansion of lymphocytes, significantly induce IL-2 production by lymphocytes upon PPD stimulation, and inhibit IL-6 production at an early stage. It implied that rBCG prime-Rv3425 boost opted to induce Th1 immune response and provided a long-term protection against TB. These results implicated that rBCG prime-Rv3425 boost is a potent and promising strategy to prevent acute Mtb infection. PMID:26792673

  13. Activation of type I interferon signaling in the parotid and exorbital lachrymal glands during the acute phase of encephalomyocarditis (EMC) virus infection in mice.

    PubMed

    Ohguchi, Atsuko; Yamauchi, Hirofumi; Doi, Kunio; Nakayama, Hiroyuki

    2016-06-01

    The present study was carried out to clarify the mechanisms of EMC virus-induced sialodacryoadenitis in mice during the acute phase infection focusing on the activation of type I interferon (IFN) signaling in the parotid and exorbital lachrymal glands. In the parotid gland, a few apoptotic acinar cells were detected at 2days post inoculation (DPI). The ratio of apoptotic acinar cells increased at 3 and 4DPI. On the other hand, in the exorbital lachrymal gland, apoptosis of acinar cells and infiltration of inflammatory cells mainly composed of mononuclear cells started at 3DPI, and prominent acinar cell damage developed at 4DPI. Viral RNA was detected at 3 and 4DPI in both glands and the expression level was higher in the exorbital lachrymal gland than in the parotid gland. The up-regulation of IFN-stimulated genes (ISGs), such as Irf7, Pkr and Oas, was quickly induced at 2DPI in the parotid gland, and this probably contributed to suppress viral replication and to eliminate affected cells by apoptosis. In the exorbital lachrymal gland, the expression levels of ISGs mRNAs were not elevated at 2DPI, suggesting no induction of an effective anti-viral response such as apoptosis at this time point. In the exorbital lachrymal gland, the mRNA expression of IFN beta and IFN alpha (type I IFNs) was weak- to strong-positive at 1DPI, and became negative at 2DPI. The weak- to strong-positive expression of IFNs at 1DPI is likely related to the abrupt viral replication and pathological changes in the exorbital lachrymal gland through activating the negative feedback regulation that depressed the IFN signaling cascade at 2DPI. In conclusion, the present study showed the changes in factors involved in the activation of type I IFN signaling cascade in the parotid and exorbital lachrymal glands and their differences between the two glands during the acute phase of EMC virus infection in mice. PMID:27079771

  14. Adoptive transfer of CD4(+)Foxp3(+) regulatory T cells to C57BL/6J mice during acute infection with Toxoplasma gondii down modulates the exacerbated Th1 immune response.

    PubMed

    Olguín, Jonadab E; Fernández, Jacquelina; Salinas, Nohemí; Juárez, Imelda; Rodriguez-Sosa, Miriam; Campuzano, Jaime; Castellanos, Carlos; Saavedra, Rafael

    2015-08-01

    Infection of C57BL/6J mice with the parasite Toxoplasma gondii triggers a powerful Th1 immune response that is detrimental to the host. During acute infection, a reduction in CD4(+)Foxp3(+) regulatory T cells (Treg) has been reported. We studied the role of Treg during T. gondii infection by adoptive transfer of cells purified from transgenic Foxp3(EGFP) mice to infected wild type animals. We found a less severe weight loss, a significant delayed mortality in infected Treg-transferred mice, and reduced pathology of the small intestine that were associated with lower IFN-γ and TNF-α levels. Nevertheless, higher cyst number and parasite load in brain were observed in these mice. Treg-transferred infected mice showed reduced levels of both IFN-γ and TNF-α in sera. A reduced number of CD4(+) T cells producing IFN-γ was detected in these mice, while IL-2 producing CD4(+) T cells were restored to levels nearly similar to uninfected mice. CD25 and CD69 expression of CD4(+) T cells were also down modulated. Our data show that the low Treg cell number are insufficient to modulate the activation of CD4(+) T cells and the production of high levels of IFN-γ. Thus, a delicate balance between an optimal immune response and its modulation by Treg cells must exist. PMID:25899946

  15. Long-Term Immunity to Lethal Acute or Chronic Type II Toxoplasma gondii Infection Is Effectively Induced in Genetically Susceptible C57BL/6 Mice by Immunization with an Attenuated Type I Vaccine Strain▿

    PubMed Central

    Gigley, Jason P.; Fox, Barbara A.; Bzik, David J.

    2009-01-01

    C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-immunized B6 mice chronically infected with ME49 survived for at least 12 months without succumbing to the chronic infection. Potent immunity to type II challenge infections persisted for at least 10 months after vaccination. While the cps1-1 strain-elicited immunity did not prevent the establishment of a chronic infection or clear established brain cysts, cps1-1 strain-elicited CD8+ immune T cells significantly inhibited recrudescence of brain cysts during chronic ME49 infection. In addition, we show that uracil starvation of the cps1-1 strain induces early markers of bradyzoite differentiation. Collectively, these results suggest that more effective immune control of chronic type II infection in the genetically susceptible B6 background is established by vaccination with the nonreplicating type I uracil auxotroph cps1-1 strain. PMID:19797073

  16. Long-term immunity to lethal acute or chronic type II Toxoplasma gondii infection is effectively induced in genetically susceptible C57BL/6 mice by immunization with an attenuated type I vaccine strain.

    PubMed

    Gigley, Jason P; Fox, Barbara A; Bzik, David J

    2009-12-01

    C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-immunized B6 mice chronically infected with ME49 survived for at least 12 months without succumbing to the chronic infection. Potent immunity to type II challenge infections persisted for at least 10 months after vaccination. While the cps1-1 strain-elicited immunity did not prevent the establishment of a chronic infection or clear established brain cysts, cps1-1 strain-elicited CD8(+) immune T cells significantly inhibited recrudescence of brain cysts during chronic ME49 infection. In addition, we show that uracil starvation of the cps1-1 strain induces early markers of bradyzoite differentiation. Collectively, these results suggest that more effective immune control of chronic type II infection in the genetically susceptible B6 background is established by vaccination with the nonreplicating type I uracil auxotroph cps1-1 strain. PMID:19797073

  17. [Digestive tract dilation in mice infected with Trypanosoma cruzi].

    PubMed

    Guillén-Pernía, B; Lugo-Yarbuh, A; Moreno, E

    2001-09-01

    This paper will analyze alterations in the digestive tract (DT) of mice with chronic Chagas' disease infection produced by Trypanosoma cruzi from different sources. X-rays of the DT of 18 mice infected with T. cruzi and 6 control mice were compared after the ingestion of a barium sulfate solution over a period of 6 hours. 120 days post-infection (pi) the X-rays of the DT of the 5 mice of group 1A infected with trypanosomes DMI isolated from the opossum Didelphis marsupialis, and 4 mice in group 2A infected with the isolate EP taken from a patient with acute Chagas' disease, showed swelling of the stomach and the colon (C). 180 days pi, the X-rays of the DT of the 5 mice of group 1B infected with isolated DMI and the 4 mice in group 2B infected with isolate EP, showed an even greater swelling of the C. Histological examination of the DT of all infected mice showed extensive changes of the intestinal muscle layer, such as the diminution of the muscular and mucous layers and the loss of colonic folds and myoenteric plexus. These results suggest that T. cruzi populations caused severe alterations in the digestive system of the mice used in the experiment, and that the same alterations could occur in the digestive organs of humans, especially those living in areas where Chagas' disease is endemic, but where these abnormalities have not yet been reported. PMID:11552508

  18. Acute cytomegalovirus (CMV) infection

    MedlinePlus

    ... by: Blood transfusions Organ transplants Respiratory droplets Saliva Sexual contact Urine Most people come into contact with ... with another person. You should avoid kissing and sexual contact with an infected person. The virus may ...

  19. TNF-α is expressed at sites of parasite and tissue destruction in the spleen of mice acutely infected with Trypanosoma cruzi

    PubMed Central

    LIMA, ELIANITA SUZART; ANDRADE, ZILTON A; ANDRADE, SONIA G

    2001-01-01

    Mice infected with a macrophagotropic strain of Trypanosoma cruzi develop progressive splenomegaly due to reactive hyperplasia with increased number of lymphocytes and macrophages, culminating in parasite disintegration and necrosis of parasitized cells. Necrotic changes have been attributed to the liberation of toxic cytokines, including TNF-α, from parasitized macrophages. In the present study, the presence of TNF‐α was investigated in situ. In addition the participation of destroyed parasites in inducing the liberation of TNF-α was examined in two highly susceptible mice strains (C3H and Swiss) and a more resistant strain (DBA). Swiss (90) C3H/He (83) and DBA (30) mice were infected with the Peruvian strain of T. cruzi. Nineteen infected Swiss mice, and 22 infected C3H/He were treated with Benznidazole (one or two doses, 100 mg/kg bw/day), on the 8th and 9th days after infection. Necrotic splenic lesions occurred in both susceptible and resistant strains of mice. Although differing in degree, lesions were more intense in C3H and Swiss than in DBA mice. Comparing untreated and treated susceptible mice, necrotic lesions were significantly less intense in the latter. By specific monoclonal antibody immunolabelling, TNF-α was demonstrated in the cytoplasm of macrophages and within necrotic areas, from Swiss, C3H/He and DBA mouse spleens. In conclusion, TNF-α, probably synthesized by macrophages, was strongly expressed at the sites of parasite and cell destruction, thus appearing to play a pivotal role in splenic necrotic changes associated with severe experimental T. cruzi infection. PMID:11846839

  20. Acetaminophen-induced acute liver injury in HCV transgenic mice

    SciTech Connect

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U.; Tech, Katherine; Macdonald, Jeffrey M.; Boorman, Gary A.; Chatterjee, Saurabh; Mason, Ronald P.; Melnyk, Stepan B.; Tryndyak, Volodymyr P.; Pogribny, Igor P.; Rusyn, Ivan

    2013-01-15

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  1. SCID mouse models of acute and relapsing chronic Toxoplasma gondii infections.

    PubMed Central

    Johnson, L L

    1992-01-01

    Lymphodeficient scid/scid (SCID) mice died from acute infection with a strain of Toxoplasma gondii that causes chronic infection with mild symptoms in immunocompetent non-SCID mice. However, most SCID mice reconstituted with spleen cells from immunocompetent mice 1 month prior to T. gondii infection survived in good health after a transient period during which they appeared ill. Unreconstituted SCID mice given sulfadiazine in their drinking water from day 10 of Toxoplasma infection onward survived the acute phase of infection and lived for many weeks without overt symptoms. Histological examination revealed Toxoplasma cysts in their brains. However, if sulfadiazine was withdrawn from the drinking water of these chronically infected SCID mice, the mice died within 1 week with large numbers of trophozoites throughout their brains. These findings establish SCID mice as a potentially useful resource with which to study various aspects of immunological control of T. gondii infection during either its acute or chronic phase. Furthermore, the ability to produce chronic infections with avirulent T. gondii in SCID mice and to cause acute relapsing infections at will suggests that SCID mice may be helpful in evaluating potential therapies for acute and chronic T. gondii infections in immunocompromised patients. Images PMID:1500181

  2. Protection of Cftr knockout mice from acute lung infection by a helper-dependent adenoviral vector expressing Cftr in airway epithelia

    PubMed Central

    Koehler, David R.; Sajjan, Umadevi; Chow, Yu-Hua; Martin, Bernard; Kent, Geraldine; Tanswell, A. Keith; McKerlie, Colin; Forstner, Janet F.; Hu, Jim

    2003-01-01

    We developed a helper-dependent adenoviral vector for cystic fibrosis lung gene therapy. The vector expresses cystic fibrosis transmembrane conductance regulator (Cftr) using control elements from cytokeratin 18. The vector expressed properly localized CFTR in cultured cells and in the airway epithelia of mice. Cftr RNA and protein were present in whole lung and bronchioles, respectively, for 28 days after a vector dose. Acute inflammation was minimal to moderate. To test the therapeutic potential of the vector, we challenged mice with a clinical strain of Burkholderia cepacia complex (Bcc). Cftr knockout mice (but not Cftr+/+ littermates) challenged with Bcc developed severe lung histopathology and had high lung bacteria counts. Cftr knockout mice receiving gene therapy 7 days before Bcc challenge had less severe histopathology, and the number of lung bacteria was reduced to the level seen in Cftr+/+ littermates. These data suggest that gene therapy could benefit cystic fibrosis patients by reducing susceptibility to opportunistic pathogens. PMID:14673110

  3. Protection of Cftr knockout mice from acute lung infection by a helper-dependent adenoviral vector expressing Cftr in airway epithelia.

    PubMed

    Koehler, David R; Sajjan, Umadevi; Chow, Yu-Hua; Martin, Bernard; Kent, Geraldine; Tanswell, A Keith; McKerlie, Colin; Forstner, Janet F; Hu, Jim

    2003-12-23

    We developed a helper-dependent adenoviral vector for cystic fibrosis lung gene therapy. The vector expresses cystic fibrosis transmembrane conductance regulator (Cftr) using control elements from cytokeratin 18. The vector expressed properly localized CFTR in cultured cells and in the airway epithelia of mice. Cftr RNA and protein were present in whole lung and bronchioles, respectively, for 28 days after a vector dose. Acute inflammation was minimal to moderate. To test the therapeutic potential of the vector, we challenged mice with a clinical strain of Burkholderia cepacia complex (Bcc). Cftr knockout mice (but not Cftr+/+ littermates) challenged with Bcc developed severe lung histopathology and had high lung bacteria counts. Cftr knockout mice receiving gene therapy 7 days before Bcc challenge had less severe histopathology, and the number of lung bacteria was reduced to the level seen in Cftr+/+ littermates. These data suggest that gene therapy could benefit cystic fibrosis patients by reducing susceptibility to opportunistic pathogens. PMID:14673110

  4. Severe acute malnutrition and infection

    PubMed Central

    Jones, Kelsey D J; Berkley, James A

    2014-01-01

    Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice. PMID:25475887

  5. Activation of A1-Adenosine Receptors Promotes Leukocyte Recruitment to the Lung and Attenuates Acute Lung Injury in Mice Infected with Influenza A/WSN/33 (H1N1) Virus

    PubMed Central

    Aeffner, Famke; Woods, Parker S.

    2014-01-01

    ABSTRACT We have shown that bronchoalveolar epithelial A1-adenosine receptors (A1-AdoR) are activated in influenza A virus-infected mice. Alveolar macrophages and neutrophils also express A1-AdoRs, and we hypothesized that activation of A1-AdoRs on these cells will promote macrophage and neutrophil chemotaxis and activation and thereby play a role in the pathogenesis of influenza virus-induced acute lung injury. Wild-type (WT) C57BL/6 mice, congenic A1-AdoR knockout (A1-KO) mice, and mice that had undergone reciprocal bone marrow transfer were inoculated intranasally with 10,000 PFU/mouse influenza A/WSN/33 (H1N1) virus. Alternatively, WT mice underwent daily treatment with the A1-AdoR antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) from 1 day prior to inoculation. Infection increased bronchoalveolar lining fluid (BALF) adenosine comparably in WT and A1-KO mice. Infection of WT mice resulted in reduced carotid arterial O2 saturation (hypoxemia), lung pathology, pulmonary edema, reduced lung compliance, increased basal airway resistance, and hyperresponsiveness to methacholine. These effects were absent or significantly attenuated in A1-KO mice. Levels of BALF leukocytes, gamma interferon (IFN-γ), and interleukin 10 (IL-10) were significantly reduced in infected A1-KO mice, but levels of KC, IP-10, and MCP-1 were increased. Reciprocal bone marrow transfer resulted in WT-like lung injury severity, but BALF leukocyte levels increased only in WT and A1-KO mice with WT bone barrow. Hypoxemia, pulmonary edema, and levels of BALF alveolar macrophages, neutrophils, IFN-γ, and IL-10 were reduced in DPCPX-treated WT mice. Levels of viral replication did not differ between mouse strains or treatment groups. These findings indicate that adenosine activation of leukocyte A1-AdoRs plays a significant role in their recruitment to the infected lung and contributes to influenza pathogenesis. A1-AdoR inhibitor therapy may therefore be beneficial in patients with influenza

  6. Sleep and fatigue in mice infected with murine gammaherpesvirus 68.

    PubMed

    Olivadoti, Melissa D; Weinberg, Jason B; Toth, Linda A; Opp, Mark R

    2011-05-01

    Fatigue, a common symptom of many acute and chronic medical conditions, reduces both quality of life and workplace productivity and can be disabling. However, the pathophysiologic mechanisms that underlie fatigue can be difficult to study in human populations due to the patient heterogeneity, the variety of underlying causes and potential triggering events, and an inability to collect samples that may be essential to elucidation of mechanisms (e.g., brain). Although the etiology of chronic fatigue syndrome (CFS) remains elusive, some studies have implicated viral infections, including Epstein-Barr virus (EBV), a human gammaherpesvirus, as a potential factor in the pathogenesis of CFS. Murine gammaherpesvirus 68 (γHV68) is a mouse pathogen that shares many similarities with human γHVs, including EBV. In this study, we use γHV68-infected C57BL/6J mice as a model system for studying the impact of chronic viral infection on sleep-wake behavior, activity patterns, and body temperature profiles. Our data show that γHV68 alters sleep, activity, and temperature in a manner suggestive of fatigue. In mice infected with the highest dose used in this study (40,000plaque forming units), food intake, body weight, wheel running, body temperature, and sleep were normal until approximately 7days after infection. These parameters were significantly altered during days 7 through 11, returned to baseline levels at day 12 after infection, and remained within the normal range for the remainder of the 30-day period after inoculation. At that time, both infected and uninfected mice were injected with lipopolysaccharide (LPS), and their responses monitored. Uninfected mice given LPS developed a modest and transient febrile response during the initial light phase (hours 12 through 24) after injection. In contrast, infected mice developed changes in core body temperatures that persisted for at least 5days. Infected mice showed an initial hypothermia that lasted for approximately 12h

  7. Dengue Virus Infection with Highly Neutralizing Levels of Cross-Reactive Antibodies Causes Acute Lethal Small Intestinal Pathology without a High Level of Viremia in Mice

    PubMed Central

    Watanabe, Satoru; Chan, Kitti Wing Ki; Wang, Jiaqi; Rivino, Laura; Lok, Shee-Mei

    2015-01-01

    ABSTRACT Severe dengue virus (DENV)-associated diseases can occur in patients who have preexisting DENV antibodies (Abs) through antibody-dependent enhancement (ADE) of infection. It is well established that during ADE, DENV-antibody immune complexes (ICs) infect Fcγ receptor-bearing cells and increase the systemic viral burden that can be measured in the blood. For protection against infection with DENV serotypes 1 to 4, strongly neutralizing Abs must be elicited to overcome the effect of ADE. Clinical observations in infants who have maternal DENV Abs or recent phase II/III clinical trials with a leading tetravalent dengue vaccine suggested a lack of correlation between Ab neutralization and in vivo disease prevention. In addressing this gap in knowledge, we found that inoculation of ICs formed with serotype cross-reactive Abs that are more than 98% neutralized in vitro promotes high mortality in AG129 mice even though peak viremia was lower than that in direct virus infection. This suggests that the serum viremia level is not always correlated with disease severity. We further demonstrated that infection with the ICs resulted in increased vascular permeability, specifically in the small intestine, accompanied with increased tissue viral load and cytokine production, which can be suppressed by anti-tumor necrosis factor alpha (anti-TNF-α) Abs. Flow cytometric analysis identified increased infection in CD11bint CD11cint/hi CD103− antigen-presenting cells by IC inoculation, suggesting that these infected cells may be responsible for the increase in TNF-α production and vascular permeability in the small intestine that lead to mortality in mice. Our findings may have important implications for the development of dengue therapeutics. IMPORTANCE We examined the relationship between the neutralizing level of Abs at the time of infection and subsequent disease progression in a mouse model in order to understand why patients who are shown to have a neutralizing

  8. Acute Chagas Disease Induces Cerebral Microvasculopathy in Mice

    PubMed Central

    Nisimura, Lindice Mitie; Estato, Vanessa; de Souza, Elen Mello; Reis, Patricia A.; Lessa, Marcos Adriano; Castro-Faria-Neto, Hugo Caire; Pereira, Mirian Claudia de Souza; Tibiriçá, Eduardo; Garzoni, Luciana Ribeiro

    2014-01-01

    Cardiomyopathy is the main clinical form of Chagas disease (CD); however, cerebral manifestations, such as meningoencephalitis, ischemic stroke and cognitive impairment, can also occur. The aim of the present study was to investigate functional microvascular alterations and oxidative stress in the brain of mice in acute CD. Acute CD was induced in Swiss Webster mice (SWM) with the Y strain of Trypanosoma cruzi (T. cruzi). Cerebral functional capillary density (the number of spontaneously perfused capillaries), leukocyte rolling and adhesion and the microvascular endothelial-dependent response were analyzed over a period of fifteen days using intravital video-microscopy. We also evaluated cerebral oxidative stress with the thiobarbituric acid reactive species TBARS method. Compared with the non-infected group, acute CD significantly induced cerebral functional microvascular alterations, including (i) functional capillary rarefaction, (ii) increased leukocyte rolling and adhesion, (iii) the formation of microvascular platelet-leukocyte aggregates, and (iv) alteration of the endothelial response to acetylcholine. Moreover, cerebral oxidative stress increased in infected animals. We concluded that acute CD in mice induced cerebral microvasculopathy, characterized by a reduced incidence of perfused capillaries, a high number of microvascular platelet-leukocyte aggregates, a marked increase in leukocyte-endothelium interactions and brain arteriolar endothelial dysfunction associated with oxidative stress. These results suggest the involvement of cerebral microcirculation alterations in the neurological manifestations of CD. PMID:25010691

  9. Trypanosoma cruzi Infection through the Oral Route Promotes a Severe Infection in Mice: New Disease Form from an Old Infection?

    PubMed Central

    Barreto-de-Albuquerque, Juliana; Silva-dos-Santos, Danielle; Pérez, Ana Rosa; Berbert, Luiz Ricardo; de Santana-van-Vliet, Eliane; Farias-de-Oliveira, Désio Aurélio; Moreira, Otacilio C.; Roggero, Eduardo; de Carvalho-Pinto, Carla Eponina; Jurberg, José; Cotta-de-Almeida, Vinícius; Bottasso, Oscar; Savino, Wilson; de Meis, Juliana

    2015-01-01

    Oral transmission of Chagas disease has been documented in Latin American countries. Nevertheless, significant studies on the pathophysiology of this form of infection are largely lacking. The few studies investigating oral route infection disregard that inoculation in the oral cavity (Oral infection, OI) or by gavage (Gastrointestinal infection, GI) represent different infection routes, yet both show clear-cut parasitemia and heart parasitism during the acute infection. Herein, BALB/c mice were subjected to acute OI or GI infection using 5x104 culture-derived Trypanosoma cruzi trypomastigotes. OI mice displayed higher parasitemia and mortality rates than their GI counterparts. Heart histopathology showed larger areas of infiltration in the GI mice, whereas liver lesions were more severe in the OI animals, accompanied by higher Alanine Transaminase and Aspartate Transaminase serum contents. A differential cytokine pattern was also observed because OI mice presented higher pro-inflammatory cytokine (IFN-γ, TNF) serum levels than GI animals. Real-time PCR confirmed a higher TNF, IFN-γ, as well as IL-10 expression in the cardiac tissue from the OI group compared with GI. Conversely, TGF-β and IL-17 serum levels were greater in the GI animals. Immunolabeling revealed macrophages as the main tissue source of TNF in infected mice. The high mortality rate observed in the OI mice paralleled the TNF serum rise, with its inhibition by an anti-TNF treatment. Moreover, differences in susceptibility between GI versus OI mice were more clearly related to the host response than to the effect of gastric pH on parasites, since infection in magnesium hydroxide-treated mice showed similar results. Overall, the present study provides conclusive evidence that the initial site of parasite entrance critically affects host immune response and disease outcome. In light of the occurrence of oral Chagas disease outbreaks, our results raise important implications in terms of the current

  10. Vaccination of mice against Mycobacterium leprae infection.

    PubMed Central

    Singh, N B; Lowe, A C; Rees, R J; Colston, M J

    1989-01-01

    Intradermal immunization with killed Mycobacterium leprae renders mice immune to infection with viable M. leprae. This protection is long lasting and systemic in that immunization in the left flank results in protection in both the left and right footpads. Immunization with Mycobacterium vaccae was ineffective in protecting mice against M. leprae infection, while Mycobacterium bovis BCG provided partial protection. Mycobacterium habana TMC 5135 (now known as Mycobacterium simiae) was found to be as effective as M. leprae in protecting mice against footpad infection. PMID:2643581

  11. Pathogenesis of anemia in Trypanosoma brucei-infected mice.

    PubMed Central

    Amole, B O; Clarkson, A B; Shear, H L

    1982-01-01

    The pathogenesis of anemia was studied in trypanosome-infected mice. A strain of Trypanosoma brucei, TREU 667, was used which first produces an acute phase marked by waves of parasitemia. Erythrocytes from infected animals were coated with immunoglobulin M during or just before the waves of anemia and parasitological crises. Erythrocytes from normal animals could be sensitized with "precrisis" sera presumably containing antigen and antibody. These data suggest that anemia during the acute phase is due to sensitization of erythrocytes with immunoglobulin M-antigen complexes. The anemia is partially compensated by a strong erythropoietic response. The acute phase is followed by a chronic phase marked by a constant high parasitemia and immunosuppression. The less marked anemia occurring during this latter phase is due to hemodilution and perhaps a low but significant immune response to the parasites, which causes continuing erythrocyte sensitization by immunoglobulin M-antigen complexes. PMID:7201455

  12. Noninvasive monitoring of salmonella infections in young mice

    NASA Astrophysics Data System (ADS)

    Olomu, Isoken N.; Reilly-Contag, Pamela; Stevenson, David K.; Contag, Christopher H.

    1999-07-01

    A recently developed bioluminescent assay was used to study the influence of age and inoculum size on the acute susceptibility of newborn and juvenile BALB/c mice to Salmonella gastrointestinal infection. Three strains of Salmonella were tagged by expression of the lux operon from Photohabdus luminescenes. Using a range of inoculum sizes varied over 6 orders of magnitude, mice aged 0-6 weeks were infected by oral inoculation. LIght emitted from the tagged bacteria and transmitted through mouse tissues was used to noninvasively monitor disease progression over 7 days. In neonatal mice there was evidence of gastrointestinal infection at 24 hours even with small inocular, and at 4-7 days, the patterns of photon emission and remained and healthy throughout the study period. Inoculation of neonates with tagged LB5000 and BJ66 resulted in severe gastrointestinal infections with low and intermediate sizes of inocula respectively. These strains are known to be of reduced virulence in adult mice. These age-related differences in susceptibility emphasize the need to define virulence in the context of age of the host, and implicate maturation of innate resistance factors in determining disease patterns. Identifying these host-factors and further defining the bacterial determinants of virulence in the neonatal host will be facilitated by this noninvasive study of infection using bioluminenscent methods.

  13. Acute toxicity of karlotoxins to mice

    PubMed Central

    Place, Allen R.; Munday, R.; Munday, J.S.

    2015-01-01

    Karlotoxins, polyketide derivatives produced by the dinoflagellate Karlodinium veneficum, are associated with fish kills in temperate estuaries world wide. In this study, the acute effects of 3 pure karlotoxin analogs (KmTx 1, KmTx 3 and KmTx 2) have been examined in mice. Transient lethargy and increased respiratory rates were observed soon after dosing with the karlotoxins by intraperitoneal injection, but no deaths were recorded in animals dosed with KmTx 2 at up to 500 μg/kg or with KmTx 1 or KmTx 3 at up to 4000 μg/kg. Animals dosed intraperitoneally with KmTx 1 and KmTx 3 at 4000 μg/kg showed a pronounced decrease in food and water intake, lasting 3–4 days after dosing, accompanied by a significant decrease in body weight. After this time, the lost body weight was regained and the behavior and appearance of the mice remained normal throughout the following 10 day observation period. No effects were seen in mice dosed orally with KmTx 1 or KmTx 3 at a dose of 4000 μg/kg. It is concluded that contamination of seafood if it were to occur with these karlotoxins is unlikely to pose a major risk of acute intoxication in consumers. PMID:25150200

  14. A HIV-Tat/C4-binding protein chimera encoded by a DNA vaccine is highly immunogenic and contains acute EcoHIV infection in mice

    PubMed Central

    Tomusange, Khamis; Wijesundara, Danushka; Gummow, Jason; Garrod, Tamsin; Li, Yanrui; Gray, Lachlan; Churchill, Melissa; Grubor-Bauk, Branka; Gowans, Eric J.

    2016-01-01

    DNA vaccines are cost-effective to manufacture on a global scale and Tat-based DNA vaccines have yielded protective outcomes in preclinical and clinical models of human immunodeficiency virus (HIV), highlighting the potential of such vaccines. However, Tat-based DNA vaccines have been poorly immunogenic, and despite the administration of multiple doses and/or the addition of adjuvants, these vaccines are not in general use. In this study, we improved Tat immunogenicity by fusing it with the oligomerisation domain of a chimeric C4-binding protein (C4b-p), termed IMX313, resulting in Tat heptamerisation and linked Tat to the leader sequence of tissue plasminogen activator (TPA) to ensure that the bulk of heptamerised Tat is secreted. Mice vaccinated with secreted Tat fused to IMX313 (pVAX-sTat-IMX313) developed higher titres of Tat-specific serum IgG, mucosal sIgA and cell-mediated immune (CMI) responses, and showed superior control of EcoHIV infection, a surrogate murine HIV challenge model, compared with animals vaccinated with other test vaccines. Given the crucial contribution of Tat to HIV-1 pathogenesis and the precedent of Tat-based DNA vaccines in conferring some level of protection in animal models, we believe that the virologic control demonstrated with this novel multimerised Tat vaccine highlights the promise of this vaccine candidate for humans. PMID:27358023

  15. A HIV-Tat/C4-binding protein chimera encoded by a DNA vaccine is highly immunogenic and contains acute EcoHIV infection in mice.

    PubMed

    Tomusange, Khamis; Wijesundara, Danushka; Gummow, Jason; Garrod, Tamsin; Li, Yanrui; Gray, Lachlan; Churchill, Melissa; Grubor-Bauk, Branka; Gowans, Eric J

    2016-01-01

    DNA vaccines are cost-effective to manufacture on a global scale and Tat-based DNA vaccines have yielded protective outcomes in preclinical and clinical models of human immunodeficiency virus (HIV), highlighting the potential of such vaccines. However, Tat-based DNA vaccines have been poorly immunogenic, and despite the administration of multiple doses and/or the addition of adjuvants, these vaccines are not in general use. In this study, we improved Tat immunogenicity by fusing it with the oligomerisation domain of a chimeric C4-binding protein (C4b-p), termed IMX313, resulting in Tat heptamerisation and linked Tat to the leader sequence of tissue plasminogen activator (TPA) to ensure that the bulk of heptamerised Tat is secreted. Mice vaccinated with secreted Tat fused to IMX313 (pVAX-sTat-IMX313) developed higher titres of Tat-specific serum IgG, mucosal sIgA and cell-mediated immune (CMI) responses, and showed superior control of EcoHIV infection, a surrogate murine HIV challenge model, compared with animals vaccinated with other test vaccines. Given the crucial contribution of Tat to HIV-1 pathogenesis and the precedent of Tat-based DNA vaccines in conferring some level of protection in animal models, we believe that the virologic control demonstrated with this novel multimerised Tat vaccine highlights the promise of this vaccine candidate for humans. PMID:27358023

  16. Therapeutic Use of Soluble Fas Ligand Ameliorates Acute and Recurrent Herpetic Stromal Keratitis in Mice

    PubMed Central

    Rogge, Megan; Yin, Xiao-Tang; Godfrey, Lisa; Lakireddy, Priya; Potter, Chloe A.; Del Rosso, Chelsea R.; Stuart, Patrick M.

    2015-01-01

    Purpose The present study was designed to test the therapeutic value of soluble FasL (sFasL) in an acute model of herpetic stromal keratitis (HSK) and, more importantly, a recurrent model of HSK using BALB/c, BALB-lpr, and National Institutes of Health (NIH) mice. Methods Mice were infected either acutely with the KOS strain of herpes simplex virus 1 (HSV-1) or latently with the McKrae strain of HSV-1. Acutely infected mice as well as ultraviolet-B (UV-B) reactivated mice (recurrent infection) were treated with sFasL, or soluble TNF-related apoptosis inducing ligand (sTRAIL), or BSA daily or 3 times/wk by using either a combination of subconjunctival injection and topical ointment, or with topical ointment alone. These mice then were evaluated for corneal opacity and neovascularization for 6 weeks. Results Following acute and recurrent HSV-1 infection, wild-type BALB/c mice treated with sFasL displayed significantly reduced incidence of corneal opacity and neovascularization compared to the control animals. However, BALB-lpr mice, which are deficient in Fas+ inflammatory cells, displayed no such differences in ocular disease, as expected. Latently infected NIH mice treated with sFasL displayed similar results. Flow cytometric analysis revealed that the corneal inflammatory infiltrate in those treated with sFasL was significantly less than in sTRAIL- or BSA-treated mice. Furthermore, corneas from sFasL-treated mice displayed relatively more cells undergoing apoptosis. Conclusions This study provides evidence that sFasL treatment has potential therapeutic benefit in reducing inflammatory infiltrate and neovascularization in primary and recurrent forms of HSK, and that it does so by augmenting the restriction of Fas+ inflammatory cells mediated by membrane FasL. PMID:26444718

  17. Dengue infection presenting as acute hypokalemic quadriparesis.

    PubMed

    Gupta, N; Garg, A; Chhabra, P

    2014-01-01

    Dengue infection is one of the most common viral hemorrhagic fevers seen in the tropical countries, including India. Its presentation varies from an acute self-resolving febrile illness to life-threatening hemorrhagic shock and multiorgan dysfunction leading to death. Neurological presentations are uncommon and limited to case reports only. Most common neurological manifestations being encephalitis, acute inflammatory demyelinating polyradiculoneuropathy, transverse myelitis, and acute disseminated encephalomyelitis.Hypokalemic quadriparesis as a presenting feature of dengue is extremely rare. Here, we report this case of a 33-year-old female, who presented with hypokalemic quadriparesis and was subsequently diagnosed as dengue infection. PMID:25121379

  18. Intensification of acute Trypanosoma cruzi myocarditis in BALB/c mice pretreated with low doses of cyclophosphamide or gamma irradiation.

    PubMed Central

    Silva, J. S.; Rossi, M. A.

    1990-01-01

    This study was carried out to examine the development of acute myocarditis in Trypanosoma cruzi-infected BALB/c mice after they were treated with low doses of cylophosphamide or gamma irradiation. It has been claimed that, in mice, such treatments temporarily interfere with the host-immune suppressor network, but cause no immunodepression. A severe extensive and diffuse acute myocarditis developed in the treated mice infected with T. cruzi, whereas a slight to moderate focal or occasionally diffuse acute myocarditis developed in control mice infected with T. cruzi. It is very likely that the transient abolition of T-suppressor activity facilitates the anti-myocardium immune response in the acute phase of experimental Chagas' disease in mice. Images Fig. 3 PMID:2138024

  19. Tsutsugamushi infection-associated acute rhabdomyolysis and acute renal failure.

    PubMed

    Young, Park Chi; Hae, Chung Choon; Lee, Kim Hyun; Hoon, Chung Jong

    2003-12-01

    Rhabdomyolysis is a rare complication that emerges in a variety of infectious diseases, such as tsutsugamushi infection. In this study, we report a 71-year-old female patient with tsutsugamushi infection who exhibiting rhabdomyolysis and acute renal failure. On admission, an eschar, which is characteristic of tsutsugamushi infection, was found on her right flank area. Moreover, her tsutsugamushi antibody titer was 1:40960. The elevated values of serum creatinine phosphokinase (CPK), aldolase, creatinine and dark brown urine secondary to myoglobinuria are consistent with indications of rhabdomyolysis and acute renal failure due to tsutsugamushi infection. Her health improved without any residual effects after treatment with doxycyclin and hydration with normal saline. PMID:14717236

  20. [Associated infections in acute bronchopulmonary infections in children].

    PubMed

    Lykova, E A; Vorob'ev, A A; Bokovoĭ, A G; Karazhas, N V; Evseeva, L F

    2003-01-01

    A total of 189 children with bacterial complications of the acute respiratory viral infection (ARVI)--primarily with pneumonia and bronchitis--were dynamically examined for typical and atypical pneumotropic causative agents of the infection process (Mycoplasma pneumoniae, Chlamydia spp., Streptococcus pneumoniae, Haemophilus influenzae, Pneumocystis carini, and Citomegalovirus). A high frequency rate of the associative infection involving mycoplasmas and pneumocysts was registered (45-50%); it was lower in the cases involving Chlamydias, hemophilic bacteria, pneumococcus, and cytomegalovirus--up to 25-30%. No sharp difference was found between the indices of an infection degree and those of an active clinical infectious process involving the same pneumotropic agent: the biggest difference was observed in Chlamydia infections (9.4%) and the lowest one--in mycoplasma infections (3%). A dynamic comparison of different classes of immunoglobulins revealed that, in acute bronchitis and pneumonias, the Chlamydia and cytomegalovirus infections are, primarily, of the persistent nature; the hemophilic and pneumocystic infections are of a mixed nature; and the pneumococcus one is of the acute nature. The Mycoplasma infection, which is more often encountered in pre-school children, is of the primary type with a trend towards a prolonged clinical course. All pneumonias had a typical clinical course; the clinical picture was compared in 128 patients with the etiological factor (including a description of characteristic symptoms). PMID:12861708

  1. Polyphasic innate immune responses to acute and chronic LCMV infection

    PubMed Central

    Norris, Brian A.; Uebelhoer, Luke S.; Nakaya, Helder I.; Price, Aryn A.; Grakoui, Arash; Pulendran, Bali

    2013-01-01

    Summary Resolution of acute and chronic viral infections requires activation of innate cells to initiate and maintain adaptive immune responses. Here we report that infection with acute Armstrong (ARM) or chronic Clone 13 (C13) strains of lymphocytic choriomeningitis virus (LCMV) led to two distinct phases of innate immune response. During the first 72hr of infection, dendritic cells upregulated activation markers, and stimulated anti-viral CD8+ T cells, independent of viral strain. Seven days after infection, there was an increase in Ly6Chi monocytic and Gr-1hi neutrophilic cells in lymphoid organs and blood. This expansion in cell numbers was enhanced and sustained in C13 infection, whereas it occurred only transiently with ARM infection. These cells resembled myeloid-derived suppressor cells, and potently suppressed T cell proliferation. The reduction of monocytic cells in Ccr2−/− mice or after Gr-1 antibody depletion enhanced anti-viral T cell function. Thus, innate cells have an important immunomodulatory role throughout chronic infection. PMID:23438822

  2. Exogenous interferon prolongs survival of rabies infected mice.

    PubMed

    Mehta, S; Roy, S; Mukherjee, S; Yadav, N; Patel, N; Chowdhary, A

    2015-09-01

    Rabies is an acute viral infection that causes encephalomyelitis in almost all warm blooded animals and is invariably fatal once the clinical signs appear. The present study was carried out to assess the effect of recombinant human interferon alpha (rhIFN α-2A) treatment on the survival of rabies infected mice and its correlation with cytokines expression. The gene expression of TNF-α and IL-6 was measured by SYBR Green Real Time PCR for two groups-"Pre-exposure" (mice were inoculated with rhIFN α-2A prior to rabies infection) and "Post-exposure" (mice were inoculated with rhIFN α-2A post rabies virus infection). Delayed mortality was observed in interferon treated infected groups. In addition, statistically significant decrease (P < 0.0001) in the expression of TNF-α and IL-6 was observed, both in the pre-exposure and post-exposure groups. These findings indicate that modulation of cytokine secretion using exogenous biologicals such as rhIFN may offer novel therapeutic approaches to treat diseases such as rabies. PMID:26396983

  3. Interferon-γ-Induced Nitric Oxide Causes Intrinsic Intestinal Denervation in Trypanosoma cruzi-Infected Mice

    PubMed Central

    Arantes, Rosa M.E.; Marche, Homero H.F.; Bahia, Maria T.; Cunha, Fernando Q.; Rossi, Marcos A.; Silva, João S.

    2004-01-01

    In this study, the role of nitric oxide (NO) in neuronal destruction during acute-phase Trypanosoma cruzi infection was evaluated in male C57BL/6 (WT, wild-type) mice and knockout mice [inducible nitric oxide synthase (iNOS)−/− and interferon (IFN)−/−]. Selected animals were infected by intraperitoneal injection of 100 trypomastigote forms of the Y strain of T. cruzi. Others were injected intraperitoneally with an equal volume of saline solution and served as controls. Our findings support those of previous studies regarding myenteric denervation in acute-phase T. cruzi infection. In addition, we clearly demonstrate that, despite the fact that parasite nests and similar inflammatory infiltrate in the intestinal wall were more pronounced in infected iNOS−/− mice than in infected WT mice, the former presented no reduction in myenteric plexus neuron numbers. Neuronal nerve profile expression, as revealed by the general nerve marker PGP 9.5, was preserved in all knockout animals. Infected IFN−/− mice suffered no significant neuronal loss and there was no inflammatory infiltrate in the intestinal wall. On days 5 and 10 after infection, iNOS activity was greater in infected WT mice than in controls, whereas iNOS activity in infected knockout mice remained unchanged. These findings clearly demonstrate that neuronal damage does not occur in NO-impaired infected knockout mice, regardless of whether inflammatory infiltrate is present (iNOS−/−) or absent (IFN−/−). In conclusion, our observations strongly indicate that myenteric denervation in acute-phase T. cruzi infection is because of IFN-γ-elicited NO production resulting from iNOS activation in the inflammatory foci along the intestinal wall. PMID:15039223

  4. Kocuria kristinae infection associated with acute cholecystitis

    PubMed Central

    Ma, Edmond SK; Wong, Chris LP; Lai, Kristi TW; Chan, Edmond CH; Yam, WC; Chan, Angus CW

    2005-01-01

    Background Kocuria, previously classified into the genus of Micrococcus, is commonly found on human skin. Two species, K. rosea and K. kristinae, are etiologically associated with catheter-related bacteremia. Case presentation We describe the first case of K. kristinae infection associated with acute cholecystitis. The microorganism was isolated from the bile of a 56-year old Chinese man who underwent laparoscopic cholecystectomy. He developed post-operative fever that resolved readily after levofloxacin treatment. Conclusion Our report of K. kristinae infection associated with acute cholecystitis expands the clinical spectrum of infections caused by this group of bacteria. With increasing number of recent reports describing the association between Kocuria spp. and infectious diseases, the significance of their isolation from clinical specimens cannot be underestimated. A complete picture of infections related to Kocuria spp. will have to await the documentation of more clinical cases. PMID:16029488

  5. Studies of retroviral infection in humanized mice

    PubMed Central

    Marsden, Matthew D.; Zack, Jerome A.

    2015-01-01

    Many important aspects of human retroviral infections cannot be fully evaluated using only in vitro systems or unmodified animal models. An alternative approach involves the use of humanized mice, which consist of immunodeficient mice that have been transplanted with human cells and/or tissues. Certain humanized mouse models can support robust infection with human retroviruses including different strains of human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV). These models have provided wide-ranging insights into retroviral biology, including detailed information on primary infection, in vivo replication and pathogenesis, latent/persistent reservoir formation, and novel therapeutic interventions. Here we describe the humanized mouse models that are most commonly utilized to study retroviral infections, and outline some of the important discoveries that these models have produced during several decades of intensive research. PMID:25680625

  6. [The Most Common Acute Gastrointestinal Infections].

    PubMed

    Greuter, Thomas; Magdeburg, Bernhard

    2015-10-14

    Acute gastrointestinal infections and diarrhea with vomiting as its main presentation are a frequently encountered entity in an outpatient setting. Due to a mostly self-limiting disease course a diagnostic work-up is often futile. Viral infections caused by Noro- or Rotavirus are most frequent, while bacterial infections are second line due to high hygienic standards in developed countries. In an inpatient setting and after a precedent antibiotic treatment one should think of clostridium difficile. Traveler’s diarrhea represents a special case, with most of the cases caused by enterovirulent E. coli. In this mini review we describe the most important pathogens in detail. PMID:26463905

  7. Characterization of Lethal Zika Virus Infection in AG129 Mice

    PubMed Central

    Walker, Emma C.; Larkin, Katrina E.; Camacho, Erwin; Osorio, Jorge E.

    2016-01-01

    Background Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever, which often is accompanied by maculopapular rash, headache, and myalgia. During the current outbreak in South America, ZIKV infection during pregnancy has been hypothesized to cause microcephaly and other diseases. The detection of ZIKV in fetal brain tissue supports this hypothesis. Because human infections with ZIKV historically have remained sporadic and, until recently, have been limited to small-scale epidemics, neither the disease caused by ZIKV nor the molecular determinants of virulence and/or pathogenicity have been well characterized. Here, we describe a small animal model for wild-type ZIKV of the Asian lineage. Methodology/Principal Findings Using mice deficient in interferon α/β and Ɣ receptors (AG129 mice), we report that these animals were highly susceptible to ZIKV infection and disease, succumbing within seven to eight days. Rapid viremic dissemination was observed in visceral organs and brain; but only was associated with severe pathologies in the brain and muscle. Finally, these results were consistent across challenge routes, age of mice, and inoculum doses. These data represent a mouse model for ZIKV that is not dependent on adapting ZIKV to intracerebral passage in mice. Conclusions/Significance Foot pad injection of AG129 mice with ZIKV represents a biologically relevant model for studying ZIKV infection and disease development following wild-type virus inoculation without the requirement for adaptation of the virus or intracerebral delivery of the virus. This newly developed Zika disease model can be exploited to identify determinants of ZIKV virulence and reveal molecular mechanisms that control the virus-host interaction, providing a framework for rational design of acute phase therapeutics and for vaccine efficacy testing. PMID:27093158

  8. Infectivity of pestivirus following persistence of acute infection.

    PubMed

    Collins, Margaret E; Heaney, Judith; Thomas, Carole J; Brownlie, Joe

    2009-09-18

    Bovine viral diarrhoea virus (BVDV) is an endemic pathogen worldwide and eradication strategies focus on the identification and removal of persistently infected (PI) animals arising after in utero infection. Despite this, acute infections with BVDV can persist for months or years after the removal of the PI source despite repeated screening for PIs and tight biosecurity measures. Recent evidence for a prolonged duration of viraemia in the testicles of bulls following acute BVDV infection suggests the possibility of a form of chronic persistence that may more closely resemble the persistence strategies of hepatitis C virus (HCV). To investigate the potential for virus transmission from infected and recovered cattle to virus naïve hosts we established an acute infection of 5 BVDV-naïve calves and monitored animals over 129 days. Infectious BVDV was detected in white blood cells between days 3 and 7 post-challenge. The animals seroconverted by day 21 post-infection and subsequently were apparently immune and free from infectious virus and viral antigen. Animals were further monitored and purified white blood cells were stimulated in vitro with phytohaemagglutinin A (PHA) during which time BVDV RNA was detected intermittently. Ninety-eight days following challenge, blood was transferred from these apparently virus-free and actively immune animals to a further group of 5 BVDV-naïve calves and transmission of infection was achieved. This indicates that BVDV-infected, recovered and immune animals have the potential to remain infectious for BVDV-naïve cohorts for longer than previously demonstrated. PMID:19443139

  9. Sarcocystis neurona infection in gamma interferon gene knockout (KO) mice: comparative infectivity of sporocysts in two strains of KO mice, effect of trypsin digestion on merozoite viability, and infectivity of bradyzoites to KO mice and cell culture.

    PubMed

    Dubey, J P; Sundar, N; Kwok, O C H; Saville, W J A

    2013-09-01

    The protozoan Sarcocystis neurona is the primary cause of Equine Protozoal Myeloencephalitis (EPM). EPM or EPM-like illness has been reported in horses, sea otters, and several other mammals. The gamma interferon gene knockout (KO) mouse is often used as a model to study biology and discovery of new therapies against S. neurona because it is difficult to induce clinical EPM in other hosts, including horses. In the present study, infectivity of three life cycle stages (merozoites, bradyzoites, sporozoites) to KO mice and cell culture was studied. Two strains of KO mice (C57-black, and BALB/c-derived, referred here as black or white) were inoculated orally graded doses of S. neurona sporocysts; 12 sporocysts were infective to both strains of mice and all infected mice died or became ill within 70 days post-inoculation. Although there was no difference in infectivity of sporocysts to the two strains of KO mice, the disease was more severe in black mice. S. neurona bradyzoites were not infectious to KO mice and cell culture. S. neurona merozoites survived 120 min incubation in 0.25% trypsin, indicating that trypsin digestion can be used to recover S. neurona from tissues of acutely infected animals. PMID:23375195

  10. CD8+ T cells control Ross River virus infection in musculoskeletal tissues of infected mice.

    PubMed

    Burrack, Kristina S; Montgomery, Stephanie A; Homann, Dirk; Morrison, Thomas E

    2015-01-15

    Ross River virus (RRV), chikungunya virus, and related alphaviruses cause debilitating polyarthralgia and myalgia. Mouse models of RRV and chikungunya virus have demonstrated a role for the adaptive immune response in the control of these infections. However, questions remain regarding the role for T cells in viral control, including the magnitude, location, and dynamics of CD8(+) T cell responses. To address these questions, we generated a recombinant RRV expressing the H-2(b)-restricted glycoprotein 33 (gp33) determinant derived from the glycoprotein of lymphocytic choriomeningitis virus. Using tetramers, we tracked gp33-specific CD8(+) T cells during RRV-lymphocytic choriomeningitis virus infection. We found that acute RRV infection induces activation of CD8(+) T cell responses in lymphoid and musculoskeletal tissues that peak from 10-14 d postinoculation, suggesting that CD8(+) T cells contribute to control of acute RRV infection. Mice genetically deficient for CD8(+) T cells or wild-type mice depleted of CD8(+) T cells had elevated RRV loads in skeletal muscle tissue, but not joint-associated tissues, at 14 d postinoculation, suggesting that the ability of CD8(+) T cells to control RRV infection is tissue dependent. Finally, adoptively transferred T cells were capable of reducing RRV loads in skeletal muscle tissue of Rag1(-/-) mice, indicating that T cells can contribute to the control of RRV infection in the absence of B cells and Ab. Collectively, these data demonstrate a role for T cells in the control of RRV infection and suggest that the antiviral capacity of T cells is controlled in a tissue-specific manner. PMID:25488988

  11. CD8+ T cells control Ross River virus infection in musculoskeletal tissues of infected mice

    PubMed Central

    Burrack, Kristina S.; Montgomery, Stephanie A.; Homann, Dirk; Morrison, Thomas E.

    2014-01-01

    Ross River virus (RRV), chikungunya virus (CHIKV), and related alphaviruses cause debilitating polyarthralgia and myalgia. Mouse models of RRV and CHIKV have demonstrated a role for the adaptive immune response in the control of these infections. However, questions remain regarding the role for T cells in viral control, including the magnitude, location, and dynamics of CD8+ T cell responses. To address these questions, we generated a recombinant RRV expressing the H-2b-restricted gp33 determinant derived from the glycoprotein (gp) of lymphocytic choriomeningitis virus (LCMV) (“RRV-LCMV”). Utilizing tetramers, we tracked gp33-specific CD8+ T cells during RRV-LCMV infection. We found that acute RRV infection induces activation of CD8+ T cell responses in lymphoid and musculoskeletal tissues that peak from 10 to 14 days post-inoculation (dpi), suggesting that CD8+ T cells contribute to control of acute RRV infection. Mice genetically deficient for CD8+ T cells or wild-type mice depleted of CD8+ T cells had elevated RRV loads in skeletal muscle tissue, but not joint-associated tissues, at 14 dpi, suggesting that the ability of CD8+ T cells to control RRV infection is tissue-dependent. Finally, adoptively transferred T cells were capable of reducing RRV loads in skeletal muscle tissue of Rag1−/− mice, indicating that T cells can contribute to the control of RRV infection in the absence of B cells and antibody. Collectively, these data demonstrate a role for T cells in the control of RRV infection and suggest that the antiviral capacity of T cells is controlled in a tissue-specific manner. PMID:25488988

  12. Pulmonary embolism and acute cytomegalovirus infection in an immunocompetent patient.

    PubMed

    Del Borgo, Cosmo; Gianfreda, Romina; Belvisi, Valeria; Citton, Rita; Soscia, Fabrizio; Notarianni, Ermanno; Tieghi, Tiziana; Mastroianni, Claudio Maria

    2010-12-01

    A case of an immunocompetent man with acute CMV infection associated with a pulmonary embolism is described. Acute CMV infection could be a risk factor for developing thromboembolism. Pulmonary embolism should be included in differential diagnosis in patients with acute CMV infections and pulmonary opacities. PMID:21196823

  13. When to consider acute HIV infection in the differential diagnosis.

    PubMed

    Grimes, Richard M; Hardwicke, Robin L; Grimes, Deanna E; DeGarmo, D Sean

    2016-01-16

    Patients presenting with fever, pharyngitis, and lymphadenopathy are likely to have mononucleosis; however, patients with acute HIV infection may present with similar symptoms. Acute HIV infection should be considered as a differential diagnosis if test results for mononucleosis are negative. This article describes when to order HIV testing and discusses the importance of early intervention for acute HIV infection. PMID:26678418

  14. Swaddling and acute respiratory infections.

    PubMed

    Yurdakok, K; Yavuz, T; Taylor, C E

    1990-07-01

    In Turkey and China the ancient practice of swaddling is still commonly practiced. Both countries have extremely high rates of pneumonia, especially during the neonatal period. Preliminary evidence on the possibility that swaddling may interfere with normal respiratory function and thereby predispose to pneumonia was gathered in a teaching health center in Ankara. Babies who had been swaddled for at least three months were four times more likely to have developed pneumonia (confirmed radiologically) and upper respiratory infections than babies who were unswaddled. These preliminary findings were highly significant and are being followed up by further studies. PMID:2356917

  15. Macrophages Are the Determinant of Resistance to and Outcome of Nonlethal Babesia microti Infection in Mice

    PubMed Central

    Terkawi, Mohamad Alaa; Cao, Shinuo; Herbas, Maria S.; Nishimura, Maki; Li, Yan; Moumouni, Paul Franck Adjou; Pyarokhil, Asadullah Hamid; Kondoh, Daisuke; Kitamura, Nobuo; Nishikawa, Yoshifumi; Kato, Kentaro; Yokoyama, Naoaki; Zhou, Jinlin; Suzuki, Hiroshi; Igarashi, Ikuo

    2014-01-01

    In the present study, we examined the contributions of macrophages to the outcome of infection with Babesia microti, the etiological agent of human and rodent babesiosis, in BALB/c mice. Mice were treated with clodronate liposome at different times during the course of B. microti infection in order to deplete the macrophages. Notably, a depletion of host macrophages at the early and acute phases of infection caused a significant elevation of parasitemia associated with remarkable mortality in the mice. The depletion of macrophages at the resolving and latent phases of infection resulted in an immediate and temporal exacerbation of parasitemia coupled with mortality in mice. Reconstituting clodronate liposome-treated mice at the acute phase of infection with macrophages from naive mice resulted in a slight reduction in parasitemia with improved survival compared to that of mice that received the drug alone. These results indicate that macrophages play a crucial role in the control of and resistance to B. microti infection in mice. Moreover, analyses of host immune responses revealed that macrophage-depleted mice diminished their production of Th1 cell cytokines, including gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Furthermore, depletion of macrophages at different times exaggerated the pathogenesis of the infection in deficient IFN-γ−/− and severe combined immunodeficiency (SCID) mice. Collectively, our data provide important clues about the role of macrophages in the resistance and control of B. microti and imply that the severity of the infection in immunocompromised patients might be due to impairment of macrophage function. PMID:25312951

  16. DSCG reduces RSV-induced illness in RSV-infected mice.

    PubMed

    Hashimoto, Koichi; Mori, Syuichi; Hashimoto, Yuko; Kaneko, Hisatoshi; Ishibashi, Kei; Ishioka, Ken; Kawasaki, Yukihiko; Peebles, Ray Stokes; Munakata, Mitsuru; Hosoya, Mitsuaki; Suzutani, Tatsuo

    2009-02-01

    Respiratory syncytial virus (RSV) is one of the pathogens generally associated with the common cold, lower respiratory infection, and exacerbation of asthma. Disodium cromoglycate (DSCG) is a safe and widely used drug for the prevention of bronchial asthma and allergic rhinitis attacks. The effect of DSCG on acute upper respiratory tract viral infections remains controversial. The purpose of the study was to investigate the effects of DSCG on parameters of RSV induced-illness. Using a well-characterized murine model of RSV infection, the effect of DSCG on RSV-induced illness was evaluated by body weight, respiratory function, viral replication, level of IFN-gamma in lungs, serology, and histopathology. Mice treated with DSCG were protected against RSV-induced weight loss. The baseline Penh in RSV-infected mice treated with DSCG was less than that in mice treated with saline. In methacholine challenge, the increase in Penh in RSV-infected mice treated with DSCG was suppressed to the same level as that in the mock-infected group. Further, there were no differences in viral replication between the mice treated with DSCG and those treated with saline, and the level of inflammation observed in the lungs in RSV-infected mice treated with DSCG was not as severe as that in mice treated with saline. These findings indicate that DSCG may be an effective agent for the prevention of RSV induced disease and the relief of symptoms of RSV infection. PMID:19107959

  17. Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection

    PubMed Central

    Li, Sam X.; Barrett, Bradley S.; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J.; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L.

    2016-01-01

    Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation. PMID:26846717

  18. Acute Systemic Infection with Dengue Virus Leads to Vascular Leakage and Death through Tumor Necrosis Factor-α and Tie2/Angiopoietin Signaling in Mice Lacking Type I and II Interferon Receptors

    PubMed Central

    Limkittikul, Kriengsak; Sakai, Yusuke; Takakura, Nobuyuki; Saijo, Masayuki

    2016-01-01

    Severe dengue is caused by host responses to viral infection, but the pathogenesis remains unknown. This is, in part, due to the lack of suitable animal models. Here, we report a non-mouse-adapted low-passage DENV-3 clinical isolate, DV3P12/08, derived from recently infected patients. DV3P12/08 caused a lethal systemic infection in type I and II IFN receptor KO mice (IFN-α/β/γR KO mice), which have the C57/BL6 background. Infection with DV3P12/08 induced a cytokine storm, resulting in severe vascular leakage (mainly in the liver, kidney and intestine) and organ damage, leading to extensive hemorrhage and rapid death. DV3P12/08 infection triggered the release of large amounts of TNF-α, IL-6, and MCP-1. Treatment with a neutralizing anti-TNF-α antibody (Ab) extended survival and reduced liver damage without affecting virus production. Anti-IL-6 neutralizing Ab partly prolonged mouse survival. The anti-TNF-α Ab suppressed IL-6, MCP-1, and IFN-γ levels, suggesting that the severe response to infection was triggered by TNF-α. High levels of TNF-α mRNA were expressed in the liver and kidneys, but not in the small intestine, of infected mice. Conversely, high levels of IL-6 mRNA were expressed in the intestine. Importantly, treatment with Angiopoietin-1, which is known to stabilize blood vessels, prolonged the survival of DV3P12/08-infected mice. Taken together, the results suggest that an increased level of TNF-α together with concomitant upregulation of Tie2/Angiopoietin signaling have critical roles in severe dengue infection. PMID:26844767

  19. Persistent hepatitis C virus infections and hepatopathological manifestations in immune-competent humanized mice

    PubMed Central

    Chen, Jizheng; Zhao, Yang; Zhang, Chao; Chen, Hairong; Feng, Jin; Chi, Xiumei; Pan, Yu; Du, Jun; Guo, Min; Cao, Huang; Chen, Honghe; Wang, Zilong; Pei, Rongjuan; Wang, Qian; Pan, Lei; Niu, Junqi; Chen, Xinwen; Tang, Hong

    2014-01-01

    The majority of hepatitis C virus (HCV) infection develops chronic infection, which causes steatosis, cirrhosis and hepatocellular carcinoma. However, understanding HCV chronicity and pathogenesis is hampered by its narrow host range, mostly restricted to human and chimpanzee. Recent endeavour to infect a variety of humanized mice has not been able to achieve persistent HCV infection unless the essential innate immune responsive genes are knocked out. Nevertheless, such immune-compromised humanized mice still lacked HCV infection-induced hepatopathogenesis. Here we report that transgenic mice in ICR background harboring both human CD81 and occludin genes (C/OTg) are permissive to HCV infection at a chronicity rate comparable to humans. In this mouse model, HCV accomplishes its replication cycle, leading to sustained viremia and infectivity for more than 12 months post infection with expected fibrotic and cirrhotic progression. Host factors favorable for HCV replication, and inadequate innate immune-response may contribute to the persistence. Lastly, NS3/4 protease inhibitor telaprevir can effectively inhibit de novo RNA synthesis and acute HCV infection of C/OTg mice. Thus, chronic HCV infection with complete replication cycle and hepatopathologic manifestations is recapitulated, for the first time, in immune-competent mice. This model will open a new venue to study the mechanisms of chronic hepatitis C and develop better treatments. PMID:25155355

  20. Efficacy of the Bunium persicum (Boiss) Essential Oil against Acute Toxoplasmosis in Mice Model

    PubMed Central

    TAVAKOLI KARESHK, Amir; KEYHANI, Amir; MAHMOUDVAND, Hossein; TAVAKOLI OLIAEI, Razieh; ASADI, Arash; ANDISHMAND, Moazameh; AZZIZIAN, Hossein; BABAEI, Zahra; ZIA-ALI, Naser

    2015-01-01

    Background: We evaluated the in vivo activity of Bunium persicum (Boiss) essential oil on infected mice with acute toxoplasmosis. Methods: To evaluate prophylactic effects, male NMRI mice received B. persicum essential oil at the concentrations of 0.05 and 0.1 mL/kg for 14 days. After 24 h mice were infected intraperitonealy with 1×104 tachyzoites of T. gondii, RH strain. In order to investigate therapeutic effects, mice were infected and then received B. persicum oil at the concentrations of 0.05 and 0.1 ml/kg two times a day for 5 days. The time/mean time of death in all infected mice and the number of tachyzoites from infected mice were recorded. Results: The time/mean time of death of infected mice was 8 and 9 days after oral administration of B. persicum oil at the concentration of 0.05 and 0.1 mL/kg, respectively (P<0.05). In contrast, the time/mean time of death control group was 5 days. In addition, B. persicum significantly reduced the mean number of tachyzoites compared with control group. The time/mean time of death of infected mice was 6 and 7 days after oral administration of B. persicum essential oil at the concentration of 0.05 and 0.1 mL/kg, respectively. In contrast, the time/mean time of death control group was 5 days. B. persicum especially at the concentration of 0.1 ml/kg significantly reduced the mean number of tachyzoites compared with control group. Conclusion: The results showed the potential of B. persicum essential oil as a natural source for the production of new prophylactic agent for use in toxoplasmosis. PMID:26811730

  1. Proteomic Profiling of Mouse Liver following Acute Toxoplasma gondii Infection.

    PubMed

    He, Jun-Jun; Ma, Jun; Elsheikha, Hany M; Song, Hui-Qun; Zhou, Dong-Hui; Zhu, Xing-Quan

    2016-01-01

    Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while the top 10 transcription factors of downregulated genes were Hnf4A, Ewsr1, Fli1, Hnf4g, Nr2f1, Pparg, Rxra, Hnf1A, Foxa1 and Foxo1. These findings indicate global reprogramming of the metabolism of the mouse liver after acute T. gondii infection. Functional characterization of the altered proteins may enhance understanding of the host responses to T. gondii infection and lead to the identification of new therapeutic targets. PMID:27003162

  2. Proteomic Profiling of Mouse Liver following Acute Toxoplasma gondii Infection

    PubMed Central

    He, Jun-Jun; Ma, Jun; Elsheikha, Hany M.; Song, Hui-Qun; Zhou, Dong-Hui; Zhu, Xing-Quan

    2016-01-01

    Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while the top 10 transcription factors of downregulated genes were Hnf4A, Ewsr1, Fli1, Hnf4g, Nr2f1, Pparg, Rxra, Hnf1A, Foxa1 and Foxo1. These findings indicate global reprogramming of the metabolism of the mouse liver after acute T. gondii infection. Functional characterization of the altered proteins may enhance understanding of the host responses to T. gondii infection and lead to the identification of new therapeutic targets. PMID:27003162

  3. High Pathogenicity of Wild-Type Measles Virus Infection in CD150 (SLAM) Transgenic Mice

    PubMed Central

    Sellin, Caroline I.; Davoust, Nathalie; Guillaume, Vanessa; Baas, Dominique; Belin, Marie-Françoise; Buckland, Robin; Wild, T. Fabian; Horvat, Branka

    2006-01-01

    Measles virus (MV) infection causes an acute childhood disease, associated in certain cases with infection of the central nervous system and development of a severe neurological disease. We have generated transgenic mice ubiquitously expressing the human protein SLAM (signaling lymphocytic activation molecule), or CD150, recently identified as an MV receptor. In contrast to all other MV receptor transgenic models described so far, in these mice infection with wild-type MV strains is highly pathogenic. Intranasal infection of SLAM transgenic suckling mice leads to MV spread to different organs and the development of an acute neurological syndrome, characterized by lethargy, seizures, ataxia, weight loss, and death within 3 weeks. In addition, in this model, vaccine and wild-type MV strains can be distinguished by virulence. Furthermore, intracranial MV infection of adult transgenic mice generates a subclinical infection associated with a high titer of MV-specific antibodies in the serum. Finally, to analyze new antimeasles therapeutic approaches, we created a recombinant soluble form of SLAM and demonstrated its important antiviral activity both in vitro and in vivo. Taken together, our results show the high susceptibility of SLAM transgenic mice to MV-induced neurological disease and open new perspectives for the analysis of the implication of SLAM in the neuropathogenicity of other morbilliviruses, which also use this molecule as a receptor. Moreover, this transgenic model, in allowing a simple readout of the efficacy of an antiviral treatment, provides unique experimental means to test novel anti-MV preventive and therapeutic strategies. PMID:16775330

  4. Helminth infections predispose mice to pneumococcal pneumonia but not to other pneumonic pathogens.

    PubMed

    Apiwattanakul, Nopporn; Thomas, Paul G; Kuhn, Raymond E; Herbert, De'Broski R; McCullers, Jonathan A

    2014-10-01

    Pneumonia is the leading killer of children worldwide. Here, we report that helminth-infected mice develop fatal pneumonia when challenged with Streptococcus pneumoniae. Mice were chronically infected with either the flatworm Taenia crassiceps or the roundworm Heligmosomoides polygyrus. Upon challenge with a pneumonic type 3 strain of S. pneumoniae (A66.1), the worm-infected mice developed pneumonia at a rate and to a degree higher than age-matched control mice as measured by bioluminescent imaging and lung titers. This predisposition to pneumonia appears to be specific to S. pneumoniae, as worm-infected mice did not show evidence of increased morbidity when challenged with a lethal dose of influenza virus or sublethal doses of Staphylococcus aureus or Listeria monocytogenes. The defect was also present when worm-infected mice were challenged with a type 2 sepsis-causing strain (D39); an increased rate of pneumonia, decreased survival, and increased lung and blood titers were found. Pneumococcal colonization and immunity against acute otitis media were unaffected. Anti-helminthic treatment in the H. polygyrus model reversed this susceptibility. We conclude that helminth coinfection predisposes mice to fatal pneumococcal pneumonia by promoting increased outgrowth of bacteria in the lungs and blood. These data have broad implications for the prevention and treatment for pneumonia in the developing world, where helminth infections are endemic and pneumococcal pneumonia is common. PMID:24952091

  5. Impact of Benznidazole on Infection Course in Mice Experimentally Infected with Trypanosoma cruzi I, II, and IV

    PubMed Central

    Gruendling, Ana Paula; Massago, Miyoko; Teston, Ana Paula M.; Monteiro, Wuelton M.; Kaneshima, Edilson N.; Araújo, Silvana M.; Gomes, Mônica L.; Barbosa, Maria das Graças V.; Toledo, Max Jean O.

    2015-01-01

    American trypanosomiasis is an emerging zoonosis in the Brazilian Amazon. Studies on benznidazole (BZ) chemotherapy with Trypanosoma cruzi from this region have great relevance, given the different discrete typing units (DTUs) that infect humans in the Amazon and other regions of Brazil. We performed a parasitological, histopathological, and molecular analysis of mice inoculated with strains of T. cruzi I, II, and IV that were BZ-treated during the acute phase of infection. Groups of Swiss mice were inoculated; 13 received oral BZ, whereas the other 13 comprised the untreated controls. Unlike parasitemia, the infectivity and mortality did not vary among the DTUs. Trypanosoma cruzi DNA was detected in all tissues analyzed and the proportion of organs parasitized varied with the parasite DTU. The BZ treatment reduced the most parasitological parameters, tissue parasitism and the inflammatory processes at all infection stages and for all DTUs. However, the number of significant reductions varied according to the DTU and infection phase. PMID:25940197

  6. Management of infection in acute pancreatitis.

    PubMed

    Hartwig, Werner; Werner, Jens; Uhl, Waldemar; Büchler, Markus W

    2002-01-01

    The clinical course of acute pancreatitis varies from a mild, transitory illness to a severe, rapidly fatal disease. In about 80% to 90% of cases pancreatitis presents as a mild, self-limiting disease with low morbidity and mortality. Unlike mild pancreatitis, necrotizing pancreatitis develops in about 15% of patients, with infection of pancreatic and peripancreatic necrosis representing the single most important risk factor for a fatal outcome. Infection of pancreatic necrosis in the natural course develops in the second and third week after onset of the disease and is reported in 40% to 70% of patients with necrotizing pancreatitis. Just recently, prevention of infection by prophylactic antibiotic treatment and assessment of the infection status of pancreatic necrosis by fine-needle aspiration have been established in the management of severe pancreatitis. Because medical treatment alone will result in a mortality rate of almost 100% in patients with signs of local and systemic septic complications, patients with infected necrosis must undergo surgical intervention, which consists of an organ-preserving necrosectomy combined with a postoperative closed lavage concept that maximizes further evacuation of infected debris and exudate. However, intensive care treatment, including prophylactic antibiotics, reduces the infection rate and delays the need for surgery in most patients until the third or fourth week after the onset of symptoms. At that time, debridement of necrosis is technically easier to perform, due to better demarcation between viable and necrotic tissue compared with necrosectomy earlier in the disease. In contrast, surgery is rarely needed in the presence of sterile pancreatic necrosis. In those patients the conservative approach is supported by the present data. PMID:12483263

  7. Sexual dimorphism in lung function responses to acute influenza A infection

    PubMed Central

    Larcombe, Alexander N.; Foong, Rachel E.; Bozanich, Elizabeth M.; Berry, Luke J.; Garratt, Luke W.; Gualano, Rosa C.; Jones, Jessica E.; Dousha, Lovisa F.; Zosky, Graeme R.; Sly, Peter D.

    2011-01-01

    Please cite this paper as: Larcombe et al. (2011) Sexual dimorphism in lung function responses to acute influenza A infection. Influenza and Other Respiratory Viruses 5(5), 334–342. Background  Males are generally more susceptible to respiratory infections; however, there are few data on the physiological responses to such infections in males and females. Objectives  To determine whether sexual dimorphism exists in the physiological/inflammatory responses of weanling and adult BALB/c mice to influenza. Methods  Weanling and adult mice of both sexes were inoculated with influenza A or appropriate control solution. Respiratory mechanics, responsiveness to methacholine (MCh), viral titre and bronchoalveolar lavage (BAL) cellular inflammation/cytokines were measured 4 (acute) and 21 (resolution) days post‐inoculation. Results  Acute infection impaired lung function and induced hyperresponsiveness and cellular inflammation in both sexes at both ages. Males and females responded differently with female mice developing greater abnormalities in tissue damping and elastance and greater MCh responsiveness at both ages. BAL inflammation, cytokines and lung viral titres were similar between the sexes. At resolution, all parameters had returned to baseline levels in adults and weanling males; however, female weanlings had persisting hyperresponsiveness. Conclusions  We identified significant differences in the physiological responses of male and female mice to infection with influenza A, which occurred in the absence of variation in viral titre and cellular inflammation. PMID:21668688

  8. Acute stress affects the physiology and behavior of allergic mice.

    PubMed

    Sutherland, M A; Shome, G P; Hulbert, L E; Krebs, N; Wachtel, M; McGlone, J J

    2009-09-01

    Physical and psychological stressors have been implicated in acute asthma exacerbation. The objective of the current study was to determine the effects of forced swimming stress (FST) on allergic pulmonary inflammation in BALB/c mice. Eighty female mice were allocated to one of four treatments arranged in a 2 x 2 factorial consisting of two levels of allergy and two levels of stress. The effects of stress and allergy were assessed by examination of cytokines and leukocyte differentials in the bronchoalveolar lavage fluid, corticosterone and immunoglobulin (Ig) E in the plasma, leukocyte differentials in the peripheral blood, natural killer cytotoxicity, and histopathology of the lungs. Behavior was recorded during the FST. Stress and allergy increased plasma corticosterone in mice. Allergy increased IgE concentrations and pulmonary inflammation. Interleukin-4 was greater among allergic stressed and non-stressed mice and stressed, non-allergic mice compared with non-stressed, non-allergic mice. Interleukin-5 (IL-5) and 6 (IL-6) were greater among allergic stressed and non-stressed mice compared with non-allergic mice. Interleukin-5 and 6 were reduced among stressed-allergic mice compared with non-stressed, allergic mice. Stress and allergy shifted mice towards a T-helper 2 response as shown by increased interleukin-4. Stress reduced IL-5 and IL-6 in allergic mice but not non-allergic mice. Pulmonary inflammation was not reduced among allergic stressed mice in spite of elevated glucocorticoids. Mice induced to be allergic responded to FST differently than non-allergic mice. Our findings suggest that stress induces a differential response among allergic and non-allergic mice. PMID:19527741

  9. Acute encephalitis as initial presentation of primary HIV infection.

    PubMed

    Nzwalo, Hipólito; Añón, Rosário Pazos; Àguas, Maria João

    2012-01-01

    Acute encephalitis is a life-threatening condition. A wide variety of infectious agents are implicated and in many patients no cause is found. HIV acute seroconversion illness can rarely present as acute encephalitis. Although most experts agree in starting antiretroviral treatment in severe acute HIV infection, the evidence of the benefits are still lacking. The authors report a case of severe acute encephalitis as a primary presentation of HIV infection in which introduction of highly active antiretroviral treatment resulted in clinical recovery. This case highlights the need to consider HIV infection in the differential diagnosis of treatable viral encephalitis. PMID:22761210

  10. Lupus-Prone Mice Fail to Raise Antigen-Specific T Cell Responses to Intracellular Infection

    PubMed Central

    Lieberman, Linda A.; Tsokos, George C.

    2014-01-01

    Systemic lupus erythematosus (SLE) is characterized by multiple cellular abnormalities culminating in the production of autoantibodies and immune complexes, resulting in tissue inflammation and organ damage. Besides active disease, the main cause of morbidity and mortality in SLE patients is infections, including those from opportunistic pathogens. To understand the failure of the immune system to fend off infections in systemic autoimmunity, we infected the lupus-prone murine strains B6.lpr and BXSB with the intracellular parasite Toxoplasma gondii and survival was monitored. Furthermore, mice were sacrificed days post infection and parasite burden and cellular immune responses such as cytokine production and cell activation were assessed. Mice from both strains succumbed to infection acutely and we observed greater susceptibility to infection in older mice. Increased parasite burden and a defective antigen-specific IFN-gamma response were observed in the lupus-prone mice. Furthermore, T cell:dendritic cell co-cultures established the presence of an intrinsic T cell defect responsible for the decreased antigen-specific response. An antigen-specific defect in IFN- gamma production prevents lupus-prone mice from clearing infection effectively. This study reveals the first cellular insight into the origin of increased susceptibility to infections in SLE disease and may guide therapeutic approaches. PMID:25360768

  11. Thrombosis associated with acute cytomegalovirus infection: a narrative review

    PubMed Central

    Sherman, Shany; Eytan, Ori

    2014-01-01

    Thrombosis associated with acute cytomegalovirus infection has been reported many times in the literature since the mid 1980s – mainly in case reports and in small case series, but also in four controlled studies. Still, many physicians are unaware of this association although acute cytomegalovirus infection diagnosis in a thrombosis patient may warrant antiviral therapy and may affect anticoagulation therapy duration. Accordingly, the clinical characteristics of patients with thrombosis and acute cytomegalovirus infection are reviewed, and the current knowledge concerning this unique association is presented herein. We believe it is time to add acute cytomegalovirus infection to the list of thrombosis triggers. PMID:25624857

  12. Immune Protection against Virus Challenge in Aging Mice Is Not Affected by Latent Herpesviral Infections

    PubMed Central

    Marandu, Thomas F.; Oduro, Jennifer D.; Borkner, Lisa; Dekhtiarenko, Iryna; Uhrlaub, Jennifer L.; Drabig, Anja; Kröger, Andrea; Nikolich-Zugich, Janko

    2015-01-01

    Latent herpesvirus infections alter immune homeostasis. To understand if this results in aging-related loss of immune protection against emerging infections, we challenged old mice carrying latent mouse cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), and/or murine gammaherpesvirus 68 (MHV-68) with influenza virus, West Nile virus (WNV), or vesicular stomatitis virus (VSV). We observed no increase in mortality or weight loss compared to results seen with herpesvirus-negative counterparts and a relative but not absolute reduction in CD8 responses to acute infections. Therefore, the presence of herpesviruses does not appear to increase susceptibility to emerging infections in aging patients. PMID:26339051

  13. Identification of Candidate Serum Biomarkers for Schistosoma mansoni Infected Mice Using Multiple Proteomic Platforms

    PubMed Central

    Kardoush, Manal I.

    2016-01-01

    Background Schistosomiasis is an important helminth infection of humans. There are few reliable diagnostic biomarkers for early infection, for recurrent infection or to document successful treatment. In this study, we compared serum protein profiles in uninfected and infected mice to identify disease stage-specific biomarkers. Methods Serum collected from CD1 mice infected with 50–200 Schistosoma mansoni cercariae were analyzed before infection and at 3, 6 and 12 weeks post-infection using three mass spectrometric (MS) platforms. Results Using SELDI-TOF MS, 66 discriminating m/z peaks were detected between S. mansoni infected mice and healthy controls. Used in various combinations, these peaks could 1) reliably diagnose early-stage disease, 2) distinguish between acute and chronic infection and 3) diagnose S. mansoni infection regardless the parasite burden. The most important contributors to these diagnostic algorithms were peaks at 3.7, 13 and 46 kDa. Employing sample fractionation and differential gel electrophoresis, we analyzed gel slices either by MALDI-TOF MS or Velos Orbitrap MS. The former yielded eight differentially-expressed host proteins in the serum at different disease stages including transferrin and alpha 1- antitrypsin. The latter suggested the presence of a surprising number of parasite-origin proteins in the serum during both the acute (n = 200) and chronic (n = 105) stages. The Orbitrap platform also identified many differentially-expressed host-origin serum proteins during the acute and chronic stages (296 and 220 respectively). The presence of one of the schistosome proteins, glutathione S transferase (GST: 25 KDa), was confirmed by Western Blot. This study provides proof-of-principle for an approach that can yield a large number of novel candidate biomarkers for Schistosoma infection. PMID:27138990

  14. Programmatic Implications of Acute and Early HIV Infection.

    PubMed

    Suthar, Amitabh B; Granich, Reuben M; Kato, Masaya; Nsanzimana, Sabin; Montaner, Julio S G; Williams, Brian G

    2015-11-01

    Human immunodeficiency virus (HIV) infection includes acute, early, chronic, and late stages. Acute HIV infection lasts approximately 3 weeks and early HIV infection, which includes acute HIV infection, lasts approximately 7 weeks. Many testing and blood screening algorithms detect HIV antibodies about 3 weeks after HIV infection. Incidence estimates are based on results of modeling, cohort studies, surveillance, and/or assays. Viral load is the key modifiable risk factor for HIV transmission and peaks during acute and early HIV infection. Empirical evidence characterizing the impact of acute and early HIV infection on the spread of the HIV epidemic are limited. Time trends of HIV prevalence collected from concentrated and generalized epidemics suggest that acute and early HIV infection may have a limited role in population HIV transmission. Collectively, these data suggest that acute and early HIV infection is relatively short and does not currently require fundamentally different programmatic approaches to manage the HIV/AIDS epidemic in most settings. Research and surveillance will inform which epidemic contexts and phases may require tailored strategies for these stages of HIV infection. PMID:26310309

  15. Helicobacter pylori infection and acute myocardial infarction.

    PubMed

    Nakić, Dario; Vcev, Aleksandar; Jović, Albino; Patrk, Jogen; Zekanović, Drazen; Klarin, Ivo; Ivanac, Kresimir; Mrden, Anamarija; Balen, Sanja

    2011-09-01

    The aim of this investigation was to determine whether H. pylori infection is an independent risk factor for acute myocardial infarction (AMI), determine is there a link between H. pylori infection and severity of disease. In this prospective, single centre study, were enrolled 100 patients with AMI and control group was consisted 93 healthy individuals. The results of this study showed no difference between H. pylori seropositivity distribution in the investigate and control group (29 vs. 26 %) and there was no significant difference on the severity of the disease. There was significant association in the patients with three and more risk factors, where the patients with lower blood pressure (124.4/77.4 vs. 145.9/87.7 mmHg) and better controlled diabetes (HbA1c 6.1% vs. 6.9%) had greater risk for AMI if they are H. pylori seropositive. The large multicentric trials would be needed to define a precise role of H. pylori infection on the developement of AMI. PMID:22053556

  16. Critical role for the AIM2 inflammasome during acute central nervous system bacterial infection

    PubMed Central

    Hanamsagar, Richa; Aldrich, Amy; Kielian, Tammy

    2014-01-01

    Interleukin-1β (IL-1β) is essential for eliciting protective immunity during the acute phase of Staphylococcus aureus (S. aureus) infection in the central nervous system (CNS). We previously demonstrated that microglial IL-1β production in response to live S. aureus is mediated through the Nod-like receptor protein 3 (NLRP3) inflammasome, including the adapter protein ASC (apoptosis-associated, speck-like, caspase-1 recruiting domain-containing protein), and pro-caspase-1. Here we utilized NLRP3, ASC, and caspase-1/11 knockout (KO) mice to demonstrate the functional significance of inflammasome activity during CNS S. aureus infection. ASC and caspase-1/11 KO animals were exquisitely sensitive, with approximately 50% of mice succumbing to infection within 24 h. Unexpectedly, the survival of NLRP3 KO mice was similar to WT animals, suggesting the involvement of an alternative upstream sensor, which was later identified as absent in melanoma 2 (AIM2) based on the similar disease patterns between AIM2 and ASC KO mice. Besides IL-1β, other key inflammatory mediators, including IL-6, CXCL1, CXCL10, and CCL2 were significantly reduced in the CNS of AIM2 and ASC KO mice, implicating autocrine/paracrine actions of IL-1β, since these mediators do not require inflammasome processing for secretion. These studies demonstrate a novel role for the AIM2 inflammasome as a critical molecular platform for regulating IL-1β release and survival during acute CNS S. aureus infection. PMID:24484406

  17. Acute HIV infection - New York City, 2008.

    PubMed

    2009-11-27

    Acute human immunodeficiency virus (HIV) infection (AHI) is a highly infectious phase of disease that lasts approximately 2 months and is characterized by nonspecific clinical symptoms. AHI contributes disproportionately to HIV transmission because it is associated with a high level of viremia, despite negative or indeterminate antibody (Ab) tests. Diagnosis of AHI with individual or pooled nucleic acid amplification tests (p-NAAT) can enable infected persons to adopt behaviors that reduce HIV transmission, facilitate partner referral for counseling and testing, and identify social networks of persons with elevated rates of HIV transmission. The national HIV surveillance case definition does not distinguish AHI from other stages of HIV infection, and the frequency of AHI among reported HIV cases is unknown. In 2008, to increase detection of AHI and demonstrate the feasibility of AHI surveillance, the New York City Department of Health and Mental Hygiene (NYC DOHMH) initiated p-NAAT screening at four sexually transmitted disease (STD) clinics and enhanced citywide HIV surveillance (using a standard case definition) to differentiate AHI among newly reported cases. Seventy cases of AHI (representing 1.9% of all 3,635 HIV diagnoses reported in New York City) were identified: 53 cases from enhanced surveillance and 17 cases from p-NAAT screening (representing 9% of 198 HIV diagnoses at the four clinics). Men who have sex with men (MSM) constituted 81% of AHI cases. Screening STD clinic patients, especially MSM, with p-NAAT can identify additional cases of HIV infection. Surveillance for AHI is feasible and can identify circumstances in which HIV prevention efforts should be intensified. PMID:19940835

  18. Hepatitis D Virus Infection of Mice Expressing Human Sodium Taurocholate Co-transporting Polypeptide

    PubMed Central

    Mao, Fengfeng; Jing, Zhiyi; Li, Yunfei; Liu, Yang; Peng, Bo; Yan, Huan; Qi, Yonghe; Sun, Yinyan; Guo, Ju-Tao; Sui, Jianhua; Wang, Fengchao; Li, Wenhui

    2015-01-01

    Hepatitis D virus (HDV) is the smallest virus known to infect human. About 15 million people worldwide are infected by HDV among those 240 million infected by its helper hepatitis B virus (HBV). Viral hepatitis D is considered as one of the most severe forms of human viral hepatitis. No specific antivirals are currently available to treat HDV infection and antivirals against HBV do not ameliorate hepatitis D. Liver sodium taurocholate co-transporting polypeptide (NTCP) was recently identified as a common entry receptor for HDV and HBV in cell cultures. Here we show HDV can infect mice expressing human NTCP (hNTCP-Tg). Antibodies against critical regions of HBV envelope proteins blocked HDV infection in the hNTCP-Tg mice. The infection was acute yet HDV genome replication occurred efficiently, evident by the presence of antigenome RNA and edited RNA species specifying large delta antigen in the livers of infected mice. The resolution of HDV infection appears not dependent on adaptive immune response, but might be facilitated by innate immunity. Liver RNA-seq analyses of HDV infected hNTCP-Tg and type I interferon receptor 1 (IFNα/βR1) null hNTCP-Tg mice indicated that in addition to induction of type I IFN response, HDV infection was also associated with up-regulation of novel cellular genes that may modulate HDV infection. Our work has thus proved the concept that NTCP is a functional receptor for HDV infection in vivo and established a convenient small animal model for investigation of HDV pathogenesis and evaluation of antiviral therapeutics against the early steps of infection for this important human pathogen. PMID:25902143

  19. Innate resistance of mice to experimental infection with Naegleria fowleri.

    PubMed Central

    Haggerty, R M; John, D T

    1978-01-01

    The mouse system provides an excellent model for studying host resistance to Naegleria fowleri, the agent of primary amoebic meningoencephalitis. Innate resistance to infection with N. fowleri was examined with respect to infecting dose and the age, sex, and strain of mice. Intravenous inoculation with 10(7) amoebae per mouse produced 100% mortality in 9 days, whereas inoculation with fewer amoebae reduced the cumulative mortality. Male and female DUB/ICR mice of varying ages were inoculated intravenously with 2.5 X 10(5) N. fowleri per g of body weight. The youngest mice died first, with 100% mortality for both males and females, and mortality decreased with increasing age. Female mice were significantly more resistant to infection than males. Five strains of mice weighing approximately 20 g were inoculated intravenously with weight-adjusted doses; mortality ranged from 10% in C57BL/6 mice to 95% in A/HeCr mice. PMID:669800

  20. Serospecific protection of mice against intranasal infection with Bordetella pertussis.

    PubMed

    Robinson, A; Gorringe, A R; Funnell, S G; Fernandez, M

    1989-08-01

    The ability of purified serospecific agglutinogens from Bordetella pertussis to protect mice against intranasal infection has been examined. Immunization with agglutinogen 2 protected mice against infection with 1.2.0 or 1.2.3 serotypes of B. pertussis, whereas immunization with agglutinogen 3 protected mice against infection with all serotypes. More importantly immunization with serospecific agglutinogen resulted in immune selection so that organisms recovered following infection did not express the immunizing antigen. The results are consistent with the suggestions that protection of children with whole cell pertussis vaccine is to some extent serospecific and that agglutinogens should be considered as constituents of acellular pertussis vaccines. PMID:2573215

  1. Pathogenesis of Lassa Fever Virus Infection: I. Susceptibility of Mice to Recombinant Lassa Gp/LCMV Chimeric Virus

    PubMed Central

    Lee, Andrew M.; Cruite, Justin; Welch, Megan J.; Sullivan, Brian; Oldstone, Michael B.A.

    2013-01-01

    Lassa virus (LASV) is a BSL-4 restricted agent. To allow study of infection by LASV under BSL-2 conditions, we generated a recombinant virus in which the LASV glycoprotein (Gp) was placed on the backbone of lymphocytic choriomeningitis virus (LCMV) Cl13 nucleoprotein, Z and polymerase genes (rLCMV Cl13/LASV Gp). The recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection. Inoculation of immunocompetent adults resulted in an acute infection, generation of virus-specific CD8+ T cells and clearance of the infection. Inoculation of newborn mice with rLCMV Cl13/LASV Gp resulted in a life-long persistent infection. Interestingly, adoptive transfer of rLCMV Cl13/LASV Gp immune memory cells into such persistently infected mice failed to purge virus but, in contrast, cleared virus from mice persistently infected with wt LCMV Cl13. PMID:23684417

  2. Pathogenesis of Lassa fever virus infection: I. Susceptibility of mice to recombinant Lassa Gp/LCMV chimeric virus.

    PubMed

    Lee, Andrew M; Cruite, Justin; Welch, Megan J; Sullivan, Brian; Oldstone, Michael B A

    2013-08-01

    Lassa virus (LASV) is a BSL-4 restricted agent. To allow study of infection by LASV under BSL-2 conditions, we generated a recombinant virus in which the LASV glycoprotein (Gp) was placed on the backbone of lymphocytic choriomeningitis virus (LCMV) Cl13 nucleoprotein, Z and polymerase genes (rLCMV Cl13/LASV Gp). The recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection. Inoculation of immunocompetent adults resulted in an acute infection, generation of virus-specific CD8(+) T cells and clearance of the infection. Inoculation of newborn mice with rLCMV Cl13/LASV Gp resulted in a life-long persistent infection. Interestingly, adoptive transfer of rLCMV Cl13/LASV Gp immune memory cells into such persistently infected mice failed to purge virus but, in contrast, cleared virus from mice persistently infected with wt LCMV Cl13. PMID:23684417

  3. Experimental infection of mice with bovine viral diarrhea virus.

    PubMed

    Seong, Giyong; Oem, Jae-Ku; Lee, Kyung-Hyun; Choi, Kyoung-Seong

    2015-06-01

    The objective of this study was to test the ability of bovine viral diarrhea virus (BVDV) to infect mice. Two mice each were either mock infected or inoculated with one of three BVDV strains by the intraperitoneal (IP) (n = 8) or intranasal (IN) (n = 8) route. All mice were euthanized at day 7 postinfection (p.i.). None of the infected mice exhibited any clinical signs of illness; however, the tissues harvested after BVDV challenge showed significant histopathological changes. Blood samples from five mice that were injected IP and one mouse that was inoculated IN were positive for BVDV by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemistry (IHC) was used to assess the presence of viral antigen in the organs of mice infected with three BVDV strains. In IP-injected mice, BVDV antigen was detected in the spleen (5/6), mesenteric lymph nodes (4/6), lymphatic tissue of the lung (3/6), lung (1/6), and stomach (1/6) of the infected mice; however, it was not detected in the liver (0/6) or kidney (0/6). In IN-inoculated mice, BVDV antigen was detected in the lung and mesenteric lymph nodes of one BVDV-infected mouse but was not detected in other tissues. The results of this study suggest that the spleen is the most reliable tissue for BVDV antigen detection using IHC in the IP-injected group. Our study demonstrates that mice can be infected by BVDV. This is the first report of BVDV infection in mice. PMID:25850760

  4. Pseudomonas aeruginosa forms Biofilms in Acute InfectionIndependent of Cell-to-Cell Signaling

    SciTech Connect

    Schaber, J. Andy; Triffo, W.J.; Suh, Sang J.; Oliver, Jeffrey W.; Hastert, Mary C.; Griswold, John A.; Auer, Manfred; Hamood, Abdul N.; Rumbaugh, Kendra P.

    2006-09-20

    Biofilms are bacterial communities residing within a polysaccharide matrix that are associated with persistence and antibiotic resistance in chronic infections. We show that the opportunistic pathogen Pseudomonas aeruginosa forms biofilms within 8 hours of infection in thermally-injured mice, demonstrating that biofilms contribute to bacterial colonization in acute infections. P. aeruginosa biofilms were visualized within burned tissue surrounding blood vessels and adipose cells. Although quorum sensing (QS), a bacterial signaling mechanism, coordinates differentiation of biofilms in vitro, wild type and QS-deficient P. aeruginosa formed similar biofilms in vivo. Our findings demonstrate that P. aeruginosa forms biofilms on specific host tissues independent of QS.

  5. Treatment of Acute HIV Infection and the Potential Role of Acutely HIV-Infected Persons in Cure Studies.

    PubMed

    Little, Susan J

    Diagnosis of acute HIV infection is important for accurate estimation of HIV incidence, identifying persons who are unaware of their HIV infection, and offering immediate treatment and risk-reduction strategies. The higher viral loads associated with acute HIV infection are associated with an increased risk of transmission. Current treatment recommendations are the same for acute and established infections. Studies of acute HIV infection indicate that initiation of antiretroviral therapy during this period may allow greater recovery of CD4+ T-cell count and function and may result in a smaller latent viral reservoir and a skewing of infection away from central memory CD4+ T cells toward shorter-lived transitional memory CD4+ T cells. This article summarizes a presentation by Susan J. Little, MD, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Los Angeles, California, in April 2015. PMID:27398768

  6. Neuralgic amyotrophy complicating acute hepatitis E infection: a rare association.

    PubMed

    Theochari, Evangelia; Vincent-Smith, Lisa; Ellis, Cathy

    2015-01-01

    Hepatitis E virus infection (HEV) is an emerging pathogen that is under-recognised in developed countries. Preceding infection manifested by acute transaminitis has been associated with neurological manifestations, predominately involving the peripheral nervous system, even in immunocompetent patients. We present a case of a 65-year-old previously fit and well Caucasian man with bilateral neuralgic amyotrophy (NA) and acute transaminitis. Serology testing for immunoglobulin (Ig) M and G established the diagnosis of acute HEV infection. The patient received immunomodulatory treatment with an excellent long-term outcome. The temporal association of the clinical presentation of bilateral NA and acute transaminitis from HEV infection suggested the causal association of HEV to NA. We propose screening for HEV in patients presenting with NA and acute hepatitis. PMID:25739795

  7. Macrophage Migration Inhibitory Factor Contributes to Host Defense against Acute Trypanosoma cruzi Infection

    PubMed Central

    Reyes, José L.; Terrazas, Luis I.; Espinoza, Bertha; Cruz-Robles, David; Soto, Virgilia; Rivera-Montoya, Irma; Gómez-García, Lorena; Snider, Heidi; Satoskar, Abhay R.; Rodríguez-Sosa, Miriam

    2006-01-01

    Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is involved in the host defense against several pathogens. Here we used MIF−/− mice to determine the role of endogenous MIF in the regulation of the host immune response against Trypanosoma cruzi infection. MIF−/− mice displayed high levels of blood and tissue parasitemia, developed severe heart and skeletal muscle immunopathology, and succumbed to T. cruzi infection faster than MIF+/+ mice. The enhanced susceptibility of MIF−/− mice to T. cruzi was associated with reduced levels of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-12 (IL-12), IL-18, gamma interferon (IFN-γ), and IL-1β, in their sera and reduced production of IL-12, IFN-γ, and IL-4 by spleen cells during the early phase of infection. At all time points, antigen-stimulated splenocytes from MIF+/+ and MIF−/− mice produced comparable levels of IL-10. MIF−/− mice also produced significantly less Th1-associated antigen-specific immunoglobulin G2a (IgG2a) throughout the infection, but both groups produced comparable levels of Th2-associated IgG1. Lastly, inflamed hearts from T. cruzi-infected MIF−/− mice expressed increased transcripts for IFN-γ, but fewer for IL-12 p35, IL-12 p40, IL-23, and inducible nitric oxide synthase, compared to MIF+/+ mice. Taken together, our findings show that MIF plays a role in controlling acute T. cruzi infection. PMID:16714544

  8. Apoptosis of hippocampal pyramidal neurons is virus independent in a mouse model of acute neurovirulent picornavirus infection.

    PubMed

    Buenz, Eric J; Sauer, Brian M; Lafrance-Corey, Reghann G; Deb, Chandra; Denic, Aleksandar; German, Christopher L; Howe, Charles L

    2009-08-01

    Many viruses, including picornaviruses, have the potential to infect the central nervous system (CNS) and stimulate a neuroinflammatory immune response, especially in infants and young children. Cognitive deficits associated with CNS picornavirus infection result from injury and death of neurons that may occur due to direct viral infection or during the immune responses to virus in the brain. Previous studies have concluded that apoptosis of hippocampal neurons during picornavirus infection is a cell-autonomous event triggered by direct neuronal infection. However, these studies assessed neuron death at time points late in infection and during infections that lead to either death of the host or persistent viral infection. In contrast, many neurovirulent picornavirus infections are acute and transient, with rapid clearance of virus from the host. We provide evidence of hippocampal pathology in mice acutely infected with the Theiler's murine encephalomyelitis picornavirus. We found that CA1 pyramidal neurons exhibited several hallmarks of apoptotic death, including caspase-3 activation, DNA fragmentation, and chromatin condensation within 72 hours of infection. Critically, we also found that many of the CA1 pyramidal neurons undergoing apoptosis were not infected with virus, indicating that neuronal cell death during acute picornavirus infection of the CNS occurs in a non-cell-autonomous manner. These observations suggest that therapeutic strategies other than antiviral interventions may be useful for neuroprotection during acute CNS picornavirus infection. PMID:19608874

  9. Immunofluorescence studies of disseminated Hantaan virus infection of suckling mice.

    PubMed Central

    Kurata, T; Tsai, T F; Bauer, S P; McCormick, J B

    1983-01-01

    Hantaan virus, the etiological agent of Korean hemorrhagic fever, was inoculated intracerebrally or intraperitoneally into suckling mice, and the course of the infection was followed by infectivity titration and immunofluorescence studies. Mice became ill and were moribund by 13 to 14 days postinfection. In mice inoculated either intracerebrally or intraperitoneally, virus antigen was present in brain, heart, lungs, liver, and kidney. Less consistently, specific fluorescence was observed in spleen, pituitary gland, thymus, lymph nodes, adrenal, pancreas, salivary glands, trigeminal ganglia, adipose tissue, intestine, and muscle. In all of these tissues, the primary target of infection was the capillary endothelium. In mice inoculated intracerebrally, virus antigen was present mainly in choroid plexus, hippocampal nuclei, and meninges, but in mice inoculated intraperitoneally, central nervous system infection was marked by antigen accumulation in cortical nuclei and thalamus. Images PMID:6134678

  10. Acute Viral Respiratory Infection Rapidly Induces a CD8+ T Cell Exhaustion-like Phenotype.

    PubMed

    Erickson, John J; Lu, Pengcheng; Wen, Sherry; Hastings, Andrew K; Gilchuk, Pavlo; Joyce, Sebastian; Shyr, Yu; Williams, John V

    2015-11-01

    Acute viral infections typically generate functional effector CD8(+) T cells (TCD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung TCD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to TCD8 impairment during viral lower respiratory infection, but how it regulates TCD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung TCD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung TCD8 to functional spleen TCD8 in the same human metapneumovirus-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung TCD8. We then compared the gene expression of TCD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung TCD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for TCD8 impairment or inhibitory receptor upregulation, but that viral Ag-induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung TCD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors. PMID:26401005

  11. Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice

    PubMed Central

    Koeppen, Michael; Eckle, Tobias; Eltzschig, Holger K.

    2011-01-01

    Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged mechanical ventilation, contributes to morbidity and mortality of critical illness, and studies on novel genetic or pharmacological targets are areas of intense investigation (1-3, 5, 8, 26, 30, 33-36). ALI is defined by the acute onset of the disease, which leads to non-cardiac pulmonary edema and subsequent impairment of pulmonary gas exchange (36). We have developed a murine model of ALI by using a pressure-controlled ventilation to induce ventilator-induced lung injury (2). For this purpose, C57BL/6 mice are anesthetized and a tracheotomy is performed followed by induction of ALI via mechanical ventilation. Mice are ventilated in a pressure-controlled setting with an inspiratory peak pressure of 45 mbar over 1 - 3 hours. As outcome parameters, pulmonary edema (wet-to-dry ratio), bronchoalveolar fluid albumin content, bronchoalveolar fluid and pulmonary tissue myeloperoxidase content and pulmonary gas exchange are assessed (2). Using this technique we could show that it sufficiently induces acute lung inflammation and can distinguish between different treatment groups or genotypes (1-3, 5). Therefore this technique may be helpful for researchers who pursue molecular mechanisms involved in ALI using a genetic approach in mice with gene-targeted deletion. PMID:21587159

  12. Antibacterial resistance in mice infected with Mycobacterium lepraemurium.

    PubMed Central

    Patel, P J

    1981-01-01

    The differences in susceptibility among C57Bl/6, DBA/2 mice and their F1 hybrids to infections with M. lepraemurium were shown to depend upon the route of infection and size of the inoculum. A method was developed to measure the ability of lymphocytes obtained from M. lepraemurium-infected donors to effect adoptive immunization of syngeneic naive mice against infection with M. tuberculosis. This required sublethal irradiation of recipient mice prior to cell transfer and bacterial challenge. Using this method, it was found that mice infected subcutaneously generated antituberculous immune mechanisms concordantly with the development of delayed-hypersensitivity to antigens of M. lepraemurium. In contrast, intravenously infected mice demonstrated only a transient from of delayed hypersensitivity and little or no antimycobacterial immunity in that progression of infection was associated with a rapid decay of both these functions. Moreover, during the terminal stage, M. lepraemurium-infected mice lost the ability to control the growth of a sublethal intravenous inoculum of the antigenically unrelated bacterium. Listeria monocytogenes. PMID:7039875

  13. Infections of Brugia pahangi in conventional and nude (athymic) mice.

    PubMed

    Suswillo, R R; Owen, D G; Denham, D A

    1980-12-01

    AKR, BALB/c and CBA/Ca and T.O. mice were completely resistant to infection with third stage infective larvae of Brugia pahangi. Third, fourth and fifth stage worms transplanted from the peritoneal cavity of jirds into the peritoneal cavity of mice continued to develop. BALB/c mice were the most susceptible of the strains tested and adult worms were obtained after each type of transplanted infection. Congenitally athymic nude mice were much less resistant to transplanted worms and infective larvae developed to full maturity in most of them. Ten of 14 athymic mice infected by the intraperitoneal (ip) inoculation of infective larvae had microfilariae in their blood or peritoneal cavities. At autopsy a percentage recovery of adult worms of 0-38% (mean 11.1%) was obtained. Microfilariae were only found in the blood of 2 of 6 athymic mice infected by subcutaneous (sc) infection and at autopsy 0-19.1% (mean 6.1%) recoveries were obtained. The thymic littermates of the nudes were more resistant than those most of the other strains used. PMID:6110323

  14. PcrV antibody-antibiotic combination improves survival in Pseudomonas aeruginosa-infected mice.

    PubMed

    Song, Y; Baer, M; Srinivasan, R; Lima, J; Yarranton, G; Bebbington, C; Lynch, S V

    2012-08-01

    The type III secretion system (TTSS) of Pseudomonas aeruginosa, associated with acute infection, facilitates the direct injection of cytotoxins into the host cell cytoplasm. Mab166, a murine monoclonal antibody against PcrV, a protein located at the tip of the injectisome, has demonstrated efficacy against P. aeruginosa infection, resulting in reduced lung injury and increased survival in murine models of infection. We hypothesised that the administration of Mab166 in combination with an antibiotic would further improve the survival of P. aeruginosa-infected mice. A murine model of P. aeruginosa acute infection, three clinically relevant antibiotics (ciprofloxacin, tobramycin and ceftazidime) and the Mab166 antibody were used for this study. Consistently, compared to other treatment groups (antibiotic or antibody administered in isolation), the combination of Mab166 and antibiotic significantly improved the survival of mice infected with three times the lethal dose (LD(90)) of the highly cytotoxic ExoU-secreting strain, PA103. This synergistic effect was primarily due to enhanced bactericidal effect and protection against lung injury, which prevented bacterial dissemination to other organs. Hence, the combination of Mab166 with antibiotic administration provides a new, more effective strategy against P. aeruginosa airway infection, especially when large numbers of highly virulent strains are present. PMID:22187351

  15. Interferon-Gamma Release Assay: An Effective Tool to Detect Early Toxoplasma gondii Infection in Mice

    PubMed Central

    Liu, Hongbin; Sun, Ximeng; Zhao, Xinxin; Liu, Xianyong; Suo, Xun

    2015-01-01

    Early diagnosis of Toxoplasma gondii infection before the formation of tissue cysts is vital for treatment, as drugs available for toxoplasmosis cannot kill bradyzoites contained in the cysts. However, current methods, such as antibody-based ELISA, are ineffective for detection of early infection. Here, we developed an interferon-gamma release assay (IGRA), measuring the IFN-γ released by T lymphocytes stimulated by Toxoplasma antigen peptides in vitro, for the detection of T. gondii infection in mice. Splenocytes isolated from infected mice were stimulated by peptides derived from dense granule proteins GRA4 and GRA6 and rhoptry protein ROP7, and released IFN-γ was measured by ELISA. Results showed that both acute and chronic infection could be detected by IGRA. More importantly, IGRA detected infection as early as the third day post infection; while serum IgM and IgG were detected 9 days and 13 days post infection, respectively. Our findings demonstrated that an IGRA-positive and ELISA-negative sample revealed an early infection, indicating the combination of IGRA and ELISA can be employed for the early diagnosis of T. gondii infection in human beings, cats and livestock. PMID:26378802

  16. A Magnetic Resonance Imaging Study of Intestinal Dilation in Trypanosoma cruzi–infected Mice Deficient in Nitric Oxide Synthase

    PubMed Central

    Ny, Lars; Li, Hua; Mukherjee, Shankar; Persson, Katarina; Holmqvist, Bo; Zhao, Dazhi; Shtutin, Vitaliy; Huang, Huan; Weiss, Louis M.; Machado, Fabiana S.; Factor, Stephen M.; Chan, John; Tanowitz, Herbert B.; Jelicks, Linda A.

    2009-01-01

    Infection with Trypanosoma cruzi causes megasyndromes of the gastrointestinal (GI) tract. We used magnetic resonance imaging (MRI) to monitor alterations in the GI tract of T. cruzi–infected mice, and to assess the role of nitric oxide (NO) in the development of intestinal dilation. Brazil strain–infected C57BL/6 wild-type (WT) mice exhibited dilatation of the intestines by 30 days post-infection. Average intestine lumen diameter increased by 72%. Levels of intestinal NO synthase (NOS) isoforms, NOS2 and NOS3, were elevated in infected WT mice. Inflammation and ganglionitis were observed in all infected mice. Intestinal dilation was observed in infected WT, NOS1, NOS2, and NOS3 null mice. This study demonstrates that MRI is a useful tool to monitor intestinal dilation in living mice and that these alterations may begin during acute infection. Furthermore, our data strongly suggests that NO may not be the sole contributor to intestinal dysfunction resulting from this infection. PMID:18981519

  17. Acute and delayed thermoregulatory response of mice exposed to brevetoxin.

    PubMed

    Gordon, C J; Kimm-Brinson, K L; Padnos, B; Ramsdell, J S

    2001-09-01

    Thermal dysthesia, characterized by a painful sensation of warm and cool surfaces, is one of many ailments in humans exposed to various marine algal toxins such as brevetoxin (PbTx). There is no animal model to study thermal dysthesia and little is known of the mechanism of action. There is also little known on the acute and delayed thermoregulatory effects of PbTx. In this study, we developed a behavioral system to assess the possible development of thermal dysthesia in mice exposed to PbTx. Female mice were implanted with radiotransmitters to monitor core temperature (Tc) and motor activity (MA). In one experiment, mice were dosed with the control vehicle or 180 microg/kg PbTx and placed on a floor temperature gradient to measure the selected foot temperature (SFT) while air temperature was kept constant. PbTx-treated mice underwent a 10 degrees C reduction in SFT concomitant with a 3 degrees C reduction in Tc within 30 min after exposure. In another study, Tc and MA were monitored in mice maintained in their home cages after dosing with 180 microg/kg PbTx. Tc but not MA increased for 2-5 days after exposure. SFT was unaffected by PbTx when tested 1-12 days after exposure. However, PbTx-treated mice underwent an increase in Tc when placed in the temperature gradient for up to 12 days after exposure. This suggests that PbTx augments the stress-induced hyperthermia from being placed in a novel environment. Overall, acute PbTx exposure leads to a regulated reduction in Tc as characterized by a preference for cooler SFTs and a reduced Tc. Thermal dysthesia was not apparent, but the exaggerated hyperthermic response with a normal SFT in the temperature gradient may suggest an altered processing of thermal stimuli in mice treated with PbTx. PMID:11384725

  18. Meditation or Exercise May Help Acute Respiratory Infections

    MedlinePlus

    ... U V W X Y Z Meditation or Exercise May Help Acute Respiratory Infections, Study Finds Share: © ... of three groups: a mindfulness meditation group, an exercise group, or a wait-list control group. Participants ...

  19. Behavioral assessment of NIH Swiss mice acutely intoxicated with tetramethylenedisulfotetramine.

    PubMed

    Flannery, Brenna M; Silverman, Jill L; Bruun, Donald A; Puhger, Kyle R; McCoy, Mark R; Hammock, Bruce D; Crawley, Jacqueline N; Lein, Pamela J

    2015-01-01

    Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison that is thought to trigger seizures by inhibiting the function of the type A gamma-aminobutyric acid receptor (GABAAR). Acute intoxication with TETS can cause vomiting, convulsions, status epilepticus (SE) and even death. Clinical case reports indicate that individuals who survive poisoning may exhibit long-term neuropsychological issues and cognitive deficits. Therefore, the objective of this research was to determine whether a recently described mouse model of acute TETS intoxication exhibits persistent behavioral deficits. Young adult male NIH Swiss mice received a seizure-inducing dose of TETS (0.15mg/kg, ip) and then were rescued from lethality by administration of diazepam (5mg/kg, ip) approximately 20min post-TETS-exposure. TETS-intoxicated mice typically exhibited 2 clonic seizures prior to administration of diazepam with no subsequent seizures post-diazepam injection as assessed using behavioral criteria. Seizures lasted an average of 72s. Locomotor activity, anxiety-like and depression-relevant behaviors and cognition were assessed at 1week, 1month and 2months post-TETS exposure using open field, elevated-plus maze, light↔dark transitions, tail suspension, forced swim and novel object recognition tasks. Interestingly, preliminary validation tests indicated that NIH Swiss mice do not respond to the shock in fear conditioning tasks. Subsequent evaluation of hot plate and tail flick nociception tasks revealed that this strain exhibits significantly decreased pain sensitivity relative to age- and sex-matched C57BL/6J mice, which displayed normal contextual fear conditioning. NIH Swiss mice acutely intoxicated with TETS exhibited no significant anxiety-related, depression-relevant, learning or memory deficits relative to vehicle controls at any of the time points assessed with the exception of significantly increased locomotor activity at 2months post-TETS intoxication. The general absence

  20. Acute tubular nephropathy in a patient with acute HIV infection: review of the literature.

    PubMed

    Ananworanich, Jintanat; Datta, Anandita A; Fletcher, James Lk; Townamchai, Natavudh; Chomchey, Nitiya; Kroon, Eugene; Sereti, Irini; Valcour, Victor; Kim, Jerome H

    2014-01-01

    We report a 57-year old man with diabetes mellitus and hypertension who presented with acute HIV infection. Routine blood tests showed an elevated blood urea nitrogen and creatinine. Renal biopsy showed acute tubular nephropathy, which has not been reported to occur during acute HIV infection, in the absence of rhabdomyolysis or multiple organ system failure. Antiretroviral therapy was initiated. His renal failure gradually resolved without further intervention. At one year of follow-up his HIV RNA was undetectable, and his renal function was normal. The case illustrates a rare manifestation of acute HIV infection - acute renal failure - in an older man with diabetes and hypertension. In this setting acute kidney injury might mistakenly have been attributed to his chronic comorbidities, and this case supports early HIV-1 testing in the setting of a high index of suspicion. PMID:25745498

  1. Natural History of Helicobacter hepaticus Infection in Conventional A/J Mice, with Special Reference to Liver Involvement

    PubMed Central

    Avenaud, Philippe; Le Bail, Brigitte; Mayo, Kathryn; Marais, Armelle; Fawaz, Rabia; Bioulac-Sage, Paulette; Megraud, Francis

    2003-01-01

    It has been reported that Helicobacter hepaticus infection of mice leads to chronic hepatitis and hepatocarcinoma. Our aim was to monitor a cohort of 80 conventional A/J mice in which half of the mice were infected by H. hepaticus in order to study the evolution of the infection and the pathological changes in comparison to uninfected mice. H. hepaticus was detected by culture only in some colon and cecum specimens after 17 months of age, while PCR detected H. hepaticus in the intestines of all inoculated mice after only 5 months of infection. The percentage of mice in which H. hepaticus was detected in the gallbladder, bile ducts, and liver by PCR, as well as the number of bacteria present in the liver, tended to increase with increasing age and longer infection time. Anti-H. hepaticus immunoglobulin G antibodies were positive by enzyme-linked immunosorbent assay only in inoculated mice. Pathological findings were also more frequent as the mice grew older: fibrosis was present (especially in the peripheral part of the liver), and significant portal inflammation including lymphoid nodules was present in almost all infected animals. Biliary lesions of neutrophilic acute cholangitis or lymphocytic cholangitis were noted. However, lesions were also observed in uninfected animals, although at a significantly lower level, and the only hepatocellular carcinoma occurred in an uninfected mouse. The evolution towards hepatocarcinoma is not always the endpoint and may depend on the bacterial strain and on the environmental conditions. PMID:12761159

  2. Infectivity of hepatic strain Klebsiella pneumoniae in diabetic mice.

    PubMed

    Wu, June Hsieh; Tsai, Cheng Gie

    2005-11-01

    Besides urinary tract infection (UTI) and pneumonia, increased severe liver abscesses caused by Klebsiella pneumoniae (KP), especially in diabetic patients, have been observed in infections acquired in hospitals. This indicates that different KP strains with higher virulence have emerged in recent years. Our goal was to investigate the infectivity of KP isolates in mice from liver abscess or UTI patients. Mice were injected with streptozotocin to induce diabetes. Male ICR mice were infected with KpU1 (UTI strain CG3 for survival experiment only) and KpL1 (liver abscess strain CG5) by tail-vein injection of 5 x 10(4) colony-forming units (CFU) bacterial suspension. The mice survival rates, cytokine level by enzyme-linked immunosorbent assay (ELISA), and bacterial presence in liver tissue by Giemsa stain were examined. The survival rates for the KpL1-infected animals were 28% and 0% in normal and diabetic groups, respectively, whereas, for the KpU1-infected mice, the rates were 100% and 75% during a 30-day observation. Nonsurviving KpL1-infected mice showed > 10(5) bacteria/ml blood and the bacteria appeared in the liver sinus area and inside liver cells. The KpL1-infected mice showed a tendency to increase the blood interleukin 1beta (IL-1beta) level in both nondiabetic and diabetic groups, whereas the tumor necrosis factor-alpha (TNF-alpha) level was significantly decreased in the KpL1-infected diabetic mice (P = 0.002). In conclusion, the KP strain from liver abscess showed a greater virulence in mice than the KP from UTI and was more virulent in diabetic than in nondiabetic mice. The infection with KP from liver abscess significantly decreased the blood TNF-alpha level in diabetes mellitus (DM) mice and the blood IL-1beta level tended to increase in both infected nondiabetic and diabetic groups. High blood bacterial count and appearance of bacteria in liver sinus and cells usually contribute to death of the animals. PMID:16246903

  3. Oral Exposure to Phytomonas serpens Attenuates Thrombocytopenia and Leukopenia during Acute Infection with Trypanosoma cruzi

    PubMed Central

    da Silva, Rosiane V.; Malvezi, Aparecida D.; Augusto, Leonardo da Silva; Kian, Danielle; Tatakihara, Vera Lúcia H.; Yamauchi, Lucy M.; Yamada-Ogatta, Sueli F.; Rizzo, Luiz V.; Schenkman, Sergio; Pinge-Filho, Phileno

    2013-01-01

    Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS), which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease. PMID:23844182

  4. Oral exposure to Phytomonas serpens attenuates thrombocytopenia and leukopenia during acute infection with Trypanosoma cruzi.

    PubMed

    da Silva, Rosiane V; Malvezi, Aparecida D; Augusto, Leonardo da Silva; Kian, Danielle; Tatakihara, Vera Lúcia H; Yamauchi, Lucy M; Yamada-Ogatta, Sueli F; Rizzo, Luiz V; Schenkman, Sergio; Pinge-Filho, Phileno

    2013-01-01

    Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS), which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease. PMID:23844182

  5. Identification of an acute-phase reactant in murine infections with Trypanosoma brucei.

    PubMed Central

    Shapiro, S Z; Black, S J

    1992-01-01

    A 42-kDa protein appeared at a much higher concentration in plasma from Trypanosoma brucei-resistant (C57BL/6) mice after infection than in plasma from trypanosome-susceptible (C3H/He) mice. This protein was purified by sequential steps of gel filtration, protein A-Sepharose affinity chromatography, isoelectric focusing, and ammonium sulfate precipitation. The purified protein was identified as a subunit of the acute-phase reactant haptoglobin. Causes of elevated plasma haptoglobin and its implications for resistance to trypanosomiasis are discussed. Images PMID:1500201

  6. Role of the Fas/FasL system in a model of RSV infection in mechanically ventilated mice

    PubMed Central

    van den Berg, Elske; van Woensel, Job B. M.; Bos, Albert P.; Bem, Reinout A.; Altemeier, William A.; Gill, Sean E.; Martin, Thomas R.

    2011-01-01

    Infection with respiratory syncytial virus (RSV) in children can progress to respiratory distress and acute lung injury necessitating mechanical ventilation (MV). MV enhances apoptosis and inflammation in mice infected with pneumonia virus of mice (PVM), a mouse pneumovirus that has been used as a model for severe RSV infection in mice. We hypothesized that the Fas/Fas ligand (FasL) system, a dual proapoptotic/proinflammatory system involved in other forms of lung injury, is required for enhanced lung injury in mechanically ventilated mice infected with PVM. C57BL/6 mice and Fas-deficient (“lpr”) mice were inoculated intratracheally with PVM. Seven or eight days after PVM inoculation, the mice were subjected to 4 h of MV (tidal volume 10 ml/kg, fraction of inspired O2 = 0.21, and positive end-expiratory pressure = 3 cm H2O). Seven days after PVM inoculation, exposure to MV resulted in less severe injury in lpr mice than in C57BL/6 mice, as evidenced by decreased numbers of polymorphonuclear neutrophils in the bronchoalveolar lavage (BAL), and lower concentrations of the proinflammatory chemokines KC, macrophage inflammatory protein (MIP)-1α, and MIP-2 in the lungs. However, when PVM infection was allowed to progress one additional day, all of the lpr mice (7/7) died unexpectedly between 0.5 and 3.5 h after the onset of ventilation compared with three of the seven ventilated C57BL/6 mice. Parameters of lung injury were similar in nonventilated mice, as was the viral content in the lungs and other organs. Thus, the Fas/FasL system was partly required for the lung inflammatory response in ventilated mice infected with PVM, but attenuation of lung inflammation did not prevent subsequent mortality. PMID:21743025

  7. Oxygen effects on mortality of mice infected with Diplococcus pneumoniae

    NASA Technical Reports Server (NTRS)

    Angrick, E. J.; Somerson, N. L.; Weiss, H. S.

    1974-01-01

    Mice infected by intraperitoneal injection of Diplococcus pneumoniae were held at 1 atm in either hypoxic (12%), hyperoxic (75%), or a normal (21%) oxygen environment. Mortality rates indicated prolongation of survival in hypoxia and shortened survival in hyperoxia. Exposure of mice to the experimental gas mixtures prior to inoculation did not alter the results.

  8. Tenascin C protects aorta from acute dissection in mice

    NASA Astrophysics Data System (ADS)

    Kimura, Taizo; Shiraishi, Kozoh; Furusho, Aya; Ito, Sohei; Hirakata, Saki; Nishida, Norifumi; Yoshimura, Koichi; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Ikeda, Yasuhiro; Miyamoto, Takanobu; Ueno, Takafumi; Hamano, Kimikazu; Hiroe, Michiaki; Aonuma, Kazutaka; Matsuzaki, Masunori; Imaizumi, Tsutomu; Aoki, Hiroki

    2014-02-01

    Acute aortic dissection (AAD) is caused by the disruption of intimomedial layer of the aortic walls, which is immediately life-threatening. Although recent studies indicate the importance of proinflammatory response in pathogenesis of AAD, the mechanism to keep the destructive inflammatory response in check is unknown. Here, we report that induction of tenascin-C (TNC) is a stress-evoked protective mechanism against the acute hemodynamic and humoral stress in aorta. Periaortic application of CaCl2 caused stiffening of abdominal aorta, which augmented the hemodynamic stress and TNC induction in suprarenal aorta by angiotensin II infusion. Deletion of Tnc gene rendered mice susceptible to AAD development upon the aortic stress, which was accompanied by impaired TGFβ signaling, insufficient induction of extracellular matrix proteins and exaggerated proinflammatory response. Thus, TNC works as a stress-evoked molecular damper to maintain the aortic integrity under the acute stress.

  9. Experimental chemotherapy of Trypanosoma cruzi infection: persistence of parasite antigens and positive serology in parasitologically cured mice.

    PubMed Central

    Andrade, S. G.; Freitas, L. A.; Peyrol, S.; Pimentel, A. R.; Sadigursky, M.

    1991-01-01

    Mice infected with Trypanosoma cruzi, but parasitologically cured after specific chemotherapy, continued to exhibit positive indirect immunofluorescence serological tests 3-6 months after the therapy. Treatment of trypanosome antigens with monospecific antisera produced in rabbits, and examination by immunoelectron-microscopy following peroxidase labelling disclosed the presence of membrane deposits in cell processes in the spleens of the mice. Similar deposits were observed in the external membranes of T. cruzi amastigotes in the spleens of acutely infected mice, but not in normal control mice. No reaction occurred in tissues not previously treated with the monospecific anti-T. cruzi serum. Positive cells in treated and cured mice, as well as in the not cured or untreated control mice, were located in germinal centres of the splenic white pulp and presented long and branching cytoplasmic processes, which are indicative of dendritic cells of the lymphoid follicles of the spleen. Images Fig. 1 Fig. 2 Fig. 3 PMID:1907221

  10. Acute pancreatitis, ascites, and acute renal failure in Plasmodium vivax malaria infection, a rare complication.

    PubMed

    Lakhotia, Manoj; Pahadiya, Hans Raj; Kumar, Harish; Singh, Jagdish; Sangappa, Jainapur Ravi; Choudhary, Prakash Kumar

    2015-01-01

    A 22-year-old male presented with 6 days history of intermittent fever with chills, 2 days history of upper abdomen pain, distension of abdomen, and decreased urine output. He was diagnosed to have Plasmodium vivax malaria, acute pancreatitis, ascites, and acute renal failure. These constellations of complications in P. vivax infection have never been reported in the past. The patient responded to intravenous chloroquine and supportive treatment. For renal failure, he required hemodialysis. Acute pancreatitis, ascites, and acute renal failure form an unusual combination in P. vivax infection. PMID:26629455

  11. Tumor development after polyoma infection in athymic nude mice.

    PubMed

    Stutman

    1975-04-01

    Nude (nu/nu) mice in a CBA/H background show an age-dependent ssuceptibility to tumor development after polyoma virus infection (strain LID-1) when compared with nu/ + or CBA/H mice, which is apparent when 15- or 30-day-old mice are used: tumor incidence was 83 to 90% in nudes and 0 to 10% in controls. Latent perids for tumor development were also shortened in nudes. However, with increasing age nude mice become partially resistant and only 25% develop tumors when infected at 120 days of age. This partial resistance could be transferred with spleen cells to newborn mice. The cells in spleen responsible for this transfer can be eliminated by lysis with anti-Ig and complement or by pre-treatment of the donor with 100 mg/kg of cyclophosphamide and were not affected by treatment in vitro with anti-Thy.1.2 or procedures that remove adherent cells and/or macrophages. When the cells in 15-day-old nu/ + spleen were studied, both anti-Ig or anti-Thy.1.2 treatment eliminated tranfer of resistance to newborn. Virus replication in tissues of nude mice was increased 5 days after infection when compared with nu/ + but became comparable by day 15 after infection. Hemagglutination-inhibition antibodies in serum of nude and nu/ + had comparable titers when measured early after infection but higher titers were observed in nu/ + later after infection. PMID:163861

  12. Modeling Zika Virus Infection in Mice.

    PubMed

    Rossi, Shannan L; Vasilakis, Nikos

    2016-07-01

    Understanding the link between Zika virus (ZIKV) infection and microcephaly requires in vivo models of ZIKV infection in pregnant adults and fetuses. Three studies recently generated such mouse models of ZIKV infection, which corroborate previous in vitro evidence linking ZIKV infection and apoptosis induction in neurons and progenitors to microcephaly. PMID:27392219

  13. Central adiponectin acutely improves glucose tolerance in male mice.

    PubMed

    Koch, Christiane E; Lowe, Chrishanthi; Legler, Karen; Benzler, Jonas; Boucsein, Alisa; Böttiger, Gregor; Grattan, David R; Williams, Lynda M; Tups, Alexander

    2014-05-01

    Adiponectin, an adipocyte-derived hormone, regulates glucose and lipid metabolism. It is also antiinflammatory. During obesity, adiponectin levels and sensitivity are reduced. Whereas the action of adiponectin in the periphery is well established the neuroendocrine role of adiponectin is largely unknown. To address this we analyzed the expression of adiponectin and the 2 adiponectin receptors (AdipoR1 and AdipoR2) in response to fasting and to diet-induced and genetic obesity. We also investigated the acute impact of adiponectin on central regulation of glucose homeostasis. Adiponectin (1 μg) was injected intracerebroventricularly (ICV), and glucose tolerance tests were performed in dietary and genetic obese mice. Finally, the influence of ICV adiponectin administration on central signaling cascades regulating glucose homeostasis and on markers of hypothalamic inflammation was assessed. Gene expression of adiponectin was down-regulated whereas AdipoR1 was up-regulated in the arcuate nucleus of fasted mice. High-fat (HF) feeding increased AdipoR1 and AdipoR2 gene expression in this region. In mice on a HF diet and in leptin-deficient mice acute ICV adiponectin improved glucose tolerance 60 minutes after injection, whereas normoglycemia in control mice was unaffected. ICV adiponectin increased pAKT, decreased phospho-AMP-activated protein kinase, and did not change phospho-signal transducer and activator of transcription 3 immunoreactivity. In HF-fed mice, ICV adiponectin reversed parameters of hypothalamic inflammation and insulin resistance as determined by the number of phospho-glycogen synthase kinase 3 β(Ser9) and phospho-c-Jun N-terminal kinase (Thr183/Tyr185) immunoreactive cells in the arcuate nucleus and ventromedial hypothalamus. This study demonstrates that the insulin-sensitizing properties of adiponectin are at least partially based on a neuroendocrine mechanism that involves centrally synthesized adiponectin. PMID:24564394

  14. Acute Legionella pneumophila infection masquerading as acute alcoholic hepatitis

    PubMed Central

    Hunter, Jonathan Michael; Chan, Julian; Reid, Angeline Louise; Tan, Chistopher

    2013-01-01

    A middle-aged man had deteriorated rapidly in hospital after being misdiagnosed with acute alcoholic hepatitis. Acute Legionnaires disease (Legionellosis) was subsequently diagnosed on rapid antigen urinary testing and further confirmed serologically. This led to appropriate antibiotic treatment and complete clinical resolution. Physicians caring for patients with alcohol-related liver disease should consider Legionella pneumophila in their differential diagnosis even with a paucity of respiratory symptoms. PMID:23355576

  15. Acute hemiplegia with lacunar infarct after varicella infection in childhood.

    PubMed

    Eda, I; Takashima, S; Takeshita, K

    1983-01-01

    We report 4 cases of acute hemiplegia and a small low-density lesion on computerized tomography (CT) after varicella infection. In 3 of them, CT in the acute hemiplegic stage, and later, reveals the development of lacunar infarct around the internal capsule. Focal low density may be caused by occlusive vascular lesions of the penetrating arteries. Varicella infection may play an important role as one of the causes of acute hemiplegia in childhood producing lacunar infarct, as well as delayed hemiplegia, reported previously in herpes zoster ophthalmicus. PMID:6660422

  16. Influenza A infection enhances antigen-induced airway inflammation and hyper-responsiveness in young but not aged mice

    PubMed Central

    Birmingham, Janette M.; Gillespie, Virginia L.; Srivastava, Kamal; Li, Xiu-Min; Busse, Paula J.

    2015-01-01

    Background Although morbidity and mortality rates from asthma are highest in patients > 65 years of age, the effect of older age on airway inflammation in asthma is not well established. Objective To investigate age-related differences in the promotion of allergic inflammation after influenza A viral respiratory infection on antigen specific IgE production, antigen-induced airway inflammation and airway hyper-responsiveness in mice. Methods To accomplish this objective, the following model system was used. Young (six-week) and aged (18-month) BALB/c mice were first infected with a non-lethal dose of influenza virus A (H/HK×31). Mice were then ovalbumin (OVA) sensitized during the acute-infection (3-days post inoculation) and then chronically underwent challenge to the airways with OVA. Forty-eight hours after the final OVA-challenge, airway hyperresponsiveness (AHR), bronchoalveolar fluid (BALF) cellular and cytokine profile, antigen-specific IgE and IgG1, and lung tissue inflammation were measured. Results Age-specific differences were noted on the effect of a viral infection, allergic sensitization, airway inflammation and airway hyperresponsiveness. Serum OVA-specific IgE was significantly increased in only the aged mice infected with influenza virus. Despite greater morbidity (e.g. weight loss and sickness scores) during the acute infection in the 18-month old mice that were OVA-sensitized there was little effect on the AHR and BALF cellular differential. In contrast, BALF neutrophils and AHR increased, but eosinophils decreased in 6-week mice that were OVA-sensitized during an acute influenza infection. Conclusion With increased age in a mouse model, viral infection prior to antigen sensitization affects the airway and systemic allergic response differently. These differences may reflect distinct phenotypic features of allergic inflammation in older patients with asthma PMID:25039815

  17. Acute intestinal infections of non-dysenteric etiology*

    PubMed Central

    Linetskaya-Novgorodskaya, E. M.

    1959-01-01

    Recent work on the epidemiology and microbiology of acute intestinal infections has brought about a revision of long-held views as to many of their characteristics and as to their grouping. This paper deals with these infections in the light of this recent work, with particular reference to findings made in Leningrad. PMID:14417237

  18. Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2016-04-08

    Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  19. Acute Cytomegalovirus Infection as a Cause of Venous Thromboembolism

    PubMed Central

    Rinaldi, Francesca; Lissandrin, Raffaella; Mojoli, Francesco; Baldanti, Fausto; Brunetti, Enrico; Pascarella, Michela; Giordani, Maria Teresa

    2014-01-01

    Acute Human Cytomegalovirus (HCMV) infection is an unusual cause of venous thromboembolism, a potentially life-threatening condition. Thrombus formation can occur at the onset of the disease or later during the recovery and may also occur in the absence of acute HCMV hepatitis. It is likely due to both vascular endothelium damage caused by HCMV and impairment of the clotting balance caused by the virus itself. Here we report on two immunocompetent women with splanchnic thrombosis that occurred during the course of acute HCMV infection. Although the prevalence of venous thrombosis in patients with acute HCMV infection is unknown, physicians should be aware of its occurrence, particularly in immunocompetent patients presenting with fever and unexplained abdominal pain. PMID:24959338

  20. Protective role of TNF-α, IL-10 and IL-2 in mice infected with the Oshima strain of Tick-borne encephalitis virus

    PubMed Central

    Tun, Mya Myat Ngwe; Aoki, Kotaro; Senba, Masachika; Buerano, Corazon C.; Shirai, Kenji; Suzuki, Ryuji; Morita, Kouichi; Hayasaka, Daisuke

    2014-01-01

    Tick-borne encephalitis virus (TBEV) causes acute central nervous system disease. Here, we investigated the roles of the TNF-α, IL-10 and other cytokines in appropriate KO mice following infection with Oshima and Sofjin strains of TBEV. Following infection with the Oshima strain, mortality rates were significantly increased in TNF-α KO and IL-10 KO mice compared with wild type (WT) mice. These results suggested that TNF-α and IL-10 play protective roles against fatal infection due to Oshima strain infection. However, viral loads and proinflammatory cytokine levels in the brain of TNF-α KO andIL-10 KO mice were not significantly different compared with those of WT mice. On the other hand, all WT, TNF-α KO and IL-10 KO mice died following infection with Sofjin strain. Interestingly, Sofjin-infected mice did not exhibit an up-regulated mRNA level of IL-2 in the spleen in all groups of mice, whereas Oshima-infected mice showed significantly increased level of IL-2 compared with mock-infected mice. From these results, we suggest that TNF-α, IL-10 and IL-2 are key factors for disease remission from fatal encephalitis due to infection with Oshima strain of TBEV. PMID:24938868

  1. Acute Human Inkoo and Chatanga Virus Infections, Finland

    PubMed Central

    Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli

    2016-01-01

    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001–2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross-neutralization tests confirmed presence of INKV or CHATV infections. All children (<16 years of age) with INKV infection were hospitalized; adults were outpatients with mild disease, except for 1 who was hospitalized with CHATV infection. Symptoms included fever, influenza-like illness, nausea or vomiting, disorientation, nuchal rigidity, headache, drowsiness, and seizures. Although many INKV and CHATV infections appear to be subclinical, these viruses can cause more severe disease, especially in children. PMID:27088268

  2. Soluble epoxide hydrolase deficiency ameliorates acute pancreatitis in mice.

    PubMed

    Bettaieb, Ahmed; Morisseau, Christophe; Hammock, Bruce; Haj, Fawaz

    2014-10-01

    Acute pancreatitis (AP) is a frequent gastrointestinal disorder that causes significant morbidity and its incidence has been progressively increasing. AP starts as a local inflammation in the pancreas that often leads to systemic inflammatory response and complications. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition in murine models has beneficial effects in inflammatory diseases, but its significance in AP remains unexplored. To investigate whether sEH may have a causal role in AP we utilized sEH knockout (KO) mice to determine the effects of sEH deficiency on ceruelin- and arginine-induced AP. sEH expression increased at the protein and messenger RNA levels, as well as sEH activity in the early phase of cerulein- and arginine-induced AP in mice. In addition, amylase and lipase levels were lower in cerulein-treated sEH KO mice compared with non-treated controls. Moreover, pancreatic mRNA and serum concentrations of the inflammatory cytokines IL-1ß and IL-6 were lower in sEH KO mice compared with controls. Further, sEH KO mice exhibited decreased cerulein- and arginine-induced NF-?B inflammatory response, MAPKs activation and decreased cell death. These findings demonstrate a novel role for sEH in the progression of cerulein- and arginine-induced AP. PMID:26461340

  3. Adenosine A2A receptor activation reduces recurrence and mortality from Clostridium difficile infection in mice following vancomycin treatment

    PubMed Central

    2012-01-01

    Background Activation of the A2A adenosine receptor (A2AAR) decreases production of inflammatory cytokines, prevents C. difficile toxin A-induced enteritis and, in combination with antibiotics, increases survival from sepsis in mice. We investigated whether A2AAR activation improves and A2AAR deletion worsens outcomes in a murine model of C. difficile (strain VPI10463) infection (CDI). Methods C57BL/6 mice were pretreated with an antibiotic cocktail prior to infection and then treated with vancomycin with or without an A2AAR agonist. A2AAR-/- and littermate wild-type (WT) mice were similarly infected, and IFNγ and TNFα were measured at peak of and recovery from infection. Results Infected, untreated mice rapidly lost weight, developed diarrhea, and had mortality rates of 50-60%. Infected mice treated with vancomycin had less weight loss and diarrhea during antibiotic treatment but mortality increased to near 100% after discontinuation of antibiotics. Infected mice treated with both vancomycin and an A2AAR agonist, either ATL370 or ATL1222, had minimal weight loss and better long-term survival than mice treated with vancomycin alone. A2AAR KO mice were more susceptible than WT mice to death from CDI. Increases in cecal IFNγ and blood TNFα were pronounced in the absence of A2AARs. Conclusion In a murine model of CDI, vancomycin treatment resulted in reduced weight loss and diarrhea during acute infection, but high recurrence and late-onset death, with overall mortality being worse than untreated infected controls. The administration of vancomycin plus an A2AAR agonist reduced inflammation and improved survival rates, suggesting a possible benefit of A2AAR agonists in the management of CDI to prevent recurrent disease. PMID:23217055

  4. Epstein-Barr Virus Infection with Acute Acalculous Cholecystitis

    PubMed Central

    Kim, Ahlee; Moon, Jin Soo; Chang, Ju Young; Ko, Jae Sung

    2014-01-01

    Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder in the absence of demonstrated stones. AAC is frequently associated with severe systemic inflammation. However, the exact etiology and pathogenesis of AAC still remain unclear. Acute infection with Epstein Barr virus (EBV) in childhood is usually aymptomatic, whereas it often presents as typical infectious mononucleosis symptoms such as fever, cervical lymphadenopathy, and hepatosplenomegaly. AAC may occur during the course of acute EBV infection, which is rarely encountered in the pediatric population. AAC complicating the course of a primary EBV infection is usually associated with a favorable outcome. Most of the patients recover without any surgical treatment. Therefore, the detection of EBV in AAC would be important for prediction of better prognosis. We describe the case of a 10-year-old child who presented with AAC during the course of primary EBV infection, the first in Korea, and review the relevant literature. PMID:24749090

  5. Epstein-barr virus infection with acute acalculous cholecystitis.

    PubMed

    Kim, Ahlee; Yang, Hye Ran; Moon, Jin Soo; Chang, Ju Young; Ko, Jae Sung

    2014-03-01

    Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder in the absence of demonstrated stones. AAC is frequently associated with severe systemic inflammation. However, the exact etiology and pathogenesis of AAC still remain unclear. Acute infection with Epstein Barr virus (EBV) in childhood is usually aymptomatic, whereas it often presents as typical infectious mononucleosis symptoms such as fever, cervical lymphadenopathy, and hepatosplenomegaly. AAC may occur during the course of acute EBV infection, which is rarely encountered in the pediatric population. AAC complicating the course of a primary EBV infection is usually associated with a favorable outcome. Most of the patients recover without any surgical treatment. Therefore, the detection of EBV in AAC would be important for prediction of better prognosis. We describe the case of a 10-year-old child who presented with AAC during the course of primary EBV infection, the first in Korea, and review the relevant literature. PMID:24749090

  6. Acetaminophen-induced acute liver injury in mice.

    PubMed

    Mossanen, J C; Tacke, F

    2015-04-01

    The induction of acute hepatic damage by acetaminophen (N-acetyl-p-aminophenol [APAP]), also termed paracetamol, is one of the most commonly used experimental models of acute liver injury in mice. The specific values of this model are the highly reproducible, dose-dependent hepatotoxicity of APAP and its outstanding translational importance, because acetaminophen overdose is one of the most frequent reasons for acute liver failure (ALF) in humans. However, preparation of concentrated APAP working solutions, application routes, fasting period and variability due to sex, genetic background or barrier environment represent important considerations to be taken into account before implementing this model. This standard operating procedure (SOP) provides a detailed protocol for APAP preparation and application in mice, aimed at facilitating comparability between research groups as well as minimizing animal numbers and distress. The mouse model of acetaminophen poisoning therefore helps to unravel the pathogenesis of APAP-induced toxicity or subsequent immune responses in order to explore new therapeutic interventions for improving the prognosis of ALF in patients. PMID:25835736

  7. The concanavalin A model of acute hepatitis in mice.

    PubMed

    Heymann, F; Hamesch, K; Weiskirchen, R; Tacke, F

    2015-04-01

    The intravenous injection of the plant lectin concanavalin A (ConA) is a widely used model for acute immune-mediated hepatitis in mice. In contrast to several other models for acute hepatic damage, ConA-induced injury is primarily driven by the activation and recruitment of T cells to the liver. Hence, the ConA model has unique features with respect to its pathogenesis and important similarities to immune-mediated hepatitis in humans, such as autoimmune hepatitis, acute viral hepatitis or distinct entities of drug toxicity leading to immune activation. However, the ConA model has considerable variability, depending on the preparation of the compound, genetic background of the mice, sex, age and microbial environment of the animal facility barrier. This standard operating procedure (SOP) comprises a detailed protocol for the ConA application, including preparation of ConA working solution, handling of the animals, choice of the appropriate conditions and endpoints, as well as efficient dose-finding. PMID:25835734

  8. Acute and subchronic toxicity of danshensu in mice and rats.

    PubMed

    Gao, Yonglin; Liu, Zhifeng; Li, Guisheng; Li, Chunmei; Li, Min; Li, Bafang

    2009-06-01

    Danshensu (3-(3,4-dihydroxyphenyl) lactic acid), a natural phenolic acid, is isolated from Salvia miltiorrhiza root, and is the most widely used traditional Chinese medicine for the treatment of various cardiovascular diseases. It has been reported to have potential protective effects from oxidative injury. However, there is a little information about its possible toxicity. In this study, acute and subchronic toxicity of danshensu in mice and rats have been evaluated. In the acute study, danshensu intraveniouslly administered to rats failed to induce any signs of toxicity or mortality up to a maximum practical dosage of 1500 mg/kg body weight. Test substance administered acutely to mice caused dose-dependent general behavior adverse effects and mortality with the medial lethal dose of 2356.33 mg/kg. The no observed adverse effect level and the lowest observed adverse effect level were 1835 mg/kg and 2000 mg/kg, respectively. In the subchronic study, rats were tested by daily intraperitoneal injection of danshensu at the doses of 50, 150, and 450 mg/kg for 90 days, resulting in no mortality, no changes in body weight, food consumption, hematological and serum chemistry parameters, organ weights, or gross pathology or histopathology. The only treatment-related finding was transient writhing response observed in the 450 mg/kg group after administration. PMID:19778213

  9. Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice

    PubMed Central

    Facchini, Marcella; De Fino, Ida; Riva, Camilla; Bragonzi, Alessandra

    2014-01-01

    A mouse model of chronic airway infection is a key asset in cystic fibrosis (CF) research, although there are a number of concerns regarding the model itself. Early phases of inflammation and infection have been widely studied by using the Pseudomonas aeruginosa agar-beads mouse model, while only few reports have focused on the long-term chronic infection in vivo. The main challenge for long term chronic infection remains the low bacterial burden by P. aeruginosa and the low percentage of infected mice weeks after challenge, indicating that bacterial cells are progressively cleared by the host. This paper presents a method for obtaining efficient long-term chronic infection in mice. This method is based on the embedding of the P. aeruginosa clinical strains in the agar-beads in vitro, followed by intratracheal instillation in C57Bl/6NCrl mice. Bilateral lung infection is associated with several measurable read-outs including weight loss, mortality, chronic infection, and inflammatory response. The P. aeruginosa RP73 clinical strain was preferred over the PAO1 reference laboratory strain since it resulted in a comparatively lower mortality, more severe lesions, and higher chronic infection. P. aeruginosa colonization may persist in the lung for over three months. Murine lung pathology resembles that of CF patients with advanced chronic pulmonary disease. This murine model most closely mimics the course of the human disease and can be used both for studies on the pathogenesis and for the evaluation of novel therapies. PMID:24686327

  10. Antiplasmodial Effect of Anthocleista vogelii on Albino Mice Experimentally Infected with Plasmodium berghei berghei (NK 65)

    PubMed Central

    Gboeloh, Lebari Barine; Okon, Okpok Eta; Udoh, Samuel Effiong

    2014-01-01

    The objective of the present study was to investigate the antiplasmodial effect of the ethanolic stem bark extract of Anthocleista vogelii at different doses in albino mice infected with Plasmodium berghei berghei (NK 65). Thirty-six mice were divided into six groups of six mice each. Five groups (B1–B3, D, and G) were infected with Plasmodium berghei berghei parasitized red blood cells. Groups D, H, and G served as the controls. Six days after infection, mice in groups B1, B2, and B3 were treated orally with 100, 200, and 400 mg/kg body weight of Anthocleista vogelii, respectively, for six executive days. Group D was treated with 5 mg/kg body weight of chloroquine while Group G was given distilled water. Group H was not infected and was not treated. It served as the normal control. The extracts exhibited significant (P < 0.05) dose-dependent chemosuppression of P. berghei. The extract exhibited average chemosuppressive effects of 48.5%, 78.5%, and 86.6% at dose levels of 100, 200, and 400 mg/kg body weight, respectively. Phytochemical screening of the plant extract revealed the presence of saponins, cardiac glycosides, flavonoids, terpenes, alkaloids, and steroid. The acute toxicity (LD50) of the plant was estimated to be 3162 mg/kg body weight. It showed that the stem bark of A. vogelii possesses antiplasmodial property. PMID:24900913

  11. Human bocavirus in children with acute respiratory infections in Vietnam.

    PubMed

    Tran, Dinh Nguyen; Nguyen, Tran Quynh Nhu; Nguyen, Tuan Anh; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

    2014-06-01

    Acute respiratory infections are the major cause of morbidity and mortality globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly associate with previously unknown etiology respiratory infections in young children. In this study, the epidemiological, clinical, and molecular characteristics of HBoV infections were described in hospitalized Vietnamese pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab samples were obtained from patients with acute respiratory infections at the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV by PCR and further molecularly characterized by sequencing. HBoV was found in 78 (7.2%) children. Co-infection with other viruses was observed in 66.7% of patients infected with HBoV. Children 12-24 months old were the most affected age group. Infections with HBoV were found year-round, though most cases occurred in the dry season (December-April). HBoV was possible to cause severe diseases as determined by higher rates of hypoxia, pneumonia, and longer hospitalization duration in patients with HBoV infection than in those without (P-value <0.05). Co-infection with HBoV did not affect the disease severity. The phylogenetic analysis of partial VP1 gene showed minor variations and all HBoV sequences belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam and detected frequently in young children during dry season. Acute respiratory infections caused by HBoV1 were severe enough for hospitalization, which implied that HBoV1 may have an important role in acute respiratory infections among children. PMID:24123072

  12. Retention of anergy and inhibition of antibody responses during acute γ herpesvirus 68 infection.

    PubMed

    Getahun, Andrew; Smith, Mia J; Kogut, Igor; van Dyk, Linda F; Cambier, John C

    2012-09-15

    The majority of the human population becomes infected early in life by the gammaherpesvirus EBV. Some findings suggest that there is an association between EBV infection and the appearance of pathogenic Abs found in lupus. Gammaherpesvirus 68 infection of adult mice (an EBV model) was shown to induce polyclonal B cell activation and hypergammaglobulinemia, as well as increased production of autoantibodies. In this study, we explored the possibility that this breach of tolerance reflects loss of B cell anergy. Our findings show that, although anergic B cells transiently acquire an activated phenotype early during infection, they do not become responsive to autoantigen, as measured by the ability to mobilize Ca2+ following AgR cross-linking or mount Ab responses following immunization. Indeed, naive B cells also acquire an activated phenotype during acute infection but are unable to mount Ab responses to either T cell-dependent or T cell-independent Ags. In acutely infected animals, Ag stimulation leads to upregulation of costimulatory molecules and relocalization of Ag-specific B cells to the B-T cell border; however, these cells do not proliferate or differentiate into Ab-secreting cells. Adoptive-transfer experiments show that the suppressed state is reversible and is dictated by the environment in the infected host. Finally, B cells in infected mice deficient of CD4+ T cells are not suppressed, suggesting a role for CD4+ T cells in enforcing unresponsiveness. Thus, rather than promoting loss of tolerance, gammaherpesvirus 68 infection induces an immunosuppressed state, reminiscent of compensatory anti-inflammatory response syndrome. PMID:22904300

  13. Corticosteroid Treatment Ameliorates Acute Lung Injury Induced by 2009 Swine Origin Influenza A (H1N1) Virus in Mice

    PubMed Central

    Sun, Yang; Wang, Wei; Zou, Zhen; Xing, Li; Chen, Zhongwei; Tang, Chong; Guo, Feng; Deng, Jiejie; Zhao, Yan; Yan, Yiwu; Tang, Jun; Wang, Xiliang; Jiang, Chengyu

    2012-01-01

    Background The 2009 influenza pandemic affected people in almost all countries in the world, especially in younger age groups. During this time, the debate over whether to use corticosteroid treatment in severe influenza H1N1 infections patients resurfaced and was disputed by clinicians. There is an urgent need for a susceptible animal model of 2009 H1N1 infection that can be used to evaluate the pathogenesis and the therapeutic effect of corticosteroid treatment during infection. Methodology/Principal Findings We intranasally inoculated two groups of C57BL/6 and BALB/c mice (using 4- or 6-to 8-week-old mice) to compare the pathogenesis of several different H1N1 strains in mice of different ages. Based on the results, a very susceptible 4-week-old C57BL/6 mouse model of Beijing 501 strain of 2009 H1N1 virus infection was established, showing significantly elevated lung edema and cytokine levels compared to controls. Using our established animal model, the cytokine production profile and lung histology were assessed at different times post-infection, revealing increased lung lesions in a time-dependent manner. In additional,the mice were also treated with dexamethasone, which significantly improved survival rate and lung lesions in infected mice compared to those in control mice. Our data showed that corticosteroid treatment ameliorated acute lung injury induced by the 2009 A/H1N1 virus in mice and suggested that corticosteroids are valid drugs for treating 2009 A/H1N1 infection. Conclusions/Significance Using the established, very susceptible 2009 Pandemic Influenza A (H1N1) mouse model, our studies indicate that corticosteroids are a potential therapeutic remedy that may address the increasing concerns over future 2009 A/H1N1pandemics. PMID:22952892

  14. High tumor necrosis factor alpha (TNF-alpha) production in Trypanosoma cruzi-infected pregnant mice and increased TNF-alpha gene transcription in their offspring.

    PubMed Central

    Rivera, M T; Marques de Araujo, S; Lucas, R; Deman, J; Truyens, C; Defresne, M P; de Baetselier, P; Carlier, Y

    1995-01-01

    Since tumor necrosis factor alpha (TNF-alpha) is known to be involved in the feto-maternal relationship, this cytokine was studied in Trypanosoma cruzi-infected pregnant BALB/c mice and their fetuses and offspring. Pregnant chronically infected mice displayed significantly higher levels of circulating TNF-alpha than animals either only infected or only pregnant. TNF-alpha was undetectable in sera of uninfected and nonpregnant mice as well as in breast milk obtained from infected and uninfected animals. Fetuses from infected mice exhibited significantly more cells containing TNF-alpha mRNA in their thymus than fetuses from uninfected mothers. When infected 2 months after birth, offspring born to infected and uninfected mothers displayed similar amounts of circulating TNF-alpha during chronic infection, whereas this cytokine was only weakly detectable during the acute phase of the disease. An intravenous injection of lipopolysaccharide during acute infection strongly increased the production of TNF-alpha in offspring born to infected mothers to levels higher than those in progeny from uninfected mice. These results suggest that TNF-alpha is an important cytokine in the feto-maternal relationship during T. cruzi infection and that fetuses and offspring of infected mothers are primed to produce elevated levels of TNF-alpha. PMID:7822027

  15. Buparvaquone is active against Neospora caninum in vitro and in experimentally infected mice

    PubMed Central

    Müller, Joachim; Aguado-Martinez, Adriana; Manser, Vera; Balmer, Vreni; Winzer, Pablo; Ritler, Dominic; Hostettler, Isabel; Arranz-Solís, David; Ortega-Mora, Luis; Hemphill, Andrew

    2015-01-01

    The naphthoquinone buparvaquone is currently the only drug used against theileriosis. Here, the effects of buparvaquone were investigated in vitro and in an experimental mouse model for Neospora caninum infection. In 4-day proliferation assays, buparvaquone efficiently inhibited N. caninum tachyzoite replication (IC50 = 4.9 nM; IC100 = 100 nM). However, in the long term tachyzoites adapted and resumed proliferation in the presence of 100 nM buparvaquone after 20 days of cultivation. Parasiticidal activity was noted after 9 days of culture in 0.5 µM or 6 days in 1 µM buparvaquone. TEM of N. caninum infected fibroblasts treated with 1 µM buparvaquone showed that the drug acted rather slowly, and ultrastructural changes were evident only after 3–5 days of treatment, including severe alterations in the parasite cytoplasm, changes in the composition of the parasitophorous vacuole matrix and a diminished integrity of the vacuole membrane. Treatment of N. caninum infected mice with buparvaquone (100 mg/kg) either by intraperitoneal injection or gavage prevented neosporosis symptoms in 4 out of 6 mice in the intraperitoneally treated group, and in 6 out of 7 mice in the group receiving oral treatment. In the corresponding controls, all 6 mice injected intraperitoneally with corn oil alone died of acute neosporosis, and 4 out of 6 mice died in the orally treated control group. Assessment of infection intensities in the treatment groups showed that, compared to the drug treated groups, the controls showed a significantly higher parasite load in the lungs while cerebral parasite load was higher in the buparvaquone-treated groups. Thus, although buparvaquone did not eliminate the parasites infecting the CNS, the drug represents an interesting lead with the potential to eliminate, or at least diminish, fetal infection during pregnancy. PMID:25941626

  16. Acute colitis produced by chemotactic peptides in rats and mice.

    PubMed Central

    Chester, J. F.; Ross, J. S.; Malt, R. A.; Weitzman, S. A.

    1985-01-01

    Colonic inflammation was produced in rats and mice by peptides chemotactic for polymorphonuclear leukocytes. Instillation of formylmethionyl-leucyl-phenylalanine (FMLP) and formylnorleucyl-leucyl-phenylalanine (FNLP) into isolated segments of rat colon caused marked mucosal edema and polymorphonuclear leukocyte infiltration within 2 hours. Higher concentrations of FNLP caused ulceration and necrosis as well. Formylmethionine (FMet), a compound with less chemotactic activity, caused much less inflammation. In mice, rectal instillation of FNLP caused dose-dependent acute mucosal inflammation which persisted for longer than 12 hours. Twice-weekly rectal instillation of FNLP provided a model of colitis based on neutrophil chemotaxis. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:4061566

  17. Acute Myopericarditis Likely Secondary to Disseminated Gonococcal Infection.

    PubMed

    Bunker, Daniel; Kerr, Leslie Dubin

    2015-01-01

    Disseminated gonococcal infection (DGI) is a rare complication of primary infection with Neisseria gonorrhoeae. Cardiac involvement in this condition is rare, and is usually limited to endocarditis. However, there are a number of older reports suggestive of direct myocardial involvement. We report a case of a 38-year-old male with HIV who presented with chest pain, pharyngitis, tenosynovitis, and purpuric skin lesions. Transthoracic echocardiogram showed acute biventricular dysfunction. Skin biopsy showed diplococci consistent with disseminated gonococcal infection, and treatment with ceftriaxone improved his symptoms and ejection fraction. Though gonococcal infection was never proven with culture or nucleic acid amplification testing, the clinical picture and histologic findings were highly suggestive of DGI. Clinicians should consider disseminated gonococcal infection when a patient presents with acute myocarditis, especially if there are concurrent skin and joint lesions. PMID:26246922

  18. Lupeol Protects Against Cerulein-Induced Acute Pancreatitis in Mice.

    PubMed

    Kim, Min-Jun; Bae, Gi-Sang; Choi, Sun Bok; Jo, Il-Joo; Kim, Dong-Goo; Shin, Joon-Yeon; Lee, Sung-Kon; Kim, Myoung-Jin; Song, Ho-Joon; Park, Sung-Joo

    2015-10-01

    Lupeol is a triterpenoid commonly found in fruits and vegetables and is known to exhibit a wide range of biological activities, including antiinflammatory and anti-cancer effects. However, the effects of lupeol on acute pancreatitis specifically have not been well characterized. Here, we investigated the effects of lupeol on cerulein-induced acute pancreatitis in mice. Acute pancreatitis was induced via an intraperitoneal injection of cerulein (50 µg/kg). In the lupeol treatment group, lupeol was administered intraperitoneally (10, 25, or 50 mg/kg) 1 h before the first cerulein injection. Blood samples were taken to determine serum cytokine and amylase levels. The pancreas was rapidly removed for morphological examination and used in the myeloperoxidase assay, trypsin activity assay, and real-time reverse transcription polymerase chain reaction. In addition, we isolated pancreatic acinar cells using a collagenase method to examine the acinar cell viability. Lupeol administration significantly attenuated the severity of pancreatitis, as was shown by reduced pancreatic edema, and neutrophil infiltration. In addition, lupeol inhibited elevation of digestive enzymes and cytokine levels, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and interleukin (IL)-6. Furthermore, lupeol inhibited the cerulein-induced acinar cell death. In conclusion, these results suggest that lupeol exhibits protective effects on cerulein-induced acute pancreatitis. PMID:26179197

  19. Induction of ulcerative colitis in mice influences the course of infection with the nematode Trichuris muris.

    PubMed

    Vegas-Sánchez, M C; Rollán-Landeras, E; García-Rodríguez, J J; Bolás-Fernández, F

    2015-09-01

    The aim of this study was to assess the effect of infection with the nematode whipworm Trichuris muris on the course of chemically induced acute ulcerative colitis in CBA/J mice, a strain proven to be highly resistant to infection with T. muris. Each mouse was infected with 50 embryonated eggs of T. muris by oral gavage. Acute colitis was triggered by administering 4% dextran sulphate sodium (DSS) in the drinking water for nine consecutive days at different times after infection. Concurrent infection and DSS administration exacerbate the severity of the colitis while favouring the permanence of parasites in the intestine. The induction of ulcerative colitis from days 54 to 62 post-infection (p.i.), when all worms had been expelled, ameliorated the course of the inflammatory disease. When ulcerative colitis was triggered earlier on, from days 27 to 35 p.i., the beneficial effects on inflammatory events were clearly shown with signs of mucosal epithelization and regeneration as early as day 1 after DSS administration. Previous infections by T. muris therefore accelerate recovery from subsequently induced inflammatory bowel disease and such an effect assists the nematode to persist in the intestinal niche. PMID:25007240

  20. Acute hantavirus infection induces galectin-3-binding protein.

    PubMed

    Hepojoki, Jussi; Strandin, Tomas; Hetzel, Udo; Sironen, Tarja; Klingström, Jonas; Sane, Jussi; Mäkelä, Satu; Mustonen, Jukka; Meri, Seppo; Lundkvist, Ake; Vapalahti, Olli; Lankinen, Hilkka; Vaheri, Antti

    2014-11-01

    Hantaviruses are zoonotic viruses that cause life-threatening diseases when transmitted to humans. Severe hantavirus infection is manifested by impairment of renal function, pulmonary oedema and capillary leakage. Both innate and adaptive immune responses contribute to the pathogenesis, but the underlying mechanisms are not fully understood. Here, we showed that galectin-3-binding protein (Gal-3BP) was upregulated as a result of hantavirus infection both in vitro and in vivo. Gal-3BP is a secreted glycoprotein found in human serum, and increased Gal-3BP levels have been reported in chronic viral infections and in several types of cancer. Our in vitro experiments showed that, whilst Vero E6 cells (an African green monkey kidney cell line) constitutively expressed and secreted Gal-3BP, this protein was detected in primary human cells only as a result of hantavirus infection. Analysis of Gal-3BP levels in serum samples of cynomolgus macaques infected experimentally with hantavirus indicated that hantavirus infection induced Gal-3BP also in vivo. Finally, analysis of plasma samples collected from patients hospitalized because of acute hantavirus infection showed higher Gal-3BP levels during the acute than the convalescent phase. Furthermore, the Gal-3BP levels in patients with haemorrhagic fever with renal syndrome correlated with increased complement activation and with clinical variables reflecting the severity of acute hantavirus infection. PMID:25013204

  1. Antimicrobial blue light therapy for Candida albicans burn infection in mice

    NASA Astrophysics Data System (ADS)

    Zhang, Yunsong; Wang, Yucheng; Murray, Clinton K.; Hamblin, Michael R.; Gu, Ying; Dai, Tianhong

    2015-05-01

    In this preclinical study, we investigated the utility of antimicrobial blue light therapy for Candida albicans infection in acutely burned mice. A bioluminescent strain of C. albicans was used. The susceptibilities to blue light inactivation were compared between C. albicans and human keratinocyte. In vitro serial passaging of C. albicans on blue light exposure was performed to evaluate the potential development of resistance to blue light inactivation. A mouse model of acute thermal burn injury infected with the bioluminescent strain of C. albicans was developed. Blue light (415 nm) was delivered to mouse burns for decolonization of C. albicans. Bioluminescence imaging was used to monitor in real time the extent of fungal infection in mouse burns. Experimental results showed that C. albicans was approximately 42-fold more susceptible to blue light inactivation in vitro than human keratinocyte (P=0.0022). Serial passaging of C. albicans on blue light exposure implied a tendency for the fungal susceptibility to blue light inactivation to decrease with the numbers of passages. Blue light reduced fungal burden by over 4-log10 (99.99%) in acute mouse burns infected with C. albicans in comparison to infected mouse burns without blue light therapy (P=0.015).

  2. Crocin attenuates lipopolysacchride-induced acute lung injury in mice

    PubMed Central

    Wang, Jian; Kuai, Jianke; Luo, Zhonghua; Wang, Wuping; Wang, Lei; Ke, Changkang; Li, Xiaofei; Ni, Yunfeng

    2015-01-01

    Crocin, a representative of carotenoid compounds, exerts a spectrum of activities including radical scavenger, anti-microbial and anti-inflammatory properties. To investigate the protective effect of crocin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg). The mice received intragastric injection of crocin (50 mg/kg) 1 h before LPS administration. Pulmonary histological changes were evaluated by hematoxylineosin stain and lung wet/dry weight ratios were observed. Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and nitric oxide (NO), and myeloperoxidase (MPO) activity were measured by enzymelinked immunosorbent assay. Expression of inducible nitric oxide synthase (iNOS) in lung tissues was determined by Western blot analysis. Crocin pretreatment significantly alleviated the severity of lung injury and inhibited the production of TNF-α and IL-1β in mice with ALI. After LPS administration, the lung wet/dry weight ratios, as an index of lung edema, and MPO activity were also markedly reduced by crocin pretreatment. Crocin pretreatment also reduced the concentrations of NO in lung tissues. Furthermore, the expression of iNOS was significantly suppressed by crocin pretreatment. Croncin potently protected against LPS-induced ALI and the protective effects of crocin may attribute partly to the suppression of iNOS expression. PMID:26191176

  3. Effect of Three Drugs against Encephalitozoon cuniculi Infection in Immunosuppressed Mice

    PubMed Central

    da Costa, Lidiana F. Vidoto; de Castro, João Manoel

    2013-01-01

    Microsporidia comprise a large group of obligate intracellular parasites. The microsporidian Encephalitozoon cuniculi causes disseminated infection in immunosuppressed patients with HIV, cancer, or transplants and in the elderly. In vivo and in vitro studies on the effectiveness of drugs are controversial. Currently, there is no effective treatment. We tested albendazole, albendazole sulfoxide, metronidazole, and cyclosporine in mice immunosuppressed with cyclophosphamide and inoculated by the intraperitoneal route with 107 E. cuniculi spores. One week after experimental inoculation, the mice were treated with albendazole, albendazole sulfoxide, metronidazole, and cyclosporine. Histological and morphometric analyses were performed to compare the treated groups. The state of immunosuppression was evaluated by phenotyping CD4+ and CD8+ T cells by flow cytometry. Nontreated mice showed acute disseminated and fatal encephalitozoonosis. The treatment with benzimidazoles significantly reduced infection until 30 days posttreatment (p.t.), but at 60 days p.t., the infection had recurred. Metronidazole decreased infection by a short time, and cyclosporine was not effective. All animals were immunosuppressed by all the experiments, as demonstrated by the low number of CD4+ and CD8+ T cells. We conclude that no drug was effective against E. cuniculi, but the benzimidazoles controlled the infection transiently. PMID:23612191

  4. UVC Light Prophylaxis for Cutaneous Wound Infections in Mice

    PubMed Central

    Dai, Tianhong; Garcia, Barbara; Murray, Clinton K.; Vrahas, Mark S.

    2012-01-01

    UVC light has long been known to be highly germicidal but has not been much developed as a therapy for infections. This study investigated the potential of UVC light for the prophylaxis of infections developing in highly contaminated superficial cutaneous wounds. In vitro studies demonstrated that the pathogenic bacteria Pseudomonas aeruginosa and Staphylococcus aureus were inactivated at UVC light exposures much lower than those needed for a similar effect on mammalian keratinocytes. Mouse models of partial-thickness skin abrasions infected with bioluminescent P. aeruginosa and S. aureus were developed. Approximately 107 bacterial cells were inoculated onto wounds measuring 1.2 by1.2 cm on the dorsal surfaces of mice. UVC light was delivered at 30 min after bacterial inoculation. It was found that for both bacterial infections, UVC light at a single radiant exposure of 2.59 J/cm2 reduced the bacterial burden in the infected mouse wounds by approximately 10-fold in comparison to those in untreated mouse wounds (P < 0.00001). Furthermore, UVC light increased the survival rate of mice infected with P. aeruginosa by 58.3% (P = 0.0023) and increased the wound healing rate in mice infected with S. aureus by 31.2% (P < 0.00001). DNA lesions were observed in the UVC light-treated mouse wounds; however, the lesions were extensively repaired by 48 h after UVC light exposure. These results suggested that UVC light may be used for the prophylaxis of cutaneous wound infections. PMID:22564833

  5. Human metapneumovirus infection activates the TSLP pathway that drives excessive pulmonary inflammation and viral replication in mice.

    PubMed

    Lay, Margarita K; Céspedes, Pablo F; Palavecino, Christian E; León, Miguel A; Díaz, Rodrigo A; Salazar, Francisco J; Méndez, Gonzalo P; Bueno, Susan M; Kalergis, Alexis M

    2015-06-01

    Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infections in children and the elderly. The mechanism by which this virus triggers an inflammatory response still remains unknown. Here, we evaluated whether the thymic stromal lymphopoietin (TSLP) pathway contributes to lung inflammation upon hMPV infection. We found that hMPV infection promotes TSLP expression both in human airway epithelial cells and in the mouse lung. hMPV infection induced lung infiltration of OX40L(+) CD11b(+) DCs. Mice lacking the TSLP receptor deficient mice (tslpr(-/-) ) showed reduced lung inflammation and hMPV replication. These mice displayed a decreased number of neutrophils as well a reduction in levels of thymus and activation-regulated chemokine/CCL17, IL-5, IL-13, and TNF-α in the airways upon hMPV infection. Furthermore, a higher frequency of CD4(+) and CD8(+) T cells was found in tslpr(-/-) mice compared to WT mice, which could contribute to controlling viral spread. Depletion of neutrophils in WT and tslpr(-/-) mice decreased inflammation and hMPV replication. Remarkably, blockage of TSLP or OX40L with specific Abs reduced lung inflammation and viral replication following hMPV challenge in mice. Altogether, these results suggest that activation of the TSLP pathway is pivotal in the development of pulmonary pathology and pulmonary hMPV replication. PMID:25763996

  6. Differential Diagnosis and Treatment Proposal for Acute Endodontic Infection.

    PubMed

    Keine, Kátia Cristina; Kuga, Milton Carlos; Pereira, Kamila Figueiredo; Diniz, Ana Carolina Soares; Tonetto, Mateus Rodrigues; Galoza, Marina Oliveira Gonçalves; Magro, Miriam Graziele; de Barros, Yolanda Benedita Abadia Martins; Bandéca, Matheus Coelho; de Andrade, Marcelo Ferrarezi

    2015-12-01

    The objective of this study was to describe the main lesions that simulate clinically and propose a treatment protocol for acute endodontic infection. Signs and clinical symptoms of periodontal abscess, gingival abscess, odontoma, herpes simplex, pericoronitis, acute pulpitis and necrotizing ulcerative gingivitis/periodontitis (NUG/NUP) were described and compared with acute endodontic infections. A treatment protocol was described by optimizing the procedures in access cavity, microbial decontamination and detoxification of the root canal, apical debridement, intracanal and systemic medication and surgical drainage procedures. The convenience of the use of 5.25% sodium hypochlorite, root canal instrumentation using a crown-down technique, intracanal medication with 2% chlorhexidine or triple antibiotic paste and the convenience of the use of antibiotics, analgesics, and surgical drainage to solve cases of acute dentoalveolar abscess was discussed. PMID:27018033

  7. Screening for acute HIV infection in South Africa: finding acute and chronic disease

    PubMed Central

    Bassett, Ingrid V.; Chetty, Senica; Giddy, Janet; Reddy, Shabashini; Bishop, Karen; Lu, Zhigang; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2010-01-01

    Background The yield of screening for acute HIV infection among general medical patients in resource-scarce settings remains unclear. Our objective was to evaluate a strategy of pooled HIV plasma RNA to diagnose acute HIV infection in patients with negative or discordant rapid HIV antibody tests in Durban, South Africa. Methods We prospectively enrolled patients with negative or discordant rapid HIV antibody tests from a routine HIV screening program in an outpatient department in Durban with an HIV prevalence of 48%. Study participants underwent venipuncture for pooled qualitative HIV RNA, and if positive, quantitative RNA, enzyme immunoassay and Western Blot (WB). Patients with negative or indeterminate WB and positive quantitative HIV RNA were considered acutely infected. Those with chronic infection (positive RNA and WB) despite negative or discordant rapid HIV tests were considered false negative rapid antibody tests. Results Nine hundred ninety-four participants were enrolled with either negative (N=976) or discordant (N=18) rapid test results. Eleven (1.1%, 95% CI: 0.6–2.0%) had acute HIV infection. Of the 994 patients, an additional 20 (2.0%, 95% CI: 1.3–.3.1%) had chronic HIV infection (false negative rapid test). Conclusions One percent of outpatients with negative or discordant rapid HIV tests in Durban, South Africa had acute HIV infection readily detectable through pooled serum HIV RNA screening. Pooled RNA testing also identified an additional 2% of patients with chronic HIV infection. HIV RNA screening has the potential to identify both acute and chronic HIV infections that are otherwise missed by standard HIV testing algorithms. PMID:20553336

  8. Fish Oil-Fed Mice Have Impaired Resistance to Influenza Infection12

    PubMed Central

    Schwerbrock, Nicole M. J.; Karlsson, Erik A.; Shi, Qing; Sheridan, Patricia A.; Beck, Melinda A.

    2009-01-01

    Dietary fish oils, rich in (n-3) PUFA, including eicosapentaenoic acid and docosahexaenoic acid, have been shown to have antiinflammatory properties. Although the antiinflammatory properties of fish oil may be beneficial during a chronic inflammatory illness, the same antiinflammatory properties can suppress the inflammatory responses necessary to combat acute viral infection. Given that (n-3) fatty acid-rich fish oil supplementation is on the rise and with the increasing threat of an influenza pandemic, we tested the effect of fish oil feeding for 2 wk on the immune response to influenza virus infection. Male C57BL/6 mice fed either a menhaden fish oil/corn oil diet (4 g fish oil:1 g corn oil, wt:wt at 5 g/100 g diet) or a control corn oil diet were infected with influenza A/PuertoRico/8/34 and analyzed for lung pathology and immune function. Although fish oil-fed mice had lower lung inflammation compared with controls, fish oil feeding also resulted in a 40% higher mortality rate, a 70% higher lung viral load at d 7 post infection, and a prolonged recovery period following infection. Although splenic natural killer (NK) cell activity was suppressed in fish oil-fed mice, lung NK activity was not affected. Additionally, lungs of infected fish oil-fed mice had significantly fewer CD8+ T cells and decreased mRNA expression of macrophage inflammatory protein-1-α, tumor necrosis factor-α, and interleukin-6. These results suggest that the antiinflammatory properties of fish oil feeding can alter the immune response to influenza infection, resulting in increased morbidity and mortality. PMID:19549756

  9. Influenza A (H1N1) Virus Infection Triggers Severe Pulmonary Inflammation in Lupus-Prone Mice following Viral Clearance

    PubMed Central

    Slight-Webb, Samantha R.; Bagavant, Harini; Crowe, Sherry R.; James, Judith A.

    2015-01-01

    Each year, up to one fifth of the United States population is infected with influenza virus. Although mortality rates are low, hundreds of thousands are hospitalized each year in the United States. Specific high risk groups, such as those with suppressed or dysregulated immune systems, are at greater danger for influenza complications. Respiratory infections are a common cause of hospitalizations and early mortality in patients with systemic lupus erythematosus (SLE); however, whether this increased infection risk is a consequence of the underlying dysregulated immune background and/or immunosuppressing drugs is unknown. To evaluate the influenza immune response in the context of lupus, as well as assess the effect of infection on autoimmune disease in a controlled setting, we infected lupus-prone MRL/MpJ-Faslpr mice with influenza virus A PR/8/34 H1N1. Interestingly, we found that Faslpr mice generated more influenza A virus specific T cells with less neutrophil accumulation in the lung during acute infection. Moreover, Faslpr mice produced fewer flu-specific IgG and IgM antibodies, but effectively cleared the virus. Further, increased extrinsic apoptosis during influenza infection led to a delay in autoimmune disease pathology with decreased severity of splenomegaly and kidney disease. Following primary influenza A infection, Faslpr mice had severe complications during the contraction and resolution phase with widespread severe pulmonary inflammation. Our findings suggest that influenza infection may not exacerbate autoimmune pathology in mice during acute infection as a direct result of virus induced apoptosis. Additionally, autoimmunity drives an enhanced antigen-specific T cell response to clear the virus, but persisting pulmonary inflammation following viral clearance may cause complications in this lupus animal model. PMID:25563403

  10. Multiple mechanisms contribute to impairment of type 1 interferon production during chronic lymphocytic choriomeningitis virus infection of mice.

    PubMed

    Lee, Lian Ni; Burke, Shannon; Montoya, Maria; Borrow, Persephone

    2009-06-01

    Type 1 IFNs, innate cytokines with important effector and immunomodulatory properties, are rapidly induced in the acute phase of many virus infections; however, this is generally a transient response that is not sustained during virus persistence. To gain insight into mechanisms that can contribute to down-regulation of type 1 IFN production during virus persistence, we analyzed type 1 IFN production during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection. High-level type 1 IFN production was transiently up-regulated in cells including plasmacytoid and conventional dendritic cells (DCs) following LCMV infection of mice, but LCMV persistence was associated with only low-level type 1 IFN production. Nonetheless, chronically infected mice were able to up-regulate type 1 IFN production in response to TLR3, 7, and 9 ligands, albeit less efficiently than uninfected mice. Splenic DC numbers in mice chronically infected with LCMV were decreased, and the remaining cells exhibited a reduced response to TLR stimulation. LCMV-infected cell lines efficiently up-regulated type 1 IFN production following TLR ligation and infection with a DNA virus, but exhibited a defect in type 1 IFN induction following infection with Sendai, an RNA virus. This block in type 1 IFN production by infected cells, together with abnormalities in DC numbers and functions, likely contribute to the low-level type 1 IFN production in mice chronically infected with LCMV. Impairment of type 1 IFN production may both promote virus persistence and impact on host immunocompetence. Understanding the mechanisms involved may assist in development of strategies for control of virus persistence and superinfection. PMID:19454715

  11. Imaging in acute renal infection in children

    SciTech Connect

    Sty, J.R.; Wells, R.G.; Starshak, R.J.; Schroeder, B.A.

    1987-03-01

    Infection is the most common disease of the urinary tract in children, and various imaging techniques have been used to verify its presence and location. On retrospective analysis, 50 consecutive children with documented upper urinary tract infection had abnormal findings on renal cortical scintigraphy with 99mTc-glucoheptonate. The infection involved the renal poles only in 38 and the poles plus other renal cortical areas in eight. Four had abnormalities that spared the poles. Renal sonograms were abnormal in 32 of 50 children. Excretory urograms were abnormal in six of 23 children in whom they were obtained. Vesicoureteral reflux was found in 34 of 40 children in whom voiding cystourethrography was performed. These data show the high sensitivity of renal cortical scintigraphy with 99mTc-glucoheptonate in documenting upper urinary tract infection. The location of the abnormalities detected suggests that renal infections spread via an ascending mode and implies that intrarenal reflux is a major contributing factor.

  12. Role of neutralizing antibodies and T-cells in pathogenesis of herpes simplex virus infection in congenitally athymic mice.

    PubMed

    Kapoor, A K; Buckmaster, A; Nash, A A; Field, H J; Wildy, P

    1982-11-01

    Congenitally athymic nude mice were infected with 10(4) p.f.u. herpes simplex type 1 (strain SC16). Following the passive transfer of neutralizing monoclonal antibodies (AP7, AP8 and AP12) it was observed that AP7 alone reduced the virus infectivity in the nervous system; AP8 and AP12 failed to protect mice probably due to poor in vivo binding to the neutralization site on the virus. Latent ganglionic infection could be established in nude mice following adoptive transfer of optimum number (2 x 10(7) cells/mouse) of immune lymph node cells from day 7 herpes virus-infected hairy immunocompetent donor mice. Moreover, in some of the immune lymph node cell protected nudes, latency could be maintained even in complete absence of neutralizing antibodies. Results of ear-ablation experiments revealed that removal of primary source of infection after day 5 of infection reduced the amount of virus in the ganglia and spinal cord. Acute neurological infection was not detected following transfer of protective anti-gp-D neutralizing antibody (LP2) in combination with removal of infected pinna. These data suggest that continuous seeding of virus occurs in related ganglia via the axonal route from infected ear pinna. It appears that local T-cell-mediated immune mechanisms are involved in maintenance of latency. PMID:6984425

  13. Effect of different stages of Schistosoma mansoni infection on the parasite burden and immune response to Strongyloides venezuelensis in co-infected mice.

    PubMed

    de Rezende, Michelle Carvalho; Araújo, Emília Souza; Moreira, João Marcelo Peixoto; Rodrigues, Vanessa Fernandes; Rodrigues, Jailza Lima; Pereira, Cíntia A de Jesus; Negrão-Corrêa, Deborah

    2015-12-01

    Multiple schistosome and soil-transmitted nematode infections are frequently reported in human populations living in tropical areas of developing countries. In addition to exposure factors, the host immune response plays an important role in helminth control and morbidity in hosts with multiple infections; however, these aspects are difficult to evaluate in human populations. In the current study, female Swiss mice were simultaneously co-infected with Strongyloides venezuelensis and Schistosoma mansoni or infected with St. venezuelensis at 2, 4, or 14 weeks after Sc. mansoni infection. The simultaneously infected mice showed a similar parasite burden for St. venezuelensis compared with mono-infected mice. In contrast, there was a significant reduction of St. venezuelensis burden (primarily during the migration of the larvae) in mice that were previously infected with Sc. mansoni at the acute or chronic phase. Independent of the stage of Sc. mansoni infection, the St. venezuelensis co-infection was capable of inducing IL-4 production in the small intestine, increasing the IgE concentration in the serum and increasing eosinophilia in the lungs and intestine. This result suggests that the nematode infection stimulates local type 2 immune responses independently of the schistosomiasis stage. Moreover, previous Sc. mansoni infection stimulated early granulocyte infiltration in the lungs and trematode-specific IgM and IgG1 production that recognized antigens from St. venezuelensis infective larvae; these immune responses would act in the early control of St. venezuelensis larvae. Our data suggest that the effect of multiple helminth infections on host susceptibility and morbidity largely depends on the species of parasite and the immune response. PMID:26350380

  14. Effect of host age on experimental K virus infection in mice.

    PubMed Central

    Greenlee, J E

    1981-01-01

    Mice were inoculated by the oral route with K virus at 4, 8, 12, and 23 days and at 4 months of age. The effect of host age on the pathogenesis of infection was studied by immunofluorescence, virus assay, and histopathology. K virus produced a systemic infection in all animals, although the infection because progressively more limited as animals matured. In mice inoculated at 4 days of age, K virus infection resulted in a fatal interstitial pneumonia identical to that seen in newborn animals and was characterized by the presence of virus and viral antigen in pulmonary and extrapulmonary vascular endothelia, reticuloendothelial organs, and brains. In older animals, K virus infection was clinically inapparent; organ involvement was similar in distribution to that seen in fatally infected suckling ice, but cells exhibiting specific viral fluorescence were fewer in number and viral titers were lower. Although animals surviving K virus infection developed high titers of hemagglutination inhibition antibody to the virus, positive cells and infectious virus could still be detected in intestines 2 months after inoculation. In animals inoculated at 8 and 12 days of age, in which K virus produced an extensive initial infection, virus could also be detected 56 days after inoculation in lungs, livers, spleens, and brains. The present study indicates that murine K virus produces a systemic infection throughout the life of its host and that the maturation of host defenses and the development of specific humoral immunity, although they limit dissemination of virus during acute infection, may not eliminate viral persistence in intestines or other organs once infection has occurred. Images PMID:7263066

  15. Cyclophilin A protects mice against infection by influenza A virus

    PubMed Central

    Li, Jing; Chen, Can; Wong, Gary; Dong, Wei; Zheng, Weinan; Li, Yun; Sun, Lei; Zhang, Lianfeng; Gao, George F.; Bi, Yuhai; Liu, Wenjun

    2016-01-01

    Our previous studies indicate that Cyclophilin A (CypA) impairs the replication of influenza A virus in vitro. To further evaluate the antiviral functions of CypA and explore its mechanism, transgenic mice with overexpression of CypA by two specific promoters with SPC (CypA-SPC) or CMV (CypA-CMV) were developed. After challenge with the A/WSN/33(H1N1) influenza virus, CypA-SPC and CypA-CMV transgenic mice displayed nearly 2.5- and 3.8-fold stronger disease resistance to virus infection, respectively, compared to wild-type animals. Virus replication, pathological lesions and inflammatory cytokines were substantially reduced in both lines of transgenic mice. In addition, after infection there was an upregulation of genes associated with cell migration, immune function, and organ development; and a downregulation of genes associated with the positive regulation of immune cells and apoptosis in the peritoneal macrophages of CypA-overexpressing transgenic mice (CypA+). These results indicate that CypA is a key modulator of influenza virus resistance in mice, and that CypA+ mice constitutes an important model to study the roles of CypA in the regulation of immune responses and infections. PMID:27354005

  16. Cyclophilin A protects mice against infection by influenza A virus.

    PubMed

    Li, Jing; Chen, Can; Wong, Gary; Dong, Wei; Zheng, Weinan; Li, Yun; Sun, Lei; Zhang, Lianfeng; Gao, George F; Bi, Yuhai; Liu, Wenjun

    2016-01-01

    Our previous studies indicate that Cyclophilin A (CypA) impairs the replication of influenza A virus in vitro. To further evaluate the antiviral functions of CypA and explore its mechanism, transgenic mice with overexpression of CypA by two specific promoters with SPC (CypA-SPC) or CMV (CypA-CMV) were developed. After challenge with the A/WSN/33(H1N1) influenza virus, CypA-SPC and CypA-CMV transgenic mice displayed nearly 2.5- and 3.8-fold stronger disease resistance to virus infection, respectively, compared to wild-type animals. Virus replication, pathological lesions and inflammatory cytokines were substantially reduced in both lines of transgenic mice. In addition, after infection there was an upregulation of genes associated with cell migration, immune function, and organ development; and a downregulation of genes associated with the positive regulation of immune cells and apoptosis in the peritoneal macrophages of CypA-overexpressing transgenic mice (CypA+). These results indicate that CypA is a key modulator of influenza virus resistance in mice, and that CypA+ mice constitutes an important model to study the roles of CypA in the regulation of immune responses and infections. PMID:27354005

  17. Mice lack of LRG-47 display the attenuated outcome of infection with Schistosoma japonicum.

    PubMed

    Gao, Yanan; Wu, Jingjiao; Zhang, Meijuan; Hou, Min; Ji, Minjun

    2016-03-01

    Interferon-inducible GTPase LRG-47 (also named immune-related GTPase M, Irgm1) is a member of the p47 GTPase family that has been shown to regulate host resistance to intracellular pathogens. Little knowledge has been known about the role of LRG-47 in host's responses to extracellular pathogens. To investigate possible roles of LRG-47 in the course of Schistosoma japonicum infection, LRG-47-deficient (LRG-47(-/-)) and wild-type (WT) mice were challenged with cercariae of S. japonicum, and the cellular and humoral responses in mice were analyzed. At the acute stage of S. japonicum infection, in contrast to WT mice, LRG-47(-/-) mice showed the significantly decreased egg burden, low schistosome-specific antibody response, and the decreased Th1 and increased Tc1 responses. Additionally, Schistosoma japonicum-specific egg antigen immunization also produced the similar humoral and cellular immune responses as S. japonicum infection. Taken together, these data suggested that the deficiency of LRG-47 might affect host's CD4(+) T cell immune response via the weakening of IFN-γ downstream signaling; however, the specific function of LRG-47 on dealing with extracellular worm needs to be further studied. PMID:26660918

  18. Proteomic analysis of bronchoalveolar lavage fluid proteins from mice infected with Francisella tularensis ssp novicida

    SciTech Connect

    Varnum, Susan M.; Webb-Robertson, Bobbie-Jo M.; Pounds, Joel G.; Moore, Ronald J.; Smith, Richard D.; Frevert, Charles; Skerret, Shawn J.; Wunschel, David S.

    2012-07-06

    Francisella tularensis causes the zoonosis tularemia in humans and is one of the most virulent bacterial pathogens. We utilized a global proteomic approach to characterize protein changes in bronchoalveolar lavage fluid from mice exposed to one of three organisms, F. tularensis ssp. novicida, an avirulent mutant of F. tularensis ssp. novicida (F.t. novicida-ΔmglA); and Pseudomonas aeruginosa. The composition of BALF proteins was altered following infection, including proteins involved in neutrophil activation, oxidative stress and inflammatory responses. Components of the innate immune response were induced including the acute phase response and the complement system, however the timing of their induction varied. Francisella tularensis ssp. novicida infected mice do not appear to have an effective innate immune response in the first hours of infection, however within 24 hours they show an upregulation of innate immune response proteins. This delayed response is in contrast to P. aeruginosa infected animals which show an early innate immune response. Likewise, F.t. novicida-ΔmglA infection initiates an early innate immune response, however this response is dimished by 24 hours. Finally, this study identifies several candidate biomarkers, including Chitinase 3-like-1 (CHI3L1 or YKL-40) and peroxiredoxin 1, that are associated with F. tularensis ssp. novicida but not P. aeruginosa infection.

  19. Proteomic analysis of bronchoalveolar lavage fluid proteins from mice infected with Francisella tularensis ssp novicida

    PubMed Central

    Varnum, Susan M.; Webb-Robertson, Bobbie-Jo M.; Pounds, Joel G.; Moore, Ronald J.; Smith, Richard D.; Frevert, Charles W.; Skerrett, Shawn J.; Wunschel, David

    2012-01-01

    Francisella tularensis causes the zoonosis tularemia in humans and is one of the most virulent bacterial pathogens. We utilized a global proteomic approach to characterize protein changes in bronchoalveolar lavage fluid from mice exposed to one of three organisms, F. tularensis ssp. novicida, an avirulent mutant of F. tularensis ssp. novicida (F.t. novicida-ΔmglA); and Pseudomonas aeruginosa. The composition of BALF proteins was altered following infection, including proteins involved in neutrophil activation, oxidative stress and inflammatory responses. Components of the innate immune response were induced including the acute phase response and the complement system, however the timing of their induction varied. Francisella tularensis ssp. novicida infected mice do not appear to have an effective innate immune response in the first hours of infection, however within 24 hours they show an upregulation of innate immune response proteins. This delayed response is in contrast to P. aeruginosa infected animals which show an early innate immune response. Likewise, F.t. novicida-ΔmglA infection initiates an early innate immune response, however this response is dimished by 24 hours. Finally, this study identifies several candidate biomarkers, including Chitinase 3-like-1 (CHI3L1 or YKL-40) and peroxiredoxin 1, that are associated with F. tularensis ssp. novicida but not P. aeruginosa infection. PMID:22663564

  20. Wogonoside ameliorates lipopolysaccharide-induced acute lung injury in mice.

    PubMed

    Zhang, Liang; Ren, Yi; Yang, Chengliang; Guo, Yue; Zhang, Xiaojing; Hou, Gang; Guo, Xinjin; Sun, Nan; Liu, Yongyu

    2014-12-01

    Wogonoside has been reported to have anti-inflammatory properties. In this study, we evaluated the effect of wogonoside on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Male BALB/c mice with ALI, induced by intranasal instillation of LPS, were treated with wogonoside 1 h prior to LPS exposure. Mice treated with LPS alone showed significantly increased TNF-α, IL-6, and IL-1β levels in the bronchoalveolar lavage fluid (BALF). When pretreated with wogonoside, the TNF-α, IL-6, and IL-1β levels were significantly decreased. Meanwhile, wogonoside significantly inhibited LPS-induced increases in the macrophage and neutrophil infiltration of lung tissues and markedly attenuated myeloperoxidase activity. Furthermore, wogonoside inhibited the TLR4 expression and the phosphorylation of NF-κB p65, and IκB induced by LPS. In conclusion, our results indicate that wogonoside exhibits a protective effect on LPS-induced ALI via suppression of TLR4-mediated NF-κB signaling pathways. PMID:24854163

  1. Acute Infection in Total Knee Arthroplasty: Diagnosis and Treatment

    PubMed Central

    Martínez-Pastor, Juan Carlos; Maculé-Beneyto, Francisco; Suso-Vergara, Santiago

    2013-01-01

    Infection is one of the most serious complications after total knee arthroplasty (TKA). The current incidence of prosthetic knee infection is 1-3%, depending on the series. For treatment and control to be more cost effective, multidisciplinary groups made up of professionals from different specialities who can work together to eradicate these kinds of infections need to be assembled. About the microbiology, Staphylococcus aureus and coagulase-negative staphylococcus were among the most frequent microorganisms involved (74%). Anamnesis and clinical examination are of primary importance in order to determine whether the problem may point to a possible acute septic complication. The first diagnosis may then be supported by increased CRP and ESR levels. The surgical treatment for a chronic prosthetic knee infection has been perfectly defined and standardized, and consists in a two-stage implant revision process. In contrast, the treatment for acute prosthetic knee infection is currently under debate. Considering the different surgical techniques that already exist, surgical debridement with conservation of the prosthesis and polythene revision appears to be an attractive option for both surgeon and patient, as it is less aggressive than the two-stage revision process and has lower initial costs. The different results obtained from this technique, along with prognosis factors and conclusions to keep in mind when it is indicated for an acute prosthetic infection, whether post-operative or haematogenous, will be analysed by the authors. PMID:23919094

  2. B-Cell-Deficient Mice Show an Exacerbated Inflammatory Response in a Model of Chlamydophila abortus Infection

    PubMed Central

    Buendía, Antonio J.; Del Río, Laura; Ortega, Nieves; Sánchez, Joaquín; Gallego, María C.; Caro, María R.; Navarro, Jose A.; Cuello, Francisco; Salinas, Jesús

    2002-01-01

    The resolution of Chlamydophila abortus (Chlamydia psittaci serotype 1) infection is dependent on gamma interferon and CD8+ T cells, and classically, B cells have been considered to play a minimal role in host defense. The role of B cells in the immune response was studied by using a model of infection in mice with genetically modified immunoglobulin M transmembrane domains (μMT). In the absence of B cells, infection with C. abortus leads to an acute severe fatal disease that involves a disseminated intravascular coagulation syndrome. μMT mice displayed an increased level of proinflammatory cytokines in serum, and an increased number of neutrophils was observed in the lesions. The possible deleterious role of neutrophils in the pathogenesis of disease in μMT mice was determined by depletion of the neutrophils with the monoclonal antibody RB6-8C5. This led to an enhancement of the bacterial burden and early mortality in both μMT and wild-type mice, while necrotic lesions remained. Analysis of the presence of immunoregulatory cytokines showed significantly lower levels of transforming growth factor β in the sera of μMT mice. However, mice lacking mature B cells were able to establish a specific immune response that protected them from a secondary challenge. Taken together, these data suggest an immunomodulatory role for B cells in the early events of C. abortus primary infection that can protect mice against an exaggerated inflammatory response. PMID:12438369

  3. Colonic Expression of Genes Encoding Inflammatory Mediators and Gelatinases During Campylobacter Jejuni Infection of Conventional Infant Mice

    PubMed Central

    Heimesaat, Markus M.; Grundmann, Ursula; Alutis, Marie E.; Fischer, André; Göbel, Ulf B.; Bereswill, Stefan

    2016-01-01

    Within 1 week following peroral Campylobacter jejuni infection, infant mice develop acute enteritis resolving thereafter. We here assessed colonic expression profiles of mediators belonging to the IL-23/IL-22/IL-18 axis and of matrix-degrading gelatinases MMP-2 and MMP-9 at day 6 post C. jejuni strain 81-176 infection. Whereas the pathogen readily colonized the intestines of infant IL-18–/– mice only, colonic mucin-2 mRNA, a pivotal mucus constituent, was downregulated in IL-22–/– mice and accompanied by increased expression of pro-inflammatory cytokines including IFN-γ, TNF, IL-17A, and IL-1β. Furthermore, in both naive and infected IL-22–/– mice, colonic expression of IL-23p19 and IL-18 was lower as compared to wildtype mice, whereas, conversely, colonic IL-22 mRNA levels were lower in IL-18–/– and colonic IL-18 expression lower in IL-23p19–/– as compared to wildtype mice. Moreover, colonic expression of MMP-2 and MMP-9 and their endogenous inhibitor TIMP-1 were lower in IL-22–/– as compared to wildtype mice at day 6 postinfection. In conclusion, mediators belonging of the IL-23/IL-22/IL-18 axis as well as the gelatinases MMP-2 and MMP-9 are involved in mediating campylobacteriosis of infant mice in a differentially regulated fashion. PMID:27429796

  4. [Trypanosoma cruzi infection in pregnant mice induces a cellular immune response with citokines production in their fetuses].

    PubMed

    Alarcón, Maritza; Goncalves, Loredana; Colasante, Cesare; Araujo, Sonia; Moreno, Elio; Pérez-Aguilar, Mary Carmen

    2011-06-01

    The objective of this study was to detect the cytokines IFN-gamma, IL-4 and IL-10 expressed by CD4+ T cells in tissues of fetal mice with acute chagasic infection. For this, we examined the fetuses of NMRI mice whose mothers were infected with 22x10(3) metacyclic trypomastigotes of the M/HOM/BRA/53/Y strain of T. cruzi and made pregnant during the acute phase of infection. For the detection and localization of inflammatory infiltrates, nest parasites, antigens of T. cruzi a nd cytokines w eused hematoxylin-eosin techniques, peroxidase-anti-peroxidase and immunofluorescence. The immunohistochemical study revealed the presence of inflammatory infiltrates and antigens with amastigote nests in fetal skeletal muscle. CD4 + T cells producing IFN-gamma, as well as deposits of IFN-gamma and IL-10, were detected in sections of placenta, heart and skeletal muscle of fetuses of mice infected, while CD4+/IL-10+ was found only in skeletal muscle; in addition, deposits of IL-4 were detected only in placentas of healthy mice. These results indicate that fetuses are capable of generating their own immune response to antigens transmitted by their mother, which induces the secretion of cytokines and that, acting in synergy with the maternal antibodies, confer them a state of protection against infection; and that the transmission of the parasite depends on factors specific to each mother, which may modify its ability to control such transmission at the placental or systemic levels. PMID:21866787

  5. Immunochromatography-based Diagnosis of Rotavirus Infection in Acute Diarrhea.

    PubMed

    Vashishtha, Vipin M; Thacker, Sandeep; Namjoshi, Gajanan Sudhir

    2016-07-01

    Documentation of rotavirus diarrhea in a rural, resource-poor setting is a difficult task. We analyzed stool samples of 103 children admitted for acute diarrhea in a pediatric hospital in Bijnor, UP, India, using a simple bedside immunochromatography kit. Rotavirus infection was detected in 47 out of total of 103 children (45.6%). PMID:27508549

  6. Acute Borrelia infection inducing an APMPPE-like picture.

    PubMed

    Al Mousa, Munjid; Koch, Frank

    2016-12-01

    Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an uncommon disorder of unknown etiology affecting the retina, the retinal pigment epithelium, and the choroid. Although several etiological factors have been suggested, none has been confirmed. We report a case of APMPPE associated with acute infection of Borreliosis. A 30-year-old man presented with a decrease in vision in the right eye of about 1-week duration. His visual acuity in the right eye was 6/36. Fundus exam revealed the presence of multiple placoid creamy retinal/subretinal lesions in the right eye. Fundus fluorescein angiography supported the diagnosis of APMPPE. Blood tests revealed the presence of concomitant acute Borreliosis infection, as confirmed by IgM. The patient received oral prednisone therapy and amoxicillin. Six weeks later, the visual acuity returned to 6/6, and the patient was symptom free. Borreliosis can have several manifestations in the eye. One of the less common presentations is an APMPPE-like picture. The clinician should suspect acute Borreliosis infection in patients presenting with APMPPE, especially when there is a history of a tick bite, when the patient has systemic symptoms, or when living in/visiting endemic areas. This may help in the prompt management of APMPPE, avoiding complications due to the condition itself, or systemic involvement secondary to the Borreliosis infection. PMID:27294731

  7. Infection with Porphyromonas gingivalis Exacerbates Endothelial Injury in Obese Mice

    PubMed Central

    Inubushi, Toshihiro; Kitagawa, Masae; Furusho, Hisako; Ando, Toshinori; Ayuningtyas, Nurina Febriyanti; Nagasaki, Atsuhiro; Ishihara, Kazuyuki; Tahara, Hidetoshi; Kozai, Katsuyuki; Takata, Takashi

    2014-01-01

    Background A number of studies have revealed a link between chronic periodontitis and cardiovascular disease in obese patients. However, there is little information about the influence of periodontitis-associated bacteria, Porphyromonas gingivalis (Pg), on pathogenesis of atherosclerosis in obesity. Methods In vivo experiment: C57BL/6J mice were fed with a high-fat diet (HFD) or normal chow diet (CD), as a control. Pg was infected from the pulp chamber. At 6 weeks post-infection, histological and immunohistochemical analysis of aortal tissues was performed. In vitro experiment: hTERT-immortalized human umbilical vein endothelial cells (HuhT1) were used to assess the effect of Pg/Pg-LPS on free fatty acid (FFA) induced endothelial cells apoptosis and regulation of cytokine gene expression. Results Weaker staining of CD31 and increased numbers of TUNEL positive cells in aortal tissue of HFD mice indicated endothelial injury. Pg infection exacerbated the endothelial injury. Immunohistochemically, Pg was detected deep in the smooth muscle of the aorta, and the number of Pg cells in the aortal wall was higher in HFD mice than in CD mice. Moreover, in vitro, FFA treatment induced apoptosis in HuhT1 cells and exposure to Pg-LPS increased this effect. In addition, Pg and Pg-LPS both attenuated cytokine production in HuhT1 cells stimulated by palmitate. Conclusions Dental infection of Pg may contribute to pathogenesis of atherosclerosis by accelerating FFA-induced endothelial injury. PMID:25334003

  8. Type I interferon signaling protects mice from lethal henipavirus infection.

    PubMed

    Dhondt, Kévin P; Mathieu, Cyrille; Chalons, Marie; Reynaud, Joséphine M; Vallve, Audrey; Raoul, Hervé; Horvat, Branka

    2013-01-01

    Hendra virus (HeV) and Nipah virus (NiV) are closely related, recently emerged paramyxoviruses that form Henipavirus genus and are capable of causing considerable morbidity and mortality in a number of mammalian species, including humans. However, in contrast to many other species and despite expression of functional virus entry receptors, mice are resistant to henipavirus infection. We report here the susceptibility of mice deleted for the type I interferon receptor (IFNAR-KO) to both HeV and NiV. Intraperitoneally infected mice developed fatal encephalitis, with pathology and immunohistochemical features similar to what was found in humans. Viral RNA was found in the majority of analyzed organs, and sublethally infected animals developed virus-specific neutralizing antibodies. Altogether, these results reveal IFNAR-KO mice as a new small animal model to study HeV and NiV pathogenesis, prophylaxis, and treatment and suggest the critical role of type I interferon signaling in the control of henipavirus infection. PMID:23089589

  9. In Vivo Antimalarial Activity of Annona muricata Leaf Extract in Mice Infected with Plasmodium berghei

    PubMed Central

    Somsak, Voravuth; Polwiang, Natsuda; Chachiyo, Sukanya

    2016-01-01

    Malaria is one of the most important infectious diseases in the world. The choice for the treatment is highly limited due to drug resistance. Hence, finding the new compounds to treat malaria is urgently needed. The present study was attempted to evaluate the antimalarial activity of the Annona muricata aqueous leaf extract in Plasmodium berghei infected mice. Aqueous leaf extract of A. muricata was prepared and tested for acute toxicity in mice. For efficacy test in vivo, standard 4-day suppressive test was carried out. ICR mice were inoculated with 107 parasitized erythrocytes of P. berghei ANKA by intraperitoneal injection. The extracts (100, 500, and 1000 mg/kg) were then given orally by gavage once a day for 4 consecutive days. Parasitemia, percentage of inhibition, and packed cell volume were subsequently calculated. Chloroquine (10 mg/kg) was given to infected mice as positive control while untreated control was given only distilled water. It was found that A. muricata aqueous leaf extract at doses of 100, 500, and 1000 mg/kg resulted in dose dependent parasitemia inhibition of 38.03%, 75.25%, and 85.61%, respectively. Survival time was prolonged in infected mice treated with the extract. Moreover, no mortality to mice was observed with this extract up to a dose of 4000 mg/kg. In conclusion, the A. muricata aqueous leaf extract exerted significant antimalarial activity with no toxicity and prolonged survival time. Therefore, this extract might contain potential lead molecule for the development of a new drug for malaria treatment. PMID:27092277

  10. In Vivo Antimalarial Activity of Annona muricata Leaf Extract in Mice Infected with Plasmodium berghei.

    PubMed

    Somsak, Voravuth; Polwiang, Natsuda; Chachiyo, Sukanya

    2016-01-01

    Malaria is one of the most important infectious diseases in the world. The choice for the treatment is highly limited due to drug resistance. Hence, finding the new compounds to treat malaria is urgently needed. The present study was attempted to evaluate the antimalarial activity of the Annona muricata aqueous leaf extract in Plasmodium berghei infected mice. Aqueous leaf extract of A. muricata was prepared and tested for acute toxicity in mice. For efficacy test in vivo, standard 4-day suppressive test was carried out. ICR mice were inoculated with 10(7) parasitized erythrocytes of P. berghei ANKA by intraperitoneal injection. The extracts (100, 500, and 1000 mg/kg) were then given orally by gavage once a day for 4 consecutive days. Parasitemia, percentage of inhibition, and packed cell volume were subsequently calculated. Chloroquine (10 mg/kg) was given to infected mice as positive control while untreated control was given only distilled water. It was found that A. muricata aqueous leaf extract at doses of 100, 500, and 1000 mg/kg resulted in dose dependent parasitemia inhibition of 38.03%, 75.25%, and 85.61%, respectively. Survival time was prolonged in infected mice treated with the extract. Moreover, no mortality to mice was observed with this extract up to a dose of 4000 mg/kg. In conclusion, the A. muricata aqueous leaf extract exerted significant antimalarial activity with no toxicity and prolonged survival time. Therefore, this extract might contain potential lead molecule for the development of a new drug for malaria treatment. PMID:27092277

  11. A Defect in Interleukin-10 Leads to Enhanced Malarial Disease in Plasmodium chabaudi chabaudi Infection in Mice

    PubMed Central

    Li, Ching; Corraliza, Inés; Langhorne, Jean

    1999-01-01

    Infection of interleukin-10 (IL-10)-nonexpressing (IL-10−/−) mice with Plasmodium chabaudi chabaudi (AS) leads to exacerbated pathology in female mice and death in a proportion of them. Hypoglycemia, hypothermia, and loss in body weight were significantly greater in female IL-10−/− mice than in male knockout mice and all wild-type (WT) mice during the acute phase of infection. At this time, both female and male IL-10−/− mice produced more gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-12p40 mRNA than their respective WT counterparts. Inactivation of IFN-γ in IL-10−/− mice by the injection of anti-IFN-γ antibodies or by the generation of IL-10−/− IFN-γ receptor−/− double-knockout mice resulted in reduced mortality but did not affect body weight, temperature, or blood glucose levels. The data suggest that IFN-γ-independent pathways may be responsible for these pathological features of P. chabaudi malaria and may be due to direct stimulation of TNF-α by the parasite. Since male and female knockout mice both produce more inflammatory cytokines than their WT counterparts, it is likely that the mortality seen in females is due to the nature or magnitude of the response to these cytokines rather than the amount of IFN-γ or TNF-α produced. PMID:10456884

  12. Acute toxicity of pinnatoxins E, F and G to mice.

    PubMed

    Munday, Rex; Selwood, Andrew I; Rhodes, Lesley

    2012-11-01

    The acute toxicities to mice of pinnatoxins E, F and G, members of the cyclic imine group of phycotoxins, by intraperitoneal injection and/or oral administration, have been determined. These substances were all very toxic by intraperitoneal injection, with LD(50) values between 12.7 and 57 μg/kg. Pinnatoxin E was much less toxic by oral administration than by intraperitoneal injection, but this was not the case for pinnatoxin F. The median lethal doses of the latter substance by gavage and by voluntary intake were only 2 and 4 times higher than that by injection. The high oral toxicity of pinnatoxin F raises concerns as to the possibility of adverse effects of this substance in shellfish consumers, although it should be noted that no toxic effects in humans have been recorded with pinnatoxins or with any other compound of the cyclic imine group. PMID:22813782

  13. Nonreplicating, Cyst-Defective Type II Toxoplasma gondii Vaccine Strains Stimulate Protective Immunity against Acute and Chronic Infection

    PubMed Central

    2015-01-01

    Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph mutants, are highly effective in eliciting lifelong immunity to virulent acute infection by Toxoplasma gondii. However, it is currently unknown whether vaccine-elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem, we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II Δku80 genetic background by targeting the deletion of the orotidine 5′-monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes. Deletion of OMPDC induced a severe uracil auxotrophy with loss of replication, loss of virulence in mice, and loss of the ability to develop cysts and chronic infection. Vaccination of mice using type II Δku80 Δompdc mutants stimulated a fully protective CD8+ T cell-dependent immunity that prevented acute infection by type I and type II strains of T. gondii, and this vaccination also severely reduced or prevented cyst formation after type II challenge infection. Nonreverting, nonreplicating, and non-cyst-forming Δompdc mutants provide new tools to examine protective immune responses elicited by vaccination with a live attenuated type II vaccine. PMID:25776745

  14. Nonreplicating, cyst-defective type II Toxoplasma gondii vaccine strains stimulate protective immunity against acute and chronic infection.

    PubMed

    Fox, Barbara A; Bzik, David J

    2015-05-01

    Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph mutants, are highly effective in eliciting lifelong immunity to virulent acute infection by Toxoplasma gondii. However, it is currently unknown whether vaccine-elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem, we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II Δku80 genetic background by targeting the deletion of the orotidine 5'-monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes. Deletion of OMPDC induced a severe uracil auxotrophy with loss of replication, loss of virulence in mice, and loss of the ability to develop cysts and chronic infection. Vaccination of mice using type II Δku80 Δompdc mutants stimulated a fully protective CD8(+) T cell-dependent immunity that prevented acute infection by type I and type II strains of T. gondii, and this vaccination also severely reduced or prevented cyst formation after type II challenge infection. Nonreverting, nonreplicating, and non-cyst-forming Δompdc mutants provide new tools to examine protective immune responses elicited by vaccination with a live attenuated type II vaccine. PMID:25776745

  15. Impairment of T cell development and acute inflammatory response in HIV-1 Tat transgenic mice

    PubMed Central

    Fiume, Giuseppe; Scialdone, Annarita; Albano, Francesco; Rossi, Annalisa; Maria Tuccillo, Franca; Rea, Domenica; Palmieri, Camillo; Caiazzo, Elisabetta; Cicala, Carla; Bellevicine, Claudio; Falcone, Cristina; Vecchio, Eleonora; Pisano, Antonio; Ceglia, Simona; Mimmi, Selena; Iaccino, Enrico; Laurentiis, Annamaria de; Pontoriero, Marilena; Agosti, Valter; Troncone, Giancarlo; Mignogna, Chiara; Palma, Giuseppe; Arra, Claudio; Mallardo, Massimo; Maria Buonaguro, Franco; Scala, Giuseppe; Quinto, Ileana

    2015-01-01

    Immune activation and chronic inflammation are hallmark features of HIV infection causing T-cell depletion and cellular immune dysfunction in AIDS. Here, we addressed the issue whether HIV-1 Tat could affect T cell development and acute inflammatory response by generating a transgenic mouse expressing Tat in lymphoid tissue. Tat-Tg mice showed thymus atrophy and the maturation block from DN4 to DP thymic subpopulations, resulting in CD4+ and CD8+ T cells depletion in peripheral blood. In Tat-positive thymus, we observed the increased p65/NF-κB activity and deregulated expression of cytokines/chemokines and microRNA-181a-1, which are involved in T-lymphopoiesis. Upon LPS intraperitoneal injection, Tat-Tg mice developed an abnormal acute inflammatory response, which was characterized by enhanced lethality and production of inflammatory cytokines. Based on these findings, Tat-Tg mouse could represent an animal model for testing adjunctive therapies of HIV-1-associated inflammation and immune deregulation. PMID:26343909

  16. Impairment of T cell development and acute inflammatory response in HIV-1 Tat transgenic mice.

    PubMed

    Fiume, Giuseppe; Scialdone, Annarita; Albano, Francesco; Rossi, Annalisa; Tuccillo, Franca Maria; Rea, Domenica; Palmieri, Camillo; Caiazzo, Elisabetta; Cicala, Carla; Bellevicine, Claudio; Falcone, Cristina; Vecchio, Eleonora; Pisano, Antonio; Ceglia, Simona; Mimmi, Selena; Iaccino, Enrico; de Laurentiis, Annamaria; Pontoriero, Marilena; Agosti, Valter; Troncone, Giancarlo; Mignogna, Chiara; Palma, Giuseppe; Arra, Claudio; Mallardo, Massimo; Buonaguro, Franco Maria; Scala, Giuseppe; Quinto, Ileana

    2015-01-01

    Immune activation and chronic inflammation are hallmark features of HIV infection causing T-cell depletion and cellular immune dysfunction in AIDS. Here, we addressed the issue whether HIV-1 Tat could affect T cell development and acute inflammatory response by generating a transgenic mouse expressing Tat in lymphoid tissue. Tat-Tg mice showed thymus atrophy and the maturation block from DN4 to DP thymic subpopulations, resulting in CD4(+) and CD8(+) T cells depletion in peripheral blood. In Tat-positive thymus, we observed the increased p65/NF-κB activity and deregulated expression of cytokines/chemokines and microRNA-181a-1, which are involved in T-lymphopoiesis. Upon LPS intraperitoneal injection, Tat-Tg mice developed an abnormal acute inflammatory response, which was characterized by enhanced lethality and production of inflammatory cytokines. Based on these findings, Tat-Tg mouse could represent an animal model for testing adjunctive therapies of HIV-1-associated inflammation and immune deregulation. PMID:26343909

  17. [Anaerobic-aerobic infection in acute appendicitis].

    PubMed

    Mamchich, V I; Ulitovskiĭ, I V; Savich, E I; Znamenskiĭ, V A; Beliaeva, O A

    1998-01-01

    362 patients with acute appendicitis (AA) were examined. For microbiological diagnosis of aerobic and anaerobic nonclostridial microflora we used complex accelerated methods (including evaluation of gram-negative microorganisms in comparison with tinctorial-fermentative method of differential staining according to oxygen sensitivity of catalasopositive together with aerobic and cathalasonegative anaerobic microorganisms) as well as complete bacteriologic examination with determination of sensitivity of the above microorganism to antimicrobial remedies. High rate of aerobic-anaerobic microbial associations and substantial identity of microflora from appendicis and exudate from abdominal cavity was revealed, which evidenced the leading role of endogenous microorganisms in etiology and pathogenesis of AA and peritonitis i. e. autoinfection. In patients with destructive forms of AA, complicated by peritonitis it is recommended to use the accelerated method of examination of pathologic material as well as the complete scheme of examination with the identification of the isolated microorganisms and the correction of antibiotic treatment. PMID:9511291

  18. The CC Chemokine Receptor 5 Is Important in Control of Parasite Replication and Acute Cardiac Inflammation following Infection with Trypanosoma cruzi

    PubMed Central

    Hardison, Jenny L.; Wrightsman, Ruth A.; Carpenter, Philip M.; Kuziel, William A.; Lane, Thomas E.; Manning, Jerry E.

    2006-01-01

    Infection of susceptible mice with the Colombiana strain of Trypanosoma cruzi results in an orchestrated expression of chemokines and chemokine receptors within the heart that coincides with parasite burden and cellular infiltration. CC chemokine receptor 5 (CCR5) is prominently expressed during both acute and chronic disease, suggesting a role in regulating leukocyte trafficking and accumulation within the heart following T. cruzi infection. To better understand the functional role of CCR5 and its ligands with regard to both host defense and/or disease, CCR5−/− mice were infected with T. cruzi, and the disease severity was evaluated. Infected CCR5−/− mice develop significantly higher levels of parasitemia (P ≤ 0.05) and cardiac parasitism (P ≤ 0.01) during acute infection that correlated with reduced survival. Further, we show that CCR5 is essential for directing the migration of macrophages and T cells to the heart early in acute infection with T. cruzi. In addition, data are provided demonstrating that CCR5 does not play an essential role in maintaining inflammation in the heart during chronic infection. Collectively, these studies clearly demonstrate that CCR5 contributes to the control of parasite replication and the development of a protective immune response during acute infection but does not ultimately participate in maintaining a chronic inflammatory response within the heart. PMID:16368966

  19. USE OF MICRO ASSAY TECHNOLOGY TO COMPARE GENE EXPRESSION OF MICE INFECTED OR NOT INFECTED WITH CRYPTOSPORIDIUM PARVUM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cryptosporidium parvum is a protozoan parasite that is a frequent cause of diarrheal disease in young calves. In laboratory models of infection, infant mice are susceptible to C. parvum infection, while normal adult mice are not. Various immunodeficient strains of mice are, however, susceptible to...

  20. The Acute Gastrointestinal Syndrome in High-Dose Irradiated Mice

    PubMed Central

    Booth, Catherine; Tudor, Gregory; Tudor, Julie; Katz, Barry P; MacVittie, Thomas

    2012-01-01

    The most detailed reports of the response of the gastrointestinal system to high dose acute radiation have focused mainly on understanding the histopathology. However, to enable medical countermeasure assessment under the animal rule criteria, it is necessary to have a robust model in which the relationship between radiation dose and intestinal radiation syndrome incidence, timing and severity are established and correlated with histopathology. Although many mortality studies have been published, they have used a variety of mouse strains, ages, radiation sources and husbandry conditions, all of which influence the dose response. Further, it is clear that the level of bone marrow irradiation and supportive care can influence endpoints. In order to create robust baseline data we have generated dose response data in adult male mice, maintained under identical conditions, and exposed to either total or partial-body irradiation. Partial-body irradiation includes both extensive (40%) and minimal (5%) bone marrow sparing models, the latter designed to correlate with an established primate model and allow assessment of effects of any medical countermeasure on all three major radiation syndromes (intestinal, bone marrow and lung) in the surviving mice. Lethal dose (LD30, LD50 and LD70) data are described in the various models, along with the impact of enteric flora and response to supportive care. Correlation with diarrhea severity and histopathology are also described. This data can be used to aid the design of good laboratory practice (GLP) compliant Animal Rule studies that are reflective of the conditions following accidental radiation exposure. PMID:23091876

  1. Escin attenuates acute lung injury induced by endotoxin in mice.

    PubMed

    Xin, Wenyu; Zhang, Leiming; Fan, Huaying; Jiang, Na; Wang, Tian; Fu, Fenghua

    2011-01-18

    Endotoxin causes multiple organ dysfunctions, including acute lung injury (ALI). The current therapeutic strategies for endotoxemia are designed to neutralize one or more of the inflammatory mediators. Accumulating experimental evidence suggests that escin exerts anti-inflammatory and anti-edematous effects. The aim of this study was to evaluate the effect of escin on ALI induced by endotoxin in mice. ALI was induced by injection of lipopolysaccharide (LPS) intravenously. The mice were given dexamethasone or escin before injection of LPS. The mortality rate was recorded. Tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and nitric oxide (NO) were measured. Pulmonary superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, glutathione (GSH), malondialdehyde (MDA) contents, and myeloperoxidase (MPO) activity were also determined. The expression of glucocorticoid receptor (GR) level was detected by Western blotting. Pretreatment with escin could decrease the mortality rate, attenuate lung injury resulted from LPS, down-regulate the level of the inflammation mediators, including NO, TNF-α, and IL-1β, enhance the endogenous antioxidant capacity, and up-regulating the GR expression in lung. The results suggest that escin may have potent protective effect on the LPS-induced ALI by inhibiting of the inflammatory response, and its mechanism involves in up-regulating the GR and enhancing the endogenous antioxidant capacity. PMID:21040784

  2. Baylisascaris procyonis infection in white-footed mice: predicting patterns of infection from landscape habitat attributes.

    PubMed

    Beasley, J C; Eagan, T S; Page, L K; Hennessy, C A; Rhodes, O E

    2013-10-01

    There is a growing body of evidence that habitat fragmentation resulting from anthropogenic land use can alter the transmission dynamics of infectious disease. Baylisascaris procyonis , a parasitic roundworm with the ability to cause fatal central nervous system disease in many mammals, including humans, is a zoonotic threat, and research suggests that parasite recruitment rates by intermediate hosts are highly variable among forest patches in fragmented landscapes. During 2008, we sampled 353 white-footed mice ( Peromyscus leucopus ) from 22 forest patches distributed throughout a fragmented agricultural ecosystem to determine the influence of landscape-level habitat attributes on infection rates of B. procyonis in mice. We characterized each mouse in terms of infection status and intensity of infection, and calculated (on a patch-wide basis) prevalence, mean abundance of B. procyonis , and mean intensity of infection. We used an information-theoretic approach to develop a suite of candidate models characterizing the influence of landscape attributes on each of our measured characteristics of B. procyonis infection in white-footed mice, based on previous knowledge of raccoon ( Procyon lotor ) ecology and B. procyonis distribution in agricultural ecosystems. We observed evidence of B. procyonis infection in mice across all 22 habitat patches sampled. However, parasite recruitment rates and intensity were highly variable among patches, and the results of our analyses suggest that spatial variability in B. procyonis infections was primarily driven by emergent properties of fragmented ecosystems. In particular, prevalence, abundance, and intensity of B. procyonis infections in mice were negatively associated with the size and connectivity of forest patches. These results support previous studies indicating that habitat fragmentation can alter the transmission dynamics of infectious disease, and suggest that factors below the scale of landscape, i.e., fine

  3. Pulmonary Tuberculosis in Humanized Mice Infected with HIV-1

    PubMed Central

    Nusbaum, Rebecca J.; Calderon, Veronica E.; Huante, Matthew B.; Sutjita, Putri; Vijayakumar, Sudhamathi; Lancaster, Katrina L.; Hunter, Robert L.; Actor, Jeffrey K.; Cirillo, Jeffrey D.; Aronson, Judith; Gelman, Benjamin B.; Lisinicchia, Joshua G.; Valbuena, Gustavo; Endsley, Janice J.

    2016-01-01

    Co-infection with HIV increases the morbidity and mortality associated with tuberculosis due to multiple factors including a poorly understood microbial synergy. We developed a novel small animal model of co-infection in the humanized mouse to investigate how HIV infection disrupts pulmonary containment of Mtb. Following dual infection, HIV-infected cells were localized to sites of Mtb-driven inflammation and mycobacterial replication in the lung. Consistent with disease in human subjects, we observed increased mycobacterial burden, loss of granuloma structure, and increased progression of TB disease, due to HIV co-infection. Importantly, we observed an HIV-dependent pro-inflammatory cytokine signature (IL-1β, IL-6, TNFα, and IL-8), neutrophil accumulation, and greater lung pathology in the Mtb-co-infected lung. These results suggest that in the early stages of acute co-infection in the humanized mouse, infection with HIV exacerbates the pro-inflammatory response to pulmonary Mtb, leading to poorly formed granulomas, more severe lung pathology, and increased mycobacterial burden and dissemination. PMID:26908312

  4. Pulmonary Tuberculosis in Humanized Mice Infected with HIV-1.

    PubMed

    Nusbaum, Rebecca J; Calderon, Veronica E; Huante, Matthew B; Sutjita, Putri; Vijayakumar, Sudhamathi; Lancaster, Katrina L; Hunter, Robert L; Actor, Jeffrey K; Cirillo, Jeffrey D; Aronson, Judith; Gelman, Benjamin B; Lisinicchia, Joshua G; Valbuena, Gustavo; Endsley, Janice J

    2016-01-01

    Co-infection with HIV increases the morbidity and mortality associated with tuberculosis due to multiple factors including a poorly understood microbial synergy. We developed a novel small animal model of co-infection in the humanized mouse to investigate how HIV infection disrupts pulmonary containment of Mtb. Following dual infection, HIV-infected cells were localized to sites of Mtb-driven inflammation and mycobacterial replication in the lung. Consistent with disease in human subjects, we observed increased mycobacterial burden, loss of granuloma structure, and increased progression of TB disease, due to HIV co-infection. Importantly, we observed an HIV-dependent pro-inflammatory cytokine signature (IL-1β, IL-6, TNFα, and IL-8), neutrophil accumulation, and greater lung pathology in the Mtb-co-infected lung. These results suggest that in the early stages of acute co-infection in the humanized mouse, infection with HIV exacerbates the pro-inflammatory response to pulmonary Mtb, leading to poorly formed granulomas, more severe lung pathology, and increased mycobacterial burden and dissemination. PMID:26908312

  5. Innate immunity against bacterial infection following hyperoxia exposure is impaired in Nrf2-deficient mice

    PubMed Central

    Reddy, Narsa M.; Suryanarayana, Vegiraju; Kalvakolanu, Dhananjaya V; Yamamoto, Masayuki; Kensler, Thomas W.; Hassoun, Paul M.; Kleeberger, Steven R.; Reddy, Sekhar P.

    2010-01-01

    Summary Oxygen supplementation is used as therapy to support critically ill patients with severe respiratory impairment. Although hyperoxia has been shown to enhance the lung susceptibility to subsequent bacterial infection, the mechanisms underlying enhanced susceptibility remain enigmatic. We have reported that disruption of Nrf2, a master transcription regulator of various stress response pathways, enhances susceptibility to hyperoxia-induced acute lung injury (ALI) in mice, and have also demonstrated an association between a polymorphism in the NRF2 promoter and increased susceptibility to ALI. In this study, we show that Nrf2-deficient (Nrf2−/−) but not wild-type (Nrf2+/+) mice exposed to sub-lethal hyperoxia succumbed to death during recovery after P. aeruginosa infection. Nrf2-deficiency caused persistent bacterial pulmonary burden and enhanced levels of inflammatory cell infiltration as well as edema. Alveolar macrophages isolated from Nrf2−/− mice exposed to hyperoxia displayed persistent oxidative stress and inflammatory cytokine expression concomitant with diminished levels of antioxidant enzymes, such as Gclc, required for GSH biosynthesis. In vitro exposure of Nrf2−/− macrophages to hyperoxia strongly diminished their antibacterial activity and enhanced inflammatory cytokine expression compared to Nrf2+/+ cells. However, GSH supplementation during hyperoxic insult restored the ability of Nrf2−/− cells to mount antibacterial response and suppressed cytokine expression. Thus, loss of Nrf2 impairs lung innate immunity and promotes susceptibility to bacterial infection after hyperoxia exposure, ultimately leading to death of the host. PMID:19734219

  6. Nematode infection: A rare mimic of acute appendicitis

    PubMed Central

    Hotchen, Andrew; Chin, Kian; Raja, Mahzar

    2014-01-01

    INTRODUCTION Acute appendicitis is a common condition seen in all surgical units. One rare condition that can mimic acute appendicitis is a nematode infection of the bowel. There have been few reported cases of nematode infection within the appendix and none that have been accompanied by intra-operative pictures. PRESENTATION OF CASE A 16-year-old female presented with a 12 h history of right iliac fossa pain and mild pyrexia. Bloods showed a neutrophilia and normal C-reactive protein. Laparoscopy was performed which revealed a non-inflamed appendix. The appendix was dissected and a live nematode was visualised exiting the base of the appendix. Anti-helminthics were given and the infection resolved. DISCUSSION Nematode infection is most commonly seen in Africa, Asia and South America. When seen within the United Kingdom (UK), it is seen most commonly within high-risk populations. Testing for these infections is not routine within the UK and when they are performed, the results take a considerable amount of time to return. These tests should be considered within high-risk populations so that unnecessary surgery can be avoided. CONCLUSION This case highlights the importance of considering rare causes of right iliac fossa pain including nematode infection in a young patient. The case highlights this by giving intra-operative pictures of live nematodes upon dissection of the appendix. PMID:25024022

  7. Early cytokine and antibody responses against Coxiella burnetii in aerosol infection of BALB/c mice.

    PubMed

    Schoffelen, Teske; Self, Joshua S; Fitzpatrick, Kelly A; Netea, Mihai G; van Deuren, Marcel; Joosten, Leo A B; Kersh, Gilbert J

    2015-04-01

    Coxiella burnetii, a Gram-negative intracellular bacterium, can give rise to Q fever in humans and is transmitted mainly by inhalation of infected aerosols from animal reservoirs. Serology is commonly used to diagnose Q fever, but the early cellular immune response-i.e., C. burnetii-specific interferon γ (IFN-γ) production in response to antigen challenge-might be an additional diagnostic. Detection of IFN-γ responses has been used to identify past and chronic Q fever infections, but the IFN-γ response in acute Q fever has not been described. By challenging immunocompetent BALB/c mice with aerosols containing phase I C. burnetii, the timing and extent of IFN-γ recall responses were evaluated in an acute C. burnetii infection. Other cytokines were also measured in an effort to identify other potential diagnostic markers. The data show that after initial expansion of bacteria first in lungs and then in other tissues, the infection was cleared from day 10 onwards as reflected by the decreasing number of bacteria. The antigen-induced IFN-γ production by splenocytes coincided with emergence of IgM phase II antibodies at day 10 postinfection and preceded appearance of IgG antibodies. This was accompanied by the production of proinflammatory cytokines including interleukin (IL) 6, keratinocyte-derived cytokine, and IFN-γ-induced protein 10, followed by monocyte chemotactic protein 1, but not by IL-1β and tumor necrosis factor α, and only very low production of the anti-inflammatory cytokine IL-10. These data suggest that analysis of antigen-specific IFN-γ responses could be a useful tool for diagnosis of acute Q fever. Moreover, the current model of C. burnetii infection could be used to give new insights into immunological factors that predispose to development of persistent infection. PMID:25618420

  8. Deltamethrin Increases Candida albicans infection susceptibility in mice.

    PubMed

    Rehman, H; Mohan, A; Tabassum, H; Ahmad, F; Rahman, S; Parvez, S; Raisuddin, S

    2011-05-01

    Deltamethrin, an alpha-cyano type II synthetic pyrethroid insecticide, is used to control a wide range of insects on a variety of crops and vectors of diseases. Deltamethrin has been previously reported for its immunotoxic effects and therefore its exposure may affect the host resistance to infection and tumour challenge. Effect of exposure of deltamethrin on host resistance to Candida albicans infection was examined in Swiss albino mice. The objective of this study was to investigate the modulatory action of deltamethrin in C. albicans infected mice. The dose of deltamethrin was initially tested and selected from our previous study (18 mg/kg). Percentage of infection in deltamethrin treated animals increased faster when compared to that of the controls. Deltamethrin exposure along with C. albicans infection caused alteration of humoral immune response. The number of colony forming unit in liver and spleen were also found to be significantly increased in the treated group. The results from our present study suggest that deltamethrin exhibits an immunosuppressive effect and has a negative impact on host resistance to C. albicans infection. PMID:21272049

  9. Serum and aqueous humour cytokine response and histopathological alterations during ocular Toxoplasma gondii infection in C57BL/6 mice.

    PubMed

    Calabrese, K S; Tedesco, R C; Zaverucha do Valle, T; Barbosa, H S

    2008-12-01

    Toxoplasma gondii, an obligate intracellular protozoan parasite, infects most species of warm-blooded animals, and in humans it causes toxoplasmosis. Healthy people that become infected rarely present clinical symptoms because the immune system prevents the parasite from causing illness. Congenital toxoplasmosis may result in abortion, hydrocephalus, as well as neurological and ocular disease (most frequently retinochoroiditis) of the newborn. In immunocompromised patients, reactivation of latent disease can cause encephalitis. Cell-mediated immunity to T. gondii antigens involves innate acute inflammatory responses and antigen-specific adaptive immunity. Considering the complexity of the immunological events triggered during toxoplasmosis, systemic and local responses were evaluated by cytokine measurements. Aqueous humour and serum were obtained from non-infected and T. gondii Me-49 strain infected C57BL/6 mice for cytokine quantification. Histopathological analyses were made with eyes enucleated from mice after 30 days of infection. ELISA assays showed an increase of IFN-gamma levels both in serum and aqueous humour of infected mice in opposition to a decrease in IL-10 levels. On the other hand, TGF-beta was high, whereas IL-12 and TNF-alpha were present in small levels in both groups. We also detected higher levels of IL-4 and IL-6 in aqueous humour than in serum of infected mice when compared to the control group. MIP-2 presented no significant differences between the two groups. Fas and Fas-L were also present in similar levels in serum of non-infected and infected mice, but both chemokines were increased in the aqueous humour of infected mice. Histopathological analysis of infected mice showed inflammatory infiltrates around blood vessels and alteration of the outer photoreceptor segments, on the external and inner nuclear layer. Parasites were observed in 82% of eyes, inside the blood vessels associated with inflammatory infiltrate. Edema, characterized by

  10. An Atypical Splenic B Cell Progenitor Population Supports Antibody Production during Plasmodium Infection in Mice.

    PubMed

    Ghosh, Debopam; Wikenheiser, Daniel J; Kennedy, Brian; McGovern, Kathryn E; Stuart, Johnasha D; Wilson, Emma H; Stumhofer, Jason S

    2016-09-01

    Hematopoietic stem and progenitor cells (HSPCs) function to replenish the immune cell repertoire under steady-state conditions and in response to inflammation due to infection or stress. Whereas the bone marrow serves as the primary niche for hematopoiesis, extramedullary mobilization and differentiation of HSPCs occur in the spleen during acute Plasmodium infection, a critical step in the host immune response. In this study, we identified an atypical HSPC population in the spleen of C57BL/6 mice, with a lineage(-)Sca-1(+)c-Kit(-) (LSK(-)) phenotype that proliferates in response to infection with nonlethal Plasmodium yoelii 17X. Infection-derived LSK(-) cells upon transfer into naive congenic mice were found to differentiate predominantly into mature follicular B cells. However, when transferred into infection-matched hosts, infection-derived LSK(-) cells gave rise to B cells capable of entering into a germinal center reaction, and they developed into memory B cells and Ab-secreting cells that were capable of producing parasite-specific Abs. Differentiation of LSK(-) cells into B cells in vitro was enhanced in the presence of parasitized RBC lysate, suggesting that LSK(-) cells expand and differentiate in direct response to the parasite. However, the ability of LSK(-) cells to differentiate into B cells was not dependent on MyD88, as myd88(-/-) LSK(-) cell expansion and differentiation remained unaffected after Plasmodium infection. Collectively, these data identify a population of atypical lymphoid progenitors that differentiate into B lymphocytes in the spleen and are capable of contributing to the ongoing humoral immune response against Plasmodium infection. PMID:27448588

  11. Acute, lethal, natural killer cell-resistant myeloproliferative disease induced by polyomavirus in severe combined immunodeficient mice.

    PubMed Central

    Szomolanyi-Tsuda, E.; Dundon, P. L.; Joris, I.; Shultz, L. D.; Woda, B. A.; Welsh, R. M.

    1994-01-01

    Infection of severe combined immunodeficient mice, which lack T and B lymphocytes, with polyomavirus (PyV) induced an acute hematological disorder leading to the death of the mice by 2 weeks postinfection. The disease was characterized by a dramatic decrease in megakaryocytes, multiple hemorrhages, anemia, thrombocytopenia, splenomegaly, a massive myeloproliferation and splenic erythroproliferation with a defect in maturation of the myeloid elements similar to that in acute leukemia. This pathology in severe combined immunodeficient mice is very different from that of the well-characterized tumor profiles induced by PyV in normal newborn or nude mice. Viral T and capsid (VP1) antigens and viral genome were detected in some cells in the spleen, but not in the majority of the proliferating myeloid cells. This suggests that the myeloproliferation is induced by some indirect mechanism, such as secretion of growth factors or cytokines by virus-infected cells, rather than by direct transformation by PyV. Neither the spread of PyV, its replication in different organs, nor the pathogenesis or the time of death were altered by depleting natural killer cells in vivo by anti-natural killer cell antibodies. Analysis of the spleen leukocyte population indicated that the cells expressed high levels of class I major histocompatibility complex antigens and were resistant to lysis by activated natural killer cells. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8311119

  12. Protective effects of intravenous immunoglobulin and antimicrobial agents on acute pneumonia in leukopenic mice.

    PubMed

    Shimizu, Masaru; Katoh, Hideya; Hamaoka, Saeko; Kinoshita, Mao; Akiyama, Koichi; Naito, Yoshifumi; Sawa, Teiji

    2016-04-01

    Multi-drug resistant Pseudomonas aeruginosa causes the type of acute lung injury that is strongly associated with bacteremia, sepsis, and mortality, especially under immunocompromised conditions. Although administration of immunoglobulin solution is an applicable immunotherapy in immunocompromised patients, efficacy of immunoglobulin administration against multi-drug resistant P. aeruginosa pneumonia has not been well evaluated. In this study, we investigated the effectiveness of prophylactic administration of immunoglobulin solution (IVIG) in comparison with that of other types of antimicrobial agents, such as anti-PcrV IgG, piperacillin/tazobactam, or colistin in an immunocompromised mouse model of P. aeruginosa pneumonia. Colistin was the most effective agent for preventing acute lung injury, bacteremia, cytokinemia, and sepsis. Among the four tested antimicrobial agents, after colistin, anti-PcrV IgG and IVIG were the most effective at protecting mice from mortality. Piperacillin/tazobactam did not prevent acute lung injury or bacteremia; rather, it worsened lung histology. The data suggest that using an agent for which a positive result in an in vitro susceptibility test has been obtained may not always prevent acute lung injury in a leukopenic host infected with P. aeruginosa. Clinicians should consider the possibility of discrepancies between in vitro and in vivo tests because the absence of in vitro bactericidal activity in an antimicrobial agent is not always a reliable predictor of its lack of ability to eradicate bacteria in vivo, even in immunocompromised hosts. Based on our findings, the potential protective effects of IVIG against the acute lung injury induced by P. aeruginosa should be reevaluated. PMID:26867796

  13. Bone marrow is a major site of long-term antibody production after acute viral infection.

    PubMed Central

    Slifka, M K; Matloubian, M; Ahmed, R

    1995-01-01

    Antiviral antibody production is often sustained for long periods after resolution of an acute viral infection. Despite extensive documentation of this phenomenon, the mechanisms involved in maintaining long-term antibody production remain poorly defined. As a first step towards understanding the nature of long-term humoral immunity, we examined the anatomical location of antibody-producing cells during acute viral infection. Using the lymphocytic choriomeningitis virus (LCMV) model, we found that after resolution of the acute infection, when antiviral plasma cells in the spleen decline, a population of virus-specific plasma cells appears in the bone marrow and constitutes the major source of long-term antibody production. Following infection of adult mice, LCMV-specific antibody-secreting cells (ASC) peaked in the spleen at 8 days postinfection but were undetectable in the bone marrow at that time. The infection was essentially cleared by 15 days, and the ASC numbers in the spleen rapidly declined while an increasing population of LCMV-specific ASC began to appear in the bone marrow. Compared with the peak response at 8 days postinfection, time points from 30 days to more than 1 year later demonstrated greater-than-10-fold reductions in splenic ASC. In contrast, LCMV-specific plasma cell numbers in the bone marrow remained high and correlated with the high levels of antiviral serum antibody. The presence of LCMV-specific plasma cells in the bone marrow was not due to persistent infection at this site, since the virus was cleared from both the spleen and bone marrow with similar kinetics as determined by infectivity and PCR assays. The immunoglobulin G subclass profile of antibody-secreting cells derived from bone marrow and the spleen correlated with the immunoglobulin G subclass distribution of LCMV-specific antibody in the serum. Upon rechallenge with LCMV, the spleen exhibited a substantial increase in virus-specific plasma cell numbers during the early phase

  14. Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii

    PubMed Central

    Martins-Duarte, Erica S.; Dubar, Faustine; Lawton, Philippe; França da Silva, Cristiane; C. Soeiro, Maria de Nazaré; de Souza, Wanderley; Biot, Christophe; Vommaro, Rossiane C.

    2015-01-01

    Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is a worldwide disease whose clinical manifestations include encephalitis and congenital malformations in newborns. Previously, we described the synthesis of new ethyl-ester derivatives of the antibiotic ciprofloxacin with ~40-fold increased activity against T. gondii in vitro, compared with the original compound. Cipro derivatives are expected to target the parasite’s DNA gyrase complex in the apicoplast. The activity of these compounds in vivo, as well as their mode of action, remained thus far uncharacterized. Here, we examined the activity of the Cipro derivatives in vivo, in a model of acute murine toxoplasmosis. In addition, we investigated the cellular effects T. gondii tachyzoites in vitro, by immunofluorescence and transmission electron microscopy (TEM). When compared with Cipro treatment, 7-day treatments with Cipro derivatives increased mouse survival significantly, with 13–25% of mice surviving for up to 60 days post-infection (vs. complete lethality 10 days post-infection, with Cipro treatment). Light microscopy examination early (6 and 24h) post-infection revealed that 6-h treatments with Cipro derivatives inhibited the initial event of parasite cell division inside host cells, in an irreversible manner. By TEM and immunofluorescence, the main cellular effects observed after treatment with Cipro derivatives and Cipro were cell scission inhibition - with the appearance of ‘tethered’ parasites – malformation of the inner membrane complex, and apicoplast enlargement and missegregation. Interestingly, tethered daughter cells resulting from Cipro derivatives, and also Cipro, treatment did not show MORN1 cap or centrocone localization. The biological activity of Cipro derivatives against C. parvum, an apicomplexan species that lacks the apicoplast, is, approximately, 50 fold lower than that in T. gondii tachyzoites, supporting that these compounds targets the apicoplast. Our results show

  15. Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii.

    PubMed

    Martins-Duarte, Erica S; Dubar, Faustine; Lawton, Philippe; da Silva, Cristiane França; Soeiro, Maria de Nazaré C; de Souza, Wanderley; Biot, Christophe; Vommaro, Rossiane C

    2015-01-01

    Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is a worldwide disease whose clinical manifestations include encephalitis and congenital malformations in newborns. Previously, we described the synthesis of new ethyl-ester derivatives of the antibiotic ciprofloxacin with ~40-fold increased activity against T. gondii in vitro, compared with the original compound. Cipro derivatives are expected to target the parasite's DNA gyrase complex in the apicoplast. The activity of these compounds in vivo, as well as their mode of action, remained thus far uncharacterized. Here, we examined the activity of the Cipro derivatives in vivo, in a model of acute murine toxoplasmosis. In addition, we investigated the cellular effects T. gondii tachyzoites in vitro, by immunofluorescence and transmission electron microscopy (TEM). When compared with Cipro treatment, 7-day treatments with Cipro derivatives increased mouse survival significantly, with 13-25% of mice surviving for up to 60 days post-infection (vs. complete lethality 10 days post-infection, with Cipro treatment). Light microscopy examination early (6 and 24h) post-infection revealed that 6-h treatments with Cipro derivatives inhibited the initial event of parasite cell division inside host cells, in an irreversible manner. By TEM and immunofluorescence, the main cellular effects observed after treatment with Cipro derivatives and Cipro were cell scission inhibition--with the appearance of 'tethered' parasites--malformation of the inner membrane complex, and apicoplast enlargement and missegregation. Interestingly, tethered daughter cells resulting from Cipro derivatives, and also Cipro, treatment did not show MORN1 cap or centrocone localization. The biological activity of Cipro derivatives against C. parvum, an apicomplexan species that lacks the apicoplast, is, approximately, 50 fold lower than that in T. gondii tachyzoites, supporting that these compounds targets the apicoplast. Our results show that Cipro

  16. Adoptive transfer of resistance to acute Trypanosoma cruzi infection with T-lymphocyte-enriched spleen cells.

    PubMed Central

    Reed, S G

    1980-01-01

    Inbred C57BL/10 mice immunized with live culture forms of Trypanosoma cruzi were resistant to acute infection after challenge with bloodstream forms. Splenic leukocytes or serum from immunized mice were transferred to syngeneic recipients 2 days before of 2 days after challenge. Protection was not observed in recipients of serum, although the serum contained high levels of agglutinating antibody. Unfractionated splenic leukocytes from immunized donors conferred partial protection, and preparations enriched for T lymphocytes were significantly more effective than preparations enriched for B lymphocytes. Recipients of T-lymphocyte-enriched spleen cells had significantly higher survival times and significantly lower parasitemias than did recipients of B-lymphocyte-enriched spleen cells. PMID:6772557

  17. 2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice

    NASA Technical Reports Server (NTRS)

    Miller, E. S.; Bates, R. A.; Koebel, D. A.; Fuchs, B. B.; Sonnenfeld, G.

    1998-01-01

    Exposure to different forms of psychological and physiological stress can elicit a host stress response, which alters normal parameters of neuroendocrine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administered to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial growth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infection demonstrated an enhanced resistance to the listeria challenge. The enhanced bacterial clearance in vivo could not be explained by 2-DG exerting a toxic effect on the listeria, based on the results of two experiments. First, 2-DG did not inhibit listeria replication in trypticase soy broth. Second, replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2-DG, which correlated with the increased resistance to L. monocytogenes. These results support the contention that the host response to 2-DG-induced metabolic stress can influence the capacity of the immune system to resist infection by certain classes of microbial pathogens.

  18. Dental Infection of Porphyromonas gingivalis Induces Preterm Birth in Mice

    PubMed Central

    Ao, Min; Miyauchi, Mutsumi; Furusho, Hisako; Inubushi, Toshihiro; Kitagawa, Masae; Nagasaki, Atsuhiro; Sakamoto, Shinichi; Kozai, Katsuyuki; Takata, Takashi

    2015-01-01

    Background Epidemiological studies have revealed a link between dental infection and preterm birth or low birth weight (PTB/LBW), however, the underlying mechanisms remain unclear. Progress in understanding the associated mechanisms has been limited in part by lack of an animal model for chronic infection-induced PTB/LBW, mimicking pregnancy under conditions of periodontitis. We aimed to establish a mouse model of chronic periodontitis in order to investigate the link between periodontitis and PTB/LBW. Methods To establish chronic inflammation beginning with dental infection, we surgically opened mouse (female, 8 weeks old) 1st molar pulp chambers and directly infected with w83 strain Porphyromonas gingivalis (P.g.), a keystone periodontal pathogen. Mating was initiated at 6 wks post-infection, by which time dental granuloma tissue had developed and live P.g. was cultured from extracted tooth root, which serves as a persistent source of P.g. The gestational day (gd) and birth weight were recorded during for P.g.-infected and control mice, and serum and placental tissues were collected at gd 15 to evaluate the systemic and local conditions during pregnancy. Results Dental infection with P.g. significantly increased circulating TNF-α (2.5-fold), IL-17 (2-fold), IL-6 (2-fold) and IL-1β (2-fold). The P.g.-infected group delivered at gd 18.25 vs. gd 20.45 in the non-infected control (NC) group (p < 0.01), and pups exhibited LBW compared to controls (p < 0.01). P.g. was localized to placental tissues by immunohistochemistry and PCR, and defects in placental tissues of P.g. infected mice included premature rupture of membrane, placental detachment, degenerative changes in trophoblasts and endothelial cells, including necrotic areas. P.g. infection caused significantly increased numbers of polymorphonuclear leukocytes (PMNLs) and macrophages in placental tissues, associated with increased local expression of pro-inflammatory mediators including TNF-α and COX-2. Further

  19. Pathological Lesions and Inducible Nitric Oxide Synthase Expressions in the Liver of Mice Experimentally Infected with Clonorchis sinensis

    PubMed Central

    Yang, Qing-Li; Shen, Ji-Qing; Xue, Yan; Cheng, Xiao-Bing; Jiang, Zhi-Hua; Yang, Yi-Chao; Chen, Ying-Dan; Zhou, Xiao-Nong

    2015-01-01

    The nitric oxide (NO) formation and intrinsic nitrosation may be involved in the possible mechanisms of liver fluke-associated carcinogenesis. We still do not know much about the responses of inducible NO synthase (iNOS) induced by Clonorchis sinensis infection. This study was conducted to explore the pathological lesions and iNOS expressions in the liver of mice with different infection intensity levels of C. sinensis. Extensive periductal inflammatory cell infiltration, bile duct hyperplasia, and fibrosis were commonly observed during the infection. The different pathological responses in liver tissues strongly correlated with the infection intensity of C. sinensis. Massive acute spotty necrosis occurred in the liver parenchyma after a severe infection. The iNOS activity in liver tissues increased, and iNOS-expressing cells with morphological differences were observed after a moderate or severe infection. The iNOS-expressing cells in liver tissues had multiple origins. PMID:26797449

  20. Limited Ability of Posaconazole To Cure both Acute and Chronic Trypanosoma cruzi Infections Revealed by Highly Sensitive In Vivo Imaging

    PubMed Central

    Francisco, Amanda Fortes; Lewis, Michael D.; Jayawardhana, Shiromani; Taylor, Martin C.; Chatelain, Eric

    2015-01-01

    The antifungal drug posaconazole has shown significant activity against Trypanosoma cruzi in vitro and in experimental murine models. Despite this, in a recent clinical trial it displayed limited curative potential. Drug testing is problematic in experimental Chagas disease because of difficulties in demonstrating sterile cure, particularly during the chronic stage of infection when parasite burden is extremely low and tissue distribution is ill defined. To better assess posaconazole efficacy against acute and chronic Chagas disease, we have exploited a highly sensitive bioluminescence imaging system which generates data with greater accuracy than other methods, including PCR-based approaches. Mice inoculated with bioluminescent T. cruzi were assessed by in vivo and ex vivo imaging, with cyclophosphamide-induced immunosuppression used to enhance the detection of relapse. Posaconazole was found to be significantly inferior to benznidazole as a treatment for both acute and chronic T. cruzi infections. Whereas 20 days treatment with benznidazole was 100% successful in achieving sterile cure, posaconazole failed in almost all cases. Treatment of chronic infections with posaconazole did however significantly reduce infection-induced splenomegaly, even in the absence of parasitological cure. The imaging-based screening system also revealed that adipose tissue is a major site of recrudescence in mice treated with posaconazole in the acute, but not the chronic stage of infection. This in vivo screening model for Chagas disease is predictive, reproducible and adaptable to diverse treatment schedules. It should provide greater assurance that drugs are not advanced prematurely into clinical trial. PMID:26014936

  1. Current Perspectives of Prophylaxis and Management of Acute Infective Endophthalmitis.

    PubMed

    Tranos, Paris; Dervenis, Nikolaos; Vakalis, Athanasios N; Asteriadis, Solon; Stavrakas, Panagiotis; Konstas, Anastasios G P

    2016-05-01

    Endophthalmitis is an intraocular inflammatory condition which may or may not be caused by infective agents. Noninfectious (sterile) endophthalmitis may be attributable to various causes including postoperative retained soft lens matter or toxicity following introduction of other agents into the eye. Infectious endophthalmitis is further subdivided into endogenous and exogenous. In endogenous endophthalmitis there is hematogenous spread of organisms from a distant source of infection whereas in exogenous endophthalmitis direct microbial inoculation may occur usually following ocular surgery or penetrating eye injury with or without intraocular foreign bodies. Acute infective endophthalmitis is usually exogenous induced by inoculation of pathogens following ocular surgery, open-globe injury and intravitreal injections. More infrequently the infective source is internal and septicemia spreads to the eye resulting in endogenous endophthalmitis. Several risk factors have been implicated including immunosuppression, ocular surface abnormalities, poor surgical wound construction, complicated cataract surgery with vitreous loss and certain types of intraocular lens. Comprehensive guidelines and recommendations on prophylaxis and monitoring of surgical cases have been proposed to minimize the risk of acute endophthalmitis. Early diagnosis and prompt management of infective endophthalmitis employing appropriately selected intravitreal antibiotics are essential to optimize visual outcome. PMID:26935830

  2. ANA testing in the presence of acute and chronic infections.

    PubMed

    Litwin, Christine M; Binder, Steven R

    2016-01-01

    Autoantibody testing is performed to help diagnose patients who have clinical symptoms suggestive of possible autoimmune diseases. Antinuclear antibodies (ANA) are present in many systemic autoimmune conditions such as systemic lupus erythematosus (SLE). However, a positive ANA test may also be seen with non-autoimmune inflammatory diseases, including both acute and chronic infections. When the ANA test is used as an initial screen in patients with non-specific clinical symptoms, such as fever, joint pain, myalgias, fatigue, rash, or anemia, the likelihood of a positive result due to infection will increase, especially in children. This article identifies acute and chronic infectious diseases that are likely to produce a positive ANA result and summarizes recent literature addressing both the causes and consequences of these findings. PMID:27050929

  3. Ferret hepatitis E virus infection induces acute hepatitis and persistent infection in ferrets.

    PubMed

    Li, Tian-Cheng; Yang, Tingting; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Ishii, Koji; Kishida, Noriko; Shirakura, Masayuki; Asanuma, Hideki; Takeda, Naokazu; Wakita, Takaji

    2016-02-01

    Ferret hepatitis E virus (HEV), a novel hepatitis E virus, has been identified in ferrets. However, the pathogenicity of ferret HEV remains unclear. In the present study, we compared the HEV RNA-positivity rates and alanine aminotransferase (ALT) levels of 63 ferrets between before and after import from the US to Japan. We found that the ferret HEV-RNA positivity rates were increased from 12.7% (8/63) to 60.3% (38/63), and ALT elevation was observed in 65.8% (25/38) of the ferret HEV RNA-positive ferrets, indicating that ferret HEV infection is responsible for liver damage. From long term-monitoring of ferret HEV infection we determined that this infection in ferrets exhibits three patterns: sub-clinical infection, acute hepatitis, and persistent infection. The ALT elevation was also observed in ferret HEV-infected ferrets in a primary infection experiment. These results indicate that the ferret HEV infection induced acute hepatitis and persistent infection in ferrets, suggesting that the ferrets are a candidate animal model for immunological as well as pathological studies of hepatitis E. PMID:26790932

  4. Transient acute adrenal insufficiency associated with adenovirus serotype 40 infection

    PubMed Central

    Rai, Birendra; Ali, Muhammad; Kumar, Varun; Krebit, Ibraheem

    2014-01-01

    We present an instance of a 6-year-old boy who was admitted with adenovirus infection and developed transient acute adrenal insufficiency, which required supplementation with glucocorticoids and mineralocorticoids for 8 weeks. Adenovirus has got adrenotropic potential and can cause adrenal insufficiency. We could not find any similar reported case in medical literature. We hope our case would add to the existing knowledge of adenoviral complications in paediatric patients. PMID:24928932

  5. An Intradermal Inoculation Mouse Model for Immunological Investigations of Acute Scrub Typhus and Persistent Infection

    PubMed Central

    Rockx-Brouwer, Dedeke; Xu, Guang; Goez-Rivillas, Yenny; Drom, Claire; Shelite, Thomas R.; Valbuena, Gustavo; Walker, David H.; Bouyer, Donald H.

    2016-01-01

    Scrub typhus is a neglected tropical disease, caused by Orientia tsutsugamushi, a Gram-negative bacterium that is transmitted to mammalian hosts during feeding by Leptotrombidium mites and replicates predominantly within endothelial cells. Most studies of scrub typhus in animal models have utilized either intraperitoneal or intravenous inoculation; however, there is limited information on infection by the natural route in murine model skin or its related early host responses. Here, we developed an intradermal (i.d.) inoculation model of scrub typhus and focused on the kinetics of the host responses in the blood and major infected organs. Following ear inoculation with 6 x 104 O. tsutsugamushi, mice developed fever at 11–12 days post-infection (dpi), followed by marked hypothermia and body weight loss at 14–19 dpi. Bacteria in blood and tissues and histopathological changes were detected around 9 dpi and peaked around 14 dpi. Serum cytokine analyses revealed a mixed Th1/Th2 response, with marked elevations of MCP-1/CCL2, MIP-1α/CCL3 and IL-10 at 9 dpi, followed by increased concentrations of pro-inflammatory markers (IL-6, IL-12, IFN-γ, G-CSF, RANTES/CCL5, KC/CCL11, IL-1α/β, IL-2, TNF-α, GM-CSF), as well as modulatory cytokines (IL-9, IL-13). Cytokine levels in lungs had similar elevation patterns, except for a marked reduction of IL-9. The Orientia 47-kDa gene and infectious bacteria were detected in several organs for up to 84 dpi, indicating persistent infection. This is the first comprehensive report of acute scrub typhus and persistent infection in i.d.-inoculated C57BL/6 mice. This is a significant improvement over current murine models for Orientia infection and will permit detailed studies of host immune responses and infection control interventions. PMID:27479584

  6. An Intradermal Inoculation Mouse Model for Immunological Investigations of Acute Scrub Typhus and Persistent Infection.

    PubMed

    Soong, Lynn; Mendell, Nicole L; Olano, Juan P; Rockx-Brouwer, Dedeke; Xu, Guang; Goez-Rivillas, Yenny; Drom, Claire; Shelite, Thomas R; Valbuena, Gustavo; Walker, David H; Bouyer, Donald H

    2016-08-01

    Scrub typhus is a neglected tropical disease, caused by Orientia tsutsugamushi, a Gram-negative bacterium that is transmitted to mammalian hosts during feeding by Leptotrombidium mites and replicates predominantly within endothelial cells. Most studies of scrub typhus in animal models have utilized either intraperitoneal or intravenous inoculation; however, there is limited information on infection by the natural route in murine model skin or its related early host responses. Here, we developed an intradermal (i.d.) inoculation model of scrub typhus and focused on the kinetics of the host responses in the blood and major infected organs. Following ear inoculation with 6 x 104 O. tsutsugamushi, mice developed fever at 11-12 days post-infection (dpi), followed by marked hypothermia and body weight loss at 14-19 dpi. Bacteria in blood and tissues and histopathological changes were detected around 9 dpi and peaked around 14 dpi. Serum cytokine analyses revealed a mixed Th1/Th2 response, with marked elevations of MCP-1/CCL2, MIP-1α/CCL3 and IL-10 at 9 dpi, followed by increased concentrations of pro-inflammatory markers (IL-6, IL-12, IFN-γ, G-CSF, RANTES/CCL5, KC/CCL11, IL-1α/β, IL-2, TNF-α, GM-CSF), as well as modulatory cytokines (IL-9, IL-13). Cytokine levels in lungs had similar elevation patterns, except for a marked reduction of IL-9. The Orientia 47-kDa gene and infectious bacteria were detected in several organs for up to 84 dpi, indicating persistent infection. This is the first comprehensive report of acute scrub typhus and persistent infection in i.d.-inoculated C57BL/6 mice. This is a significant improvement over current murine models for Orientia infection and will permit detailed studies of host immune responses and infection control interventions. PMID:27479584

  7. Ligand Induction of Retinoic Acid Receptors Alters an Acute Infection by Murine Cytomegalovirus†

    PubMed Central

    Angulo, Ana; Chandraratna, Roshantha A. S.; LeBlanc, James F.; Ghazal, Peter

    1998-01-01

    Here we report that administration of retinoids can alter the outcome of an acute murine cytomegalovirus (MCMV) infection. We show that a crucial viral control element, the major immediate-early enhancer, can be activated by retinoic acid (RA) via multiple RA-responsive elements (DR2) that bind retinoid X receptor-retinoic acid receptor (RAR) heterodimers with apparent dissociation constants ranging from 15 to 33 nM. Viral growth is dramatically increased upon RA treatment of infected tissue culture cells. Using synthetic retinoid receptor-specific agonists and antagonists, we provide evidence that RAR activation in cells is required for mediating the response of MCMV to RA. Oral administration of RA to infected immunocompetent mice selectively exacerbates an infection by MCMV, while cotreatment with an RAR antagonist protects against the adverse effects of RA on MCMV infection. In conclusion, these chemical genetic experiments provide evidence that an RAR-mediated pathway can modulate in vitro and in vivo infections by MCMV. PMID:9573222

  8. Pteropine orthoreovirus infection among out-patients with acute upper respiratory tract infection in Malaysia.

    PubMed

    Voon, Kenny; Tan, Yeh Fong; Leong, Pooi Pooi; Teng, Cheong Lieng; Gunnasekaran, Rajasekaran; Ujang, Kamsiah; Chua, Kaw Bing; Wang, Lin-Fa

    2015-12-01

    This study aims to assess the incidence rate of Pteropine orthreovirus (PRV) infection in patients with acute upper respiratory tract infection (URTI) in a suburban setting in Malaysia, where bats are known to be present in the neighborhood. Using molecular detection of PRVs directly from oropharyngeal swabs, our study demonstrates that PRV is among one of the common causative agents of acute URTI with cough and sore throat as the commonest presenting clinical features. Phylogenetic analysis on partial major outer and inner capsid proteins shows that these PRV strains are closely related to Melaka and Kampar viruses previously isolated in Malaysia. Further study is required to determine the public health significance of PRV infection in Southeast Asia, especially in cases where co-infection with other pathogens may potentially lead to different clinical outcomes. PMID:26106066

  9. A Child with Acute Encephalopathy Associated with Quadruple Viral Infection

    PubMed Central

    Nakata, Keiko; Kashiwagi, Mitsuru; Masuda, Midori; Shigehara, Seiji; Oba, Chizu; Murata, Shinya; Kase, Tetsuo; Komano, Jun A.

    2015-01-01

    Pediatric acute encephalopathy (AE) was sometimes attributed to virus infection. However, viral infection does not always result in AE. The risk factors for developing infantile AE upon virus infection remain to be determined. Here, we report an infant with AE co-infected with human herpesvirus-6 (HHV-6) and three picornaviruses, including coxsackievirus A6 (CVA6), Enterovirus D68 (EV-D68), and human parechovirus (HPeV). EV-D68 was vertically transmitted to the infant from his mother. CVA6 and HPeV were likely transmitted to the infant at the nursery school. HHV-6 might be re-activated in the patient. It remained undetermined, which pathogen played the central role in the AE pathogenesis. However, active, simultaneous infection of four viruses should have evoked the cytokine storm, leading to the pathogenesis of AE. Conclusion: an infant case with active quadruple infection of potentially AE-causing viruses was seldom reported partly because systematic nucleic acid-based laboratory tests on picornaviruses were not common. We propose that simultaneous viral infection may serve as a risk factor for the development of AE. PMID:25883930

  10. Infection in acute leukemia patients receiving oral nonabsorable antibiotics.

    PubMed

    Hahn, D M; Schimpff, S C; Fortner, C L; Smyth, A C; Young, V M; Wiernik, P H

    1978-06-01

    During a 20-month period all acute nonlymphocytic patients (87 patient trials) receiving cytotoxic chemotherapy were placed on an oral nonabsorbable antibiotic regimen consisting of gentamicin, vancomycin, and nystatin in addition to an intensive program of infection prevention aimed at reducing exogenously acquired and body-surface potential pathogens. Although side effects of anorexia, diarrhea, and nausea were common, gentamicin-vancomycin-nystatin was ingested 80% of the study time. Microbial growth in gingival and rectal cultures was substantially reduced. The incidence of bacteremias and other serious infections was low. Pseudomonas aeruginosa, other gram-negative bacilli, and Candida species caused few infections along the alimentary canal, whereas infections of the skin (especially Staphylococcus aureus) were not reduced compared with those occurring in former years. A total of the 104 acquired gram-negative bacilli were gentamicin resistant; 5 subsequently caused infection. Thus, despite certain definite drawbacks, the use of oral nonabsorbable antibiotics to suppress alimentary tract microbial flora in combination with other infection prevention techniques in granulocytopenic cancer patients has proven feasible and tolerable and has been associated with a low order of life-threatening infections. PMID:98107

  11. Cytotoxic cells induced after Chlamydia psittaci infection in mice

    SciTech Connect

    Lammert, J.K.

    1982-03-01

    The ability of spleen cells from Chlamydia psittaci-infected mice to lyse C. psittaci-infected and uninfected target cell monolayers was studied. The cytotoxicity assay used was a terminal label method in which the number of adherent target cells surviving the interaction with effector cells was determined by measuring the uptake of (3H)uridine by such cells. It was observed that in the first few days postinfection (3 to 5), spleens contained cells that lysed infected and uninfected targets with equal efficiency. Subsequently, infected targets were killed primarily. The activity of effector spleen cells for infected targets continued, although at a reduced level, beyond 21 days postinfection. Intact effector cells were required since a disruption by sonication resulted in a loss of cytotoxicity. The enhanced killing observed with infected targets was also observed when target cells were sensitized with heat- or UV-inactivated C. psittaci. This study suggests that the induction of cytotoxic cells after C. psittaci infection may contribute to the ability of the host to control multiplication of the microorganism.

  12. The requirements of protein & amino acid during acute & chronic infections.

    PubMed

    Kurpad, Anura V

    2006-08-01

    Nutrition and infection interact with each other in a synergistic vicious cycle, leading to an adverse nutritional status and increased susceptibility to infection. Infectious episodes result in hypermetabolism and a negative nitrogen balance which is modulated by hormones, cytokines and other pro-inflammatory mediators, and is compounded by a reduced food intake. The extent of the negative nitrogen balance varies with the type of infection and its duration; however, it is reasonable to suggest that the loss of body protein could be minimized by the provision of dietary nitrogen, although anorexia will limit this. Further, distinctions need to be made about the provision of nutrients or protein during the catabolic and anabolic or recovery phase of the infection, since the capacity of the body to retain protein is enhanced in the anabolic recovery phase. Meeting the increased requirement for protein (and other nutrients) in infection does not imply a complete therapeutic strategy. Infections need to be treated appropriately, with nutrition as an adjunct to the treatment. Prior undernutrition could also impair the body's response to infection, although the weight of the evidence would suggest that this happens more particularly in oedematous undernutrition. In general, the amount of extra protein that would appear to be needed is of the order of 20-25 per cent of the recommended intake, for most infections. In acute infections, this is particularly relevant during the convalescence period. Community trials have suggested that lysine supplementation to the level required for normal daily nutriture, in predominantly wheat eating or potentially lysine deficient communities, improves immune function among other functional nutritional parameters; however, there is as yet insufficient evidence to suggest a specific requirement for amino acids in infections over and above the normal daily requirement as based on recent evidence. Some clinical studies that have showed

  13. Toxoplasma gondii Actively Inhibits Neuronal Function in Chronically Infected Mice

    PubMed Central

    Haroon, Fahad; Händel, Ulrike; Angenstein, Frank; Goldschmidt, Jürgen; Kreutzmann, Peter; Lison, Holger; Fischer, Klaus-Dieter; Scheich, Henning; Wetzel, Wolfram; Schlüter, Dirk; Budinger, Eike

    2012-01-01

    Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii–infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca2+) imaging studies revealed that tachyzoites actively manipulated Ca2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host. PMID:22530040

  14. Toxoplasma gondii actively inhibits neuronal function in chronically infected mice.

    PubMed

    Haroon, Fahad; Händel, Ulrike; Angenstein, Frank; Goldschmidt, Jürgen; Kreutzmann, Peter; Lison, Holger; Fischer, Klaus-Dieter; Scheich, Henning; Wetzel, Wolfram; Schlüter, Dirk; Budinger, Eike

    2012-01-01

    Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii-infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca(2+)) imaging studies revealed that tachyzoites actively manipulated Ca(2+) signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca(2+) uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca(2+) stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host. PMID:22530040

  15. Effects of Injected Iron and Siderophores on Infections in Normal and Immune Mice

    PubMed Central

    Kochan, Ivan; Wasynczuk, John; McCabe, Martha A.

    1978-01-01

    The fate of virulent and avirulent strains of Salmonella typhimurium in untreated and iron-injected mice and in transferrin-containing media demonstrated a direct relationship between bacterial virulence and the ability of bacteria to acquire transferrin-bound iron. Effects of injected iron on the development of infections with virulent and avirulent bacterial strains were determined in normal and immune mice by determinations of bacterial numbers in tissue homogenates and the mortality of infected animals. Results showed that infected and iron-injected mice died much more rapidly and frequently from overwhelming infections than infected and saline-injected mice. The infection-promoting effect of iron varied with the degree of bacterial virulence; the more virulent the bacteria, the more helpful was iron for the development of lethal infections. Siderophores promoted lethal infections in mice infected with virulent but not with avirulent bacteria. Experiments with vaccinated animals showed that iron exerted a deleterious effect on acquired immunity. Immune mice infected with virulent bacteria and injected with iron developed lethal infections as rapidly and nearly as frequently as similarly treated normal mice. Siderophores did not promote the development of lethal infections in immune mice. The effectiveness of iron, but not of siderophores, to promote bacterial infections in vaccinated mice revealed that acquired immunity is dependent upon the activity of an iron-neutralizable antibacterial system. Images PMID:365761

  16. Pivmecillinam for the treatment of acute uncomplicated urinary infection.

    PubMed

    Nicolle, L E

    1999-12-01

    Pivmecillinam is a beta-lactam antimicrobial marketed almost two decades ago. It has been used widely for the treatment of acute cystitis in selected areas of the world, particularly in Scandinavia. With increasing resistance of community Escherichia coli isolates to trimethoprim and trimethoprim/sulphamethoxazole, as previously observed for ampicillin and sulphonamides, reassessment of empiric antimicrobial regimens for acute uncomplicated urinary infection is necessary. Thus, it is timely to revisit the role of pivmecillinam for the treatment of acute cystitis. Clinical studies document the efficacy of this antimicrobial with short course therapy for acute cystitis, and clinical practice in countries where it has been used for many years confirms its efficacy and tolerability. If this agent were more widely used for empiric treatment for acute cystitis, use of antimicrobials such as the quinolones might be avoided. Further trials to define the comparative efficacy of pivmecillinam with other antimicrobials, and further studies of community resistance in E. coli isolates to this agent are needed. PMID:10692756

  17. Borrelia persica Infection in Immunocompetent Mice - A New Tool to Study the Infection Kinetics In Vivo

    PubMed Central

    Schwarzer, Sandra; Overzier, Evelyn; Hermanns, Walter; Baneth, Gad; Straubinger, Reinhard K.

    2016-01-01

    Borrelia persica, a bacterium transmitted by the soft tick Ornithodoros tholozani, causes tick-borne relapsing fever in humans in the Middle East, Central Asia and the Indian peninsula. Immunocompetent C3H/HeOuJ mice were infected intradermally with B. persica at varying doses: 1 x 106, 1 x 104, 1 x 102 and 4 x 100 spirochetes/mouse. Subsequently, blood samples were collected and screened for the presence of B. persica DNA. Spirochetes were detected in all mice infected with 1 x 106, 1 x 104 and 1 x 102 borrelia by real-time PCR targeting the flaB gene of the bacterium. Spirochetemia developed with a one- to two-day delay when 1 x 104 and 1 x 102 borrelia were inoculated. Mice injected with only four organisms were negative in all tests. No clinical signs were observed when infected mice were compared to negative control animals. Organs (heart, spleen, urinary bladder, tarsal joint, skin and brain) were tested for B. persica-specific DNA and cultured for the detection of viable spirochetes. Compiled data show that the target organs of B. persica infections are the brain and the skin. A newly developed serological two-tiered test system (ELISA and western blot) for the detection of murine IgM, IgG and IgA antibody titers against B. persica showed a vigorous antibody response of the mice during infection. In conclusion, the infection model described here for B. persica is a platform for in vivo studies to decipher the so far unexplored survival strategies of this Borrelia species. PMID:26890814

  18. Bone and Joint Infections in Children: Acute Hematogenous Osteomyelitis.

    PubMed

    Agarwal, Anil; Aggarwal, Aditya N

    2016-08-01

    Acute hematogenous osteomyelitis (AHO) is one of the commonest bone infection in childhood. Staphylococcus aureus is the commonest organism causing AHO. With use of advanced diagnostic methods, fastidious Kingella kingae is increasingly becoming an important organism in etiology of osteoarticular infections in children under the age of 3 y. The diagnosis of AHO is primarily clinical. The main clinical symptom and sign in AHO is pain and tenderness over the affected bone especially in the metaphyseal region. However, in a neonate the clinical presentation may be subtle and misleading. Laboratory and radiological investigations supplement the clinical findings. The acute phase reactants such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are frequently elevated. Ultrasonography and MRI are key imaging modalities for early detection of AHO. Determination of infecting organism in AHO is the key to the correct antibiotic choice, treatment duration and overall management and therefore, organism isolation using blood cultures and site aspiration should be attempted. Several effective antibiotics regimes are available for managing AHO in children. The choice of antibiotic and its duration and mode of delivery requires individualization depending upon severity of infection, causative organism, regional sensitivity patterns, time elapsed between onset of symptoms and child's presentation and the clinical and laboratory response to the treatment. If pus has been evidenced in the soft tissues or bone region, surgical decompression of abscess is mandatory. PMID:26096866

  19. In vivo imaging of mice infected with bioluminescent Trypanosoma cruzi unveils novel sites of infection

    PubMed Central

    2014-01-01

    Background The development of techniques that allow the imaging of animals infected with parasites expressing luciferase opens up new possibilities for following the fate of parasites in infected mammals. Methods D-luciferin potassium salt stock solution was prepared in phosphate-buffered saline (PBS) at 15 mg/ml. To produce bioluminescence, infected and control mice received an intraperitoneal injection of luciferin stock solution (150 mg/kg). All mice were immediately anesthetized with 2% isofluorane, and after 10 minutes were imaged. Ex vivo evaluation of infected tissues and organs was evaluated in a 24-well plate in 150 μg/ml D-luciferin diluted in PBS. Images were captured using the IVIS Lumina image system (Xenogen). Dissected organs were also evaluated by microscopy of hematoxylin-eosin stained sections. Results Here we describe the results obtained using a genetically modified Dm28c strain of T. cruzi expressing the firefly luciferase to keep track of infection by bioluminescence imaging. Progression of infection was observed in vivo in BALB/c mice at various intervals after infection with transgenic Dm28c-luc. The bioluminescent signal was immediately observed at the site of T. cruzi inoculation, and one day post infection (dpi) it was disseminated in the peritoneal cavity. A similar pattern in the cavity was observed on 7 dpi, but the bioluminescence was more intense in the terminal region of the large intestine, rectum, and gonads. On 14 and 21 dpi, bioluminescent parasites were also observed in the heart, snout, paws, hind limbs, and forelimbs. From 28 dpi to 180 dpi in chronically infected mice, bioluminescence declined in regions of the body but was concentrated in the gonad region. Ex vivo evaluation of dissected organs and tissues by bioluminescent imaging confirmed the in vivo bioluminescent foci. Histopathological analysis of dissected organs demonstrated parasite nests at the rectum and snout, in muscle fibers of mice infected with Dm28c

  20. Photodynamic therapy for Staphylococcus aureus infected burn wounds in mice.

    PubMed

    Lambrechts, Saskia A G; Demidova, Tatiana N; Aalders, Maurice C G; Hasan, Tayyaba; Hamblin, Michael R

    2005-07-01

    The rise of multiply antibiotic resistant bacteria has led to searches for novel antimicrobial therapies to treat infections. Photodynamic therapy (PDT) is a potential candidate; it uses the combination of a photosensitizer with visible light to produce reactive oxygen species that lead to cell death. We used PDT mediated by meso-mono-phenyl-tri(N-methyl-4-pyridyl)-porphyrin (PTMPP) to treat burn wounds in mice with established Staphylococcus aureus infections The third degree burn wounds were infected with bioluminescent S. aureus. PDT was applied after one day of bacterial growth by adding a 25% DMSO/500 microM PTMPP solution to the wound followed by illumination with red light and periodic imaging of the mice using a sensitive camera to detect the bioluminescence. More than 98% of the bacteria were eradicated after a light dose of 210 J cm(-2) in the presence of PTMPP. However, bacterial re-growth was observed. Light alone or PDT both delayed the wound healing. These data suggest that PDT has the potential to rapidly reduce the bacterial load in infected burns. The treatment needs to be optimized to reduce wound damage and prevent recurrence. PMID:15986057

  1. Host-microbiome interactions in acute and chronic respiratory infections.

    PubMed

    Taylor, Steven L; Wesselingh, Steve; Rogers, Geraint B

    2016-05-01

    Respiratory infection is a leading cause of global morbidity and mortality. Understanding the factors that influence risk and outcome of these infections is essential to improving care. We increasingly understand that interactions between the microbial residents of our mucosal surfaces and host regulatory systems is fundamental to shaping local and systemic immunity. These mechanisms are most well defined in the gastrointestinal tract, however analogous systems also occur in the airways. Moreover, we now appreciate that the host-microbiota interactions at a given mucosal surface influence systemic host processes, in turn, affecting the course of infection at other anatomical sites. This review discusses the mechanisms by which the respiratory microbiome influences acute and chronic airway disease and examines the contribution of cross-talk between the gastrointestinal and respiratory compartments to microbe-mucosa interactions. PMID:26972325

  2. Contemporary management of infected necrosis complicating severe acute pancreatitis

    PubMed Central

    Jamdar, Saurabh; Siriwardena, Ajith K

    2006-01-01

    Pancreatic necrosis complicating severe acute pancreatitis is a challenging scenario in contemporary critical care practice; it requires multidisciplinary care in a setting where there is a relatively limited evidence base to support decision making. This commentary provides a concise overview of current management of patients with infected necrosis, focusing on detection, the role of pharmacologic intervention, and the timing and nature of surgical interventions. Fine-needle aspiration of necrosis remains the mainstay for establishment of infection. Pharmacological intervention includes antibiotic therapy as an adjunct to surgical debridement/drainage and, more recently, drotrecogin alfa. Specific concerns remain regarding the suitability of drotrecogin alfa in this setting. Early surgical intervention is unhelpful; surgery is indicated when there is strong evidence for infection of necrotic tissue, with the current trend being toward 'less drastic' surgical interventions. PMID:16356213

  3. CLOCK modulates survival and acute lung injury in mice with polymicrobial sepsis.

    PubMed

    Wang, Chao-Yung; Hsieh, Ming-Jer; Hsieh, I-Chang; Shie, Shian-Sen; Ho, Ming-Yun; Yeh, Jih-Kai; Tsai, Ming-Lung; Yang, Chia-Hung; Hung, Kuo-Chun; Wang, Chun-Chieh; Wen, Ming-Shien

    2016-09-16

    Polymicrobial sepsis is a potentially fatal condition and a significant burden on health care systems. Acute lung injury is the most common complication of sepsis and results in high mortality. However, there has been no recent significant progress in the treatment of sepsis or acute lung injury induced by sepsis. Here we show that mice deficient in the circadian protein CLOCK had better survival than wild-type mice after induction of polymicrobial sepsis by cecal ligation and puncture. Inflammatory cytokine production was attenuated and bacterial clearance was improved in CLOCK-deficient mice. Moreover, acute lung injury after induction of sepsis was significantly decreased in CLOCK-deficient mice. Genome-wide profiling analysis showed that inhibin signaling was reduced in CLOCK-deficient mice. These data establish the importance of circadian CLOCK-inhibin signaling in sepsis, which may have potential therapeutic implications. PMID:27520377

  4. Experimental infection magnifies inbreeding depression in house mice.

    PubMed

    Ilmonen, P; Penn, D J; Damjanovich, K; Clarke, J; Lamborn, D; Morrison, L; Ghotbi, L; Potts, W K

    2008-05-01

    It is often assumed that inbreeding reduces resistance to pathogens, yet there are few experimental tests of this idea in vertebrates, and no tests for the effects of moderate levels of inbreeding more commonly found in nature. We mated wild-derived mice with siblings or first cousins and compared the resistance of their offspring to Salmonella infection with outbred controls under laboratory and seminatural conditions. In the laboratory, full-sib inbreeding reduced resistance to Salmonella and survivorship, whereas first-cousin inbreeding had no detectable effects. In competitive population enclosures, we found that first-cousin inbreeding reduced male fitness by 57% in infected vs. only 34% in noninfected control populations. Our study provides experimental evidence that inbreeding reduces resistance and ability to survive pathogenic infection, and moreover, it shows that even moderate inbreeding can cause significant fitness declines under naturalistic conditions of social stress, and especially with exposure to infectious agents. PMID:18312317

  5. Kinetics of interleukin-6 production after experimental infection of mice with Schistosoma mansoni.

    PubMed Central

    Khalil, R M; Hültner, L; Mailhammer, R; Luz, A; Moeller, J; Mohamed, A A; Omran, S; Dörmer, P

    1996-01-01

    It has been reported that interleukin-6 (IL-6) is expressed in cells of acute inflammatory granulomas experimentally induced in mice by eggs of Schistosoma mansoni. Moreover, in vitro IL-6 was shown to enhance the cytotoxic activity of human platelets against larvae of S. mansoni. To elucidate further a proposed biological significance of this cytokine during the course of schistosomiasis, we studied the kinetics of IL-6 production and concomitantly performed a histopathological analysis of the livers in BALB/c mice subcutaneously infected with S. mansoni cercariae. Over a period of 24 weeks postinfection (p.i.) we monitored serum IL-6 levels, IL-6 production in vitro by pokeweed mitogen (PWM)-stimulated spleen cells as well as IL-6 mRNA expression in livers, spleens and kidneys. We found significantly elevated IL-6 levels in PWM-stimulated spleen cell-conditioned media (SCM) at weeks 6 to 20 p.i., peaking at week 10 p.i. In contrast, serum IL-6 concentrations started to rise not before week 8 but remained significantly elevated above normal control values until week 24 p.i. The time pattern of enhanced IL-6 mRNA expression detected in spleens and livers, but not in kidneys, as well as the rises of IL-6 in SCM and with a delay of 2 weeks in serum samples correlated with the onset of the egg-induced inflammatory reactions as well as the incidence and the number of the granulomas observed histopathologically in the livers of infected mice. Our data emphasize both a local and a systemic role of IL-6 in the host immune response following infection of mice with S. mansoni. Images Figure 3 PMID:8943723

  6. Plasticity of the Systemic Inflammatory Response to Acute Infection during Critical Illness: Development of the Riboleukogram

    PubMed Central

    Burykin, Anton; Ruan, Jianhua; Li, Qing; Schierding, William; Lin, Nan; Dixon, David; Zhang, Weixiong; Coopersmith, Craig M.; Dunne, W. Michael; Colonna, Marco; Ghosh, Bijoy K.; Cobb, J. Perren

    2008-01-01

    Background Diagnosis of acute infection in the critically ill remains a challenge. We hypothesized that circulating leukocyte transcriptional profiles can be used to monitor the host response to and recovery from infection complicating critical illness. Methodology/Principal Findings A translational research approach was employed. Fifteen mice underwent intratracheal injections of live P. aeruginosa, P. aeruginosa endotoxin, live S. pneumoniae, or normal saline. At 24 hours after injury, GeneChip microarray analysis of circulating buffy coat RNA identified 219 genes that distinguished between the pulmonary insults and differences in 7-day mortality. Similarly, buffy coat microarray expression profiles were generated from 27 mechanically ventilated patients every two days for up to three weeks. Significant heterogeneity of VAP microarray profiles was observed secondary to patient ethnicity, age, and gender, yet 85 genes were identified with consistent changes in abundance during the seven days bracketing the diagnosis of VAP. Principal components analysis of these 85 genes appeared to differentiate between the responses of subjects who did versus those who did not develop VAP, as defined by a general trajectory (riboleukogram) for the onset and resolution of VAP. As patients recovered from critical illness complicated by acute infection, the riboleukograms converged, consistent with an immune attractor. Conclusions/Significance Here we present the culmination of a mouse pneumonia study, demonstrating for the first time that disease trajectories derived from microarray expression profiles can be used to quantitatively track the clinical course of acute disease and identify a state of immune recovery. These data suggest that the onset of an infection-specific transcriptional program may precede the clinical diagnosis of pneumonia in patients. Moreover, riboleukograms may help explain variance in the host response due to differences in ethnic background, gender, and

  7. Antiplasmodial activity of Xanthium strumarium against Plasmodium berghei-infected BALB/c mice.

    PubMed

    Chandel, Sanjeev; Bagai, Upma; Vashishat, Nisha

    2012-03-01

    The present work was undertaken to evaluate the antiplasmodial activity of ethanolic leaves extract of traditional medicinal plant Xanthium strumarium in Plasmodium berghei-infected BALB/c mice along with phytochemical screening and acute toxicity test to support its traditional medicinal use as a malaria remedy. The ethanolic leaves extract of X. strumarium (ELEXS) 150, 250, 350 and 500 mg/kg/day demonstrated dose-dependent chemosuppression during early and established infection long with significant (p < 0.001) repository activity. The oral administration of 500 mg/kg/day concentration showed a maximum of 88.6% chemosuppression during early infection, which was more than that of the standard drug chloroquine (5 mg/kg/day) with 88.3% chemosuppression. However, 60% mortality has been found in this group. The LD(50) of ELEXS was found to be 1.5 g/kg/mouse. The administration of 350 mg/kg/day concentration of extract have been found to exert 90.40% chemosuppression during repository infection, which was well comparable to standard drug pyrimethamine (1.2 mg/kg/day) exerting 92.91% chemosuppression. The extract has been found to enhance mean survival time of mice from 21 to 26 days with 250 and 350 mg/kg/day concentrations, while 150 mg/kg/day concentration has been found to sustain all the mice up to 29 days which was similar to the employed standard drug chloroquine (5 mg/kg/day). All these findings support the ethanopharmacological use of X. strumarium as malarial remedy and indicate the potential of plant for active antiplasmodial components. PMID:21847597

  8. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice

    PubMed Central

    Amin, Bahareh; Nakhsaz, Alireza; Hosseinzadeh, Hossein

    2015-01-01

    Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron) using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p.) were evaluated using forced swim test (FST). In sub-acute study (21 times with 24-h intervals), antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST). Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively. Results: Acute treatment with crocin (40 mg/kg) and crocetin (20 and 40 mg/kg) produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg). Crocetin (12.5, 25 and 50 mg/kg) was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin. Conclusion: Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration. PMID:26468466

  9. COMPARATIVE STUDY ON IMMUNOBLOT VERSUS PCR IN DIAGNOSIS OF SCHISTOSOMIASIS MANSONI IN EXPERIMENTAL INFECTED MICE.

    PubMed

    Ismail, Mousa A M; Mousa, Wahed Mohammed Ali; Abu-Sarea, Enas Yahia; Basyouni, Maha M A; Mohammed, Samah Sayed

    2016-04-01

    This study compared PCR and Western blot techniques in diagnosis of schistosomiasis mansoni. Forty Swiss albino mice were used, thirty two mice were infected with cercariae of S. mansoni and eight mice were kept uninfected which were used as a control. Blood was obtained from four infected mice weekly beginning from the 1st week to the 8th week post infection. The study found that PCR was positive from the first week post infection, while Western blot technique was positive from the second week post infection. Thus, PCR diagnosed schistosomiasis mansoni earlier than Western blot technique, but both were able to diagnose. PMID:27363045

  10. Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus

    PubMed Central

    Qiu, Hongjie; Gao, Tongtong; Zeng, Yang; Guo, Yan; Yu, Hong; Li, Junfeng; Kou, Zhihua; Du, Lanying; Tan, Wenjie; Jiang, Shibo; Sun, Shihui; Zhou, Yusen

    2015-01-01

    The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4), the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection. PMID:26701103

  11. Evaluation of effects of ozone exposure on influenza infection in mice using several indicators of susceptibility

    SciTech Connect

    Selgrade, M.K.; Illing, J.W.; Starnes, D.M.; Stead, A.G.; Menache, M.G.; Stevens, M.A.

    1988-07-01

    Mice were exposed to 1 ppm O3, 3 hr/day, for 5 consecutive days. Separate groups of mice were infected with influenza following each of the individual exposures. A twofold increase in the incidence of mortality and a 3-day decrease in mean survival time were observed in mice infected after the second exposure. There were no effects on percentage mortality or mean survival time due to exposure to 1 ppm O3 in mice infected after the first, third, fourth, or fifth exposure. When the exposure concentration was lowered to 0.5 ppm, there were no effects on mortality in mice infected after the second exposure. Five, daily, 3-hr exposures to 1 ppm O3 had no effect on virus titers in the lungs of mice infected after either the second or fifth exposure. In contrast, wet lung weights were significantly enhanced over infected air controls in mice infected after the second O3 exposure at both 1 and 0.5 ppm but not at 0.25 ppm exposure concentrations. This effect on lung wet weight was observed in mice infected with a dose of virus which produced 7-33% mortality in controls as well as in mice infected with a sublethal dose of virus. Histopathologic changes due to sublethal influenza infection, including nonsuppurative pneumonitis and necrosis, squamous metaplasia and hyperplasia of the epithelium lining the bronchi and bronchioles, were more severe in mice infected after the second of five, 1 ppm O3 exposure than in comparable air controls. Sublethal infection caused a loss of lung volume with secondary reduction in diffusing capability and homogenity of ventilation distribution. These latter two effects were also exacerbated in mice infected after the second of five, 1 ppm O3 exposures as compared to air controls. When mice were infected after the fifth, 1 ppm O3 exposure, there was no effect due to ozone on either lung wet weight or histopathology.

  12. Comparing the Bacterial Diversity of Acute and Chronic Dental Root Canal Infections

    PubMed Central

    Santos, Adriana L.; Siqueira, José F.; Rôças, Isabela N.; Jesus, Ederson C.; Rosado, Alexandre S.; Tiedje, James M.

    2011-01-01

    This study performed barcoded multiplex pyrosequencing with a 454 FLX instrument to compare the microbiota of dental root canal infections associated with acute (symptomatic) or chronic (asymptomatic) apical periodontitis. Analysis of samples from 9 acute abscesses and 8 chronic infections yielded partial 16S rRNA gene sequences that were taxonomically classified into 916 bacterial species-level operational taxonomic units (OTUs) (at 3% divergence) belonging to 67 genera and 13 phyla. The most abundant phyla in acute infections were Firmicutes (52%), Fusobacteria (17%) and Bacteroidetes (13%), while in chronic infections the dominant were Firmicutes (59%), Bacteroidetes (14%) and Actinobacteria (10%). Members of Fusobacteria were much more prevalent in acute (89%) than in chronic cases (50%). The most abundant/prevalent genera in acute infections were Fusobacterium and Parvimonas. Twenty genera were exclusively detected in acute infections and 18 in chronic infections. Only 18% (n = 165) of the OTUs at 3% divergence were shared by acute and chronic infections. Diversity and richness estimators revealed that acute infections were significantly more diverse than chronic infections. Although a high interindividual variation in bacterial communities was observed, many samples tended to group together according to the type of infection (acute or chronic). This study is one of the most comprehensive in-deep comparisons of the microbiota associated with acute and chronic dental root canal infections and highlights the role of diverse polymicrobial communities as the unit of pathogenicity in acute infections. The overall diversity of endodontic infections as revealed by the pyrosequencing technique was much higher than previously reported for endodontic infections. PMID:22132218

  13. Comparing the bacterial diversity of acute and chronic dental root canal infections.

    PubMed

    Santos, Adriana L; Siqueira, José F; Rôças, Isabela N; Jesus, Ederson C; Rosado, Alexandre S; Tiedje, James M

    2011-01-01

    This study performed barcoded multiplex pyrosequencing with a 454 FLX instrument to compare the microbiota of dental root canal infections associated with acute (symptomatic) or chronic (asymptomatic) apical periodontitis. Analysis of samples from 9 acute abscesses and 8 chronic infections yielded partial 16S rRNA gene sequences that were taxonomically classified into 916 bacterial species-level operational taxonomic units (OTUs) (at 3% divergence) belonging to 67 genera and 13 phyla. The most abundant phyla in acute infections were Firmicutes (52%), Fusobacteria (17%) and Bacteroidetes (13%), while in chronic infections the dominant were Firmicutes (59%), Bacteroidetes (14%) and Actinobacteria (10%). Members of Fusobacteria were much more prevalent in acute (89%) than in chronic cases (50%). The most abundant/prevalent genera in acute infections were Fusobacterium and Parvimonas. Twenty genera were exclusively detected in acute infections and 18 in chronic infections. Only 18% (n = 165) of the OTUs at 3% divergence were shared by acute and chronic infections. Diversity and richness estimators revealed that acute infections were significantly more diverse than chronic infections. Although a high interindividual variation in bacterial communities was observed, many samples tended to group together according to the type of infection (acute or chronic). This study is one of the most comprehensive in-deep comparisons of the microbiota associated with acute and chronic dental root canal infections and highlights the role of diverse polymicrobial communities as the unit of pathogenicity in acute infections. The overall diversity of endodontic infections as revealed by the pyrosequencing technique was much higher than previously reported for endodontic infections. PMID:22132218

  14. The effect of vitamin E on secondary bacterial infection after influenza infection in young and old mice.

    PubMed

    Gay, Raina; Han, Sung Nim; Marko, Melissa; Belisle, Sarah; Bronson, Roderick; Meydani, Simin Nikbin

    2004-12-01

    Mortality from influenza is high in the elderly. Deaths are mainly due to secondary complications, including Staphylococcus aureus (SA) infections. Vitamin E (E) supplementation reduces influenza in aged mice. This study determined the efficacy of E supplementation on secondary bacterial infections after influenza in young and old mice. C57BL/6 mice were fed diets containing 30 or 500 ppm E for 4 weeks. Priming with influenza significantly increased SA in the lungs of infected mice fed control diet. Age did not have a significant effect on SA infection alone or SA infection after influenza infection. E supplementation did not have a significant effect on SA infection alone. However, E supplementation abolished the priming effect of influenza on SA. PMID:15753185

  15. The Diagnosis, Evaluation and Treatment of Acute and Recurrent Pediatric Urinary Tract Infections

    PubMed Central

    Becknell, Brian; Schober, Megan; Korbel, Lindsey; Spencer, John David

    2015-01-01

    Urinary tract infection is one of the most common bacterial infections encountered by pediatricians. Currently, the diagnosis and management of acute urinary tract infection and recurrent urinary tract infection in children remains controversial. Recently published guidelines and large clinical trials have attempted to clarify UTI diagnostic and management strategies. In this manuscript, we review the diagnosis and management of acute and recurrent urinary tract infection in the pediatric population. PMID:25421102

  16. Actinomyces infection causing acute right iliac fossa pain

    PubMed Central

    Govindarajah, Narendranath; Hameed, Waseem; Middleton, Simon; Booth, Michael

    2014-01-01

    This is a case of a 75-year-old man being admitted to the on-call surgical department with acute abdominal pain. On arrival he was clinically dehydrated and shocked with localised pain over McBurney's point and examination findings were suggestive of appendiceal or other colonic pathology. Full blood testing revealed a white cell count of 38×109/L and a C reactive protein (CRP) of 278 mg/L. A CT scan revealed a gallbladder empyema that extended into the right iliac fossa. This case highlights the potential for a hyperdistended gallbladder empyema to present as acute right iliac fossa pain with blood tests suggestive of complicated disease. Further analysis confirmed Actinomyces infection as the underlying aetiology prior to a laparoscopic subtotal cholecystectomy. This case serves to remind clinicians of this as a rare potential cause of atypical gallbladder pathology. PMID:24872493

  17. Histone lysine crotonylation during acute kidney injury in mice

    PubMed Central

    Ruiz-Andres, Olga; Sanchez-Niño, Maria Dolores; Cannata-Ortiz, Pablo; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto; Sanz, Ana Belen

    2016-01-01

    ABSTRACT Acute kidney injury (AKI) is a potentially lethal condition for which no therapy is available beyond replacement of renal function. Post-translational histone modifications modulate gene expression and kidney injury. Histone crotonylation is a recently described post-translational modification. We hypothesized that histone crotonylation might modulate kidney injury. Histone crotonylation was studied in cultured murine proximal tubular cells and in kidneys from mice with AKI induced by folic acid or cisplatin. Histone lysine crotonylation was observed in tubular cells from healthy murine and human kidney tissue. Kidney tissue histone crotonylation increased during AKI. This was reproduced by exposure to the protein TWEAK in cultured tubular cells. Specifically, ChIP-seq revealed enrichment of histone crotonylation at the genes encoding the mitochondrial biogenesis regulator PGC-1α and the sirtuin-3 decrotonylase in both TWEAK-stimulated tubular cells and in AKI kidney tissue. To assess the role of crotonylation in kidney injury, crotonate was used to increase histone crotonylation in cultured tubular cells or in the kidneys in vivo. Crotonate increased the expression of PGC-1α and sirtuin-3, and decreased CCL2 expression in cultured tubular cells and healthy kidneys. Systemic crotonate administration protected from experimental AKI, preventing the decrease in renal function and in kidney PGC-1α and sirtuin-3 levels as well as the increase in CCL2 expression. For the first time, we have identified factors such as cell stress and crotonate availability that increase histone crotonylation in vivo. Overall, increasing histone crotonylation might have a beneficial effect on AKI. This is the first observation of the in vivo potential of the therapeutic manipulation of histone crotonylation in a disease state. PMID:27125278

  18. Microbial transformation from normal oral microbiota to acute endodontic infections

    PubMed Central

    2012-01-01

    Background Endodontic infections are a leading cause of oro-facial pain and tooth loss in western countries, and may lead to severe life-threatening infections. These infections are polymicrobial with high bacterial diversity. Understanding the spatial transition of microbiota from normal oral cavities through the infected root canal to the acute periapical abscess can improve our knowledge of the pathogenesis of endodontic infections and lead to more effective treatment. We obtained samples from the oral cavity, infected root canal and periapical abscess of 8 patients (5 with localized and 3 with systemic infections). Microbial populations in these samples were analyzed using next-generation sequencing of 16S rRNA amplicons. Bioinformatics tools and statistical tests with rigorous criteria were used to elucidate the spatial transition of the microbiota from normal to diseased sites. Results On average, 10,000 partial 16S rRNA gene sequences were obtained from each sample. All sequences fell into 11 different bacterial phyla. The microbial diversity in root canal and abscess samples was significantly lower than in the oral samples. Streptococcus was the most abundant genus in oral cavities while Prevotella and Fusobacterium were most abundant in diseased samples. The microbiota community structures of root canal and abscess samples were, however, more similar to each other than to the oral cavity microbiota. Using rigorous criteria and novel bioinformatics tools, we found that Granulicatella adiacens, Eubacterium yurii, Prevotella melaninogenica, Prevotella salivae, Streptococcus mitis, and Atopobium rimae were over-represented in diseased samples. Conclusions We used a novel approach and high-throughput methodologies to characterize the microbiota associated normal and diseased oral sites in the same individuals. PMID:22839737

  19. F. novicida-Infected A. castellanii Does Not Enhance Bacterial Virulence in Mice

    PubMed Central

    Ozanic, Mateja; Gobin, Ivana; Brezovec, Martin; Marecic, Valentina; Trobonjaca, Zlatko; Abu Kwaik, Yousef; Santic, Marina

    2016-01-01

    Francisella tularensis is a facultative intracellular bacterium that causes tularemia in humans and animals. Epidemiology of tularemia worldwide is often associated with water-borne transmission, which includes mosquitoes and amoebae as the potential host reservoirs of the bacteria in water environment. In vitro studies showed intracellular replication of F. tularensis within Acanthamoeba castellanii and Hartmanella vermiformis cells. While infection of amoeba by Legionella pneumophila has been shown to enhance infectivity of L. pneumophila the role of F. tularensis-infected protozoa in the pathogenesis of tularemia is not known. We used 6 h coculture of A. castellanii and F. novicida for investigation of the effect of inhaled amoeba on the pathogenesis of tularemia on in vivo model. Balb/c mice were infected intratracheally with F. novicida or with F. novicida-infected A. castellanii. Surprisingly, infection with F. novicida-infected A. castellanii did not lead to bronchopneumonia in Balb/c mice, and Francisella did not disseminate into the liver and spleen. Upon inhalation, F. novicida infects a variety of host cells, though neutrophils are the predominant cells early during infection in the lung infiltrates of pulmonary tularemia. The numbers of neutrophils in the lungs of Balb/c mice were significantly lower in the infection of mice with F. novicida-infected A. castellanii in comparison to group of mice infected only with F. novicida. These results demonstrate that following inoculation of mice with F. novicida-infected A. castellanii, mice did not develop tularemia. PMID:27242974

  20. Suppressor cells in Trypanosoma congolense-infected mice.

    PubMed

    Pearson, T W; Roelants, G E; Lundin, L B; Mayor-Withey, K S

    1979-01-01

    Spleen cells from mice infected with T. congolense strongly suppressed lymphocyte stimulation induced in normal spleen cells by incubation with mitogens or allogeneic cells. Cell dilution studies showed that suppressor activity was extremely strong. Suppressor cell activity was markedly reduced by treatment of spleen cell populations with mitomycin-C and was unaffected by treatment with anti-Thy.1 sera and complement. Removal of cells which bound carbonyl iron or which bound to nylon columns, decreased but did not abolish suppressor activity. PMID:313686

  1. Partial resistance to homologous challenge infections of the digenean Echinostoma caproni in ICR mice.

    PubMed

    Muñoz-Antoli, C; Cortés, A; Martín-Grau, C; Fried, B; Esteban, J G; Toledo, R

    2016-07-01

    In the present paper, we analyse the effect of a primary infection of ICR mice with Echinostoma caproni (Trematoda: Echinostomatidae) on the generation of resistance against homologous challenge infections. In ICR mice, E. caproni induces chronic infections concomitantly with strong responses characterized by the development of T-helper 1 (Th1)-type local immune responses with elevated levels of local interferon-gamma (IFN-γ) and inflammatory and antibody responses. Here, the effect of the response generated against a primary infection with E. caproni in the generation of resistance against subsequent homologous infections was analysed. For this purpose, ICR mice were challenged with metacercariae of E. caproni and the results obtained showed that primary infection induces partial resistance against subsequent homologous infections in ICR mice. This resistance was expressed as a reduced rate of infection, worm recovery and worm size, indicating that primary infection induces changes in the host, making a hostile environment for the development of the parasite. PMID:26202834

  2. Serum amyloid A protein in acute viral infections.

    PubMed Central

    Miwata, H; Yamada, T; Okada, M; Kudo, T; Kimura, H; Morishima, T

    1993-01-01

    Concentrations of serum amyloid A protein (SAA) were measured in 254 children with viral diseases, including measles, varicella, rubella, mumps, echo-30 meningitis, chronic hepatitis B and C, and in eight with Kawasaki disease. Latex agglutination nephelometric immunoassay was used for assaying SAA. In 191 out of 195 patients (98%), SAA concentrations became markedly raised in the acute phase of the viral disease: measles (97%), varicella (100%), mumps (95%), and echo-30 meningitis (99%) with mean titres of 82.4, 80.5, 60.2, 75.2, and 101.1 micrograms/ml respectively. This increase in SAA was followed by a rapid return to normal concentrations (< 5 micrograms/ml) during convalescence. Remarkably higher concentrations of SAA (mean 1630 micrograms/ml) were detected in the acute phase of patients with Kawasaki disease, but in most of the children with chronic hepatitis B or C, the titres of SAA remained normal. There was no close correlation between SAA and serum concentrations for alpha 1-acid glycoprotein, beta 2-microglobulin, transferrin, and IgG. There was a clear correlation between SAA and C reactive protein concentrations, although SAA showed a greater incremental change than C reactive protein in the acute phase. In the acute phase of these viral diseases, 56% of the patients had raised SAA concentrations (> or = 5 micrograms/ml) with normal C reactive protein concentrations (< 5 micrograms/ml). These results indicate that SAA could be useful as an inflammatory marker in children with acute viral infections. PMID:8481043

  3. Acute prevertebral abscess secondary to infected pancreatic pseudocyst

    PubMed Central

    Bhandarkar, Ajay M; Pillai, Suresh; Venkitachalam, Shruti; Anand, Aishwarya

    2014-01-01

    We report a case of a middle aged, man with diabetes who presented with dysphagia and odynophagia. On evaluation, he was diagnosed to have an acute prevertebral abscess with an unusual aetiology, an infected pseudocyst of pancreas. Contrast-enhanced CT revealed an enhancing collection in the prevertebral space extending to the retrogastric space and communicating with the body of the pancreas via the oesophageal hiatus. Transoral incision and drainage of the prevertebral abscess were performed. Nasogastric tube was placed in the prevertebral space for continuous drainage and daily irrigation. Supportive intravenous broad spectrum antibiotic therapy along with the surgical intervention led to the resolution of the prevertebral abscess and the infected pancreatic pseudocyst. PMID:24408943

  4. Cerebral aspergillus infection in pediatric acute lymphoblastic leukemia induction therapy

    PubMed Central

    Prakash, Gaurav; Thulkar, Sanjay; Arava, Sudheer Kumar; Bakhshi, Sameer

    2012-01-01

    Angioinvasive pulmonary infection from filamentous fungi is not an uncommon occurrence in immunocompromised patients like acute lymphoblastic leukemia (ALL). Rarely, these lesions can spread via the hematogenous route and involve multiple visceral organs. We report a case of a 14-year-old boy with ALL who developed angioinvasive pulmonary aspergillosis early in the course of induction therapy, which was followed by hematogenous dissemination and formation of multiple brain abscesses. The patient was treated with intravenous amphotericin B. There was no response to the therapy and the patient succumbed to disseminated infection. Postmortem lung biopsy confirmed angioinvasive pulmonary aspergillosis. Poor penetration of amphotericin B across the blood-brain barrier could be one of the contributory factors for poor response to antifungal therapy. We discuss the various antifungal agents with respect to their penetration in brain. PMID:23580827

  5. Pifithrin-μ Attenuates Acute Sickness Response to Lipopolysaccharide in C57BL/6J Mice.

    PubMed

    Zhang, Rongping; Wang, Jili; Hu, Yanling; Lu, Xu; Jiang, Bo; Zhang, Wei; Huang, Chao

    2016-01-01

    Sickness behavior is a coordinated set of behavioral changes that happen as a response to acute infectious pathogens. Its well-known benefit is to reorganize the organism's priorities to cope with infection, but the uncontrolled development of sickness behavior may trigger negative feelings or chronic depressive events. This study aims at investigating the potential effect of pifithrin-μ, an inhibitor of heat shock protein 70 substrate binding activity, on lipopolysaccharide (LPS)-induced sickness response. C57BL/6J mice were submitted to the forced swimming test (FST), tail suspension test (TST), open field test (OFT) and light-dark box test. Food intake and body weight were also evaluated. The serum corticosterone level was measured using an ELISA kit. Treatment of mice with LPS (0.33 mg/kg, i.p.) markedly increased the floating and immobility time in the FST and TST, respectively, and depressed locomotor activity in the OFT. LPS administration prolonged the latency to first transition and reduced the total number of transitions in the light-dark box test. In addition, LPS induced anorexia and increased serum corticosterone levels. Pretreatment with pifithrin-μ (1 or 5 mg/kg) attenuated behavioral changes induced by LPS in the FST, TST, OFT and light-dark box test. Pifithrin-μ also prevented the formation of anorexia as well as the increase in serum corticosterone levels in LPS-treated mice. Our previous studies showed that pifithrin-μ prevents the production of pro-inflammatory factors in both microglia and macrophages. These findings presented here extend the role of pifithrin-μ beyond an anti-inflammatory molecule to a modulator of sickness behavior. PMID:26881748

  6. [Circulating immune complexes in acute and prolonged hepatitis A infection].

    PubMed

    Dautović-Krkić, Sajma; Gribajcević, Mehmed

    2002-01-01

    Level and dynamics activity of circulating immune complexes (CiC) and persistence CiC in the sera in the acute and prolonged HAV-infection was examined. In the same time we explored the relation of level and dynamics CiC compared with level, dynamics and persistence length ALT and IgM anti-HAV in sera, longitude excretion HAV Ag in stool and intensity patohistological damage in liver. Research have been undertaken in the prospected study on two groups with 90 patients in total: 60 patients with prolonged form of the hepatitis A, and 30 patients with HAV-infection with normal development. CiC was prescribe with fotometer in sediment of poliethilenglicol, and IgM anti HAV with ELISA technique. Ag-HAV in stool was prescribe with methodImmuno/electro/osmophoresis. Results of examination showed that high level values of CiC had present in all patients with HAV-infection, bat yet middle values of CiC had significantly higher in prolonged forms (p < 0.01). In a case of patients with PTHA CiC persistence almost three times longer than in HAV infection with normal development. The highest value of CiC have been found from one to two weeks after e peak ALT in HAV and in PTHA 4-6 weeks later. Persistence of elevated values CiC responded to the middle length persistence of Igm anti HAV-in the sera. PMID:12378858

  7. Acutely Decreased Thermoregulatory Energy Expenditure or Decreased Activity Energy Expenditure Both Acutely Reduce Food Intake in Mice

    PubMed Central

    Kaiyala, Karl J.; Morton, Gregory J.; Thaler, Joshua P.; Meek, Thomas H.; Tylee, Tracy; Ogimoto, Kayoko; Wisse, Brent E.

    2012-01-01

    Despite the suggestion that reduced energy expenditure may be a key contributor to the obesity pandemic, few studies have tested whether acutely reduced energy expenditure is associated with a compensatory reduction in food intake. The homeostatic mechanisms that control food intake and energy expenditure remain controversial and are thought to act over days to weeks. We evaluated food intake in mice using two models of acutely decreased energy expenditure: 1) increasing ambient temperature to thermoneutrality in mice acclimated to standard laboratory temperature or 2) exercise cessation in mice accustomed to wheel running. Increasing ambient temperature (from 21°C to 28°C) rapidly decreased energy expenditure, demonstrating that thermoregulatory energy expenditure contributes to both light cycle (40±1%) and dark cycle energy expenditure (15±3%) at normal ambient temperature (21°C). Reducing thermoregulatory energy expenditure acutely decreased food intake primarily during the light cycle (65±7%), thus conflicting with the delayed compensation model, but did not alter spontaneous activity. Acute exercise cessation decreased energy expenditure only during the dark cycle (14±2% at 21°C; 21±4% at 28°C), while food intake was reduced during the dark cycle (0.9±0.1 g) in mice housed at 28°C, but during the light cycle (0.3±0.1 g) in mice housed at 21°C. Cumulatively, there was a strong correlation between the change in daily energy expenditure and the change in daily food intake (R2 = 0.51, p<0.01). We conclude that acutely decreased energy expenditure decreases food intake suggesting that energy intake is regulated by metabolic signals that respond rapidly and accurately to reduced energy expenditure. PMID:22936977

  8. Upregulation of ICOS on CD43+ CD4+ murine small intestinal intraepithelial lymphocytes during acute reovirus infection

    SciTech Connect

    Montufar-Solis, Dina; Garza, Tomas; Teng, B.-B.; Klein, John R. . E-mail: john.r.klein@uth.tmc.edu

    2006-04-14

    Murine intestinal intraepithelial lymphocytes (IELs) can be classified according to expression of a CD43 glycoform recognized by the S7 monoclonal antibody. In this study, we examined the response of S7+ and S7- IELs in mice during acute reovirus serotype 3 (Dearing strain) infection, which was confirmed by virus-specific real-time PCR. In vivo proliferation increased significantly for both S7- and S7+ IELs on day 4 post-infection as determined by BrdU incorporation; however, expression of the inducible costimulatory (ICOS) molecule, which peaked on day 7 post-infection, was upregulated on S7+ CD4+ T cells, most of which were CD4+8- IELs. In vitro ICOS stimulation by syngeneic peritoneal macrophages induced IFN-{gamma} secretion from IELs from day 7 infected mice, and was suppressed by treatment with anti-ICOS mAb. Additionally, IFN-{gamma} mRNA increased in CD4+ IELs on day 6 post-infection. These findings indicate that S7- and S7+ IELs are differentially mobilized during the immune response to reovirus infection; that the regulated expression of ICOS is associated with S7+ IELs; and that stimulation of IELs through ICOS enhances IFN-{gamma} synthesis during infection.

  9. Anticoccidial activities of Chitosan on Eimeria papillata-infected mice.

    PubMed

    Abdel-Latif, Mahmoud; Abdel-Haleem, Heba M; Abdel-Baki, Abdel-Azeem S

    2016-07-01

    Eimeria spp. multiply within the intestinal tract causing severe inflammatory responses. Chitosan (CS), meanwhile, has been shown to exhibit anti-inflammatory activities in different experimental models. Here, we investigated the effect of CS on the outcome of inflammation caused by Eimeria papillata in the mouse intestine. Investigations were undertaken into the oocyst output in feces and developmental stages and goblet cells in intestinal tissue. Assays for lipid peroxidation, nitric oxide (NO), and myeloperoxidase (MPO) were also performed. T cells in intestinal tissue were counted using immunohistochemistry while total IgA in serum or intestinal wash was assayed using ELISA. In addition, mRNA expression of tumor necrosis factor alpha (TNF-α), transforming growth factor β (TGF-β), interleukin (IL)-10, and IL-4 were detected using real-time PCR. The data indicated a reduction in both oocyst output and in the number of parasite developmental stages following CS treatment, while the goblet cell hypoplasia in infected mice was also inhibited. CS decreased lipid peroxidation, NO, and MPO but did not alter the T cell count or IgA levels in comparison to the infected group. The expression of TNF-α and TGF-β decreased but IL-10 and IL-4 increased after CS treatment in comparison to the non-treated infected group. In conclusion, CS showed anti-inflammatory and protective effects against E. papillata infection. PMID:27041340

  10. Oxidative stress fuels Trypanosoma cruzi infection in mice

    PubMed Central

    Paiva, Claudia N.; Feijó, Daniel F.; Dutra, Fabianno F.; Carneiro, Vitor C.; Freitas, Guilherme B.; Alves, Letícia S.; Mesquita, Jacilene; Fortes, Guilherme B.; Figueiredo, Rodrigo T.; Souza, Heitor S.P.; Fantappié, Marcelo R.; Lannes-Vieira, Joseli; Bozza, Marcelo T.

    2012-01-01

    Oxidative damage contributes to microbe elimination during macrophage respiratory burst. Nuclear factor, erythroid-derived 2, like 2 (NRF2) orchestrates antioxidant defenses, including the expression of heme-oxygenase–1 (HO-1). Unexpectedly, the activation of NRF2 and HO-1 reduces infection by a number of pathogens, although the mechanism responsible for this effect is largely unknown. We studied Trypanosoma cruzi infection in mice in which NRF2/HO-1 was induced with cobalt protoporphyrin (CoPP). CoPP reduced parasitemia and tissue parasitism, while an inhibitor of HO-1 activity increased T. cruzi parasitemia in blood. CoPP-induced effects did not depend on the adaptive immunity, nor were parasites directly targeted. We also found that CoPP reduced macrophage parasitism, which depended on NRF2 expression but not on classical mechanisms such as apoptosis of infected cells, induction of type I IFN, or NO. We found that exogenous expression of NRF2 or HO-1 also reduced macrophage parasitism. Several antioxidants, including NRF2 activators, reduced macrophage parasite burden, while pro-oxidants promoted it. Reducing the intracellular labile iron pool decreased parasitism, and antioxidants increased the expression of ferritin and ferroportin in infected macrophages. Ferrous sulfate reversed the CoPP-induced decrease in macrophage parasite burden and, given in vivo, reversed their protective effects. Our results indicate that oxidative stress contributes to parasite persistence in host tissues and open a new avenue for the development of anti–T. cruzi drugs. PMID:22728935

  11. Finding those at risk: Acute HIV infection in Newark, NJ

    PubMed Central

    Martin, Eugene G.; Salaru, Gratian; Mohammed, Debbie; Coombs, Robert W.; Paul, Sindy M.; Cadoff, Evan M.

    2014-01-01

    Background A screening strategy combining rapid HIV-1/2 (HIV) antibody testing with pooled HIV-1 RNA testing increases identification of HIV infections, but may have other limitations that restrict its usefulness to all but the highest incidence populations. Objective By combining rapid antibody detection and pooled nucleic acid amplification testing (NAAT) testing, we sought to improve detection of early HIV-1 infections in an urban Newark, NJ hospital setting. Study design Pooled NAAT HIV-1 RNA testing was offered to emergency department patients and out-patients being screened for HIV antibodies by fingerstick-rapid HIV testing. For those negative by rapid HIV and agreeing to NAAT testing, pooled plasma samples were prepared and sent to the University of Washington where real-time reverse transcription-polymerase chain reaction (RT-PCR) amplification was performed. Results Of 13,226 individuals screened, 6381 had rapid antibody testing alone, and 6845 agreed to add NAAT HIV screening. Rapid testing identified 115 antibody positive individuals. Pooled NAAT increased HIV-1 case detection by 7.0% identifying 8 additional cases. Overall, acute HIV infection yield was 0.12%. While males represent only 48.1% of those tested by NAAT, all samples that screened positive for HIV-1 RNA were obtained from men. Conclusion HIV-1 RNA testing of pooled, HIV antibody-negative specimens permits identification of recent infections. In Newark, pooled NAAT increased HIV-1 case detection and provided an opportunity to focus on treatment and prevention messages for those most at risk of transmitting infection. Although constrained by client willingness to participate in testing associated with a need to return to receive further results, use of pooled NAAT improved early infection sensitivity. PMID:23953941

  12. Major histocompatibility complex heterozygosity reduces fitness in experimentally infected mice.

    PubMed

    Ilmonen, Petteri; Penn, Dustin J; Damjanovich, Kristy; Morrison, Linda; Ghotbi, Laleh; Potts, Wayne K

    2007-08-01

    It is often suggested that heterozygosity at major histocompatibility complex (MHC) loci confers enhanced resistance to infectious diseases (heterozygote advantage, HA, hypothesis), and overdominant selection should contribute to the evolution of these highly polymorphic genes. The evidence for the HA hypothesis is mixed and mainly from laboratory studies on inbred congenic mice, leaving the importance of MHC heterozygosity for natural populations unclear. We tested the HA hypothesis by infecting mice, produced by crossbreeding congenic C57BL/10 with wild ones, with different strains of Salmonella, both in laboratory and in large population enclosures. In the laboratory, we found that MHC influenced resistance, despite interacting wild-derived background loci. Surprisingly, resistance was mostly recessive rather than dominant, unlike in most inbred mouse strains, and it was never overdominant. In the enclosures, heterozygotes did not show better resistance, survival, or reproductive success compared to homozygotes. On the contrary, infected heterozygous females produced significantly fewer pups than homozygotes. Our results show that MHC effects are not masked on an outbred genetic background, and that MHC heterozygosity provides no immunological benefits when resistance is recessive, and can actually reduce fitness. These findings challenge the HA hypothesis and emphasize the need for studies on wild, genetically diverse species. PMID:17603099

  13. Pharmacological characterization of standard analgesics on oxaliplatin-induced acute cold hypersensitivity in mice.

    PubMed

    Zhao, Meng; Nakamura, Saki; Miyake, Takahito; So, Kanako; Shirakawa, Hisashi; Tokuyama, Shogo; Narita, Minoru; Nakagawa, Takayuki; Kaneko, Shuji

    2014-01-01

    Oxaliplatin, a platinum-based chemotherapeutic agent, causes an acute peripheral neuropathy triggered by cold in almost all patients during or within hours after its infusion. We recently reported that a single administration of oxaliplatin induced cold hypersensitivity 2 h after the administration in mice. In this study, we examined whether standard analgesics relieve the oxaliplatin-induced acute cold hypersensitivity. Gabapentin, tramadol, mexiletine, and calcium gluconate significantly inhibited and morphine and milnacipran decreased the acute cold hypersensitivity, while diclofenac and amitriptyline had no effects. These results suggest that gabapentin, tramadol, mexiletine, and calcium gluconate are effective against oxaliplatin-induced acute peripheral neuropathy. PMID:24671055

  14. Using luciferase to image bacterial infections in mice.

    PubMed

    Chang, Mi Hee; Cirillo, Suat L G; Cirillo, Jeffrey D

    2011-01-01

    Imaging is a valuable technique that can be used to monitor biological processes. In particular, the presence of cancer cells, stem cells, specific immune cell types, viral pathogens, parasites and bacteria can be followed in real-time within living animals. Application of bioluminescence imaging to the study of pathogens has advantages as compared to conventional strategies for analysis of infections in animal models. Infections can be visualized within individual animals over time, without requiring euthanasia to determine the location and quantity of the pathogen. Optical imaging allows comprehensive examination of all tissues and organs, rather than sampling of sites previously known to be infected. In addition, the accuracy of inoculation into specific tissues can be directly determined prior to carrying forward animals that were unsuccessfully inoculated throughout the entire experiment. Variability between animals can be controlled for, since imaging allows each animal to be followed individually. Imaging has the potential to greatly reduce animal numbers needed because of the ability to obtain data from numerous time points without having to sample tissues to determine pathogen load. This protocol describes methods to visualize infections in live animals using bioluminescence imaging for recombinant strains of bacteria expressing luciferase. The click beetle (CBRLuc) and firefly luciferases (FFluc) utilize luciferin as a substrate. The light produced by both CBRluc and FFluc has a broad wavelength from 500 nm to 700 nm, making these luciferases excellent reporters for the optical imaging in living animal models. This is primarily because wavelengths of light greater than 600 nm are required to avoid absorption by hemoglobin and, thus, travel through mammalian tissue efficiently. Luciferase is genetically introduced into the bacteria to produce light signal. Mice are pulmonary inoculated with bioluminescent bacteria intratracheally to allow monitoring of

  15. Absence of a role for natural killer cells in the control of acute infection by Toxoplasma gondii oocysts.

    PubMed Central

    Hughes, H P; Kasper, L H; Little, J; Dubey, J P

    1988-01-01

    The active phase of primary and challenge oral infections of Toxoplasma gondii was investigated with respect to natural killer (NK) activity against YAC-1 tumour cell targets in vitro and serum interferon (IFN) titres. Primary (non-lethal) oral infection of BALB/c mice with Me49 oocysts resulted in a rapid increase of serum IFN titres, followed by augmented NK activity. NK levels became depressed, rising again by 15 days after infection to normal levels, again preceded by elevated IFN titres. In challenge infections NK was not augmented and IFN titres rose only if a high dose of oocysts was given. IFN activity was pH2-labile in all cases and considered to be due to IFN-gamma. Cold target inhibition studies indicated that T. gondii did not bind to NK cells. A bioassay for the effects of NK cells on T. gondii tachyzoites was developed and there was no evidence of killing in vitro by cells with NK function; T. gondii survived better when cultured with NK cells than when cultured alone. Studies using C57BL/6bg/bg,bg/+ and +/+ mice showed that there was no difference in mean time to death after administration of a lethal ME49 oocyst infection by mouth. Cytotoxicity against YAC-1 in both spleen and mesenteric lymph node (MLN) cell populations was highly augmented in bg/+ and +/+, but not in bg/bg mice. Genetic deficiency of NK activity had no effect on survival of mice after infection. Therefore NK has at best a minimal role to play in protection during the acute phase of Toxoplasma infection. PMID:3139341

  16. Mouse Adenovirus Type 1 Infection of Natural Killer Cell-Deficient Mice

    PubMed Central

    Welton, Amanda R.; Gralinski, Lisa E.; Spindler, Katherine R.

    2008-01-01

    Natural killer (NK) cells contribute to the initial nonspecific response to viral infection, and viruses exhibit a range of sensitivities to NK cells in vivo. We investigated the role of NK cells in infection of mice by mouse adenovirus type 1 (MAV-1) using antibody-mediated depletion and knockout mice. MAV-1 causes encephalomyelitis and replicates to highest levels in brains. NK cell-depleted mice infected with MAV-1 showed brain viral loads 8-20 days p.i. that were similar to wild-type control non-depleted mice. Mice genetically deficient for NK cells behaved similarly to wild-type control mice with respect to brain viral loads and survival. We conclude that NK cells are not required to control virus replication in the brains of MAV-1-infected mice. PMID:18155121

  17. Fr-MLV infection induces erythroleukaemia instead of lymphoid leukaemia in mice given pituitary grafts.

    PubMed Central

    Fontanini, G.; Basolo, F.; Garzelli, C.; Squartini, F.; Toniolo, A.

    1990-01-01

    Here we report that the slow-transforming helper component of Friend murine leukaemia virus (Fr-MLV), which produces lymphoid leukaemias in normal mice, induces erythroleukaemia in mice given syngeneic pituitary grafts (SPG). Newborn mice were infected with Fr-MLV and, at one month of age, were transplanted with two pituitary glands under the kidney capsule. Sham-operated infected mice and uninfected transplanted mice served as controls. SPG selectively reduced the mean survival times of infected mice. Histopathology showed that, while most infected non-transplanted mice developed lymphoid leukaemias, virtually all Fr-MLF-infected mice given SPG developed erythroleukaemias. Experiments in vitro showed that Fr-MLV infection markedly depressed concanavalin A induced DNA synthesis in cells from spleen, thymus and lymph nodes. Addition of prolactin or growth hormone further suppressed lectin-induced mitogenesis of lymphoid cells from infected mice, but failed to influence the response of uninfected controls. These experiments indicate that, in mice, pituitary hormones modulate the development and the histological features of Fr-MLV induced leukaemias, and suggest that endocrine-immunological interactions play a role in retrovirus induced tumorigenesis. Images Figure 2 PMID:2372485

  18. Influence of adjuvant and antigen dose on protection induced by an inactivated whole vaccine against Neospora caninum infection in mice.

    PubMed

    Rojo-Montejo, Silvia; Collantes-Fernández, Esther; Regidor-Cerrillo, Javier; Rodríguez-Bertos, Antonio; Prenafeta, Antoni; Gomez-Bautista, Mercedes; Ortega-Mora, Luis M

    2011-02-10

    In this study, the protection afforded by a Neospora caninum inactivated vaccine formulated with three different adjuvants (water-in-oil emulsion, aluminum hydroxide with CpG oligodeoxynucleotides and aluminum hydroxide with ginseng extract) and three different parasite doses (10(5), 5 × 10(5) or 10(6) inactivated whole tachyzoites) was evaluated using a mouse model. Mice were immunized subcutaneously twice at three-week intervals with inactivated Nc-Spain 1H tachyzoites and challenged by intraperitoneal inoculation with 10(6) live Nc-1 tachyzoites. The efficacy of the immunization was evaluated in non-pregnant BALB/c mice on days 1 and 5 (acute infection phase) and days 14 and 30 (chronic infection phase) post-challenge. The results showed the ability of water-in-oil emulsion combined with inactivated 5 × 10(5) tachyzoites to induce protection against neosporosis during the chronic stage, limiting parasite multiplication in the brain. Aluminum hydroxide-ginseng extract and inactivated tachyzoites reduced the number of parasites circulating in the blood during acute phase but failed to limit the establishment of chronic infection. On the other hand, a dose-effect was observed in groups vaccinated with aluminum hydroxide-ginseng extract in which the lesion severity increased as the inactivated tachyzoite dose. This study demonstrates that efficacy can significantly vary depending on the adjuvant, the dose of antigen and the phase of N. caninum infection in which the vaccine is tested. PMID:21067865

  19. Sublingual immunotherapy as an alternative to induce protection against acute respiratory infections.

    PubMed

    Muñoz-Wolf, Natalia; Rial, Analía; Saavedra, José M; Chabalgoity, José A

    2014-01-01

    Sublingual route has been widely used to deliver small molecules into the bloodstream and to modulate the immune response at different sites. It has been shown to effectively induce humoral and cellular responses at systemic and mucosal sites, namely the lungs and urogenital tract. Sublingual vaccination can promote protection against infections at the lower and upper respiratory tract; it can also promote tolerance to allergens and ameliorate asthma symptoms. Modulation of lung's immune response by sublingual immunotherapy (SLIT) is safer than direct administration of formulations by intranasal route because it does not require delivery of potentially harmful molecules directly into the airways. In contrast to intranasal delivery, side effects involving brain toxicity or facial paralysis are not promoted by SLIT. The immune mechanisms underlying SLIT remain elusive and its use for the treatment of acute lung infections has not yet been explored. Thus, development of appropriate animal models of SLIT is needed to further explore its potential advantages. This work shows how to perform sublingual administration of therapeutic agents in mice to evaluate their ability to protect against acute pneumococcal pneumonia. Technical aspects of mouse handling during sublingual inoculation, precise identification of sublingual mucosa, draining lymph nodes and isolation of tissues, bronchoalveolar lavage and lungs are illustrated. Protocols for single cell suspension preparation for FACS analysis are described in detail. Other downstream applications for the analysis of the immune response are discussed. Technical aspects of the preparation of Streptococcus pneumoniae inoculum and intranasal challenge of mice are also explained. SLIT is a simple technique that allows screening of candidate molecules to modulate lungs' immune response. Parameters affecting the success of SLIT are related to molecular size, susceptibility to degradation and stability of highly concentrated

  20. Molecular Signatures of the Evolving Immune Response in Mice following a Bordetella pertussis Infection

    PubMed Central

    Raeven, René H. M.; Brummelman, Jolanda; Pennings, Jeroen L. A.; Nijst, Olaf E. M.; Kuipers, Betsy; Blok, Laura E. R.; Helm, Kina; van Riet, Elly; Jiskoot, Wim; van Els, Cecile A. C. M.; Han, Wanda G. H.; Kersten, Gideon F. A.; Metz, Bernard

    2014-01-01

    Worldwide resurgence of pertussis necessitates the need for improvement of pertussis vaccines and vaccination strategies. Since natural infections induce a longer-lasting immunity than vaccinations, detailed knowledge of the immune responses following natural infection can provide important clues for such improvement. The purpose was to elucidate the kinetics of the protective immune response evolving after experimental Bordetella pertussis (B. pertussis) infection in mice. Data were collected from (i) individual analyses, i.e. microarray, flow cytometry, multiplex immunoassays, and bacterial clearance; (ii) twelve time points during the infection; and (iii) different tissues involved in the immune responses, i.e. lungs, spleen and blood. Combined data revealed detailed insight in molecular and cellular sequence of events connecting different phases (innate, bridging and adaptive) of the immune response following the infection. We detected a prolonged acute phase response, broad pathogen recognition, and early gene signatures of subsequent T-cell recruitment in the lungs. Activation of particular transcription factors and specific cell markers provided insight into the time course of the transition from innate towards adaptive immune responses, which resulted in a broad spectrum of systemic antibody subclasses and splenic Th1/Th17 memory cells against B. pertussis. In addition, signatures preceding the local generation of Th1 and Th17 cells as well as IgA in the lungs, considered key elements in protection against B. pertussis, were established. In conclusion, molecular and cellular immunological processes in response to live B. pertussis infection were unraveled, which may provide guidance in selecting new vaccine candidates that should evoke local and prolonged protective immune responses. PMID:25137043

  1. Interleukin-13 is involved in the formation of liver fibrosis in Clonorchis sinensis-infected mice.

    PubMed

    Xu, Yanquan; Liang, Pei; Bian, Meng; Chen, Wenjun; Wang, Xiaoyun; Lin, Jinsi; Shang, Mei; Qu, Hongling; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

    2016-07-01

    Clonorchiasis is a chronic infection disease often accompanied by formation of liver fibrosis. Previous study has identified that Clonorchis sinensis (C. sinensis, Cs) infection and CsRNASET2 (a member of CsESPs) immunization can drive Th2 immune response. IL-13, a multifunctional Th2 cytokine, has been widely confirmed to be profibrotic mediator. We want to determine whether IL-13 is involved in the generation of liver fibrosis during C. sinensis infection. A part of mice were infected with C. sinensis or immunized with CsRNASET2, respectively. Another part of mice were intravenously injected with rIL-13. Liver tissues of C. sinensis-infected mice were stained with hematoxylin-eosin and Masson's trichrome, respectively. The transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1 in the livers of infected mice and rIL-13-treated mice were measured by quantitative RT-PCR. Besides, splenocytes of C. sinensis-infected and CsRNASET2-immunized mice were isolated, respectively. The levels of IL-13 in splenocytes were detected by ELISA. Our results displayed that the livers of C. sinensis-infected mice had serious chronic inflammation and collagen deposition. The transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1 in the livers of C. sinensis-infected mice were obviously increased. Splenocytes from both C. sinensis-infected and CsRNASET2-immunized mice expressed high levels of IL-13. Moreover, rIL-13 treatment markedly promoted the transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1. These data implied that hepatic fibrosis was formed in the livers of C. sinensis-infected mice, and IL-13 induced by C. sinensis infection and CsRNASET2 immunization might favor this progression. PMID:26993324

  2. Epsilon Toxin Is Essential for the Virulence of Clostridium perfringens Type D Infection in Sheep, Goats, and Mice

    PubMed Central

    Garcia, J. P.; Adams, V.; Beingesser, J.; Hughes, M. L.; Poon, R.; Lyras, D.; Hill, A.; McClane, B. A.; Rood, J. I.

    2013-01-01

    Clostridium perfringens type D causes disease in sheep, goats, and other ruminants. Type D isolates produce, at minimum, alpha and epsilon (ETX) toxins, but some express up to five different toxins, raising questions about which toxins are necessary for the virulence of these bacteria. We evaluated the contribution of ETX to C. perfringens type D pathogenicity in an intraduodenal challenge model in sheep, goats, and mice using a virulent C. perfringens type D wild-type strain (WT), an isogenic ETX null mutant (etx mutant), and a strain where the etx mutation has been reversed (etx complemented). All sheep and goats, and most mice, challenged with the WT isolate developed acute clinical disease followed by death in most cases. Sheep developed various gross and/or histological changes that included edema of brain, lungs, and heart as well as hydropericardium. Goats developed various effects, including necrotizing colitis, pulmonary edema, and hydropericardium. No significant gross or histological abnormalities were observed in any mice infected with the WT strain. All sheep, goats, and mice challenged with the isogenic etx mutant remained clinically healthy for ≥24 h, and no gross or histological abnormalities were observed in those animals. Complementation of etx knockout restored virulence; most goats, sheep, and mice receiving this complemented mutant developed clinical and pathological changes similar to those observed in WT-infected animals. These results indicate that ETX is necessary for type D isolates to induce disease, supporting a key role for this toxin in type D disease pathogenesis. PMID:23630957

  3. Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

    PubMed Central

    Elias, Rosa Maria; Correa-Costa, Matheus; Barreto, Claudiene Rodrigues; Silva, Reinaldo Correia; Hayashida, Caroline Y.; Castoldi, Ângela; Gonçalves, Giselle Martins; Braga, Tarcio Teodoro; Barboza, Renato; Rios, Francisco José; Keller, Alexandre Castro; Cenedeze, Marcos Antonio; Hyane, Meire Ioshie; D'Império-Lima, Maria Regina; Figueiredo-Neto, Antônio Martins; Reis, Marlene Antônia; Marinho, Cláudio Romero Farias; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

    2012-01-01

    Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA. PMID:22952850

  4. Aptamer Based, Non-PCR, Non-Serological Detection of Chagas Disease Biomarkers in Trypanosoma cruzi Infected Mice

    PubMed Central

    Nagarkatti, Rana; de Araujo, Fernanda Fortes; Gupta, Charu; Debrabant, Alain

    2014-01-01

    Chagas disease affects about 5 million people across the world. The etiological agent, the intracellular parasite Trypanosoma cruzi (T. cruzi), can be diagnosed using microscopy, serology or PCR based assays. However, each of these methods has their limitations regarding sensitivity and specificity, and thus to complement these existing diagnostic methods, alternate assays need to be developed. It is well documented that several parasite proteins called T. cruzi Excreted Secreted Antigens (TESA), are released into the blood of an infected host. These circulating parasite antigens could thus be used as highly specific biomarkers of T. cruzi infection. In this study, we have demonstrated that, using a SELEx based approach, parasite specific ligands called aptamers, can be used to detect TESA in the plasma of T. cruzi infected mice. An Enzyme Linked Aptamer (ELA) assay, similar to ELISA, was developed using biotinylated aptamers to demonstrate that these RNA ligands could interact with parasite targets. Aptamer L44 (Apt-L44) showed significant and specific binding to TESA as well as T. cruzi trypomastigote extract and not to host proteins or proteins of Leishmania donovani, a related trypanosomatid parasite. Our result also demonstrated that the target of Apt-L44 is conserved in three different strains of T. cruzi. In mice infected with T. cruzi, Apt-L44 demonstrated a significantly higher level of binding compared to non-infected mice suggesting that it could detect a biomarker of T. cruzi infection. Additionally, Apt-L44 could detect these circulating biomarkers in both the acute phase, from 7 to 28 days post infection, and in the chronic phase, from 55 to 230 days post infection. Our results show that Apt-L44 could thus be used in a qualitative ELA assay to detect biomarkers of Chagas disease. PMID:24454974

  5. Dynamics of changes in physiological parameters of mice with different radiosensitivity after acute γ-irradiation.

    PubMed

    Alchinova, I B; Arkhipova, E N; Medvedeva, Yu S; Cherepov, A B; Karganov, M Yu

    2014-06-01

    We studied radiosensitivity of 101/Hf, C3H/Sn, and C57Bl mice exposed to sublethal doses of γ-radiation. C57Bl mice responded to radiation much later than 101/Hf and C3H/Sn mice, while their adaptability was high enough. 101/Hf and C3H/Sn mice developed acute radiation sickness in a similar way. However, C3H/Sn mice showed better physiological indicators after radiation crisis. There was no noticeable improvement after the development of radiation sickness in 101/Hf mice. To assess individual radiosensitivity, integrated approach should be applied using the data obtained by different methods on several physiological levels. PMID:24958371

  6. Antihyperglycaemic effect and acute toxicity of Securigera Securidaca L. seed extracts in mice.

    PubMed

    Hosseinzadeh, H; Ramezani, M; Danaei, A R

    2002-12-01

    The antihyperglycaemic activity of a Securigera securidaca aqueous infusion and an ethanol maceration extract of seeds was studied in normoglycaemic, glucose-induced hyperglycaemic and alloxan-induced diabetic mice. The acute toxicity of the ethanol extract was more than that of the aqueous one. The phytochemical analysis showed that the seed extracts were rich in flavonoids. The intraperitoneal and oral administration of the aqueous and ethanol extracts significantly reduced blood glucose in alloxan-induced diabetic mice. In normoglycaemic and glucose-induced hyperglycaemic mice, the blood glucose levels were not significantly different from the control. Glibenclamide was not able to lower blood glucose in alloxan-induced diabetic mice, while it significantly lowered the blood sugar in normoglycaemic mice. The results indicate that S. securidaca seed extracts significantly reduce blood glucose in alloxan-induced diabetic mice by a mechanism different from that of sulfonylurea agents. PMID:12458478

  7. Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

    PubMed Central

    Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

    2015-01-01

    Background Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. Methods A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. Results A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). Conclusion The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis. PMID:26332375

  8. Evaluation of effects of ozone exposure on influenza infection in mice using several indicators of susceptibility.

    PubMed

    Selgrade, M K; Illing, J W; Starnes, D M; Stead, A G; Ménache, M G; Stevens, M A

    1988-07-01

    Mice were exposed to 1 ppm O3, 3 hr/day, for 5 consecutive days. Separate groups of mice were infected with influenza following each of the individual exposures. A twofold increase in the incidence of mortality and a 3-day decrease in mean survival time were observed in mice infected after the second exposure. There were no effects on percentage mortality or mean survival time due to exposure to 1 ppm O3 in mice infected after the first, third, fourth, or fifth exposure. When the exposure concentration was lowered to 0.5 ppm, there were no effects on mortality in mice infected after the second exposure. Five, daily, 3-hr exposures to 1 ppm O3 had no effect on virus titers in the lungs of mice infected after either the second or fifth exposure. In contrast, wet lung weights were significantly enhanced over infected air controls in mice infected after the second O3 exposure at both 1 and 0.5 ppm but not at 0.25 ppm exposure concentrations. This effect on lung wet weight was observed in mice infected with a dose of virus which produced 7-33% mortality in controls as well as in mice infected with a sublethal dose of virus. Histopathologic changes due to sublethal influenza infection, including nonsuppurative pneumonitis and necrosis, squamous metaplasia and hyperplasia of the epithelium lining the bronchi and bronchioles, were more severe in mice infected after the second of five, 1 ppm O3 exposure than in comparable air controls. Sublethal infection caused a loss of lung volume with secondary reduction in diffusing capability and homogenity of ventilation distribution. These latter two effects were also exacerbated in mice infected after the second of five, 1 ppm O3 exposures as compared to air controls. When mice were infected after the fifth, 1 ppm O3 exposure, there was no effect due to ozone on either lung wet weight or histopathology. The data indicate that O3 has little if any effect on antiviral defense mechanisms since virus titers in the lungs were not

  9. Viral Infection of the Central Nervous System Exacerbates Interleukin-10 Receptor Deficiency-Mediated Colitis in SJL Mice.

    PubMed

    Uhde, Ann-Kathrin; Herder, Vanessa; Akram Khan, Muhammad; Ciurkiewicz, Malgorzata; Schaudien, Dirk; Teich, René; Floess, Stefan; Baumgärtner, Wolfgang; Huehn, Jochen; Beineke, Andreas

    2016-01-01

    Theiler´s murine encephalomyelitis virus (TMEV)-infection is a widely used animal model for studying demyelinating disorders, including multiple sclerosis (MS). The immunosuppressive cytokine Interleukin (IL)-10 counteracts hyperactive immune responses and critically controls immune homeostasis in infectious and autoimmune disorders. In order to investigate the effect of signaling via Interleukin-10 receptor (IL-10R) in infectious neurological diseases, TMEV-infected SJL mice were treated with IL-10R blocking antibody (Ab) in the acute and chronic phase of the disease. The findings demonstrate that (i) Ab-mediated IL-10 neutralization leads to progressive colitis with a reduction in Foxp3+ regulatory T cells and increased numbers of CD8+CD44+ memory T cells as well as activated CD4+CD69+ and CD8+CD69+ T cells in uninfected mice. (ii) Concurrent acute TMEV-infection worsened enteric disease-mediated by IL-10R neutralization. Virus-triggered effects were associated with an enhanced activation of CD4+ T helper cells and CD8+ cytotoxic T lymphocytes and augmented cytokine expression. By contrast, (iii) IL-10R neutralization during chronic TMEV-infection was not associated with enhanced peripheral immunopathology but an increased CD3+ T cell influx in the spinal cord. IL-10R neutralization causes a breakdown in peripheral immune tolerance in genetically predisposed mice, which leads to immune-mediated colitis, resembling inflammatory bowel disease. Hyperactive immune state following IL-10R blockade is enhanced by central nervous system-restricted viral infection in a disease phase-dependent manner. PMID:27611574

  10. Localization of latency-associated transcripts in the uterovaginal plexus of herpes simplex virus type 1 and 2 latently infected mice.

    PubMed

    Podlech, J; Hengerer, F; Fleck, M; Kunkel, J; Falke, D

    1997-05-01

    The vagina and medulla of the adrenal gland of mice vaginally infected with herpes simplex virus (HSV) types 1 and 2 were examined in the latent stage of infection (5 to 51 weeks post-infection). RNA in situ hybridization with HSV-1 and -2 latency-associated transcript (LAT) RNA probes resulted in positively stained neuronal cell nuclei in the uterovaginal plexus, but not in the medulla of the adrenal gland. These organs were chosen because HSV antigens can be detected not only in the vaginal epithelium, but also in neurons of the uterovaginal plexus and in the medulla of the adrenal gland at the acute stage of genital infection. To our knowledge, this is the first report describing LATs in neurons of the uterovaginal plexus in the genital tract of latently HSV-infected mice. PMID:9152429

  11. Immunopathological assessments of human Blastocystis spp. in experimentally infected immunocompetent and immunosuppresed mice.

    PubMed

    Abdel-Hafeez, Ekhlas H; Ahmad, Azza K; Abdelgelil, Noha H; Abdellatif, Manal Z M; Kamal, Amany M; Hassanin, Kamel M A; Abdel-Razik, Abdel-Razik H; Abdel-Raheem, Ehab M

    2016-05-01

    Blastocystis spp., one of the most common parasites colonizing the human intestine, is an extracellular, luminal protozoan with controversial pathogenesis. The host's immune response against Blastocystis spp. infection has also not been defined yet. Therefore, this research aimed to assess the potential pathogenicity of this parasite and its ability to modulate the immune response in experimental infected immunocompetent and immunosuppresed mice. These results demonstrated that the infected immunosuppressed mice were more affected than infected immunocompetent mice. Histopathological examination of the small intestine in the infected immunosuppressed mice showed that Blastocystis spp. infiltrated all the layers. Moreover, the epithelia showed exfoliation and inflammatory cell infiltration in submucosa compared to that of the infected immunocompetent mice. As well, examination of the large intestine of the infected immunosuppressed group showed severe goblet cell hyperplasia. Blastocystis spp. infiltrated all the large intestine layers compared to that of the infected immunocompetent group. Furthermore, there was a significant upregulation of the expression of proinflammatory cytokines: interleukin 12 (IL-12) and tumor necrosis factor alpha (TNF-α) in the infected immunosuppressed mice compared to that of the infected immunocompetent ones (p ≤ 0.004 and p ≤ 0.002, respectively). However, the expression of anti-inflammatory cytokines (IL-4 and IL-10) was significantly downregulated in the infected immunosuppressed group compared to that of the infected immunocompetent group one at 10 days postinfection (p ≤ 0.002 and p ≤ 0.001, respectively). The results of this study revealed that Blastocystis spp. affected the production of pro- and anti-inflammatory cytokines in both groups of mice compared to healthy normal (naive) group. Additionally, these data showed that there was a significant upregulation (p ≤ 0.005) of the locally

  12. Acute disseminated encephalomyelitis associated with hepatitis A virus infection.

    PubMed

    Alehan, Füsun K; Kahveci, Suat; Uslu, Yasemin; Yildirim, Tülin; Yilmaz, Başak

    2004-06-01

    We describe the case of a 30-month-old boy who developed acute disseminated encephalomyelitis (ADEM) after hepatitis A virus (HAV) infection and ultimately died. As far as we know, this is only the second case of HAV-associated ADEM to be reported in the literature. The child was brought to hospital with fever, lethargy and weakness of 2 days duration. He had developed jaundice, abdominal pain and malaise 2 weeks beforehand and these problems had resolved within 2 days. Neurological examination revealed lethargy, generalised weakness and positive Babinski's signs bilaterally. Cerebrospinal fluid examination showed mild lymphocytic pleocytosis, increased protein and elevated anti-HAV IgM and IgG titres. Serum HAV IgM and IgG titres were also elevated. Despite aggressive treatment with ceftriaxone, acyclovir and anti-oedema measures, he developed papilloedema and coma within 24 hours of admission. Magnetic resonance imaging of the brain revealed diffuse cerebral oedema and multifocal hyperintensities on T2-weighted images, with most lesions in the white matter of both cerebral hemispheres. The diagnosis of ADEM was established and high-dose steroids and intravenous immunoglobulin were added to the treatment regimen. However, his clinical condition continued to deteriorate and he died on the 20th day in hospital. This case shows that HAV infection can be linked with ADEM. Patients with HAV infection should be examined carefully for central nervous system symptoms during follow-up. Likewise, the possibility of HAV infection should be investigated in cases of ADEM. PMID:15186542

  13. Photodynamic therapy for Acinetobacter baumannii burn infections in mice.

    PubMed

    Dai, Tianhong; Tegos, George P; Lu, Zongshun; Huang, Liyi; Zhiyentayev, Timur; Franklin, Michael J; Baer, David G; Hamblin, Michael R

    2009-09-01

    Multidrug-resistant Acinetobacter baumannii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment with traditional antibiotics can be extremely difficult, and new antimicrobial approaches are being investigated. One of these alternatives to antimicrobials could be the combination of nontoxic photosensitizers (PSs) and visible light, known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full-thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by the covalent conjugation of chlorin(e6) to polyethylenimine, followed by illumination of the burn surface with red light. Application of 10(8) A. baumannii cells to the surface of 10-s burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted, on average, 22 days and that were characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after application of the bacteria gave over 3 log units of loss of bacterial luminescence in a light exposure-dependent manner, while PDT carried out on day 1 and day 2 gave an approximately 1.7-log reduction. The application of PS dissolved in 10% or 20% dimethyl sulfoxide without light gave only a modest reduction in the bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to the inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multidrug-resistant localized A. baumannii infections. PMID:19564369

  14. Therapeutic effect of mefloquine on Schistosoma mansoni in experimental infection in mice.

    PubMed

    Abou-Shady, Omaima Mohammed; Mohammed, Soheir Sayed; Attia, Samar Sayed; Yusuf, Hebat-Allah Salah; Helmy, Dina Omar

    2016-06-01

    Schistosomiasis is one of the most prevalent parasitic infections worldwide. Praziquantel is the drug of choice for treatment of schistosomiasis for its high efficacy. The present work was carried out on 160 mice to evaluate the therapeutic effect of mefloquine on experimental schistosomiasis mansoni. Mice were classified into 3 groups; group I (20 infected non-treated mice), group II included 60 infected mice which were further divided into group IIm (20 mice treated with 400 mg/kg mefloquine), group IIp (20 mice treated with 1,000 mg/kg/2 days praziquantel) and group IIpm (20 mice treated with 200 mg/kg mefloquine and 500 mg/kg praziquantel), group III included 80 non-infected mice subdivided into group IIIn (20 non-treated mice), group IIIm (20 mice treated with 400 mg/kg mefloquine), group IIIp (20 mice treated with 1,000 mg/kg/2 days praziquantel), group IIIpm (20 mice treated with 200 mg mefloquine and 500 mg praziquantel). Mefloquine significantly reduced worm burden, tissue egg load, number of liver granulomas and increased the percent of dead ova within granulomas. Combination of mefloquine and praziquantel gave better curative effects than praziquantel or mefloquine given alone. PMID:27413290

  15. Airway microbiota and acute respiratory infection in children.

    PubMed

    Hasegawa, Kohei; Camargo, Carlos A

    2015-01-01

    Acute respiratory infections (ARIs), such as bronchiolitis and pneumonia, are the leading cause of hospitalization of infants in the US. While the incidence and severity of ARI can vary widely among children, the reasons for these differences are not fully explained by traditional risk factors (e.g., prematurity, viral pathogens). The recent advent of molecular diagnostic techniques has revealed the presence of highly functional communities of microbes inhabiting the human body (i.e., microbiota) that appear to influence development of local and systemic immune response. We propose a 'risk and resilience' model in which airway microbiota are associated with an increased (risk microbiota) or decreased (resilience microbiota) incidence and severity of ARI in children. We also propose that modulating airway microbiota (e.g., from risk to resilience microbiota) during early childhood will optimize airway immunity and, thereby, decrease ARI incidence and severity in children. PMID:25961472

  16. Acute phase response to Mycoplasma haemofelis and 'Candidatus Mycoplasma haemominutum' infection in FIV-infected and non-FIV-infected cats.

    PubMed

    Korman, R M; Cerón, J J; Knowles, T G; Barker, E N; Eckersall, P D; Tasker, S

    2012-08-01

    The pathogenicity of Haemoplasma spp. in cats varies with 'Candidatus Mycoplasma haemominutum' (CMhm) causing subclinical infection while Mycoplasma haemofelis (Mhf) often induces haemolytic anaemia. The aims of this study were to characterise the acute phase response (APR) of the cat to experimental infection with Mhf or CMhm, and to determine whether chronic feline immunodeficiency virus (FIV) infection influences this response. The acute phase proteins serum amyloid A (SAA), haptoglobin (Hp) and α-1-acid glycoprotein (AGP) concentrations were measured pre-infection and every 7-14 days up to day 100 post-infection (pi) in cats infected with either Mhf or CMhm. Half of each group of cats (6/12) were chronically and subclinically infected with FIV. Marbofloxacin treatment was given on days 16-44 pi to half of the Mhf-infected cats, and on days 49-77 pi to half of the CMhm-infected cats. FIV-infected animals had significantly lower AGP concentrations, and significantly greater Hp concentrations than non-FIV-infected cats when infected with CMhm and Mhf, respectively. Both CMhm and Mhf infection were associated with significant increases in SAA concentrations, while AGP concentrations were only significantly increased by Mhf infection. Mhf-infected cats had significantly greater SAA concentrations than CMhm-infected animals. Both Mhf and CMhm infections were associated with an APR, with Mhf infection inducing a greater response. Chronic FIV infection appeared to modify the APR, which varied with the infecting Haemoplasma species. PMID:22763129

  17. [Acute tubulointerstitial nephritis following adenovirus and respiratory syncytial virus infection].

    PubMed

    de Suremain, A; Somrani, R; Bourdat-Michel, G; Pinel, N; Morel-Baccard, C; Payen, V

    2015-05-01

    Acute tubulointerstitial nephritis (TIN) is responsible for nearly 10% of acute renal failure (ARF) cases in children. It is mostly drug-induced, but in a few cases viruses are involved, probably by an indirect mechanism. An immune-competent 13-month-old boy was admitted to the intensive care unit for severe ARF with anuria in a context of fever, cough, and rhinorrhea lasting 1 week. The kidney biopsy performed early brought out tubulointerstitial damage with mild infiltrate of lymphocytes, without any signs of necrosis. There were no virus inclusion bodies, no interstitial hemorrhage, and no glomerular or vascular damage. Other causes of TIN were excluded: there was no biological argument for an immunological, immune, or drug-induced cause. Adenovirus (ADV) and respiratory syncytial virus (RSV) were positive in respiratory multiplex polymerase chain reaction (PCR) in nasal aspirate but not in blood, urine, and renal tissue. The patient underwent dialysis for 10 days but the response to corticosteroid therapy was quickly observed within 48 h. The mechanism of TIN associated with virus infection is unknown. However, it may be immune-mediated to be able to link severe renal dysfunction and ADV and/or RSV invasion of the respiratory tract. PMID:25842199

  18. An enterovirus 71 strain causes skeletal muscle damage in infected mice

    PubMed Central

    Lin, Peixin; Gao, Lulu; Huang, Yeen; Chen, Qing; Shen, Hong

    2015-01-01

    Objective: To study the target organs for enterovirus 71 (EV71) in infected suckling mice. Methods: 5-day-old BALB/c suckling mice were infected with an EV71 strain. Tissues of the infected mice were processed for histopathological examination, including immunohistochemistry, in situ hybridization, ultrastructural observation. Results: Some mice developed limb paralysis, trouble walking and loss of balance. Results of the histopathological study showed that a large amount of EV71 existed in the skeletal muscle tissues, accounting for the damage of the skeletal muscles. Conclusion: The EV71 clinical isolate used in this study presented evident myotropism. Skeletal muscles are important target organs for EV71 in the infected suckling mice. To clarify the relationship between EV71 infection and muscle diseases may contribute to a better understanding of the pathogenesis of EV71. PMID:26097530

  19. ACG Clinical Guideline: Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults.

    PubMed

    Riddle, Mark S; DuPont, Herbert L; Connor, Bradley A

    2016-05-01

    Acute diarrheal infections are a common health problem globally and among both individuals in the United States and traveling to developing world countries. Multiple modalities including antibiotic and non-antibiotic therapies have been used to address these common infections. Information on treatment, prevention, diagnostics, and the consequences of acute diarrhea infection has emerged and helps to inform clinical management. In this ACG Clinical Guideline, the authors present an evidence-based approach to diagnosis, prevention, and treatment of acute diarrhea infection in both US-based and travel settings. PMID:27068718

  20. Activation of P2X7 Receptor by ATP Plays an Important Role in Regulating Inflammatory Responses during Acute Viral Infection

    PubMed Central

    Lee, Benjamin H.; Hwang, David M.; Palaniyar, Nades; Grinstein, Sergio; Philpott, Dana J.; Hu, Jim

    2012-01-01

    Acute viral infection causes damages to the host due to uncontrolled viral replication but even replication deficient viral vectors can induce systemic inflammatory responses. Indeed, overactive host innate immune responses to viral vectors have led to devastating consequences. Macrophages are important innate immune cells that recognize viruses and induce inflammatory responses at the early stage of infection. However, tissue resident macrophages are not easily activated by the mere presence of virus suggesting that their activation requires additional signals from other cells in the tissue in order to trigger inflammatory responses. Previously, we have shown that the cross-talk between epithelial cells and macrophages generates synergistic inflammatory responses during adenoviral vector infection. Here, we investigated whether ATP is involved in the activation of macrophages to induce inflammatory responses during an acute adenoviral infection. Using a macrophage-epithelial cell co-culture system we demonstrated that ATP signaling through P2X7 receptor (P2X7R) is required for induction of inflammatory mediators. We also showed that ATP-P2X7R signaling regulates inflammasome activation as inhibition or deficiency of P2X7R as well as caspase-1 significantly reduced IL-1β secretion. Furthermore, we found that intranasal administration of replication deficient adenoviral vectors in mice caused a high mortality in wild-type mice with symptoms of acute respiratory distress syndrome but the mice deficient in P2X7R or caspase-1 showed increased survival. In addition, wild-type mice treated with apyrase or inhibitors of P2X7R or caspase-1 showed higher rates of survival. The improved survival in the P2X7R deficient mice correlated with diminished levels of IL-1β and IL-6 and reduced neutrophil infiltration in the early phase of infection. These results indicate that ATP, released during viral infection, is an important inflammatory regulator that activates the

  1. Role of CCL3/MIP-1α and CCL5/RANTES during acute Trypanosoma cruzi infection in rats

    PubMed Central

    Roffê, Ester; Oliveira, Fabiano; Souza, Adriano L.S.; Pinho, Vanessa; Souza, Danielle G.; Souza, Patrícia R.S.; Russo, Remo C.; Santiago, Helton C.; Romanha, Álvaro J.; Tanowitz, Herbert B.; Valenzuela, Jesus G.; Teixeira, Mauro M.

    2011-01-01

    Chagas’ disease is caused by Trypanosoma cruzi infection and is characterized by chronic fibrogenic inflammation and heart dysfunction. Chemokines are produced during infection and drive tissue inflammation. In rats, acute infection is characterized by intense myocarditis and regression of inflammation after control of parasitism. We investigated the role of CCL3 and CCL5 during infection by using DNA vaccination encoding for each chemokine separately or simultaneously. MetRANTES treatment was used to evaluate the role of CCR1 and CCR5, the receptors for CCL3 and CCL5. Vaccination with CCL3 or CCL5 increased heart parasitism and decreased local IFN-γ production, but did not influence intensity of inflammation. Simultaneous treatment with both plasmids or treatment with MetRANTES enhanced cardiac inflammation, fibrosis and parasitism. In conclusion, chemokines CCL3 and CCL5 are relevant, but not essential, for control of T. cruzi infection in rats. On the other hand, combined blockade of these chemokines or their receptors enhanced tissue inflammation and fibrosis, clearly contrasting with available data in murine models of T. cruzi infection. These data reinforce the important role of chemokines during T. cruzi infection but suggest that caution must be taken when expanding the therapeutic modulation of the chemokine system in mice to the human infection. PMID:20452453

  2. Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection

    PubMed Central

    Gironès, Núria; Carbajosa, Sofía; Guerrero, Néstor A.; Poveda, Cristina; Chillón-Marinas, Carlos; Fresno, Manuel

    2014-01-01

    Chagas disease is caused by Trypanosoma cruzi infection, being cardiomyopathy the more frequent manifestation. New chemotherapeutic drugs are needed but there are no good biomarkers for monitoring treatment efficacy. There is growing evidence linking immune response and metabolism in inflammatory processes and specifically in Chagas disease. Thus, some metabolites are able to enhance and/or inhibit the immune response. Metabolite levels found in the host during an ongoing infection could provide valuable information on the pathogenesis and/or identify deregulated metabolic pathway that can be potential candidates for treatment and being potential specific biomarkers of the disease. To gain more insight into those aspects in Chagas disease, we performed an unprecedented metabolomic analysis in heart and plasma of mice infected with T. cruzi. Many metabolic pathways were profoundly affected by T. cruzi infection, such as glucose uptake, sorbitol pathway, fatty acid and phospholipid synthesis that were increased in heart tissue but decreased in plasma. Tricarboxylic acid cycle was decreased in heart tissue and plasma whereas reactive oxygen species production and uric acid formation were also deeply increased in infected hearts suggesting a stressful condition in the heart. While specific metabolites allantoin, kynurenine and p-cresol sulfate, resulting from nucleotide, tryptophan and phenylalanine/tyrosine metabolism, respectively, were increased in heart tissue and also in plasma. These results provide new valuable information on the pathogenesis of acute Chagas disease, unravel several new metabolic pathways susceptible of clinical management and identify metabolites useful as potential specific biomarkers for monitoring treatment and clinical severity in patients. PMID:25412247

  3. Global metabolomic profiling of acute myocarditis caused by Trypanosoma cruzi infection.

    PubMed

    Gironès, Núria; Carbajosa, Sofía; Guerrero, Néstor A; Poveda, Cristina; Chillón-Marinas, Carlos; Fresno, Manuel

    2014-11-01

    Chagas disease is caused by Trypanosoma cruzi infection, being cardiomyopathy the more frequent manifestation. New chemotherapeutic drugs are needed but there are no good biomarkers for monitoring treatment efficacy. There is growing evidence linking immune response and metabolism in inflammatory processes and specifically in Chagas disease. Thus, some metabolites are able to enhance and/or inhibit the immune response. Metabolite levels found in the host during an ongoing infection could provide valuable information on the pathogenesis and/or identify deregulated metabolic pathway that can be potential candidates for treatment and being potential specific biomarkers of the disease. To gain more insight into those aspects in Chagas disease, we performed an unprecedented metabolomic analysis in heart and plasma of mice infected with T. cruzi. Many metabolic pathways were profoundly affected by T. cruzi infection, such as glucose uptake, sorbitol pathway, fatty acid and phospholipid synthesis that were increased in heart tissue but decreased in plasma. Tricarboxylic acid cycle was decreased in heart tissue and plasma whereas reactive oxygen species production and uric acid formation were also deeply increased in infected hearts suggesting a stressful condition in the heart. While specific metabolites allantoin, kynurenine and p-cresol sulfate, resulting from nucleotide, tryptophan and phenylalanine/tyrosine metabolism, respectively, were increased in heart tissue and also in plasma. These results provide new valuable information on the pathogenesis of acute Chagas disease, unravel several new metabolic pathways susceptible of clinical management and identify metabolites useful as potential specific biomarkers for monitoring treatment and clinical severity in patients. PMID:25412247

  4. Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia

    PubMed Central

    Remolina, Yuly Andrea; Ulloa, María Mercedes; Vargas, Hernán; Díaz, Liliana; Gómez, Sandra Liliana; Saavedra, Alfredo; Sánchez, Edgar; Cortés, Jorge Alberto

    2015-01-01

    Objectives To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. Design A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Setting Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. Participants Ninety-one adult patients with acute respiratory infection (55% were female). Measurements Viral identification, intensive care unit admission, hospital stay, and mortality. Results Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. Conclusions The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality. PMID:26576054

  5. An Overview of Typical Infections of Research Mice: Health Monitoring and Prevention of Infection.

    PubMed

    Fahey, James R; Olekszak, Haiyan

    2015-01-01

    There are many reasons to keep research mice healthy and free from infections. The two most important of these are to protect the health and welfare of research mice and to prevent infections from negatively impacting research. Just as the genetic integrity of a mouse strain will influence the reproducibility and validity of research data, so too will the microbiologic integrity of the animals. This has been repeatedly demonstrated in the literature of laboratory animal sciences wherein the direct impact of infections on physiologic parameters under study have been described. Therefore, it is of great importance that scientists pay close attention to the health status of their research animal colonies and maintain good communications with the animal facility personnel at their institution about mouse health issues. This overview provides information about animal health monitoring (HM) in research mouse colonies including commonly monitored agents, diagnostic methods, HM program, risk assessment, and animal facility biosecurity. Lastly, matters of communication with laboratory animal professionals at research institutions are also addressed. PMID:26331758

  6. Virological and clinico-pathological features of orf virus infection in experimentally infected rabbits and mice.

    PubMed

    Cargnelutti, J F; Masuda, E K; Martins, M; Diel, D G; Rock, D L; Weiblen, R; Flores, E F

    2011-01-01

    Many aspects of the biology of orf virus (ORFV) infection remain poorly understood and attempts to establish animal models have yielded conflicting and non-reproducible results. We herein describe the characterization of ORFV infection and disease in rabbits and mice. A protocol of intradermal inoculation was employed to inoculate 10(8.5)TCID₅₀/mL of ORFV strain IA-82 in the skin of ears, of the back and labial commissures. All inoculated rabbits presented a clinical course characterized by erythema, macules, papules/vesicles or pustules that eventually dried originating scabs. Local signs started around days 3 and 4 post-inoculation (pi) and lasted 3-10 days. Virus was recovered from lesions between days 2 and 14pi. Histological examination of lesions revealed focal proliferative dermatitis with ballooning degeneration and eosinophilic intracytoplasmic inclusion bodies in keratinocytes, histological hallmarks of contagious ecthyma in sheep. A similar, albeit milder clinical course occurred in 5/10 inoculated mice; virus was recovered from lesions from three animals. Inoculated lambs - used as controls - developed severe lesions of contagious ecthyma. VN tests performed at day 28pi failed to detect neutralizing antibodies in all inoculated animals. In contrast, convalescent rabbit sera were positive by ELISA at dilutions from 100 to 400. These results show that rabbits are susceptible to ORFV infection and thus may be used to study selected aspects of ORFV biology. PMID:20833245

  7. Oritavancin for acute bacterial skin and skin structure infection

    PubMed Central

    Messina, Julia A.; Fowler, Vance G.; Corey, G. Ralph

    2015-01-01

    Introduction Inpatient treatment of acute bacterial skin and skin structure infections (ABSSSI) exerts a significant economic burden on the healthcare system. Oritavancin is a concentration-dependent, rapidly bactericidal agent approved for the treatment of ABSSSI. Its prolonged half-life with one-time intravenous (IV) dosing offers a potential solution to this burden. In addition, oritavancin represents an alternative therapy for Streptococci and multidrug resistant gram-positive bacteria including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Animal models have also shown promising results with oritavancin for other disease states including those that require long courses of IV therapy. Areas covered This review covers oritavancin’s basic chemistry, spectrum of activity, pharmacodynamics/ pharmacokinetics, efficacy in clinical trials, and provides expert opinion on future directions. To compose this review, a search of PubMed was performed, and articles written in the English language were selected based on full text availability. Expert Opinion If oritavancin is proven to be a cost-effective strategy for outpatient treatment and prevents complications of prolonged IV therapy, it will be sought as an alternative antibiotic therapy for ABSSSI. In addition, further clinical data demonstrating efficacy in gram-positive infections requiring prolonged therapy such as endocarditis and osteomyelitis could support oritavancin’s success in the current market. PMID:25803197

  8. Prolonged survival of scavenger receptor class A-deficient mice from pulmonary Mycobacterium tuberculosis infection

    PubMed Central

    Sever-Chroneos, Zvjezdana; Tvinnereim, Amy; Hunter, Robert L.; Chroneos, Zissis C.

    2016-01-01

    SUMMARY The present study tested the hypothesis that the scavenger receptor SR-A modulates granuloma formation in response to pulmonary infection with Mycobacterium tuberculosis (MTB). To test this hypothesis, we monitored survival and histopathology in WT and SR-A-deficient mice following aerosol infection with MTB Rv. SR-A-deficient (SR-A−/−) mice infected with MTB survived significantly longer than WT mice; the mean survival of SR-A−/− mice exceeded 430 days compared to 230 days for WT mice. Early granuloma formation was not impaired in SR-A−/− mice. The extended survival of SR-A−/− mice was associated with 13- and 3-fold higher number of CD4+ lymphocytes and antigen presenting cells in SR-A−/− lungs compared to WT mice 280 after infection. The histopathology of chronically infected SR-A−/− lungs, however, was marked by abundant cholesterol clefts in parenchymal lesions containing infection in multinucleated giant cells. The present study indicates SR-A as a candidate gene of the innate immune system influencing the chronic phase of M. tuberculosis infection. PMID:22088322

  9. Progression of visceral leishmaniasis due to Leishmania infantum in BALB/c mice is markedly slowed by prior infection with Trichinella spiralis.

    PubMed Central

    Rousseau, D; Le Fichoux, Y; Stien, X; Suffia, I; Ferrua, B; Kubar, J

    1997-01-01

    We investigated in BALB/c mice the influence of the immunological environment created by the nematode Trichinella spiralis on the course of visceral leishmaniasis due to Leishmania infantum. On the day of Leishmania inoculation (day 0), mice, T. spiralis infected 7 days earlier, presented increased gamma interferon (IFN-gamma), interleukin-4 (IL-4), and IL-5 mRNA levels locally and systemically and increased the potential of spleen cells to synthesize IFN-gamma and IL-4 after activation in vitro. Eighteen days after Leishmania inoculation (day 18), corresponding to the acute phase of leishmaniasis, the hepatic amastigote burden in mice coinfected with L. infantum and T. spiralis (LT mice) was significantly lower (P < 0.001) than that in mice infected with L. infantum only (L mice). IFN-gamma and IL-4 mRNAs were overexpressed in livers of LT and L mice. On day 70, corresponding to the chronic phase, the splenic amastigote load was significantly lower (P = 0.004) in LT mice than it was in L mice. Splenic IFN-gamma transcripts were overexpressed in both L and LT mice. After Leishmania-specific in vitro stimulation, cytokine production was enhanced in both groups, but spleen cells from L mice produced significantly more IFN-gamma than did spleen cells from LT mice. Our data (i) generalize previous results indicating the lack of a clear-cut correlation between the outcome of murine visceral leishmaniasis and the type of cytokine pattern and (ii) demonstrate that in LT mice, leishmaniasis takes a markedly milder course than it does in L mice, providing information on the potential consequences of coinfection in a mammalian host. PMID:9393785

  10. Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice

    PubMed Central

    Agollah, Germaine D; Wu, Grace; Peng, Ho-Lan; Kwon, Sunkuk

    2015-01-01

    AIM: To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis. METHODS: Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. RESULTS: Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels

  11. Mucosal immunization with PsaA protein, using chitosan as a delivery system, increases protection against acute otitis media and invasive infection by Streptococcus pneumoniae.

    PubMed

    Xu, J-H; Dai, W-J; Chen, B; Fan, X-Y

    2015-03-01

    As infection with Streptococcus pneumoniae (mainly via the mucosal route) is a leading cause of acute otitis media, sinus and bacterial pneumonia, the mucosal immunity plays an important role in the prevention of pneumococcal diseases. Therefore, intranasal vaccination may be an effective immunization strategy, but requires appropriate mucosal vaccine delivery systems. In this work, chitosan was used as a mucosal delivery system to form chitosan-PsaA nanoparticles based on ionotropic gelation methods and used to immunize BALB/c mice intranasally. Compared to mice immunized with naked PsaA, levels of IFN-γ, IL-17A and IL-4 in spleen lymphocytes, the systemic (IgG in serum) and mucosal (IgA in mucosal lavage) specific antibodies were enhanced significantly in mice inoculated with chitosan-PsaA. Furthermore, increased protection against acute otitis media following middle ear challenge with pneumococcus serotype 14, and improved survival following intraperitoneal challenge with pneumococcus serotype 3 or serotype 14, was found in the mice immunized with chitosan-PsaA nanoparticles. Thus, intranasal immunization with chitosan-PsaA can successfully induce mucosal and systemic immune responses and increase protection against pneumococcal acute otitis media and invasive infections. Hence, intranasal immunization with PsaA protein, based on chitosan as a delivery system, is an efficient immunization strategy for preventing pneumococcal infections. PMID:25565478

  12. The therapeutic effect of 16 antimicrobial agents on Cryptosporidium infection in mice.

    PubMed

    Tzipori, S R; Campbell, I; Angus, K W

    1982-04-01

    The therapeutic efficiency of 16 anti-microbial agents (Ethopabate, Nicarbazin, Sulphaquinoxaline, Furaltadone, Enterolyte-N, Sulphamethazine, Trinamide, Amprol, Phenamidine, Zoaquin, Halofuginone, Salinomycin, Monensin, Emtryl, Arprinocid and Amprolium) were examined against Cryptosporidium infections in mice. The Cryptosporidium was originally isolated from a field outbreak of calf diarrhoea. The drugs neither prevented nor modified the course of the infection as compared with infected, untreated mice. PMID:7115220

  13. Cytokine patterns in experimental schistosomiasis mansoni infected mice treated with silymarin.

    PubMed

    El-Sayed, Nagwa Mostafa; Fathy, Ghada Mahmoud; Abdel-Rahman, Sara Abdel-Rahman; El-Shafei, Mahmoud Abdel-Atei

    2016-09-01

    The purpose of this study was to determine cytokine patterns in experimental schistosomiasis mansoni infected mice treated with silymarin. The study was conducted upon 100 mice that were divided into five groups; 20 each: uninfected control group, Schistosoma mansoni infected untreated mice (infected control), infected mice treated with praziquantel (PZQ), infected mice treated with silymarin and infected mice treated with both praziquantel and silymarin. 10 mice from each group were sacrificed at 10th and 18th weeks post infection respectively. Histopathological investigations were performed. Liver sections were stained with hematoxylin-eosin and Masson's trichrome stain to evaluate changes of granuloma sizes and numbers. Serum levels of the cytokines (TNF-α, IFN-γ, IL-4 and TGF-β1) were assessed in the sera of all groups by immunoassay. The measured levels of cytokines (IFN-γ, IL-4, TNF-α, TGF-β1) were found to be significantly increased in infected mice compared to normal control. At the same time, treated groups with silymarin alone or combined with PZQ showed significant decrease in IL-4, TNF-α and TGF-β1 levels compared to infected control. On the other hand, there was a significant increase in IFN-γ level observed in all treated groups compared to infected control. In addition, the histopathological examination of the liver in the group treated with PZQ showed a reduction in the number of livers eggs granuloma at all periods of sacrification compared with the infected untreated group. However, there was more decrease in granulomas diameter in both silymarin treated group or combined with PZQ at all periods of sacrification when compared to infected untreated group. In conclusion; treatment with silymarin combined with PZQ in murine schistosomiasis could reduce hepatic fibrosis by their action on the production of pro-inflammatory cytokines. PMID:27605811

  14. Acetazolamide attenuates chemical-stimulated but not thermal-stimulated acute pain in mice

    PubMed Central

    Sun, Ya-jie; Chen, Ying; Pang, Chong; Wu, Ning; Li, Jin

    2014-01-01

    Aim: Acetazolamide (AZA), a carbonic anhydrase (CA) inhibitor, has been found to alleviate inflammatory and neuropathic pain in rats. In the present study, we investigated the effects of AZA on thermal- and chemical-stimulated acute pain in mice and the possible mechanisms underlying the effects. Methods: Five acute pain models based on thermal and chemical stimuli were established to investigate the effects of AZA on different types of nociception in mice. The antinociceptive effects of methazolamide (another CA inhibitor) and diazepam (a positive allosteric modulator of GABAA receptor) were also examined. The drugs were administered either intraperitoneally (ip) or intrathecally. Results: AZA (50–200 mg/kg, ip) did not produce analgesia in two thermal-stimulated acute pain models, ie, mouse tail-flick and hot-plate tests. In contrast, AZA (50–200 mg/kg, ip) dose-dependently reduced paw licking time in both capsaicin and formalin tests in mice. A similar result was observed in a mouse acetic acid-induced writhing test. However, AZA (10 nmol/mouse, intrathecally) did not produce significant analgesia in the 3 chemical-stimulated acute pain models. In addition, methazolamide (50–200 mg/kg, ip) and diazepam (0.25–1.0 mg/kg, ip) did not produce significant analgesia in either thermal- or chemical-stimulated acute pain. Conclusion: AZA produces analgesia in chemical-stimulated, but not thermal-stimulated acute pain in mice. The attenuation of chemical-stimulated acute pain by AZA may not be due to enhancement of GABAA receptor-mediated inhibition via inhibiting CA activity but rather a peripheral ion channel-related mechanism. PMID:24335844

  15. TNF-α from hippocampal microglia induces working memory deficits by acute stress in mice.

    PubMed

    Ohgidani, Masahiro; Kato, Takahiro A; Sagata, Noriaki; Hayakawa, Kohei; Shimokawa, Norihiro; Sato-Kasai, Mina; Kanba, Shigenobu

    2016-07-01

    The role of microglia in stress responses has recently been highlighted, yet the underlying mechanisms of action remain unresolved. The present study examined disruption in working memory due to acute stress using the water-immersion resistant stress (WIRS) test in mice. Mice were subjected to acute WIRS, and biochemical, immunohistochemical, and behavioral assessments were conducted. Spontaneous alternations (working memory) significantly decreased after exposure to acute WIRS for 2h. We employed a 3D morphological analysis and site- and microglia-specific gene analysis techniques to detect microglial activity. Morphological changes in hippocampal microglia were not observed after acute stress, even when assessing ramification ratios and cell somata volumes. Interestingly, hippocampal tumor necrosis factor (TNF)-α levels were significantly elevated after acute stress, and acute stress-induced TNF-α was produced by hippocampal-ramified microglia. Conversely, plasma concentrations of TNF-α were not elevated after acute stress. Etanercept (TNF-α inhibitor) recovered working memory deficits in accordance with hippocampal TNF-α reductions. Overall, results suggest that TNF-α from hippocampal microglia is a key contributor to early-stage stress-to-mental responses. PMID:26551431

  16. Effects of acute and chronic administration of neurosteroid dehydroepiandrosterone sulfate on neuronal excitability in mice

    PubMed Central

    Svob Strac, Dubravka; Vlainic, Josipa; Samardzic, Janko; Erhardt, Julija; Krsnik, Zeljka

    2016-01-01

    Background Neurosteroid dehydroepiandrosterone sulfate (DHEAS) has been associated with important brain functions, including neuronal survival, memory, and behavior, showing therapeutic potential in various neuropsychiatric and cognitive disorders. However, the antagonistic effects of DHEAS on γ-amino-butyric acidA receptors and its facilitatory action on glutamatergic neurotransmission might lead to enhanced brain excitability and seizures and thus limit DHEAS therapeutic applications. The aim of this study was to investigate possible age and sex differences in the neuronal excitability of the mice following acute and chronic DHEAS administration. Methods DHEAS was administered intraperitoneally in male and female adult and old mice either acutely or repeatedly once daily for 4 weeks in a 10 mg/kg dose. To investigate the potential proconvulsant properties of DHEAS, we studied the effects of acute and chronic DHEAS treatment on picrotoxin-, pentylentetrazole-, and N-methyl-D-aspartate-induced seizures in mice. The effects of acute and chronic DHEAS administration on the locomotor activity, motor coordination, and body weight of the mice were also studied. We also investigated the effects of DHEAS treatment on [3H]flunitrazepam binding to the mouse brain membranes. Results DHEAS did not modify the locomotor activity, motor coordination, body weight, and brain [3H]flunitrazepam binding of male and female mice. The results failed to demonstrate significant effects of single- and long-term DHEAS treatment on the convulsive susceptibility in both adult and aged mice of both sexes. However, small but significant changes regarding sex differences in the susceptibility to seizures were observed following DHEAS administration to mice. Conclusion Although our findings suggest that DHEAS treatment might be safe for various potential therapeutic applications in adult as well as in old age, they also support subtle interaction of DHEAS with male and female hormonal status

  17. Reduced acute nociception and chronic pain in Shank2-/- mice.

    PubMed

    Ko, Hyoung-Gon; Oh, Seog-Bae; Zhuo, Min; Kaang, Bong-Kiun

    2016-01-01

    Autism spectrum disorder is a debilitating mental illness and social issue. Autism spectrum disorder patients suffer from social isolation, cognitive deficits, compulsive behavior, and sensory deficits, including hyposensitivity to pain. However, recent studies argued that autism spectrum disorder patients show physiological pain response and, in some cases, even extremely intense pain response to harmless stimulation. Recently, Shank gene family was reported as one of the genetic risk factors of autism spectrum disorder. Thus, in this study, we used Shank2(-) (/) (-) (Shank2 knock-out, KO) mice to investigate the controversial pain sensitivity issue and found that Shank2 KO mice showed reduced tactile perception and analgesia to chronic pain. PMID:27145803

  18. Immunization with Pneumococcal Polysaccharide Serotype 3 and Lipopolysaccharide Modulates Lung and Liver Inflammation during a Virulent Streptococcus pneumoniae Infection in Mice

    PubMed Central

    Restori, Katherine H.; Kennett, Mary J.

    2013-01-01

    Vaccination reduces morbidity and mortality from pneumonia, but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute-phase response, and lung gene expression profiles in mice inoculated intranasally with virulent Gram-positive Streptococcus pneumoniae serotype 3 (ST 3) with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3) or after coimmunization with PPS3 and a low dose of lipopolysaccharide (PPS3+LPS). Pneumonia severity was assessed in the acute phase at 5, 12, 24 and 48 h postinoculation (p.i.) and in the resolution phase at 7 days p.i. Primary PPS3-specific antibody production was upregulated, and IgM binding to pneumococci increased in PPS3-immunized mice. Immunizations with PPS3 or PPS3+LPS decreased bacterial recovery in the lung and blood at 24 and 48 h and increased survival. Microarray analysis of whole-lung RNA revealed significant changes in the acute-phase protein serum amyloid A (SAA) levels between noninfected and infected mice, and these changes were attenuated by immunization. SAA transcripts were higher in the liver and lungs of infected controls, and SAA protein was elevated in serum but decreased in PPS3-immunized mice. Thus, during a virulent pneumonia infection, prior immunization with PPS3 in an IgM-dependent manner as well as immunization with PPS3+LPS attenuated pneumonia severity and promoted resolution of infection, concomitant with significant regulation of cytokine gene expression levels in the lungs and acute-phase proteins in the lungs, liver, and serum. PMID:23389932

  19. ADAMTS13 deficiency exacerbates VWF-dependent acute myocardial ischemia/reperfusion injury in mice

    PubMed Central

    Gandhi, Chintan; Motto, David G.; Jensen, Melissa; Lentz, Steven R.

    2012-01-01

    Epidemiologic studies suggest that elevated VWF levels and reduced ADAMTS13 activity in the plasma are risk factors for myocardial infarction. However, it remains unknown whether the ADAMTS13-VWF axis plays a causal role in the pathophysiology of myocardial infarction. In the present study, we tested the hypothesis that ADAMTS13 reduces VWF-mediated acute myocardial ischemia/reperfusion (I/R) injury in mice. Infarct size, neutrophil infiltration, and myocyte apoptosis in the left ventricular area were quantified after 30 minutes of ischemia and 23.5 hours of reperfusion injury. Adamts13−/− mice exhibited significantly larger infarcts concordant with increased neutrophil infiltration and myocyte apoptosis compared with wild-type (WT) mice. In contrast, Vwf−/− mice exhibited significantly reduced infarct size, neutrophil infiltration, and myocyte apoptosis compared with WT mice, suggesting a detrimental role for VWF in myocardial I/R injury. Treating WT or Adamts13−/− mice with neutralizing Abs to VWF significantly reduced infarct size compared with control Ig–treated mice. Finally, myocardial I/R injury in Adamts13−/−/Vwf−/− mice was similar to that in Vwf−/− mice, suggesting that the exacerbated myocardial I/R injury observed in the setting of ADAMTS13 deficiency is VWF dependent. These findings reveal that ADAMTS13 and VWF are causally involved in myocardial I/R injury. PMID:22983446

  20. The expression of thioredoxin-1 in acute epinephrine stressed mice.

    PubMed

    Jia, Jin-Jing; Zeng, Xian-Si; Li, Kun; Ma, Li-Fang; Chen, Lei; Song, Xin-Qiang

    2016-09-01

    Stress, a state of perceived threat to homeostasis, regulates a panel of important physiological functions. The human mind and body respond to stress by activating the sympathetic nervous system and secreting the catecholamines epinephrine and norepinephrine in the "fight-or-flight" response. However, the protective mechanism of acute stress is still unknown. In the present study, an acute stress mouse model was constructed by intraperitoneal injection of epinephrine (0.2 mg kg(-1)) for 4 h. Epinephrine treatment induced heat shock 70(Hsp70) expression in the stress responsive tissues, such as the cortex, hippocampus, thymus, and kidney. Further, the expression of thioredoxin-1(Trx-1), a cytoprotective protein, was also upregulated in these stress responsive tissues. In addition, the phosphorylation of cAMP-response element binding protein (CREB), a transcription factor of Trx-1, was increased after treatment with epinephrine. The block of CREB activation by H89 inhibited the acute epinephrine stress-induced Trx-1 and Hsp70 expression. Taken together, our data suggest that acute stimuli of epinephrine induced Trx-1 expression through activating CREB and may represent a protective role against stress. PMID:27511023

  1. Dietary lactosucrose suppresses influenza A (H1N1) virus infection in mice

    PubMed Central

    KISHINO, Eriko; TAKEMURA, Naho; MASAKI, Hisaharu; ITO, Tetsuya; NAKAZAWA, Masatoshi

    2015-01-01

    This study examined the effects of lactosucrose (4G-β-D-galactosylsucrose) on influenza A virus infections in mice. First, the effects of lactosucrose on fermentation in the cecum and on immune function were investigated. In female BALB/c mice, lactosucrose supplementation for 6 weeks promoted cecal fermentation and increased both secretory IgA (SIgA) levels in feces and total IgA and IgG2a concentrations in serum. Both the percentage of CD4+ T cells in Peyer’s patches and the cytotoxic activity of splenic natural killer (NK) cells increased significantly in response to lactosucrose. Next, we examined the effects of lactosucrose on low-dose influenza A virus infection in mice. After 2 weeks of dietary supplementation with lactosucrose, the mice were infected with low-dose influenza A virus. At 7 days post infection, a comparison with control mice showed that weight loss was suppressed, as were viral titers in the lungs. In the spleens of lactosucrose-fed mice, there was an increase in the percentage of NK cells. Lastly, mice fed lactosucrose were challenged with a lethal dose of influenza A virus. The survival rate of these mice was significantly higher than that of mice fed a control diet. These results suggested that lactosucrose supplementation suppresses influenza A virus infection by augmenting innate immune responses and enhancing cellular and mucosal immunity. PMID:26594606

  2. Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014

    PubMed Central

    Messacar, Kevin; Pastula, Daniel M.; Robinson, Christine C.; Leshem, Eyal; Sejvar, James J.; Nix, W. Allan; Oberste, M. Steven; Feikin, Daniel R.; Dominguez, Samuel R.

    2016-01-01

    During August 8, 2014–October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case–control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non–EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis. PMID:27434186

  3. Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014.

    PubMed

    Aliabadi, Negar; Messacar, Kevin; Pastula, Daniel M; Robinson, Christine C; Leshem, Eyal; Sejvar, James J; Nix, W Allan; Oberste, M Steven; Feikin, Daniel R; Dominguez, Samuel R

    2016-08-01

    During August 8, 2014-October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case-control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non-EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis. PMID:27434186

  4. Use of a safe, reproducible, and rapid aerosol delivery method to study infection by Burkholderia pseudomallei and Burkholderia mallei in mice.

    PubMed

    Lafontaine, Eric R; Zimmerman, Shawn M; Shaffer, Teresa L; Michel, Frank; Gao, Xiudan; Hogan, Robert J

    2013-01-01

    Burkholderia pseudomallei, the etiologic agent of melioidosis, is a saprophytic bacterium readily isolated from wet soils of countries bordering the equator. Burkholderia mallei is a host-adapted clone of B. pseudomallei that does not persist outside of its equine reservoir and causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by these organisms typically occurs via percutaneous inoculation or inhalation of aerosols, and the most common manifestation is severe pneumonia leading to fatal bacteremia. Glanders and melioidosis are difficult to diagnose and require prolonged antibiotic therapy with low success rates. There are no vaccines available to protect against either Burkholderia species, and there is concern regarding their use as biological warfare agents given that B. mallei has previously been utilized in this manner. Hence, experiments were performed to establish a mouse model of aerosol infection to study the organisms and develop countermeasures. Using a hand-held aerosolizer, BALB/c mice were inoculated intratracheally with strains B. pseudomallei 1026b and B. mallei ATCC23344 and growth of the agents in the lungs, as well as dissemination to the spleen, were examined. Mice infected with 10(2), 10(3) and 10(4) organisms were unable to control growth of B. mallei in the lungs and bacteria rapidly disseminated to the spleen. Though similar results were observed in mice inoculated with 10(3) and 10(4) B. pseudomallei cells, animals infected with 10(2) organisms controlled bacterial replication in the lungs, dissemination to the spleen, and the extent of bacteremia. Analysis of sera from mice surviving acute infection revealed that animals produced antibodies against antigens known to be targets of the immune response in humans. Taken together, these data show that small volume aerosol inoculation of mice results in acute disease, dose-dependent chronic infection, and immune responses that correlate

  5. Use of a Safe, Reproducible, and Rapid Aerosol Delivery Method to Study Infection by Burkholderia pseudomallei and Burkholderia mallei in Mice

    PubMed Central

    Lafontaine, Eric R.; Zimmerman, Shawn M.; Shaffer, Teresa L.; Michel, Frank; Gao, Xiudan; Hogan, Robert J.

    2013-01-01

    Burkholderia pseudomallei, the etiologic agent of melioidosis, is a saprophytic bacterium readily isolated from wet soils of countries bordering the equator. Burkholderia mallei is a host-adapted clone of B. pseudomallei that does not persist outside of its equine reservoir and causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by these organisms typically occurs via percutaneous inoculation or inhalation of aerosols, and the most common manifestation is severe pneumonia leading to fatal bacteremia. Glanders and melioidosis are difficult to diagnose and require prolonged antibiotic therapy with low success rates. There are no vaccines available to protect against either Burkholderia species, and there is concern regarding their use as biological warfare agents given that B. mallei has previously been utilized in this manner. Hence, experiments were performed to establish a mouse model of aerosol infection to study the organisms and develop countermeasures. Using a hand-held aerosolizer, BALB/c mice were inoculated intratracheally with strains B. pseudomallei 1026b and B. mallei ATCC23344 and growth of the agents in the lungs, as well as dissemination to the spleen, were examined. Mice infected with 102, 103 and 104 organisms were unable to control growth of B. mallei in the lungs and bacteria rapidly disseminated to the spleen. Though similar results were observed in mice inoculated with 103 and 104 B. pseudomallei cells, animals infected with 102 organisms controlled bacterial replication in the lungs, dissemination to the spleen, and the extent of bacteremia. Analysis of sera from mice surviving acute infection revealed that animals produced antibodies against antigens known to be targets of the immune response in humans. Taken together, these data show that small volume aerosol inoculation of mice results in acute disease, dose-dependent chronic infection, and immune responses that correlate with those

  6. Motor neuropathy in porphobilinogen deaminase–deficient mice imitates the peripheral neuropathy of human acute porphyria

    PubMed Central

    Lindberg, Raija L.P.; Martini, Rudolf; Baumgartner, Matthias; Erne, Beat; Borg, Jacques; Zielasek, Jürgen; Ricker, Kenneth; Steck, Andreas; Toyka, Klaus V.; Meyer, Urs A.

    1999-01-01

    Acute porphyrias are inherited disorders caused by partial deficiency of specific heme biosynthesis enzymes. Clinically, porphyrias are manifested by a neuropsychiatric syndrome that includes peripheral neuropathy. Although much is known about the porphyrias’ enzyme defects and their biochemical consequences, the cause of the neurological manifestations remains unresolved. We have studied porphyric neuropathy in mice with a partial deficiency of porphobilinogen deaminase (PBGD). PBGD-deficient mice (PBGD–/–) imitate acute porphyria through massive induction of hepatic δ-aminolevulinic acid synthase by drugs such as phenobarbital. Here we show that PBGD–/– mice develop impairment of motor coordination and muscle weakness. Histologically femoral nerves of PBGD–/– mice exhibit a marked decrease in large-caliber (>8 μm) axons and ultrastructural changes consistent with primary motor axon degeneration, secondary Schwann cell reactions, and axonal regeneration. These findings resemble those found in studies of affected nerves of patients with acute porphyria and thus provide strong evidence that PBGD deficiency causes degeneration of motor axons without signs of primary demyelination, thereby resolving a long-standing controversy. Interestingly, the neuropathy in PBGD–/– mice developed chronically and progressively and in the presence of normal or only slightly (twofold) increased plasma and urinary levels of the putative neurotoxic heme precursor δ-aminolevulinic acid. These data suggest that heme deficiency and consequent dysfunction of hemeproteins can cause porphyric neuropathy. PMID:10207164

  7. Acute and chronic nephrotoxicity of platinum nanoparticles in mice

    NASA Astrophysics Data System (ADS)

    Yamagishi, Yoshiaki; Watari, Akihiro; Hayata, Yuya; Li, Xiangru; Kondoh, Masuo; Yoshioka, Yasuo; Tsutsumi, Yasuo; Yagi, Kiyohito

    2013-09-01

    Platinum nanoparticles are being utilized in various industrial applications, including in catalysis, cosmetics, and dietary supplements. Although reducing the size of the nanoparticles improves the physicochemical properties and provides useful performance characteristics, the safety of the material remains a major concern. The aim of the present study was to evaluate the biological effects of platinum particles less than 1 nm in size (snPt1). In mice administered with a single intravenous dose of snPt1, histological analysis revealed necrosis of tubular epithelial cells and urinary casts in the kidney, without obvious toxic effects in the lung, spleen, and heart. These mice exhibited dose-dependent elevation of blood urea nitrogen, an indicator of kidney damage. Direct application of snPt1 to in vitro cultures of renal cells induced significant cytotoxicity. In mice administered for 4 weeks with twice-weekly intraperitoneal snPt1, histological analysis of the kidney revealed urinary casts, tubular atrophy, and inflammatory cell accumulation. Notably, these toxic effects were not observed in mice injected with 8-nm platinum particles, either by single- or multiple-dose administration. Our findings suggest that exposure to platinum particles of less than 1 nm in size may induce nephrotoxicity and disrupt some kidney functions. However, this toxicity may be reduced by increasing the nanoparticle size.

  8. Acute Middle East Respiratory Syndrome Coronavirus Infection in Livestock Dromedaries, Dubai, 2014

    PubMed Central

    Corman, Victor M.; Wong, Emily Y.M.; Tsang, Alan K.L.; Muth, Doreen; Lau, Susanna K. P.; Khazanehdari, Kamal; Zirkel, Florian; Ali, Mansoor; Nagy, Peter; Juhasz, Jutka; Wernery, Renate; Joseph, Sunitha; Syriac, Ginu; Elizabeth, Shyna K.; Patteril, Nissy Annie Georgy; Woo, Patrick C. Y.; Drosten, Christian

    2015-01-01

    Camels carry Middle East respiratory syndrome coronavirus, but little is known about infection age or prevalence. We studied >800 dromedaries of all ages and 15 mother–calf pairs. This syndrome constitutes an acute, epidemic, and time-limited infection in camels <4 years of age, particularly calves. Delayed social separation of calves might reduce human infection risk. PMID:25989145

  9. Effect of a Clostridium difficile Infection Prevention Initiative in Veterans Affairs Acute Care Facilities.

    PubMed

    Evans, Martin E; Kralovic, Stephen M; Simbartl, Loretta A; Jain, Rajiv; Roselle, Gary A

    2016-06-01

    Rates of clinically confirmed hospital-onset healthcare facility-associated Clostridium difficile infections from July 1, 2012, through March 31, 2015, in 127 acute care Veterans Affairs facilities were evaluated. Quarterly pooled national standardized infection ratios decreased 15% from baseline by the final quarter of the analysis period (P=.01, linear regression). Infect Control Hosp Epidemiol 2016;37:720-722. PMID:26864803

  10. NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice

    PubMed Central

    Hofstetter, Amelia R.; De La Cruz, Juan A.; Cao, Weiping; Patel, Jenish; Belser, Jessica A.; McCoy, James; Liepkalns, Justine S.; Amoah, Samuel; Cheng, Guangjie; Ranjan, Priya; Diebold, Becky A.; Shieh, Wun-Ju; Zaki, Sherif; Katz, Jacqueline M.; Sambhara, Suryaprakash; Lambeth, J. David; Gangappa, Shivaprakash

    2016-01-01

    The role of the reactive oxygen species-producing NADPH oxidase family of enzymes in the pathology of influenza A virus infection remains enigmatic. Previous reports implicated NADPH oxidase 2 in influenza A virus-induced inflammation. In contrast, NADPH oxidase 1 (Nox1) was reported to decrease inflammation in mice within 7 days post-influenza A virus infection. However, the effect of NADPH oxidase 1 on lethality and adaptive immunity after influenza A virus challenge has not been explored. Here we report improved survival and decreased morbidity in mice with catalytically inactive NADPH oxidase 1 (Nox1*/Y) compared with controls after challenge with A/PR/8/34 influenza A virus. While changes in lung inflammation were not obvious between Nox1*/Y and control mice, we observed alterations in the T cell response to influenza A virus by day 15 post-infection, including increased interleukin-7 receptor-expressing virus-specific CD8+ T cells in lungs and draining lymph nodes of Nox1*/Y, and increased cytokine-producing T cells in lungs and spleen. Furthermore, a greater percentage of conventional and interstitial dendritic cells from Nox1*/Y draining lymph nodes expressed the co-stimulatory ligand CD40 within 6 days post-infection. Results indicate that NADPH oxidase 1 modulates the innate and adaptive cellular immune response to influenza virus infection, while also playing a role in host survival. Results suggest that NADPH oxidase 1 inhibitors may be beneficial as adjunct therapeutics during acute influenza infection. PMID:26910342

  11. Tularemia among Free-Ranging Mice without Infection of Exposed Humans, Switzerland, 2012

    PubMed Central

    Origgi, Francesco C.; König, Barbara; Lindholm, Anna K.; Mayor, Désirée

    2015-01-01

    The animals primarily infected by Francisella tularensis are rapidly consumed by scavengers, hindering ecologic investigation of the bacterium. We describe a 2012 natural tularemia epizootic among house mice in Switzerland and the assessment of infection of exposed humans. The humans were not infected, but the epizootic coincided with increased reports of human cases in the area. PMID:25531919

  12. Activation of Endogenous Anti-Inflammatory Mediator Cyclic AMP Attenuates Acute Pyelonephritis in Mice Induced by Uropathogenic Escherichia coli

    PubMed Central

    Wei, Yang; Li, Ke; Wang, Na; Cai, Gui-Dong; Zhang, Ting; Lin, Yan; Gui, Bao-Song; Liu, En-Qi; Li, Zong-Fang; Zhou, Wuding

    2015-01-01

    The pathogenesis of pyelonephritis caused by uropathogenic Escherichia coli (UPEC) is not well understood. Here, we show that besides UPEC virulence, the severity of the host innate immune response and invasion of renal epithelial cells are important pathogenic factors. Activation of endogenous anti-inflammatory mediator cAMP significantly attenuated acute pyelonephritis in mice induced by UPEC. Administration of forskolin (a potent elevator of intracellular cAMP) reduced kidney infection (ie, bacterial load, tissue destruction); this was associated with attenuated local inflammation, as evidenced by the reduction of renal production of proinflammatory mediators, renal infiltration of inflammatory cells, and renal myeloperoxidase activity. In primary cell culture systems, forskolin not only down-regulated UPEC-stimulated production of proinflammatory mediators by renal tubular epithelial cells and inflammatory cells (eg, monocyte/macrophages) but also reduced bacterial internalization by renal tubular epithelial cells. Our findings clearly indicate that activation of endogenous anti-inflammatory mediator cAMP is beneficial for controlling UPEC-mediated acute pyelonephritis in mice. The beneficial effect can be explained at least in part by limiting excessive inflammatory responses through acting on both renal tubular epithelial cells and inflammatory cells and by inhibiting bacteria invasion of renal tubular epithelial cells. PMID:25478807

  13. Activation of endogenous anti-inflammatory mediator cyclic AMP attenuates acute pyelonephritis in mice induced by uropathogenic Escherichia coli.

    PubMed

    Wei, Yang; Li, Ke; Wang, Na; Cai, Gui-Dong; Zhang, Ting; Lin, Yan; Gui, Bao-Song; Liu, En-Qi; Li, Zong-Fang; Zhou, Wuding

    2015-02-01

    The pathogenesis of pyelonephritis caused by uropathogenic Escherichia coli (UPEC) is not well understood. Here, we show that besides UPEC virulence, the severity of the host innate immune response and invasion of renal epithelial cells are important pathogenic factors. Activation of endogenous anti-inflammatory mediator cAMP significantly attenuated acute pyelonephritis in mice induced by UPEC. Administration of forskolin (a potent elevator of intracellular cAMP) reduced kidney infection (ie, bacterial load, tissue destruction); this was associated with attenuated local inflammation, as evidenced by the reduction of renal production of proinflammatory mediators, renal infiltration of inflammatory cells, and renal myeloperoxidase activity. In primary cell culture systems, forskolin not only down-regulated UPEC-stimulated production of proinflammatory mediators by renal tubular epithelial cells and inflammatory cells (eg, monocyte/macrophages) but also reduced bacterial internalization by renal tubular epithelial cells. Our findings clearly indicate that activation of endogenous anti-inflammatory mediator cAMP is beneficial for controlling UPEC-mediated acute pyelonephritis in mice. The beneficial effect can be explained at least in part by limiting excessive inflammatory responses through acting on both renal tubular epithelial cells and inflammatory cells and by inhibiting bacteria invasion of renal tubular epithelial cells. PMID:25478807

  14. Effects of chronic methamphetamine exposure on heart function in uninfected and retrovirus-infected mice.

    PubMed

    Yu, Qianli; Montes, Sergio; Larson, Douglas F; Watson, Ronald R

    2002-07-12

    Methamphetamine (MA) increases catecholamine levels, which have detrimental effects on heart function through vasoconstriction, myocardial hypertrophy, and fibrosis. Murine retrovirus infection induces dilated cardiomyopathy (DCM). The present study investigated the cardiovascular effects of chronic MA treatment on uninfected and retrovirus-infected mice. C57BL/6 mice were studied after 12 weeks treatment. The four study groups were (group I) uninfected, MA placebo; (group II) infected, MA placebo; (group III) uninfected, MA treatment; and (group IV) infected and MA treatment. MA injections were given i.p. once a day for 5 days/week with a increasing dose from 15 mg/kg to 40 mg/kg. Left ventricular mechanics were measured in situ a using Millar conductance catheter system for pressure-volume loop analysis. Cardiac pathology was determined with histological analysis. In the uninfected mice, the load independent contractile parameters, pre-load recruitable stroke work (PRSW) and dP/dt(max) vs. Ved, significantly decreased by 32% and 35% in MA treated mice when compared to the saline injected mice. In retrovirus-infected mice, although there were no significant difference in Ees, PRSW, and dP/dt(max) vs. Ved due to MA treatment, they were increased 45%, 15% and 42% respectively when compared to saline treated mice. No further lowered heart function during murine AIDS may be due to the counteraction of the retroviral DCM and the MA induced myocardial fibrosis and hypertrophy (thickening of the ventricular walls). This is supported by increases in the End-diastolic volume (Ved, 38%) and End-systolic volume (Ves, 84%) in the retrovirus-infected saline injected mice, the decreases of 33% and 17% in the uninfected MA-treated mice, but no significant changes in the retrovirus-infected MA treated mice when compared to uninfected saline injected mice. These data suggest that MA induced myocardial cellular changes compensate for retrovirus induced DCM. PMID:12084392

  15. Acute oral toxicity of Pereskia bleo and Pereskia grandifolia in mice

    PubMed Central

    Sim, K. S.; Sri Nurestri, A. M.; Sinniah, S. K.; Kim, K. H.; Norhanom, A. W.

    2010-01-01

    Pereskia bleo and Pereskia grandifolia, belonging to the botanical family Cactaceae, have been traditionally used by the locals in Malaysia for treatment of various ailments. The current study reports the outcome of acute oral toxicity investigation of Pereskia bleo and Pereskia grandifolia, on ICR mice. No mortalities or evidence of adverse effects have been observed in ICR mice following acute oral administration at the highest dose of 2500 mg/ kg crude extracts of Pereskia bleo and Pereskia grandifolia. This is the first report on the acute oral toxicity of Pereskia bleo and Pereskia grandifolia and the findings of this study are in agreement with those of in vitro experiments and thus provide scientific validation on the use of the leaves of Pereskia bleo and Pereskia grandifolia. PMID:20548939

  16. Acute oral toxicity of Pereskia bleo and Pereskia grandifolia in mice.

    PubMed

    Sim, K S; Sri Nurestri, A M; Sinniah, S K; Kim, K H; Norhanom, A W

    2010-01-01

    Pereskia bleo and Pereskia grandifolia, belonging to the botanical family Cactaceae, have been traditionally used by the locals in Malaysia for treatment of various ailments. The current study reports the outcome of acute oral toxicity investigation of Pereskia bleo and Pereskia grandifolia, on ICR mice. No mortalities or evidence of adverse effects have been observed in ICR mice following acute oral administration at the highest dose of 2500 mg/ kg crude extracts of Pereskia bleo and Pereskia grandifolia. This is the first report on the acute oral toxicity of Pereskia bleo and Pereskia grandifolia and the findings of this study are in agreement with those of in vitro experiments and thus provide scientific validation on the use of the leaves of Pereskia bleo and Pereskia grandifolia. PMID:20548939

  17. Neospora caninum: Chronic and congenital infection in consecutive pregnancies of mice.

    PubMed

    Mazuz, Monica L; Shkap, Varda; Wollkomirsky, Ricardo; Leibovich, Benjamin; Savitsky, Igor; Fleiderovitz, Ludmila; Noam, Sugar; Elena, Blinder; Molad, Thea; Golenser, Jacob

    2016-03-30

    Neospora caninum, the causative agent of bovine neosporosis is the major cause of abortion in cattle worldwide. The principal route of transmission is via in utero infection of the offspring. Congenitally-infected dams remain persistently infected for life and might undergo abortions in consecutive pregnancies. In the present study, the effect of N. caninum in chronic and congenital infection was examined. CD1 mice were infected intra-peritoneally with live tachyzoites of the NcIs491 isolate, while non-infected mice served as a control. There were no clinical signs of infection observed following inoculation, but high titers of specific anti- N. caninum antibodies were detected. A month after infection, when chronic-infection was established, mice were mated. Fertility, litter size and mortality rate were monitored within two generations of four consecutive pregnancies. During a nine months period of the study all females maintained high level of antibodies, while the non- infected control mice remained seronegative. There was no difference in the fertility rate of the dams, or in the litter size of infected and control mice. Mortality of offspring of the first and second generations of the infected dams was observed within the two first weeks of life. The vertical transmission was analyzed by PCR assay of offspring brains. PCR positive results were found in all 13 litters of the first generation tested during four consecutive pregnancies. The rate of vertical transmission slightly decreased in successive pregnancies being 74.2%, 59.5%, 48.1% and 40% for the first to fourth pregnancies respectively. In the second generation 21 out of 28 litters were found positive and the overall rate of vertical transmission was 28.5%. In chronically and congenitally infected dams N. caninum infection was maintained during all successive pregnancies for about 9 months. The results show that CD-1 outbred mice are a suitable model for studying chronic and congenital neosporosis

  18. Critical role of phospholipase A2 group IID in age-related susceptibility to severe acute respiratory syndrome–CoV infection

    PubMed Central

    Vijay, Rahul; Hua, Xiaoyang; Meyerholz, David K.; Miki, Yoshimi; Yamamoto, Kei; Gelb, Michael; Murakami, Makoto

    2015-01-01

    Oxidative stress and chronic low-grade inflammation in the lungs are associated with aging and may contribute to age-related immune dysfunction. To maintain lung homeostasis, chronic inflammation is countered by enhanced expression of proresolving/antiinflammatory factors. Here, we show that age-dependent increases of one such factor in the lungs, a phospholipase A2 (PLA2) group IID (PLA2G2D) with antiinflammatory properties, contributed to worse outcomes in mice infected with severe acute respiratory syndrome-coronavirus (SARS-CoV). Strikingly, infection of mice lacking PLA2G2D expression (Pla2g2d−/− mice) converted a uniformly lethal infection to a nonlethal one (>80% survival), subsequent to development of enhanced respiratory DC migration to the draining lymph nodes, augmented antivirus T cell responses, and diminished lung damage. We also observed similar effects in influenza A virus–infected middle-aged Pla2g2d−/− mice. Furthermore, oxidative stress, probably via lipid peroxidation, was found to induce PLA2G2D expression in mice and in human monocyte–derived macrophages. Thus, our results suggest that directed inhibition of a single inducible phospholipase, PLA2G2D, in the lungs of older patients with severe respiratory infections is potentially an attractive therapeutic intervention to restore immune function. PMID:26392224

  19. EFFICACY OF NITAZOXANIDE AGAINST Toxocara canis: LARVAL RECOVERY AND HUMORAL IMMUNE RESPONSE IN EXPERIMENTALLY INFECTED MICE.

    PubMed

    Lescano, Susana A Zevallos; Santos, Sergio Vieira dos; Assis, Jesiel Maurício Lemos; Chieffi, Pedro Paulo

    2015-01-01

    The efficacy of nitazoxanide (NTZ) against toxocariasis was investigated in an experimental murine model and results were compared to those obtained using mebendazole. Sixty male BALB/c mice, aged six to eight weeks-old, were divided into groups of 10 each; fifty were orally infected with 300 larvaed eggs of T. canis and grouped as follows, G I: infected untreated mice; G II: infected mice treated with MBZ (15 mg/kg/day) 10 days postinfection (dpi); G III: infected mice treated with NTZ (20 mg/kg/day) 10 dpi; G IV: infected mice treated with MBZ 60 dpi; G V: infected mice treated with NTZ 60 dpi; GVI: control group comprising uninfected mice. Mice were bled via retro-orbital plexus on four occasions between 30 and 120 dpi. Sera were processed using the ELISA technique to detect IgG anti- Toxocara antibodies. At 120 dpi, mice were sacrificed for larval recovery in the CNS, liver, lungs, kidneys, eyes and carcass. Results showed similar levels of anti- Toxocara IgG antibodies among mice infected but not submitted to treatment and groups treated with MBZ or NTZ, 10 and 60 dpi. Larval recovery showed similar values in groups treated with NTZ and MBZ 10 dpi. MBZ showed better efficacy 60 dpi, with a 72.6% reduction in the parasite load compared with NTZ, which showed only 46.5% reduction. We conclude that administration of these anthelmintics did not modify the humoral response in experimental infection by T. canis. No parasitological cure was observed with either drug; however, a greater reduction in parasite load was achieved following treatment with MBZ. PMID:26422159

  20. EFFICACY OF NITAZOXANIDE AGAINST Toxocara canis: LARVAL RECOVERY AND HUMORAL IMMUNE RESPONSE IN EXPERIMENTALLY INFECTED MICE

    PubMed Central

    LESCANO, Susana A. Zevallos; dos SANTOS, Sergio Vieira; ASSIS, Jesiel Maurício Lemos; CHIEFFI, Pedro Paulo

    2015-01-01

    SUMMARY The efficacy of nitazoxanide (NTZ) against toxocariasis was investigated in an experimental murine model and results were compared to those obtained using mebendazole. Sixty male BALB/c mice, aged six to eight weeks-old, were divided into groups of 10 each; fifty were orally infected with 300 larvaed eggs of T. canisand grouped as follows, G I: infected untreated mice; G II: infected mice treated with MBZ (15 mg/kg/day) 10 days postinfection (dpi); G III: infected mice treated with NTZ (20 mg/kg/day) 10 dpi; G IV: infected mice treated with MBZ 60 dpi; G V: infected mice treated with NTZ 60 dpi; GVI: control group comprising uninfected mice. Mice were bled via retro-orbital plexus on four occasions between 30 and 120 dpi. Sera were processed using the ELISA technique to detect IgG anti- Toxocaraantibodies. At 120 dpi, mice were sacrificed for larval recovery in the CNS, liver, lungs, kidneys, eyes and carcass. Results showed similar levels of anti- ToxocaraIgG antibodies among mice infected but not submitted to treatment and groups treated with MBZ or NTZ, 10 and 60 dpi. Larval recovery showed similar values in groups treated with NTZ and MBZ 10 dpi. MBZ showed better efficacy 60 dpi, with a 72.6% reduction in the parasite load compared with NTZ, which showed only 46.5% reduction. We conclude that administration of these anthelmintics did not modify the humoral response in experimental infection by T. canis. No parasitological cure was observed with either drug; however, a greater reduction in parasite load was achieved following treatment with MBZ. PMID:26422159

  1. TGF-β1 levels and intraocular tissue alterations in mice infected with a virulent type I RH Toxoplasma gondii strain.

    PubMed

    Iqbal, Jamshaid; Al-Awadhi, Mohammad Ahmed; Raghupathy, Raj Gopal

    2016-03-01

    Toxoplasmosis is generally self-limiting in healthy adults but it may cause toxoplasmic retinochoroiditis in cases of congenital infection leading to blindness. The importance of host genetics in determining disease severity in ocular toxoplasmosis has been shown in different inbred mouse strains using low-virulence toxoplasma strain. In this study, we studied intraocular immune response and tissue alterations in the genetically resistant BALB/c and susceptible MF1 mice infected with a virulent type I RH Toxoplasma gondii strain by intravitreal route. We observed a significant up-regulation of IFN-γ and TNF-α to >2200 pg/ml and >300 pg/ml respectively in the blood of both BALB/c and MF1mice during the early stages of post intraocular infection (p < 0.01) but the levels dropped sharply to normal during the late stages of the infection on day 26. The cytokine levels detected were higher in the MF1 mice compared with the BALB/c mice and a relatively higher levels were observed in the aqueous humour (AqH) than in the blood of both group of mice. The TGF-β1 level in the blood and AqH of BALB/c mice remained low throughout the infection period compared with MF1 mice which showed gradual increase to 50 pg/ml in the blood and AqH during the early stages of infection which then further increased 2-fold-132 pg/ml on day 11 (p < 0.01) and remained high till the last day of observation on day 26 except that the TGF-β1 level in AqH dropped sharply to normal level. In summary, our results support that TGF-β1 may down-regulate the effector functions of anti-Toxoplasma cellular immunity during acute toxoplasmosis. We document that a mild Th1 pro-inflammatory response in the BALB/c mice with high IFN-γ and TNF-α and, low TGF-β1 levels during the early stages of infection may have contributed to an effective cellular immune response leading to lower morbidity, mortality and less ocular tissue damage. However in the MF1 mice, a significantly high TGF-β1 level in the blood as

  2. Th17: A New Participant in Gut Dysfunction in Mice Infected with Trichinella spiralis

    PubMed Central

    Fu, Yu; Wang, Wenfeng; Tong, Jingjing; Pan, Qi; Long, Yanqing; Qian, Wei; Hou, Xiaohua

    2009-01-01

    Trichinella spiralis infection in rodents is a well-known model of intestinal inflammation associated with hypermotility. Our aim was to elucidate if Th17 cells were involved in the development of gastrointestinal hypermotility in this experimental model. Intestinal inflammation was observed by hematoxylin-eosin (HE) staining. Jejunal smooth muscle contractility was investigated in response to acetylcholine (Ach). The effects of IL-17 on jejunum smooth muscle contractility were explored. Flow cytometry was used to analyze the proportion of Th17 cells in jejunum. The levels of IL-17, IL-23, and TGF-β1 in jejunum were measured by Western blot. Our results showed that the inflammation in jejunum was severe at 2 weeks postinfection (PI), which was not discernible at 8 weeks PI. Jejunal smooth muscle contractility was increased at 2 weeks PI and kept higher at 12 weeks PI. The proportion of Th17 cells and the expression of IL-17 were upregulated in jejunum at 2 weeks PI and normalized at 8 weeks PI. When jejunual smooth muscle strips were cultured with IL-17, contractions elicited by Ach were enhanced in a concentration-dependent manner. Our data suggest that Th17 cells are increased during acute infection with Trichinella spiralis and IL-17 may contribute to jejunal muscle contractility in mice. PMID:20016839

  3. Macrophage dysfunction and susceptibility to pulmonary Pseudomonas aeruginosa infection in surfactant protein C-deficient mice.

    PubMed

    Glasser, Stephan W; Senft, Albert P; Whitsett, Jeffrey A; Maxfield, Melissa D; Ross, Gary F; Richardson, Theresa R; Prows, Daniel R; Xu, Yan; Korfhagen, Thomas R

    2008-07-01

    To determine the role of surfactant protein C (SP-C) in host defense, SP-C-deficient (Sftpc-/-) mice were infected with the pulmonary pathogen Pseudomonas aeruginosa by intratracheal injection. Survival of young, postnatal day 14 Sftpc-/- mice was decreased in comparison to Sftpc+/+ mice. The sensitivity to Pseudomonas bacteria was specific to the 129S6 strain of Sftpc-/- mice, a strain that spontaneously develops interstitial lung disease-like lung pathology with age. Pulmonary bacterial load and leukocyte infiltration were increased in the lungs of Sftpc-/- mice 24 h after infection. Early influx of polymorphonuclear leukocytes in the lungs of uninfected newborn Sftpc-/- mice relative to Sftpc+/+ mice indicate that the lack of SP-C promotes proinflammatory responses in the lung. Mucin expression, as indicated by Alcian blue staining, was increased in the airways of Sftpc-/- mice following infection. Phagocytic activity of alveolar macrophages from Sftpc-/- mice was reduced. The uptake of fluorescent beads in vitro and the number of bacteria phagocytosed by alveolar macrophages in vivo was decreased in the Sftpc-/- mice. Alveolar macrophages from Sftpc-/- mice expressed markers of alternative activation that are associated with diminished pathogen response and advancing pulmonary fibrosis. These findings implicate SP-C as a modifier of alveolar homeostasis. SP-C plays an important role in innate host defense of the lung, enhancing macrophage-mediated Pseudomonas phagocytosis, clearance and limiting pulmonary inflammatory responses. PMID:18566429

  4. Intracellular Hmgb1 Inhibits Inflammatory Nucleosome Release and Limits Acute Pancreatitis in Mice

    PubMed Central

    Kang, Rui; Zhang, Qiuhong; Hou, Wen; Yan, Zhenwen; Chen, Ruochan; Bonaroti, Jillian; Bansal, Preeti; Billiar, Timothy R.; Tsung, Allan; Wang, Qingde; Bartlett, David L.; Whitcomb, David C; Chang, Eugene B.; Zhu, Xiaorong; Wang, Haichao; Lu, Ben; Tracey, Kevin J.; Cao, Lizhi; Fan, Xue-Gong; Lotze, Michael T.; Zeh, Herbert J.; Tang, Daolin

    2014-01-01

    BACKGROUND & AIMS: High mobility group box 1 (HMGB1) is an abundant protein that regulates chromosome architecture and also functions as a damage-associated molecular pattern molecule. Little is known about its intracellular roles in response to tissue injury or during subsequent local and systemic inflammatory responses. We investigated the function of Hmgb1 in mice following induction of acute pancreatitis. METHODS: We utilized a Cre/LoxP system to create mice with pancreas-specific disruption in Hmbg1 (Pdx1-Cre; HMGB1flox/flox mice). Acute pancreatitis was induced in these mice (HMGB1flox/flox mice served as controls) following injection of L-arginine or cerulein. Pancreatic tissues and acinar cells were collected and analyzed by histologic, immunoblot, and immunohistochemical analyses. RESULTS: Following injection of L-arginine or cerulein, Pdx1-Cre; HMGB1flox/flox mice developed acute pancreatitis more rapidly than controls, with increased mortality. Pancreatic tissues of these mice also had higher levels of serum amylase, acinar cell death, leukocyte infiltration, and interstitial edema than controls. Pancreatic tissues and acinar cells collected from the Pdx1-Cre; HMGB1flox/flox mice following L-arginine- or cerulein injection demonstrated nuclear catastrophe with greater nucleosome release when compared with controls, along with increased phosphorylation/activation of RELA Nfκb, degradation of Iκb, and phosphorylation of Mapk. Inhibitors of reactive oxygen species (N-acetyl-L-cysteine) blocked L-arginine–induced DNA damage, necrosis, apoptosis, release of nucleosomes, and activation of Nfκb in pancreatic tissues and acinar cells from Pdx1-Cre; HMGB1flox/flox and control mice. Exogenous genomic DNA and recombinant histone H3 proteins significantly induced release of HMGB1 from mouse macrophages; administration of antibodies against H3 to mice reduced serum levels of HMGB1 and increased survival following L-arginine injection. CONCLUSIONS: In 2 mouse

  5. Cathelicidin-related antimicrobial peptide modulates the severity of acute pancreatitis in mice

    PubMed Central

    DENG, YUAN-YUAN; SHAMOON, MUHAMMAD; HE, YUE; BHATIA, MADHAV; SUN, JIA

    2016-01-01

    The present study aimed to investigate the immunomodulatory effects of mouse cathelicidin-related antimicrobial peptide (CRAMP) on experimental acute pancreatitis (AP). AP is a common clinical condition characterized by acute abdominal inflammation. Innate immune cells and mediators are intrinsically linked to the pathogenesis of AP. Cathelicidins are innate immunity-derived antimicrobial peptides that exert immunomodulatory effects on various host cells. However, how cathelicidins are involved and modulate the severity and inflammatory responses of AP remains unclear. In the present study, the mouse CRAMP gene-deficient cnlp−/− mice and their wild-type C57BL/6J littermates were induced with AP by multiple hourly injections of supramaximal doses of caerulein. Serum amylase levels, pancreatic myeloperoxidase activity and histological examination were performed in order to determine the disease severity and the levels of inflammatory cytokines. Disease severity and inflammatory markers were subsequently evaluated in the control mice, cnlp−/− C57BL/6J mice with AP, and wild-type C57BL/6J mice with AP. The results demonstrated that cnlp−/− mice exhibited a more severe phenotype and inflammatory response following AP induction compared with the wild-type mice, as evidenced by increased serum amylase levels, pancreatic myeloperoxidase release, and early inflammatory mediator tumor necrosis factor-α production. Histological examination confirmed that CRAMP deficiency worsened the pancreatic inflammatory condition. These results indicate that CRAMP may be considered a novel modulatory mediator in mouse experimental AP. PMID:27035328

  6. Cathelicidin-related antimicrobial peptide modulates the severity of acute pancreatitis in mice.

    PubMed

    Deng, Yuan-Yuan; Shamoon, Muhammad; He, Yue; Bhatia, Madhav; Sun, Jia

    2016-05-01

    The present study aimed to investigate the immunomodulatory effects of mouse cathelicidin-related antimicrobial peptide (CRAMP) on experimental acute pancreatitis (AP). AP is a common clinical condition characterized by acute abdominal inflammation. Innate immune cells and mediators are intrinsically linked to the pathogenesis of AP. Cathelicidins are innate immunity-derived antimicrobial peptides that exert immunomodulatory effects on various host cells. However, how cathelicidins are involved and modulate the severity and inflammatory responses of AP remains unclear. In the present study, the mouse CRAMP gene‑deficient cnlp‑/‑ mice and their wild‑type C57BL/6J littermates were induced with AP by multiple hourly injections of supramaximal doses of caerulein. Serum amylase levels, pancreatic myeloperoxidase activity and histological examination were performed in order to determine the disease severity and the levels of inflammatory cytokines. Disease severity and inflammatory markers were subsequently evaluated in the control mice, cnlp‑/‑ C57BL/6J mice with AP, and wild‑type C57BL/6J mice with AP. The results demonstrated that cnlp‑/‑ mice exhibited a more severe phenotype and inflammatory response following AP induction compared with the wild‑type mice, as evidenced by increased serum amylase levels, pancreatic myeloperoxidase release, and early inflammatory mediator tumor necrosis factor‑α production. Histological examination confirmed that CRAMP deficiency worsened the pancreatic inflammatory condition. These results indicate that CRAMP may be considered a novel modulatory mediator in mouse experimental AP. PMID:27035328

  7. Acute stress blocks the caffeine-induced enhancement of contextual memory retrieval in mice.

    PubMed

    Pierard, Chistophe; Krazem, Ali; Henkous, Nadia; Decorte, Laurence; Béracochéa, Daniel

    2015-08-15

    This study investigated in mice the dose-effect of caffeine on memory retrieval in non-stress and stress conditions. C57 Bl/6 Jico mice learned two consecutive discriminations (D1 and D2) in a four-hole board which involved either distinct contextual (CSD) or similar contextual (SSD) cues. All mice received an i.p. injection of vehicle or caffeine (8, 16 or 32mg/kg) 30min before the test session. Results showed that in non-stress conditions, the 16mg/kg caffeine dose induced a significant enhancement of D1 performance in CSD but not in SSD. Hence, we studied the effect of an acute stress (electric footshocks) administered 15min before the test session on D1 performance in caffeine-treated mice. Results showed that stress significantly decreased D1 performance in vehicle-treated controls and the memory-enhancing effect induced by the 16mg/kg caffeine dose in non-stress condition is no longer observed. Interestingly, whereas caffeine-treated mice exhibited weaker concentrations of plasma corticosterone as compared to vehicles in non-stress condition, stress significantly increased plasma corticosterone concentrations in caffeine-treated mice which reached similar level to that of controls. Overall, the acute stress blocked both the endocrinological and memory retrieval enhancing effects of caffeine. PMID:25934571

  8. Acute cholecystitis associated with infection of Enterobacteriaceae from gut microbiota.

    PubMed

    Liu, J; Yan, Q; Luo, F; Shang, D; Wu, D; Zhang, H; Shang, X; Kang, X; Abdo, M; Liu, B; Ma, Y; Xin, Y

    2015-09-01

    Acute cholecystitis (AC) is one of the most common surgical diseases. Bacterial infection accounts for 50% to 85% of the disease's onset. Since there is a close relationship between the biliary system and the gut, the aims of this study were to characterize and determine the influence of gut microbiota on AC, to detect the pathogenic microorganism in the biliary system, and to explore the relationship between the gut and bile microbiota of patients with AC. A total of 185 713 high-quality sequence reads were generated from the faecal samples of 15 patients and 13 healthy controls by 16S rRNA gene pyrosequencing. Patients' samples were significantly enriched in Akkermansia, Enterobacter and Escherichia/Shigella group. The healthy controls, however, showed significant enrichment of Clostridiales, Coprococcus, Coprobacillaceae, Paraprevotella, Turicibacter and TM7-3 in their faecal samples. Escherichia coli was the main biliary pathogenic microorganism, among others such as Klebsiella spp., Clostridium perfringens, Citrobacter freundii and Enterobacter cloacae in the bile of the patients. Additionally, the amount of bile endotoxin significantly correlated with the number of Enterobacteriaceae, especially E. coli. Our data indicate that Enterobacteriaceae might play essential role in the pathogenesis and/or progress of AC. This was verified in an in vivo model using a pathogenic E. coli isolated from one of the patients in guinea pigs and observed marked gallbladder inflammation and morphologic changes. This study thus provides insight which could be useful for the prevention, diagnosis and treatment of AC and related diseases by controlling the growth of Enterobacteriaceae to alleviate the infection. PMID:26025761

  9. Incubation periods of acute respiratory viral infections: a systematic review

    PubMed Central

    Lessler, Justin; Reich, Nicholas G; Brookmeyer, Ron; Perl, Trish M; Nelson, Kenrad E; Cummings, Derek A T

    2015-01-01

    Knowledge of the incubation period is essential in the investigation and control of infectious disease, but statements of incubation period are often poorly referenced, inconsistent, or based on limited data. In a systematic review of the literature on nine respiratory viral infections of public-health importance, we identified 436 articles with statements of incubation period and 38 with data for pooled analysis. We fitted a log-normal distribution to pooled data and found the median incubation period to be 5·6 days (95% CI 4·8–6·3) for adenovirus, 3·2 days (95% CI 2·8–3·7) for human coronavirus, 4·0 days (95% CI 3·6–4·4) for severe acute respiratory syndrome coronavirus, 1·4 days (95% CI 1·3–1·5) for influenza A, 0·6 days (95% CI 0·5–0·6) for influenza B, 12·5 days (95% CI 11·8–13·3) for measles, 2·6 days (95% CI 2·1–3·1) for parainfluenza, 4·4 days (95% CI 3·9–4·9) for respiratory syncytial virus, and 1·9 days (95% CI 1·4–2·4) for rhinovirus. When using the incubation period, it is important to consider its full distribution: the right tail for quarantine policy, the central regions for likely times and sources of infection, and the full distribution for models used in pandemic planning. Our estimates combine published data to give the detail necessary for these and other applications. PMID:19393959

  10. Detection Of Viral And Bacterial Pathogens In Acute Respiratory Infections

    PubMed Central

    Obasi, Chidi N.; Barrett, Bruce; Brown, Roger; Vrtis, Rose; Barlow, Shari; Muller, Daniel; Gern, James

    2013-01-01

    Objectives The role of bacteria in acute respiratory illnesses (ARI) of adults and interactions with viral infections is incompletely understood. This study tested the hypothesis that bacterial co-infection during ARI adds to airway inflammation and illness severity. Methods Two groups of 97 specimens each were randomly selected from multiplex-PCR identified virus-positive and virus-negative nasal specimens obtained from adults with new onset ARI, and 40 control specimens were collected from healthy adults. All specimens were analyzed for Haemophilus influenza(HI), Moraxella catarrhalis(MC) and Streptococcus pneumonia(SP) by quantitative-PCR. General linear models tested for relationships between respiratory pathogens, biomarkers (nasal wash neutrophils and CXCL8), and ARI-severity. Results Nasal specimens from adults with ARIs were more likely to contain bacteria (37% overall; HI=28%, MC=14%, SP=7%) compared to specimens from healthy adults (5% overall; HI=0%, MC=2.5%, SP=2.5%;p<0.001). Among ARI specimens, bacteria were more likely to be detected among virus-negative specimens compared to virus-positive specimens (46% vs. 27%;p=0.0046). The presence of bacteria was significantly associated with increased CXCL8 and neutrophils, but not increased symptoms. Conclusion Pathogenic bacteria were more often detected in virus-negative ARI, and also associated with increased inflammatory biomarkers. These findings suggest the possibility that bacteria may augment virus-induced ARI and contribute to airway inflammation. Summary We tested whether bacterial pathogens were associated with ARI illness and inflammation. Bacteria were detected more often in nasal secretions during ARI, especially in samples without detectable viruses, and were associated with increased airway inflammation, but not increased symptoms. PMID:24211414

  11. The Protective Effects of Buzui on Acute Alcoholism in Mice

    PubMed Central

    Wen, Da-Chao; Gao, Shu-di; Hu, Xiao-yu; Yi, Cheng

    2016-01-01

    This study was designed to investigate the role of a traditional buzui recipe in anti-inebriation treatment. Buzui consists of Fructus Schisandrae Chinensis, Fructus Chebulae, Fructus Mume, Fructus Crataegi, Endothelium Corneum Gigeriae Galli, and Excrementum Bombycis. The buzui mixture was delivered by gavage, and ethanol was delivered subsequent to the final treatment. The effects of buzui on the righting reflex, inebriation rates, and the survival curve are depicted. Blood alcohol concentrations, alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST) levels, and alkaline phosphatase (ALP) levels were recorded. The activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and superoxide dismutase (SOD), as well as malonaldehyde (MDA) levels, were also measured. Our results demonstrated that a traditional buzui recipe showed significant effects on promoting wakefulness and the prevention of acute alcohol intoxication, accelerating the metabolism of alcohol in the liver and reducing the oxidative damage caused by acute alcoholism. PMID:26884793

  12. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-08-23

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  13. Contribution of Proteus mirabilis urease to persistence, urolithiasis, and acute pyelonephritis in a mouse model of ascending urinary tract infection.

    PubMed

    Johnson, D E; Russell, R G; Lockatell, C V; Zulty, J C; Warren, J W; Mobley, H L

    1993-07-01

    Proteus mirabilis, a significant cause of bacteriuria and acute pyelonephritis in humans, produces urease. This high-molecular-weight, multimeric, cytoplasmic enzyme hydrolyzes urea to ammonia and carbon dioxide. To assess the role of urease in colonization, urolithiasis, and acute pyelonephritis in an animal model of ascending urinary tract infection, we compared a uropathogenic strain of P. mirabilis with its isogenic urease-negative mutant, containing an insertion mutation within ureC, the gene encoding the large subunit of the enzyme. Mice challenged transurethrally with the parent strain developed significant bacteriuria and urinary stones. The urease-negative mutant had a 50% infective dose of 2.7 x 10(9) CFU, a value more than 1,000-fold greater than that of the parent strain (2.2 x 10(6) CFU). The urease-positive parent strain reached significantly higher concentrations and persisted significantly longer in the bladder and kidney than did the mutant. Indeed, in the kidney, the parent strain increased in concentration while the mutant concentration fell so that, by 1 week, the parent strain concentration was 10(6) times that of the mutant. Similarly, the urease-positive parent produced significantly more severe renal pathology than the mutant. The initial abnormalities were in and around the pelvis and consisted of acute inflammation and epithelial necrosis. By 1 week, pyelitis was more severe, crystals were seen in the pelvis, and acute pyelonephritis, with acute interstitial inflammation, tubular epithelial cell necrosis, and in some cases abscesses, had developed. By 2 weeks, more animals had renal abscesses and radial bands of fibrosis. We conclude that the urease of P. mirabilis is a critical virulence determinant for colonization, urolithiasis, and severe acute pyelonephritis. PMID:8514376

  14. Acute inhalation toxicity and sensory irritation of dimethylamine. [Rats, mice

    SciTech Connect

    Steinhagen, W.H.; Swenberg, J.A.; Barrow, C.S.

    1982-06-01

    The sensory irritation potential of dimethylamine (DMA) inhalation on male Fischer-344 rats and male Swiss-Webster mice was evaluated by measuring the reflex decrease in respiratory rate. In addition, the six hour LC/sub 50/ for rats exposed to dimetylamine was established. Groups of 3 or 4 rats and mice were exposed for 10 minutes to concentrations of DMA ranging from 49 to 1576 ppm during which time the respiratory rate was monitored and recorded. Sensory irritation concentration-response curves were obtained and RD/sub 50/ values (concentration which elicits a 50% decrease in respiratory rate) were determined to be 573 and 511 ppm for rats and mice, respectively. In another set of experiments seven groups of male rats were exposed to concentrations of DMA ranging from 600 to 6119 ppm for six hours. Mortality counts were made during and for 48 hours post exposure. The six hour LC/sub 50/ was determined to be 4540 ppm. Histopathologic examination of the respiratory tract revealed concentration related changes ranging from ulceration and necrosis to rhinitis, tracheitis, and emphysema. Overall, DMA was found to be less potent as a sensory irritant than other airborne irritants.

  15. Short-Term Heat Shock Affects Host–Virus Interaction in Mice Infected with Highly Pathogenic Avian Influenza Virus H5N1

    PubMed Central

    Xue, Jia; Fan, Xiaoxu; Yu, Jing; Zhang, Shouping; Xiao, Jin; Hu, Yanxin; Wang, Ming

    2016-01-01

    Highly pathogenic avian influenza virus (HPAIV) H5N1 is a highly contagious virus that can cause acute respiratory infections and high human fatality ratio due to excessive inflammatory response. Short-term heat shock, as a stressful condition, could induce the expression of heat shock proteins that function as molecular chaperones to protect cells against multiple stresses. However, the protective effect of short-term heat shock in influenza infection is far from being understood. In this study, mice were treated at 39°C for 4 h before being infected with HPAIV H5N1. Interestingly, short-term heat shock significantly increased the levels of HSP70 and pro-inflammatory cytokines IL-6, TNF-α, IFN-β, and IFN-γ in the lung tissues of mice. Following HPAIV H5N1 infection, short-term heat shock alleviated immunopathology and viral replication in lung tissue and repressed the weight loss and increased the survival rate of H5N1-infected mice. Our data reported that short-term heat shock provided beneficial anti-HPAIV H5N1 properties in mice model, which offers an alternative strategy for non-drug prevention for influenza infection. PMID:27379054

  16. Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice.

    PubMed

    Duerschmied, Daniel; Suidan, Georgette L; Demers, Melanie; Herr, Nadine; Carbo, Carla; Brill, Alexander; Cifuni, Stephen M; Mauler, Maximilian; Cicko, Sanja; Bader, Michael; Idzko, Marco; Bode, Christoph; Wagner, Denisa D

    2013-02-01

    The majority of peripheral serotonin is stored in platelets, which secrete it on activation. Serotonin releases Weibel-Palade bodies (WPBs) and we asked whether absence of platelet serotonin affects neutrophil recruitment in inflammatory responses. Tryptophan hydroxylase (Tph)1–deficient mice, lacking non-neuronal serotonin, showed mild leukocytosis compared with wild-type (WT), primarily driven by an elevated neutrophil count. Despite this, 50% fewer leukocytes rolled on unstimulated mesenteric venous endothelium of Tph1(-/-) mice. The velocity of rolling leukocytes was higher in Tph1(-/-) mice, indicating fewer selectin-mediated interactions with endothelium. Stimulation of endothelium with histamine, a secretagogue of WPBs, or injection of serotonin normalized the rolling in Tph1(-/-) mice. Diminished rolling in Tph1(-/-) mice resulted in reduced firm adhesion of leukocytes after lipopolysaccharide treatment. Blocking platelet serotonin uptake with fluoxetine in WT mice reduced serum serotonin by > 80% and similarly reduced leukocyte rolling and adhesion. Four hours after inflammatory stimulation, neutrophil extravasation into lung, peritoneum, and skin wounds was reduced in Tph1(-/-) mice, whereas in vitro neutrophil chemotaxis was independent of serotonin. Survival of lipopolysaccharide-induced endotoxic shock was improved in Tph1(-/-) mice. In conclusion, platelet serotonin promotes the recruitment of neutrophils in acute inflammation, supporting an important role for platelet serotonin in innate immunity. PMID:23243271

  17. Pulmonary immunostimulation with MALP-2 in influenza virus-infected mice increases survival after pneumococcal superinfection.

    PubMed

    Reppe, Katrin; Radünzel, Peter; Dietert, Kristina; Tschernig, Thomas; Wolff, Thorsten; Hammerschmidt, Sven; Gruber, Achim D; Suttorp, Norbert; Witzenrath, Martin

    2015-12-01

    Pulmonary infection with influenza virus is frequently complicated by bacterial superinfection, with Streptococcus pneumoniae being the most prevalent causal pathogen and hence often associated with high morbidity and mortality rates. Local immunosuppression due to pulmonary influenza virus infection has been identified as a major cause of the pathogenesis of secondary bacterial lung infection. Thus, specific local stimulation of the pulmonary innate immune system in subjects with influenza virus infection might improve the host defense against secondary bacterial pathogens. In the present study, we examined the effect of pulmonary immunostimulation with Toll-like receptor 2 (TLR-2)-stimulating macrophage-activating lipopeptide 2 (MALP-2) in influenza A virus (IAV)-infected mice on the course of subsequent pneumococcal superinfection. Female C57BL/6N mice infected with IAV were treated with MALP-2 on day 5 and challenged with S. pneumoniae on day 6. Intratracheal MALP-2 application increased proinflammatory cytokine and chemokine release and enhanced the recruitment of leukocytes, mainly neutrophils, into the alveolar space of IAV-infected mice, without detectable systemic side effects. Local pulmonary instillation of MALP-2 in IAV-infected mice 24 h before transnasal pneumococcal infection considerably reduced the bacterial number in the lung tissue without inducing exaggerated inflammation. The pulmonary viral load was not altered by MALP-2. Clinically, MALP-2 treatment of IAV-infected mice increased survival rates and reduced hypothermia and body weight loss after pneumococcal superinfection compared to those of untreated coinfected mice. In conclusion, local immunostimulation with MALP-2 in influenza virus-infected mice improved pulmonary bacterial elimination and increased survival after subsequent pneumococcal superinfection. PMID:26371127

  18. Pulmonary Immunostimulation with MALP-2 in Influenza Virus-Infected Mice Increases Survival after Pneumococcal Superinfection

    PubMed Central

    Reppe, Katrin; Radünzel, Peter; Dietert, Kristina; Tschernig, Thomas; Wolff, Thorsten; Hammerschmidt, Sven; Gruber, Achim D.; Suttorp, Norbert

    2015-01-01

    Pulmonary infection with influenza virus is frequently complicated by bacterial superinfection, with Streptococcus pneumoniae being the most prevalent causal pathogen and hence often associated with high morbidity and mortality rates. Local immunosuppression due to pulmonary influenza virus infection has been identified as a major cause of the pathogenesis of secondary bacterial lung infection. Thus, specific local stimulation of the pulmonary innate immune system in subjects with influenza virus infection might improve the host defense against secondary bacterial pathogens. In the present study, we examined the effect of pulmonary immunostimulation with Toll-like receptor 2 (TLR-2)-stimulating macrophage-activating lipopeptide 2 (MALP-2) in influenza A virus (IAV)-infected mice on the course of subsequent pneumococcal superinfection. Female C57BL/6N mice infected with IAV were treated with MALP-2 on day 5 and challenged with S. pneumoniae on day 6. Intratracheal MALP-2 application increased proinflammatory cytokine and chemokine release and enhanced the recruitment of leukocytes, mainly neutrophils, into the alveolar space of IAV-infected mice, without detectable systemic side effects. Local pulmonary instillation of MALP-2 in IAV-infected mice 24 h before transnasal pneumococcal infection considerably reduced the bacterial number in the lung tissue without inducing exaggerated inflammation. The pulmonary viral load was not altered by MALP-2. Clinically, MALP-2 treatment of IAV-infected mice increased survival rates and reduced hypothermia and body weight loss after pneumococcal superinfection compared to those of untreated coinfected mice. In conclusion, local immunostimulation with MALP-2 in influenza virus-infected mice improved pulmonary bacterial elimination and increased survival after subsequent pneumococcal superinfection. PMID:26371127

  19. Impact of gold nanoparticles on brain of mice infected with Schistosoma mansoni.

    PubMed

    Dkhil, Mohamed A; Bauomy, Amira A; Diab, Marwa S M; Wahab, Rizwan; Delic, Denis; Al-Quraishy, Saleh

    2015-10-01

    Schistosomiasis is a condition characterized by high rates of morbidity and cognitive impairment. It afflicts many people in tropical and sub-tropical countries. Our study aimed to investigate the protective role of gold nanoparticles (GNPs) on the brain of mice infected with Schistosoma mansoni. Characterizations of GNPs were determined by using high-resolution transmission electron microscopy. Three doses of GNPs (0.25, 0.5, and 1.0 mg/kg body weight) were used to treat animals after S. mansoni infection. The infection induced impairments in histological picture as a result of schistosome infection resulting in a disturbance in the content of the brain neurotransmitters, norepinephrine (NE), and dopamine (DA). Also, the infection induced significant reduction in glutathione level; oppositely, the levels of nitric oxide and malondialdehyde were increased significantly. In addition, S. mansoni was able to disregulate the infected mice brain Cacnb4, Cabp4, Vdac3, Glrb, and Adam23 messenger RNA (mRNA). On the other hand, treatment of mice with GNPs could alleviate the histological impairments, the changes in the content of NE and DA, and the brain oxidative damage. Also, GNPs could regulate the gene expression due to S. mansoni infection. Generally, GNPs could decrease the neurooxidative stress and regulated the gene expression in the brain of infected mice. Consequently, our results revealed an anti-neuroschistosomal effect of GNPs in mice infected with S. mansoni. PMID:26122996

  20. Arginine reduces Cryptosporidium parvum infection in undernourished suckling mice involving both nitric oxide synthase and arginase

    PubMed Central

    Castro, Ibraim C.; Oliveira, Bruna B.; Slowikowski, Jacek J.; Coutinho, Bruna P.; Siqueira, Francisco Júlio W.S.; Costa, Lourrany B.; Sevilleja, Jesus Emmanuel; Almeida, Camila A.; Lima, Aldo A.M.; Warren, Cirle A.; Oriá, Reinaldo B.; Guerrant, Richard L.

    2011-01-01

    Objective This study investigated the role of L-arginine supplementation to undernourished and Cryptosporidium parvum-infected suckling mice. Methods The following regimens were initiated on the 4th day of life and given subcutaneously daily: either 200mM of L-arginine or PBS for the C. parvum-infected controls. L-arginine-treated mice were grouped to receive either 20mM of NG-nitroarginine-methyl-ester (L-NAME) or PBS. Infected mice received orally 106 excysted-C. parvum oocysts on day 6 and were euthanized on day 14th at the infection peak. Results L-arginine improved weight gain compared to the untreated infected controls. L-NAME profoundly impaired body weight gain as compared to all other groups. Cryptosporidiosis was associated with ileal crypt hyperplasia, villus blunting, and inflammation. L-arginine improved mucosal histology following infection. L-NAME abrogated these arginine-induced improvements. Infected control mice showed an intense arginase expression, which was even greater with L-NAME. L-arginine reduced parasite burden, an effect that was reversed by L-NAME. C. parvum infection increased urine NO3-/NO2- concentration when compared to uninfected controls, which was increased by L-arginine supplementation, an effect that was also reversed by L-NAME. Conclusion These findings show a protective role of L-arginine during C. parvum infection in undernourished mice with involvement of arginase I and nitric oxide synthase enzymatic actions. PMID:22261576

  1. Perturbation of the intestinal microbiota of mice infected with Cryptosporidium parvum.

    PubMed

    Ras, Refaat; Huynh, Kevin; Desoky, Enas; Badawy, Ahmed; Widmer, Giovanni

    2015-07-01

    Understanding the interaction between the intestinal microbiota (microbiome) and enteric pathogens is of interest in the development of alternative treatments that do not rely on chemotherapy and do not lead to drug resistance. We undertook research in a rodent model of cryptosporidiosis to assess whether the bacterial gut microbiota is impacted by infection with the protozoan pathogen Cryptosporidium parvum. The profile of the faecal bacterial microbiota in infected and uninfected animals was compared using 16S amplicon sequencing. In four independent experiments, the intestinal microbiota of infected mice differed from that of uninfected animals, regardless of the C. parvum isolate used to infect mice. The use of replicated treatment groups demonstrated that microbiota divergence between treatments was driven by the infection and did not result from spontaneous changes in the intestinal ecosystem unrelated to the infection. Microbiota perturbation induced by C. parvum appeared to be reversible, as we observed a tendency for the phylogenetic distance between infected and uninfected mice to diminish after mice cleared the infection. As mice infected with C. parvum do not develop diarrhoea, these observations indicate that microbiota perturbation results from other mechanisms than an accelerated movement of gut content. PMID:25913477

  2. Pathogenicity of Helicobacter ganmani in Mice Susceptible and Resistant to Infection with H. hepaticus

    PubMed Central

    Alvarado, Cynthia G; Kocsis, Andrew G; Hart, Marcia L; Crim, Marcus J; Myles, Matthew H; Franklin, Craig L

    2015-01-01

    Helicobacter spp. are some of the most prevalent bacterial contaminants of laboratory mice. Although abundant data regarding the diseases associated with H. hepaticus infection are available, little is known about the pathogenicity of H. ganmani, which was first isolated in 2001 from the intestines of laboratory mice. The objective of this study was to evaluate the host response to H. ganmani colonization in H. hepaticus disease-resistant C57BL/6 and disease-susceptible A/J and IL10-deficient mice. Mice were inoculated with H. ganmani, H. hepaticus, or Brucella broth. Cecal lesion scores, cecal gene expression, and Helicobacter load were measured at 4 and 90 d after inoculation. At both time points, mice inoculated with H. ganmani had similar or significantly more copies of cecum-associated Helicobacter DNA than did mice inoculated with H. hepaticus. When compared with those of sham-inoculated control mice, cecal lesion scores at 4 and 90 d after inoculation were not significantly greater in H. ganmani-inoculated A/J, C57BL/6, or IL10-deficient mice. Analysis of cecal gene expression demonstrated that H. ganmani infection failed to cause significant elevations of IFNγ in A/J, C57BL/6, or IL10-deficient mice. However, in IL10-deficient mice, H. ganmani infection was associated with a significant increase in the expression of the proinflammatory cytokine IL12/23p40. Although H. ganmani infection in this study failed to induce the typhlitis that is the hallmark of H. hepaticus infection, infection with H. ganmani was associated with alterations in inflammatory cytokines in IL10-deficient mice. PMID:25730753

  3. Protection against lethal bacterial infection in mice by monocyte-chemotactic and -activating factor.

    PubMed Central

    Nakano, Y; Kasahara, T; Mukaida, N; Ko, Y C; Nakano, M; Matsushima, K

    1994-01-01

    Chemotactic factors regulate the recruitment of neutrophils, lymphocytes, or monocytes-macrophages to infectious and inflammatory sites. The purpose of this study was to determine whether monocyte-chemotactic and -activating factor (MCAF [MCP-1], a JE gene product) also influences the host defense mechanism against microbial infection. We evaluated the effect of recombinant human MCAF on the survival rate of mice systemically infected with Pseudomonas aeruginosa or Salmonella typhimurium. The administration of 2.5 micrograms of MCAF 6 h before infection completely protected the mice from lethal infection. Mice with cyclophosphamide-induced leukopenia exhibiting increased susceptibility to P. aeruginosa were also endowed with resistance by the same dose of MCAF. Administration of MCAF at -6 h was critical, since MCAF given either earlier or later than -6 h failed to rescue mice from lethal infection. The in vivo effect on the survival of mice paralleled the reduced recovery of viable P. aeruginosa or S. typhimurium from the peritoneal cavity, i.e., the number of recovered bacteria from the MCAF (2.5 micrograms per mouse)-treated mice was reduced to less than 2% of control mice for P. aeruginosa and 4% of control mice for S. typhimurium at 24 h. Since MCAF exhibited chemotaxis on murine macrophages as well as enhanced phagocytosis and killing of bacteria in vitro, the activation of macrophages, followed by the recruitment into the peritoneal cavity, is responsible for eliminating bacteria and thus enhancing the survival rate. PMID:8300198

  4. Profiling Acute Respiratory Tract Infections in Children from Assam, India

    PubMed Central

    Islam, Farzana; Sarma, Ratna; Debroy, Arup; Kar, Sumit; Pal, Ranabir

    2013-01-01

    Background: Acute respiratory infections (ARI) are leading global cause of under-five mortality and morbidity. Objective: To elicit the prevalence and risk factors associated with ARI among under-five children. Materials and Methods: A community-based cross-sectional study was undertaken in 21 registered urban slums of Guwahati in Assam to determine the prevalence and risk factors associated with ARI among 370 under-five children from 184 households and 370 families. Results: The prevalence of ARI was found to be 26.22%; infants and female children were more affected. Majority of the ARI cases were from nuclear families (84.54%), living in kutcha houses (90.72%) with inadequate ventilation (84.54%), overcrowded living condition (81.44%), with kitchen attached to the living room (65.98%) and using biomass fuel for cooking (89.69%). ARI was significantly associated with ventilation, location of kitchen in household; presence of overcrowding, nutritional status, and primary immunization status also had impacts on ARI. Conclusion: The present study had identified a high prevalence of the disease among under-fives. It also pointed out various socio-demographic, nutritional, and environmental modifiable risk factors which can be tackled by effective education of the community. PMID:23599611

  5. Effect of acute cytomegalovirus infection on drug-induced SLE.

    PubMed Central

    Schattner, A.; Sthoeger, Z.; Geltner, D.

    1994-01-01

    A 58 year old woman developed systemic symptoms, interstitial lung disease, splenomegaly, leukopenia and anti-histone and anti-nuclear antibodies (ANA), while treated with hydralazine for hypertension. Five months after presentation she was admitted with high fever, skin rash and atypical lymphocytosis due to acute cytomegalovirus (CMV) infection. Worsening leukopenia and increased ANA were found, and high titres of anti-DNA antibodies, anti-cardiolipin antibodies and rheumatoid factors appeared. Hydralazine was stopped and the patient gradually became asymptomatic. All autoantibodies spontaneously disappeared (over 16 weeks), and the white cell count and spleen size became normal. The patient was found to be a slow acetylator and to have both HLA-DR4 and selective IgA deficiency. Thus, a multifactorial genetic susceptibility to develop drug-induced lupus was brought out in stages first by hydralazine and then by CMV, yet all manifestations and autoantibodies resolved spontaneously, demonstrating the complex interplay of varied environmental factors with a genetic predisposition in the pathogenesis of autoimmunity. PMID:7831173

  6. Fecundity reduction of BALB/c mice after survival from lethal Neodiplostomum seoulense infection.

    PubMed

    Shin, Eun-Hee; Im, Tai-Kyun; Park, Yun-Kyu; Cho, Jaeeun; Kim, Jae-Lip; Chai, Jong-Yil

    2016-05-01

    Neodiplostomum seoulense (Digenea: Neodiplostomidae), an intestinal trematode infecting humans and rodents, is known to be highly pathogenic and lethal to experimentally infected mice. Only a small proportion of mice can survive from its infection. This study aimed to assess the reproductive capacity of surviving BALB/c mice. The fertility of male and female mice, birth time (period from mating to birth of litters), number of litters, size and weight of testes or ovary-oviduct-uterus, apoptosis of testicular cells, and serum levels of sex hormones were determined. Our results revealed that surviving mice underwent severe fecundity reduction and finally became infertile. They could not be able to produce generations beyond F4. Fertility rate, birth time, and number of litters of N. seoulense-infected mice were all significantly (p < 0.05) lower than those of uninfected controls, Metagonimus miyatai (less pathogenic intestinal trematode)-infected, or castor oil (severe diarrheal agent)-administered controls. The size and weight of testes or ovary-oviduct-uterus were markedly (p < 0.05) decreased after N. seoulense infection. Moreover, the number of apoptotic cells in the testicular tissue was significantly (p < 0.05) increased (up to 10-50-folds) during weeks 1-3 post-infection. Serum testosterone levels in infertile mice were reduced to 1/10 level of fertile mice. These results indicated that BALB/c mice surviving N. seoulense infection underwent destruction and apoptosis of gonad tissues with fecundity reduction. They were finally infertile, with no ability to produce their next generations. PMID:26857130

  7. Rhinovirus infection of allergen-sensitized and -challenged mice induces eotaxin release from functionally polarized macrophages.

    PubMed

    Nagarkar, Deepti R; Bowman, Emily R; Schneider, Dina; Wang, Qiong; Shim, Jee; Zhao, Ying; Linn, Marisa J; McHenry, Christina L; Gosangi, Babina; Bentley, J Kelley; Tsai, Wan C; Sajjan, Umadevi S; Lukacs, Nicholas W; Hershenson, Marc B

    2010-08-15

    Human rhinovirus is responsible for the majority of virus-induced asthma exacerbations. To determine the immunologic mechanisms underlying rhinovirus (RV)-induced asthma exacerbations, we combined mouse models of allergic airways disease and human rhinovirus infection. We inoculated OVA-sensitized and challenged BALB/c mice with rhinovirus serotype 1B, a minor group strain capable of infecting mouse cells. Compared with sham-infected, OVA-treated mice, virus-infected mice showed increased lung infiltration with neutrophils, eosinophils and macrophages, airway cholinergic hyperresponsiveness, and increased lung expression of cytokines including eotaxin-1/CCL11, IL-4, IL-13, and IFN-gamma. Administration of anti-eotaxin-1 attenuated rhinovirus-induced airway eosinophilia and responsiveness. Immunohistochemical analysis showed eotaxin-1 in the lung macrophages of virus-infected, OVA-treated mice, and confocal fluorescence microscopy revealed colocalization of rhinovirus, eotaxin-1, and IL-4 in CD68-positive cells. RV inoculation of lung macrophages from OVA-treated, but not PBS-treated, mice induced expression of eotaxin-1, IL-4, and IL-13 ex vivo. Macrophages from OVA-treated mice showed increased expression of arginase-1, Ym-1, Mgl-2, and IL-10, indicating a shift in macrophage activation status. Depletion of macrophages from OVA-sensitized and -challenged mice reduced eosinophilic inflammation and airways responsiveness following RV infection. We conclude that augmented airway eosinophilic inflammation and hyperresponsiveness in RV-infected mice with allergic airways disease is directed in part by eotaxin-1. Airway macrophages from mice with allergic airways disease demonstrate a change in activation state characterized in part by altered eotaxin and IL-4 production in response to RV infection. These data provide a new paradigm to explain RV-induced asthma exacerbations. PMID:20644177

  8. Nef gene evolution from a single transmitted strain in acute SIV infection

    PubMed Central

    Bimber, Benjamin N; Chugh, Pauline; Giorgi, Elena E; Kim, Baek; Almudevar, Anthony L; Dewhurst, Stephen; O'Connor, David H; Lee, Ha Youn

    2009-01-01

    Background The acute phase of immunodeficiency virus infection plays a crucial role in determining steady-state virus load and subsequent progression of disease in both humans and nonhuman primates. The acute period is also the time when vaccine-mediated effects on host immunity are likely to exert their major effects on virus infection. Recently we developed a Monte-Carlo (MC) simulation with mathematical analysis of viral evolution during primary HIV-1 infection that enables classification of new HIV-1 infections originating from multiple versus single transmitted viral strains and the estimation of time elapsed following infection. Results A total of 322 SIV nef SIV sequences, collected during the first 3 weeks following experimental infection of two rhesus macaques with the SIVmac239 clone, were analyzed and found to display a comparable level of genetic diversity, 0.015% to 0.052%, with that of env sequences from acute HIV-1 infection, 0.005% to 0.127%. We confirmed that the acute HIV-1 infection model correctly identified the experimental SIV infections in rhesus macaques as "homogenous" infections, initiated by a single founder strain. The consensus sequence of the sampled strains corresponded to the transmitted sequence as the model predicted. However, measured sequential decrease in diversity at day 7, 11, and 18 post infection violated the model assumption, neutral evolution without any selection. Conclusion While nef gene evolution over the first 3 weeks of SIV infection originating from a single transmitted strain showed a comparable rate of sequence evolution to that observed during acute HIV-1 infection, a purifying selection for the founder nef gene was observed during the early phase of experimental infection of a nonhuman primate. PMID:19505314

  9. The Effects of Acute Blood Loss for Diagnostic Bloodwork and Fluid Replacement in Clinically Ill Mice

    PubMed Central

    Marx, James O; Jensen, JanLee A; Seelye, Stacie; Walton, Raquel M; Hankenson, F Claire

    2015-01-01

    Despite the great value of diagnostic bloodwork for identifying disease in animals, the volume of blood required for these analyses limits its use in laboratory mice, particularly when they are clinically ill. We sought to determine the effects of acute blood loss (ABL) following blood collection for diagnostic bloodwork in healthy mice compared with streptozotocin-induced diabetic and dextran sulfate sodium (DSS)-treated dehydrated mice. ABL caused several mild changes in the control mice, with significant decreases in body weight, temperature, and activity in both experimental groups; increased dehydration and azotemia in the DSS-treated mice; and a significant drop in the blood pressure of the diabetic mice. To determine whether these negative outcomes could be ameliorated, we treated mice with intraperitoneal lactated Ringers solution either immediately after or 30 min before ABL. Notably, preABL administration of fluids helped prevent the worsening of the dehydration and azotemia in the DSS-treated mice and the changes in blood pressure in the diabetic mice. However, fluid administration provided no benefit in control of blood pressure when administered after ABL in the diabetic mice. Furthermore, fluid therapy did not prevent ABL-induced drops in body weight and activity. Although one mouse not receiving fluid therapy became moribund at the 24-h time point, no animals died during the 24-h study. This investigation demonstrates that blood for diagnostic bloodwork can be collected safely from clinically ill mice and that preemptive fluid therapy mitigates some of the negative changes associated with this blood loss. PMID:26141445

  10. Unexpected gender difference in sensitivity to the acute toxicity of dioxin in mice

    SciTech Connect

    Pohjanvirta, Raimo; Miettinen, Hanna; Sankari, Satu; Hegde, Nagabhooshan; Lindén, Jere

    2012-07-15

    The acute toxicity of the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) varies widely among species and strains. Previous studies in rats have established that females are approximately 2-fold more sensitive to TCDD lethality than males. However, there is a surprising gap in the literature regarding possible gender-related sensitivity differences in mice. In the present study, by using three substrains of TCDD-sensitive C57BL/6 mice and transgenic mice on this background, we demonstrated that: 1) in contrast to the situation in rats, female mice are the more resistant gender; 2) the magnitude of the divergence between male and female mice depends on the substrain, but can amount to over 10-fold; 3) AH receptor protein expression levels or mutations in the primary structure of this receptor are not involved in the resistance of female mice of a C57BL/6 substrain, despite their acute LD{sub 50} for TCDD being over 5000 μg/kg; 4) transgenic mice that globally express the rat wildtype AH receptor follow the mouse type of gender difference; 5) in gonadectomized mice, ovarian estrogens appear to enhance TCDD resistance, whereas testicular androgens seem to augment TCDD susceptibility; and 6) the gender difference correlates best with the severity of liver damage, which is also reflected in hepatic histopathology and the expression of pro-inflammatory cytokines, especially IL-6. Hence, the two closely related rodent species most often employed in toxicological risk characterization studies, rat and mouse, represent opposite examples of the influence of gender on dioxin sensitivity, further complicating the risk assessment of halogenated aromatic hydrocarbons. -- Highlights: ► In contrast to rats, male mice are more sensitive to TCDD toxicity than female mice. ► The resistance of female C57BL/6Kuo mice matches or exceeds that of male DBA/2 mice. ► The resistance of female C57BL/6Kuo mice is not based on AHR structure or abundance.

  11. Acute Scedosporium apiospermum Endobronchial Infection in Cystic Fibrosis.

    PubMed

    Padoan, Rita; Poli, Piercarlo; Colombrita, Domenico; Borghi, Elisa; Timpano, Silviana; Berlucchi, Marco

    2016-06-01

    Fungi are known pathogens in cystic fibrosis patients. A boy with cystic fibrosis boy presented with acute respiratory distress. Bronchoscopy showed airways obstruction by mucus plugs and bronchial casts. Scedosporium apiospermum was identified as the only pathogen. Bronchoalveolar lavage successfully resolved the acute obstruction. Plastic bronchitis is a new clinical picture of acute Scedosporium endobronchial colonization in cystic fibrosis patients. PMID:26967814

  12. Co-infection with Plasmodium berghei and Trypanosoma brucei increases severity of malaria and trypanosomiasis in mice.

    PubMed

    Ademola, Isaiah Oluwafemi; Odeniran, Paul Olalekan

    2016-07-01

    Individuals in natural populations may be infected with multiple different parasites at a time. These parasites may interact with each other or act independently in the host, and this may result to varying outcomes on host health and survival. This study therefore aimed at investigating the health impact of co-infection of mice with Plasmodium berghei and Trypanosoma brucei. Forty Swiss albino mice (14-17g) were divided into four groups of ten. Mice in groups A and B received 10(6)P. berghei and groups B and C 10(5)T. brucei, while group D were uninfected. The co-infected mice had higher P. berghei and T. brucei parasitaemia, compared with the mono-infected mice. The co-infected mice had significantly (p<0.05) lower survival rate compared with the mono-infected mice. Co-infection of mice with P. berghei and T. brucei resulted in rapid P. berghei and T. brucei development and increased parasitaemia. The leukocyte numbers significantly (p<0.05) reduced on days 12 and 15 post infection among P. berghei infected mice, in the presence or absence of T. brucei. Anaemia and hypoglycaemia was more severe in the co-infected mice. Therefore, co-infection of mice with P. berghei and T. brucei may increase pathologic impact to the host by increasing parasitaemia. PMID:27021269

  13. Kinetics of immune responses in deer mice experimentally infected with Sin Nombre virus.

    PubMed

    Schountz, Tony; Acuña-Retamar, Mariana; Feinstein, Shira; Prescott, Joseph; Torres-Perez, Fernando; Podell, Brendan; Peters, Staci; Ye, Chunyan; Black, William C; Hjelle, Brian

    2012-09-01

    Deer mice are the principal reservoir hosts of Sin Nombre virus, the etiologic agent of most hantavirus cardiopulmonary syndrome cases in North America. Infection of deer mice results in persistence without conspicuous pathology, and most, if not all, infected mice remain infected for life, with periods of viral shedding. The kinetics of viral load, histopathology, virus distribution, and immune gene expression in deer mice were examined. Viral antigen was detected as early as 5 days postinfection and peaked on day 15 in the lungs, hearts, kidneys, and livers. Viral RNA levels varied substantially but peaked on day 15 in the lungs and heart, and antinucleocapsid IgG antibodies appeared in some animals on day 10, but a strong neutralizing antibody response failed to develop during the 20-day experiment. No clinical signs of disease were observed in any of the infected deer mice. Most genes were repressed on day 2, suggesting a typical early downregulation of gene expression often observed in viral infections. Several chemokine and cytokine genes were elevated, and markers of a T cell response occurred but then declined days later. Splenic transforming growth factor beta (TGF-β) expression was elevated early in infection, declined, and then was elevated again late in infection. Together, these data suggest that a subtle immune response that fails to clear the virus occurs in deer mice. PMID:22787210

  14. Protective effect of carvacrol on acute lung injury induced by lipopolysaccharide in mice.

    PubMed

    Feng, Xiaosheng; Jia, Aiqing

    2014-08-01

    Carvacrol, the major component of Plectranthus amboinicus, has been known to exhibit anti-inflammatory activities. The aim of this study was to investigate the effects of carvacrol on lipopolysaccharide (LPS)-induced endotoxemia and acute lung injury (ALI) in mice. Mice were injected intraperitoneally (i.p.) with LPS and the mortality of mice for 7 days were observed twice a day. Meanwhile, the protective effect of carvacrol (20, 40 or 80 mg/kg) on LPS-induced endotoxemia were detected. Using an experimental model of LPS-induced ALI, we examined the effect of carvacrol in resolving lung injury. The results showed that carvacrol could improve survival during lethal endotoxemia and attenuate LPS-induced ALI in mice. The anti-inflammatory mechanisms of carvacrol may be due to its ability to inhibit NF-κB and MAPKs signaling pathways, thereby inhibiting inflammatory cytokines TNF-α, IL-6 and IL-1β production. PMID:24577726

  15. MicroRNA Transcriptome Profiling in Heart of Trypanosoma cruzi-Infected Mice: Parasitological and Cardiological Outcomes

    PubMed Central

    Navarro, Isabela Cunha; Ferreira, Frederico Moraes; Nakaya, Helder I.; Baron, Monique Andrade; Vilar-Pereira, Gláucia; Pereira, Isabela Resende; Silva, Ana Maria Gonçalves; Real, Juliana Monte; De Brito, Thales; Chevillard, Christophe; Lannes-Vieira, Joseli; Kalil, Jorge; Cunha-Neto, Edecio; Ferreira, Ludmila Rodrigues Pinto

    2015-01-01

    Chagas disease is caused by the parasite Trypanosoma cruzi, and it begins with a short acute phase characterized by high parasitemia followed by a life-long chronic phase with scarce parasitism. Cardiac involvement is the most prominent manifestation, as 30% of infected subjects will develop abnormal ventricular repolarization with myocarditis, fibrosis and cardiomyocyte hypertrophy by undefined mechanisms. Nevertheless, follow-up studies in chagasic patients, as well as studies with murine models, suggest that the intensity of clinical symptoms and pathophysiological events that occur during the acute phase of disease are associated with the severity of cardiac disease observed during the chronic phase. In the present study we investigated the role of microRNAs (miRNAs) in the disease progression in response to T. cruzi infection, as alterations in miRNA levels are known to be associated with many cardiovascular disorders. We screened 641 rodent miRNAs in heart samples of mice during an acute infection with the Colombiana T.cruzi strain and identified multiple miRNAs significantly altered upon infection. Seventeen miRNAs were found significantly deregulated in all three analyzed time points post infection. Among these, six miRNAs had their expression correlated with clinical parameters relevant to the disease, such as parasitemia and maximal heart rate-corrected QT (QTc) interval. Computational analyses identified that the gene targets for these six miRNAs were involved in networks and signaling pathways related to increased ventricular depolarization and repolarization times, important factors for QTc interval prolongation. The data presented here will guide further studies about the contribution of microRNAs to Chagas heart disease pathogenesis. PMID:26086673

  16. Antinociceptive, antiinflammatory and acute toxicity effects of Salvia leriifolia Benth seed extract in mice and rats.

    PubMed

    Hosseinzadeh, Hossein; Haddadkhodaparast, Mohammad H; Arash, Ali R

    2003-04-01

    The antinociceptive and antiinflammatory effects as well as the acute toxicity of Salvia leriifolia aqueous seed extract were studied in mice and rats. Antinociceptive activity was assessed using the hot-plate and tail flick tests. The effect on acute inflammation was studied using vascular permeability increased by acetic acid and xylene-induced ear oedema in mice. The activity against chronic inflammation was assessed using the cotton pellet test in rats. The LD(50) of the extract was found to be 19.5 g/kg (i.p.) in mice. The aqueous seed extract showed significant and dose-dependent (1.25-10 g/kg) antinociceptive activity over 7 h, and was inhibited by naloxone pretreatment. Significant and dose-dependent (2.5-10 g/kg) activity was observed against acute inflammation induced by acetic acid and in the xylene ear oedema test. In the chronic inflammation test the extract (2.5-5 g/kg) showed significant and dose-dependent antiinflammatory activity. The aqueous seed extract of S. leriifolia may therefore have supraspinal antinociceptive effects which may be mediated by opioid receptors, and showed considerable effects against acute and chronic inflammation. PMID:12722156

  17. The oral administration of trans-caryophyllene attenuates acute and chronic pain in mice.

    PubMed

    Paula-Freire, L I G; Andersen, M L; Gama, V S; Molska, G R; Carlini, E L A

    2014-02-15

    Trans-caryophyllene is a sesquiterpene present in many medicinal plants' essential oils, such as Ocimum gratissimum and Cannabis sativa. In this study, we evaluated the antinociceptive activity of trans-caryophyllene in murine models of acute and chronic pain and the involvement of trans-caryophyllene in the opioid and endocannabinoid systems. Acute pain was determined using the hot plate test (thermal nociception) and the formalin test (inflammatory pain). The chronic constriction injury (CCI) of the sciatic nerve induced hypernociception was measured by the hot plate and von Frey tests. To elucidate the mechanism of action, mice were pre-treated with naloxone or AM630 30 min before the trans-caryophyllene treatment. Afterwards, thermal nociception was evaluated. The levels of IL-1β were measured in CCI-mice by ELISA. Trans-caryophyllene administration significantly minimized the pain in both the acute and chronic pain models. The antinociceptive effect observed during the hot plate test was reversed by naloxone and AM630, indicating the participation of both the opioid and endocannabinoid system. Trans-caryophyllene treatment also decreased the IL-1β levels. These results demonstrate that trans-caryophyllene reduced both acute and chronic pain in mice, which may be mediated through the opioid and endocannabinoid systems. PMID:24055516

  18. Clinical and laboratory predictive markers for acute dengue infection

    PubMed Central

    2013-01-01

    Background Early diagnosis of dengue virus infection during the febrile stage is essential for adjusting appropriate management. This study is to identify the predictive markers of clinical and laboratory findings in the acute stage of dengue infection during a major outbreak of dengue virus type 1 that occurred in southern Taiwan during 2007. A retrospective, hospital-based study was conducted at a university hospital in southern Taiwan from January to December, 2007. Patient who was reported for clinically suspected dengue infection was enrolled. Laboratory-positive dengue cases are confirmed by enzyme-linked immunosorbent assay of specific dengue IgM, fourfold increase of dengue-specific IgG titers in convalescent serum, or by reverse transcription-polymerase chain reaction (RT-PCR) of dengue virus. Results The suspected dengue cases consist of 100 children (≤ 18 years) and 481 adults. Among the 581 patients, 67 (67%) children and 309 (64.2%) adults were laboratory-confirmed. Patients who had laboratory indeterminate were excluded. Most cases were uncomplicated and 3.8% of children and 2.9% of adults developed dengue hemorrhagic fever or dengue shock syndrome (DHF/DSS). The overall mortality rate in those with DHF/DSS was 7.1%, and the average duration of hospitalization was 20 days. The most common symptoms/signs at admission were myalgia (46.8%), petechiae (36.9%) and nausea/vomiting (33.5%). The most notable laboratory findings included leukopenia (2966 ± 1896/cmm), thrombocytopenia (102 ± 45 × 103/cmm), prolonged activated partial thromboplastin time (aPTT) (45 ± 10 s), and elevated serum levels of aminotransferase (AST, 166 ± 208 U/L; ALT, 82 ± 103 U/L) and low C - reactive protein (CRP) (6 ± 11 mg/L). Based on the clinical features for predicting laboratory-confirmed dengue infection, the sensitivities of typical rash, myalgia, and positive tourniquet test are 59.2%, 46.8%, and 34.2%, while the specificities for

  19. Protective Effects of Lactobacillus plantarum CCFM8610 against Acute Cadmium Toxicity in Mice

    PubMed Central

    Zhai, Qixiao; Wang, Gang; Zhao, Jianxin; Liu, Xiaoming; Zhang, Hao

    2013-01-01

    This study evaluated the protective effects of Lactobacillus plantarum CCFM8610, a selected probiotic with good cadmium binding capacity, against acute cadmium toxicity in mice. Ninety mice were divided into prevention and therapy groups. In the prevention groups, CCFM8610 was administered at 109 CFU once daily for 7 days, followed by a single oral dose of cadmium chloride at 1.8 mg cadmium for each mouse. In the therapy groups, the same dose of CCFM8610 was administered for 2 days after an identical single dose of cadmium exposure. Mice that received neither cadmium nor culture or that received cadmium alone served as negative and positive controls, respectively. The effects of both living and dead CCFM8610 on cadmium ion concentrations in feces, liver, and kidney were determined. Moreover, the alterations in reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and histopathology in the liver and kidney were investigated. The results showed that compared to the mice that received cadmium only, CCFM8610 treatment can effectively decrease intestinal cadmium absorption, reduce tissue cadmium accumulation, alleviate renal and hepatic oxidative stress, and ameliorate hepatic histopathological changes. Living CCFM8610 administered after cadmium exposure offered the most significant protection. Our results suggested that CCFM8610 is more effective against acute cadmium toxicity than a simple antioxidant treatment due to its special physiological functions and that it can be considered a new dietary therapeutic strategy against acute cadmium toxicity. PMID:23263961

  20. Biocompatible lutein-polymer-lipid nanocapsules: Acute and subacute toxicity and bioavailability in mice.

    PubMed

    Ranganathan, Arunkumar; Hindupur, Ravi; Vallikannan, Baskaran

    2016-12-01

    Lutein-poly-(lactic-co-glycolic acid) (PLGA)-phospholipid (PL) nanocapsules were prepared (henceforth referred as lutein nanocapsules) and studied for acute, subacute oral toxicity and bioavailability of lutein in mice. Prior to examining the safety of lutein nanocapsules, particle size, zeta potential, surface morphology and interaction between lutein, PLGA and PL were studied. In acute study, mice were gavaged with a single dose of lutein nanocapsules at 0.1, 1, 10 and 100mg/kg body weight (BW) and examined for 2weeks, while in subacute study, daily mice were gavaged with a dose of 1 and 10mg/kg BW for 4weeks. Results revealed that mean size and zeta value of lutein nanocapsules were 140nm and -44mV, respectively. Acute and subacute toxicity studies did not show any mortality or treatment related adverse effect in clinical observations, ophthalmic examinations, body and organ weights. No toxicity related findings were observed in hematology, histopathology and other blood and tissue clinical chemistry parameters. In subacute study, no observed adverse effect level (NOAEL) of lutein nanocapsules was found to be at a dose of 10mg/kg BW. Feeding lutein nanocapsules resulted in a significant (p<0.01) increase in lutein level in plasma and tissue compared to the control group. Lutein nanocapsules did not cause toxicity in mice. However, human trials are warranted. PMID:27612832

  1. NK cells contribute to persistent airway inflammation and AHR during the later stage of RSV infection in mice.

    PubMed

    Long, Xiaoru; Xie, Jun; Zhao, Keting; Li, Wei; Tang, Wei; Chen, Sisi; Zang, Na; Ren, Luo; Deng, Yu; Xie, Xiaohong; Wang, Lijia; Fu, Zhou; Liu, Enmei

    2016-10-01

    RSV can lead to persistent airway inflammation and AHR and is intimately associated with childhood recurrent wheezing and asthma, but the underlying mechanisms remain unclear. There are high numbers of NK cells in the lung, which not only play important roles in the acute stage of RSV infection, but also are pivotal in regulating the pathogenesis of asthma. Therefore, in this study, we assumed that NK cells might contribute to persistent airway disease during the later stage of RSV infection. Mice were killed at serial time points after RSV infection to collect samples. Leukocytes in bronchoalveolar lavage fluid (BALF) were counted, lung histopathology was examined, and airway hyperresponsiveness (AHR) was measured by whole-body plethysmography. Cytokines were detected by ELISA, and NK cells were determined by flow cytometry. Rabbit anti-mouse asialo-GM-1 antibodies and resveratrol were used to deplete or suppress NK cells. Inflammatory cells in BALF, lung tissue damage and AHR were persistent for 60 days post-RSV infection. Type 2 cytokines and NK cells were significantly increased during the later stage of infection. When NK cells were decreased by the antibodies or resveratrol, type 2 cytokines, the persistent airway inflammation and AHR were all markedly reduced. NK cells can contribute to the RSV-associated persistent airway inflammation and AHR at least partially by promoting type 2 cytokines. Therefore, therapeutic targeting of NK cells may provide a novel approach to alleviating the recurrent wheezing subsequent to RSV infection. PMID:27329138

  2. Disseminated Neocosmospora vasinfecta infection in a patient with acute nonlymphocytic leukemia.

    PubMed Central

    Cornely, O. A.; Chemnitz, J.; Brochhagen, H. G.; Lemmer, K.; Schütt, H.; Söhngen, D.; Staib, P.; Wickenhauser, C.; Diehl, V.; Tintelnot, K.

    2001-01-01

    We report Neocosmospora vasinfecta infection following chemotherapy for acute nonlymphocytic leukemia. N. vasinfecta, a plant pathogen, was identified by culture and genetic sequencing. Susceptibility testing revealed in vitro resistance for common antifungals. PMID:11266308

  3. Interleukin-1β biosynthesis inhibition reduces acute seizures and drug resistant chronic epileptic activity in mice.

    PubMed

    Maroso, Mattia; Balosso, Silvia; Ravizza, Teresa; Iori, Valentina; Wright, Christopher Ian; French, Jacqueline; Vezzani, Annamaria

    2011-04-01

    Experimental evidence and clinical observations indicate that brain inflammation is an important factor in epilepsy. In particular, induction of interleukin-converting enzyme (ICE)/caspase-1 and activation of interleukin (IL)-1β/IL-1 receptor type 1 axis both occur in human epilepsy, and contribute to experimentally induced acute seizures. In this study, the anticonvulsant activity of VX-765 (a selective ICE/caspase-1 inhibitor) was examined in a mouse model of chronic epilepsy with spontaneous recurrent epileptic activity refractory to some common anticonvulsant drugs. Moreover, the effects of this drug were studied in one acute model of seizures in mice, previously shown to involve activation of ICE/caspase-1. Quantitative analysis of electroencephalogram activity was done in mice exposed to acute seizures or those developing chronic epileptic activity after status epilepticus to assess the anticonvulsant effects of systemic administration of VX-765. Histological and immunohistochemical analysis of brain tissue was carried out at the end of pharmacological experiments in epileptic mice to evaluate neuropathology, glia activation and IL-1β expression, and the effect of treatment. Repeated systemic administration of VX-765 significantly reduced chronic epileptic activity in mice in a dose-dependent fashion (12.5-200 mg/kg). This effect was observed at doses ≥ 50 mg/kg, and was reversible with discontinuation of the drug. Maximal drug effect was associated with inhibition of IL-1β synthesis in activated astrocytes. The same dose regimen of VX-765 also reduced acute seizures in mice and delayed their onset time. These results support a new target system for anticonvulsant pharmacological intervention to control epileptic activity that does not respond to some common anticonvulsant drugs. PMID:21431948

  4. Changes in ovarian follicles following acute infection with bovine viral diarrhea virus.

    PubMed

    Grooms, D L; Brock, K V; Pate, J L; Day, M L

    1998-02-01

    Bovine viral diarrhea virus (BVDV) has been associated with several reproductive problems in cattle, including poor fertility, early embryonic deaths, abortion and congenital anomalies. Little is known about the cause of poor fertility in cows acutely infected with BVDV. The purpose of this study was to identify changes in ovarian function following acute infection with noncytopathic BVDV. The ovaries of 5 BVDV sero-negative and virus-negative pubertal heifers were monitored daily for 4 consecutive estrous cycles. The position and diameter of all follicles (> 5 mm) and luteal structures were recorded. Daily plasma samples were collected to measure peripheral progesterone and estradiol levels. Each heifer was infected intranasally with noncytopathic BVDV following ovulation of the second estrous cycle. The maximum diameter and growth rate of dominant anovulatory and ovulatory follicles were significantly reduced following acute BVDV infection. Similarly, the number of subordinate follicles associated with both the anovulatory and ovulatory follicle was reduced following infection. There were no significant differences in other follicle or luteal dynamic parameters or in peripheral progesterone or estradiol levels. Ovarian follicular growth was different during the first 2 estrous cycles following acute infection with BVDV when compared with the 2 estrous cycles preceding infection. These differences may be important in explaining reduced fertility in herds with acute BVDV infection. PMID:10732038

  5. Enhancing the detection and management of acute hepatitis C virus infection.

    PubMed

    Martinello, Marianne; Matthews, Gail V

    2015-10-01

    Acute HCV infection refers to the 6-month period following infection acquisition, although this definition is somewhat arbitrary. While spontaneous clearance occurs in approximately 25%, the majority will develop chronic HCV infection with the potential for development of cirrhosis, end stage liver disease and hepatocellular carcinoma. Detection of acute HCV infection has been hampered by its asymptomatic or non-specific presentation, lack of specific diagnostic tests and the inherent difficulties in identifying and following individuals at highest risk of transmitting and acquiring HCV infection, such as people who inject drugs (PWID). However, recognition of those with acute infection may have individual and population level benefits and could represent an ideal opportunity for intervention. Despite demonstration that HCV treatment is feasible and successful in PWID, treatment uptake remains low with multiple barriers to care at an individual and systems level. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment, treatment and prevention in this group are urgently needed. As the therapeutic landscape of chronic HCV management is revolutionised by the advent of simple, highly effective directly-acting antiviral (DAA) therapy, similar opportunities may exist in acute infection. This review will discuss issues surrounding improving the detection and management of acute HCV infection, particularly in PWID. PMID:26254495

  6. Differences between Mycobacterium-Host Cell Relationships in Latent Tuberculous Infection of Mice Ex Vivo and Mycobacterial Infection of Mouse Cells In Vitro

    PubMed Central

    Ufimtseva, Elena

    2016-01-01

    The search for factors that account for the reproduction and survival of mycobacteria, including vaccine strains, in host cells is the priority for studies on tuberculosis. A comparison of BCG-mycobacterial loads in granuloma cells obtained from bone marrow and spleens of mice with latent tuberculous infection and cells from mouse bone marrow and peritoneal macrophage cultures infected with the BCG vaccine in vitro has demonstrated that granuloma macrophages each normally contained a single BCG-Mycobacterium, while those acutely infected in vitro had increased mycobacterial loads and death rates. Mouse granuloma cells were observed to produce the IFNγ, IL-1α, GM-CSF, CD1d, CD25, CD31, СD35, and S100 proteins. None of these activation markers were found in mouse cell cultures infected in vitro or in intact macrophages. Lack of colocalization of lipoarabinomannan-labeled BCG-mycobacteria with the lysosomotropic LysoTracker dye in activated granuloma macrophages suggests that these macrophages were unable to destroy BCG-mycobacteria. However, activated mouse granuloma macrophages could control mycobacterial reproduction in cells both in vivo and in ex vivo culture. By contrast, a considerable increase in the number of BCG-mycobacteria was observed in mouse bone marrow and peritoneal macrophages after BCG infection in vitro, when no expression of the activation-related molecules was detected in these cells. PMID:27066505

  7. Infection trials in mice suggest that Macrorhabdus ornithogaster is not capable of growth in mammals.

    PubMed

    Hanafusa, Yasuko; Costa, Enrica; Phalen, David N

    2013-08-01

    The objective of this study was to determine if Macrorhabdus ornithogaster, a yeast recovered from the junction of the proventriculus and ventriculus of the stomach of parrots and other birds, can infect mice. Fifteen healthy ARC (S) female mice (age 10 weeks) were incoculated with M. ornithogaster by gavage at (two different dosage rates [n = 5]) or intraperitoneal injection (n = 5) (one dosage rate). They were euthanized 5 days later and examined for gross and microscopic evidence of infection. Macrorhabdus ornithogaster was not found to colonize the stomach, peritoneum, or viscera of the challeneged mice. The results of this study show that M. ornithogaster is not able to infect mice by the oral and intraperitoneal routes of administration and suggest that infection in mammals is unlikely to occur. PMID:23330673

  8. Acute two-photon imaging of the neurovascular unit in the cortex of active mice

    PubMed Central

    Tran, Cam Ha T.; Gordon, Grant R.

    2015-01-01

    In vivo two-photon scanning fluorescence imaging is a powerful technique to observe physiological processes from the millimeter to the micron scale in the intact animal. In neuroscience research, a common approach is to install an acute cranial window and head bar to explore neocortical function under anesthesia before inflammation peaks from the surgery. However, there are few detailed acute protocols for head-restrained and fully awake animal imaging of the neurovascular unit during activity. This is because acutely performed awake experiments are typically untenable when the animal is naïve to the imaging apparatus. Here we detail a method that achieves acute, deep-tissue two-photon imaging of neocortical astrocytes and microvasculature in behaving mice. A week prior to experimentation, implantation of the head bar alone allows mice to train for head-immobilization on an easy-to-learn air-supported ball treadmill. Following just two brief familiarization sessions to the treadmill on separate days, an acute cranial window can subsequently be installed for immediate imaging. We demonstrate how running and whisking data can be captured simultaneously with two-photon fluorescence signals with acceptable movement artifacts during active motion. We also show possible applications of this technique by (1) monitoring dynamic changes to microvascular diameter and red blood cells in response to vibrissa sensory stimulation, (2) examining responses of the cerebral microcirculation to the systemic delivery of pharmacological agents using a tail artery cannula during awake imaging, and (3) measuring Ca2+ signals from synthetic and genetically encoded Ca2+ indicators in astrocytes. This method will facilitate acute two-photon fluorescence imaging in awake, active mice and help link cellular events within the neurovascular unit to behavior. PMID:25698926

  9. Radiculoplexopathy with conduction block caused by acute Epstein-Barr virus infection.

    PubMed

    Vucic, Steve; Palmer, William; Cros, Didier

    2005-02-01

    The authors report a case of cervicobrachial radiculoplexopathy with proximal conduction block (CB), associated with acute Epstein-Barr virus (EBV) infection. The patient presented with pain, paresthesias, and monomelic weakness in the left C7-8, and T1 myotomes. The illness was monophasic with rapid recovery. Neurophysiologic studies demonstrated CB in the proximal left median and ulnar nerve segments. The authors conclude that this syndrome resulted from a postinfectious process following acute EBV infection. PMID:15699388

  10. Acute Hepatitis as a Manifestation of Parvovirus B19 Infection

    PubMed Central

    Hatakka, Aleisha; Klein, Julianne; He, Runtao; Piper, Jessica; Tam, Edward; Walkty, Andrew

    2011-01-01

    There are few reports in the literature of hepatitis as a manifestation of parvovirus B19 infection. We describe a case of parvovirus B19-associated acute hepatitis diagnosed based on a positive serologic test (IgM) and molecular detection of parvovirus B19 DNA in a liver biopsy specimen. Parvovirus B19 infection should be considered in the differential diagnosis of patients presenting with acute hepatitis. PMID:21734024

  11. Protection of mice against encephalomyocarditis virus infection by preparations of transfer RNA.

    PubMed

    Stebbing, N; Grantham, C A; Kaminski, F; Lindley, I J

    1977-01-01

    Preparations of bacterial transfer RNA (tRNA), give dose-dependent protection of mice against encephalomyocarditis (EMC) virus infection at up to I mg tRNA per mouse with maximum response when the tRNA is administered around 6 h before infection. Protection occurs with intraperitoneally and intravenously administered tRNA against infections by both these routes. In some experiments significant protection occurs by single treatments of tRNA up to 24 h after infection with virus doses of I X LD100. Some tRNA preparations of eukaryotic origin do not give significant protection. Protection is not a feature of all species of bacterial tRNA; partially purified valine, tyrosine and phenylalanine tRNAs from Escherichia coli are not protective. tRNA treatment does not induce circulating interferon nor does it 'hypo-reactivate' the protective effect of poly (I).poly (C) treatment of mice. Humoral and cell mediated immune responses do not seem to be involved in tRNA mediated protection since first, cytosine arabinoside treatment does not affect protection by tRNA; second, serum from mice treated with tRNA and an EMC vaccine does not protect other mice against infection, and third, mice that survive normally lethal infections as a result of tRNA treatment are generally just as susceptible to re-infection as previously untreated, uninfected mice. Silica treatment abolishes protection of mice by tRNA implying that macrophages are necessary. However, tRNA does not seem to act by clearance of virus particles since vaccination of mice by inactivated EMC virus is not affected by tRNA treatment. These results are considered in relation to the presence of a tRNA-like structure in EMC virus RNA and protection of mice by other single stranded polynucleotides. PMID:188982

  12. Evaluation of Nitrofurantoin Combination Therapy of Metronidazole-Sensitive and -Resistant Helicobacter pylori Infections in Mice

    PubMed Central

    Jenks, Peter J.; Ferrero, Richard L.; Tankovic, Jacques; Thiberge, Jean-Michel; Labigne, Agnès

    2000-01-01

    The main objectives of this study were to determine whether the nitroreductase enzyme encoded by the rdxA gene of Helicobacter pylori was responsible for reductive activation of nitrofurantoin and whether a triple-therapy regimen with nitrofurantoin was able to eradicate metronidazole-sensitive and -resistant H. pylori infections from mice. The susceptibilities to nitrofurantoin of parent and isogenic rdxA mutant strains (three pairs), as well as a series of matched metronidazole-sensitive and -resistant strains isolated from mice (30) and patients (20), were assessed by agar dilution determination of the MIC. Groups of mice colonized with the metronidazole-sensitive H. pylori SS1 strain or a metronidazole-resistant rdxA SS1 mutant were treated with either metronidazole or nitrofurantoin as part of a triple-therapy regimen. One month after the completion of treatment the mice were sacrificed and their stomachs were cultured for H. pylori. The nitrofurantoin MICs for all strains tested were between 0.5 and 4.0 μg/ml. There was no significant difference between the susceptibility to nitrofurantoin of the parental strains and those of respective rdxA mutants or between those of matched metronidazole-sensitive and -resistant H. pylori isolates. The regimen with metronidazole eradicated infection from all eight SS1-infected mice and from one of eight mice inoculated with the rdxA mutant (P ≤ 0.001). The regimen with nitrofurantoin failed to eradicate infection from any of the six SS1-infected mice (P ≤ 0.001) and cleared infection from one of seven mice inoculated with the rdxA mutant. These results demonstrate that, despite the good in vitro activity of nitrofurantoin against H. pylori and the lack of cross-resistance between metronidazole and nitrofurantoin, eradication regimens involving nitrofurantoin are unable to eradicate either metronidazole-sensitive or -resistant H. pylori infections from mice. PMID:10991835

  13. CAF1-knockout mice are more susceptive to lipopolysaccharide-induced acute lung injury

    PubMed Central

    Shi, Jia-Xin; Li, Jia-Shu; Hu, Rong; Li, Xiao-Min; Wang, Hong

    2016-01-01

    The carbon catabolite repressor protein 4 (CCR4)–negative on TATA (NOT) complex includes multiple subunits and is conserved in the eukaryotic cells. The CCR4–NOT complex can regulate gene expression at different levels. Two subunits of the CCR4–NOT complex, CCR4 and CCR4-associated factor 1 (CAF1), possess deadenylase activity. In yeast, the deadenylase activity is mainly provided by the CCR4 subunit; however, the deadenylase activity is provided by both CCR4 and CAF1 in other eukaryotes. A previous study reported that CAF1 but not CCR4 is required for the decay of a reporter mRNA with AU-rich elements. Our previous study showed that CAF1 is involved in the regulation of intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8) expression. Both ICAM-1 and IL-8 play crucial roles in acute lung injury. In the present study, we examined the effects of CAF1 deficiency on IL-8 and ICAM-1 expression and acute lung injury in mice. Here we showed that there were no differences between the wild-type and CAF1-knockout mice on phenotypes. The lung histology and protein and mRNA levels of IL-8 and ICAM-1 in unstimulated wild-type mice were comparable to those in unstimulated CAF1-knockout mice. However, lipopolysaccharide stimulation led to more severe lung histological injury and greatly higher IL-8 and ICAM-1 expression in CAF1-knockout mice compared to the wild-type mice. These results, together with our previous study, suggest that CAF1 is involved in the regulation of lipopolysaccharide-stimulated IL-8 and ICAM-1 expression in vivo and affects the progression of acute lung injury. PMID:27358572

  14. Resistin deficiency in mice has no effect on pulmonary responses induced by acute ozone exposure.

    PubMed

    Razvi, Shehla S; Richards, Jeremy B; Malik, Farhan; Cromar, Kevin R; Price, Roger E; Bell, Cynthia S; Weng, Tingting; Atkins, Constance L; Spencer, Chantal Y; Cockerill, Katherine J; Alexander, Amy L; Blackburn, Michael R; Alcorn, Joseph L; Haque, Ikram U; Johnston, Richard A

    2015-11-15

    Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines-including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1β)-promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1β, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-β-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology. PMID:26386120

  15. Flaxseed lignans enriched in secoisolariciresinol diglucoside prevent acute asbestos-induced peritoneal inflammation in mice

    PubMed Central

    Pietrofesa, Ralph A.; Velalopoulou, Anastasia; Arguiri, Evguenia; Menges, Craig W.; Testa, Joseph R.; Hwang, Wei-Ting; Albelda, Steven M.

    2016-01-01

    Malignant mesothelioma (MM), linked to asbestos exposure, is a highly lethal form of thoracic cancer with a long latency period, high mortality and poor treatment options. Chronic inflammation and oxidative tissue damage caused by asbestos fibers are linked to MM development. Flaxseed lignans, enriched in secoisolariciresinol diglucoside (SDG), have antioxidant, anti-inflammatory and cancer chemopreventive properties. As a prelude to chronic chemoprevention studies for MM development, we tested the ability of flaxseed lignan component (FLC) to prevent acute asbestos-induced inflammation in MM-prone Nf2+/mu mice. Mice (n = 16–17 per group) were placed on control (CTL) or FLC-supplemented diets initiated 7 days prior to a single intraperitoneal bolus of 400 µg of crocidolite asbestos. Three days post asbestos exposure, mice were evaluated for abdominal inflammation, proinflammatory/profibrogenic cytokine release, WBC gene expression changes and oxidative and nitrosative stress in peritoneal lavage fluid (PLF). Asbestos-exposed mice fed CTL diet developed acute inflammation, with significant (P < 0.0001) elevations in WBCs and proinflammatory/profibrogenic cytokines (IL-1ß, IL-6, TNFα, HMGB1 and active TGFß1) relative to baseline (BL) levels. Alternatively, asbestos-exposed FLC-fed mice had a significant (P < 0.0001) decrease in PLF WBCs and proinflammatory/profibrogenic cytokine levels relative to CTL-fed mice. Importantly, PLF WBC gene expression of cytokines (IL-1ß, IL-6, TNFα, HMGB1 and TGFß1) and cytokine receptors (TNFαR1 and TGFßR1) were also downregulated by FLC. FLC also significantly (P < 0.0001) blunted asbestos-induced nitrosative and oxidative stress. FLC reduces acute asbestos-induced peritoneal inflammation, nitrosative and oxidative stress and may thus prove to be a promising agent in the chemoprevention of MM. PMID:26678224

  16. Pancreatic Protein Tyrosine Phosphatase 1B Deficiency Exacerbates Acute Pancreatitis in Mice.

    PubMed

    Bettaieb, Ahmed; Koike, Shinichiro; Chahed, Samah; Bachaalany, Santana; Griffey, Stephen; Sastre, Juan; Haj, Fawaz G

    2016-08-01

    Acute pancreatitis (AP) is a common and devastating gastrointestinal disorder that causes significant morbidity. The disease starts as local inflammation in the pancreas that may progress to systemic inflammation and complications. Protein tyrosine phosphatase 1B (PTP1B) is implicated in inflammatory signaling, but its significance in AP remains unclear. To investigate whether PTP1B may have a role in AP, we used pancreas PTP1B knockout (panc-PTP1B KO) mice and determined the effects of pancreatic PTP1B deficiency on cerulein- and arginine-induced acute pancreatitis. We report that PTP1B protein expression was increased in the early phase of AP in mice and rats. In addition, histological analyses of pancreas samples revealed enhanced features of AP in cerulein-treated panc-PTP1B KO mice compared with controls. Moreover, cerulein- and arginine-induced serum amylase and lipase were significantly higher in panc-PTP1B KO mice compared with controls. Similarly, pancreatic mRNA and serum concentrations of the inflammatory cytokines IL-1B, IL-6, and tumor necrosis factor-α were increased in panc-PTP1B KO mice compared with controls. Furthermore, panc-PTP1B KO mice exhibited enhanced cerulein- and arginine-induced NF-κB inflammatory response accompanied with increased mitogen-activated protein kinases activation and elevated endoplasmic reticulum stress. Notably, these effects were recapitulated in acinar cells treated with a pharmacological inhibitor of PTP1B. These findings reveal a novel role for pancreatic PTP1B in cerulein- and arginine-induced acute pancreatitis. PMID:27461362

  17. Flaxseed lignans enriched in secoisolariciresinol diglucoside prevent acute asbestos-induced peritoneal inflammation in mice.

    PubMed

    Pietrofesa, Ralph A; Velalopoulou, Anastasia; Arguiri, Evguenia; Menges, Craig W; Testa, Joseph R; Hwang, Wei-Ting; Albelda, Steven M; Christofidou-Solomidou, Melpo

    2016-02-01

    Malignant mesothelioma (MM), linked to asbestos exposure, is a highly lethal form of thoracic cancer with a long latency period, high mortality and poor treatment options. Chronic inflammation and oxidative tissue damage caused by asbestos fibers are linked to MM development. Flaxseed lignans, enriched in secoisolariciresinol diglucoside (SDG), have antioxidant, anti-inflammatory and cancer chemopreventive properties. As a prelude to chronic chemoprevention studies for MM development, we tested the ability of flaxseed lignan component (FLC) to prevent acute asbestos-induced inflammation in MM-prone Nf2(+/mu) mice. Mice (n = 16-17 per group) were placed on control (CTL) or FLC-supplemented diets initiated 7 days prior to a single intraperitoneal bolus of 400 µg of crocidolite asbestos. Three days post asbestos exposure, mice were evaluated for abdominal inflammation, proinflammatory/profibrogenic cytokine release, WBC gene expression changes and oxidative and nitrosative stress in peritoneal lavage fluid (PLF). Asbestos-exposed mice fed CTL diet developed acute inflammation, with significant (P < 0.0001) elevations in WBCs and proinflammatory/profibrogenic cytokines (IL-1ß, IL-6, TNFα, HMGB1 and active TGFß1) relative to baseline (BL) levels. Alternatively, asbestos-exposed FLC-fed mice had a significant (P < 0.0001) decrease in PLF WBCs and proinflammatory/profibrogenic cytokine levels relative to CTL-fed mice. Importantly, PLF WBC gene expression of cytokines (IL-1ß, IL-6, TNFα, HMGB1 and TGFß1) and cytokine receptors (TNFαR1 and TGFßR1) were also downregulated by FLC. FLC also significantly (P < 0.0001) blunted asbestos-induced nitrosative and oxidative stress. FLC reduces acute asbestos-induced peritoneal inflammation, nitrosative and oxidative stress and may thus prove to be a promising agent in the chemoprevention of MM. PMID:26678224

  18. CCL5-glutamate interaction in central nervous system: Early and acute presynaptic defects in EAE mice.

    PubMed

    Di Prisco, Silvia; Merega, Elisa; Milanese, Marco; Summa, Maria; Casazza, Simona; Raffaghello, Lizzia; Pistoia, Vito; Uccelli, Antonio; Pittaluga, Anna

    2013-12-01

    We investigated the CCL5-glutamate interaction in the cortex and in the spinal cord from mice with Experimental Autoimmune Encephalomyelitis (EAE) at 13 and 21/30 days post immunization (d.p.i.), representing the onset and the peak of the disease, respectively. An early reduction of the KCl-evoked glutamate release was observed in cortical terminals from EAE mice at 13 d.p.i., persisting until 21/30 d.p.i. A concomitant reduction of the depolarization-evoked cyclic adenosine monophosphate (cAMP), but not of the inositol 1,4,5-trisphosphate (IP3) cortical production also occurred at 13 d.p.i, that still was detectable at the acute stage of disease (21 dp.i.). Inasmuch, the CCL5-mediated inhibition of glutamate exocytosis observed in control mice turned to facilitation in EAE mouse cortex at 13 d.p.i., then becoming undetectable at 21/30 d.p.i. Differently, glutamate exocytosis, as well as IP3 and cAMP productions were unaltered in spinal cord synaptosomes from EAE mice at 13 d.p.i., but significantly increased at 21/30 d.p.i., while the presynaptic CCL5-mediated facilitation of glutamate exocytosis observed in control mice remained unchanged. In both CNS regions, the presynaptic defects were parallelled by increased CCL5 availability. Inasmuch, the presynaptic defects so far described in EAE mice were reminiscent of the effects acute CCL5 exerts in control conditions. Based on these observations we propose that increased CCL5 bioavailability could have a role in determining the abovedescribed impaired presynaptic impairments in both CNS regions. These presynaptic defects could be relevant to the onset of early cognitive impairments and acute neuroinflammation and demyelinating processes observed in multiple sclerosis patients. PMID:23958452

  19. Functional genomics of chlorine-induced acute lung injury in mice.

    PubMed

    Leikauf, George D; Pope-Varsalona, Hannah; Concel, Vincent J; Liu, Pengyuan; Bein, Kiflai; Brant, Kelly A; Dopico, Richard A; Di, Y Peter; Jang, An-Soo; Dietsch, Maggie; Medvedovic, Mario; Li, Qian; Vuga, Louis J; Kaminski, Naftali; You, Ming; Prows, Daniel R

    2010-07-01

    Acute lung injury can be induced indirectly (e.g., sepsis) or directly (e.g., chlorine inhalation). Because treatment is still limited to supportive measures, mortality remains high ( approximately 74,500 deaths/yr). In the past, accidental (railroad derailments) and intentional (Iraq terrorism) chlorine exposures have led to deaths and hospitalizations from acute lung injury. To better understand the molecular events controlling chlorine-induced acute lung injury, we have developed a functional genomics approach using inbred mice strains. Various mouse strains were exposed to chlorine (45 ppm x 24 h) and survival was monitored. The most divergent strains varied by more than threefold in mean survival time, supporting the likelihood of an underlying genetic basis of susceptibility. These divergent strains are excellent models for additional genetic analysis to identify critical candidate genes controlling chlorine-induced acute lung injury. Gene-targeted mice then could be used to test the functional significance of susceptibility candidate genes, which could be valuable in revealing novel insights into the biology of acute lung injury. PMID:20601635

  20. Varicella Zoster Infection: A Rare Cause of Abdominal Pain Mimicking Acute Abdomen

    PubMed Central

    Olmez, Deniz; Boz, Alper; Erkan, Nazif

    2009-01-01

    Varicella zoster is an acute viral infection that results from reactivation of a latent varicella zoster virus. It usually occurs in adult population and immune compromised patients. It rarely occurs in healthy children. Here we present a 14 years old male with varicella zoster that had abdominal pain mimicking acute abdomen to alert others who are consulted for the differentiation of acute abdomen and others who may be consulted for pain management. Keywords Varicella zoster; Abdominal pain PMID:22461879

  1. Nogo-B protects mice against lipopolysaccharide-induced acute lung injury

    PubMed Central

    Xu, Wujian; Zhu, Ying; Ning, Yunye; Dong, Yuchao; Huang, Haidong; Zhang, Wei; Sun, Qinying; Li, Qiang

    2015-01-01

    Nogo-B, a member of the reticulon 4 protein family, plays a critical role in tissue repair and acute inflammation. Its role in acute lung injury (ALI) remains unclear. Here, we assessed the function of Nogo-B during tissue injury in a lipopolysaccharide (LPS)-induced ALI mouse model. We found that pulmonary Nogo-B was significantly repressed after LPS instillation in C57BL/6 mice. Over-expression of pulmonary Nogo-B using an adenovirus vector carrying the Nogo-B-RFP-3flag gene (Ad-Nogo-B) significantly prolonged the survival of mice challenged with a lethal dose of LPS. The Ad-Nogo-B-treated mice also had less severe lung injury, less alveolar protein exudation, and a higher number of macrophages but less neutrophil infiltration compared with Ad-RFP-treated mice. Interestingly, microarray analysis showed that the Ad-Nogo-B-treated mice had different gene expression profiles compared with the controls and the prominent expression of genes related to wound healing and the humoral immune response after LPS induction. Of the 49 differently expressed genes, we found that the expression of PTX3 was significantly up-regulated following Nogo-B over-expression as observed in lung tissues and RAW264.7 cells. In conclusion, Nogo-B plays a protective role against LPS-induced ALI, and this effect might be exerted through the modulation of alveolar macrophage recruitment and PTX3 production. PMID:26174362

  2. Acute respiratory distress syndrome and acute renal failure from Plasmodium ovale infection with fatal outcome

    PubMed Central

    2013-01-01

    Background Plasmodium ovale is one of the causative agents of human malaria. Plasmodium ovale infection has long been thought to be non-fatal. Due to its lower morbidity, P. ovale receives little attention in malaria research. Methods Two Malaysians went to Nigeria for two weeks. After returning to Malaysia, they fell sick and were admitted to different hospitals. Plasmodium ovale parasites were identified from blood smears of these patients. The species identification was further confirmed with nested PCR. One of them was successfully treated with no incident of relapse within 12-month medical follow-up. The other patient came down with malaria-induced respiratory complication during the course of treatment. Although parasites were cleared off the circulation, the patient’s condition worsened. He succumbed to multiple complications including acute respiratory distress syndrome and acute renal failure. Results Sequencing of the malaria parasite DNA from both cases, followed by multiple sequence alignment and phylogenetic tree construction suggested that the causative agent for both malaria cases was P. ovale curtisi. Discussion In this report, the differences between both cases were discussed, and the potential capability of P. ovale in causing severe complications and death as seen in this case report was highlighted. Conclusion Plasmodium ovale is potentially capable of causing severe complications, if not death. Complete travel and clinical history of malaria patient are vital for successful diagnoses and treatment. Monitoring of respiratory and renal function of malaria patients, regardless of the species of malaria parasites involved is crucial during the course of hospital admission. PMID:24180319

  3. Activity of Clarithromycin or Rifampin Alone or in Combination against Experimental Rhodococcus equi Infection in Mice

    PubMed Central

    Burton, Alexandra J.; Berghaus, Londa J.; Hondalus, Mary K.

    2015-01-01

    Treatment of mice with the combination of clarithromycin with rifampin resulted in a significantly lower number of Rhodococcus equi CFU in the organs of mice than treatment with either drug alone or placebo. There was no significant difference in the number of R. equi CFU between mice treated with clarithromycin monotherapy, rifampin monotherapy, or placebo. The combination of clarithromycin with rifampin conferred a clear advantage over either drug as monotherapy in this model of chronic R. equi infection. PMID:25824218

  4. Resistance of neonatal mice to scrapie is associated with inefficient infection of the immature spleen.

    PubMed

    Ierna, Michelle; Farquhar, Christine F; Outram, George W; Bruce, Moira E

    2006-01-01

    Previous studies demonstrated that neonatal mice up to about a week old are less susceptible than adult mice to infection by intraperitoneal inoculation with mouse-passaged scrapie. In peripherally inoculated adult mice, scrapie replicates in lymphoid tissues such as the spleen before invading the central nervous system. Here, we investigated scrapie susceptibility in neonatal mice in more detail, concentrating on spleen involvement. First, we demonstrated that neonatal mice are about 10 times less susceptible than adults to intraperitoneal scrapie inoculation. Then we injected mice intraperitoneally with a scrapie dose that produced disease in all mice inoculated at 10 days or older but in only about a third of neonatally inoculated mice. In this experiment, spleens collected 70 days after scrapie injection of mice 10 days old or older almost all contained pathological prion protein, PrPSc, and those that were bioassayed all contained high infectivity levels. In contrast, at this early stage, only two of six spleens from neonatally inoculated mice had detectable, low infectivity levels; no PrPSc was detected, even in the two spleens. Therefore, neonatal mice have an impaired ability to replicate scrapie in their spleens, suggesting that replication sites are absent or sparse at birth but mature within 10 days. The increase in susceptibility with age correlated with the first immunocytochemical detection of the normal cellular form of prion protein, PrPc, on maturing follicular dendritic cell networks. As lymphoid tissues are more mature at birth in sheep, cattle, and humans than in mice, our results suggest that in utero infection with scrapie-like agents is theoretically possible in these species. PMID:16352571

  5. Chlamydia trachomatis Antigens Recognized by Women With Tubal Factor Infertility, Normal Fertility, and Acute Infection

    PubMed Central

    Budrys, Nicole M.; Gong, Siqi; Rodgers, Allison K.; Wang, Jie; Louden, Christopher; Shain, Rochelle; Schenken, Robert S.; Zhong, Guangming

    2015-01-01

    Objective To identify Chlamydia trachomatis antigens associated with tubal factor infertility and acute infection. Methods A C. trachomatis proteome array was used to compare antibody profiles among women with tubal factor infertility, normal fertility, and acute C. trachomatis infection. Results Thirteen immunodominant antigens reacted with 50% or more sera from all women (N=73). Six C. trachomatis antigens were uniquely recognized by women diagnosed with tubal factor infertility. Combining fragmentation of the six antigens with serum sample dilution, chlamydial antigens HSP60, CT376, CT557, and CT443 could discriminate between women with tubal factor infertility and women with normal fertility with a sensitivity of 63% (95% CI: 0.41–0.77) and specificity of 100% (95% CI: 0.91–1), respectively. These antigens were designated as tubal factor infertility-associated antigens. However, these tubal factor antigens were unable to distinguish tubal factor infertility patients from those with acute infection. A combination of CT875 and CT147 distinguished women with acute infection from all other C. trachomatis-exposed women with a detection sensitivity of 63% (95% CI: 0.41–0.77) and specificity of 100% (95% CI: 0.95–1), respectively. Thus, CT875 and CT147 were designated as acute infection-associated antigens. Conclusion A sequential screening of antibodies against panels of C. trachomatis antigens can be used to identify women with tubal factor infertility and acute C. trachomatis infection. PMID:22525912

  6. Rapid and widely disseminated acute phase protein response after experimental bacterial infection of pigs

    PubMed Central

    Skovgaard, Kerstin; Mortensen, Shila; Boye, Mette; Poulsen, Karin T.; Campbell, Fiona M.; Eckersall, P. David; Heegaard, Peter M.H.

    2009-01-01

    The acute phase protein response is a well-described generalized early host response to tissue injury, inflammation and infection, observed as pronounced changes in the concentrations of a number of circulating serum proteins. The biological function of this response and its interplay with other parts of innate host defence reactions remain somewhat elusive. In order to gain new insight into this early host defence response in the context of bacterial infection we studied gene expression changes in peripheral lymphoid tissues as compared to hepatic expression changes, 14–18 h after lung infection in pigs. The lung infection was established with the pig specific respiratory pathogen Actinobacillus pleuropneumoniae. Quantitative real-time PCR based expression analysis were performed on samples from liver, tracheobronchial lymph node, tonsils, spleen and on blood leukocytes, supplemented with measurements of interleukin-6 and selected acute phase proteins in serum. C-reactive protein and serum amyloid A were clearly induced 14–18 h after infection. Extrahepatic expression of acute phase proteins was found to be dramatically altered as a result of the lung infection with an extrahepatic acute phase protein response occurring concomitantly with the hepatic response. This suggests that the acute phase protein response is a more disseminated systemic response than previously thought. The current study provides to our knowledge the first example of porcine extrahepatic expression and regulation of C-reactive protein, haptoglobin, fibrinogen, pig major acute phase protein, and transferrin in peripheral lymphoid tissues. PMID:19236838

  7. Cystitis induced by infection with the Lyme disease spirochete, Borrelia burgdorferi, in mice.

    PubMed Central

    Czub, S.; Duray, P. H.; Thomas, R. E.; Schwan, T. G.

    1992-01-01

    Previous studies have demonstrated that the urinary bladder is a consistent source for isolating the Lyme disease spirochete, Borrelia burgdorferi, from both experimentally infected and naturally exposed rodents. We examined histopathologic changes in the urinary bladder of different types of rodents experimentally infected with Lyme spirochetes, including BALB/c mice (Mus musculus), nude mice (M. musculus), white-footed mice (Peromyscus leucopus), and grasshopper mice (Onychomys leucogaster). Animals were inoculated intraperitoneally, subcutaneously, or intranasally with low-passaged spirochetes, high-passaged spirochetes, or phosphate-buffered saline. At various times after inoculation, animals were killed and approximately one-half of each urinary bladder and kidney were cultured separately in BSK-II medium while the other half of each organ was prepared for histologic examination. Spirochetes were cultured from the urinary bladder of all 35 mice inoculated with low-passaged spirochetes while we were unable to isolate spirochetes from any kidneys of the same mice. The pathologic changes observed most frequently in the urinary bladder of the infected mice were the presence of lymphoid aggregates, vascular changes, including an increase in the number of vessels and thickening of the vessel walls, and perivascular infiltrates. Our results demonstrate that nearly all individuals (93%) of the four types of mice examined had a cystitis associated with spirochetal infection. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1443051

  8. Helicobacter pylori infection can affect energy modulating hormones and body weight in germ free mice

    PubMed Central

    Khosravi, Yalda; Seow, Shih Wee; Amoyo, Arlaine Anne; Chiow, Kher Hsin; Tan, Tuan Lin; Wong, Whye Yen; Poh, Qian Hui; Sentosa, Ignatius Mario Doli; Bunte, Ralph M.; Pettersson, Sven; Loke, Mun Fai; Vadivelu, Jamuna

    2015-01-01

    Helicobacter pylori, is an invariably commensal resident of the gut microbiome associated with gastric ulcer in adults. In addition, these patients also suffered from a low grade inflammation that activates the immune system and thus increased shunting of energy to host defense mechanisms. To assess whether a H. pylori infection could affect growth in early life, we determined the expression levels of selected metabolic gut hormones in germ free (GF) and specific pathogen-free (SPF) mice with and without the presence of H. pylori. Despite H. pylori-infected (SPFH) mice display alteration in host metabolism (elevated levels of leptin, insulin and peptide YY) compared to non-infected SPF mice, their growth curves remained the same. SPFH mice also displayed increased level of eotaxin-1. Interestingly, GF mice infected with H. pylori (GFH) also displayed increased levels of ghrelin and PYY. However, in contrast to SPFH mice, GFH showed reduced weight gain and malnutrition. These preliminary findings show that exposure to H. pylori alters host metabolism early in life; but the commensal microbiota in SPF mice can attenuate the growth retarding effect from H. pylori observed in GF mice. Further investigations of possible additional side effects of H. pylori are highly warranted. PMID:25736205

  9. Helicobacter pylori infection can affect energy modulating hormones and body weight in germ free mice.

    PubMed

    Khosravi, Yalda; Seow, Shih Wee; Amoyo, Arlaine Anne; Chiow, Kher Hsin; Tan, Tuan Lin; Wong, Whye Yen; Poh, Qian Hui; Sentosa, Ignatius Mario Doli; Bunte, Ralph M; Pettersson, Sven; Loke, Mun Fai; Vadivelu, Jamuna

    2015-01-01

    Helicobacter pylori, is an invariably commensal resident of the gut microbiome associated with gastric ulcer in adults. In addition, these patients also suffered from a low grade inflammation that activates the immune system and thus increased shunting of energy to host defense mechanisms. To assess whether a H. pylori infection could affect growth in early life, we determined the expression levels of selected metabolic gut hormones in germ free (GF) and specific pathogen-free (SPF) mice with and without the presence of H. pylori. Despite H. pylori-infected (SPFH) mice display alteration in host metabolism (elevated levels of leptin, insulin and peptide YY) compared to non-infected SPF mice, their growth curves remained the same. SPFH mice also displayed increased level of eotaxin-1. Interestingly, GF mice infected with H. pylori (GFH) also displayed increased levels of ghrelin and PYY. However, in contrast to SPFH mice, GFH showed reduced weight gain and malnutrition. These preliminary findings show that exposure to H. pylori alters host metabolism early in life; but the commensal microbiota in SPF mice can attenuate the growth retarding effect from H. pylori observed in GF mice. Further investigations of possible additional side effects of H. pylori are highly warranted. PMID:25736205

  10. Phenylalanine prevents acute poisoning by ochratoxina in mice.

    PubMed

    Creppy, E E; Schlegel, M; Röschenthaler, R; Dirheimer, G

    1980-07-01

    Ochratoxin-A (OT-A) a mycotoxin isolated from Aspergillus ochraceus is toxic for animals and man causing a fatal chronic kidney disease and liver damages. OT-A is a competitive inhibitor of phenylalanine in the phenylalanyl-tRNA synthetase-catalyzed reaction thus inhibiting protein synthesis. This inhibition can be reversed by phenylalanine. When injected intraperitoneally (i.p.) to mice a dose of 0.8 mg of OT-A is lethal within 24h. However, when this lethal dose is injected together with 1 mg of phenylalanine 100% of the animals survive. When phenylalanine was injected 30 min after OT-A the doses required for the survival of 92% of the animals had to be about 25 times higher. PMID:7414623

  11. Genetic identification of unique immunological responses in mice infected with virulent and attenuated Francisella tularensis

    PubMed Central

    Kingry, Luke C.; Troyer, Ryan M.; Marlenee, Nicole L.; Bielefeldt-Ohmann, Helle; Bowen, Richard A.; Schenkel, Alan R.; Dow, Steven W.; Slayden, Richard A.

    2010-01-01

    Francisella tularensis is a category A select agent based on its infectivity and virulence but disease mechanisms in Francisella tularensis infection remain poorly understood. Murine pulmonary models of infection were therefore employed to assess and compare dissemination and pathology and to elucidate the host immune response to infection with the highly virulent Type A F. tularensis strain Schu4 versus the less virulent Type B live vaccine strain (LVS). We found that dissemination and pathology in the spleen was significantly greater in mice infected with F. tularensis Schu4 compared to mice infected with F. tularensis LVS. Using gene expression profiling to compare the response to infection with the two F. tularensis strains, we found that there were significant differences in the expression of genes involved in the apoptosis pathway, antigen processing and presentation pathways, and inflammatory response pathways in mice infected with Schu4 when compared to LVS. These transcriptional differences coincided with marked differences in dissemination and severity of organ lesions in mice infected with the Schu4 and LVS strains. Therefore, these findings indicate that altered apoptosis, antigen presentation and production of inflammatory mediators explain the differences in pathogenicity of F. tularensis Schu4 and LVS. PMID:21070859

  12. Pancreatitis and cholecystitis in primary acute symptomatic Epstein-Barr virus infection - Systematic review of the literature.

    PubMed

    Kottanattu, Lisa; Lava, Sebastiano A G; Helbling, Rossana; Simonetti, Giacomo D; Bianchetti, Mario G; Milani, Gregorio P

    2016-09-01

    Acute pancreatitis and acalculous cholecystitis have been occasionally reported in primary acute symptomatic Epstein-Barr virus infection. We completed a review of the literature and retained 48 scientific reports published between 1966 and 2016 for the final analysis. Acute pancreatitis was recognized in 14 and acalculous cholecystitis in 37 patients with primary acute symptomatic Epstein-Barr virus infection. In all patients, the features of acute pancreatitis or acalculous cholecystitis concurrently developed with those of primary acute symptomatic Epstein-Barr virus infection. Acute pancreatitis and acalculous cholecystitis resolved following a hospital stay of 25days or less. Acalculous cholecystitis was associated with Gilbert-Meulengracht syndrome in two cases. In conclusion, this thorough analysis indicates that acute pancreatitis and acalculous cholecystitis are unusual but plausible complications of primary acute symptomatic Epstein-Barr virus infection. Pancreatitis and cholecystitis deserve consideration in cases with severe abdominal pain. These complications are usually rather mild and resolve spontaneously without sequelae. PMID:27434148

  13. Colorectal Disorders in Acute Human Immunodeficiency Virus Infection: A Case Series

    PubMed Central

    Panichsillapakit, Theppharit; Patel, Derek; Santangelo, Joanne; Richman, Douglas D.; Little, Susan J.; Smith, Davey M.

    2016-01-01

    Background. The gastrointestinal (GI) tract is important in the pathogenesis of human immunodeficiency virus (HIV) infection. We report a case series of lower GI endoscopic and histopathologic findings of HIV-infected individuals after presentation with acute infection. Methods. We performed a retrospective case review of individuals infected with HIV who enrolled between August 2010 and April 2013 in a primary infection treatment trial. All participants started the trial during acute infection and underwent colonoscopy with biopsies at baseline and after the start of antiretroviral treatment. Results. Twenty acutely infected individuals were included in the study (mean age, 33 years; range, 20–54 years). All participants were male who reported having receptive anal sex as an HIV risk factor. Nine individuals (45%) had at least 1 finding by colorectal pathology; 1 person had 2 diagnoses (diverticulosis and focal active proctitis). The histopathological findings revealed anal dysplasia in 3 cases: 2 had high-grade anal intraepithelial neoplasia (AIN) and 1 had low-grade AIN. Two persons had a colorectal polyp, 1 hyperplastic and 1 adenomatous. Three persons were diagnosed with diverticulosis, and 2 persons were diagnosed with proctitis, including 1 with focal active proctitis and 1 with cytomegalovirus proctitis. Conclusions. To our knowledge, this is the first case series report of lower GI disorders in acute HIV-infected individuals. Although the causal relationship remains uncertain, we describe the endoscopic findings that were observed during acute HIV infection among men who have sex with men. Understanding the prevalence of these pathologies may likely shed light on how acute HIV infection damages the lower GI tract. PMID:26925432

  14. Acute behavioral effects of nicotine in male and female HINT1 knockout mice.

    PubMed

    Jackson, K J; Wang, J B; Barbier, E; Chen, X; Damaj, M I

    2012-11-01

    Human genetic association and brain expression studies, and mouse behavioral and molecular studies implicate a role for the histidine triad nucleotide-binding protein 1 (HINT1) in schizophrenia, bipolar disorder, depression and anxiety. The high comorbidity between smoking and psychiatric disorders, schizophrenia in particular, is well established. Associations with schizophrenia and HINT1 are also sex specific, with effects more predominant in males; however, it is unknown if sex differences associated with the gene extend to other phenotypes. Thus, in this study, using a battery of behavioral tests, we elucidated the role of HINT1 in acute nicotine-mediated behaviors using male and female HINT1 wild-type (+/+) and knockout (-/-) mice. The results show that male HINT1 -/- mice were less sensitive to acute nicotine-induced antinociception in the tail-flick, but not hot-plate test. At low nicotine doses, male and female HINT1 -/- mice were less sensitive to nicotine-induced hypomotility, although the effect was more pronounced in females. Baseline differences in locomotor activity observed in male HINT1 +/+ and -/- mice were absent in females. Nicotine did not produce an anxiolytic effect in male HINT1 -/- mice, but rather an anxiogenic response. Diazepam also failed to induce an anxiolytic response in these mice, suggesting a general anxiety phenotype not specific to nicotine. Differences in anxiety-like behavior were not observed in female mice. These results further support a role for HINT1 in nicotine-mediated behaviors and suggest that alterations in the gene may have differential effects on phenotype in males and females. PMID:22827509

  15. Differential Lymphocyte and Antibody Responses in Deer Mice Infected with Sin Nombre Hantavirus or Andes Hantavirus

    PubMed Central

    Quackenbush, Sandra; Rovnak, Joel; Haddock, Elaine; Black, William C.; Feldmann, Heinz; Prescott, Joseph

    2014-01-01

    ABSTRACT Hantavirus cardiopulmonary syndrome (HCPS) is a rodent-borne disease with a high case-fatality rate that is caused by several New World hantaviruses. Each pathogenic hantavirus is naturally hosted by a principal rodent species without conspicuous disease and infection is persistent, perhaps for life. Deer mice (Peromyscus maniculatus) are the natural reservoirs of Sin Nombre virus (SNV), the etiologic agent of most HCPS cases in North America. Deer mice remain infected despite a helper T cell response that leads to high-titer neutralizing antibodies. Deer mice are also susceptible to Andes hantavirus (ANDV), which causes most HCPS cases in South America; however, deer mice clear ANDV. We infected deer mice with SNV or ANDV to identify differences in host responses that might account for this differential outcome. SNV RNA levels were higher in the lungs but not different in the heart, spleen, or kidneys. Most ANDV-infected deer mice had seroconverted 14 days after inoculation, but none of the SNV-infected deer mice had. Examination of lymph node cell antigen recall responses identified elevated immune gene expression in deer mice infected with ANDV and suggested maturation toward a Th2 or T follicular helper phenotype in some ANDV-infected deer mice, including activation of the interleukin 4 (IL-4) pathway in T cells and B cells. These data suggest that the rate of maturation of the immune response is substantially higher and of greater magnitude during ANDV infection, and these differences may account for clearance of ANDV and persistence of SNV. IMPORTANCE Hantaviruses persistently infect their reservoir rodent hosts without pathology. It is unknown how these viruses evade sterilizing immune responses in the reservoirs. We have determined that infection of the deer mouse with its homologous hantavirus, Sin Nombre virus, results in low levels of immune gene expression in antigen-stimulated lymph node cells and a poor antibody response. However, infection

  16. Host Transcriptional Profiles and Immunopathologic Response following Mycobacterium avium subsp. paratuberculosis Infection in Mice

    PubMed Central

    Shin, Min-Kyoung; Park, Hongtae; Shin, Seung Won; Jung, Myunghwan; Lee, Su-Hyung; Kim, Dae-Yong; Yoo, Han Sang

    2015-01-01

    Paratuberculosis or Johne’s disease is a chronic granulomatous enteropathy in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection. In the present study, we examined the host response to MAP infection in spleens of mice in order to investigate the host immunopathology accompanying host-pathogen interaction. Transcriptional profiles of the MAP-infected mice at 3 and 6 weeks p.i. showed severe histopathological changes, whereas those at 12 weeks p.i. displayed reduced lesion severity in the spleen and liver. MAP-infected mice at 3 and 6 weeks p.i. showed up-regulation of interferon-related genes, scavenger receptor, and complement components, suggesting an initial innate immune reaction, such as macrophage activation, bactericidal activity, and macrophage invasion of MAP. Concurrently, MAP-infected mice at 3 and 6 weeks p.i. were also suggested to express M2 macrophage phenotype with up-regulation of Mrc1, and Marco and down-regulation of MHC class II, Ccr7, and Irf5, and canonical pathways related to the T cell response including ICOS-ICOSL signaling in T helper cells, calcium-induced T lymphocyte apoptosis, and CD28 signaling in T helper cell. These results provide information which furthers the understanding of the immunopathologic response to MAP infection in mice, thereby providing insights valuable for research into the pathogenesis for MAP infection. PMID:26439498

  17. Blue Light Rescues Mice from Potentially Fatal Pseudomonas aeruginosa Burn Infection: Efficacy, Safety, and Mechanism of Action

    PubMed Central

    Dai, Tianhong; Gupta, Asheesh; Huang, Ying-Ying; Yin, Rui; Murray, Clinton K.; Vrahas, Mark S.; Sherwood, Margaret E.; Tegos, George P.

    2013-01-01

    Blue light has attracted increasing attention due to its intrinsic antimicrobial effect without the addition of exogenous photosensitizers. However, the use of blue light for wound infections has not been established yet. In this study, we demonstrated the efficacy of blue light at 415 nm for the treatment of acute, potentially lethal Pseudomonas aeruginosa burn infections in mice. Our in vitro studies demonstrated that the inactivation rate of P. aeruginosa cells by blue light was approximately 35-fold higher than that of keratinocytes (P = 0.0014). Transmission electron microscopy revealed blue light-mediated intracellular damage to P. aeruginosa cells. Fluorescence spectroscopy suggested that coproporphyrin III and/or uroporphyrin III are possibly the intracellular photosensitive chromophores associated with the blue light inactivation of P. aeruginosa. In vivo studies using an in vivo bioluminescence imaging technique and an area-under-the-bioluminescence-time-curve (AUBC) analysis showed that a single exposure of blue light at 55.8 J/cm2, applied 30 min after bacterial inoculation to the infected mouse burns, reduced the AUBC by approximately 100-fold in comparison with untreated and infected mouse burns (P < 0.0001). Histological analyses and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assays indicated no significant damage in the mouse skin exposed to blue light at the effective antimicrobial dose. Survival analyses revealed that blue light increased the survival rate of the infected mice from 18.2% to 100% (P < 0.0001). In conclusion, blue light therapy might offer an effective and safe alternative to conventional antimicrobial therapy for P. aeruginosa burn infections. PMID:23262998

  18. Blue light rescues mice from potentially fatal Pseudomonas aeruginosa burn infection: efficacy, safety, and mechanism of action.

    PubMed

    Dai, Tianhong; Gupta, Asheesh; Huang, Ying-Ying; Yin, Rui; Murray, Clinton K; Vrahas, Mark S; Sherwood, Margaret E; Tegos, George P; Hamblin, Michael R

    2013-03-01

    Blue light has attracted increasing attention due to its intrinsic antimicrobial effect without the addition of exogenous photosensitizers. However, the use of blue light for wound infections has not been established yet. In this study, we demonstrated the efficacy of blue light at 415 nm for the treatment of acute, potentially lethal Pseudomonas aeruginosa burn infections in mice. Our in vitro studies demonstrated that the inactivation rate of P. aeruginosa cells by blue light was approximately 35-fold higher than that of keratinocytes (P = 0.0014). Transmission electron microscopy revealed blue light-mediated intracellular damage to P. aeruginosa cells. Fluorescence spectroscopy suggested that coproporphyrin III and/or uroporphyrin III are possibly the intracellular photosensitive chromophores associated with the blue light inactivation of P. aeruginosa. In vivo studies using an in vivo bioluminescence imaging technique and an area-under-the-bioluminescence-time-curve (AUBC) analysis showed that a single exposure of blue light at 55.8 J/cm(2), applied 30 min after bacterial inoculation to the infected mouse burns, reduced the AUBC by approximately 100-fold in comparison with untreated and infected mouse burns (P < 0.0001). Histological analyses and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assays indicated no significant damage in the mouse skin exposed to blue light at the effective antimicrobial dose. Survival analyses revealed that blue light increased the survival rate of the infected mice from 18.2% to 100% (P < 0.0001). In conclusion, blue light therapy might offer an effective and safe alternative to conventional antimicrobial therapy for P. aeruginosa burn infections. PMID:23262998

  19. Ecto-5'-nucleotidase CD73 modulates the innate immune response to influenza infection but is not required for development of influenza-induced acute lung injury.

    PubMed

    Aeffner, Famke; Woods, Parker S; Davis, Ian C

    2015-12-01

    Extracellular nucleotides and nucleosides are important signaling molecules in the lung. Nucleotide and nucleoside concentrations in alveolar lining fluid are controlled by a complex network of surface ectonucleotidases. Previously, we demonstrated that influenza A/WSN/33 (H1N1) virus resulted in increased levels of the nucleotide ATP and the nucleoside adenosine in bronchoalveolar lavage fluid (BALF) of wild-type (WT) C57BL/6 mice. Influenza-induced acute lung injury (ALI) was highly attenuated in A1-adenosine receptor-knockout mice. Because AMP hydrolysis by the ecto-5'-nucleotidase (CD73) plays a central role in and is rate-limiting for generation of adenosine in the normal lung, we hypothesized that ALI would be attenuated in C57BL/6-congenic CD73-knockout (CD73-KO) mice. Infection-induced hypoxemia, bradycardia, viral replication, and bronchoconstriction were moderately increased in CD73-KO mice relative to WT controls. However, postinfection weight loss, pulmonary edema, and parenchymal dysfunction were not altered. Treatment of WT mice with the CD73 inhibitor 5'-(α,β-methylene) diphosphate (APCP) also had no effect on infection-induced pulmonary edema but modestly attenuated hypoxemia. BALF from CD73-KO and APCP-treated WT mice contained more IL-6 and CXCL-10/IFN-γ-induced protein 10, less CXCL-1/keratinocyte chemoattractant, and fewer neutrophils than BALF from untreated WT controls. BALF from APCP-treated WT mice also contained fewer alveolar macrophages and more transforming growth factor-β than BALF from untreated WT mice. These results indicate that CD73 is not necessary for development of ALI following influenza A virus infection and suggest that tissue-nonspecific alkaline phosphatase may be responsible for increased adenosine generation in the infected lung. However, they do suggest that CD73 has a previously unrecognized immunomodulatory role in influenza. PMID:26432867

  20. BOVINE VIRAL DIARRHEA VIRUS PERSISTENTLY INFECTED AND ACUTELY INFECTED CALVES: ASSAYS FOR VIRAL INFECTIVITY, POLYMERASE CHAIN REACTION ANALYSIS, AND ANTIGEN DETECTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are numerous assays for bovine viral diarrhea virus (BVDV) detecting infectious virus, nucleic material, and antigen. Persistently infected (PI) and acutely/transiently infected calves with BVDV represent two different manifestations. Diagnostic test results impact on differentiation of PI o...

  1. Effect of age on susceptibility to Salmonella Typhimurium infection in C57BL/6 mice.

    PubMed

    Ren, Zhihong; Gay, Raina; Thomas, Adam; Pae, Munkyong; Wu, Dayong; Logsdon, Lauren; Mecsas, Joan; Meydani, Simin Nikbin

    2009-12-01

    Ageing is associated with a decline in immune function, which predisposes the elderly to a higher incidence of infections. Information on the mechanism of the age-related increase in susceptibility to Salmonella enterica serovar Typhimurium (S. Typhimurium) is limited. In particular, little is known regarding the involvement of the immune response in this age-related change. We employed streptomycin (Sm)-pretreated C57BL/6 mice to develop a mouse model that would demonstrate age-related differences in susceptibility and immune response to S. Typhimurium. In this model, old mice inoculated orally with doses of 3 x 10(8) or 1 x 10(6) c.f.u. S. Typhimurium had significantly greater S. Typhimurium colonization in the ileum, colon, Peyer's patches, spleen and liver than young mice. Old mice had significantly higher weight loss than young mice on days 1 and 2 post-infection. In response to S. Typhimurium infection, old mice failed to increase ex vivo production of IFN-gamma and TNF-alpha in the spleen and mesenteric lymph node cells to the same degree as observed in young mice; this was associated with their inability to maintain the presence of neutrophils and macrophages at a 'youthful' level. These results indicate that Sm-pretreated C57BL/6 old mice are more susceptible to S. Typhimurium infection than young mice, which might be due to impaired IFN-gamma and TNF-alpha production as well as a corresponding change in the number of neutrophils and macrophages in response to S. Typhimurium infection compared to young mice. PMID:19729455

  2. Murine Norovirus Infection Variably Alters Atherosclerosis in Mice Lacking Apolipoprotein E

    PubMed Central

    Hsu, Charlie C; Paik, Jisun; Brabb, Thea L; O'Brien, Kevin D; Kim, Jinkyu; Sullivan, Brittany G; Hudkins, Kelly L; Seamons, Audrey; Finley, Jennifer C; Meeker, Stacey M; Maggio-Price, Lillian

    2015-01-01

    Macrophages play a key role in the development of atherosclerosis. Murine noroviruses (MNV) are highly prevalent in research mouse colonies and infect macrophages and dendritic cells. Our laboratory found that MNV4 infection in mice lacking the LDL receptor alters the development of atherosclerosis, potentially confounding research outcomes. Therefore, we investigated whether MNV4 likewise altered atherosclerosis in ApoE−/− mice. In the presence of oxidized LDL, MNV4 infection of ApoE−/− bone marrow-derived macrophages increased the gene expression of the inflammatory markers inducible nitric oxide synthase, monocyte chemoattractant protein 1, and IL6. In addition, proteins involved in cholesterol transport were altered in MNV4-infected ApoE−/− bone marrow-derived macrophages and consisted of increased CD36 and decreased ATP-binding cassette transporter A1. MNV4 infection of ApoE−/− mice at 12 wk of age (during the development of atherosclerosis) had a variable effect on atherosclerotic lesion size. In one study, MNV4 significantly increased atherosclerotic plaque area whereas in a second study, no effect was observed. Compared with controls, MNV4-infected mice had higher circulating Ly6C-positive monocytes, and viral RNA was detected in the aortas of some mice, suggesting potential mechanisms by which MNV4 alters disease progression. Plaque size did not differ when ApoE−/− mice were infected at 4 wk of age (early during disease development) or in ApoE−/− mice maintained on a high-fat, high-cholesterol diet. Therefore, these data show that MNV4 has the potential to exert a variable and unpredictable effect on atherosclerosis in ApoE−/− mice. We therefore propose that performing experiments in MNV-free mouse colonies is warranted. PMID:26473341

  3. Murine Norovirus Infection Variably Alters Atherosclerosis in Mice Lacking Apolipoprotein E.

    PubMed

    Hsu, Charlie C; Paik, Jisun; Brabb, Thea L; O'Brien, Kevin D; Kim, Jinkyu; Sullivan, Brittany G; Hudkins, Kelly L; Seamons, Audrey; Finley, Jennifer C; Meeker, Stacey M; Maggio-Price, Lillian

    2015-10-01

    Macrophages play a key role in the development of atherosclerosis. Murine noroviruses (MNV) are highly prevalent in research mouse colonies and infect macrophages and dendritic cells. Our laboratory found that MNV4 infection in mice lacking the LDL receptor alters the development of atherosclerosis, potentially confounding research outcomes. Therefore, we investigated whether MNV4 likewise altered atherosclerosis in ApoE(-/-) mice. In the presence of oxidized LDL, MNV4 infection of ApoE(-/-) bone marrow-derived macrophages increased the gene expression of the inflammatory markers inducible nitric oxide synthase, monocyte chemoattractant protein 1, and IL6. In addition, proteins involved in cholesterol transport were altered in MNV4-infected ApoE -/- bone marrow-derived macrophages and consisted of increased CD36 and decreased ATP-binding cassette transporter A1. MNV4 infection of ApoE(-/-) mice at 12 wk of age (during the development of atherosclerosis) had a variable effect on atherosclerotic lesion size. In one study, MNV4 significantly increased atherosclerotic plaque area whereas in a second study, no effect was observed. Compared with controls, MNV4-infected mice had higher circulating Ly6C-positive monocytes, and viral RNA was detected in the aortas of some mice, suggesting potential mechanisms by which MNV4 alters disease progression. Plaque size did not differ when ApoE -/- mice were infected at 4 wk of age (early during disease development) or in ApoE -/- mice maintained on a high-fat, high-cholesterol diet. Therefore, these data show that MNV4 has the potential to exert a variable and unpredictable effect on atherosclerosis in ApoE(-/-) mice. We therefore propose that performing experiments in MNV-free mouse colonies is warranted. PMID:26473341

  4. EVALUATION OF EFFECTS OF OZONE EXPOSURE ON INFLUENZA INFECTION IN MICE USING SEVERAL INDICATORS OF SUSCEPTIBILITY (JOURNAL VERSION)

    EPA Science Inventory

    Mice were exposed to 1 ppm O3, 3hrs/day, for 5 consecutive days. A 2-fold increase in % mortality and a 3 day decrease in survival time were observed in mice infected with influenza virus after the 2nd exposure. These endpoints were not affected in mice infected after the 1st, 3r...

  5. Pharmacological Inhibition of Transforming Growth Factor β Signaling Decreases Infection and Prevents Heart Damage in Acute Chagas' Disease▿

    PubMed Central

    Waghabi, Mariana C.; de Souza, Elen M.; de Oliveira, Gabriel M.; Keramidas, Michelle; Feige, Jean-Jacques; Araújo-Jorge, Tania C.; Bailly, Sabine

    2009-01-01

    Chagas' disease induced by Trypanosoma cruzi infection is an important cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are largely inadequate. We previously reported that transforming growth factor β (TGF-β) is implicated in several regulatory aspects of T. cruzi invasion and growth and in host tissue fibrosis. This prompted us to evaluate the therapeutic action of an inhibitor of TGF-β signaling (SB-431542) administered during the acute phase of experimental Chagas' disease. Male Swiss mice were infected intraperitoneally with 104 trypomastigotes of T. cruzi (Y strain) and evaluated clinically for the following 30 days. SB-431542 treatment significantly reduced mortality and decreased parasitemia. Electrocardiography showed that SB-431542 treatment was effective in protecting the cardiac conduction system. By 14 day postinfection, enzymatic biomarkers of tissue damage indicated that muscle injury was decreased by SB-431542 treatment, with significantly lower blood levels of aspartate aminotransferase and creatine kinase. In conclusion, inhibition of TGF-β signaling in vivo appears to potently decrease T. cruzi infection and to prevent heart damage in a preclinical mouse model. This suggests that this class of molecules may represent a new therapeutic agent for acute and chronic Chagas' disease that warrants further clinical exploration. PMID:19738024

  6. Age-dependent effects of UCP2 deficiency on experimental acute pancreatitis in mice.

    PubMed

    Müller, Sarah; Kaiser, Hannah; Krüger, Burkhard; Fitzner, Brit; Lange, Falko; Bock, Cristin N; Nizze, Horst; Ibrahim, Saleh M; Fuellen, Georg; Wolkenhauer, Olaf; Jaster, Robert

    2014-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of acute pancreatitis (AP) for many years but experimental evidence is still limited. Uncoupling protein 2 (UCP2)-deficient mice are an accepted model of age-related oxidative stress. Here, we have analysed how UCP2 deficiency affects the severity of experimental AP in young and older mice (3 and 12 months old, respectively) triggered by up to 7 injections of the secretagogue cerulein (50 μg/kg body weight) at hourly intervals. Disease severity was assessed at time points from 3 hours to 7 days based on pancreatic histopathology, serum levels of alpha-amylase, intrapancreatic trypsin activation and levels of myeloperoxidase (MPO) in lung and pancreatic tissue. Furthermore, in vitro studies with pancreatic acini were performed. At an age of 3 months, UCP2-/- mice and wild-type (WT) C57BL/6 mice were virtually indistinguishable with respect to disease severity. In contrast, 12 months old UCP2-/- mice developed a more severe pancreatic damage than WT mice at late time points after the induction of AP (24 h and 7 days, respectively), suggesting retarded regeneration. Furthermore, a higher peak level of alpha-amylase activity and gradually increased MPO levels in pancreatic and lung tissue were observed in UCP2-/- mice. Interestingly, intrapancreatic trypsin activities (in vivo studies) and intraacinar trypsin and elastase activation in response to cerulein treatment (in vitro studies) were not enhanced but even diminished in the knockout strain. Finally, UCP2-/- mice displayed a diminished ratio of reduced and oxidized glutathione in serum but no increased ROS levels in pancreatic acini. Together, our data indicate an aggravating effect of UCP2 deficiency on the severity of experimental AP in older but not in young mice. We suggest that increased severity of AP in 12 months old UCP2-/- is caused by an imbalanced inflammatory response but is unrelated to acinar cell functions. PMID:24721982

  7. Age-Dependent Effects of UCP2 Deficiency on Experimental Acute Pancreatitis in Mice

    PubMed Central

    Krüger, Burkhard; Fitzner, Brit; Lange, Falko; Bock, Cristin N.; Nizze, Horst; Ibrahim, Saleh M.; Fuellen, Georg; Wolkenhauer, Olaf; Jaster, Robert

    2014-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of acute pancreatitis (AP) for many years but experimental evidence is still limited. Uncoupling protein 2 (UCP2)-deficient mice are an accepted model of age-related oxidative stress. Here, we have analysed how UCP2 deficiency affects the severity of experimental AP in young and older mice (3 and 12 months old, respectively) triggered by up to 7 injections of the secretagogue cerulein (50 μg/kg body weight) at hourly intervals. Disease severity was assessed at time points from 3 hours to 7 days based on pancreatic histopathology, serum levels of alpha-amylase, intrapancreatic trypsin activation and levels of myeloperoxidase (MPO) in lung and pancreatic tissue. Furthermore, in vitro studies with pancreatic acini were performed. At an age of 3 months, UCP2-/- mice and wild-type (WT) C57BL/6 mice were virtually indistinguishable with respect to disease severity. In contrast, 12 months old UCP2-/- mice developed a more severe pancreatic damage than WT mice at late time points after the induction of AP (24 h and 7 days, respectively), suggesting retarded regeneration. Furthermore, a higher peak level of alpha-amylase activity and gradually increased MPO levels in pancreatic and lung tissue were observed in UCP2-/- mice. Interestingly, intrapancreatic trypsin activities (in vivo studies) and intraacinar trypsin and elastase activation in response to cerulein treatment (in vitro studies) were not enhanced but even diminished in the knockout strain. Finally, UCP2-/- mice displayed a diminished ratio of reduced and oxidized glutathione in serum but no increased ROS levels in pancreatic acini. Together, our data indicate an aggravating effect of UCP2 deficiency on the severity of experimental AP in older but not in young mice. We suggest that increased severity of AP in 12 months old UCP2-/- is caused by an imbalanced inflammatory response but is unrelated to acinar cell functions. PMID:24721982

  8. Circulating Trypanosoma cruzi populations differ from those found in the tissues of the same host during acute experimental infection.

    PubMed

    Lo Presti, M Silvina; Esteves, Blanca H; Moya, Diego; Bazán, P Carolina; Strauss, Mariana; Báez, Alejandra L; Pizzi, Rogelio; Quispe Ricalde, M Antonieta; Valladares, Basilio; Rivarola, H Walter; Paglini-Oliva, Patricia A

    2014-05-01

    We evaluated the presence and distribution of two Trypanosoma cruzi natural isolates in blood, heart, skeletal muscle, liver, and spleen tissues in the acute phase of the experimental infection (35 days postinfection) in order to determine if the populations present in blood were different to those found in the tissues of the same host. Thirty mice were infected with 50 forms of each isolate or with a combination of them. Presence and molecular characterization of the parasites in the host tissues were determined by specific PCR. Cardiac and skeletal muscle alterations were analyzed by histological studies. T. cruzi variability in the host tissues was analyzed through RFLP studies. Both isolates used consisted of a mixture of two T. cruzi lineages. Specific PCRs were positive for most of the samples from the 3 groups analyzed. Cardiac and skeletal muscle sections from the groups infected with one isolate presented mild to moderate inflammatory infiltrates; the group infected with both isolates showed severe inflammatory infiltrates and the presence of amastigote nests in both tissues. Different parasite populations were found in circulation and in the tissues from the same host. These results are important for patients with high probability of mixed infections in endemic areas and contribute to the knowledge of parasite/host interactions. PMID:24560963

  9. Iron and copper accumulation in the brain of coxsackievirus-infected mice exposed to cadmium

    SciTech Connect

    Ilbaeck, N.-G. . E-mail: nils-gunnar.ilback@slv.se; Lindh, U.; Minqin, R.; Friman, G.; Watt, F.

    2006-11-15

    Cadmium (Cd) is a potentially toxic metal widely distributed in the environment and known to cause adverse health effects in humans. During coxsackievirus infection, the concentrations of essential and nonessential trace elements (e.g., iron (Fe), copper (Cu), and Cd) change in different target organs of the infection. Fe and Cu are recognized cofactors in host defence reactions, and Fe is known to be associated with certain pathological conditions of the brain. However, whether nonessential trace elements could influence the balance of essential trace elements in the brain is unknown. In this study the brain Fe, Cu, and Cd contents were measured through inductively coupled plasma mass spectrometry and their distributions determined by nuclear microscopy in the early phase (day 3) of coxsackievirus B3 (CB3) infection in nonexposed and in Cd-exposed female Balb/c mice. In CB3 infection the brain is a well-known target that has not been studied with regard to trace element balance. The brain concentration of Cu compared with that of noninfected control mice was increased by 9% (P<0.05) in infected mice not exposed to Cd and by 10% (not significant) in infected Cd-exposed mice. A similar response was seen for Fe, which in infected Cd-exposed mice, compared to noninfected control mice, tended to increase by 16%. Cu showed an even tissue distribution, whereas Fe was distributed in focal deposits. Changes in Cd concentration in the brain of infected mice were less consistent but evenly distributed. Further studies are needed to define whether the accumulation and distribution of trace elements in the brain have an impact on brain function.

  10. Cardiac Physiologic and Genetic Predictors of Hyperoxia-Induced Acute Lung Injury in Mice

    PubMed Central

    Cho, Hye-Youn; Miller-DeGraff, Laura; Walker, Christopher; Clark, James A.; Myers, Page H.; Rouse, D. Clay; Kleeberger, Steven R.

    2012-01-01

    Exposure of mice to hyperoxia produces pulmonary toxicity similar to acute lung injury/acute respiratory distress syndrome, but little is known about the interactions within the cardiopulmonary system. This study was designed to characterize the cardiopulmonary response to hyperoxia, and to identify candidate susceptibility genes in mice. Electrocardiogram and ventilatory data were recorded continuously from 4 inbred and 29 recombinant inbred strains during 96 hours of hyperoxia (100% oxygen). Genome-wide linkage analysis was performed in 27 recombinant inbred strains against response time indices (TIs) calculated from each cardiac phenotype. Reductions in minute ventilation, heart rate (HR), low-frequency (LF) HR variability (HRV), high-frequency HRV, and total power HRV were found in all mice during hyperoxia exposure, but the lag time before these changes began was strain dependent. Significant (chromosome 9) or suggestive (chromosomes 3 and 5) quantitative trait loci were identified for the HRTI and LFTI. Functional polymorphisms in several candidate susceptibility genes were identified within the quantitative trait loci and were associated with hyperoxia susceptibility. This is the first study to report highly significant interstrain variation in hyperoxia-induced changes in minute ventilation, HR, and HRV, and to identify polymorphisms in candidate susceptibility genes that associate with cardiac responses. Results indicate that changes in HR and LF HRV could be important predictors of subsequent adverse outcome during hyperoxia exposure, specifically the pathogenesis of acute lung injury. Understanding the genetic mechanisms of these responses may have significant diagnostic clinical value. PMID:22052878

  11. Ionizing irradiation induces acute haematopoietic syndrome and gastrointestinal syndrome independently in mice.

    PubMed

    Leibowitz, Brian J; Wei, Liang; Zhang, Lin; Ping, Xiaochun; Epperly, Michael; Greenberger, Joel; Cheng, Tao; Yu, Jian

    2014-01-01

    The role of bone marrow (BM) and BM-derived cells in radiation-induced acute gastrointestinal (GI) syndrome is controversial. Here we use bone marrow transplantation (BMT), total body irradiation (TBI) and abdominal irradiation (ABI) models to demonstrate a very limited, if any, role of BM-derived cells in acute GI injury and recovery. Compared with WT BM recipients, mice receiving BM from radiation-resistant PUMA KO mice show no protection from crypt and villus injury or recovery after 15 or 12 Gy TBI, but have a significant survival benefit at 12 Gy TBI. PUMA KO BM significantly protects donor-derived pan-intestinal haematopoietic (CD45+) and endothelial (CD105+) cells after IR. We further show that PUMA KO BM fails to enhance animal survival or crypt regeneration in radiosensitive p21 KO-recipient mice. These findings clearly separate the effects of radiation on the intestinal epithelium from those on the BM and endothelial cells in dose-dependent acute radiation toxicity. PMID:24637717

  12. Ionizing irradiation induces acute haematopoietic syndrome and gastrointestinal syndrome independently in mice

    PubMed Central

    Leibowitz, Brian J.; Wei, Liang; Zhang, Lin; Ping, Xiaochun; Epperly, Michael; Greenberger, Joel; Cheng, Tao; Yu, Jian

    2015-01-01

    The role of bone marrow (BM) and BM-derived cells in radiation-induced acute gastrointestinal (GI) syndrome is controversial. Here we use bone marrow transplantation (BMT), total body irradiation (TBI) and abdominal irradiation (ABI) models to demonstrate a very limited, if any, role of BM-derived cells in acute GI injury and recovery. Compared with WT BM recipients, mice receiving BM from radiation-resistant PUMA KO mice show no protection from crypt and villus injury or recovery after 15 or 12 Gy TBI, but have a significant survival benefit at 12 Gy TBI. PUMA KO BM significantly protects donor-derived pan-intestinal haematopoietic (CD45 +) and endothelial (CD105 +) cells after IR. We further show that PUMA KO BM fails to enhance animal survival or crypt regeneration in radiosensitive p21 KO-recipient mice. These findings clearly separate the effects of radiation on the intestinal epithelium from those on the BM and endothelial cells in dose-dependent acute radiation toxicity. PMID:24637717

  13. Enteropathogenic Escherichia coli (EPEC) infection in association with acute gastroenteritis in 7 dogs from Saskatchewan.

    PubMed

    Kjaergaard, Astrid B; Carr, Anthony P; Gaunt, M Casey

    2016-09-01

    Seven dogs diagnosed with enteropathogenic Escherichia coli (EPEC) infection in association with acute gastroenteritis are described. Disease severity ranged from mild in adults to fatal disease in young dogs. Enteropathogenic E. coli infection should be considered as a possible differential diagnosis in dogs with diarrhea. PMID:27587889

  14. Development of Chronic and Acute Golden Syrian Hamster Infection Models with Leptospira borgpetersenii serovar Hardjo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The golden Syrian hamster (Mesocricetus auratus) is frequently used as a model to study virulence for several species of Leptospira. Onset of an acute, lethal infection following infection with several pathogenic Leptospira species has been widely adopted for vaccine testing. An important exceptio...

  15. Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection.

    PubMed

    Wang, Kun; Langevin, Stanley; O'Hern, Corey S; Shattuck, Mark D; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G; Kirby, Michael

    2016-01-01

    Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical