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Sample records for chronically infected mice

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

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    Fahad Haroon

    Full Text Available 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.

  2. Sex influence on chronic intestinal inflammation in Helicobacter hepaticus-infected A/JCr mice.

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    Livingston, Robert S; Myles, Mathew H; Livingston, Beth A; Criley, Jennifer M; Franklin, Craig L

    2004-06-01

    Helicobacter hepaticus is a bacterial pathogen of mice that has been reported to cause chronic intestinal inflammation in A/JCr, germfree Swiss Webster, and immunodeficient mice. To the authors' knowledge, the influence of sex on development of chronic intestinal inflammation in H. hepaticus-infected mice has not been investigated. The purposes of the study reported here were to determine whether severity of intestinal inflammation differs between male and female A/JCr mice chronically infected with H. hepaticus and to characterize the mucosal immune response in these mice. The cecum of male and female A/JCr mice infected with H. hepaticus for 1 month and 3 months was objectively evaluated histologically for intestinal disease. Also, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was done to measure interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin 4 (IL-4), IL-10, macrophage inflammatory protein-1alpha (MIP-1alpha), interferon-inducible protein of 10 kDa (IP-10), and monokine induced by gamma interferon (MIG) mRNA values in the cecal tissue of these mice. Significant differences in cecal lesion scores were not present at 1 month after infection. However, infected female mice had significantly up-regulated expression of cecal IL-10, MIP-1alpha, IP-10, and MIG mRNA compared with that in uninfected females, and expression of IL-10 and MIP-1alpha was significantly greater than that detected in infected male mice (P JCr mice, females develop more severe intestinal inflammation than do males, and the chronic mucosal inflammation is polarized toward a Th1 response that is not down-regulated by increased activity of IL-10. We propose that H. hepaticus-infected A/JCr mice will serve as a good animal model with which to study the influence of sex on bacterial-induced mucosal inflammation.

  3. Therapy with bone marrow cells reduces liver alterations in mice chronically infected by Schistosoma mansoni

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    Sheilla Andrade Oliveira; Bruno Solano Freitas Souza; Cada Adriana Guimar(a)es-Ferreira; Elton Sá Barreto; Siane Campos Souza; Luiz Antonio Rodrigues Freitas; Ricardo Ribeiro-dos-Santos; Milena Botelho Pereira Soares

    2008-01-01

    AIM: To investigate the potential of bone marrow mononuclear cells (BM-MCs) in the regeneration of hepatic lesions induced by Schistosoma mansoni (S.mansoni) chronic infection.METHODS: Female mice chronically infected with S.mansoni were treated with BM-MCs obtained from male green fluorescent protein (GFP) transgenic mice by intravenous or intralobular injections. Control mice received injections of saline in similar conditions. Enzyme-linked immunosorbent assay (ELISA) assay for transforming growth factor-beta (TGF-β), polymerase chain reaction (PCR) for GFP DNA, immunofluorescence and morphometric studies were performed.RESULTS: Transplanted GFP+ cells migrated to granuloma areas and reduced the percentage of liver fibrosis. The presence of donor-derived cells was confirmed by Fluorescence in situ hybridization (FISH) analysis for detection of cells bearing Y chromosome and by PCR analysis for detection of GFP DNA. The levels of TGF-β, a cytokine associated with fibrosis deposition, in liver fragments of mice submitted to therapy were reduced. The number of oval cells in liver sections of S.rnansoni-infected mice increased 3-4 fold after transplantation. A partial recovery in albumin expression, which is decreased upon infection with S.mansoni, was found in livers of infected mice after cellular therapy.CONCLUSION: In conclusion, transplanted BMCs migrate to and reduce the damage of chronic fibrotic liver lesions caused by S.mansoni.

  4. Differential spirochetal infectivities to vector ticks of mice chronically infected by the agent of Lyme disease.

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    Shih, C M; L. P. LIU; Spielman, A.

    1995-01-01

    We determined whether the infectivity of the Lyme disease spirochete (Borrelia burgdorferi) to vector ticks varies with the duration of infection in laboratory mice. Thus, noninfected nymphal deer ticks were permitted to feed on two strains of early (2 months after infection) and late (8 months after infection) spirochete-infected mice. The attached ticks were removed from their hosts at specified time intervals and were thereafter examined for spirochetes by direct immunofluorescence microsc...

  5. Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection.

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    Dhungana, Hiramani; Malm, Tarja; Denes, Adam; Valonen, Piia; Wojciechowski, Sara; Magga, Johanna; Savchenko, Ekaterina; Humphreys, Neil; Grencis, Richard; Rothwell, Nancy; Koistinaho, Jari

    2013-10-01

    Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes, and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of Trichuris muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis, and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin-17α and tumor necrosis factor-α levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly.

  6. Effects of chronic methamphetamine exposure on heart function in uninfected and retrovirus-infected mice.

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    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

  7. Induction of depression-related behaviors by reactivation of chronic Toxoplasma gondii infection in mice.

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    Mahmoud, Motamed Elsayed; Ihara, Fumiaki; Fereig, Ragab M; Nishimura, Maki; Nishikawa, Yoshifumi

    2016-02-01

    Although Toxoplasma gondii (T. gondii) infection is relevant to many psychiatric disorders, the fundamental mechanisms of its neurobiological correlation with depression are poorly understood. Here, we show that reactivation of chronic infection by an immunosuppressive regimen caused induction of depressive-like behaviors without obvious sickness symptoms. However, the depression-related behaviors in T. gondii-infected mice, specifically, reduced sucrose preference and increased immobility in the forced-swim test were observed at the reactivation stage, but not in the chronic infection. Interestingly, reactivation of T. gondii was associated with production of interferon-gamma and activation of brain indoleamine 2, 3-dioxygenase, which converts tryptophan to kynurenine and makes it unavailable for serotonin synthesis. Furthermore, serotonin turnover to its major metabolite, 5-hydroxyindoleacetic acid, was also enhanced at the reactivation stage. Thus, enhanced tryptophan catabolic shunt and serotonin turnover may be implicated in development of depressive-like behaviors in mice with reactivated T. gondii. PMID:26554725

  8. Progression of chronic hepatitis and preneoplasia in Helicobacter hepaticus-infected A/JCr mice.

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    Rogers, Arlin B; Boutin, Samuel R; Whary, Mark T; Sundina, Nataliya; Ge, Zhongming; Cormier, Kathleen; Fox, James G

    2004-01-01

    Helicobacter hepaticus infection induces sustained inflammation and carcinoma of the liver in A/JCr mice, and serves as a model of human cancers associated with viral hepatitis and H. pylorichronic gastritis. Here we describe the pathogenesis of premalignant disease in A/JCr mice infected with H. hepaticus. We inoculated dams intragestationally and/or pups postnatally, and evaluated offspring at 3, 6, or 12 months. Mice infected at or before 3 weeks of age, but not at 12 weeks, developed disease. Male mice were most affected, but expressed a bimodal pattern of susceptibility. Males exhibited lobular necrogranulomatous and interface (chronic active) hepatitis, while females usually developed intraportal (chronic persistent) hepatitis. Portal inflammation was slowly progressive, with tertiary lymphoid nodule development by 12 months. Hepatic bacterial load and preneoplastic lesions, including clear and tigroid cell foci of cellular alteration, were correlated with lobular hepatitis severity. No extrahepatic surrogate disease marker reliably predicted individual hepatitis grade. In conclusion, gender and bacterial exposure timing are key determinants of H. hepaticus disease outcomes. Intrahepatic inflammation is driven by local signals characterized by a vigorous but nonsterilizing immune response. Continued study of chronic hepatitis progression may reveal therapeutic targets to reduce the risk of hepatocellular carcinoma.

  9. Salmonella Typhimurium undergoes distinct genetic adaption during chronic infections of mice

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    Søndberg, Emilie; Jelsbak, Lotte

    2016-01-01

    Background Typhoid fever caused by Salmonella enterica serovar Typhi (S. Typhi) is a severe systemic human disease and endemic in regions of the world with poor drinking water quality and sewage treatment facilities. A significant number of patients become asymptomatic life-long carriers of S....... In the current study genetic adaptation during experimental chronic S. Typhimurium infections of mice, an established model of chronic typhoid fever, was probed as an approach for studying the molecular mechanisms of host-adaptation during long-term host-association. Results Individually sequence-tagged wild......, the kdgR-SNP was confirmed to confer selective advantage during chronic infections and constitute a true patho-adaptive mutation. Together, the results provide evidence for rapid genetic adaptation to the host of S. Typhimurium and validate experimental evolution in the context of host infection...

  10. Persistent virus infection despite chronic cytotoxic T-lymphocyte activation in gamma interferon-deficient mice infected with lymphocytic choriomeningitis virus

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    Bartholdy, C; Christensen, Jan Pravsgaard; Wodarz, D;

    2000-01-01

    ). While wild-type mice rapidly cleared the infection, IFN-gamma -/- mice became chronically infected. Virus persistence in the latter mice did not reflect failure to generate cytotoxic T-lymphocyte (CTL) effectors, as an unimpaired primary CTL response was observed. Furthermore, while ex vivo CTL activity...

  11. Salmonella Typhimurium undergoes distinct genetic adaption during chronic infections of mice

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    Søndberg, Emilie; Jelsbak, Lotte

    2016-01-01

    , the kdgR-SNP was confirmed to confer selective advantage during chronic infections and constitute a true patho-adaptive mutation. Together, the results provide evidence for rapid genetic adaptation to the host of S. Typhimurium and validate experimental evolution in the context of host infection......Background Typhoid fever caused by Salmonella enterica serovar Typhi (S. Typhi) is a severe systemic human disease and endemic in regions of the world with poor drinking water quality and sewage treatment facilities. A significant number of patients become asymptomatic life-long carriers of S...... type strains of S. Typhimurium 4/74 were used to establish chronic infections of 129X1/SvJ mice. Over the course of infections, S. Typhimurium bacteria were isolated from feces and from livers and spleens upon termination of the experiment. In all samples dominant clones were identified and select...

  12. Reversibility of cardiac fibrosis in mice chronically infected with Trypanosoma cruzi, under specific chemotherapy

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    Sonia G. Andrade

    1991-06-01

    Full Text Available This investigation was performed to verify the effect of specific chemotherapy (Benznidazole or MK-346 on the inflammatory and fibrotic cardiac alterations in mice chronically infected with the strains 21 SF (Type II and Colombian (Type III of Trypanosoma cruzi. To obtain chronically infected mice, two groups of 100 Swiss mice each, were infected with either the 21 SF or the Colombian strain (2x 10 [raised to the power of] 4 and 5x 10 [raised to the power of] 4 blood forms respectively. The rate of morality in the acute phase was of 80% for both groups. Twenty surviving mice chronically infected with the 21 SF strain and 20 with the Colombian strain were then divided in treated and untreated groups. Excluding those that died during the course of treatment, 14 mice chronically infected with the 21 SF strain and 15 with the Colombian strain were evaluated in the present study. Chemotherapy was performed with Benznidazole (N-benzil-2-nitro-1-imidazolacetamide in the dose of 100mg/k.b.w/day, for 60 days, or with the MK-436(3(1-methyl-5 nitroimidazol-2-yl in two daily doses of 250 mg/k.b.w, for 20 days. Parasitological cure tests were performed (xenodiagnosis, haemoculture, subinovulation of the blood into newborn mice, and serological indirect immunofluorescence test. The treated and untreated mice as well as intact controls were killed at different periods after treatment and the heart were submitted to histopathological study with hematoxilineosin and picrosirius staining; ultrastructural study; collagen immunotyping, fibronectin and laminin identification by immunofluorescence tests. Results: the untreated controls either infected with 21 SF or Colombian strain, showed inflammatory and fibrotic alterations that were mild to moderate with the 21 SF strain and intense with the Colombian strain. Redpicrosirius staining showed bundles of collagen in the interstitial space and around cardiac fibers. Increased deposits of mitritial components and

  13. PD-1 blockade in chronically HIV-1-infected humanized mice suppresses viral loads.

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    Edward Seung

    Full Text Available An estimated 34 million people are living with HIV worldwide (UNAIDS, 2012, with the number of infected persons rising every year. Increases in HIV prevalence have resulted not only from new infections, but also from increases in the survival of HIV-infected persons produced by effective anti-retroviral therapies. Augmentation of anti-viral immune responses may be able to further increase the survival of HIV-infected persons. One strategy to augment these responses is to reinvigorate exhausted anti-HIV immune cells present in chronically infected persons. The PD-1-PD-L1 pathway has been implicated in the exhaustion of virus-specific T cells during chronic HIV infection. Inhibition of PD-1 signaling using blocking anti-PD-1 antibodies has been shown to reduce simian immunodeficiency virus (SIV loads in monkeys. We now show that PD-1 blockade can improve control of HIV replication in vivo in an animal model. BLT (Bone marrow-Liver-Thymus humanized mice chronically infected with HIV-1 were treated with an anti-PD-1 antibody over a 10-day period. The PD-1 blockade resulted in a very significant 45-fold reduction in HIV viral loads in humanized mice with high CD8(+ T cell expression of PD-1, compared to controls at 4 weeks post-treatment. The anti-PD-1 antibody treatment also resulted in a significant increase in CD8(+ T cells. PD-1 blockade did not affect T cell expression of other inhibitory receptors co-expressed with PD-1, including CD244, CD160 and LAG-3, and did not appear to affect virus-specific humoral immune responses. These data demonstrate that inhibiting PD-1 signaling can reduce HIV viral loads in vivo in the humanized BLT mouse model, suggesting that blockade of the PD-1-PD-L1 pathway may have therapeutic potential in the treatment of patients already infected with the AIDS virus.

  14. Besnoitia besnoiti infection in cattle and mice: ultrastructural pathology in acute and chronic besnoitiosis.

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    Langenmayer, M C; Gollnick, N S; Scharr, J C; Schares, G; Herrmann, D C; Majzoub-Altweck, M; Hermanns, W

    2015-03-01

    Current knowledge on bovine besnoitiosis, caused by the emerging apicomplexan pathogen Besnoitia besnoiti, is still fragmentary. So far, studies dealing with ultrastructural pathology focused mainly on the easily accessible chronic stage, whereas ultrastructural investigations of tachyzoites were confined to in vitro studies. In the study presented here, the ultrastructural pathology of naturally B. besnoiti-infected cattle in the acute and chronic disease stages and experimentally B. besnoiti-infected mice was monitored. Further, the ultrastructure of tachyzoites and bradyzoites was investigated. Skin samples of two adult Limousin cows and one adult Limousin bull naturally infected with B. besnoiti and liver and skin samples of gamma-interferon knockout mice infected with B. besnoiti were examined in semithin sections stained with toluidine blue and safranin and in ultrathin sections contrasted with uranyl acetate and lead citrate. Samples of vessel walls of the bull and nasal mucosa of one cow were examined by scanning electron microscopy. Few tachyzoites-like endozoites were detected for the first time in bovine skin, and large numbers of tachyzoites were detected in murine skin and liver. Within tissue cysts in bovine skin, numerous bradyzoites were observed displaying signs of degeneration. Tachyzoites had apicomplexan endozoite ultrastructure. B. besnoiti tachyzoites and bradyzoites differed in shape and the number of amylopectin granules. Transmission and scanning electron microscopy confirmed the presence of two different cyst wall layers, and the present results on cyst wall ultrastructure were in accordance with those previously obtained by histological sections.

  15. Recrudescence induced by cyclophosphamide of chronic Trypanosoma cruzi infection in mice is influenced by the parasite strain

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    Maria Elizabeth S Pereira

    1996-02-01

    Full Text Available Reactivation of chronic chagasic patients may occur upon use of immunosuppressive drugs related to kidney or heart transplantation or when they are affected by concomitant HIV infection. This recrudescence, however, does not occur in all chagasic patients exposed to immunosuppressive agents. We therefore investigated the influence of Trypanosoma cruzi strains in the recrudescence of the parasitism in mice at the chronic phase treated with cyclophosphamide, an immunosuppressor that blocks lymphocytes DNA synthesis and therefore controls B cells response. A large variation was detected in the percentages of newly established acute phases in the groups of mice inoculated with the different strains. We suggest that reactivation of chronic T. cruzi infections is influenced by the parasite intrinsic characteristics, a phenomenon that might occur in the human disease.

  16. Immune Responses of Specific-Pathogen-Free Mice to Chronic Helicobacter pylori (Strain SS1) Infection

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    Ferrero, Richard L.; Thiberge, Jean-Michel; Huerre, Michel; Labigne, Agnès

    1998-01-01

    A model permitting the establishment of persistent Helicobacter pylori infection in mice was recently described. To evaluate murine immune responses to H. pylori infection, specific-pathogen-free Swiss mice (n = 50) were intragastrically inoculated with 1.2 × 107 CFU of a mouse-adapted H. pylori isolate (strain SS1). Control animals (n = 10) received sterile broth medium alone. Animals were sacrificed at various times, from 3 days to 16 weeks postinoculation (p.i.). Quantitative culture of ga...

  17. Experimental toxoplasmosis in Balb/c mice. Prevention of vertical disease transmission by treatment and reproductive failure in chronic infection

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    B Fux

    2000-01-01

    Full Text Available In a study of congenital transmission during acute infection of Toxoplasma gondii, 23 pregnant Balb/c mice were inoculated orally with two cysts each of the P strain. Eight mice were inoculated 6-11 days after becoming pregnant (Group 1. Eight mice inoculated on the 10th-15th day of pregnancy (Group 2 were treated with 100 mg/kg/day of minocycline 48 h after inoculation. Seven mice inoculated on the 10th-15th day of pregnancy were not treated and served as a control (Group 3. Congenital transmission was evaluated through direct examination of the brains of the pups or by bioassay and serologic tests. Congenital transmission was observed in 20 (60.6% of the 33 pups of Group 1, in one (3.6% of the 28 pups of Group 2, and in 13 (54.2% of the 24 pups of Group 3. Forty-nine Balb/c mice were examined in the study of congenital transmission of T. gondii during chronic infection. The females showed reproductive problems during this phase of infection. It was observed accentuated hypertrophy of the endometrium and myometrium. Only two of the females gave birth. Our results demonstrate that Balb/c mice with acute toxoplasmosis can be used as a model for studies of congenital T. gondii infection. Our observations indicate the potential of this model for testing new chemotherapeutic agents against congenital toxoplasmosis.

  18. Chronic Pseudomonas aeruginosa lung infection is more severe in Th2 responding BALB/c mice compared to Th1 responding C3H/HeN mice

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    Moser, C; Johansen, H K; Song, Z;

    1997-01-01

    The chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) is characterized by a pronounced antibody response and microcolonies surrounded by numerous polymorphonuclear neutrophils (PMN). Poor prognosis is correlated with a high antibody response to P. aeruginosa antigens. An animal...... model of this infection was established in two strains of mice: C3H/HeN and BALB/c, generally known as Th1 and Th2 responders, respectively, which were challenged with alginate-embedded P. aeruginosa. Mortality was significantly lower in C3H/HeN compared to BALB/c mice (p P. aeruginosa...... was cleared more efficiently in C3H/HeN mice and significantly more C3H/HeN mice showed normal lung histopathology (p P. aeruginosa antigen and concanavalin A-stimulated spleen cells...

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

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    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

  20. Hepatitis E virus genotype three infection of human liver chimeric mice as a model for chronic HEV infection

    NARCIS (Netherlands)

    M.D.B. van de Garde (Martijn); S.D. Pas (Suzan); G. van der Net (Guido); R.A. de Man (Robert); A.D.M.E. Osterhaus (Albert); B.L. Haagmans (Bart); A. Boonstra (Andre); T. Vanwolleghem (Thomas)

    2016-01-01

    textabstractGenotype (gt) 3 hepatitis E virus (HEV) infections are emerging in Western countries. Immunosuppressed patients are at risk of chronic HEV infection and progressive liver damage, but no adequate model system currently mimics this disease course. Here we explore the possibilities of in vi

  1. Chronic Schistosoma japonicum infection reduces immune response to vaccine against hepatitis B in mice.

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    Lin Chen

    Full Text Available BACKGROUND: Hepatitis B and schistosomiasis are most prevalent in Africa and Asia, and co-infections of both are frequent in these areas. The immunomodulation reported to be induced by schistosome infections might restrict immune control of hepatitis B virus (HBV leading to more severe viral infection. Vaccination is the most effective measure to control and prevent HBV infection, but there is evidence for a reduced immune response to the vaccine in patients with chronic schistosomiasis japonica. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we demonstrate in a mouse model that a chronic Schistosoma japonicum infection can inhibit the immune response to hepatitis B vaccine (HBV vaccine and lead to lower production of anti-HBs antibodies, interferon-γ (IFN-γ and interleukin-2 (IL-2. After deworming with Praziquantel (PZQ, the level of anti-HBs antibodies gradually increased and the Th2-biased profile slowly tapered. At 16 weeks after deworming, the levels of anti-HBs antibodies and Th1/Th2 cytokines returned to the normal levels. CONCLUSIONS/SIGNIFICANCE: The results suggest that the preexisting Th2-dominated immune profile in the host infected with the parasite may down-regulate levels of anti-HBs antibodies and Th1 cytokines. To improve the efficacy of HBV vaccination in schistosome infected humans it may be valuable to treat them with praziquantel (PZQ some time prior to HBV vaccination.

  2. Cytokine and surface receptor diversity of NK cells in resistant C3H/HeN and susceptible BALB/c mice with chronic Pseudomonas aeruginosa lung infection

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    Calum, Henrik; Moser, Claus; Jensen, Peter Østrup;

    2003-01-01

    infection in cystic fibrosis. Lung cell suspensions were depleted of lymphocytes by magnetic cell sorting. The concentrations of IFN-gamma, IL-1beta and GM-CSF were estimated by ELISA at day 1 and 2 after infection. Non-infected mice were used as controls. Flow cytometry was used to estimate the surface...... expression of Fc receptors was significantly lower on NK cells in C3H/HeN mice at day 1 and 2. In conclusion, the present results show phenotypic differences in NK cells in the two mice strains in chronic P. aeruginosa lung infection, indicating different modulating effects in the Th1/Th2 balance....

  3. Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response

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    Moser, C; Hougen, H P; Song, Z;

    1999-01-01

    Most cystic fibrosis (CF) patients become chronically infected with Pseudomonas aeruginosa in the lungs. The infection is characterized by a pronounced antibody response and a persistant inflammation dominated by polymorphonuclear neutrophils. Moreover a high antibody response correlates...... with a poor prognosis. We speculated that a change from this Th2-like response to a Th1-like response might decrease the lung inflammation and thus improve the prognosis in CF patients. To investigate this, we infected C3H/HeN and BALB/c mice intratracheally with P. aeruginosa. In addition, we studied...... with chronic P. aeruginosa lung infection have a better disease outcome compared to the Th2-reacting BALB/c mice, indicating that a Th1 response might be beneficial in CF patients with chronic P. aeruginosa lung infection....

  4. Loss of the TGFβ-activating integrin αvβ8 on dendritic cells protects mice from chronic intestinal parasitic infection via control of type 2 immunity.

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    John J Worthington

    Full Text Available Chronic intestinal parasite infection is a major global health problem, but mechanisms that promote chronicity are poorly understood. Here we describe a novel cellular and molecular pathway involved in the development of chronic intestinal parasite infection. We show that, early during development of chronic infection with the murine intestinal parasite Trichuris muris, TGFβ signalling in CD4+ T-cells is induced and that antibody-mediated inhibition of TGFβ function results in protection from infection. Mechanistically, we find that enhanced TGFβ signalling in CD4+ T-cells during infection involves expression of the TGFβ-activating integrin αvβ8 by dendritic cells (DCs, which we have previously shown is highly expressed by a subset of DCs in the intestine. Importantly, mice lacking integrin αvβ8 on DCs were completely resistant to chronic infection with T. muris, indicating an important functional role for integrin αvβ8-mediated TGFβ activation in promoting chronic infection. Protection from infection was dependent on CD4+ T-cells, but appeared independent of Foxp3+ Tregs. Instead, mice lacking integrin αvβ8 expression on DCs displayed an early increase in production of the protective type 2 cytokine IL-13 by CD4+ T-cells, and inhibition of this increase by crossing mice to IL-4 knockout mice restored parasite infection. Our results therefore provide novel insights into how type 2 immunity is controlled in the intestine, and may help contribute to development of new therapies aimed at promoting expulsion of gut helminths.

  5. Minocycline attenuates HIV-1 infection and suppresses chronic immune activation in humanized NOD/LtsZ-scidIL-2Rγnull mice

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    Singh, Maneesh; Singh, Pratibha; Vaira, Dolores; Amand, Mathieu; Rahmouni, Souad; Moutschen, Michel

    2014-01-01

    More than a quarter of a century of research has established chronic immune activation and dysfunctional T cells as central features of chronic HIV infection and subsequent immunodeficiency. Consequently, the search for a new immunomodulatory therapy that could reduce immune activation and improve T-cell function has been increased. However, the lack of small animal models for in vivo HIV study has hampered progress. In the current study, we have investigated a model of cord blood haematopoietic progenitor cells (CB-HPCs) -transplanted humanized NOD/LtsZ-scidIL-2Rγnull mice in which progression of HIV infection is associated with widespread chronic immune activation and inflammation. Indeed, HIV infection in humanized NSG mice caused up-regulation of several T-cell immune activation markers such as CD38, HLA-DR, CD69 and co-receptor CCR5. T-cell exhaustion markers PD-1 and CTLA-4 were found to be significantly up-regulated on T cells. Moreover, increased plasmatic levels of lipopolysaccharide, sCD14 and interleukin-10 were also observed in infected mice. Treatment with minocycline resulted in a significant decrease of expression of cellular and plasma immune activation markers, inhibition of HIV replication and improved T-cell counts in HIV-infected humanized NSG mice. The study demonstrates that minocycline could be an effective, low-cost adjunctive treatment to regulate chronic immune activation and replication of HIV. PMID:24409837

  6. Chronic proliferative hepatitis in A/JCr mice associated with persistent Helicobacter hepaticus infection: a model of helicobacter-induced carcinogenesis.

    Science.gov (United States)

    Fox, J G; Li, X; Yan, L; Cahill, R J; Hurley, R; Lewis, R; Murphy, J C

    1996-05-01

    Helicobacter hepaticus causes hepatitis in selected strains of mice and in A/JCr mice is linked to liver cancer. To analyze whether H. hepaticus persists in specified ecological niches, to determine whether biomarkers of infection exist, and to analyze the influence of H. hepaticus on hepatocyte proliferation, a longitudinal study of H. hepaticus-infected A/JCr mice was undertaken. A/JCr mice were serially euthanatized from 3 through 18 months and surveyed by enzyme-linked immunosorbent assay; bacterial culture of liver, colon, and cecum; histology; electron microscopy; hepatocyte proliferation indices determined by using 5-bromo-2'-deoxyuridine; and measurement of the liver enzyme alanine aminotransferase. In infected animals throughout the 18-month study, H. hepaticus was consistently isolated from the lower bowel but only sporadically from the liver. By electron microscopy, H. hepaticus was noted infrequently and only in bile canaliculi. Infected mice, particularly males, showed chronic inflammation; oval cell, Kupffer cell, and Ito cell hyperplasia; hepatocytomegaly; and bile duct proliferation. The inflammatory and necrotizing lesion was progressive and involved the hepatic parenchyma, portal triads, and intralobular venules. Hepatic adenomas were noted only in male mice, whereas 5-bromo-2'-deoxyuridine proliferation indices were markedly increased in both sexes, but especially in males, compared to control A/J mice. Infected mice also developed sustained anti-H. hepaticus serum immunoglobulin G antibody responses and elevated alanine aminotransferase levels. H. hepaticus, which persists in the lower bowels and livers of A/JCr mice, is associated with a chronic proliferative hepatitis, and hepatomas in selected male mice indicate that this novel bacterium may cause an increased risk of hepatic cancer induction in susceptible strains of mice. This murine model should prove useful in dissecting the molecular events operable in the development of neoplasms

  7. iNOS-producing inflammatory dendritic cells constitute the major infected cell type during the chronic Leishmania major infection phase of C57BL/6 resistant mice.

    Directory of Open Access Journals (Sweden)

    Carl De Trez

    2009-06-01

    Full Text Available Leishmania major parasites reside and multiply in late endosomal compartments of host phagocytic cells. Immune control of Leishmania growth absolutely requires expression of inducible Nitric Oxide Synthase (iNOS/NOS2 and subsequent production of NO. Here, we show that CD11b+ CD11c+ Ly-6C+ MHC-II+ cells are the main iNOS-producing cells in the footpad lesion and in the draining lymph node of Leishmania major-infected C57BL/6 mice. These cells are phenotypically similar to iNOS-producing inflammatory DC (iNOS-DC observed in the mouse models of Listeria monocytogenes and Brucella melitensis infection. The use of DsRed-expressing parasites demonstrated that these iNOS-producing cells are the major infected population in the lesions and the draining lymph nodes. Analysis of various genetically deficient mouse strains revealed the requirement of CCR2 expression for the recruitment of iNOS-DC in the draining lymph nodes, whereas their activation is strongly dependent on CD40, IL-12, IFN-gamma and MyD88 molecules with a partial contribution of TNF-alpha and TLR9. In contrast, STAT-6 deficiency enhanced iNOS-DC recruitment and activation in susceptible BALB/c mice, demonstrating a key role for IL-4 and IL-13 as negative regulators. Taken together, our results suggest that iNOS-DC represent a major class of Th1-regulated effector cell population and constitute the most frequent infected cell type during chronic Leishmania major infection phase of C57BL/6 resistant mice.

  8. Mice chronically infected with chimeric HIV resist peripheral and brain superinfection: a model of protective immunity to HIV.

    Science.gov (United States)

    Kelschenbach, Jennifer L; Saini, Manisha; Hadas, Eran; Gu, Chao-Jiang; Chao, Wei; Bentsman, Galina; Hong, Jessie P; Hanke, Tomas; Sharer, Leroy R; Potash, Mary Jane; Volsky, David J

    2012-06-01

    Infection by some viruses induces immunity to reinfection, providing a means to identify protective epitopes. To investigate resistance to reinfection in an animal model of HIV disease and its control, we employed infection of mice with chimeric HIV, EcoHIV. When immunocompetent mice were infected by intraperitoneal (IP) injection of EcoHIV, they resisted subsequent secondary infection by IP injection, consistent with a systemic antiviral immune response. To investigate the potential role of these responses in restricting neurotropic HIV infection, we established a protocol for efficient EcoHIV expression in the brain following intracranial (IC) inoculation of virus. When mice were inoculated by IP injection and secondarily by IC injection, they also controlled EcoHIV replication in the brain. To investigate their role in EcoHIV antiviral responses, CD8+ T lymphocytes were isolated from spleens of EcoHIV infected and uninfected mice and adoptively transferred to isogenic recipients. Recipients of EcoHIV primed CD8+ cells resisted subsequent EcoHIV infection compared to recipients of cells from uninfected donors. CD8+ spleen cells from EcoHIV-infected mice also mounted modest but significant interferon-γ responses to two HIV Gag peptide pools. These findings suggest EcoHIV-infected mice may serve as a useful system to investigate the induction of anti-HIV protective immunity for eventual translation to human beings.

  9. Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human liver-chimeric mice from infection with a homologous hepatitis C virus strain

    DEFF Research Database (Denmark)

    Vanwolleghem, Thomas; Bukh, Jens; Meuleman, Philip;

    2008-01-01

    G can prevent a de novo HCV infection in vivo and contribute to the control of viremia in infected individuals. We addressed this question with homologous in vivo protection studies in human liver-urokinase-type plasminogen activator (uPA)(+/+) severe combined immune deficient (SCID) mice. Chimeric mice...... were loaded with chronic phase polyclonal IgG and challenged 3 days later with a 100% infectious dose of the acute phase H77C virus, both originating from patient H. Passive immunization induced sterilizing immunity in five of eight challenged animals. In the three nonprotected animals, the HCV...... infection was attenuated, as evidenced by altered viral kinetics in comparison with five control IgG-treated animals. Plasma samples obtained from the mice at viral challenge neutralized H77C-HCVpp at dilutions as high as 1/400. Infection was completely prevented when, before administration to naïve...

  10. Effect of recombinant human interleukin-2 on the course of experimental chronic respiratory tract infection caused by Klebsiella pneumoniae in mice.

    OpenAIRE

    Iizawa, Y; Nishi, T; Kondo, M.; Tsuchiya, K.; Imada, A

    1988-01-01

    The effect of recombinant human interleukin-2 (rIL-2) on the course of experimental chronic respiratory tract infection caused by Klebsiella pneumoniae in mice was examined. rIL-2 was administered subcutaneously once a day for 7 or 14 days, starting 2 weeks after the mice were infected. Administration of 2 or 20 micrograms of rIL-2 per mouse daily for 7 days reduced bacterial counts in the lungs dose dependently. At a dose of 0.2 microgram per day, proliferation of bacteria in the lungs was s...

  11. Treatment of chronically Trypanosoma cruzi-infected mice with a CCR1/CCR5 antagonist (Met-RANTES) results in amelioration of cardiac tissue damage.

    Science.gov (United States)

    Medeiros, Gabriela A; Silvério, Jaline C; Marino, Ana Paula M P; Roffê, Ester; Vieira, Valeska; Kroll-Palhares, Karina; Carvalho, Cristiano E; Silva, Andréa Alice; Teixeira, Mauro M; Lannes-Vieira, Joseli

    2009-02-01

    The comprehension of the molecular mechanisms leading to Trypanosoma cruzi-elicited heart dysfunction might contribute to design novel therapeutic strategies aiming to ameliorate chronic Chagas disease cardiomyopathy. In C3H/He mice infected with the low virulence T. cruzi Colombian strain, the persistent cardiac inflammation composed mainly of CCR5(+) T lymphocytes parallels the expression of CC-chemokines in a pro-inflammatory IFN-gamma and TNF-alpha milieu. The chronic myocarditis is accompanied by increased frequency of peripheral CCR5(+)LFA-1(+) T lymphocytes. The treatment of chronically T. cruzi-infected mice with Met-RANTES, a selective CCR1/CCR5 antagonist, led to a 20-30% decrease in CD4(+) cell numbers as well as IL-10, IL-13 and TNF-alpha expression. Further, Met-RANTES administration impaired the re-compartmentalization of the activated CD4(+)CCR5(+) lymphocytes. Importantly, Met-RANTES treatment resulted in significant reduction in parasite load and fibronectin deposition in the heart tissue. Moreover, Met-RANTES treatment significantly protected T. cruzi-infected mice against connexin 43 loss in heart tissue and CK-MB level enhancement, markers of heart dysfunction. Thus, our results corroborate that therapeutic strategies based on the modulation of CCR1/CCR5-mediated cell migration and/or effector function may contribute to cardiac tissue damage limitation during chronic Chagas disease.

  12. Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance.

    Directory of Open Access Journals (Sweden)

    Ashley Houlden

    Full Text Available Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm is an ideal model for this disease. This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. Communities were profiled using DGGE, 454 pyrosequencing, and metabolomics. Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. These data indicate that the changes in microbiota as a consequence of infection were transitory requiring the presence of the pathogen for maintenance. Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation.

  13. 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▿

    OpenAIRE

    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 cys...

  14. The conduction system of the heart in mice chronically infected with Trypanosoma cruzi: histopathological lesions and electrocardiographic correlations

    Directory of Open Access Journals (Sweden)

    Sonia G. Andrade

    1987-03-01

    Full Text Available Chronic focal and diffuse myiocarditis with interstitial fibrosis developed in Swiss outbred mice and in the inbred AKR and A/J strains of mice which were chronically infected with several Trypanosoma cruzi strains belonging to three biological types (Type I, II and III. High incidence of electrocardiographic changes with predominance of intraventricular conduction disturbances, 1st. and 2nd. degree AV block, arrhythmias, comparable with those found in human Chagas' disease, were also present. Morphological study of the conduction tissue of the heart revealed inflammatory and fibrotic changes. The presence of inflammation in the inter-atrial septum almost always coincided with the inflammatory involvement of the ventricular conduction system. Focal inflammation was associated with vacuolization and focal necrosis of the specific fibers. Most of the lesions were seen affecting the His bundel (76.3% of the cases, the right bundle branch (73.3%, AV node (43.9% and left bundle branch (37.5%. Correlation between morphological changes in the conduction tissue and electrocardiographic alteration occured in 53.0 to 62.5% of the cases, according to the experimental groups.Em camundongos suiços não isogênicos e em camundongos isogênicos das linhagens AKR e A/J, cronicamente infectados com cepas do Trypanosoma cruzi representativas de três tipos biológicos (Tipos I, II e III foi observada uma miocardite crônica difusa e focal com graus variáveis de fibrose intersticial. Observou-se alta incidência de alterações eletrocardiográficas com predominância de distúrbios da condução intraventricular, bloqueios A-V de 1º e 2º graus e arritmias, comparáveis às encontradas na doença de Chagas humana. O estudo histopatológico do sistema de condução do coração mostrou alterações inflamatórias e fibróticas. A presença de inflamação no septo inter-atrial em geral coincidiu com o envolvimento do sistema de condução pelo processo inflamat

  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▿

    Science.gov (United States)

    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.

    Science.gov (United States)

    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. Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses

    International Nuclear Information System (INIS)

    Persistent exposure to inorganic lead (Pb) is known to adversely affect the immune system. In the present study, we assessed the effect of chronic Pb exposure on susceptibility to infection by the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in drinking water for ∼ 16 weeks, resulting in a significant level of Pb in the blood (106.2 ± 8.9 μg/dl). Pb exposure rendered mice susceptible to Salmonella infection, manifested by increased bacterial burden in target organs and heightened mortality. Flow cytometric analysis of the splenic cellular composition in normal and Pb-exposed mice revealed no gross alteration in the ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and T cells to upregulate the expression of activation antigens in response to mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a marked reduction in IFN-γ and IL-12p40 production associated with Pb exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3- to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4 correlated with a shift in the in vivo anti-Salmonella antibody response from the protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that chronic exposure to high levels of Pb results in a state of immunodeficiency which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather is largely caused by a shift in immune responsiveness to Th2-type reactions

  18. EBV CHRONIC INFECTIONS

    Directory of Open Access Journals (Sweden)

    Delia Racciatti

    2010-02-01

    Full Text Available

    The infection from Epstein-Barr virus (EBV or virus of infectious mononucleosis, together with other herpesviruses’ infections, represents a prototype of persistent viral infections characterized by the property of the latency. Although the reactivations of the latent infection are associated with the resumption of the viral replication and eventually with the “shedding”, it is still not clear if this virus can determine chronic infectious diseases, more or less evolutive. These diseases could include some pathological conditions actually defined as “idiopathic”and characterized by the “viral persistence” as the more credible pathogenetic factor. Among the so-called idiopathic syndromes, the “chronic fatigue syndrome” (CFS aroused a great interest around the eighties of the last century when, just for its relationship with EBV, it was called “chronic mononucleosis” or “chronic EBV infection”.

    Today CFS, as defined in 1994 by the CDC of Atlanta (USA, really represents a multifactorial syndrome characterized by a chronic course, where reactivation and remission phases

  19. The duration of Chlamydia muridarum genital tract infection and associated chronic pathological changes are reduced in IL-17 knockout mice but protection is not increased further by immunization.

    Directory of Open Access Journals (Sweden)

    Dean W Andrew

    Full Text Available IL-17 is believed to be important for protection against extracellular pathogens, where clearance is dependent on neutrophil recruitment and local activation of epithelial cell defences. However, the role of IL-17 in protection against intracellular pathogens such as Chlamydia is less clear. We have compared (i the course of natural genital tract C. muridarum infection, (ii the development of oviduct pathology and (iii the development of vaccine-induced immunity against infection in wild type (WT BALB/c and IL-17 knockout mice (IL-17-/- to determine if IL-17-mediated immunity is implicated in the development of infection-induced pathology and/or protection. Both the magnitude and duration of genital infection was significantly reduced in IL-17-/- mice compared to BALB/c. Similarly, hydrosalpinx was also greatly reduced in IL-17-/- mice and this correlated with reduced neutrophil and macrophage infiltration of oviduct tissues. Matrix metalloproteinase (MMP 9 and MMP2 were increased in WT oviducts compared to IL-17-/- animals at day 7 post-infection. In contrast, oviducts from IL-17-/- mice contained higher MMP9 and MMP2 at day 21. Infection also elicited higher levels of Chlamydia-neutralizing antibody in serum of IL-17-/- mice than WT mice. Following intranasal immunization with C. muridarumMajor Outer Membrane Protein (MOMP and cholera toxin plus CpG adjuvants, significantly higher levels of chlamydial MOMP-specific IgG and IgA were found in serum and vaginal washes of IL-17-/- mice. T cell proliferation and IFNγ production by splenocytes was greater in WT animals following in vitro re-stimulation, however vaccination was only effective at reducing infection in WT, not IL-17-/- mice. Intranasal or transcutaneous immunization protected WT but not IL-17-/- mice against hydrosalpinx development. Our data show that in the absence of IL-17, the severity of C. muridarum genital infection and associated oviduct pathology are significantly attenuated

  20. The duration of Chlamydia muridarum genital tract infection and associated chronic pathological changes are reduced in IL-17 knockout mice but protection is not increased further by immunization.

    Science.gov (United States)

    Andrew, Dean W; Cochrane, Melanie; Schripsema, Justin H; Ramsey, Kyle H; Dando, Samantha J; O'Meara, Connor P; Timms, Peter; Beagley, Kenneth W

    2013-01-01

    IL-17 is believed to be important for protection against extracellular pathogens, where clearance is dependent on neutrophil recruitment and local activation of epithelial cell defences. However, the role of IL-17 in protection against intracellular pathogens such as Chlamydia is less clear. We have compared (i) the course of natural genital tract C. muridarum infection, (ii) the development of oviduct pathology and (iii) the development of vaccine-induced immunity against infection in wild type (WT) BALB/c and IL-17 knockout mice (IL-17-/-) to determine if IL-17-mediated immunity is implicated in the development of infection-induced pathology and/or protection. Both the magnitude and duration of genital infection was significantly reduced in IL-17-/- mice compared to BALB/c. Similarly, hydrosalpinx was also greatly reduced in IL-17-/- mice and this correlated with reduced neutrophil and macrophage infiltration of oviduct tissues. Matrix metalloproteinase (MMP) 9 and MMP2 were increased in WT oviducts compared to IL-17-/- animals at day 7 post-infection. In contrast, oviducts from IL-17-/- mice contained higher MMP9 and MMP2 at day 21. Infection also elicited higher levels of Chlamydia-neutralizing antibody in serum of IL-17-/- mice than WT mice. Following intranasal immunization with C. muridarumMajor Outer Membrane Protein (MOMP) and cholera toxin plus CpG adjuvants, significantly higher levels of chlamydial MOMP-specific IgG and IgA were found in serum and vaginal washes of IL-17-/- mice. T cell proliferation and IFNγ production by splenocytes was greater in WT animals following in vitro re-stimulation, however vaccination was only effective at reducing infection in WT, not IL-17-/- mice. Intranasal or transcutaneous immunization protected WT but not IL-17-/- mice against hydrosalpinx development. Our data show that in the absence of IL-17, the severity of C. muridarum genital infection and associated oviduct pathology are significantly attenuated, however

  1. Therapeutic Vaccines for Chronic Infections

    Science.gov (United States)

    Autran, Brigitte; Carcelain, Guislaine; Combadiere, Béhazine; Debre, Patrice

    2004-07-01

    Therapeutic vaccines aim to prevent severe complications of a chronic infection by reinforcing host defenses when some immune control, albeit insufficient, can already be demonstrated and when a conventional antimicrobial therapy either is not available or has limited efficacy. We focus on the rationale and challenges behind this still controversial strategy and provide examples from three major chronic infectious diseases-human immunodeficiency virus, hepatitis B virus, and human papillomavirus-for which the efficacy of therapeutic vaccines is currently being evaluated.

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

    Science.gov (United States)

    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

  3. Chronic Infection and Severe Asthma.

    Science.gov (United States)

    Carr, Tara F; Kraft, Monica

    2016-08-01

    Chronic bacterial infection is implicated in both the development and severity of asthma. The atypical bacteria Mycoplasma pneumoniae and Chlamydophila pneumoniae have been identified in the airways of asthmatics and correlated with clinical features such as adult onset, exacerbation risks, steroid sensitivity, and symptom control. Asthmatic patients with evidence of bacterial infection may benefit from antibiotic treatment directed towards these atypical organisms. Examination of the airway microbiome may identify microbial communities that confer risk for or protection from severe asthma. PMID:27401621

  4. Influence of long-term cadmium and selenite exposure on resistance to Listeria monocytogenes during acute and chronic infection in mice

    OpenAIRE

    Šimonytė, Sandrita; Plančiūnienė, Rita; Cherkashin, Gennadij; žekonis, Gediminas

    2006-01-01

    The aim of the present study was to evaluate the effect of long-term exposure to cadmium and selenite ions on the BALB/c mice resistance to experimental Listeria monocytogenes infection. A low-dose six-week exposure to cadmium ions (10 mg/ l in drinking water) decreased the clearance of listeria from mice liver and spleen at 24 h in the early phase of infection. Long-term treatment of mouse with selenite ions (0.15 mg/l) did not activate the elimination of bacteria from the organs. Eight week...

  5. Evolution of subpatent parasitaemia in Trypanosoma cruzi chronically infected mice with the help of a cyclophosphamide amplification transfer assay Evolução das parasitemias subpatentes na infecção crônica experimental pelo Trypanosoma cruzi através do ensaio de subinoculação modificado pelo tratamento com ciclofosfamida

    OpenAIRE

    Alvarez, José M.; Ayumi Oshima; Veronica Mozer; Liliane Guimarães; Hércules Menezes

    1991-01-01

    We have evaluated the sensitivity of the classical blood subinoculation method, modified through cyclophosphamide treatment of transferred mice, for the detection of occult parasitaemias in Trypanosoma cruzi chronically infected mice. Besides its simplicity, the method was shown to be highly sensitive for both the "chronic" phase parasites (99% of chronic cases were shown to harbour occult parasitaemias) and for the acute phase parasites (T. cruzi could be detected in 53.8% of animals transfe...

  6. Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response

    DEFF Research Database (Denmark)

    Moser, C; Jensen, P O; Kobayashi, O;

    2002-01-01

    patients, the lungs of susceptible BALB/c mice were re-infected with P. aeruginosa 14 days after the initial infection. Singly-infected BALB/c mice, as well as non-infected mice, were used as controls. Decreased mortality and milder lung inflammation in re-infected BALB/c mice, as well as a tendency......Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF...... production, in chronic P. aeruginosa lung infection in CF....

  7. Mechanisms of recrudescence of Mycobacterium bovis BCG infection in mice.

    OpenAIRE

    Cox, J H; Knight, B. C.; Ivanyi, J.

    1989-01-01

    The capacity of various immunosuppressive agents to cause a recrudescence of the replication of Mycobacterium bovis BCG in the spleens of chronically infected mice was investigated. The actions of three corticosteroid preparations, cyclosporin A, and anti-T-cell subset monoclonal antibodies were compared. Treatment of mice with hydrocortisone acetate, which depressed the number of splenic lymphocytes and suppressed T-cell responses, most effectively exacerbated the stationary BCG counts, at 4...

  8. Hepatic regeneration after partial hepatectomy in mice infected with Schistosoma mansoni, at the acute and chronic phases of the disease Regeneração hepática após hepatectomia parcial em camundongos infectados com Schistosoma mansoni, nas fases aguda e crônica da doença

    OpenAIRE

    Costa, G.(INFN Sezione di Milano, Milan, Italy); J.R. Cunha-Melo; AGUIAR B.G.; Gonçalves, S. C.; TOPPA N.H.; P. M. Z. Coelho

    1999-01-01

    Outbred male albino mice normal or infected with 30 cercariae of Schistosoma mansoni (LE strain) were submitted to 65% hepatectomy during the acute (70 days) and chronic phase (160 days) phases of the disease. A group of the infected animals was treated with 400 mg/kg of oxamniquine during the acute phase before hepatectomy. Non-infected, infected and treated but not hepatectomized animals were kept as controls. Hepatic regeneration was evaluated by incorporation of tritiated thymidine, intra...

  9. Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection

    Science.gov (United States)

    MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

    2015-01-01

    Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies. DOI: http://dx.doi.org/10.7554/eLife.04494.001 PMID:25599590

  10. Rate of red blood cell destruction varies in different strains of mice infected with Plasmodium berghei-ANKA after chronic exposure

    Directory of Open Access Journals (Sweden)

    Kikuchi Mihoko

    2009-05-01

    Full Text Available Abstract Background Severe malaria anaemia in the semi-immune individuals in the holo-endemic area has been observed to occur at low parasite density with individual variation in the responses. Thus the following has been thought to be involved: auto-immune-mediated mechanisms of uninfected red blood cell destruction, and host genetic factors to explain the differences in individual responses under the same malaria transmission. In this study, the extent of red blood cell (RBC destruction in different strains of semi-immune mice model at relatively low parasitaemia was studied. Methodology To generate semi-immunity, four strains of mice were taken through several cycles of infection and treatment. By means of immunofluorescent assay and ELISA, sera were screened for anti-erythrocyte auto-antibodies, and their relationship with haematological parameters and parasitaemia in the strains of semi-immune mice was investigated. Results Upon challenge with Plasmodium berghei ANKA after generating semi-immune status, different mean percentage haemoglobin (Hb drop was observed in the mice strains (Balb/c = 47.1%; NZW = 30.05%; C57BL/6 = 28.44%; CBA = 25.1%, which occurred on different days for each strain (for Balb/c, mean period = 13.6 days; for C57BL/6, NZW, and CBA mean period = 10.6, 10.8, 10.9 days respectively. Binding of antibody to white ghost RBCs was observed in sera of the four strains of semi-immune mice by immunofluorescence. Mean percentage Hb drop per parasitaemia was highest in Balb/c (73.6, followed by C57BL/6 (8.6, CBA (6.9 and NZW (4.0, p = 0.0005. Consequently, auto-antibodies level to ghost RBC were correlated with degree of anaemia and were highest in Balb/c, when compared with the other strains, p Conclusion The results presented in this study seem to indicate that anti-RBC auto-antibodies may be involved in the destruction of uninfected RBC in semi-immune mice at relatively low parasite burden. Host genetic factors may also

  11. Attenuation of the cytotoxic T lymphocyte response to lymphocytic choriomeningitis virus in mice subjected to chronic social stress

    OpenAIRE

    Sommershof, Annette; Basler, Michael; Riether, Carsten; Engler, Harald; Gröttrup, Marcus

    2011-01-01

    Chronic stress is suspected to increase the susceptibility to infections but experimental evidence from physiological stress models is scarce. We examined the effects of chronic social stress on virus-specific CTL responses in mice after infection with lymphocytic choriomeningitis virus (LCMV). Mice subjected to social stress on six consecutive days prior to infection showed a significant reduction of IFN-γ producing TCD8+ splenocytes and markedly lowered plasma concentrations of IFN-γ. In co...

  12. Therapeutic passive vaccination against chronic Lyme disease in mice.

    Science.gov (United States)

    Zhong, W; Stehle, T; Museteanu, C; Siebers, A; Gern, L; Kramer, M; Wallich, R; Simon, M M

    1997-11-11

    Passive and active immunization against outer surface protein A (OspA) has been successful in protecting laboratory animals against subsequent infection with Borrelia burgdorferi. Antibodies (Abs) to OspA convey full protection, but only when they are present at the time of infection. Abs inactivate spirochetes within the tick and block their transmission to mammals, but do not affect established infection because of the loss of OspA in the vertebrate host. Our initial finding that the presence of high serum titers of anti-OspC Abs (5 to 10 microg/ml) correlates with spontaneous resolution of disease and infection in experimentally challenged immunocompetent mice suggested that therapeutic vaccination with OspC may be feasible. We now show that polyclonal and monospecific mouse immune sera to recombinant OspC, but not to OspA, of B. burgdorferi resolve chronic arthritis and carditis and clear disseminated spirochetes in experimentally infected C.B.-17 severe combined immunodeficient mice in a dose-dependent manner. This was verified by macroscopical and microscopical examination of affected tissues and recultivation of spirochetes from ear biopsies. Complete resolution of disease and infection was achieved, independent of whether OspC-specific immune sera (10 microg OspC-specific Abs) were repeatedly given (4x in 3- to 4-day intervals) before the onset (day 10 postinfection) or at the time of fully established arthritis and carditis (days 19 or 60 postinfection). The results indicate that in mice spirochetes constitutively express OspC and are readily susceptible to protective OspC-specific Abs throughout the infection. Thus, an OspC-based vaccine appears to be a candidate for therapy of Lyme disease.

  13. Effect of pre-existing Schistosoma haematobium infection on Plasmodium berghei multiplications in imprinting control region mice

    Institute of Scientific and Technical Information of China (English)

    Benjamin; Amoani; Elvis; Ofori; Ameyaw; Du-Bois; Asante; Francis; Ackah; Armah; James; Prah; Collins; Paa; Kwesi; Botchey; Johnson; Nyarko; Boampong

    2015-01-01

    Objective: To investigate the effect of pre-existing Schistosoma haematobium(S. haematobium) infection on malaria disease severity.Methods: The study involved the use of twenty-i ve imprinting control region mice, i fteen of which were initially infected with S. haematobium. Five of the remaining ten schistouninfected mice together with i ve schisto-infected mice were infected with Plasmodium berghei(P. berghei) after four weeks(acute stage) of schistosoma infection. The remaining i ve schisto-uninfected mice together with i ve schisto-infected mice were also infected with P. berghei after seven weeks(chronic stage) of schistosoma infection. The last i ve schistoinfected mice were used as control group. They were then monitored for changes in P. berghei parasitaemia on Days 3, 5, 7, 9 and 11 post-infection. Records on their survivability were also taken.Results: The co-infected mice had signii cantly higher malaria parasitaemia, compared with the mono-infected mice during acute S. haematobium infection. In contrast, the co-infected mice had signii cantly lower malaria parasitaemia during chronic S. haematobium infection and a higher survival rate.Conclusions: Co-infection of mice with P. berghei during acute S. haematobium infection resulted in rapid P. berghei development and increased malaria parasitaemia. However, the co-infection resulted in slower P. berghei development and decreased malaria parasitaemia with enhanced survivability of the mice during chronic S. haematobium infection. Therefore, pre-existing chronic S. haematobium infection may provide some protection to the host by reducing parasitaemia.

  14. Helicobacter Infection and Chronic Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    Zhao-chun Chi; Xin-juan Yu; Quan-jiang Dong

    2014-01-01

    This paper reviews the recentHelicobacter infection associated with chronic liver disease. The bacteriology, prevalence, pathogenesis and diagnosis were reviewed. Future work should be conducted on the pathogenesis and treatment of this disease.

  15. Experimental Study of Mouse Cytomegalovirus Infected Mice

    Institute of Scientific and Technical Information of China (English)

    崔雯; 董永绥; 方峰

    2002-01-01

    Summary: In order to investigate the human cytomegalovirus (HCMV) infection, the mouse cytomegalovirus (MCMV) infected mice were experimentally studied. 6 to 8 week old female BALB/C mice with immunosuppression were selected to undergo the MCMV inoculations: intracranial inoculation and peritoneal inoculation. MCMV of the infected mice in various organs and tissues were detected by using β-gal staining and in situ nucleic acid hybridization assay. The pathological changes were observed in HE staining paraffin-embedded sections. It was found that all the MCMV infected mice showed the retardation of growth and development, and feather looseness. Both intracranial inoculation of 104 PFU viruses or peritoneal inoculation of 106 PFU viruses resulted in the pathological changes, to some extent, of various organs and tissues in the mice. The pathological changes in liver were consistent with the amount of β-gal staining positive cells, indicating the liver lesions were mainly caused by viral proliferation. It was also found that the viruses in the immunosuppressed mice subjected to intracranial inoculation could spread to whole body organs, while the viruses in the immunosuppressed mice subjected to intrapeitoneal inoculation couldn't spread to the brain, suggesting blood-brain barrier could prevent the virus from spreading to the brain.

  16. Infection with Porphyromonas gingivalis exacerbates endothelial injury in obese mice.

    Directory of Open Access Journals (Sweden)

    Min Ao

    Full Text Available 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.

  17. Adaptations to chronic rapamycin in mice

    Directory of Open Access Journals (Sweden)

    Sherry G. Dodds

    2016-05-01

    Full Text Available Rapamycin inhibits mechanistic (or mammalian target of rapamycin (mTOR that promotes protein production in cells by facilitating ribosome biogenesis (RiBi and eIF4E-mediated 5'cap mRNA translation. Chronic treatment with encapsulated rapamycin (eRapa extended health and life span for wild-type and cancer-prone mice. Yet, the long-term consequences of chronic eRapa treatment are not known at the organ level. Here, we report our observations of chronic eRapa treatment on mTORC1 signaling and RiBi in mouse colon and visceral adipose. As expected, chronic eRapa treatment decreased detection of phosphorylated mTORC1/S6K substrate, ribosomal protein (rpS6 in colon and fat. However, in colon, contrary to expectations, there was an upregulation of 18S rRNA and some ribosomal protein genes (RPGs suggesting increased RiBi. Among RPGs, eRapa increases rpl22l1 mRNA but not its paralog rpl22. Furthermore, there was an increase in the cap-binding protein, eIF4E relative to its repressor 4E-BP1 suggesting increased translation. By comparison, in fat, there was a decrease in the level of 18S rRNA (opposite to colon, while overall mRNAs encoding ribosomal protein genes appeared to increase, including rpl22, but not rpl22l1 (opposite to colon. In fat, there was a decrease in eIF4E relative to actin (opposite to colon but also an increase in the eIF4E/4E-BP1 ratio likely due to reductions in 4E-BP1 at our lower eRapa dose (similar to colon. Thus, in contrast to predictions of decreased protein production seen in cell-based studies, we provide evidence that colon from chronically treated mice exhibited an adaptive ‘pseudo-anabolic’ state, which is only partially present in fat, which might relate to differing tissue levels of rapamycin, cell-type-specific responses, and/or strain differences.

  18. Acute cytomegalovirus infections in leukemic mice.

    OpenAIRE

    Mayo, D. R.; Rapp, F

    1980-01-01

    Mice infected with 2 x 10(3) plaque-forming units of mouse cytomegalovirus (MCMV) 3 days after receiving 300 to 400 spleen focus-forming units of Friend leukemia virus developed a more severe MCMV infection than did normal animals. Increased severity was demonstrated by the increased amounts of MCMV recoverable from the salivary glands of leukemic mice 1 to 5 weeks postinfection. In addition, the difference in the number of virus isolations from the kidneys, spleens, livers, and lungs of anim...

  19. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

    NARCIS (Netherlands)

    Jurk, Diana; Wilson, Caroline; Passos, Joao F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia L. F.; Fullard, Nicola; Nelson, Glyn; Mann, Jelena; van de Sluis, Bart; Mann, Derek A.; von Zglinicki, Thomas

    2014-01-01

    Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-kappa B induces premature ageing in mice. We also show that these mice have reduced regenerati

  20. Early severe inflammatory responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection.

    Directory of Open Access Journals (Sweden)

    Thomas J Hannan

    Full Text Available Chronic infections are an increasing problem due to the aging population and the increase in antibiotic resistant organisms. Therefore, understanding the host-pathogen interactions that result in chronic infection is of great importance. Here, we investigate the molecular basis of chronic bacterial cystitis. We establish that introduction of uropathogenic E. coli (UPEC into the bladders of C3H mice results in two distinct disease outcomes: resolution of acute infection or development of chronic cystitis lasting months. The incidence of chronic cystitis is both host strain and infectious dose-dependent. Further, development of chronic cystitis is preceded by biomarkers of local and systemic acute inflammation at 24 hours post-infection, including severe pyuria and bladder inflammation with mucosal injury, and a distinct serum cytokine signature consisting of elevated IL-5, IL-6, G-CSF, and the IL-8 analog KC. Mice deficient in TLR4 signaling or lymphocytes lack these innate responses and are resistant, to varying degrees, to developing chronic cystitis. Treatment of C3H mice with the glucocorticoid anti-inflammatory drug dexamethasone prior to UPEC infection also suppresses the development of chronic cystitis. Finally, individuals with a history of chronic cystitis, lasting at least 14 days, are significantly more susceptible to redeveloping severe, chronic cystitis upon bacterial challenge. Thus, we have discovered that the development of chronic cystitis in C3H mice by UPEC is facilitated by severe acute inflammatory responses early in infection, which subsequently are predisposing to recurrent cystitis, an insidious problem in women. Overall, these results have significant implications for our understanding of how early host-pathogen interactions at the mucosal surface determines the fate of disease.

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

    Directory of Open Access Journals (Sweden)

    Min Ao

    Full Text Available 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.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.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 placental tissue

  2. Patient concerns regarding chronic hepatitis C infections.

    Science.gov (United States)

    Minuk, G Y; Gutkin, A; Wong, S G; Kaita, K D E

    2005-01-01

    Counselling of patients with chronic hepatitis C infections is often limited to discussions regarding how the virus is transmitted and what can be done to decrease the risk of transmission to others. The purpose of the present study was to document the principal concerns of newly diagnosed and follow-up patients with chronic hepatitis C, and thereby enhance counselling strategies and content. Seventy newly diagnosed and 115 follow-up patients with chronic hepatitis C virus (HCV) infection were initially asked in an open-ended manner (volunteered concerns) and then to prioritize from a prepared list of seven potential concerns (prioritized concerns), to identify those concerns that were of utmost importance to them. The most common volunteered concerns of newly diagnosed patients in decreasing order were: disease progression (27%), premature death (19%), infecting family members (13%), side-effects of treatment (11%) and miscellaneous others. In decreasing order, prioritized concerns included: infecting family members, development of liver cancer, infecting others, development of cirrhosis, social stigma of having liver disease, need for liver transplant and loss of employment. The principal volunteered and prioritized concerns of follow-up patients were similar to those of newly diagnosed patients. Volunteered and prioritized concerns were relatively consistent across the different genders, age groups, ethnic backgrounds, education level, marital status, employment, modes of viral acquisition and in the case of follow-up patients, duration of follow-up. These results indicate that health care providers who focus counselling efforts exclusively on viral transmission are unlikely to address other important concerns of newly diagnosed and follow-up patients with chronic HCV infection. PMID:15655048

  3. Exacerbation of Soft Tissue Lesions in Lead Exposed Virus Infected Mice

    Institute of Scientific and Technical Information of China (English)

    PRATIBHA GUPTA; M. M. HUSAIN; RAVI SHANKER; R. K. S. DOGRA; P. K. SETH; R. K. MAHESHWARI

    2003-01-01

    Objective To investigate the effect of Lead (Pb) acetate exposure on Semliki forest virus (SFV)pathogenesis in mice. Methods Different doses (62.5, 125, 250 and 500 mg/Kg body weight) of Pb dissolved in normal saline were given to mice by oral intubation in a sub-acute (28 days) and sub-chronic (90 days) regimen followed by SFV infection. Morbidity, mortality, clinical symptoms,mean survival time (MST), changes in body and organ weight, accumulation of lead in soft tissues,virus titre in brain and histopathological alterations were compared between lead exposed and infected groups. Results Early appearance of virus symptoms, increased mortality, decreased MST, enhanced SFV titre and greater tissue damage were observed in lead exposed-SFV-infected mice. Conclusion Pre-exposure to lead increases the susceptibility of mice towards SFV infection. Further studies are suggested in view of the persistence of lead in the environment and the possibility of infection bymicrobial pathogens.

  4. Induction of Chronic Myeloid Leukemia in Mice.

    Science.gov (United States)

    Zhang, Haojian; Li, Shaoguang

    2016-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder derived from a hematopoietic stem cell (HSC), harboring Philadelphia chromosome (Ph chromosome). Formation of the Ph chromosome is caused by a reciprocal translocation between the chromosomes 9 and 22 t(9;22)(q34;q11), resulting in a fusion protein known as BCR-ABL which has constitutive tyrosine kinase activity and promotes the proliferation of leukemia cells via multiple mechanisms. Studies on CML have led to the identification of the first cancer-associated chromosomal abnormality and the subsequent development of tyrosine kinase inhibitors (TKIs) that inhibit BCR-ABL kinase activity in CML. It has become clear that leukemia stem cells (LSCs) in CML are insensitive to inhibition by TKIs, and eradication of LSCs appears to be difficult. Therefore, some of the major issues in current CML therapy are to understand the biology of LSCs and to investigate why LSCs are insensitive to TKIs for developing curative therapeutic strategies. In this regard, application of mouse models recapitulating human CML disease will be critical. In this chapter, we describe methods for induction of CML in mice with BCR-ABL. PMID:27581135

  5. One episode of self-resolving Plasmodium yoelii infection transiently exacerbates chronic Mycobacterium tuberculosis infection

    Directory of Open Access Journals (Sweden)

    Jannike eBlank

    2016-02-01

    Full Text Available Malaria and tuberculosis (Tb are two of the main causes of death from infectious diseases globally. The pathogenic agents, Plasmodium parasites and Mycobacterium tuberculosis (Mtb, are co-endemic in many regions in the world however compared to other co-infections like HIV/Tb or helminth/Tb, malaria/Tb has been given less attention both in clinical and immunological studies. Due to the lack of sufficient human data, the impact of malaria on Tb and vice versa is difficult to estimate but co-infections are likely to occur very frequently. Due to its immunomodulatory properties malaria might be an underestimated risk factor for latent or active Tb patients particularly in high-endemic malaria settings were people experience reinfections very frequently. In the present study, we used the non-lethal strain of Plasmodium yoelii to investigate how one episode of self-resolving malaria impact on a chronic Mtb infection. P. yoelii co-infection resulted in exacerbation of Tb disease as demonstrated by increased pathology and cellular infiltration of the lungs which coincided with elevated levels of pro- and anti-inflammatory mediators. T cell responses were not impaired in co-infected mice but enhanced and likely contributed to increased cytokine production. We found a slight but statistically significant increase in Mtb burden in co-infected animals and increased lung CFU was positively correlated with elevated levels of TNFbut not IL-10. Infection with P. yoelii induced the recruitment of a CD11c+ population into lungs and spleens of Mtb infected mice. CD11c+ cells isolated from P. yoelii infected spleens promoted survival and growth of Mtb in vitro. 170 days after P. yoelii infection changes in immunopathology and cellular immune responses were no longer apparent while Mtb numbers were still slightly higher in lungs, but not in spleens of co-infected mice. In conclusion, one episode of P. yoelii co-infection transiently exacerbated disease

  6. [Aspergillus infection and chronic septic granulomatosis].

    Science.gov (United States)

    Mouy, R; Bremard, C; Fischer, A; Huu Trong, P; Vilmer, E; Griscelli, C

    1985-12-01

    Chronic granulomatous disease of childhood is a hereditary abnormality of phagocytic cells, frequently associated with Aspergillus infections. From 1969 to 1984, 14 of 37 children with chronic granulomatous disease have presented with pulmonary (13 cases) and/or osteo-articular (1 case) aspergillosis. The paucity of symptoms was a characteristic of these infections. Lung lesions extending to the thoracic chest wall carried the bad prognosis. Neither the Aspergillus skin test nor the Aspergillus serology could definitely confirm the diagnosis. Only broncho-alveolar lavage and biopsy with isolation of Aspergillus could confirm the diagnosis. Long-term therapy with amphotericin B alone or associated with other antifungal agents is necessary. For the past 3 years, ketoconazole prophylaxis has been used in 23 children and none of these children has developed aspergillosis.

  7. Azithromycin blocks quorum sensing and alginate polymer formation and increases the sensitivity to serum and stationary growth phase killing of P. aeruginosa and attenuates chronic P. aeruginosa lung infection in Cftr -/--mice

    DEFF Research Database (Denmark)

    Hoffmann, N.; Lee, Bao le ri; Hentzer, Morten;

    2007-01-01

    The consequences of O-acetylated alginate-producing Pseudomonas aeruginosa biofilms in the lungs of chronically infected cystic fibrosis (CF) patients are tolerance to both antibiotic treatments and effects on the innate and the adaptive defense mechanisms. In clinical trials, azithromycin (AZM......, whereas cells in the exponential phase did not. Interestingly, AZM-treated P. aeruginosa lasI mutants appeared to be particularly resistant to serum, whereas bacteria with a functional QS system did not. We show in a CF mouse model of chronic P. aeruginosa lung infection that AZM treatment results...

  8. Methamphetamine mediates immune dysregulation in a murine model of chronic viral infection.

    Directory of Open Access Journals (Sweden)

    Uma eSriram

    2015-08-01

    Full Text Available Methamphetamine (METH is a highly addictive psychostimulant that not only affects the brain and cognitive functions but also greatly impacts the host immune system, rendering the body susceptible to infections and exacerbating the severity of disease. Although there is gathering evidence about METH abuse and increased incidence of HIV and other viral infections, not much is known about the effects on the immune system in a chronic viral infection setting. We have used the lymphocytic choriomeningitis virus (LCMV chronic mouse model of viral infection in a chronic METH environment and demonstrate that METH significantly increases CD3 marker on splenocytes and programmed death -1 (PD-1 expression on T cells, a cell surface signaling molecule known to inhibit T cell function and cause exhaustion in a lymphoid organ. Many of these METH effects were more pronounced during early stage of infection, which are gradually attenuated during later stages of infection. An essential cytokine for T-lymphocyte homeostasis, Interleukin-2 (IL-2 in serum was prominently reduced in METH-exposed infected mice. In addition, the serum pro-inflammatory (TNF, IL12 p70, IL1β, IL-6 and KC-GRO and Th2 (IL-2, IL-10 and IL-4 cytokine profiles were also altered in the presence of METH. Interestingly CXCR3, an inflammatory chemokine receptor, showed significant increase in the METH treated LCMV infected mice. Similarly, compared to only infected mice, epidermal growth factor receptor (EGFR in METH exposed LCMV infected mice were up regulated. Collectively, our data suggest that METH alters systemic, peripheral immune responses and modulates key markers on T cells involved in pathogenesis of chronic viral infection.

  9. Effects of Cholinergic Stimulation with Pyridostigmine Bromide on Chronic Chagasic Cardiomyopathic Mice

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    Marília Beatriz de Cuba

    2014-01-01

    Full Text Available The aim of the present study was to assess the effects of an anticholinesterase agent, pyridostigmine bromide (Pyrido, on experimental chronic Chagas heart disease in mice. To this end, male C57BL/6J mice noninfected (control:Con or chronically infected (5 months with Trypanosoma cruzi (chagasic:Chg were treated or not (NT with Pyrido for one month. At the end of this period, electrocardiogram (ECG; cardiac autonomic function; heart histopathology; serum cytokines; and the presence of blood and tissue parasites by means of immunohistochemistry and PCR were assessed. In NT-Chg mice, significant changes in the electrocardiographic, autonomic, and cardiac histopathological profiles were observed confirming a chronic inflammatory response. Treatment with Pyrido in Chagasic mice caused a significant reduction of myocardial inflammatory infiltration, fibrosis, and hypertrophy, which was accompanied by a decrease in serum levels of IFNγ with no change in IL-10 levels, suggesting a shift of immune response toward an anti-inflammatory profile. Lower nondifferent numbers of parasite DNA copies were observed in both treated and nontreated chagasic mice. In conclusion, our findings confirm the marked neuroimmunomodulatory role played by the parasympathetic autonomic nervous system in the evolution of the inflammatory-immune response to T. cruzi during experimental chronic Chagas heart disease in mice.

  10. Lymphocytes from Chronically Stressed Mice Confer Antidepressant-Like Effects to Naive Mice

    OpenAIRE

    Brachman, Rebecca A.; Lehmann, Michael L.; Maric, Dragan; Herkenham, Miles

    2015-01-01

    We examined whether cells of the adaptive immune system retain the memory of psychosocial stress and thereby alter mood states and CNS function in the host. Lymphocytes from mice undergoing chronic social defeat stress or from unstressed control mice were isolated and adoptively transferred into naive lymphopenic Rag2−/− mice. Changes in affective behavior, hippocampal cell proliferation, microglial activation states, and blood cytokine levels were examined in reconstituted stress-naive mice....

  11. Changes in neurotransmitter levels and expression of immediate early genes in brain of mice infected with Neospora caninum

    Science.gov (United States)

    Ihara, Fumiaki; Nishimura, Maki; Muroi, Yoshikage; Furuoka, Hidefumi; Yokoyama, Naoaki; Nishikawa, Yoshifumi

    2016-01-01

    Neospora caninum is an obligate intracellular parasite that causes neurological disorders in dogs and cattle. The majority of host animals are asymptomatic at the chronic stage of infection. However, it remains unclear whether cerebral function is normal in asymptomatic animals. In this study, mice were infected with N. caninum (strain Nc-1) and their brains were examined to understand changes in cerebral function at the chronic stage of infection. Mice infected with N. caninum showed impaired locomotor activity, but no differences in clinical symptoms were observed. In the brains of infected mice, parasites were distributed throughout the brain and histological lesions were observed everywhere except for the cerebellum. Expression levels of proinflammatory cytokines, interferon-gamma and tumour necrosis factor-alpha, were highly upregulated in several brain regions of infected mice. Additionally, the level of neurotransmitters glutamate, glycine, gamma-aminobutyric acid, dopamine and 5-hydroxytryptamine, were altered in infected mice compared with those of uninfected mice. Interestingly, the expression levels of immediately early genes, c-Fos and Arc, in the brain of infected mice were lower than those of in uninfected mice. Our findings may provide insight into neurological disorders associated with N. caninum infection. PMID:26971577

  12. Respiratory syncytial virus infection facilitates acute colonization of Pseudomonas aeruginosa in mice

    DEFF Research Database (Denmark)

    de Vrankrijker, Angélica M M; Wolfs, Tom F W; Ciofu, Oana;

    2009-01-01

    Pseudomonas aeruginosa causes opportunistic infections in immunocompromised individuals and patients ventilated mechanically and is the major pathogen in patients with cystic fibrosis, in which it causes chronic infections. Epidemiological, in vitro and animal data suggest a role for respiratory...... virus infections in facilitating colonization and infection with P. aeruginosa. A study was undertaken to determine whether respiratory syncytial virus (RSV) infection could facilitate the initiation of an acute infection with P. aeruginosa in vivo. Balb/c mice were infected intranasally with P....... aeruginosa, with and without simultaneous inoculation with RSV. Lung function measurements were undertaken using Whole Body Plethysmography and lungs were harvested 24 hr after inoculation. Mice exposed to RSV and P. aeruginosa showed 2,000 times higher colony-forming units (CFU) counts of P. aeruginosa...

  13. Increased mucosal damage during parasite infection in mice fed an elemental diet.

    OpenAIRE

    Ferguson, A.; Logan, R F; MacDonald, T T

    1980-01-01

    We have examined the effects of parasite infection on the mucosal architecture of mice maintained on an elemental diet (Vivonex). Techniques used were conventional histology, micro-dissection and measurement of individual villi and crypts, and measurement of crypt cell proliferation rate by a metaphase accumulation technique. In normal, non-parasitised mice the elemental diet caused no change in villus height, crypt depth, or crypt cell proliferation. Likewise, the only effects of chronic pro...

  14. Methylotroph Infections and Chronic Granulomatous Disease.

    Science.gov (United States)

    Falcone, E Liana; Petts, Jennifer R; Fasano, Mary Beth; Ford, Bradley; Nauseef, William M; Neves, João Farela; Simões, Maria João; Tierce, Millard L; de la Morena, M Teresa; Greenberg, David E; Zerbe, Christa S; Zelazny, Adrian M; Holland, Steven M

    2016-03-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in production of phagocyte-derived reactive oxygen species, which leads to recurrent infections with a characteristic group of pathogens not previously known to include methylotrophs. Methylotrophs are versatile environmental bacteria that can use single-carbon organic compounds as their sole source of energy; they rarely cause disease in immunocompetent persons. We have identified 12 infections with methylotrophs (5 reported here, 7 previously reported) in patients with CGD. Methylotrophs identified were Granulibacter bethesdensis (9 cases), Acidomonas methanolica (2 cases), and Methylobacterium lusitanum (1 case). Two patients in Europe died; the other 10, from North and Central America, recovered after prolonged courses of antimicrobial drug therapy and, for some, surgery. Methylotrophs are emerging as disease-causing organisms in patients with CGD. For all patients, sequencing of the 16S rRNA gene was required for correct diagnosis. Geographic origin of the methylotroph strain may affect clinical management and prognosis.

  15. Mechanisms controlling anaemia in Trypanosoma congolense infected mice.

    Directory of Open Access Journals (Sweden)

    Harry A Noyes

    Full Text Available BACKGROUND: Trypanosoma congolense are extracellular protozoan parasites of the blood stream of artiodactyls and are one of the main constraints on cattle production in Africa. In cattle, anaemia is the key feature of disease and persists after parasitaemia has declined to low or undetectable levels, but treatment to clear the parasites usually resolves the anaemia. METHODOLOGY/PRINCIPAL FINDINGS: The progress of anaemia after Trypanosoma congolense infection was followed in three mouse strains. Anaemia developed rapidly in all three strains until the peak of the first wave of parasitaemia. This was followed by a second phase, characterized by slower progress to severe anaemia in C57BL/6, by slow recovery in surviving A/J and a rapid recovery in BALB/c. There was no association between parasitaemia and severity of anaemia. Furthermore, functional T lymphocytes are not required for the induction of anaemia, since suppression of T cell activity with Cyclosporin A had neither an effect on the course of infection nor on anaemia. Expression of genes involved in erythropoiesis and iron metabolism was followed in spleen, liver and kidney tissues in the three strains of mice using microarrays. There was no evidence for a response to erythropoietin, consistent with anaemia of chronic disease, which is erythropoietin insensitive. However, the expression of transcription factors and genes involved in erythropoiesis and haemolysis did correlate with the expression of the inflammatory cytokines Il6 and Ifng. CONCLUSIONS/SIGNIFICANCE: The innate immune response appears to be the major contributor to the inflammation associated with anaemia since suppression of T cells with CsA had no observable effect. Several transcription factors regulating haematopoiesis, Tal1, Gata1, Zfpm1 and Klf1 were expressed at consistently lower levels in C57BL/6 mice suggesting that these mice have a lower haematopoietic capacity and therefore less ability to recover from

  16. Unpredictable chronic mild stress not chronic restraint stress induces depressive behaviours in mice.

    Science.gov (United States)

    Zhu, Shenghua; Shi, Ruoyang; Wang, Junhui; Wang, Jun-Feng; Li, Xin-Min

    2014-10-01

    The chronic stress model was developed on the basis of the stress-diathesis hypothesis of depression. However, these behavioural responses associated with different stress paradigms are quite complex. This study examined the effects of two chronic stress regimens on anxiety-like and depressive behaviours. C57BL/6 mice were subjected to unpredictable chronic mild stress or to chronic restraint stress for 4 weeks. Subsequently, both anxiety-like behaviours (open field, elevated plus maze and novelty suppressed feeding) and depression-like behaviours (tail suspension, forced swim and sucrose preference) were evaluated. Both chronic stress models generated anxiety-like behaviours, whereas only unpredictable chronic mild stress could induce depressive behaviours such as increased immobility and decreased sucrose consumption. These results of the present study provide additional evidence on how chronic stress affects behavioural responses and point to the importance of the validity of animal models of chronic stress in studying depression. PMID:25089805

  17. Studies of membrane fluidity and heart contractile force in Trypanosoma cruzi infected mice

    Directory of Open Access Journals (Sweden)

    Julio E Enders

    2004-11-01

    Full Text Available In Chagas disease serious cardiac dysfunction can appear. We specifically studied the cardiac function by evaluating: ventricle contractile force and norepinephrine response, affinity and density of beta-adrenergic receptors, dynamic properties of myocardial membranes, and electrocardiography. Albino swiss mice (n = 250 were infected with 55 trypomastigotes, Tulahuen strain and studied at 35, 75, and 180 days post-infection, that correspond to the acute, indeterminate, and chronic phase respectively. Cardiac beta-adrenergic receptors' affinity, myocardial contractility, and norepinephrine response progressively decreased from the acute to the chronic phase of the disease (p < 0.01. The density (expressed as fmol/mg.prot of the receptors was similar to non-infected mice (71.96 ± 0.36 in both the acute (78.24 ± 1.67 and indeterminate phases (77.28 ± 0.91, but lower in the chronic disease (53.32 ± 0.71. Electrocardiographic abnormalities began in the acute phase and were found in 65% of the infected-mice during the indeterminate and chronic phases. Membrane contents of triglycerides, cholesterol, and anisotropy were similar in all groups. A quadratic correlation between the affinity to beta-adrenergic receptors and cardiac contractile force was obtained. In conclusion the changes in cardiac beta-adrenergic receptors suggests a correlation between the modified beta-adrenergic receptors affinity and the cardiac contractile force.

  18. Effect of chronic psychosocial stress on nonalcoholic steatohepatitis in mice.

    Science.gov (United States)

    Czech, Barbara; Neumann, Inga D; Müller, Martina; Reber, Stefan O; Hellerbrand, Claus

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation which may progress towards inflammation (nonalcoholic steatohepatitis (NASH)). NAFLD is regarded as a consequence of a sedentary, food-abundant lifestyle which, in the modern world, often coincides with chronically high levels of perceived psychosocial stress. Here, we aimed to characterize the effect of chronic psychosocial stress on the development of NAFLD/NASH in male mice either fed with standard chow or NASH-inducing high fat diet. Chronic psychosocial stress was induced by chronic subordinate colony housing (CSC), a pre-clinically validated paradigm relevant for human affective and somatic disorders. Single housed (SHC) mice served as controls. Under standard chow conditions CSC mice revealed lower hepatic triglyceride levels but higher hepatic TNFα, MCP-1 and HMOX mRNA expression, while serum transaminase levels did not significantly differ from SHC mice. Under the NASH-inducing high-fat diet CSC and SHC mice showed similar body weight-gain and serum levels of glucose and adiponectin. Moreover, liver histology as well as TNFα, MCP-1 and HMOX expression were similar in CSC and SHC mice fed with HFD. Surprisingly, CSC showed even significantly lower transaminase levels than SHC mice fed with the same NASH-inducing diet. Together, these data indicate that under normal dietary conditions the CSC model induces noticeable hepatic oxidative stress and inflammation without causing manifest hepatocellular injury. In contrast, CSC exhibited a protective effect on hepatocellular injury in a dietary NASH-model. Identification of the underlying mechanisms of this phenomenon may lead to novel therapeutic strategies to prevent progression of NAFLD.

  19. Hepatic temporal gene expression profiling in Helicobacter hepaticus-infected A/JCr mice.

    Science.gov (United States)

    Boutin, Samuel R; Rogers, Arlin B; Shen, Zeli; Fry, Rebecca C; Love, Jennifer A; Nambiar, Prashant R; Suerbaum, Sebastian; Fox, James G

    2004-01-01

    Helicobacter hepaticus infection of A/JCr mice is a model of infectious liver cancer. We monitored hepatic global gene expression profiles in H. hepaticus infected and control male A/JCr mice at 3 months, 6 months, and 1 year of age using an Affymetrix-based oligonucleotide microarray platform on the premise that a specific genetic expression signature at isolated time points would be indicative of disease status. Model based expression index comparisons generated by dChip yielded consistent profiles of differential gene expression for H. hepaticus infected male mice with progressive liver disease versus uninfected control mice within each age group. Linear discriminant analysis and principal component analysis allowed segregation of mice based on combined age and lesion status, or age alone. Up-regulation of putative tumor markers correlated with advancing hepatocellular dysplasia. Transcriptionally down-regulated genes in mice with liver lesions included those related to peroxisome proliferator, fatty acid, and steroid metabolism pathways. In conclusion, transcriptional profiling of hepatic genes documented gene expression signatures in the livers of H. hepaticus infected male A/JCr mice with chronic progressive hepatitis and preneoplastic liver lesions, complemented the histopathological diagnosis, and suggested molecular targets for the monitoring and intervention of disease progression prior to the onset of hepatocellular neoplasia.

  20. Imunocompetent Mice Model for Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Denise Gonçalves

    2012-01-01

    Full Text Available Dengue fever is a noncontagious infectious disease caused by dengue virus (DENV. DENV belongs to the family Flaviviridae, genus Flavivirus, and is classified into four antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The number of nations and people affected has increased steadily and today is considered the most widely spread arbovirus (arthropod-borne viral disease in the world. The absence of an appropriate animal model for studying the disease has hindered the understanding of dengue pathogenesis. In our study, we have found that immunocompetent C57BL/6 mice infected intraperitoneally with DENV-1 presented some signs of dengue disease such as thrombocytopenia, spleen hemorrhage, liver damage, and increase in production of IFNγ and TNFα cytokines. Moreover, the animals became viremic and the virus was detected in several organs by real-time RT-PCR. Thus, this animal model could be used to study mechanism of dengue virus infection, to test antiviral drugs, as well as to evaluate candidate vaccines.

  1. Phyllanthus species for chronic hepatitis B virus infection

    DEFF Research Database (Denmark)

    Yun, Xia; Luo, Hui; Liu, Jian Ping;

    2011-01-01

    Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists.......Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists....

  2. Cost of Illness of Chronic Hepatitis B Infection in Vietnam

    NARCIS (Netherlands)

    Tu, Hong Anh T.; Woerdenbag, Herman J.; Riewpaiboon, Arthorn; Kane, Sumit; Le, Diep M.; Postma, Maarten J.; Li, Shu Chuen

    2012-01-01

    To estimate the total financial burden of chronic hepatitis B virus (HBV) infection for Vietnam by quantifying the direct medical, the direct nonmedical, and indirect costs among patients with various stages of chronic HBV infection. Direct medical cost data were retrieved retrospectively from medic

  3. B Cells and Platelets Harbor Prion Infectivity in the Blood of Deer Infected with Chronic Wasting Disease▿ †

    OpenAIRE

    Candace K Mathiason; Hayes-Klug, Jeanette; Hays, Sheila A.; Powers, Jenny; Osborn, David A.; Dahmes, Sallie J.; Miller, Karl V.; Warren, Robert J., II; Mason, Gary L.; Telling, Glenn C.; Young, Alan J; Hoover, Edward A.

    2010-01-01

    Substantial evidence for prion transmission via blood transfusion exists for many transmissible spongiform encephalopathy (TSE) diseases. Determining which cell phenotype(s) is responsible for trafficking infectivity has important implications for our understanding of the dissemination of prions, as well as their detection and elimination from blood products. We used bioassay studies of native white-tailed deer and transgenic cervidized mice to determine (i) if chronic wasting disease (CWD) b...

  4. Immune response in the adipose tissue of lean mice infected with the protozoan parasite Neospora caninum.

    Science.gov (United States)

    Teixeira, Luzia; Moreira, João; Melo, Joana; Bezerra, Filipa; Marques, Raquel M; Ferreirinha, Pedro; Correia, Alexandra; Monteiro, Mariana P; Ferreira, Paula G; Vilanova, Manuel

    2015-06-01

    The adipose tissue can make important contributions to immune function. Nevertheless, only a limited number of reports have investigated in lean hosts the immune response elicited in this tissue upon infection. Previous studies suggested that the intracellular protozoan Neospora caninum might affect adipose tissue physiology. Therefore, we investigated in mice challenged with this protozoan if immune cell populations within adipose tissue of different anatomical locations could be differently affected. Early in infection, parasites were detected in the adipose tissue and by 7 days of infection increased numbers of macrophages, regulatory T (Treg) cells and T-bet(+) cells were observed in gonadal, mesenteric, omental and subcutaneous adipose tissue. Increased expression of interferon-γ was also detected in gonadal adipose tissue of infected mice. Two months after infection, parasite DNA was no longer detected in these tissues, but T helper type 1 (Th1) cell numbers remained above control levels in the infected mice. Moreover, the Th1/Treg cell ratio was higher than that of controls in the mesenteric and subcutaneous adipose tissue. Interestingly, chronically infected mice presented a marked increase of serum leptin, a molecule that plays a role in energy balance regulation as well as in promoting Th1-type immune responses. Altogether, we show that an apicomplexa parasitic infection influences immune cellular composition of adipose tissue throughout the body as well as adipokine production, still noticed at a chronic phase of infection when parasites were already cleared from that particular tissue. This strengthens the emerging view that infections can have long-term consequences for the physiology of adipose tissue.

  5. The growth of human HIV-1 infected U937 cells in immune-deprived mice.

    Science.gov (United States)

    Chernukhin, I V; Chepurnov, A A; Gaidul, K V

    1995-01-01

    We report in vivo growth of human promonocytic cells infected with HIV-1 presented in new mouse model. Cloned U937 cells chronically infected with HIV-1 were grafted in (CBA*C57B1/6)F1 mice deprived of immunity by thymectomia and total body irradiation with subsequent marrow reconstitution. Nine weeks after cell inoculation, HIV-1-positive cells were found only in mice that received an additional single dose of cyclophosphamide (100 mg/kg bw) prior to transplantation, whereas, in mice without further immune deprivation, the complete elimination of cells bearing viral antigen occurred already on the seventh day after transplantation. The approach described may be suitable for in vivo development of antiviral drugs against latent infection in macrophage-like cells which represent a serious problem in therapy of AIDS in humans. PMID:8562863

  6. IL-1 receptor blockade restores autophagy and reduces inflammation in chronic granulomatous disease in mice and in humans

    NARCIS (Netherlands)

    Luca, A. De; Smeekens, S.P.; Casagrande, A.; Iannitti, R.; Conway, K.L.; Gresnigt, M.S.; Begun, J.; Plantinga, T.S.; Joosten, L.A.B.; Meer, J.W.M. van der; Chamilos, G.; Netea, M.G.; Xavier, R.J.; Dinarello, C.A.; Romani, L.; Veerdonk, F.L. van de

    2014-01-01

    Patients with chronic granulomatous disease (CGD) have a mutated NADPH complex resulting in defective production of reactive oxygen species; these patients can develop severe colitis and are highly susceptible to invasive fungal infection. In NADPH oxidase-deficient mice, autophagy is defective but

  7. Coping with parvovirus infections in mice: health surveillance and control.

    Science.gov (United States)

    Janus, Lydia M; Bleich, Andre

    2012-01-01

    Parvoviruses of mice, minute virus of mice (MVM) and mouse parvovirus (MPV), are challenging pathogens to eradicate from laboratory animal facilities. Due to the impediment on rodent-based research, recent studies have focused on the assessment of re-derivation techniques and parvoviral potential to induce persistent infections. Summarizing recent data, this review gives an overview on studies associated with parvoviral impact on research, diagnostic methods, parvoviral persistence and re-derivation techniques, demonstrating the complex nature of parvovirus infection in mice and unfolding the challenge of controlling parvovirus infections in laboratory animal facilities.

  8. Chronic psychosocial stress induces visceral hyperalgesia in mice.

    Science.gov (United States)

    Tramullas, Mónica; Dinan, Timothy G; Cryan, John F

    2012-05-01

    Experimental and clinical evidence has shown that chronic stress plays an important role in the onset and/or exacerbation of symptoms of functional gastrointestinal disorders. Here, we aimed to investigate whether exposure to a chronic and temporally unpredictable psychosocial stressor alters visceral and somatic nociception as well as anxiety-related behaviour. In male C57BL/6J mice, chronic stress was induced by repeated exposure to social defeat (SD, 2 h) and overcrowding (OC, 24 h) during 19 consecutive days. Visceral and somatic nociception was evaluated by colorectal distension and a hot plate, respectively. The social interaction test was used to assess social anxiety. Mice exposed to psychosocial stress developed visceral hyperalgesia and somatic hypoalgesia 24 h following the last stress session. SD/OC mice also exhibited social anxiety-like behaviour. All these changes were also associated with physiological alterations, measured as a decreased faecal pellet output and hypothalamic-pituitary-adrenal (HPA) axis disruption. Taken together, these data confirm that this mouse model of chronic psychosocial stress may be useful for studies on the pathophysiological mechanisms underlying such stress-associated disorders and to further test potential therapies.

  9. Inadequate clearance of translocated bacterial products in HIV-infected humanized mice.

    Directory of Open Access Journals (Sweden)

    Ursula Hofer

    2010-04-01

    Full Text Available Bacterial translocation from the gut and subsequent immune activation are hallmarks of HIV infection and are thought to determine disease progression. Intestinal barrier integrity is impaired early in acute retroviral infection, but levels of plasma lipopolysaccharide (LPS, a marker of bacterial translocation, increase only later. We examined humanized mice infected with HIV to determine if disruption of the intestinal barrier alone is responsible for elevated levels of LPS and if bacterial translocation increases immune activation. Treating uninfected mice with dextran sodium sulfate (DSS induced bacterial translocation, but did not result in elevated plasma LPS levels. DSS-induced translocation provoked LPS elevation only when phagocytic cells were depleted with clodronate liposomes (clodrolip. Macrophages of DSS-treated, HIV-negative mice phagocytosed more LPS ex vivo than those of control mice. In HIV-infected mice, however, LPS phagocytosis was insufficient to clear the translocated LPS. These conditions allowed higher levels of plasma LPS and CD8+ cell activation, which were associated with lower CD4+/CD8+ cell ratios and higher viral loads. LPS levels reflect both intestinal barrier and LPS clearance. Macrophages are essential in controlling systemic bacterial translocation, and this function might be hindered in chronic HIV infection.

  10. Actinomyces and Nocardia Infections in Chronic Granulomatous Disease

    OpenAIRE

    Shahindokht Bassiri-Jahromi; Aida Doostkam

    2011-01-01

    Objective : Chronic granulomatous disease (CGD) is an inherited disorder of the Nicotinamide adenine dinucleotide phosphate reduced oxidase complex characterized by recurrent bacterial and fungal infections. Disseminated infection by combination of opportunistic agents is being increasingly reported in CGD patients. We presented in the retrospective review of medical records, the etiology, presentation, clinical characteristics the infections detected, predisposing condition and outcome of no...

  11. Chronic hepatitis B infection in pregnancy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    There are no standard guidelines to follow when apatient with chronic hepatitis B infection becomespregnant or desires pregnancy. Topics to considerinclude which patients to treat, when to start treatment,what treatment to use and when to stop treatment.Without any prophylaxis or antiviral therapy, a hepatitisB surface antigen and E antigen positive mother has upto a 90% likelihood of vertical transmission of hepatitisB virus (HBV) to child. Standard of care in the UnitedStates to prevent perinatal transmission consists ofadministration of hepatitis B immune globulin andHBV vaccination to the infant. The two strongest riskfactors of mother to child transmission (MTCT) of HBVinfection despite immunoprophylaxis are high maternalHBV viral load and high activity of viral replication.The goal is to prevent transmission of HBV at birthby decreasing viral load and/or decreasing activity ofthe virus. Although it is still somewhat controversial,most evidence shows that starting antivirals in thethird trimester is effective in decreasing MTCT withoutaffecting fetal development. There is a growing body ofliterature supporting the safety and efficacy of antiviraltherapies to reduce MTCT of hepatitis B. There areno formal recommendations regarding which agent tochoose. Tenofovir, lamivudine and telbivudine have allbeen proven efficacious in decreasing viral load at birthwithout known birth defects, but final decision of whichantiviral medication to use will have to be determinedby physician and patient. The antivirals may bediscontinued immediately if patient is breastfeeding, orwithin first four weeks if infant is being formula fed.

  12. Chronic toxicity study of cyclohexanone in rats and mice.

    Science.gov (United States)

    Lijinsky, W; Kovatch, R M

    1986-10-01

    A 2-year chronic toxicity assay of cyclohexanone (CAS: 108-94-1) was conducted in F344 rats and (C57BL/6 X C3H)F1 mice by administering a solution of cyclohexanone in drinking water. Two concentrations were given to rats, 6,500 and 3,300 ppm (wt/vol). Male mice received 13,000 and 6,500 ppm, while female mice were given three concentrations, 25,000, 13,000, and 6,500 ppm. Each treatment group consisted of 50 or 52 male and 50 or 52 female rats or mice, except 47 male mice treated with the highest dose and 41 female mice treated with the highest dose, and there was a group of untreated controls of each species. Survival and weight gain were similar to those of controls at the lowest cyclohexanone dose in both sexes of both species, but weight gain was depressed at all of the higher doses. Survival was good (greater than 80% at 90 wk) in all groups except in female mice at the 2 highest doses; at 25,000 ppm of cyclohexanone, only 50% of mice lived beyond 1 year. Most of the neoplasms in the treated groups did not differ significantly in number from those in the controls. Male rats receiving 3,300 ppm cyclohexanone had a 13% incidence of adrenal cortex adenomas (7 animals) compared with an incidence of 2% in controls; the incidence of this neoplasm did not increase in the male rats receiving 6,500 ppm or in the female rats given either dose. The mice had a statistically significant increase in incidence of lymphomas-leukemias among the females given 6,500 ppm, but not among the groups given higher doses of cyclohexanone. Male mice given 6,500 ppm cyclohexanone showed an increased incidence of hepatocellular adenomas and carcinomas, 50% versus 32.5% in controls, but the incidence of these neoplasms was only 37% in the male mice given 13,000 ppm cyclohexanone. The incidence of lymphomas in male mice and of hepatocellular neoplasms in female mice given cyclohexanone did not differ from that in the controls. The evidence for carcinogenic activity of cyclohexanone is

  13. Therapeutic Effects of Troglitazone in Experimental Chronic Pancreatitis in Mice

    OpenAIRE

    van Westerloo, David J.; Florquin, Sandrine; de Boer, Anita M; Daalhuisen, Joost; Alex F de Vos; Bruno, Marco J.; van der Poll, Tom

    2005-01-01

    Peroxisome proliferator-activated receptor (PPAR)-γ controls growth, differentiation, and inflammation. PPAR-γ agonists exert anti-inflammatory effects in vitro and inhibit the activation of pancreas stellate cells, implicated in the formation and progression of fibrosis. We determined the influence of troglitazone, a ligand for PPAR-γ, on pancreatic damage and fibrosis in experimental chronic pancreatitis. Mice received six hourly intraperitoneal injections with 50 μg/kg of cerulein or salin...

  14. First attempt to produce experimental Campylobacter concisus infection in mice

    Institute of Scientific and Technical Information of China (English)

    Rune Aabenhus; Unne Stenram; Leif Percival Andersen; Henrik Permin; Asa Ljungh

    2008-01-01

    AIM: To infect mice with atypical Campylobacter concisus (C. concisus) for the first time.METHODS: Three separate experiments were conducted in order to screen the ability of five clinical C concisus isolates of intestinal origin and the ATCC 33237 type strain of oral origin to colonize and produce infection in immunocompetent BALB/cA mice.The majority of the BALB/cA mice were treated with cyclophosphamide prior to C. concisus inoculation to suppress immune functions. Inoculation of C. concisus was performed by the gastric route.RESULTS: C concisus was isolated from the liver, ileum and jejunum of cyclophosphamide-treated mice in the first experiment. No C concisus strains were isolated in the two subsequent experiments. Mice infected with C concisus showed a significant loss of body weight from day two through to day five of infection but this decreased at the end of the first week. Histopathological examination did not consistently find signs of inflammation in the gut, but occasionally microabscesses were found in the liver of infected animals.CONCLUSION: Transient colonization with C. concisua was observed in mice with loss of body weight. Future studies should concentrate on the first few days after inoculation and in other strains of mice.

  15. Comparative Study of Chronic Congenital Toxoplasmosis and Re-Infection In

    Directory of Open Access Journals (Sweden)

    M Asmar

    2005-04-01

    Full Text Available Introduction: Toxoplasma gondii is a coccidian parasite and has, as intermediate hosts, many warm-blooded animals, including mammals and birds. Congenital toxoplasmosis is one of the most important infectious diseases seen in fetuses and infants born from mothers infected with Tox.gondii during pregnancy. Congenital infection, which may occur if a mother is infected for the first time during pregnancy, is often serious, resulting in abortion or severe neurological and ophthalmological disorders. Information on human cases of neonatal toxoplasmosis makes it unquestionable that Toxoplasma crosses the placenta and invades the fetus in utero in each of the two cases. . Methods: Tox. gondii infection in newborn rat litters was detected by a bioassay and parasitological method. Rat litters were billed and where possible, separated from their mothers in order to prevent feeding. Their tissues were separately homogenized in normal saline or PBS and inoculated intraperitoneally in 3 mice. The tissues used for bioassays were brain, hearts, lungs, livers, and spleen of pups, which were killed on the day of birth. In addition, control infected rat were sacrificed and their different tissues were evaluated for parasite burden at each time point of reinfection and chronic infection. Results: Data in the occurrence of congenital transmission from chronically infected mother rats given similarly graded inoculums of the RH strains (1(106 to 5(106 presented that none of the 36 pups was infected with Tox.gondii. The occurrence of congenital transmission in rats reinfected with Toxoplasma shows that none of the 14 pups was infected with Tox.gondii. Rats were reinfected intra- peritoneally with 1(106 parasite at 1,2 and 4 months after primary infection, respectively. Conclusion: Thus, this study demonstrated that Rats chronically infected with Tox.gondii, have immunity capable of protecting their embryos from congenital infection, even if they are reinfected during

  16. Bioluminescence imaging of Chlamydia muridarum ascending infection in mice.

    Science.gov (United States)

    Campbell, Jessica; Huang, Yumeng; Liu, Yuanjun; Schenken, Robert; Arulanandam, Bernard; Zhong, Guangming

    2014-01-01

    Chlamydial pathogenicity in the upper genital tract relies on chlamydial ascending from the lower genital tract. To monitor chlamydial ascension, we engineered a luciferase-expressing C. muridarum. In cells infected with the luciferase-expressing C. muridarum, luciferase gene expression and enzymatic activity (measured as bioluminescence intensity) correlated well along the infection course, suggesting that bioluminescence can be used for monitoring chlamydial replication. Following an intravaginal inoculation with the luciferase-expressing C. muridarum, 8 of 10 mice displayed bioluminescence signal in the lower with 4 also in the upper genital tracts on day 3 after infection. By day 7, all 10 mice developed bioluminescence signal in the upper genital tracts. The bioluminescence signal was maintained in the upper genital tract in 6 and 2 mice by days 14 and 21, respectively. The bioluminescence signal was no longer detectable in any of the mice by day 28. The whole body imaging approach also revealed an unexpected airway infection following the intravaginal inoculation. Although the concomitant airway infection was transient and did not significantly alter the genital tract infection time courses, caution should be taken during data interpretation. The above observations have demonstrated that C. muridarum can not only achieve rapid ascending infection in the genital tract but also cause airway infection following a genital tract inoculation. These findings have laid a foundation for further optimizing the C. muridarum intravaginal infection murine model for understanding chlamydial pathogenic mechanisms.

  17. Bioluminescence imaging of Chlamydia muridarum ascending infection in mice.

    Directory of Open Access Journals (Sweden)

    Jessica Campbell

    Full Text Available Chlamydial pathogenicity in the upper genital tract relies on chlamydial ascending from the lower genital tract. To monitor chlamydial ascension, we engineered a luciferase-expressing C. muridarum. In cells infected with the luciferase-expressing C. muridarum, luciferase gene expression and enzymatic activity (measured as bioluminescence intensity correlated well along the infection course, suggesting that bioluminescence can be used for monitoring chlamydial replication. Following an intravaginal inoculation with the luciferase-expressing C. muridarum, 8 of 10 mice displayed bioluminescence signal in the lower with 4 also in the upper genital tracts on day 3 after infection. By day 7, all 10 mice developed bioluminescence signal in the upper genital tracts. The bioluminescence signal was maintained in the upper genital tract in 6 and 2 mice by days 14 and 21, respectively. The bioluminescence signal was no longer detectable in any of the mice by day 28. The whole body imaging approach also revealed an unexpected airway infection following the intravaginal inoculation. Although the concomitant airway infection was transient and did not significantly alter the genital tract infection time courses, caution should be taken during data interpretation. The above observations have demonstrated that C. muridarum can not only achieve rapid ascending infection in the genital tract but also cause airway infection following a genital tract inoculation. These findings have laid a foundation for further optimizing the C. muridarum intravaginal infection murine model for understanding chlamydial pathogenic mechanisms.

  18. Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala.

    Science.gov (United States)

    Ihara, Fumiaki; Nishimura, Maki; Muroi, Yoshikage; Mahmoud, Motamed Elsayed; Yokoyama, Naoaki; Nagamune, Kisaburo; Nishikawa, Yoshifumi

    2016-10-01

    Chronic infection with Toxoplasma gondii becomes established in tissues of the central nervous system, where parasites may directly or indirectly modulate neuronal function. Epidemiological studies have revealed that chronic infection in humans is a risk factor for developing mental diseases. However, the mechanisms underlying parasite-induced neuronal dysfunction in the brain remain unclear. Here, we examined memory associated with conditioned fear in mice and found that T. gondii infection impairs consolidation of conditioned fear memory. To examine the brain pathology induced by T. gondii infection, we analyzed the parasite load and histopathological changes. T. gondii infects all brain areas, yet the cortex exhibits more severe tissue damage than other regions. We measured neurotransmitter levels in the cortex and amygdala because these regions are involved in fear memory expression. The levels of dopamine metabolites but not those of dopamine were increased in the cortex of infected mice compared with those in the cortex of uninfected mice. In contrast, serotonin levels were decreased in the amygdala and norepinephrine levels were decreased in the cortex and amygdala of infected mice. The levels of cortical dopamine metabolites were associated with the time spent freezing in the fear-conditioning test. These results suggest that T. gondii infection affects fear memory through dysfunction of the cortex and amygdala. Our findings provide insight into the mechanisms underlying the neurological changes seen during T. gondii infection. PMID:27456832

  19. Modeling Zika Virus Infection in Mice.

    Science.gov (United States)

    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

  20. Augmented effect of early antibiotic treatment in mice with experimental lung infections due to sequentially adapted mucoid strains of Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    van Gennip, M; Moser, Claus; Christensen, Louise D;

    2009-01-01

    Background: Effects of treatment with tobramycin initiated 1 or 24 h post-infection were investigated in a new version of a pulmonary infection model in mice. The model reflects the differentiated behaviour of Pseudomonas aeruginosa mucoid strains isolated from the lungs of one chronically infect...

  1. Genus Phyllanthus for chronic hepatitis B virus infection

    DEFF Research Database (Denmark)

    Liu, J; Lin, Haili; McIntosh, H

    2001-01-01

    To evaluate the efficacy and safety of genus Phyllanthus for chronic hepatitis B virus (HBV) infection we performed a systematic review of randomized clinical trials. Randomized trials comparing genus Phyllanthus vs. placebo, no intervention, general nonspecific treatment, other herbal medicine...

  2. Phenotypes selected during chronic lung infection in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Ciofu, Oana; Mandsberg, Lotte F; Wang, Hengzhuang;

    2012-01-01

    During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated...... the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis....

  3. Chronic inhibition of cyclooxygenase-2 attenuates antibody responses against vaccinia infection.

    Science.gov (United States)

    Bernard, Matthew P; Bancos, Simona; Chapman, Timothy J; Ryan, Elizabeth P; Treanor, John J; Rose, Robert C; Topham, David J; Phipps, Richard P

    2010-02-01

    Generation of optimal humoral immunity to vaccination is essential to protect against devastating infectious agents such as the variola virus that causes smallpox. Vaccinia virus (VV), employed as a vaccine against smallpox, provides an important model of infection. Herein, we evaluated the importance cyclooxygenase-2 (Cox-2) in immunity to VV using Cox-2 deficient mice and Cox-2 selective inhibitory drugs. The effects of Cox-2 inhibition on antibody responses to live viruses such as vaccinia have not been previously described. Here, we used VV infection in Cox-2 deficient mice and in mice chronically treated with Cox-2 selective inhibitors and show that the frequency of VV-specific B cells was reduced, as well as the production of neutralizing IgG. VV titers were approximately 70 times higher in mice treated with a Cox-2 selective inhibitor. Interestingly, Cox-2 inhibition also reduced the frequency of IFN-gamma producing CD4(+) T helper cells, important for class switching. The significance of these results is that the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), and other drugs that inhibit Cox-2 activity or expression, blunt the ability of B cells to produce anti-viral antibodies, thereby making vaccines less effective and possibly increasing susceptibility to viral infection. These new findings support an essential role for Cox-2 in regulating humoral immunity.

  4. IL-23 p19 knockout mice exhibit minimal defects in responses to primary and secondary infection with Francisella tularensis LVS.

    Directory of Open Access Journals (Sweden)

    Sherry L Kurtz

    Full Text Available Our laboratory's investigations into mechanisms of protective immunity against Francisella tularensis Live Vaccine Strain (LVS have uncovered mediators important in host defense against primary infection, as well as those correlated with successful vaccination. One such potential correlate was IL-12p40, a pleiotropic cytokine that promotes Th1 T cell function as part of IL-12p70. LVS-infected IL-12p40 deficient knockout (KO mice maintain a chronic infection, but IL-12p35 KO mice clear LVS infection; thus the role that IL-12p40 plays in immunity to LVS is independent of the IL-12p70 heterodimer. IL-12p40 can also partner with IL-23p19 to create the heterodimeric cytokine IL-23. Here, we directly tested the role of IL-23 in LVS resistance, and found IL-23 to be largely dispensable for immunity to LVS following intradermal or intranasal infection. IL-23p19 KO splenocytes were fully competent in controlling intramacrophage LVS replication in an in vitro overlay assay. Further, antibody responses in IL-23p19 KO mice were similar to those of normal wild type mice after LVS infection. IL-23p19 KO mice or normal wild type mice that survived primary LVS infection survived maximal doses of LVS secondary challenge. Thus p40 has a novel role in clearance of LVS infection that is unrelated to either IL-12 or IL-23.

  5. Chronic wasting disease of deer and elk in transgenic mice: oral transmission and pathobiology.

    Science.gov (United States)

    Trifilo, Matthew J; Ying, Ge; Teng, Chao; Oldstone, Michael B A

    2007-08-15

    To study the pathogenesis of chronic wasting disease (CWD) in deer and elk, transgenic (tg) mice were generated that expressed the prion protein (PrP) of deer containing a glycine at amino acid (aa) 96 and a serine at aa 225 under transcriptional control of the murine PrP promoter. This construct was introduced into murine PrP-deficient mice. As anticipated, neither non-tg mice nor PrP ko mice were susceptible when inoculated intracerebrally (i.c.) or orally with CWD brain material (scrapie pool from six mule deer) and followed for 600+ days (dpi). Deer PrP tg mice were not susceptible to i.c. inoculation with murine scrapie. In contrast, a fatal neurologic disease occurred accompanied by conversion of deer PrPsen to PrPres by western blot and immunohistochemistry after either i.c. inoculation with CWD brain into two lines of tg mice studied (312+32 dpi [mean+2 standard errors] for the heterozygous tg line 33, 275+46 dpi for the heterozygous tg line 39 and 210 dpi for the homozygous tg line 33) or after oral inoculation (381+55 dpi for the homozygous tg line 33 and 370+26 dpi for the homozygous tg line 39). Kinetically, following oral inoculation of CWD brain, PrPres was observed by day 200 when mice were clinically healthy in the posterior surface of the dorsum of the tongue primarily in serous and mucous glands, in the intestines, in large cells at the splenic marginal zone that anatomically resembled follicular dendritic cells and macrophages and in the olfactory bulb and brain stem but did not occur in the cerebellum, cerebral cortex or hippocampus or in hearts, lungs and livers of infected mice. After 350 days when mice become clinically ill the cerebellum, cerebral cortex and hippocampus became positive for PrPres and displayed massive spongiosis, neuronal drop out, gliosis and florid plaques. PMID:17451773

  6. EXPERIMENTAL-INFECTION IN MICE WITH BACILLUS-LICHENIFORMIS

    DEFF Research Database (Denmark)

    Agerholm, J.S.; Jensen, H.E.; Jensen, N.E.

    1995-01-01

    The pathogenicity of Bacillus licheniformis was assessed in normal and immunodepressed BALB/c mice. The animals were challenged intravenously with 4 x 10(7) colony forming units of B, licheniformis (ATCC 14580) and both normal and immunodepressed mice were susceptible. However, the infection was...... more severe in the immunosuppressed animals. In normal mice, lesions were restricted to the liver and kidneys, while lesions also occurred in other organs of immunodepressed mice. By crossed immunoelectrophoresis it was shown that antigens of B. licheniformis are potent immunogens, and the bacteria...

  7. Tumor suppressor p53 protects mice against Listeria monocytogenes infection.

    Science.gov (United States)

    Wang, Shaohui; Liu, Pingping; Wei, Jianchao; Zhu, Zixiang; Shi, Zixue; Shao, Donghua; Ma, Zhiyong

    2016-01-01

    Tumor suppressor p53 is involved in regulating immune responses, which contribute to antitumor and antiviral activity. However, whether p53 has anti-bacterial functions remains unclear. Listeria monocytogenes (LM) causes listeriosis in humans and animals, and it is a powerful model for studying innate and adaptive immunity. In the present study, we illustrate an important regulatory role of p53 during LM infection. p53 knockout (p53KO) mice were more susceptible to LM infection, which was manifested by a shorter survival time and lower survival rate. p53KO mice showed significant impairments in LM eradication. Knockdown of p53 in RAW264.7 and HeLa cells resulted in increased invasion and intracellular survival of LM. Furthermore, the invasion and intracellular survival of LM was inhibited in p53-overexpressing RAW264.7 and HeLa cells. LM-infected p53KO mice exhibited severe clinical symptoms and organ injury, presumably because of the abnormal production of the pro-inflammatory cytokines TNF-α, IL-6, IL-12, and IL-18. Decreased IFN-γ and GBP1 productions were observed in LM-infected p53-deficient mice or cells. The combination of these defects likely resulted in the overwhelming LM infection in the p53KO mice. These observations indicate that p53 serves as an important regulator of the host innate immune that protects against LM infection. PMID:27644341

  8. Ribavirin monotherapy for chronic hepatitis C infection

    DEFF Research Database (Denmark)

    Brok, Jesper; Gluud, Lise L; Gluud, Christian

    2006-01-01

    Adding ribavirin to interferon improves treatment response for patients with chronic hepatitis C, but the effects of ribavirin monotherapy are unclear. We conducted a systematic review to assess the benefits and harms of ribavirin monotherapy for patients with chronic hepatitis C....

  9. Invasive fungal infections in patients with chronic granulomatous disease

    NARCIS (Netherlands)

    Henriet, S.S.V.; Verweij, P.E.; Holland, S.M.; Warris, A.

    2013-01-01

    Invasive fungal infections are a major threat for chronic granulomatous disease (CGD) patients. The present study provides a comprehensive overview of published invasive fungal infections in the CGD host through an extensive review of epidemiological, clinical, diagnostic and therapeutic data. In ad

  10. Chronic hepatitis E infection in lung transplant recipients

    NARCIS (Netherlands)

    Riezebos-Brilman, Annelies; Puchhammer-Stockl, Elisabeth; van der Weide, Hinke Y.; Haagsma, Elizabeth B.; Jaksch, Peter; Bejvl, Isabella; Niesters, Hubert G.; Verschuuren, Erik A. M.

    2013-01-01

    BACKGROUND: Hepatitis E virus (HEV) genotype 3 has been identified in patients with autochthonous HEV infections in developed countries and is currently being recognized as an emerging zoonotic pathogen. HEV infection may lead to a chronic hepatitis in immune-compromised patients. METHODS: We studie

  11. Single-epitope DNA vaccination prevents exhaustion and facilitates a broad antiviral CD8+ T cell response during chronic viral infection

    DEFF Research Database (Denmark)

    Bartholdy, Christina; Stryhn, Anette; Christensen, Jan Pravsgaard;

    2004-01-01

    of DNA vaccines encoding immunodominant epitopes of lymphocytic choriomeningitis virus (LCMV). We analyzed the spectrum of the CD8+ T cell response and the susceptibility to infection in H-2(b) and H-2(d) mice. Priming for a monospecific, CD8+ T cell response did not render mice susceptible to viral...... variants. Thus, vaccinated mice were protected against chronic infection with LCMV, and no evidence indicating biologically relevant viral escape was obtained. In parallel, a broad and sustained CD8+ T cell response was generated upon infection, and in H-2(d) mice epitope spreading was observed. Even after...... acute LCMV infection, DNA vaccination did not significantly impair naturally induced immunity. Thus, the response to the other immunogenic epitopes was not dramatically suppressed in DNA-immunized mice undergoing normal immunizing infection, and the majority of mice were protected against rechallenge...

  12. Memory Deficit Recovery after Chronic Vanadium Exposure in Mice

    Directory of Open Access Journals (Sweden)

    Oluwabusayo Folarin

    2016-01-01

    Full Text Available Vanadium is a transitional metal with an ability to generate reactive oxygen species in the biological system. This work was designed to assess memory deficits in mice chronically exposed to vanadium. A total of 132 male BALB/c mice (4 weeks old were used for the experiment and were divided into three major groups of vanadium treated, matched controls, and animals exposed to vanadium for three months and thereafter vanadium was withdrawn. Animals were tested using Morris water maze and forelimb grip test at 3, 6, 9, and 12 months of age. The results showed that animals across the groups showed no difference in learning but had significant loss in memory abilities after 3 months of vanadium exposure and this trend continued in all vanadium-exposed groups relative to the controls. Animals exposed to vanadium for three months recovered significantly only 9 months after vanadium withdrawal. There was no significant difference in latency to fall in the forelimb grip test between vanadium-exposed groups and the controls in all age groups. In conclusion, we have shown that chronic administration of vanadium in mice leads to memory deficit which is reversible but only after a long period of vanadium withdrawal.

  13. Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice

    Directory of Open Access Journals (Sweden)

    Asquith Kelly L

    2010-02-01

    Full Text Available Abstract Background Early-life respiratory viral infections, notably with respiratory syncytial virus (RSV, increase the risk of subsequent development of childhood asthma. The purpose of this study was to assess whether early-life infection with a species-specific model of RSV and subsequent allergen exposure predisposed to the development of features of asthma. Methods We employed a unique combination of animal models in which BALB/c mice were neonatally infected with pneumonia virus of mice (PVM, which replicates severe RSV disease in human infants and following recovery, were intranasally sensitised with ovalbumin. Animals received low-level challenge with aerosolised antigen for 4 weeks to elicit changes of chronic asthma, followed by a single moderate-level challenge to induce an exacerbation of inflammation. We then assessed airway inflammation, epithelial changes characteristic of remodelling, airway hyperresponsiveness (AHR and host immunological responses. Results Allergic airway inflammation, including recruitment of eosinophils, was prominent only in animals that had recovered from neonatal infection with PVM and then been sensitised and chronically challenged with antigen. Furthermore, only these mice exhibited an augmented Th2-biased immune response, including elevated serum levels of anti-ovalbumin IgE and IgG1 as well as increased relative expression of Th2-associated cytokines IL-4, IL-5 and IL-13. By comparison, development of AHR and mucous cell change were associated with recovery from PVM infection, regardless of subsequent allergen challenge. Increased expression of IL-25, which could contribute to induction of a Th2 response, was demonstrable in the lung following PVM infection. Signalling via the IL-4 receptor α chain was crucial to the development of allergic inflammation, mucous cell change and AHR, because all of these were absent in receptor-deficient mice. In contrast, changes of remodelling were evident in mice

  14. Control of Mycobacterial Infections in Mice Expressing Human Tumor Necrosis Factor (TNF) but Not Mouse TNF.

    Science.gov (United States)

    Olleros, Maria L; Chavez-Galan, Leslie; Segueni, Noria; Bourigault, Marie L; Vesin, Dominique; Kruglov, Andrey A; Drutskaya, Marina S; Bisig, Ruth; Ehlers, Stefan; Aly, Sahar; Walter, Kerstin; Kuprash, Dmitry V; Chouchkova, Miliana; Kozlov, Sergei V; Erard, François; Ryffel, Bernard; Quesniaux, Valérie F J; Nedospasov, Sergei A; Garcia, Irene

    2015-09-01

    Tumor necrosis factor (TNF) is an important cytokine for host defense against pathogens but is also associated with the development of human immunopathologies. TNF blockade effectively ameliorates many chronic inflammatory conditions but compromises host immunity to tuberculosis. The search for novel, more specific human TNF blockers requires the development of a reliable animal model. We used a novel mouse model with complete replacement of the mouse TNF gene by its human ortholog (human TNF [huTNF] knock-in [KI] mice) to determine resistance to Mycobacterium bovis BCG and M. tuberculosis infections and to investigate whether TNF inhibitors in clinical use reduce host immunity. Our results show that macrophages from huTNF KI mice responded to BCG and lipopolysaccharide similarly to wild-type macrophages by NF-κB activation and cytokine production. While TNF-deficient mice rapidly succumbed to mycobacterial infection, huTNF KI mice survived, controlling the bacterial burden and activating bactericidal mechanisms. Administration of TNF-neutralizing biologics disrupted the control of mycobacterial infection in huTNF KI mice, leading to an increased bacterial burden and hyperinflammation. Thus, our findings demonstrate that human TNF can functionally replace murine TNF in vivo, providing mycobacterial resistance that could be compromised by TNF neutralization. This new animal model will be helpful for the testing of specific biologics neutralizing human TNF. PMID:26123801

  15. Systemic and mucosal immune reactivity upon Mycobacterium avium ssp. paratuberculosis infection in mice.

    Directory of Open Access Journals (Sweden)

    Arzu Koc

    Full Text Available Mycobacterium avium ssp. paratuberculosis (MAP is the cause of Johne's disease, an inflammatory bowel disorder of ruminants. Due to the similar pathology, MAP was also suggested to cause Crohn's disease (CD. Despite of intensive research, this question is still not settled, possibly due to the lack of versatile mouse models. The aim of this study was to identify basic immunologic mechanisms in response to MAP infection. Immune compromised C57BL/6 Rag2-/- mice were infected with MAP intraperitoneally. Such chronically infected mice were then reconstituted with CD4+ and CD8+ T cells 28 days after infection. A systemic inflammatory response, detected as enlargement of the spleen and granuloma formation in the liver, was observed in mice infected and reconstituted with CD4+ T cells. Whereby inflammation in infected and CD4+CD45RB(hi T cell reconstituted animals was always higher than in the other groups. Reconstitution of infected animals with CD8+ T cells did not result in any inflammatory signs. Interestingly, various markers of inflammation were strongly up-regulated in the colon of infected mice reconstituted with CD4+CD45RB(lo/int T cells. We propose, the usual non-colitogenic CD4+CD45RB(lo/int T cells were converted into inflammatory T cells by the interaction with MAP. However, the power of such cells might be not sufficient for a fully established inflammatory response in the colon. Nevertheless, our model system appears to mirror aspects of an inflammatory bowel disease (IBD like CD and Johne's diseases. Thus, it will provide an experimental platform on which further knowledge on IBD and the involvement of MAP in the induction of CD could be acquired.

  16. Toxoplasma gondii oral infection induces intestinal inflammation and retinochoroiditis in mice genetically selected for immune oral tolerance resistance.

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    Raul Ramos Furtado Dias

    Full Text Available Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS or resistance (TR to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis.

  17. Chronic filarial infection provides protection against bacterial sepsis by functionally reprogramming macrophages.

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    Fabian Gondorf

    2015-01-01

    Full Text Available Helminths immunomodulate their hosts and induce a regulatory, anti-inflammatory milieu that prevents allergies and autoimmune diseases. Helminth immunomodulation may benefit sepsis outcome by preventing exacerbated inflammation and severe pathology, but the influence on bacterial clearance remains unclear. To address this, mice were chronically infected with the filarial nematode Litomosoides sigmodontis (L.s. and the outcome of acute systemic inflammation caused by i.p. Escherichia coli injection was determined. L.s. infection significantly improved E. coli-induced hypothermia, bacterial clearance and sepsis survival and correlated with reduced concentrations of associated pro-inflammatory cytokines/chemokines and a less pronounced pro-inflammatory macrophage gene expression profile. Improved sepsis outcome in L.s.-infected animals was mediated by macrophages, but independent of the alternatively activated macrophage subset. Endosymbiotic Wolbachia bacteria that are present in most human pathogenic filariae, as well as L.s., signal via TLR2 and modulate macrophage function. Here, gene expression profiles of peritoneal macrophages from L.s.-infected mice revealed a downregulation of genes involved in TLR signaling, and pulsing of macrophages in vitro with L.s. extract reduced LPS-triggered activation. Subsequent transfer improved sepsis outcome in naïve mice in a Wolbachia- and TLR2-dependent manner. In vivo, phagocytosis was increased in macrophages from L.s.-infected wild type, but not TLR2-deficient animals. In association, L.s. infection neither improved bacterial clearance in TLR2-deficient animals nor ameliorated E. coli-induced hypothermia and sepsis survival. These results indicate that chronic L.s. infection has a dual beneficial effect on bacterial sepsis, reducing pro-inflammatory immune responses and improving bacterial control. Thus, helminths and their antigens may not only improve the outcome of autoimmune and allergic diseases

  18. Chronic obstructive pulmonary disease and risk of infection

    DEFF Research Database (Denmark)

    Lange, Peter

    2009-01-01

    bacteria causing acute exacerbations. Also lung infections like pneumonia, lung abscess and empyema are more often seen in patients with COPD than in healthy subjects. With regard to extrapulmonary infections, it seems that COPD patients are not at higher risk of infection compared with subjects without......This review article focuses on the risk of infections in patients with chronic obstructive pulmonary disease (COPD). Throughout the years there have been a number of studies describing the risk of pulmonary infections in patients with COPD, whereas only few studies have focused on the risk of...... infection outside the lungs. With increasing severity of COPD the risk of respiratory tract infection also increases. The impairment of the innate immune system is most likely responsible for both the colonization of respiratory tract with bacteria and for an increased risk of infection with new strains of...

  19. Chronic obstructive pulmonary disease and risk of infection

    DEFF Research Database (Denmark)

    Lange, Peter

    2009-01-01

    This review article focuses on the risk of infections in patients with chronic obstructive pulmonary disease (COPD). Throughout the years there have been a number of studies describing the risk of pulmonary infections in patients with COPD, whereas only few studies have focused on the risk...... of infection outside the lungs. With increasing severity of COPD the risk of respiratory tract infection also increases. The impairment of the innate immune system is most likely responsible for both the colonization of respiratory tract with bacteria and for an increased risk of infection with new strains...... of bacteria causing acute exacerbations. Also lung infections like pneumonia, lung abscess and empyema are more often seen in patients with COPD than in healthy subjects. With regard to extrapulmonary infections, it seems that COPD patients are not at higher risk of infection compared with subjects without...

  20. Transplacental murine cytomegalovirus infection in the brain of SCID mice

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    Jaquish Dawn V

    2007-03-01

    Full Text Available Abstract Background Congenital cytomegalovirus (CMV infection is the most common congenital viral infection in humans and the major nonhereditary cause of central nervous system (CNS developmental disorders. Previous attempts to develop a murine CMV (MCMV model of natural congenital human CMV (HCMV infection have failed because MCMV does not cross the placenta in immunocompetent mice. Results In marked contrast with immunocompetent mice, C.B-17 SCID (severe combined immunodeficient mice were found to be highly susceptible to natural MCMV transplacental transmission and congenital infection. Timed-pregnant SCID mice were intraperitoneally (IP injected with MCMV at embryonic (E stages E0-E7, and vertical MCMV transmission was evaluated using nested polymerase chain reaction (nPCR, in situ hybridization (ISH and immunohistochemical (IHC assays. SCID mouse dams IP injected at E0 with 102 PFU of MCMV died or resorbed their fetuses by E18. Viable fetuses collected at E18 from SCID mice IP injected with 102–104 PFU of MCMV at E7 did not demonstrate vertical MCMV transmission. Notably, transplacental MCMV transmission was confirmed in E18 fetuses from SCID mice IP injected with 103 PFU of MCMV at stages E3-E5. The maximum rate of transplacental MCMV transmission (53% at E18 occurred when SCID mouse dams were IP injected with 103 PFU of MCMV at E4. Congenital infection was confirmed by IHC immunostaining of MCMV antigens in 26% of the MCMV nPCR positive E18 fetuses. Transplacental MCMV transmission was associated with intrauterine growth retardation and microcephaly. Additionally, E18 fetuses with MCMV nPCR positive brains had cerebral interleukin-1α (IL-1α expression significantly upregulated and cerebral IL-1 receptor II (IL-1RII transcription significantly downregulated. However, MCMV-induced changes in cerebral cytokine expression were not associated with any histological signs of MCMV infection or inflammation in the brain. Conclusion Severe T

  1. Chronic hepatitis caused by persistent parvovirus B19 infection

    Directory of Open Access Journals (Sweden)

    Mogensen Trine H

    2010-08-01

    Full Text Available Abstract Background Human infection with parvovirus B19 may lead to a diverse spectrum of clinical manifestations, including benign erythema infectiosum in children, transient aplastic crisis in patients with haemolytic anaemia, and congenital hydrops foetalis. These different diseases represent direct consequences of the ability of parvovirus B19 to target the erythroid cell lineage. However, accumulating evidence suggests that this virus can also infect other cell types resulting in diverse clinical manifestations, of which the pathogenesis remains to be fully elucidated. This has prompted important questions regarding the tropism of the virus and its possible involvement in a broad range of infectious and autoimmune medical conditions. Case Presentation Here, we present an unusual case of persistent parvovirus B19 infection as a cause of chronic hepatitis. This patient had persistent parvovirus B19 viraemia over a period of more than four years and displayed signs of chronic hepatitis evidenced by fluctuating elevated levels of ALAT and a liver biopsy demonstrating chronic hepatitis. Other known causes of hepatitis and liver damage were excluded. In addition, the patient was evaluated for immunodeficiency, since she had lymphopenia both prior to and following clearance of parvovirus B19 infection. Conclusions In this case report, we describe the current knowledge on the natural history and pathogenesis of parvovirus B19 infection, and discuss the existing evidence of parvovirus B19 as a cause of acute and chronic hepatitis. We suggest that parvovirus B19 was the direct cause of this patient's chronic hepatitis, and that she had an idiopathic lymphopenia, which may have predisposed her to persistent infection, rather than bone marrow depression secondary to infection. In addition, we propose that her liver involvement may have represented a viral reservoir. Finally, we suggest that clinicians should be aware of parvovirus B19 as an unusual

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  4. Incidence, severity, and prevention of infections in chronic granulomatous disease.

    Science.gov (United States)

    Mouy, R; Fischer, A; Vilmer, E; Seger, R; Griscelli, C

    1989-04-01

    We retrospectively analyzed the frequency and nature of infections occurring in 48 patients with chronic granulomatous disease. The long-term use of trimethoprim-sulfamethoxazole and ketoconazole as a preventive therapy for infections has also been evaluated. Lymphadenitis, lung infections, dermatitis, enteral infections, and hepatic abscesses were the most frequent infections. Staphylococcus aureus, Salmonella, and Aspergillus were the main microorganisms encountered. Twelve patients died: five from lung aspergillosis, three from hepatic abscesses, two from pneumonopathy of unknown origin, one from salmonellosis, and one from another probable infection that could not be proved. The actuarial survival rate was 50% at 10 years of age, with a prolonged plateau thereafter. There was no difference in survival rates between patients with X-linked and those with autosomal recessive chronic granulomatous disease. The 8-year actuarial survival rate was significantly higher for patients born in 1978 or afterward than for patients born before 1978 (92.9% vs 70.5%). A retrospective analysis of the occurrence of bacterial and fungal infections in patients who received trimethoprim-sulfamethoxazole and ketoconazole as infection prophylaxis indicated that the former was effective against bacterial infections but that ketoconazole provided no protection against Aspergillus infections.

  5. Borrelia burgdorferi erp genes are expressed at different levels within tissues of chronically infected mammalian hosts.

    Science.gov (United States)

    Miller, Jennifer C; Stevenson, Brian

    2006-05-01

    The spirochete Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted to humans and other vertebrate hosts through the bites of ixodid ticks. B. burgdorferi Erp (OspE-F related lipoprotein) family members are encoded on members of the 32 kb circular plasmid-like prophage family (cp32s). Many Erp proteins serve as receptors for the complement inhibitory factor H molecules of numerous vertebrate hosts, providing one mechanism by which the bacteria potentially evade the innate immune system. Indirect immunofluorescence analyses (IFA) have demonstrated that Erp expression is temporally regulated throughout the mammal-tick infectious cycle, indicating that Erp proteins perform an important role (or even roles) during mammalian infection. However, it was not previously known whether Erp proteins are continually produced by B. burgdorferi throughout the course of mammalian infection. To address this issue, quantitative RT-PCR (q-RT-PCR) was utilized to assess erp transcription levels by bacteria within numerous different tissues of both mice and non-human primates (NHPs) chronically infected with B. burgdorferi. Q-RT-PCR results obtained using both animal models indicated that while the majority of erp genes were detectably transcribed during chronic infection, differences in expression levels were noted. These data strongly suggest that Erp proteins contribute to B. burgdorferi persistence within chronically infected host tissues, perhaps by protecting the bacteria from complement-mediated killing. PMID:16530008

  6. [Association between chronic urinary tract infection and primary biliary cirrhosis].

    Science.gov (United States)

    Xu, Y; Wang, J B; Wang, S

    2016-06-01

    The etiology of primary biliary cirrhosis (PBC) remains unclear, and at present, this disease is considered to be caused by the combined effect of genetic factors, infection, autoimmunity, and environmental factors. Since infection is the major cause for PBC, scholars have been focusing on the association between chronic microbial infection. Studies have shown that Escherichia coli is the most common bacterium for urinary tract infection (UTI), and recurrent UTI has been confirmed to be a risk factor for the development and progression of autoimmune liver diseases and is closely associated with PBC. This article investigates the association between UTI and PBC and possible mechanisms. PMID:27465958

  7. Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1.

    Directory of Open Access Journals (Sweden)

    Erin McElvania Tekippe

    Full Text Available The NLR gene family mediates host immunity to various acute pathogenic stimuli, but its role in chronic infection is not known. This paper addressed the role of NLRP3 (NALP3, its adaptor protein PYCARD (ASC, and caspase-1 during infection with Mycobacterium tuberculosis (Mtb. Mtb infection of macrophages in culture induced IL-1beta secretion, and this requires the inflammasome components PYCARD, caspase-1, and NLRP3. However, in vivo Mtb aerosol infection of Nlrp3(-/-, Casp-1(-/-, and WT mice showed no differences in pulmonary IL-1beta production, bacterial burden, or long-term survival. In contrast, a significant role was observed for Pycard in host protection during chronic Mtb infection, as shown by an abrupt decrease in survival of Pycard(-/- mice. Decreased survival of Pycard(-/- animals was associated with defective granuloma formation. These data demonstrate that PYCARD exerts a novel inflammasome-independent role during chronic Mtb infection by containing the bacteria in granulomas.

  8. The role of bacterial biofilms in chronic infections.

    Science.gov (United States)

    Bjarnsholt, Thomas

    2013-05-01

    Acute infections caused by pathogenic bacteria have been studied extensively for well over 100 years. These infections killed millions of people in previous centuries, but they have been combated effectively by the development of modern vaccines, antibiotics and infection control measures. Most research into bacterial pathogenesis has focused on acute infections, but these diseases have now been supplemented by a new category of chronic infections caused by bacteria growing in slime-enclosed aggregates known as biofilms. Biofilm infections, such as pneumonia in cystic fibrosis patients, chronic wounds, chronic otitis media and implant- and catheter-associated infections, affect millions of people in the developed world each year and many deaths occur as a consequence. In general, bacteria have two life forms during growth and proliferation. In one form, the bacteria exist as single, independent cells (planktonic) whereas in the other form, bacteria are organized into sessile aggregates. The latter form is commonly referred to as the biofilm growth phenotype. Acute infections are assumed to involve planktonic bacteria, which are generally treatable with antibiotics, although successful treatment depends on accurate and fast diagnosis. However, in cases where the bacteria succeed in forming a biofilm within the human host, the infection often turns out to be untreatable and will develop into a chronic state. The important hallmarks of chronic biofilm-based infections are extreme resistance to antibiotics and many other conventional antimicrobial agents, and an extreme capacity for evading the host defences. In this thesis, I will assemble the current knowledge on biofilms with an emphasis on chronic infections, guidelines for diagnosis and treatment of these infections, before relating this to my previous research into the area of biofilms. I will present evidence to support a view that the biofilm lifestyle dominates chronic bacterial infections, where bacterial

  9. Subclinical microbial infection in patients with chronic plaque psoriasis.

    Science.gov (United States)

    Bartenjev, I; Rogl Butina, M; Potocnik, M

    2000-01-01

    Epidemiological evidence implicates bacterial infection as a common triggering stimulus for psoriasis. Recent studies suggest that continuing, subclinical streptococcal and staphylococcal infections might be responsible not only for relapse of acute guttate psoriasis but also for a new episode of chronic plaque psoriasis. In this study 195 patients suffering from a severe form of chronic plaque psoriasis hospitalized between 1996 and 1998 were examined. The presence of subclinical microbial infection of the upper respiratory tract was studied by the cultivation of pathogens from this area. Patients with other provoking factors, such as a positive history of taking any drugs that may exacerbate psoriasis, endocrine and metabolic factors, alcohol abuse, trauma, dental focus and clinically evident bacterial infection, were excluded. Subclinical streptococcal and/or staphylococcal infections were detected in 68% of tested patients and in only 11% of the control group. The results of this study indicate that subclinical bacterial infections of the upper respiratory tract may be an important factor in provoking a new relapse of chronic plaque psoriasis. Searching for, and eliminating, microbial infections could be of importance in the treatment of psoriasis.

  10. PIR-B-deficient mice are susceptible to Salmonella infection.

    Science.gov (United States)

    Torii, Ikuko; Oka, Satoshi; Hotomi, Muneki; Benjamin, William H; Takai, Toshiyuki; Kearney, John F; Briles, David E; Kubagawa, Hiromi

    2008-09-15

    Paired Ig-like receptors of activating (PIR-A) and inhibitory (PIR-B) isoforms are expressed by many hematopoietic cells, including B lymphocytes and myeloid cells. To determine the functional roles of PIR-A and PIR-B in primary bacterial infection, PIR-B-deficient (PIR-B(-/-)) and wild-type (WT) control mice were injected i.v. with an attenuated strain of Salmonella enterica Typhimurium (WB335). PIR-B(-/-) mice were found to be more susceptible to Salmonella infection than WT mice, as evidenced by high mortality rate, high bacterial loads in the liver and spleen, and a failure to clear bacteria from the circulation. Although blood levels of major cytokines and Salmonella-specific Abs were mostly comparable in the two groups of mice, distinct patterns of inflammatory lesions were found in their livers at 7-14 days postinfection: diffuse spreading along the sinusoids in PIR-B(-/-) mice vs nodular restricted localization in WT mice. PIR-B(-/-) mice have more inflammatory cells in the liver but fewer B cells and CD8(+) T cells in the spleen than WT mice at 14 days postinfection. PIR-B(-/-) bone marrow-derived macrophages (BMMphi) failed to control intracellular replication of Salmonella in vitro, in part due to inefficient phagosomal oxidant production, when compared with WT BMMphi. PIR-B(-/-) BMMphi also produced more nitrite and TNF-alpha upon exposure to Salmonella than WT BMMphi did. These findings suggest that the disruption of PIR-A and PIR-B balance affects their regulatory roles in host defense to bacterial infection.

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

    Directory of Open Access Journals (Sweden)

    Juliana Barreto-de-Albuquerque

    2015-06-01

    Full Text Available 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 5x10(4 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

  12. Biofilms in chronic infections - a matter of opportunity - monospecies biofilms in multispecies infections

    DEFF Research Database (Denmark)

    Burmølle, Mette; Thomsen, Trine Rolighed; Fazli, Mustafa;

    2010-01-01

    It has become evident that aggregation or biofilm formation is an important survival mechanism for bacteria in almost any environment. In this review, we summarize recent visualizations of bacterial aggregates in several chronic infections (chronic otitis media, cystic fibrosis, infection due...... to permanent tissue fillers and chronic wounds) both as to distribution (such as where in the wound bed) and organization (monospecies or multispecies microcolonies). We correlate these biofilm observations to observations of commensal biofilms (dental and intestine) and biofilms in natural ecosystems (soil......). The observations of the chronic biofilm infections point toward a trend of low bacterial diversity and sovereign monospecies biofilm aggregates even though the infection in which they reside are multispecies. In contrast to this, commensal and natural biofilm aggregates contain multiple species that are believed...

  13. Chronic mucus hypersecretion in COPD and death from pulmonary infection

    DEFF Research Database (Denmark)

    Prescott, E; Lange, P; Vestbo, J

    1995-01-01

    The association of chronic mucus hypersecretion and mortality is a matter of debate. We wished to determine whether the relationship between chronic mucus hypersecretion and chronic obstructive pulmonary disease (COPD)-related mortality could be explained by proneness to pulmonary infection. We...... followed 14,223 subjects of both sexes for 10-12 yrs. Cases where COPD was an underlying or contributory cause of death (n = 214) were included, and hospital records were obtained when possible (n = 101). From the presence of increased mucus, purulent mucus, fever, leucocytosis and infiltration on chest...... without chronic mucus hypersecretion. Controlling for covariates, in particular smoking habits, a Cox analysis showed a strong inverse relationship between ventilatory function and COPD-related mortality. Chronic mucus hypersecretion was found to be a significant predictor of COPD-related death with...

  14. Chronic Pseudomonas aeruginosa infection definition: EuroCareCF Working Group report

    DEFF Research Database (Denmark)

    Pressler, T; Bohmova, C; Conway, S;

    2011-01-01

    Chronic pulmonary infection with P. aeruginosa develops in most patients with cystic fibrosis (CF); by adulthood 80% of patients are infected and chronic P. aeruginosa infection is the primary cause of increased morbidity and mortality in CF. Chronic infection is preceded by an intermittent stage...

  15. Species-specific immunity induced by infection with Entamoeba histolytica and Entamoeba moshkovskii in mice.

    Science.gov (United States)

    Shimokawa, Chikako; Culleton, Richard; Imai, Takashi; Suzue, Kazutomo; Hirai, Makoto; Taniguchi, Tomoyo; Kobayashi, Seiki; Hisaeda, Hajime; Hamano, Shinjiro

    2013-01-01

    Entamoeba histolytica, the parasitic amoeba responsible for amoebiasis, causes approximately 100,000 deaths every year. There is currently no vaccine against this parasite. We have previously shown that intracecal inoculation of E. histolytica trophozoites leads to chronic and non-healing cecitis in mice. Entamoeba moshkovskii, a closely related amoeba, also causes diarrhea and other intestinal disorders in this model. Here, we investigated the effect of infection followed by drug-cure of these species on the induction of immunity against homologous or heterologous species challenge. Mice were infected with E. histolytica or E. moshkovskii and treated with metronidazole 14 days later. Re-challenge with E. histolytica or E. moshkovskii was conducted seven or 28 days following confirmation of the clearance of amoebae, and the degree of protection compared to non-exposed control mice was evaluated. We show that primary infection with these amoebae induces a species-specific immune response which protects against challenge with the homologous, but not a heterologous species. These findings pave the way, therefore, for the identification of novel amoebae antigens that may become the targets of vaccines and provide a useful platform to investigate host protective immunity to Entamoeba infections.

  16. First attempt to produce experimental Campylobacter concisus infection in mice

    DEFF Research Database (Denmark)

    Aabenhus, R.; Stenram, U.; Andersen, L.P.;

    2008-01-01

    AIM: To infect mice with atypical Campylobacter concisus (C. concisus) for the first time. METHODS: Three separate experiments were conducted in order to screen the ability of five clinical C. concisus isolates of intestinal origin and the ATCC 33237 type strain of oral origin to colonize and...

  17. Turnover of T cells in murine gammaherpesvirus 68-infected mice

    DEFF Research Database (Denmark)

    Hamilton-Easton, A M; Christensen, Jan Pravsgaard; Doherty, P C

    1999-01-01

    Respiratory challenge of C57BL/6 mice with murine gammaherpesvirus 68 induces proliferation of T lymphocytes early after infection, as evidenced by incorporation of the DNA precursor bromodeoxyuridine. Using pulse-chase analysis, splenic and peripheral blood activated T lymphocytes were found...

  18. Case 1: chronic infected donor site.

    Science.gov (United States)

    2016-03-01

    Following a coronary bypass surgery, a vein donor site became infected and failed to heal despite use of antibiotics and a variety of topical treatments. Octenilin Wound Gel not only helped to promote healing, but also increased the patient's ability to tolerate dressing changes. PMID:26949845

  19. Development of Biomarkers for Chronic Beryllium Disease in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, Terry

    2013-01-25

    Beryllium is a strategic metal, indispensable for national defense programs in aerospace, telecommunications, electronics, and weaponry. Exposure to beryllium is an extensively documented occupational hazard that causes irreversible, debilitating granulomatous lung disease in as much as 3 - 5% of exposed workers. Mechanistic research on beryllium exposure-disease relationships has been severely limited by a general lack of a sufficient CBD animal model. We have now developed and tested an animal model which can be used for dissecting dose-response relationships and pathogenic mechanisms and for testing new diagnostic and treatment paradigms. We have created 3 strains of transgenic mice in which the human antigen-presenting moiety, HLA-DP, was inserted into the mouse genome. Each mouse strain contains HLA-DPB1 alleles that confer different magnitude of risk for chronic beryllium disease (CBD): HLA-DPB1*0401 (odds ratio = 0.2), HLA-DPB1*0201 (odds ratio = 15), HLA-DPB1*1701 (odds ratio = 240). Our preliminary work has demonstrated that the *1701 allele, as predicted by human studies, results in the greatest degree of sensitization in a mouse ear swelling test. We have also completed dose-response experiments examining beryllium-induced lung granulomas and identified susceptible and resistant inbred strains of mice (without the human transgenes) as well as quantitative trait loci that may contain gene(s) that modify the immune response to beryllium. In this grant application, we propose to use the transgenic and normal inbred strains of mice to identify biomarkers for the progression of beryllium sensitization and CBD. To achieve this goal, we propose to compare the sensitivity and accuracy of the lymphocyte proliferation test (blood and bronchoalveolar lavage fluid) with the ELISPOT test in the three HLA-DP transgenic mice strains throughout a 6 month treatment with beryllium particles. Because of the availability of high-throughput proteomics, we will also identify

  20. Protective effect of Lactobacillus casei on Pseudomonas aeruginosa infection in mice.

    OpenAIRE

    Miake, S; Yokokura, T; Yoshikai, Y; Mutai, M; Nomoto, K.

    1985-01-01

    The protective effect of heat-killed Lactobacillus casei YIT9018 (LC 9018) against Pseudomonas aeruginosa infection in mice was compared with that of Corynebacterium parvum. Survival of mice after intraperitoneal (i.p.) infection with P. aeruginosa was augmented in mice that had been pretreated i.p. with LC 9018 5 days previously. Similar treatment of mice with C. parvum, however, was not effective at all. Moreover, mice became more susceptible to infection with P. aeruginosa after such treat...

  1. Syphacia obvelata and Radfordia affinis infection in mice

    DEFF Research Database (Denmark)

    Harslund, Jakob le Fèvre; Mandrupsen, Karina; Bollen, Peter

    serology to PCR based monitoringMaterials & methods:Drinking water containing 0.3 mg/ml fenbendazole (Panacur® Vet 10% Oral Suspension) was made by mixing 0.75 ml of Panacur® Vet with drinking water in 250 ml bottles. Precipitation in drinking water was minimized by handling the bottles on regular basis....... Mice were treated for one week followed by one week without fenbendazole. This was repeated 5 times consecutively. Topical treatment of mice with selamectin (Stronghold® Vet, selamectin 120 mg/ml) was performed by dripping 0.01 ml of Stronghold stock solution in the neck using a micropipette (1). Every...... was initially diagnosed by microscopy of fur/skin smears from clinically affected mice demonstrating live fur mites. Subsequently, fur mite infection was diagnosed by PCR analysis on fur swabs and swabs from exhaust manifolds of IVC (2). Results: Following fenbendazole treatment of mice all subsequent...

  2. Detection of prion infectivity in fat tissues of scrapie-infected mice.

    Directory of Open Access Journals (Sweden)

    Brent Race

    2008-12-01

    Full Text Available Distribution of prion infectivity in organs and tissues is important in understanding prion disease pathogenesis and designing strategies to prevent prion infection in animals and humans. Transmission of prion disease from cattle to humans resulted in banning human consumption of ruminant nervous system and certain other tissues. In the present study, we surveyed tissue distribution of prion infectivity in mice with prion disease. We show for the first time detection of infectivity in white and brown fat. Since high amounts of ruminant fat are consumed by humans and also incorporated into animal feed, fat-containing tissues may pose a previously unappreciated hazard for spread of prion infection.

  3. H pylori infection causes chronic pancreatitis in Mongolian gerbils

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type Ⅳ secretion system.METHODS: Mongolian gerbils were infected with wild type (WT) H pyloritype Ⅰ strain B128 or its isogenic mutant B128 Acag Y (defective type Ⅳ secretion). After seven months of infection, H pylori was reisolated from antrum and corpus and H pylori DNA was analyzed by seminested polymerase chain reaction (PCR). Inflammation and histological changes were documented in the gastric antrum, corpus, and pancreas by immunohistochemistry.Cytokine mRNA, gastric pH, plasma gastrin, amylase,lipase, and glucose levels were determined.RESULTS: The H pylori infection rate was 95%.Eight infected animals, but none of the uninfected group, developed transmural inflammation and chronic pancreatitis. Extensive interstitial fibrosis and inflammation of the pancreatic lobe adjacent to the antrum was confirmed by trichrome stain, and immunohistochemically. Pro-inflammatory cytokine mRNA was significantly increased in the antral mucosa of all infected gerbils. In the corpus, only cytokine levels of WT-infected animals and those developing transmural inflammation and pancreatitis were significantly increased.Levels of lipase, but not glucose or amylase levels, were significantly reduced in the pancreatitis group. H pylori DNA was detected in infected antral and corpus tissue,but not in the pancreas.CONCLUSION: H pylori infection is able to induce chronic pancreatitis in Mongolian gerbils independently of the type Ⅳ secretion system, probably by an indirect mechanism associated with a penetrating ulcer.

  4. Extensive Mycobacterium bovis BCG Infection of Liver Parenchymal Cells in Immunocompromised Mice

    OpenAIRE

    Mills, John W.; Ryan, Lynn; LaCourse, Ronald; North, Robert J.

    2001-01-01

    A histologic study was performed on the livers of wild-type (WT), severe combined immunodeficient (SCID), hydrocortisone acetate (HC)-treated WT, and HC-treated SCID mice infected intravenously with 105 CFU of Mycobacterium bovis BCG. It was found that infection progressed faster in SCID mice than in WT mice and that HC treatment caused exacerbation of infection in both types of mice. In all cases infection in the liver was confined to granulomas that were populated predominantly by macrophag...

  5. Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection.

    Directory of Open Access Journals (Sweden)

    Yee Suan Poo

    2014-12-01

    Full Text Available The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA.

  6. Regulatory T Cells in Chronic Hepatitis B Virus Infection

    NARCIS (Netherlands)

    J.N. Stoop (Jeroen Nicolaas)

    2007-01-01

    textabstractWorldwide 400 million people suffer from chronic hepatitis B virus (HBV) infection and approximately 1 million people die annually from HBV-related disease. To clear HBV, an effective immune response, in which several cell types and cytokines play a role, is important. It is known that p

  7. Therapeutic vaccination against chronic hepatitis C virus infection

    NARCIS (Netherlands)

    Ip, Peng Peng; Nijman, Hans W.; Wilschut, Jan; Daemen, Toos

    2012-01-01

    Approximately 170 million people worldwide are chronic carriers of Hepatitis C virus (HCV). To date, there is no prophylactic vaccine available against HCV. The standard-of-care therapy for HCV infection involves a combination of pegylated interferon-α and ribavirin. This therapy, which is commonly

  8. Effects of Chronic Stress on Cognition in Male SAMP8 Mice

    Directory of Open Access Journals (Sweden)

    Jinhua Wang

    2016-08-01

    Full Text Available Background/Aims: Chronic stress can lead to cognitive impairment. Senescence-accelerated mouse prone 8 (SAMP8 is a naturally occurring animal model that is useful for investigating the neurological mechanisms of Alzheimer's disease. Here we investigated the impact and mechanisms of chronic stress on cognition in male SAMP8 mice. Methods: Male 6-month- old SAMP8 and SAMR1 (senescence-accelerated mouse resistant 1 mice strains were randomly divided into 4 groups. Mice in the unpredictable chronic mild stress (UCMS groups were exposed to diverse stressors for 4 weeks. Then, these mice performed Morris water maze (MWM test to assess the effect of UCMS on learning and memory. To explore the neurological mechanisms of UCMS on cognition in mice, we evaluated changes in the expression of postsynaptic density 95 (PSD95 and synaptophysin (SYN, which are essential proteins for synaptic plasticity. Five mice from each group were randomly chosen for reverse transcription polymerase chain reaction (RT-PCR and western blotting analysis of SYN and PSD95. Results: The Morris water maze experiment revealed that the cognitive ability of the SAMP8 mice decreased with brain aging, and that chronic stress aggravated this cognitive deficit. In addition, chronic stress decreased the mRNA and protein expression of SYN and PSD95 in the hippocampus of the SAMP8 mice; however, the SAMR1 mice were unaffected. Conclusion: Our results demonstrate that decreased cognition and synaptic plasticity are related to aging. Moreover, we show that chronic stress aggravated this cognitive deficit and decreased SYN and PSD95 expression in the SAMP8 mice. Furthermore, the SAMP8 mice were more vulnerable to the detrimental effects of chronic stress on cognition than the SAMR1 mice. Our results suggest that the neurological mechanisms of chronic stress on cognition might be associated with a decrease in hippocampal SYN and PSD95 expression, which is critical for structural synaptic

  9. Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice

    OpenAIRE

    Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; YAMADA, Kumiko; Kubo, Kin-Ya

    2015-01-01

    Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a woode...

  10. Porphyromonas gingivalis infection induced reproductive abnormalities in mice

    Directory of Open Access Journals (Sweden)

    Ke-min WEI

    2016-09-01

    Full Text Available Objective  To establish a pregnant mouse model infected with Porphyromonas gingivalis (P.g, and investigate the relationship of P.g infection to prematurity and associated birth abnormalities. Methods  Fifty two female mice were randomly divided into P.g infection group (n=26 and control group (n=26. Mice in P.g infection group were anesthetized, the pulp cavity of the first molar was opened and directly injected with W83 strain P.g, and the tooth was then filled. Six weeks after infection, the mice were mated with males and the formation of vagina plug was recorded as 0d. The P.g extracted from the granulation tissue in tooth root was cultivated. The pregnant days and the connatal body weight of infant mouse were recorded, the serum and placental tissue were collected to assess the systemic and local conditions during pregnancy. Results  After periodontal P.g infection, the TNF-α, IL-17, IL -6 and IL -1βlevels in peripheral blood sera increased significantly. The average gestation was shorter in P.g infection group (18.25d than in control group (20.45d, P<0.01, and the connatal body weight of infant mouse was also less in the former than in the latter (P<0.01. Immunohistochemistry and PCR revealed the existence of P.g in placenta tissue. P.g infection caused premature rupture of membranes, placental abruption, degeneration and necrosis of trophoblastic and endothelial cells; significantly increased the number of neutrophils and macrophages in placenta tissues, and increased the expression of local TNF-αand COX-2 inflammatory factors at the same time. In P.g infection group, the expressions of CD-31 in endothelial cells of placenta tissues and the apoptotic factor caspase-3 decreased, and the DNA oxidative damage index 8-OHdG increased. Conclusions  P.g infection in female mice may cause premature birth and lower connatal body weight of infant mouse, and increase the expression of serous and local inflammatory factors in the placenta

  11. The role of bacterial biofilms in chronic infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas

    2013-01-01

    wounds, chronic otitis media and implant- and catheter-associated infections, affect millions of people in the developed world each year and many deaths occur as a consequence. In general, bacteria have two life forms during growth and proliferation. In one form, the bacteria exist as single, independent......Acute infections caused by pathogenic bacteria have been studied extensively for well over 100 years. These infections killed millions of people in previous centuries, but they have been combated effectively by the development of modern vaccines, antibiotics and infection control measures. Most...... cells (planktonic) whereas in the other form, bacteria are organized into sessile aggregates. The latter form is commonly referred to as the biofilm growth phenotype. Acute infections are assumed to involve planktonic bacteria, which are generally treatable with antibiotics, although successful...

  12. Effect of Chronic Lead Intoxication on Risky Behavior in Mice

    Directory of Open Access Journals (Sweden)

    L Mohammadyar

    2010-08-01

    Full Text Available Introduction: With industrialization of human societies, pollutants like lead have entered in the life cycle, causing harmful effects on body organs. No sufficient studies have been done on the effects of pollutants on behavior. The aim of this study was to investigate possible effects of lead on some measurable behaviors of an animal model. Methods: Forty eight male adult mice were divided into 4 groups of 12 each. Lead acetate was added at concentrations of 0, 5, 50, or 500 ppm to the drinking water of the animals for 4 weeks (28 days. On day 29, animals were placed on an Elevated Plus maze (EPM for 5 min and the time in sec spent was measured on closed arms, open arms and the end 1/3rd of the open arms. Increased time on open arms, particularly the end 1/3rd was considered to reflect an enhanced risk-accepting behavior. Results: In this study, it was shown that lead exposure caused an increased number of entrance (P=0.006 and time spent (P=0.034 by mice on open arms of the EPM. There was a positive correlation between the concentration of lead acetate and those two effects. Conclusion: The present study demonstrated that lead poisoning may decrease normal anxiety in mice and increase risky behavior in this species. Clinical studies on human subjects with risky behavior are strongly suggested in order to find a possible relation between chronic exposures to lead as well as plasma concentration of lead with the extent of this kind of behavior.

  13. Chronically Alternating Light Cycles Increase Breast Cancer Risk in Mice.

    Science.gov (United States)

    Van Dycke, Kirsten C G; Rodenburg, Wendy; van Oostrom, Conny T M; van Kerkhof, Linda W M; Pennings, Jeroen L A; Roenneberg, Till; van Steeg, Harry; van der Horst, Gijsbertus T J

    2015-07-20

    Although epidemiological studies in shift workers and flight attendants have associated chronic circadian rhythm disturbance (CRD) with increased breast cancer risk, causal evidence for this association is lacking. Several scenarios have been proposed to contribute to the shift work-cancer connection: (1) internal desynchronization, (2) light at night (resulting in melatonin suppression), (3) sleep disruption, (4) lifestyle disturbances, and (5) decreased vitamin D levels due to lack of sunlight. The confounders inherent in human field studies are less problematic in animal studies, which are therefore a good approach to assess the causal relation between circadian disturbance and cancer. However, the experimental conditions of many of these animal studies were far from the reality of human shift workers. For example, some involved xenografts (addressing tumor growth rather than cancer initiation and/or progression), chemically induced tumor models, or continuous bright light exposure, which can lead to suppression of circadian rhythmicity. Here, we have exposed breast cancer-prone p53(R270H/+)WAPCre conditional mutant mice (in a FVB genetic background) to chronic CRD by subjecting them to a weekly alternating light-dark (LD) cycle throughout their life. Animals exposed to the weekly LD inversions showed a decrease in tumor suppression. In addition, these animals showed an increase in body weight. Importantly, this study provides the first experimental proof that CRD increases breast cancer development. Finally, our data suggest internal desynchronization and sleep disturbance as mechanisms linking shift work with cancer development and obesity. PMID:26196479

  14. Effects of Murine Cytomegalovirus Infection on Sperm Viability in Mice

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to explore the effects of testicular infection of murine cytomegalovirus (MCMV) on mature sperm viability at different periods following MCMV inoculation in mice, 91 BALB/c mice without MCMV infection were randomly divided into two groups: an experimental group (n=56) and a control group (n= 35). The mice in the experimental group were treated by inoculating MCMV intratesticularly, while those in the controlled group were directly inoculated with DMEM without MCMV. The mice in both groups were sacrificed separately on the day 1,1.5, 2, 4, 6, 9 and 14 post-inoculation (D1, 1.5,2, 4, 6, 9 and 14 PI). The MCMV M83 mRNA gene was detected in the testis by in situ hybridization (ISH) with MCMV late-mRNA probe labeled with digoxin.Sperm viability of mature sperm in the epididymis cauda was measured. The results demonstrated the positive signal of ISH of MCMV was found mainly in the cytoplasm of the testicular interstitial cells and spermatogenic cells in the experimental group. Compared with that in the controlled group, the sperm viability in the experimental group was decreased significantly on D1 PI and D1.5PI (P< 0.05). No statistically significant difference in the sperm viability was found after D2 PI between two groups (P>0.05). This suggested that sperm viability in mice might be descended significantly shortly after MCMV infection and might return to normal with time, indicating that MCMV acute infection might temporarily degrade sperm quality and influence procreation transiently.

  15. Characterization of Lethal Zika Virus Infection in AG129 Mice.

    Directory of Open Access Journals (Sweden)

    Matthew T Aliota

    2016-04-01

    Full Text Available 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.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.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.

  16. Characterization of Lethal Zika Virus Infection in AG129 Mice

    Science.gov (United States)

    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

  17. Interferon-γ is crucial for surviving a Brucella abortus infection in both resistant C57BL/6 and susceptible BALB/c mice

    Science.gov (United States)

    Murphy, Erin A; Sathiyaseelan, Janaki; Parent, Michelle A; Zou, Baixiang; Baldwin, Cynthia L

    2001-01-01

    Brucella abortus is an intracellular bacterial pathogen that causes chronic infections in humans and a number of agriculturally important species of animals. It has been shown that BALB/c mice are more susceptible to infections with virulent strains of Brucella abortus than C57BL/6 or C57BL/10 strains. In experiments described here, gene knock-out mice were utilized to elucidate some of the salient components of resistance. Resistant C57BL/6 mice with gene deletions or disruptions in the interferon-γ (IFN-γ), perforin or β2-microglobulin genes had decreased abilities to control intracellular infections with B. abortus strain 2308 during the first week after infection. However, only the IFN-γ knock-out mice had a sustained inability to control infections and this resulted in death of the mice at approximately 6 weeks post-infection. These mice had a continual increase in the number of bacterial colony-forming units (CFU) in their spleens until death. When BALB/c mice with the disrupted IFN-γ gene were infected they had more splenic CFU at one week post-infection than control mice but the increase was not statistically significant and by 3 weeks they did not have more CFU than control mice. Moreover, the number of splenic bacteria did not increase in the BALB/c IFN-γ knock-out mice between 6 and 10·5 weeks, although they died at 10·5 weeks, the time by which normal BALB/c mice were clearing the infection. Death in both strains of IFN-γ gene disrupted mice coincided with symptoms of cachexia and macrophages comprised ≥75% of the splenic leucocytes. PMID:11529943

  18. Gene expression alterations in brains of mice infected with three strains of scrapie

    Directory of Open Access Journals (Sweden)

    Race Richard E

    2006-05-01

    Full Text Available Abstract Background Transmissible spongiform encephalopathies (TSEs or prion diseases are fatal neurodegenerative disorders which occur in humans and various animal species. Examples include Creutzfeldt-Jakob disease (CJD in humans, bovine spongiform encephalopathy (BSE in cattle, chronic wasting disease (CWD in deer and elk, and scrapie in sheep, and experimental mice. To gain insights into TSE pathogenesis, we made and used cDNA microarrays to identify disease-associated alterations in gene expression. Brain gene expression in scrapie-infected mice was compared to mock-infected mice at pre-symptomatic and symptomatic time points. Three strains of mouse scrapie that show striking differences in neuropathology were studied: ME7, 22L, and Chandler/RML. Results In symptomatic mice, over 400 significant gene expression alterations were identified. In contrast, only 22 genes showed significant alteration in the pre-symptomatic animals. We also identified genes that showed significant differences in alterations in gene expression between strains. Genes identified in this study encode proteins that are involved in many cellular processes including protein folding, endosome/lysosome function, immunity, synapse function, metal ion binding, calcium regulation and cytoskeletal function. Conclusion These studies shed light on the complex molecular events that occur during prion disease, and identify genes whose further study may yield new insights into strain specific neuropathogenesis and ante-mortem tests for TSEs.

  19. Chronic stress does not further exacerbate the abnormal psychoneuroendocrine phenotype of Cbg-deficient male mice.

    Science.gov (United States)

    de Medeiros, Gabriela F; Minni, Amandine M; Helbling, Jean-Christophe; Moisan, Marie-Pierre

    2016-08-01

    Chronic stress leads to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis which can constitute a base for pathophysiological consequences. Using mice totally deficient in Corticosteroid binding globulin (CBG), we have previously demonstrated the important role of CBG in eliciting an adequate response to an acute stressor. Here, we have studied its role in chronic stress situations. We have submitted Cbg ko and wild-type (WT) male mice to two different chronic stress paradigms - the unpredictable chronic mild stress and the social defeat. Then, their impact on neuroendocrine function - through corticosterone and CBG measurement - and behavioral responses - via anxiety and despair-like behavioral tests - was evaluated. Both chronic stress paradigms increased the display of despair-like behavior in WT mice, while that from Cbg ko mice - which was already high - was not aggravated. We have also found that control and defeated (stressed) Cbg ko mice show no difference in the social interaction test, while defeated WT mice reduce their interaction time when compared to unstressed WT mice. Interestingly, the same pattern was observed for corticosterone levels, where both chronic stress paradigms lowered the corticosterone levels of WT mice, while those from Cbg ko mice remained low and unaltered. Plasma CBG binding capacity remained unaltered in WT mice regardless of the stress paradigm. Through the use of the Cbg ko mice, which only differs genetically from WT mice by the absence of CBG, we demonstrated that CBG is crucial in modulating the effects of stress on plasma corticosterone levels and consequently on behavior. In conclusion, individuals with CBG deficiency, whether genetically or environmentally-induced, are vulnerable to acute stress but do not have their abnormal psychoneuroendocrine phenotype further affected by chronic stress. PMID:27153522

  20. Chronic stress does not further exacerbate the abnormal psychoneuroendocrine phenotype of Cbg-deficient male mice.

    Science.gov (United States)

    de Medeiros, Gabriela F; Minni, Amandine M; Helbling, Jean-Christophe; Moisan, Marie-Pierre

    2016-08-01

    Chronic stress leads to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis which can constitute a base for pathophysiological consequences. Using mice totally deficient in Corticosteroid binding globulin (CBG), we have previously demonstrated the important role of CBG in eliciting an adequate response to an acute stressor. Here, we have studied its role in chronic stress situations. We have submitted Cbg ko and wild-type (WT) male mice to two different chronic stress paradigms - the unpredictable chronic mild stress and the social defeat. Then, their impact on neuroendocrine function - through corticosterone and CBG measurement - and behavioral responses - via anxiety and despair-like behavioral tests - was evaluated. Both chronic stress paradigms increased the display of despair-like behavior in WT mice, while that from Cbg ko mice - which was already high - was not aggravated. We have also found that control and defeated (stressed) Cbg ko mice show no difference in the social interaction test, while defeated WT mice reduce their interaction time when compared to unstressed WT mice. Interestingly, the same pattern was observed for corticosterone levels, where both chronic stress paradigms lowered the corticosterone levels of WT mice, while those from Cbg ko mice remained low and unaltered. Plasma CBG binding capacity remained unaltered in WT mice regardless of the stress paradigm. Through the use of the Cbg ko mice, which only differs genetically from WT mice by the absence of CBG, we demonstrated that CBG is crucial in modulating the effects of stress on plasma corticosterone levels and consequently on behavior. In conclusion, individuals with CBG deficiency, whether genetically or environmentally-induced, are vulnerable to acute stress but do not have their abnormal psychoneuroendocrine phenotype further affected by chronic stress.

  1. Temporal and anatomical host resistance to chronic Salmonella infection is quantitatively dictated by Nramp1 and influenced by host genetic background.

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    Wendy P Loomis

    Full Text Available The lysosomal membrane transporter, Nramp1, plays a key role in innate immunity and resistance to infection with intracellular pathogens such as non-typhoidal Salmonella (NTS. NTS-susceptible C57BL/6 (B6 mice, which express the mutant Nramp1D169 allele, are unable to control acute infection with Salmonella enterica serovar Typhimurium following intraperitoneal or oral inoculation. Introducing functional Nramp1G169 into the B6 host background, either by constructing a congenic strain carrying Nramp1G169 from resistant A/J mice (Nramp-Cg or overexpressing Nramp1G169 from a transgene (Nramp-Tg, conferred equivalent protection against acute Salmonella infection. In contrast, the contributions of Nramp1 for controlling chronic infection are more complex, involving temporal and anatomical differences in Nramp1-dependent host responses. Nramp-Cg, Nramp-Tg and NTS-resistant 129×1/SvJ mice survived oral Salmonella infection equally well for the first 2-3 weeks, providing evidence that Nramp1 contributes to the initial control of NTS bacteremia preceding establishment of chronic Salmonella infection. By day 30, increased host Nramp1 expression (Tg>Cg provided greater protection as indicated by decreased splenic bacterial colonization (Tgmice, Nramp-Cg and Nramp-Tg mice eventually succumbed to infection. These data indicate: 1 discrete, anatomically localized host resistance is conferred by Nramp1 expression in NTS-susceptible mice, 2 restriction of systemic bacterial growth in the spleens of NTS-susceptible mice is enhanced by Nramp1 expression and dose-dependent, and 3 host genes other than Nramp1 also contribute to the ability of NTS-resistant 129×1/SvJ mice to control bacterial replication during chronic infection.

  2. Hepatic regeneration after partial hepatectomy in mice infected with Schistosoma mansoni, at the acute and chronic phases of the disease Regeneração hepática após hepatectomia parcial em camundongos infectados com Schistosoma mansoni, nas fases aguda e crônica da doença

    Directory of Open Access Journals (Sweden)

    G. COSTA

    1999-07-01

    Full Text Available Outbred male albino mice normal or infected with 30 cercariae of Schistosoma mansoni (LE strain were submitted to 65% hepatectomy during the acute (70 days and chronic phase (160 days phases of the disease. A group of the infected animals was treated with 400 mg/kg of oxamniquine during the acute phase before hepatectomy. Non-infected, infected and treated but not hepatectomized animals were kept as controls. Hepatic regeneration was evaluated by incorporation of tritiated thymidine, intraperitoneally injected into non-hepatectomized and hepatectomized animals, 24 hours after surgery. The results showed that removal of 65% of the hepatic parenchyma, during the acute phase, led to a statistically significant increase of thymidine incorporation, when compared with the uninfected hepatectomized controls. This phenomenon was not observed at the chronic phase. Treatment with oxamniquine administered during the acute phase led to a decrease in thymidine incorporation rate 160 days after infection (90 days after treatment and 24 hours after hepatectomy. The data suggest that infection with S. mansoni represents a considerable stimulus for the regenerative capacity of the liver during the acute, but not the chronic phase of disease.Camundongos albinos não-isogênicos, normais ou infectados com 30 cercárias de Schistosoma mansoni (cepa LE foram submetidos a hepatectomia parcial (65% na fase aguda (70 dias ou crônica (160 dias da doença. Um grupo de animais infectados foi tratado, na fase aguda, com 400 mg/kg oxamniquine antes da hepatectomia. Animais não infectados, infectados e tratados mas não hepatectomizados, foram mantidos como controles. A regeneração hepática foi avaliada pela incorporação de timidina tritiada, injetada peritonealmente em animais hepatectomizados ou não, 24 horas após cirurgia. Os resultados mostraram que a remoção de 65% do parênquina hepático, na fase aguda, levou a um aumento estatisticamente significativo da

  3. The Role of Bacterial Biofilms in Chronic Infections

    OpenAIRE

    Do, Danh Cong

    2014-01-01

    Biofilm is the virulence factor that is responsible for chronic infection in diseases such as Cystic Fibrosis (CF) and chronic wounds. In this thesis, we examine the role of AlgX, a required protein for alginate biosynthesis in P. aeruginosa. We show that the absence of AlgX resulted in the loss of mucoidy and in silico studies demonstrated that AlgX binds alginate. Alanine mutations demonstrated that K396, T398, W400, and R406 are important for alginate binding. Alginate rescue assays confir...

  4. Lipopolysaccharide modification in Gram-negative bacteria during chronic infection.

    Science.gov (United States)

    Maldonado, Rita F; Sá-Correia, Isabel; Valvano, Miguel A

    2016-07-01

    The Gram-negative bacterial lipopolysaccharide (LPS) is a major component of the outer membrane that plays a key role in host-pathogen interactions with the innate immune system. During infection, bacteria are exposed to a host environment that is typically dominated by inflammatory cells and soluble factors, including antibiotics, which provide cues about regulation of gene expression. Bacterial adaptive changes including modulation of LPS synthesis and structure are a conserved theme in infections, irrespective of the type or bacteria or the site of infection. In general, these changes result in immune system evasion, persisting inflammation and increased antimicrobial resistance. Here, we review the modifications of LPS structure and biosynthetic pathways that occur upon adaptation of model opportunistic pathogens (Pseudomonas aeruginosa, Burkholderia cepacia complex bacteria, Helicobacter pylori and Salmonella enterica) to chronic infection in respiratory and gastrointestinal sites. We also discuss the molecular mechanisms of these variations and their role in the host-pathogen interaction. PMID:27075488

  5. Progression of experimental chronic Aleutian mink disease virus infection

    DEFF Research Database (Denmark)

    Jensen, Trine Hammer; Chriél, Mariann; Hansen, Mette Sif

    2016-01-01

    AMDV inoculation. Gross pathology revealed few and inconsistent findings mainly associated with the liver, spleen and kidneys. The majority of the AMDV inoculated wild type mink (n = 41) developed various histopathological changes consistent with AMDV infection in one or more organs: infiltrations...... knowledge based on a systematically description of clinical signs, pathology and histopathology might be a tool to reduce the risk of infection from subclinically infected mink to AMDV free herds. The aim of this study was to give a histopathological description of the progression of a chronic experimental...... of mononuclear cells in liver, kidney and brain, reduced density of lymphocytes and increased numbers of plasma cells in lymph nodes and spleen. Natural infection, as occurred in the sentinel sapphire mink (four of six mink), progressed similar to the experimentally inoculated mink. Experimental AMDV inoculation...

  6. Infection of C57BL/6 mice by Trypanosoma musculi modulates host immune responses during Brucella abortus cocolonization.

    Science.gov (United States)

    Lowry, Jake E; Leonhardt, Jack A; Yao, Chaoqun; Belden, E Lee; Andrews, Gerard P

    2014-01-01

    Brucellosis, which results in fetal abortions in domestic and wildlife animal populations, is of major concern in the US and throughout much of the world. The disease, caused by Brucella abortus, poses an economic threat to agriculture-based communities. A moderately efficacious live attenuated vaccine (B. abortus strain RB51) exists. However, even with vaccine use, outbreaks occur. Evidence suggests that elk (Cervus canadensis), a wild host reservoir, are the source of recent outbreaks in domestic cattle herds in Wyoming, USA. Brucella abortus establishes a chronic, persistent infection in elk. The molecular mechanisms allowing the establishment of this persistent infective state are currently unknown. A potential mechanism could be that concurrent pathogen burdens contribute to persistence. In Wyoming, elk are chronically infected with Trypanosoma cervi, which may modulate host responses in a similar manner to that documented for other trypanosomes. To identify any synergistic relationship between the two pathogens, we simulated coinfection in the well-established murine brucellosis model using Trypanosoma musculi and B. abortus S19. Groups of C57BL/6 mice (Mus musculus) were infected with either B. abortus strain 19 (S19) or T. musculi or both. Sera were collected weekly; spleens from euthanized mice were tested to determine bacterial load near the end of normal brucellosis infection. Although changes in bacterial load were observed during the later stages of brucellosis in those mice coinfected with T. musculi, the most significant finding was the suppression of gamma interferon early during the infection along with an increase in interleukin-10 secretion compared with mice infected with either pathogen alone. These results suggest that immune modulatory events occur in the mouse during coinfection and that further experiments are warranted to determine if T. cervi impacts Brucella infection in elk. PMID:24171573

  7. Kinetics of Immune Responses in Deer Mice Experimentally Infected with Sin Nombre Virus

    OpenAIRE

    Schountz, Tony; Acuña-Retamar, Mariana; Feinstein, Shira; Prescott, Joseph; Torres-Perez, Fernando; Podell, Brendan; Peters, Staci; Ye, Chunyan; Black, William C.; Hjelle, Brian

    2012-01-01

    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 postinfe...

  8. Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease

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    Eric D. Abston

    2012-01-01

    Full Text Available Viral infections are able to induce autoimmune inflammation in the heart. Here, we investigated the role of virus-activated Toll-like receptor (TLR3 and its adaptor TRIF on the development of autoimmune coxsackievirus B3 (CVB3 myocarditis in mice. Although TLR3- or TRIF-deficient mice developed similarly worse acute CVB3 myocarditis and viral replication compared to control mice, disease was significantly worse in TRIF compared to TLR3-deficient mice. Interestingly, TLR3-deficient mice developed an interleukin (IL-4-dominant T helper (Th2 response during acute CVB3 myocarditis with elevated markers of alternative activation, while TRIF-deficient mice elevated the Th2-associated cytokine IL-33. Treatment of TLR3-deficient mice with recombinant IL-33 improved heart function indicating that elevated IL-33 in the context of a classic Th2-driven response protects against autoimmune heart disease. We show for the first time that TLR3 versus TRIF deficiency results in different Th2 responses that uniquely influence the progression to chronic myocarditis.

  9. Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice

    OpenAIRE

    Lu Zhao; Jianhua Xu; Fang Liang; Ao Li; Yong Zhang; Jue Sun

    2015-01-01

    Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also assoc...

  10. THE CYTOKINE IP-10 IN CHRONIC HBV AND HCV INFECTION

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    Nina S. Nikolova

    2013-08-01

    Full Text Available Introduction: IP-10 it has been studied as a predictor of treatment response in chronic HCV infected patients. The data for the HBV infection are not enough.Aim: To compare IP-10 levels in patients with chronic HBV /CHB/ and HCV infection /CHC/ and their relation to liver disease and treatment response. Material and methods: 20 patients - with CHC genotype 1 infection /on standard bi-therapy/ and 32 patients with CHB /21 pts - NUC; 11 pts - IFN/. Results: The IP-10 did not correlate with sex, age, ALT and liver fibrosis. The basal IP-10 were lower in patients with CHB (p=0,017. There was a difference in IP-10 baseline levels among the HCV patients with or without RVR (p=0,007. A negative correlation was found between basal IP-10 and RVR (r= -0,508; p=0,008. Conclusion: IP-10 could predict virological response in patients with CHC on standard bi-therapy, but not in HBV infected patients on standard therapy.

  11. Chronic West Nile virus infection in kea (Nestor notabilis).

    Science.gov (United States)

    Bakonyi, Tamás; Gajdon, Gyula K; Schwing, Raoul; Vogl, Wolfgang; Häbich, Annett-Carolin; Thaller, Denise; Weissenböck, Herbert; Rudolf, Ivo; Hubálek, Zdenek; Nowotny, Norbert

    2016-02-01

    Six kea (Nestor notabilis) in human care, naturally infected with West Nile virus (WNV) lineage 2 in Vienna, Austria, in 2008, developed mild to fatal neurological signs. WNV RNA persisted and the virus evolved in the birds' brains, as demonstrated by (phylo)genetic analyses of the complete viral genomes detected in kea euthanized between 2009 and 2014. WNV antibodies persisted in the birds, too. Chronic WNV infection in the brain might contribute to the circulation of the virus through oral transmission to predatory birds.

  12. Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

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    M. Naviliat

    2005-12-01

    Full Text Available Nitric oxide (·NO is a diffusible messenger implicated in Trypanosoma cruzi resistance. Excess production of ·NO and oxidants leads to the generation of nitrogen dioxide (·NO2, a strong nitrating agent. Tyrosine nitration is a post-translational modification resulting from the addition of a nitro (-NO2 group to the ortho-position of tyrosine residues. Detection of protein 3-nitrotyrosine is regarded as a marker of nitro-oxidative stress and is observed in inflammatory processes. The formation and role of nitrating species in the control and myocardiopathy of T. cruzi infection remain to be studied. We investigated the levels of ·NO and protein 3-nitrotyrosine in the plasma of C3H and BALB/c mice and pharmacologically modulated their production during the acute phase of T. cruzi infection. We also looked for protein 3-nitrotyrosine in the hearts of infected animals. Our results demonstrated that C3H animals produced higher amounts of ·NO than BALB/c mice, but their generation of peroxynitrite was not proportionally enhanced and they had higher parasitemias. While N G-nitro-arginine methyl ester treatment abolished ·NO production and drastically augmented the parasitism, mercaptoethylguanidine and guanido-ethyl disulfide, at doses that moderately reduced the ·NO and 3-nitrotyrosine levels, paradoxically diminished the parasitemia in both strains. Nitrated proteins were also demonstrated in myocardial cells of infected mice. These data suggest that the control of T. cruzi infection depends not only on the capacity to produce ·NO, but also on its metabolic fate, including the generation of nitrating species that may constitute an important element in parasite resistance and collateral myocardial damage.

  13. Whole body lymphangioscintigraphy in ferrets chronically infected with Brugia malayi

    Energy Technology Data Exchange (ETDEWEB)

    Witte, M.; McNeill, G.; Crandall, C.; Case, T.; Witte, C.; Crandall, R.; Hall, J.; Williams, W.

    1988-12-01

    Whole body lymphangioscintigraphy was performed after intradermal injection of /sup 99m/technetium human serum albumin or antimony colloid in the distal hindlimbs and forelimbs of ferrets chronically infected with Brugia malayi. The findings were compared with control ferrets and those with surgical interruption of the iliac lymphatics. While only one infected ferret manifested chronic hindlimb lymphedema, all exhibited delayed transport of radioisotope from the hindpaw with obstruction in the groin, poor or absent visualization of central lymphatic channels and regional lymph nodes, a picture similar to that following surgically induced lymphatic obstruction. In control ferrets, there was prompt visualization of peripheral lymphatic channels and regional lymph nodes with sharper and more extensive channel visualization after radiolabeled albumin and more intense sustained nodal visualization after radiolabeled antimony colloid. This noninvasive technique provides a readily repeatable investigative tool adaptable to small animals to study the evolution of lymphatic filariasis and other conditions associated with lymphatic obstruction.

  14. Female hepatology: Favorable role of estrogen in chronic liver disease with hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Chronic hepatitis B virus (HBV) infection is the most common cause of hepatic fibrosis and hepatocellular carcinoma (HCC), mainly as a result of chronic necroinflammatory liver disease. A characteristic feature of chronic hepatitis B infection, alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD) is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which, in turn, activates hepatic stellate cells (HSCs). HSCs are the primary target cells for inflammatory and oxidative stimuli, and these cells produce extracellular matrix components.Chronic hepatitis B appears to progress more rapidly in males than in females, and NAFLD, cirrhosis and HCC are predominately diseases that tend to occur in men and postmenopausal women. Premenopausal women have lower hepatic iron stores and a decreased production of proinflammatory cytokines. Hepatic steatosis has been observed in aromatase-deficient mice, and has been shown to decrease in animals after estradiol treatment. Estradiol is a potent endogenous antioxidant which suppresses hepatic fibrosis in animal models, and attenuates induction of redox sensitive transcription factors, hepatocyte apoptosis and HSC activation by inhibiting a generation of reactive oxygen species in primary cultures. Variant estrogen receptors are expressed to a greater extent in male patients with chronic liver disease than in females. These lines of evidence suggest that the greater progression of hepatic fibrosis and HCC in men and postmenopausal women may be due, at least in part, to lower production of estradiol and a reduced response to the action of estradiol. A better understanding of the basic mechanisms underlying the sex-associated differences in hepatic fibrogenesis and carciogenesis may open up new avenues for the prevention and treatment of chronic liver disease.

  15. Chronic Viral Infection and Primary Central Nervous System Malignancy

    OpenAIRE

    Saddawi-Konefka, Robert; Crawford, John R.

    2010-01-01

    Primary central nervous system (CNS) tumors cause significant morbidity and mortality in both adults and children. While some of the genetic and molecular mechanisms of neuro-oncogenesis are known, much less is known about possible epigenetic contributions to disease pathophysiology. Over the last several decades, chronic viral infections have been associated with a number of human malignancies. In primary CNS malignancies, two families of viruses, namely polyomavirus and herpesvirus, have be...

  16. Association between Celiac Disease and Chronic Hepatitis C Virus Infection

    OpenAIRE

    Garg, Ashish; Reddy, Chandrasekhar; Duseja, Ajay; Chawla, Yogesh; Radha K. Dhiman

    2011-01-01

    Celiac disease affects the proximal small intestine and is caused by a local immune response to dietary gluten. Celiac disease usually presents with chronic diarrhea; however, presentations with elevated hepatic transaminase levels in blood or with iron-deficiency anemia have been described. Celiac disease has been reported to be associated with autoimmune liver diseases. Hepatitis C virus (HCV) can also initiate autoimmune disease process. Therefore, HCV infection and celiac disease may occu...

  17. Acremonium kiliense infection in a child with chronic granulomatous disease

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Pastorino

    2005-12-01

    Full Text Available Infection by unusual microorganisms can be one of the clinical manifestations of primary immunodeficiency (PID. We report on a four-month-old child with pneumonia caused by the fungus Acremonium kiliense as the first clinical manifestation of chronic granulomatous disease. We emphasize the importance of an active search for unusual organisms in immunodeficient patients, and a precise diagnosis and early institution of specific treatment against such microorganisms for the reduction of the morbidity and mortality of these patients.

  18. Biofilms in chronic infections - a matter of opportunity - monospecies biofilms in multispecies infections

    DEFF Research Database (Denmark)

    Burmølle, Mette; Thomsen, Trine Rolighed; Fazli, Mustafa;

    2010-01-01

    to permanent tissue fillers and chronic wounds) both as to distribution (such as where in the wound bed) and organization (monospecies or multispecies microcolonies). We correlate these biofilm observations to observations of commensal biofilms (dental and intestine) and biofilms in natural ecosystems (soil......). The observations of the chronic biofilm infections point toward a trend of low bacterial diversity and sovereign monospecies biofilm aggregates even though the infection in which they reside are multispecies. In contrast to this, commensal and natural biofilm aggregates contain multiple species that are believed...

  19. Rhinovirus infection of allergen-sensitized and -challenged mice induces eotaxin release from functionally polarized macrophages

    OpenAIRE

    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.

    2010-01-01

    Human rhinovirus is responsible for the majority of virus-induced asthma exacerbations. To determine the immunologic mechanisms underlying rhinovirus-induced asthma exacerbations, we combined mouse models of allergic airways disease and human rhinovirus infection. We inoculated ovalbumin-sensitized and challenged BALB/c mice with rhinovirus serotype 1B, a minor group strain capable of infecting mouse cells. Compared to sham-infected, ovalbumin-treated mice, virus-infected mice showed increase...

  20. Depletion of Blood-Borne Macrophages Does Not Reduce Demyelination in Mice Infected with a Neurotropic Coronavirus

    OpenAIRE

    Xue, Shurong; Sun, Ning; van Rooijen, Nico; Perlman, Stanley

    1999-01-01

    Mice infected with the neurotropic coronavirus mouse hepatitis virus strain JHM (MHV-JHM) develop a chronic demyelinating disease with symptoms of hindlimb paralysis. Histological examination of the brains and spinal cords of these animals reveals the presence of large numbers of activated macrophages/microglia. In two other experimental models of demyelination, experimental allergic encephalomyelitis and Theiler’s murine encephalomyelitis virus-induced demyelination, depletion of hematogenou...

  1. Recombinant interleukin-1 alpha augments granuloma formation and cytokine production but not parasite clearance in mice infected with Leishmania donovani.

    OpenAIRE

    Curry, A J; Kaye, P. M.

    1992-01-01

    In vivo administration of various doses of recombinant interleukin-1 alpha to B10.D2/n mice chronically infected with Leishmania donovani resulted in enhanced formation of granulomas and in vitro production of gamma interferon. By direct microscopical enumeration, reduction in gross parasite burden in the viscera was not observed, however. These data highlight an important discordance between granuloma formation per se and parasite elimination and suggest that interleukin-1 deficiency alone c...

  2. Chronic experimental infection by Trypanosoma cruzi in Cebus apella monkeys

    Directory of Open Access Journals (Sweden)

    A. Riarte

    1995-12-01

    Full Text Available Twenty young male Cebus apella monkeys were infected with CAl Trypanosoma cruzi strain and reinfected with CA l or Tulahuen T.cruzi strains, with different doses and parasite source. Subpatent parasitemia was usually demonstrated in acute and chronic phases. Patent parasitemia was evident in one monkey in the acute phase and in four of them in the chronic phase after re-inoculations with high doses of CAl strain. Serological conversion was observed in all monkeys; titers were low, regardless of the methods used to investigate anti-T. cruzi specific antibodies. Higher titers were induced only when re-inoculations were perfomed with the virulent Tulahuén strain or high doses of CAl strain. Clinical electrocardiographic and ajmaline test evaluations did not reveal changes between infected and control monkeys. Histopathologically, cardiac lesions were always characterized by focal or multifocal mononuclear infiltrates and/or isolated fibrosis, as seen during the acute and chronic phases; neither amastigote nests nor active inflammation and fibrogenic processes characteristic of human acute and chronic myocarditis respectively, were observed. These morphological aspects more closely resemble those found in the "indeterminate phase" and contrast with the more diffuse and progressive pattern of the human chagasic myocarditis. All monkeys survived and no mortality was observed.

  3. A DESCRIPTIVE STUDY OF FUNGAL INFECTIONS IN CHRONICALLY DISCHARGING EARS

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    Sujatha

    2015-08-01

    Full Text Available BACKGROUND : Chronic Suppurative Otitis Media (CSOM is a disease of multiple aetiology and well known for its persis tence and recurrence inspite of treatment and are the bearbug of otologist, paediatrician and general practitioner. One of the reason s for the refractoriness to treatment and chronicity is coexist ing fungal infection of the ear. OBJECTIVES: Are to find out the prevalence of fungal infections in chronic discharging ears and to identify and isolate the type of fungus prevalent in these ears . MATERIALS AND METHOD S: Tertiary care hospital level descrip tive study was conducted in 50 cases of CSOM with actively discharging ears for a period of one year starting from February 2013. For all the cases aural swabs were collected from the diseased ear and were used for direct microscopic examination in potassi um hydroxide wet mount. Ear swab was cultured on Sabouraud’s dextrose agar plate for fungal cultures. The patient characteristics were prospectively recorded and results were analysed. CONCLUSION : There is high prevalence of coexisting fungal infection in actively discharging ears of CSOM patients

  4. Chronic Toxoplasma gondii in Nurr1-null heterozygous mice exacerbates elevated open field activity.

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    Jeffrey B Eells

    Full Text Available Latent infection with Toxoplasma gondii is common in humans (approximately 30% of the global population and is a significant risk factor for schizophrenia. Since prevalence of T. gondii infection is far greater than prevalence of schizophrenia (0.5-1%, genetic risk factors are likely also necessary to contribute to schizophrenia. To test this concept in an animal model, Nurr1-null heterozygous (+/- mice and wild-type (+/+ mice were evaluate using an emergence test, activity in an open field and with a novel object, response to bobcat urine and prepulse inhibition of the acoustic startle response (PPI prior to and 6 weeks after infection with T. gondii. In the emergence test, T. gondii infection significantly decreased the amount of time spent in the cylinder. Toxoplasma gondii infection significantly elevated open field activity in both +/+ and +/- mice but this increase was significantly exacerbated in +/- mice. T. gondii infection reduced PPI in male +/- mice but this was not statistically significant. Aversion to bobcat urine was abolished by T. gondii infection in +/+ mice. In female +/- mice, aversion to bobcat urine remained after T. gondii infection while the male +/- mice showed no aversion to bobcat urine. Antibody titers of infected mice were a critical variable associated with changes in open field activity, such that an inverted U shaped relationship existed between antibody titers and the percent change in open field activity with a significant increase in activity at low and medium antibody titers but no effect at high antibody titers. These data demonstrate that the Nurr1 +/- genotype predisposes mice to T. gondii-induced alterations in behaviors that involve dopamine neurotransmission and are associated with symptoms of schizophrenia. We propose that these alterations in murine behavior were due to further exacerbation of the altered dopamine neurotransmission in Nurr1 +/- mice.

  5. B cells and platelets harbor prion infectivity in the blood of deer infected with chronic wasting disease.

    Science.gov (United States)

    Mathiason, Candace K; Hayes-Klug, Jeanette; Hays, Sheila A; Powers, Jenny; Osborn, David A; Dahmes, Sallie J; Miller, Karl V; Warren, Robert J; Mason, Gary L; Telling, Glenn C; Young, Alan J; Hoover, Edward A

    2010-05-01

    Substantial evidence for prion transmission via blood transfusion exists for many transmissible spongiform encephalopathy (TSE) diseases. Determining which cell phenotype(s) is responsible for trafficking infectivity has important implications for our understanding of the dissemination of prions, as well as their detection and elimination from blood products. We used bioassay studies of native white-tailed deer and transgenic cervidized mice to determine (i) if chronic wasting disease (CWD) blood infectivity is associated with the cellular versus the cell-free/plasma fraction of blood and (ii) in particular if B-cell (MAb 2-104(+)), platelet (CD41/61(+)), or CD14(+) monocyte blood cell phenotypes harbor infectious prions. All four deer transfused with the blood mononuclear cell fraction from CWD(+) donor deer became PrP(CWD) positive by 19 months postinoculation, whereas none of the four deer inoculated with cell-free plasma from the same source developed prion infection. All four of the deer injected with B cells and three of four deer receiving platelets from CWD(+) donor deer became PrP(CWD) positive in as little as 6 months postinoculation, whereas none of the four deer receiving blood CD14(+) monocytes developed evidence of CWD infection (immunohistochemistry and Western blot analysis) after 19 months of observation. Results of the Tg(CerPrP) mouse bioassays mirrored those of the native cervid host. These results indicate that CWD blood infectivity is cell associated and suggest a significant role for B cells and platelets in trafficking CWD infectivity in vivo and support earlier tissue-based studies associating putative follicular B cells with PrP(CWD). Localization of CWD infectivity with leukocyte subpopulations may aid in enhancing the sensitivity of blood-based diagnostic assays for CWD and other TSEs. PMID:20219916

  6. Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice.

    Directory of Open Access Journals (Sweden)

    Rachel E Sutherland

    Full Text Available Mammals are serially infected with a variety of microorganisms, including bacteria and parasites. Each infection reprograms the immune system's responses to re-exposure and potentially alters responses to first-time infection by different microorganisms. To examine whether infection with a metazoan parasite modulates host responses to subsequent bacterial infection, mice were infected with the hookworm-like intestinal nematode Nippostrongylus brasiliensis, followed in 2-4 weeks by peritoneal injection of the pathogenic bacterium Klebsiella pneumoniae. Survival from Klebsiella peritonitis two weeks after parasite infection was better in Nippostrongylus-infected animals than in unparasitized mice, with Nippostrongylus-infected mice having fewer peritoneal bacteria, more neutrophils, and higher levels of protective interleukin 6. The improved survival of Nippostrongylus-infected mice depends on IL-4 because the survival benefit is lost in mice lacking IL-4. Because mast cells protect mice from Klebsiella peritonitis, we examined responses in mast cell-deficient Kit(W-sh/Kit(W-sh mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to Kit(W-sh/Kit(W-sh mice restored survival benefits of parasitosis. These results show that recent infection with Nippostrongylus brasiliensis protects mice from Klebsiella peritonitis by modulating mast cell contributions to host defense, and suggest more generally that parasitosis can yield survival advantages to a bacterially infected host.

  7. Antineutrophil Cytoplasmic Antibody Induction due to Infection: A Patient with Infective Endocarditis and Chronic Hepatitis C.

    Science.gov (United States)

    Kamar, Fareed B; Hawkins, T Lee-Ann

    2016-01-01

    While antineutrophil cytoplasmic antibody (ANCA) is often used as a diagnostic marker for certain vasculitides, ANCA induction in the setting of infection is much less common. In the case of infective endocarditis, patients may present with multisystem disturbances resembling an autoimmune process, cases that may be rendered even trickier to diagnose in the face of a positive ANCA. Though not always straightforward, distinguishing an infective from an inflammatory process is pivotal in order to guide appropriate therapy. We describe an encounter with a 43-year-old male with chronically untreated hepatitis C virus infection who featured ANCA positivity while hospitalized with acute bacterial endocarditis. His case serves as a reminder of two of the few infections known to uncommonly generate ANCA positivity. We also summarize previously reported cases of ANCA positivity in the context of endocarditis and hepatitis C infections. PMID:27366166

  8. Extrahepatic manifestations of chronic hepatitis C virus infection.

    Science.gov (United States)

    Cacoub, Patrice; Comarmond, Cloe; Domont, Fanny; Savey, Léa; Desbois, Anne C; Saadoun, David

    2016-02-01

    During hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined. PMID:26862398

  9. Plasmacytoid dendritic cell-derived IFNα modulates Th17 differentiation during early Bordetella pertussis infection in mice.

    Science.gov (United States)

    Wu, V; Smith, A A; You, H; Nguyen, T A; Ferguson, R; Taylor, M; Park, J E; Llontop, P; Youngman, K R; Abramson, T

    2016-05-01

    Whooping cough is a highly contagious respiratory disease caused by Bordetella pertussis (B. pertussis). T helper 17 (Th17) cells have a central role in the resolution of the infection. Emerging studies document that type I interferons (IFNs) suppress Th17 differentiation and interleukin (IL)-17 responses in models of infection and chronic inflammation. As plasmacytoid dendritic cells (pDCs) are a major source of type I IFNs, we hypothesize that during B. pertussis infection in mice, pDC-derived IFNα inhibits a rapid increase in Th17 cells. We found that IFNα-secreting pDCs appear in the lungs during the early stages of infection, while a robust rise of Th17 cells in the lungs is detected at 15 days post-infection or later. The presence of IFNα led to reduced Th17 differentiation and proliferation in vitro. Furthermore, in vivo blocking of IFNα produced by pDCs during infection with B. pertussis infection resulted in early increase of Th17 frequency, inflammation, and reduced bacterial loads in the airways of infected mice. Taken together, the experiments reported here describe an inhibitory role for pDCs and pDC-derived IFNα in modulating Th17 responses during the early stages of B. pertussis infection, which may explain the prolonged nature of whooping cough.

  10. Leishmania major infection in humanized mice induces systemic infection and provokes a nonprotective human immune response.

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    Anja Kathrin Wege

    Full Text Available BACKGROUND: Leishmania (L. species are the causative agent of leishmaniasis. Due to the lack of efficient vaccine candidates, drug therapies are the only option to deal with cutaneous leishmaniasis. Unfortunately, chemotherapeutic interventions show high toxicity in addition to an increased risk of dissemination of drug-resistant parasites. An appropriate laboratory animal based model is still missing which allows testing of new drug strategies in the context of human immune cells in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Humanized mice were infected subcutaneously with stationary phase promastigote L. major into the footpad. The human immune response against the pathogen and the parasite host interactions were analyzed. In addition we proved the versatility of this new model to conduct drug research studies by the inclusion of orally given Miltefosine. We show that inflammatory human macrophages get infected with Leishmania parasites at the site of infection. Furthermore, a Leishmania-specific human-derived T cell response is initiated. However, the human immune system is not able to prevent systemic infection. Thus, we treated the mice with Miltefosine to reduce the parasitic load. Notably, this chemotherapy resulted in a reduction of the parasite load in distinct organs. Comparable to some Miltefosine treated patients, humanized mice developed severe side effects, which are not detectable in the classical murine model of experimental leishmaniasis. CONCLUSIONS/SIGNIFICANCE: This study describes for the first time L. major infection in humanized mice, characterizes the disease development, the induction of human adaptive and innate immune response including cytokine production and the efficiency of Miltefosine treatment in these animals. In summary, humanized mice might be beneficial for future preclinical chemotherapeutic studies in systemic (visceral leishmaniasis allowing the investigation of human immune response, side effects of the drug

  11. Determinants of survival among HIV-infected chronic dialysis patients.

    Science.gov (United States)

    Rodriguez, Rudolph A; Mendelson, Michael; O'Hare, Ann M; Hsu, Ling Chin; Schoenfeld, Patricia

    2003-05-01

    Over 100 HIV-infected patients have initiated chronic dialysis at San Francisco General Hospital (SFGH) since 1985. This study employed retrospective analysis to identify determinants of and trends in survival among HIV-infected patients who have initiated chronic dialysis at SFGH from January 1, 1985 to November 1, 2002 (n = 115). Cohort patient survival was compared with survival after an AIDS-opportunistic illness in all HIV-infected patients in San Francisco during the study period. Higher CD4 count (hazard ratio [HR], 0.86 per 50 cells/mm(3) increase; 95% confidence interval [CI], 0.80 to 0.93) and serum albumin (HR, 0.53 per 1 g/dl increase; CI, 0.36 to 0.78) at initiation of dialysis were strongly associated with lower mortality. Survival for those initiating dialysis during the era of highly active antiretroviral therapy (HAART) was 16.1 mo versus 9.4 mo for those initiating dialysis before this time, but this difference was not statistically significant. In adjusted analysis, only a non-statistically significant trend toward improved survival during the HAART era was noted (HR, 0.59; CI, 0.34 to 1.04). By comparison, survival for all HIV-infected patients after an AIDS-opportunistic illness in San Francisco increased from 16 mo in 1994 to 81 mo in 1996. The dramatic improvement in survival that has occurred since the mid-1990s for patients with HIV appears to be greatly attenuated in the sub-group undergoing dialysis. Although this may partly reflect confounding by race, injection drug use and HCV co-infection, future attempts to improve survival among HIV-infected dialysis patients should focus on barriers to the effective use of HAART in this group.

  12. Effect of chronic FIV infection, and efficacy of marbofloxacin treatment, on Mycoplasma haemofelis infection.

    Science.gov (United States)

    Tasker, Séverine; Caney, Sarah M A; Day, Michael J; Dean, Rachel S; Helps, Chris R; Knowles, Toby G; Lait, Philippa J P; Pinches, Mark D G; Gruffydd-Jones, Timothy J

    2006-10-31

    The purpose of this study was to investigate the effect of chronic feline immunodeficiency virus (FIV) infection, and efficacy of marbofloxacin treatment, on Mycoplasma haemofelis infection. Six cats chronically infected with FIV-Glasgow8 (Group X) and six FIV-free cats (Group Y) were infected with M. haemofelis on Day 0 by intravenous blood inoculation. From Day 0 until Day 86 post-infection (pi), blood samples were collected for M. haemofelis and FIV provirus quantitative real-time PCR and haematology. Three of the six cats in each of Groups X and Y were randomly selected to receive marbofloxacin treatment (2 mg/kg PO q24 h) from Day 16 to 43 pi, with the remaining cats being untreated controls with no antibiotic treatment. The M. haemofelis copy numbers and haematological data were compared between Groups X and Y, and between marbofloxacin-treated and control cats using a Mann-Whitney U-test. M. haemofelis infection was associated with development of macrocytic hypochromic anaemia. In some cats, marked variation in M. haemofelis copy number over time (>100,000-fold difference within 48 h in some cats) and/or cycling of copy number was seen. No correlation was found between FIV provirus copy number and M. haemofelis copy number or haematological variables. No significant effect of chronic FIV infection on M. haemofelis copy number kinetics or haematological changes due to M. haemofelis infection was found, other than MCHC (P=0.03). Marbofloxacin treatment was associated with a significant decrease in M. haemofelis copy number (P=0.002), although consistent clearance of infection was not demonstrated. This study reveals the presence of marked fluctuations in M. haemofelis copy number kinetics in vivo and a significant response to marbofloxacin antibiotic treatment.

  13. Anti-gluten immune response following Toxoplasma gondii infection in mice.

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    Emily G Severance

    Full Text Available Gluten sensitivity may affect disease pathogenesis in a subset of individuals who have schizophrenia, bipolar disorder or autism. Exposure to Toxoplasma gondii is a known risk factor for the development of schizophrenia, presumably through a direct pathological effect of the parasite on brain and behavior. A co-association of antibodies to wheat gluten and to T. gondii in individuals with schizophrenia was recently uncovered, suggesting a coordinated gastrointestinal means by which T. gondii and dietary gluten might generate an immune response. Here, we evaluated the connection between these infectious- and food-based antigens in mouse models. BALB/c mice receiving a standard wheat-based rodent chow were infected with T. gondii via intraperitoneal, peroral and prenatal exposure methods. Significant increases in the levels of anti-gluten IgG were documented in all infected mice and in offspring from chronically infected dams compared to uninfected controls (repetitive measures ANOVAs, two-tailed t-tests, all p≤0.00001. Activation of the complement system accompanied this immune response (p≤0.002-0.00001. Perorally-infected females showed higher levels of anti-gluten IgG than males (p≤0.009 indicating that T. gondii-generated gastrointestinal infection led to a significant anti-gluten immune response in a sex-dependent manner. These findings support a gastrointestinal basis by which two risk factors for schizophrenia, T. gondii infection and sensitivity to dietary gluten, might be connected to produce the immune activation that is becoming an increasingly recognized pathology of psychiatric disorders.

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

    Science.gov (United States)

    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. Oral infection of mice with Salmonella enterica serovar Typhimurium causes meningitis and infection of the brain

    Directory of Open Access Journals (Sweden)

    Provias John

    2007-06-01

    Full Text Available Abstract Background Salmonella meningitis is a rare and serious infection of the central nervous system following acute Salmonella enterica sepsis. For this pathogen, no appropriate model has been reported in which to examine infection kinetics and natural dissemination to the brain. Methods Five mouse lines including C57BL/6, Balb/c, 129S6-Slc11a1tm1Mcg, 129S1/SvImJ, B6.129-Inpp5dtm1Rkh were used in the murine typhoid model to examine the dissemination of systemic Salmonella enterica serovar Typhimurium following oral infection. Results We report data on spontaneous meningitis and brain infection following oral infection of mice with Salmonella enterica serovar Typhimurium. Conclusion This model may provide a system in which dissemination of bacteria through the central nervous system and the influence of host and bacterial genetics can be queried.

  16. Actinomyces and Nocardia infections in chronic granulomatous disease

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    Shahindokht Bassiri-Jahromi

    2011-01-01

    Full Text Available Objective : Chronic granulomatous disease (CGD is an inherited disorder of the Nicotinamide adenine dinucleotide phosphate reduced oxidase complex characterized by recurrent bacterial and fungal infections. Disseminated infection by combination of opportunistic agents is being increasingly reported in CGD patients. We presented in the retrospective review of medical records, the etiology, presentation, clinical characteristics the infections detected, predisposing condition and outcome of nocardiosis and actinomycosis involved in a group of pediatric patients diagnosed with CGD. Materials and Methods: The clinical presentation of CGD-related infections was reviewed retrospectively from the medical records of all 12 patients with CGD. We studied respectively 12 patients between 2001 and 2008, and we analyzed two pediatric patients with CGD who acquired Nocardia and Actinomyces infections, and their clinical and microbiological characteristics were described. The material for investigations was collected from scrapings, crusts, pus from subcutaneous abscesses or exudation from sinus tracts, surgical debridement, and biopsy specimens. The microbiological diagnosis was determined by biochemical tests, histology, microscopy, and culture of clinical samples. Results: The medical records of 12 diagnosed CGD patients with suspected nocardiosis or actinomycosis were reviewed. One patient was diagnosed with actinomycosis and one patient with nocardiosis. Patients consisted of seven males and five females with ranging ages of 3 to 18 years. Nocardiosis and actinomycosis isolated in the two patients were confirmed by histology and culture methods. Neutrophil oxidative burst were absent (NBT=0 in both patients. The most common manifestations of CGD due to fungal infections, actinomycosis, and nocardiosis were osteomyelitis (42.8%, pulmonary infections (28.6%, lymphadenopathy (14.3%, and skin involvement (14.3% during their illness. Conclusion: Nocardiosis

  17. A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice

    NARCIS (Netherlands)

    HogenEsch, H.; Gijbels, M.J.J.; Offerman, E.; Hooft, J. van; Bekkum, D.W. van; Zurcher, C.

    1993-01-01

    Chronic proliferative dermatitis is a new spontaneous mutation in C57BL/Ka mice. Breeding results suggest an autosomal recessive mode of inheritance. Mutant mice develop skin lesions at the age of 5 to 6 weeks. The lesions occur in the ventral and dorsal skin of the body, whereas ears, footpads, and

  18. TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice

    DEFF Research Database (Denmark)

    Reinert, Line; Harder, Louis Andreas; Holm, Christian;

    2012-01-01

    Herpes simplex viruses (HSVs) are highly prevalent neurotropic viruses. While they can replicate lytically in cells of the epithelial lineage, causing lesions on mucocutaneous surfaces, HSVs also establish latent infections in neurons, which act as reservoirs of virus for subsequent reactivation...... responses in astrocytes. Tlr3-/- mice were hypersusceptible to HSV-2 infection in the CNS after vaginal inoculation. HSV-2 exhibited broader neurotropism in Tlr3-/- mice than it did in WT mice, with astrocytes being most abundantly infected. Tlr3-/- mice did not exhibit a global defect in innate immune...

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

    Science.gov (United States)

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

    Science.gov (United States)

    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.

  1. Atypical streptococcal infection of gingiva associated with chronic mouth breathing.

    Science.gov (United States)

    Haytac, M Cenk; Oz, I Attila

    2007-01-01

    Streptococcal infections of oral tissues are mainly seen in young children who experience a variety of upper respiratory tract infections. The disease is characterized by fever, lymphadenopathy, and ulcers on the gingiva, lips, and tonsils. This case report presents an atypical streptococcal infection of the gingiva in an 18-year-old man. The patient was referred to the periodontology department complaining of a 2-month history of gingival enlargement. He had persistent fever (39.5 degrees C) and general malaise for 2 weeks. Intraoral examination revealed extremely inflamed and enlarged gingiva with spontaneous bleeding and suppuration. Based on the otolaryngologic consultation and the hematologic, immunologic, and microbiologic tests, the final diagnosis was an atypical streptococcal gingivitis with chronic adenoid-related mouth breathing and oral hygiene neglect as contributing factors. Treatment consisted of a broad-spectrum antibiotic regimen, supragingival and subgingival debridement, adenoidectomy, and scaling and root planing. A good response to nonsurgical therapy was achieved despite poor patient compliance, and no recurrence of gingival enlargement was observed after 1 year. Streptococcal gingivitis should be included in the differential diagnosis of suppurative gingival enlargements. Furthermore, chronic mouth breathing may initiate and/or contribute to this disease.

  2. Effects of tacrolimus on infection of Friend murine leukemia virus to Fv-4 gene heterozygous mice

    Institute of Scientific and Technical Information of China (English)

    Feng-min ZHANG; Bao-feng YANG; Hong-xi GU; Xiao-bei CHEN; Zhao-hua ZHONG; Zhi CHENG

    2004-01-01

    AIM: To investigate the effect of tacrolimus (FK506) on the infection of Friend murine leukemia virus (Friend MuLV) in vivo. METHODS: Three kinds of mice were used including Friend MuLV-sensitive BALB/c mice, Friend MuLV-resistant Fv-4 gene-homozygous mice (Fv-4 mice), and Friend MuLV-resistant Fv-4 gene-heterozygous mice (Fl mice). Tacrolimus was administrated ip to those mice in every 2 d. Those treated mice were inoculated ip with Friend MuLV once on d 3. The symptoms and viral proliferations in those mice were observed to recognize the Friend MuLV infection. The expression and genotype of Fv-4 gene that resistant against the infection of Friend MuLV were analyzed to confirm the genomic background and related mechanism of the resistance. RESULTS:BALB/c mice and Fl mice, but not Fv-4 mice, appeared obvious early death, spleenomegaly, and viral proliferation after both treatments of viral inoculation and tacrolimus administration, whereas the expression and genotype of Fv-4 gene was not changed in F1 mice and Fv-4 mice with treatment of tacrolimus. Compared to the virusinoculated control, the Friend MuLV-sensitivity of tacrolimus-treated BALB/c mice and the Friend MuLV-resistance of tacrolimus-treated Fv-4 mice were the same as the controls, but only Fl mice became the symptoms and viral proliferation after both treatments. It suggested the Friend MuLV-resistant Fl mice could be converted to be Friend MuLV-sensitive by treatment of tacrolimus, and this conversion was not depended on the expression and genotype of Fv-4 gene. CONCLUSION: Tacrolimus could not inhibit the infection of Friend MuLV in all mice, furthermore,it could enhance the infection of Friend MuLV in F1 mice. The enhancement may be related to the immunosuppressive effect of tacrolimus.

  3. Strain Differences in the Chronic Mild Stress Animal Model of Depression and Anxiety in Mice

    OpenAIRE

    Jung, Yang-Hee; Hong, Sa-Ik; Ma, Shi-Xun; Hwang, Ji-Young; Kim, Jun-Sup; lee, Ju-hyun; Seo, Jee-Yeon; Lee, Seok-Yong; Jang, Choon-Gon

    2014-01-01

    Chronic mild stress (CMS) has been reported to induce an anhedonic-like state in mice that resembles some of the symptoms of human depression. In the present study, we used a chronic mild stress animal model of depression and anxiety to examine the responses of two strains of mice that have different behavioral responsiveness. An outbred ICR and an inbred C57BL/6 strain of mice were selected because they are widely used strains in behavioral tests. The results showed that the inbred C57BL/6 a...

  4. Post-parturient shedding of Listeria monocytogenes in breast milk of infected mice

    OpenAIRE

    Poulsen, Keith P; Pillers, DeAnn M; Conway, James H.; Faith, Nancy G.; Czuprynski, Charles J.

    2013-01-01

    The objectives of this study were to develop an animal model to study Listeria monocytogenes infection during the peri-parturient period and identify sources of maternal shedding of the pathogen. Peri-parturient mice were infected intragastrically with L. monocytogenes that expressed bacterial luciferase. Mice were then imaged in vivo over time. Secreted breast milk samples from mice infected after parturition were enriched and plated for culture and imaging. Bioluminescence imaging technolog...

  5. Protective immune response to experimental infection with Sarcocystis neurona in C57BL/6 mice

    OpenAIRE

    Witonsky, S. G.; Gogal, R. M.; Duncan, R. B.; Lindsay, D S

    2003-01-01

    Immunocompetent C57BL/6 mice were infected with Sarcocystis neurona merozoites to assess the protective immune response to active infection. Using a direct agglutination test, all infected mice seroconverted to S. neurona merozoite antigens by day 14 postinfection (PI). Further, mice developed splenomegaly and bilateral symmetrical lymphadenopathy by day 14 PI, which appeared to be resolving by day 28 PI. Histologic analysis revealed a marked increase in germinal center formation in the splee...

  6. Alteration in the endogenous intestinal flora of swiss webster mice by experimental Angiostrongylus costaricensis infection

    Directory of Open Access Journals (Sweden)

    Vandack Nobre

    2004-11-01

    Full Text Available The association between worm infections and bacterial diseases has only recently been emphasized. This study examined the effect of experimental Angiostrongylus costaricensis infection on endogenous intestinal flora of Swiss Webster mice. Eight mice aging six weeks were selected for this experiment. Four were infected with A. costaricensis and the other four were used as controls. Twenty eight days after the worm infection, all mice in both groups were sacrificed and samples of the contents of the ileum and colon were obtained and cultured for aerobic and anaerobic bacteria. In the mice infected with A. costaricensis there was a significant increase in the number of bacteria of the endogenous intestinal flora, accompanied by a decrease in the number of Peptostreptococcus spp. This alteration in the intestinal flora of mice infected by the nematode may help to understand some bacterial infections described in humans.

  7. Aureobasidium pullulans infection in a patient with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Leonardo Rodrigues de Oliveira

    2013-09-01

    Full Text Available Saprophytic fungi are being increasingly recognized as etiologic agents of mycoses in immunosuppressed patients. We report a case of subcutaneous infiltration by Aureobasidium pullulans, likely due to traumatic inoculation, in a neutropenic patient during chemotherapy for chronic lymphocytic leukemia. The patient was treated with amphotericin B deoxycholate but was subsequently switched to itraconazole, which improved the lesion. This case highlights the importance of considering unusual fungal infections in critically ill patients such as those who are immunosuppressed due to chemotherapy. Diagnostic techniques and effective antifungal therapy have improved the prognosis of these cases.

  8. Simotang enhances gastrointestinal motility, motilin and cholecystokinin expression in chronically stressed mice

    Institute of Scientific and Technical Information of China (English)

    Guang-Xian Cai; Bai-Yan Liu; Jian Yi; Xue-Mei Chen; Fu-Ling Liu

    2011-01-01

    AIM: To investigate the effect of Simotang (Decoction of Four Powered Drugs) on gastrointestinal motility, motilin and cholecystokinin expression in chronically stressed mice. METHODS: Forty mice were randomly divided into control group, stress group (model group), mosapride group and Simotang group, 10 in each group. A variety of unpredictable stimulations were used to induce chronic stress in mice. Then, the mice were treated with distilled water, mosapride or Simotang for 7 d. Gastric emptying and intestinal propulsion function were detected. Serum level of motilin was measured by enzyme-linked immunosorbent assay. Expression of cholecystokinin (CCK) in intestine, spinal cord and brain of mice was detected by immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction, respectively. RESULTS: Simotang improved the gastric emptying and intestinal propulsion in chronically stressed mice. Furthermore, the serum motilin level was significantly higher and the expression levels of CCK-positive cells and genes were significantly lower in intestine, spinal cord and brain of Simotang group than in those of model group (P < 0.05). No significant difference was found in serum motilin level and expression levels of CCK-positive cells and genes between the mosapride and Simotang groups. CONCLUSION: Simotang enhances the gastrointestinal motility in chronically stressed mice by regulating the serum motilin level and the expression of cholecystokinin.

  9. Chronic obstructive pulmonary disease and infection. Disruption of the microbiome?

    Science.gov (United States)

    Sethi, Sanjay

    2014-01-01

    The dynamics of infection in chronic obstructive pulmonary disease (COPD) are complex, and microbiome technology has provided us with a new research tool for its better understanding. There is compartmentalization of the microbiota in the various parts of the lung. Studies of the lower airway lumen microbiota in COPD have yielded confusing results, and additional studies with scrupulous attention to prevent and account for upper airway contamination of bronchoalveolar lavage samples are required. Lung tissue microbiota has been examined in three studies, which also demonstrate varied results based on the site of sampling (bronchial mucosa, lung parenchyma), and this variation extends to sampling sites within a lobe of the lung. The Vicious Circle Hypothesis embodies how an altered lung microbiome could contribute to COPD progression. Relating microbiota composition to airway and systemic inflammation and clinical outcomes are important research questions. Although various obstacles need to be surmounted, ultimately lung microbiome studies will provide new insights into how infection contributes to COPD.

  10. Hematopoietic Stem and Immune Cells in Chronic HIV Infection

    Directory of Open Access Journals (Sweden)

    Jielin Zhang

    2015-01-01

    Full Text Available Hematopoietic stem cell (HSC belongs to multipotent adult somatic stem cells. A single HSC can reconstitute the entire blood system via self-renewal, differentiation into all lineages of blood cells, and replenishment of cells lost due to attrition or disease in a person’s lifetime. Although all blood and immune cells derive from HSC, immune cells, specifically immune memory cells, have the properties of HSC on self-renewal and differentiation into lineage effector cells responding to the invading pathogens. Moreover, the interplay between immune memory cell and viral pathogen determines the course of a viral infection. Here, we state our point of view on the role of blood stem and progenitor cell in chronic HIV infection, with a focus on memory CD4 T-cell in the context of HIV/AIDS eradication and cure.

  11. Hematopoietic Stem and Immune Cells in Chronic HIV Infection.

    Science.gov (United States)

    Zhang, Jielin; Crumpacker, Clyde

    2015-01-01

    Hematopoietic stem cell (HSC) belongs to multipotent adult somatic stem cells. A single HSC can reconstitute the entire blood system via self-renewal, differentiation into all lineages of blood cells, and replenishment of cells lost due to attrition or disease in a person's lifetime. Although all blood and immune cells derive from HSC, immune cells, specifically immune memory cells, have the properties of HSC on self-renewal and differentiation into lineage effector cells responding to the invading pathogens. Moreover, the interplay between immune memory cell and viral pathogen determines the course of a viral infection. Here, we state our point of view on the role of blood stem and progenitor cell in chronic HIV infection, with a focus on memory CD4 T-cell in the context of HIV/AIDS eradication and cure. PMID:26300920

  12. Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats

    DEFF Research Database (Denmark)

    Johansen, H K; Espersen, F; Pedersen, S S;

    1993-01-01

    We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic changes......, and antibody responses. The rats challenged with P. aeruginosa alginate beads experienced a generally more severe lung pathology and the antibody responses were more homogeneous with less dispersion as compared to the rats having free live P. aeruginosa bacteria. In general, manifestations were more severe...... in the athymic rats compared to the normal rats. It is, however, notable that the athymic rats developed similar microscopic lung manifestations as the normal rats when given a large number of P. aeruginosa in the beads, with dense accumulation of neutrophil granulocytes and microcolonies comparable...

  13. 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.

    Science.gov (United States)

    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

  14. Resistance of Neonatal Mice to Scrapie Is Associated with Inefficient Infection of the Immature Spleen

    OpenAIRE

    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 time...

  15. Parasitological characteristics of Schistosoma mansoni infection in swiss mice with underlying malnutrition

    OpenAIRE

    Simões Carla; Neves Renata Heisler; Barros Lucas de Andrade; Brito Patrícia Dias; Cravo Cristiane Oliveira; Moura Egberto Gaspar de; Machado-Silva José Roberto

    2002-01-01

    The effects of a protein-restricted diet (8% protein, 81% carbohydrate and 11% lipids) on Schistosoma mansoni infectivity, fecal egg excretion and intestinal egg distribution in Swiss (SW) mice were studied. Pregnant mice received a deficient diet from the middle of gestation until delivery. Seven-days-old mice were exposed to 50 cercariae (BH strain, Brazil). Offspring mice had a free access to the deficient diet since lactation until adulthood. The controls were fed with a commercial mice d...

  16. Pathogenesis of occult chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    Rocio Aller de la Fuente; María L Gutiérrez; Javier Garcia-Samaniego; Conrado Fernández-Rodriguez; Jose Luis Lledó; Gregorio Castellano

    2011-01-01

    Occult hepatitis B infection (OBI) is characterized by hepatitis B virus (HBV) DNA in serum in the absence of hepatitis B surface antigen (HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns. Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays; but more frequently it is due to a strong suppression of viral replication and gene expression. OBI is an entity with world-wide diffusion. The failure to detect HBsAg, despite the persistence of the viral DNA, is due in most cases to the strong suppression of viral replication and gene expression that characterizes this "occult" HBV infection; although the mechanisms responsible for suppression of HBV are not well understood. The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection. Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma.

  17. Occult hepatitis B infection and its possible impact on chronic hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Habibollahi Peiman

    2009-01-01

    Full Text Available As a well-recognized clinical phenomenon, persistent detectable viral genome in liver or sera in the absence of other serological markers for active hepatitis B virus (HBV replication is called occult HBV infection. The main mechanism through which occult infection occurs is not completely understood and several possible explanations, such as integration into human genome and maintenance in peripheral mononuclear cells, exist. Occult HBV infection has been reported in different populations, especially among patients with Hepatitis C (HCV related liver disease. The probable impact of occult HBV in patients with chronic HCV infection has been previously investigated and the evidence suggests a possible correlation with lower response to anti-viral treatment, higher grades of liver histological changes, and also developing hepatocellular carcinoma. However, in the absence of conclusive results, further studies should be conducted to absolutely assess the impact of occult HBV contamination on the HCV related liver disease.

  18. Enterococcus faecalis subverts and invades the host urothelium in patients with chronic urinary tract infection.

    Directory of Open Access Journals (Sweden)

    Harry Horsley

    Full Text Available Bacterial urinary tract infections (UTI are a major growing concern worldwide. Uropathogenic Escherichia coli has been shown to invade the urothelium during acute UTI in mice and humans, forming intracellular reservoirs that can evade antibiotics and the immune response, allowing recurrence at a later date. Other bacterial species, such as Staphylococcus saprophyticus, Klebsiella pneumonia and Salmonella enterica have also been shown to be invasive in acute UTI. However, the role of intracellular infection in chronic UTI causing more subtle lower urinary tract symptoms (LUTS, a particular problem in the elderly population, is poorly understood. Moreover, the species of bacteria involved remains largely unknown. A previous study of a large cohort of non-acute LUTS patients found that Enterococcus faecalis was frequently found in urine specimens. E. faecalis accounts for a significant proportion of chronic bladder infections worldwide, although the invasive lifestyle of this uropathogen has yet to be reported. Here, we wanted to explore this question in more detail. We harvested urothelial cells shed in response to inflammation and, using advanced imaging techniques, inspected them for signs of bacterial pathology and invasion. We found strong evidence of intracellular E. faecalis harboured within urothelial cells shed from the bladder of LUTS patients. Furthermore, using a culture model system, these patient-isolated strains of E. faecalis were able to invade a transitional carcinoma cell line. In contrast, we found no evidence of cellular invasion by E. coli in the patient cells or the culture model system. Our data show that E. faecalis is highly competent to invade in this context; therefore, these results have implications for both the diagnosis and treatment of chronic LUTS.

  19. Effect of chronic feline immunodeficiency infection, and efficacy of marbofloxacin treatment, on 'Candidatus Mycoplasma haemominutum' infection.

    Science.gov (United States)

    Tasker, Séverine; Caney, Sarah M A; Day, Michael J; Dean, Rachel S; Helps, Chris R; Knowles, Toby G; Lait, Philippa J P; Pinches, Mark D G; Gruffydd-Jones, Timothy J

    2006-03-01

    The purpose of this study was to investigate the effect of chronic feline immunodeficiency virus (FIV) infection, and efficacy of marbofloxacin treatment, on 'Candidatus Mycoplasma haemominutum' infection. Six cats chronically infected with FIV-Glasgow8 (group A) and six FIV-free cats (group B) were infected with 'Candidatus M. haemominutum' on day 0 by intravenous inoculation of blood. From day 0 to 105 post-infection (pi), blood samples were collected for 'Candidatus M. haemominutum' and FIV provirus quantitative real-time polymerase chain reaction (PCR) and haematological examination. Three of the six cats in each of the groups were randomly selected to receive marbofloxacin treatment (2mg/kg PO SID) from day 49 to day 76 pi, with the remaining cats being untreated controls. Maximum 'Candidatus M. haemominutum' copy number was reached around day 30 pi. No overt cycling or marked variation in copy number was observed. No significant effect of FIV infection on 'Candidatus M. haemominutum' copy number kinetics or anaemia indices was found. No correlation was found between FIV provirus copy number and 'Candidatus M. haemominutum' copy number or haematological variables. Although marbofloxacin treatment was associated with a significant decrease in 'Candidatus M. haemominutum' copy number, the copy number plateaued during treatment, with no negative PCR results. Additionally, after termination of marbofloxacin treatment the copy numbers of the treated cats increased to reach levels similar to those of the untreated cats within 7-10 days. This study documents, for the first time, the infection kinetics and antibiotic responsiveness of 'Candidatus M. haemominutum' infection.

  20. Complement C3 deficiency attenuates chronic hypoxia-induced pulmonary hypertension in mice.

    Directory of Open Access Journals (Sweden)

    Eileen M Bauer

    Full Text Available Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension.Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3-/- hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3-/- mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3-/- mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3-/- mice.Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans.

  1. Chronic Wasting Disease of Deer and Elk in Transgenic Mice: Oral Transmission and Pathobiology

    OpenAIRE

    Trifilo, Matthew J.; Ying, Ge; Teng, Chao; Oldstone, Michael B. A.

    2007-01-01

    To study the pathogenesis of chronic wasting disease (CWD) in deer and elk, transgenic (tg) mice were generated that expressed the prion protein (PrP) of deer containing a glycine at amino acid (aa) 96 and a serine at aa 225 under transcriptional control of the murine PrP promoter. This construct was introduced into murine PrP-deficient mice. As anticipated, neither non-tg mice nor PrP ko mice were susceptible when inoculated intracerebrally (i.c.) or orally with CWD brain material (scrapie p...

  2. Effects of Chronic Mild Stress in Female Bax Inhibitor-1-Gene Knockout Mice

    OpenAIRE

    Sui, Zhi-Yan; Chae, Han-Jung; Huang, Guang-Biao; Zhao, Tong; Shrestha Muna, Sushma; Chung, Young-Chul

    2012-01-01

    Objective The anti-apoptotic protein Bax inhibitor-1 (BI-1) is a regulator of apoptosis linked to endoplasmic reticulum (ER) stress, and BI-1-/- mice exhibit increased sensitivity to tissue damage. The purpose of this study was to investigate the role of BI-1 in the pathogenesis of chronic mild stress (CMS)-induced depression-like behaviors in BI-1-/- mice. Methods We delivered CMS for 2 or 6 weeks in BI-1-knockout and wild-type mice. Control groups of BI-1-knockout and wild-type mice were le...

  3. HIV-1 vaccine-specific responses induced by Listeria vector vaccines are maintained in mice subsequently infected with a model helminth parasite, Schistosoma mansoni.

    Science.gov (United States)

    Shollenberger, Lisa M; Bui, Cac T; Paterson, Yvonne; Nyhoff, Lindsay; Harn, Donald A

    2013-11-19

    In areas co-endemic for helminth parasites and HIV/AIDS, infants are often administered vaccines prior to infection with immune modulatory helminth parasites. Systemic Th2 biasing and immune suppression caused by helminth infection reduces cell-mediated responses to vaccines such as tetanus toxoid and BCG. Therefore, we asked if infection with helminthes post-vaccination, alters already established vaccine induced immune responses. In our model, mice are vaccinated against HIV-1 Gag using a Listeria vaccine vector (Lm-Gag) in a prime-boost manner, then infected with the human helminth parasite Schistosoma mansoni. This allows us to determine if established vaccine responses are maintained or altered after helminth infection. Our second objective asked if helminth infection post-vaccination alters the recipient's ability to respond to a second boost. Here we compared responses between uninfected mice, schistosome infected mice, and infected mice that were given an anthelminthic, which occurred coincident with the boost or four weeks prior, as well as comparing to un-boosted mice. We report that HIV-1 vaccine-specific responses generated by Listeria vector HIV-1 vaccines are maintained following subsequent chronic schistosome infection, providing further evidence that Listeria vector vaccines induce potent vaccine-specific responses that can withstand helminth infection. We also were able to demonstrate that administration of a second Listeria boost, which markedly enhanced the immune response, was minimally impacted by schistosome infection, or anthelminthic therapy. Surprisingly, we also observed enhanced antibody responses to HIV Gag in vaccinated mice subsequently infected with schistosomes.

  4. Serial observations of chronic rotavirus infection in an immunodeficient child.

    Science.gov (United States)

    Oishi, I; Kimura, T; Murakami, T; Haruki, K; Yamazaki, K; Seto, Y; Minekawa, Y; Funamoto, H

    1991-01-01

    Chronic rotavirus infection of an infant with severe combined immunodeficiency (SCID) was studied by virological examinations in association with long-term observation of his symptoms and immune status. During eleven months of hospitalization, the patient was suffering from incurable severe diarrhea with persisting excretion of rotaviruses detected by electron microscopy and the reversed-passive hemagglutination (R-PHA) test and had transient hepatitis symptom despite multiple administrations of human gammaglobulin and high calorie fluids. The detected viruses were morphologically recognized as rotavirus with double capsid structure. Polyacrylamide gel electrophoretic (PAGE) analysis of their genomic RNAs showed the long electropherotype of group A virus with abnormal migration profiles changing considerably from the early to the late phase of illness: (1) The 11th segment became undetectable; (2) the molecular weight of the 6th segment slightly increased; (3) seven to fourteen extra segments appeared; and (4) PAGE patterns of viral genomic RNAs changed every three or four months. These findings suggest that chronic infection with rotavirus accompanied the generation of extra viral genomic segments and their unusual assortments in an immunodeficient host. PMID:1663575

  5. Serial observations of chronic rotavirus infection in an immunodeficient child.

    Science.gov (United States)

    Oishi, I; Kimura, T; Murakami, T; Haruki, K; Yamazaki, K; Seto, Y; Minekawa, Y; Funamoto, H

    1991-01-01

    Chronic rotavirus infection of an infant with severe combined immunodeficiency (SCID) was studied by virological examinations in association with long-term observation of his symptoms and immune status. During eleven months of hospitalization, the patient was suffering from incurable severe diarrhea with persisting excretion of rotaviruses detected by electron microscopy and the reversed-passive hemagglutination (R-PHA) test and had transient hepatitis symptom despite multiple administrations of human gammaglobulin and high calorie fluids. The detected viruses were morphologically recognized as rotavirus with double capsid structure. Polyacrylamide gel electrophoretic (PAGE) analysis of their genomic RNAs showed the long electropherotype of group A virus with abnormal migration profiles changing considerably from the early to the late phase of illness: (1) The 11th segment became undetectable; (2) the molecular weight of the 6th segment slightly increased; (3) seven to fourteen extra segments appeared; and (4) PAGE patterns of viral genomic RNAs changed every three or four months. These findings suggest that chronic infection with rotavirus accompanied the generation of extra viral genomic segments and their unusual assortments in an immunodeficient host.

  6. Requirements for Pseudomonas aeruginosa Acute Burn and Chronic Surgical Wound Infection

    OpenAIRE

    Turner, Keith H.; Jake Everett; Urvish Trivedi; Rumbaugh, Kendra P.; Marvin Whiteley

    2014-01-01

    Opportunistic infections caused by Pseudomonas aeruginosa can be acute or chronic. While acute infections often spread rapidly and can cause tissue damage and sepsis with high mortality rates, chronic infections can persist for weeks, months, or years in the face of intensive clinical intervention. Remarkably, this diverse infectious capability is not accompanied by extensive variation in genomic content, suggesting that the genetic capacity to be an acute or a chronic pathogen is present in ...

  7. Effect of chronic pain on fentanyl self-administration in mice.

    Directory of Open Access Journals (Sweden)

    Carrie L Wade

    Full Text Available The development of opioid addiction in subjects with established chronic pain is an area that is poorly understood. It is critically important to clearly understand the neurobiology associated with propensity toward conversion to addiction under conditions of chronic pain. To pose the question whether the presence of chronic pain influences motivation to self-administer opioids for reward, we applied a combination of rodent models of chronic mechanical hyperalgesia and opioid self-administration. We studied fentanyl self-administration in mice under three conditions that induce chronic mechanical hyperalgesia: inflammation, peripheral nerve injury, and repeated chemotherapeutic injections. Responding for fentanyl was compared among these conditions and their respective standard controls (naïve condition, vehicle injection or sham surgery. Acquisition of fentanyl self-administration behavior was reduced or absent in all three conditions of chronic hyperalgesia relative to control mice with normal sensory thresholds. To control for potential impairment in ability to learn the lever-pressing behavior or perform the associated motor tasks, all three groups were evaluated for acquisition of food-maintained responding. In contrast to the opioid, chronic hyperalgesia did not interfere with the reinforcing effect of food. These studies indicate that the establishment of chronic hyperalgesia is associated with reduced or ablated motivation to seek opioid reward in mice.

  8. Bordetella pertussis infection or vaccination substantially protects mice against B. bronchiseptica infection.

    Directory of Open Access Journals (Sweden)

    Elizabeth M Goebel

    Full Text Available Although B. bronchiseptica efficiently infects a wide range of mammalian hosts and efficiently spreads among them, it is rarely observed in humans. In contrast to the many other hosts of B. bronchiseptica, humans are host to the apparently specialized pathogen B. pertussis, the great majority having immunity due to vaccination, infection or both. Here we explore whether immunity to B. pertussis protects against B. bronchiseptica infection. In a murine model, either infection or vaccination with B. pertussis induced antibodies that recognized antigens of B. bronchiseptica and protected the lower respiratory tract of mice against three phylogenetically disparate strains of B. bronchiseptica that efficiently infect naïve animals. Furthermore, vaccination with purified B. pertussis-derived pertactin, filamentous hemagglutinin or the human acellular vaccine, Adacel, conferred similar protection against B. bronchiseptica challenge. These data indicate that individual immunity to B. pertussis affects B. bronchiseptica infection, and suggest that the high levels of herd immunity against B. pertussis in humans could explain the lack of observed B. bronchiseptica transmission. This could also explain the apparent association of B. bronchiseptica infections with an immunocompromised state.

  9. Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice

    DEFF Research Database (Denmark)

    Wu, H.; Song, Z.; Hentzer, Morten;

    2004-01-01

    Introduction: Antibiotics are used to treat bacterial infections by killing the bacteria or inhibiting their growth, but resistance to antibiotics can develop readily. The discovery that bacterial quorum-sensing regulates bacterial virulence as well as the formation of biofilms opens up new ways...... to control certain bacterial infections. Furanone compounds capable of inhibiting bacterial quorum-sensing systems have been isolated from the marine macro alga Delisea pulchra. Objectives: Two synthetic furanones were tested for their ability to attenuate bacterial virulence in the mouse models of chronic...... lung infection by targeting bacterial quorum-sensing without directly killing bacteria or inhibiting their growth. Methods: Study I. Mice with Escherichia coli MT102 [luxR-PluxI-gfp(ASV)] lung infection were injected intravenously with N-acyl homoserine lactones with or without furanones to test...

  10. Collagen arrangement in hepatic granuloma in mice infected with Schistosoma mansoni: dependence on fiber radiation centers

    Directory of Open Access Journals (Sweden)

    H.L. Lenzi

    1999-05-01

    Full Text Available The collagen structure of isolated and in situ liver granuloma from Swiss Webster mice infected with Schistosoma mansoni was sequentially and three-dimensionally analyzed during different times of infection (early acute, acute, transitional acute-chronic, and chronic phases by laser scanning confocal microscopy and electron scanning variable vacuum microscopy. The initial granuloma structure is characterized by vascular collagen residues and by anchorage points (or fiber radiation centers, from where collagenous fibers are angularly shed and self-assembled. During the exudative-productive stage, the self-assembly of these fibers minimizes energy and mass through continuous tension and focal compression. The curvature or angles between collagen fibers probably depends on the fibroblastic or myofibroblastic organization of stress fibers. Gradually, the loose unstable lattice of the exudative-productive stage transforms into a highly packed and stable architecture as a result of progressive compactness. The three-dimensional architecture of granulomas provides increased tissue integrity, efficient distribution of soluble compounds and a haptotactic background to the cells.

  11. Chronic exercise ameliorates the neuroinflammation in mice carrying NSE/htau23

    International Nuclear Information System (INIS)

    Research highlights: → The progress of neurodegeration are directly linked to the neuroinflammatory response. → We investigate whether exercise improves the neuroinflammation using Tg-NSE/htau23 mice. → This provides insights that exercise may beneficial effects on the neuroinflammatory disorders. -- Abstract: The objective of the present study was to investigate whether chronic endurance exercise attenuates the neuroinflammation in the brain of mice with NSE/htau23. In this study, the tau-transgenic (Tg) mouse, Tg-NSE/htau23, which over expresses human Tau23 in its brain, was subjected to chronic exercise for 3 months, from 16 months of age. The brains of Tg mice exhibited increased immunoreactivity and active morphological changes in GFAP (astrocyte marker) and MAC-1 (microglia marker) expression in an age-dependent manner. To identify the effects of chronic exercise on gliosis, the exercised Tg mice groups were treadmill run at a speed of 12 m/min (intermediate exercise group) or 19 m/min (high exercise group) for 1 h/day and 5 days/week during the 3 month period. The neuroinflammatory response characterized by activated astroglia and microglia was significantly repressed in the exercised Tg mice in an exercise intensity-dependent manner. In parallel, chronic exercise in Tg mice reduced the increased expression of TNF-α, IL-6, IL-1β, COX-2, and iNOS. Consistently with these changes, the levels of phospho-p38 and phospho-ERK were markedly downregulated in the brain of Tg mice after exercise. In addition, nuclear NF-κB activity was profoundly reduced after chronic exercise in an exercise intensity-dependent manner. These findings suggest that chronic endurance exercise may alleviate neuroinflammation in the Tau pathology of Alzheimer's disease.

  12. Chronic exercise ameliorates the neuroinflammation in mice carrying NSE/htau23

    Energy Technology Data Exchange (ETDEWEB)

    Leem, Yea-Hyun, E-mail: leemyy@empas.com [Exercise Biochemistry Laboratory, Korea National Sport University, Seoul 138-763 (Korea, Republic of); Lee, Young-Ik, E-mail: lee0ik@hanmail.net [Department of Oriental Sports Medicine, Daegu Hanny University, Daegu 712-715 (Korea, Republic of); Son, Hee-Jeong, E-mail: son1106@paran.com [Exercise Physiology Laboratory, Korea National Sport University, Seoul 138-763 (Korea, Republic of); Lee, Sang-Ho, E-mail: run2025@hanmail.net [Department of Sports for All, Kangnam University, Yongin 446-702 (Korea, Republic of)

    2011-03-18

    Research highlights: {yields} The progress of neurodegeration are directly linked to the neuroinflammatory response. {yields} We investigate whether exercise improves the neuroinflammation using T{sub g}-NSE/htau23 mice. {yields} This provides insights that exercise may beneficial effects on the neuroinflammatory disorders. -- Abstract: The objective of the present study was to investigate whether chronic endurance exercise attenuates the neuroinflammation in the brain of mice with NSE/htau23. In this study, the tau-transgenic (Tg) mouse, Tg-NSE/htau23, which over expresses human Tau23 in its brain, was subjected to chronic exercise for 3 months, from 16 months of age. The brains of Tg mice exhibited increased immunoreactivity and active morphological changes in GFAP (astrocyte marker) and MAC-1 (microglia marker) expression in an age-dependent manner. To identify the effects of chronic exercise on gliosis, the exercised Tg mice groups were treadmill run at a speed of 12 m/min (intermediate exercise group) or 19 m/min (high exercise group) for 1 h/day and 5 days/week during the 3 month period. The neuroinflammatory response characterized by activated astroglia and microglia was significantly repressed in the exercised Tg mice in an exercise intensity-dependent manner. In parallel, chronic exercise in Tg mice reduced the increased expression of TNF-{alpha}, IL-6, IL-1{beta}, COX-2, and iNOS. Consistently with these changes, the levels of phospho-p38 and phospho-ERK were markedly downregulated in the brain of Tg mice after exercise. In addition, nuclear NF-{kappa}B activity was profoundly reduced after chronic exercise in an exercise intensity-dependent manner. These findings suggest that chronic endurance exercise may alleviate neuroinflammation in the Tau pathology of Alzheimer's disease.

  13. Post-training reward partially restores chronic stress induced effects in mice.

    Directory of Open Access Journals (Sweden)

    Sergiu Dalm

    Full Text Available Reduced responsiveness to positive stimuli is a core symptom of depression, known as anhedonia. In the present study, we assessed the expression of anhedonia in our chronic stress mouse model using a subset of read-out parameters. In line with this, we investigated in how far chronic stress would affect the facilitating effect of post-training self-administration of sugar, as we previously observed in naïve mice. Male C57BL/6J mice were repeatedly and at unpredictable times exposed to rats (no physical contact over the course of two weeks. Following novelty exploration, (non- spatial learning and memory processes with and without post-training sugar acting as reinforcer, emotionality, reward sensitivity and corticosterone levels were determined. We found that (1 the effects of chronic stress persisted beyond the period of the actual rat exposure. (2 Post-training self-administration of sugar as reinforcer improved spatial performance in naïve mice, whereas (3 in stressed mice sugar partially "normalized" the impaired performance to the level of controls without sugar. Chronic stress (4 increased behavioral inhibition in response to novelty; (5 induced dynamic changes in the pattern of circadian corticosterone secretion during the first week after rat stress and (6 increased the intake of sucrose and water. (7 Chronic stress and sugar consumed during spatial training facilitated the memory for the location of the sucrose bottle weeks later. Concluding, our chronic stress paradigm induces the expression of anhedonia in mice, at different levels of behavior. The behavioral inhibition appears to be long lasting in stressed mice. Interestingly, sugar consumed in close context with spatial learning partially rescued the stress-induced emotional and cognitive impairments. This suggests that reward can ameliorate part of the negative consequences of chronic stress on memory.

  14. Diagnosis and Treatment of Infective Endocarditis in Chronic Hemodialysis Patients

    Institute of Scientific and Technical Information of China (English)

    Jian-ling Tao; Xue-mei Li; Xue-wang Li; Jie Ma; Guang-li Ge; Li-meng Chen; Hang Li; Bao-tong Zhou; Yang Sun; Wen-ling Ye; Qi Miao

    2010-01-01

    Objective To analyze the clinical features of hemodialysis patients complicated by infective endo-carditis.Methods The clinical features of six such patients admitted to Peking Union Medical College Hos-pital during the year 1990 to 2009 were analyzed. All of them were diagnosed based on Chinese Children Diagnostic Criteria for Infective Endocarditis.Results The average age of the six patients was 52.3±19.3 years old. Four were males. Vascular ac-cesses at the onset of infective endocarditis were as follows: permanent catheters in three, temporary cathe-ters in two, and arteriovenous fistula in one. Three were found with mitral valve involvement, two with aor-tic valve involvement, and one with both. Five vegetations were found by transthoraeic echocardiography, and one by transesophageal echocardiography. Four had positive blood culture results. The catheters were all removed. Four of the patients were improved by antibiotics treatment, in which two were still on hemodialy-sis in the following 14-24 months and the other two were lost to follow-up. One patient received surgery, but died of heart failure after further hemodialysis for three months. One was well on maintenance hemodi-alysis for three months after surgery.Conclusions Infective endocarditis should be suspected when hemodialysis patients suffer from long-term fever, for which prompt blood culture and transthoracic echocardiography confirmation could be performed. Transesophageal echocardiography could be considered even when transthoracic echocardiogra-phy produces negative findings. With catheters removed, full course of appropriate sensitive antibiotics and surgery if indicated could improve the outcome of chronic hemodialysis patients complicated by infective endocarditis.

  15. Chronic parasitic infection maintains high frequencies of short-lived Ly6C+CD4+ effector T cells that are required for protection against re-infection.

    Directory of Open Access Journals (Sweden)

    Nathan C Peters

    2014-12-01

    Full Text Available In contrast to the ability of long-lived CD8(+ memory T cells to mediate protection against systemic viral infections, the relationship between CD4(+ T cell memory and acquired resistance against infectious pathogens remains poorly defined. This is especially true for T helper 1 (Th1 concomitant immunity, in which protection against reinfection coincides with a persisting primary infection. In these situations, pre-existing effector CD4 T cells generated by ongoing chronic infection, not memory cells, may be essential for protection against reinfection. We present a systematic study of the tissue homing properties, functionality, and life span of subsets of memory and effector CD4 T cells activated in the setting of chronic Leishmania major infection in resistant C57Bl/6 mice. We found that pre-existing, CD44(+CD62L(-T-bet(+Ly6C+ effector (T(EFF cells that are short-lived in the absence of infection and are not derived from memory cells reactivated by secondary challenge, mediate concomitant immunity. Upon adoptive transfer and challenge, non-dividing Ly6C(+ T(EFF cells preferentially homed to the skin, released IFN-γ, and conferred protection as compared to CD44(+CD62L(-Ly6C(- effector memory or CD44(+CD62L(+Ly6C(- central memory cells. During chronic infection, Ly6C(+ T(EFF cells were maintained at high frequencies via reactivation of T(CM and the T(EFF themselves. The lack of effective vaccines for many chronic diseases may be because protection against infectious challenge requires the maintenance of pre-existing T(EFF cells, and is therefore not amenable to conventional, memory inducing, vaccination strategies.

  16. Hepatitis C virus infection in chronic liver disease in Somalia.

    Science.gov (United States)

    Aceti, A; Taliani, G; Bruni, R; Sharif, O S; Moallin, K A; Celestino, D; Quaranta, G; Sebastiani, A

    1993-04-01

    To assess the role of hepatitis C virus (HCV) in liver disease in Somalia, antibody to HCV (anti-HCV) was studied by enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA) in 110 patients with chronic liver diseases, in 309 healthy adults, in 179 institutionalized subjects with a high prevalence of intestinal parasites and Schistosoma haematobium, and in 287 children with diseases other than hepatitis. According to the RIBA test, anti-HCV was present in three healthy adults (0.97%), in four institutionalized individuals (2.2%), but in none of the children. The prevalence of anti-HCV was 4.8% in patients with hepatitis B surface antigen (HBsAg)-positive chronic liver diseases and 20.6% in patients with HBsAg-negative chronic liver diseases. Thus, HCV infection appears to play a minor role in HBsAg-positive liver disease in Somalia but may be an important factor in HBsAg-negative chronic liver disease. The low anti-HCV prevalence in individuals with no hepatic disorders is consistent with the fact that HCV does not spread by nonpercutaneous transfer. We found also a large proportion of both patients with hepatic disease and institutionalized individuals who tested positive by ELISA but not confirmed by RIBA. However, the likelihood of a true positive result increases proportionally with the ELISA value; thus, in most cases a low ELISA value probably represents a false-positive reaction, while a high ELISA value probably represents a true positive reaction. PMID:7683179

  17. Fecundity reduction of BALB/c mice after survival from lethal Neodiplostomum seoulense infection.

    Science.gov (United States)

    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 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

  18. Relationship Between Helicobacter Pylori Infection and Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Mohammad-Ali Seif-Rabiei

    2011-11-01

    Full Text Available There is some evidence indicating the role of Helicobacter pylori infection in pathogenesis of extragastrointestinal diseases including skin, vascular, and autoimmune disorders, as well as some respiratory diseases. The aim of this study was to investigate the association between H. pylori and chronic obstructive pulmonary disease (COPD. In a case-control study, 90 patients with COPD and 90 age- and sex- matched control subjects were included. Serum samples were tested for anti-H. pylori and anti-CagA IgG by ELISA. A physician completed a questionnaire including demographic characteristics, habitual history, and spirometric findings for each patient. Of 90 patients with COPD 66 (51% had mild, 31 (34.4% moderate, and 13 (14.4% sever disease. There was no significant association between H. pylori IgG seropositivity and COPD. Serum levels of anti-CagA IgG were significantly higher in patients with COPD than in the control subjects (P < 0.001. No association was observed between H. pylori infection and severity of COPD. The results suggest that there is an association between CagA-positive H. pylori infections and COPD. Further studies should be planned to investigate the potential pathogenic mechanisms that might underlie these associations.

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

    Science.gov (United States)

    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

  20. Immunopathologic effects associated with Sarcocystis neurona-infected interferon-gamma knockout mice

    OpenAIRE

    Witonsky, S. G.; Gogal, R. M.; Duncan, R. B.; Lindsay, D S

    2003-01-01

    Interferon-gamma knockout (IFN-gamma KO) mice were infected with Sarcocystis neurona merozoites to characterize the immunopathology associated with infection. By day 14 postinfection (PI), mice developed splenomegaly and lymphadenopathy, characterized by marked lymphoid hyperplasia with increased numbers of germinal centers. Additional histopathologic changes included increased extramedullary hematopoiesis, multifocal mixed inflammatory infiltrates in the liver, perivascular infiltrate of the...

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

    Science.gov (United States)

    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

  2. Aptamer based, non-PCR, non-serological detection of Chagas disease biomarkers in Trypanosoma cruzi infected mice.

    Directory of Open Access Journals (Sweden)

    Rana Nagarkatti

    Full Text Available 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.

  3. Chronic escalating cocaine exposure, abstinence/withdrawal, and chronic re-exposure: Effects on striatal dopamine and opioid systems in C57BL/6J mice

    OpenAIRE

    Yong ZHANG; Schlussman, Stefan D; Rabkin, Jacqui; Butelman, Eduardo R.; Ho, Ann; Kreek, Mary Jeanne

    2012-01-01

    Cocaine addiction is a chronic relapsing disease with periods of chronic escalating self-exposure, separated by periods of abstinence/withdrawal of varying duration. Few studies compare such cycles in preclinical models. This study models an “addiction-like cycle” in mice to determine neurochemical/molecular alterations that underlie the chronic, relapsing nature of this disease. Groups of male C57BL/6J mice received acute cocaine exposure (14-day saline/14-day withdrawal /13-day saline + 1-d...

  4. Clonal expansions of CD8+ T cells with IL-10 secreting capacity occur during chronic Mycobacterium tuberculosis infection.

    Directory of Open Access Journals (Sweden)

    Joshua C Cyktor

    Full Text Available The exact role of CD8(+ T cells during Mycobacterium tuberculosis (Mtb infection has been heavily debated, yet it is generally accepted that CD8(+ T cells contribute to protection against Mtb. In this study, however, we show that the Mtb-susceptible CBA/J mouse strain accumulates large numbers of CD8(+ T cells in the lung as infection progresses, and that these cells display a dysfunctional and immunosuppressive phenotype (PD-1(+, Tim-3(+, CD122(+. CD8(+ T cell expansions from the lungs of Mtb-infected CBA/J mice were also capable of secreting the immunosuppressive cytokine interleukin-10 (IL-10, although in vivo CD8(+ T cell depletion did not significantly alter Mtb burden. Further analysis revealed that pulmonary CD8(+ T cells from Mtb-infected CBA/J mice were clonally expanded, preferentially expressing T cell receptor (TcR Vβ chain 8 (8.2, 8.3 or Vβ 14. Although Vβ8(+ CD8(+ T cells were responsible for the majority of IL-10 production, in vivo depletion of Vβ8(+ did not significantly change the outcome of Mtb infection, which we hypothesize was a consequence of their dual IL-10/IFN-γ secreting profiles. Our data demonstrate that IL-10-secreting CD8(+ T cells can arise during chronic Mtb infection, although the significance of this T cell population in tuberculosis pathogenesis remains unclear.

  5. Function of monocytes in chronic HCV infection: Role for IL-10 and interferon

    NARCIS (Netherlands)

    B. Liu (Bi Sheng)

    2011-01-01

    textabstractHepatitis C virus (HCV) establishes persistent infection in about 80% of the infected individuals. The symptoms are initially mild in those persistently infected patients, and it may take decades before the serious consequences of chronic HCV infection become apparent. Up to 20% of infec

  6. Post-parturient shedding of Listeria monocytogenes in breast milk of infected mice

    Science.gov (United States)

    Poulsen, Keith P; Pillers, DeAnn M; Conway, James H; Faith, Nancy G; Czuprynski, Charles J

    2014-01-01

    The objectives of this study were to develop an animal model to study Listeria monocytogenes infection during the peri-parturient period and identify sources of maternal shedding of the pathogen. Peri-parturient mice were infected intragastrically with L. monocytogenes that expressed bacterial luciferase. Mice were then imaged in vivo over time. Secreted breast milk samples from mice infected after parturition were enriched and plated for culture and imaging. Bioluminescence imaging technology was able to detect luciferase emitting L. monocytogenes in vaginal secretions and maternal and fetal organs at 72 and 96 h post infection in mice infected prior to, or just after, parturition. The results from this study clearly show that L. monocytogenes is shed in vaginal secretions and disseminates to the mammary chain, from which it can be shed in the milk of peri-parturient mice. PMID:24246517

  7. Surfactant protein C-deficient mice are susceptible to respiratory syncytial virus infection

    OpenAIRE

    Glasser, Stephan W.; Witt, Teah L.; Senft, Albert P; Baatz, John E.; Folger, Dusti; Melissa D. Maxfield; Akinbi, Henry T.; Newton, Danforth A.; Prows, Daniel R.; Korfhagen, Thomas R.

    2009-01-01

    Patients with mutations in the pulmonary surfactant protein C (SP-C) gene develop interstitial lung disease and pulmonary exacerbations associated with viral infections including respiratory syncytial virus (RSV). Pulmonary infection with RSV caused more severe interstitial thickening, air space consolidation, and goblet cell hyperplasia in SP-C-deficient (Sftpc−/−) mice compared with SP-C replete mice. The RSV-induced pathology resolved more slowly in Sftpc−/− mice with lung inflammation per...

  8. Effects of chronic expression of the HIV-induced protein, transactivator of transcription, on circadian activity rhythms in mice, with or without morphine

    OpenAIRE

    Duncan, Marilyn J.; Bruce-Keller, Annadora J.; Conner, Clayton; Knapp, Pamela E.; Xu, Ruquiang; Nath, Avindra; Hauser, Kurt F.

    2008-01-01

    Patients with human immunodeficiency virus (HIV) infection exhibit changes in sleep patterns, motor disorders, and cognitive dysfunction; these symptoms may be secondary to circadian rhythm abnormalities. Studies in mice have shown that intracerebral injection of an HIV protein, transactivator of transcription (Tat), alters the timing of circadian rhythms in a manner similar to light. Therefore, we tested the hypothesis that chronic Tat expression alters circadian rhythms, especially their en...

  9. CXCL9 Is Important for Recruiting Immune T Cells into the Brain and Inducing an accumulation of the T Cells to the areas of tachyzoite proliferation to prevent reactivation of chronic cerebral infection with Toxoplasma gondii

    Science.gov (United States)

    T cells are required to maintain the latency of chronic infection with Toxoplasma gondii in the brain. In the present study, we examined the role of non-ELR (glutamic acid-leucine-arginine) CXC chemokine CXCL9 for T cell recruitment to prevent reactivation of infection with T. gondii. SCID mice were...

  10. Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection

    Energy Technology Data Exchange (ETDEWEB)

    Jain-Gupta, Neeta [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States); Pothayee, Nipon; Pothayee, Nikorn [Virginia Polytechnic Institute and State University, Macromolecules and Interfaces Institute (United States); Tyler, Ronald; Caudell, David L. [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States); Balasubramaniam, Sharavanan; Hu, Nan; Davis, Richey M.; Riffle, Judy S. [Virginia Polytechnic Institute and State University, Macromolecules and Interfaces Institute (United States); Sriranganathan, Nammalwar, E-mail: nathans@vt.edu [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States)

    2013-11-15

    Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30–32 weight percentage of gentamicin. The zeta potential changed from −39 to −13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log{sub 10}), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log{sub 10}). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B.melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers.

  11. Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection

    International Nuclear Information System (INIS)

    Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30–32 weight percentage of gentamicin. The zeta potential changed from −39 to −13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log10), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log10). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B.melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers

  12. Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice

    OpenAIRE

    Cai, Ping; König, Rolf; Boor, Paul J; Kondraganti, Shakuntala; Kaphalia, Bhupendra S.; Khan, M. Firoze; Ansari, G.A.S.

    2007-01-01

    Trichloroethene (TCE) exacerbates the development of autoimmune responses in autoimmune-prone MRL +/+ mice. Although TCE-mediated autoimmune responses are associated with an increase in serum immunoglobulins and autoantibodies, the underlying mechanism of autoimmunity is not known. To determine the progression of TCE-mediated immunotoxicity, female MRL +/+ mice were chronically exposed to TCE through the drinking water (0.5 mg/ml of TCE) for various periods of time. Serum concentrations of an...

  13. BDNF-Deficient Mice Show Reduced Psychosis-Related Behaviors Following Chronic Methamphetamine

    OpenAIRE

    Manning, Elizabeth E.; Halberstadt, Adam L.; van den Buuse, Maarten

    2015-01-01

    Background: One of the most devastating consequences of methamphetamine abuse is increased risk of psychosis. Brain-derived neurotrophic factor has been implicated in both psychosis and neuronal responses to methamphetamine. We therefore examined persistent psychosis-like behavioral effects of methamphetamine in brain-derived neurotrophic factor heterozygous mice. Methods: Mice were chronically treated with methamphetamine from 6 to 9 weeks of age, and locomotor hyperactivity to an acute D-am...

  14. Therapeutic effects of stress-programmed lymphocytes transferred to chronically stressed mice.

    Science.gov (United States)

    Scheinert, Rachel B; Haeri, Mitra H; Lehmann, Michael L; Herkenham, Miles

    2016-10-01

    Our group has recently provided novel insights into a poorly understood component of intercommunication between the brain and the immune system by showing that psychological stress can modify lymphocytes in a manner that may boost resilience to psychological stress. To demonstrate the influence of the adaptive immune system on mood states, we previously showed that cells from lymph nodes of socially defeated mice, but not from unstressed mice, conferred anxiolytic and antidepressant-like effects and elevated hippocampal cell proliferation when transferred into naïve lymphopenic Rag2(-/-) mice. In the present study, we asked whether similar transfer could be anxiolytic and antidepressant when done in animals that had been rendered anxious and depressed by chronic psychological stress. First, we demonstrated that lymphopenic Rag2(-/-) mice and their wild-type C57BL/6 mouse counterparts had similar levels of affect normally. Second, we found that following chronic (14days) restraint stress, both groups displayed an anxious and depressive-like phenotype and decreased hippocampal cell proliferation. Third, we showed that behavior in the open field test and light/dark box was normalized in the restraint-stressed Rag2(-/-) mice following adoptive transfer of lymph node cells from green fluorescent protein (GFP) expressing donor mice previously exposed to chronic (14days) of social defeat stress. Cells transferred from unstressed donor mice had no effect on behavior. Immunolabeling of GFP+ cells confirmed that tissue engraftment had occurred at 14days after transfer. We found GFP+ lymphocytes in the spleen, lymph nodes, blood, choroid plexus, and meninges of the recipient Rag2(-/-) mice. The findings suggest that the adaptive immune system may play a key role in promoting recovery from chronic stress. The data support using lymphocytes as a novel therapeutic target for anxiety states. PMID:27109071

  15. Dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection.

    Science.gov (United States)

    Tang, L; Ward, H; Kattakuzhy, S; Wilson, E; Kottilil, S

    2016-01-01

    Sofosbuvir is the first pan-genotypic direct acting antiviral agent to be approved. This article provides an overview of the pharmacology of sofosbuvir and ribavirin and a comprehensive summary of the phase 2 and 3 studies supporting dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection. With the production of generic formulations of sofosbuvir, we anticipate this regimen leading the first wave for widespread, IFN-free treatment and becoming first line for all genotypes (including genotype 1) for much of the world-in particular in developing and middle income countries. We discuss the continued challenges with this regimen including among patients with decompensated liver disease and post-liver transplant, and renal failure. We address concerns of emerging resistance. We also discuss the future prospects including the global uptake of sofosbuvir and ribavirin for the treatment of all genotypes.

  16. Effect of methanol extracts of nony fruit on mice infected by RH strain of Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Didik T Subekti

    2005-12-01

    Full Text Available Intraperitoneal infection of Type I Toxoplasma gondii on mice causes high mortality at a short time due to parasitic burden, immunosuppression, cell and tissue damage. The mice survival is increased after treated with drugs that reduce or destroy tachyzoite and modulate or recovered the immune system. Nony fruit (Morinda citrifolia is popular as immunomudulator and has antoxoplasma properties. The purpose of this experiment is to evaluate the effect of ethanol extract of nony fruit and Fansidar® (pyrimethamine-sulfadiazine to reduce tachyzoite and improve survival as well as immunomudulator on mice following toxoplasma infection. Mice was divided into six groups (10 mice respectively consist of infected-non treated groups, infected + Fansidar®, infected + ethanol extract of nony on several doses (100, 50, 25% and non infected-non treated groups. All mice on each groups were infected intraperitoneally by 5 x 106 and 2,5 x 103 RH strain of Toxoplasma gondii tachyzoite/mice respectively. The results have shown that Fansidar® was successfully to reduced tachyzoite and improved mice survival but the ethanol extract of nony fruit was failed.

  17. Wound Chronicity, Inpatient Care, and Chronic Kidney Disease Predispose to MRSA Infection in Diabetic Foot Ulcers

    Science.gov (United States)

    Yates, Christopher; May, Kerry; Hale, Thomas; Allard, Bernard; Rowlings, Naomi; Freeman, Amy; Harrison, Jessica; McCann, Jane; Wraight, Paul

    2009-01-01

    OBJECTIVE To determine the microbiological profile of diabetes-related foot infections (DRFIs) and the impact of wound duration, inpatient treatment, and chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS Postdebridement microbiological samples were collected from individuals presenting with DRFIs from 1 January 2005 to 31 December 2007. RESULTS A total of 653 specimens were collected from 379 individuals with 36% identifying only one isolate. Of the total isolates, 77% were gram-positive bacteria (staphylococci 43%, streptococci 13%). Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from 23%; risk factors for MRSA included prolonged wound duration (odds ratio 2.31), inpatient management (2.19), and CKD (OR 1.49). Gram-negative infections were more prevalent with inpatient management (P = 0.002) and prolonged wound duration (P < 0.001). Pseudomonal isolates were more common in chronic wounds (P < 0.001). CONCLUSIONS DRFIs are predominantly due to gram-positive aerobes but are usually polymicrobial and increase in complexity with inpatient care and ulcer duration. In the presence of prolonged duration, inpatient management, or CKD, empiric MRSA antibiotic cover should be considered. PMID:19587371

  18. Poliomyelitis in MuLV-infected ICR-SCID mice after injection of basement membrane matrix contaminated with lactate dehydrogenase-elevating virus.

    Science.gov (United States)

    Carlson Scholz, Jodi A; Garg, Rohit; Compton, Susan R; Allore, Heather G; Zeiss, Caroline J; Uchio, Edward M

    2011-10-01

    The arterivirus lactate dehydrogenase-elevating virus (LDV) causes life-long viremia in mice. Although LDV infection generally does not cause disease, infected mice that are homozygous for the Fv1(n) allele are prone to develop poliomyelitis when immunosuppressed, a condition known as age-dependent poliomyelitis. The development of age-dependent poliomyelitis requires coinfection with endogenous murine leukemia virus. Even though LDV is a common contaminant of transplantable tumors, clinical signs of poliomyelitis after inadvertent exposure to LDV have not been described in recent literature. In addition, LDV-induced poliomyelitis has not been reported in SCID or ICR mice. Here we describe the occurrence of poliomyelitis in ICR-SCID mice resulting from injection of LDV-contaminated basement membrane matrix. After exposure to LDV, a subset of mice presented with clinical signs including paresis, which was associated with atrophy of the hindlimb musculature, and tachypnea; in addition, some mice died suddenly with or without premonitory signs. Mice presenting within the first 6 mo after infection had regions of spongiosis, neuronal necrosis and astrocytosis of the ventral spinal cord, and less commonly, brainstem. Axonal degeneration of ventral roots prevailed in more chronically infected mice. LDV was identified by RT-PCR in 12 of 15 mice with typical neuropathology; positive antiLDV immunolabeling was identified in all PCR-positive animals (n = 7) tested. Three of 8 mice with neuropathology but no clinical signs were LDV negative by RT-PCR. RT-PCR yielded murine leukemia virus in spinal cords of all mice tested, regardless of clinical presentation or neuropathology.

  19. Screening and Early Treatment of Migrants for Chronic Hepatitis B Virus Infection Is Cost-Effective

    NARCIS (Netherlands)

    Veldhuijzen, Irene K.; Toy, Mehlika; Hahne, Susan J. M.; de Wit, G. Ardine; Schalm, Solko W.; de Man, Robert A.; Richardus, Jan Hendrik

    2010-01-01

    BACKGROUND & AIMS: Persons with chronic hepatitis B virus (HBV) infection are at risk of developing cirrhosis and hepatocellular carcinoma. Early detection of chronic HBV infection through screening and treatment of eligible patients has the potential to prevent these sequelae. We assessed the cost-

  20. Chronic pulmonary infection with Stenotrophomonas maltophilia and lung function in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Dalbøge, C S; Hansen, C R; Pressler, T;

    2011-01-01

    Background The clinical consequences of chronic Stenotrophomonas maltophilia infection in cystic fibrosis (CF) patient are still unclear. Method All patients treated in the Copenhagen CF centre (N=278) from 1 January 2008 to 31 December 2009 were included. Each patient chronically infected with S...

  1. Possibility of Neospora caninum infection by venereal transmission in CB-17 scid mice

    OpenAIRE

    MASUDA, Tsuneyuki; Kobayashi, Yoshiyasu; Maeda, Ryuichiro; Omata, Yoshitaka

    2007-01-01

    CB-17 scid and BALB/c male mice were inoculated intraperitoneally with Neospora caninum to examine the possibility of its venereal transmission. Some of these mice were killed on days 7 and 20 post-inoculation to examine the genital organs for presence of the parasite. The remaining scid male mice were housed with non-infected female mice from day 7 p.i. and kept with them for 14 days. These scid mice died between days 28 and 35 p.i. N. caninum DNA was detected in the testis of mice on days 7...

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

    Science.gov (United States)

    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

  3. Cytokine patterns in experimental schistosomiasis mansoni infected mice treated with silymarin.

    Science.gov (United States)

    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

  4. Attenuated Host Resistance against Mycobacterium bovis BCG Infection in Mice Lacking Osteopontin

    OpenAIRE

    Nau, Gerard J.; Liaw, Lucy; Chupp, Geoffrey L.; Berman, Jeffrey S.; Hogan, Brigid L.M.; Young, Richard A.

    1999-01-01

    Expression of the cytokine osteopontin (OPN) is elevated in granulomas caused by Mycobacterium tuberculosis. We tested the hypothesis that OPN contributes to host protection in a mouse model of mycobacterial infection. When infected with Mycobacterium bovis BCG, mice lacking a functional OPN gene had more severe infections characterized by heavier bacterial loads and a delayed clearance of the bacteria. The OPN-null mice had greater granuloma burdens consistent with the elevated bacterial loa...

  5. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

    Directory of Open Access Journals (Sweden)

    Hwang Jong-Hee

    2008-10-01

    Full Text Available Abstract Background Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. Methods To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. Results Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap, effects on host cell protein processing (ubiquitin ligase, synapse remodeling (Complement 1q, and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease. Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of

  6. Restoration of Pattern Recognition Receptor Costimulation to Treat Chromoblastomycosis, a Chronic Fungal Infection of the Skin

    OpenAIRE

    da Glória Sousa, Maria; Reid, Delyth M.; Schweighoffer, Edina; Tybulewicz, Victor; Ruland, Jürgen; Langhorne, Jean; Yamasaki, Sho; Taylor, Philip R.; Almeida, Sandro R.; Brown, Gordon D.

    2011-01-01

    Summary Chromoblastomycosis is a chronic skin infection caused by the fungus Fonsecaea pedrosoi. Exploring the reasons underlying the chronic nature of F. pedrosoi infection in a murine model of chromoblastomycosis, we find that chronicity develops due to a lack of pattern recognition receptor (PRR) costimulation. F. pedrosoi was recognized primarily by C-type lectin receptors (CLRs), but not by Toll-like receptors (TLRs), which resulted in the defective induction of proinflammatory cytokines...

  7. Chronic psychosocial stress increases the risk for inflammation-related colon carcinogenesis in male mice.

    Science.gov (United States)

    Peters, Sebastian; Grunwald, Nicole; Rümmele, Petra; Endlicher, Esther; Lechner, Anja; Neumann, Inga D; Obermeier, Florian; Reber, Stefan O

    2012-07-01

    Patients with inflammatory bowel diseases (IBDs) have a higher risk of developing colorectal cancer (CRC) than the general population. Furthermore, chronic psychosocial stress increases the likelihood of developing IBD and multiple types of malignant neoplasms, including CRC. Here, for the first time, we investigate the effects of chronic psychosocial stress in male mice on an artificially induced CRC, by employing the chronic subordinate colony (CSC) housing paradigm in combination with the reliable azoxymethane (AOM)/dextran sodium sulfate (DSS) CRC model. Colonoscopy revealed that CSC mice showed accelerated macroscopic suspect lesions. In addition, more CSC mice developed low-grade dysplasia (LGD) and/or high-grade dysplasia (HGD) in the colonic tissue compared to the single-housed control mice (SHC). CSC mice showed an increased number of Ki67+ and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling epithelial cells in colonic tissue. Colonic liver receptor homolog-1 (LRH-1), cyclooxygenase II (COXII), tumor necrosis factor, forkhead box P3 (FoxP3) mRNA as well as colonic ß-catenin, COXII, and LRH-1 protein expression were also increased in CSC compared with SHC mice. Although the number of CD4+ Th cells was increased, a tendency toward a decreased colonic interferon-γ (IFN-γ) mRNA expression was observed. Furthermore, despite an increased percentage of CD3+ cells and CD3+/FoxP3+ double-positive cells within mesenteric lymph node cells of CSC mice, IFN-γ secretion from these cells was unaffected. Altogether, our results suggest that chronic psychosocial stress increases the risk for AOM/DSS-induced and, thus, inflammation-related CRC. Finally, assessment of additional time points may test whether the shift from tumor-protective Th1 cell to regulatory T-cell immunity represents a consequence of increased carcinogenesis or a causal factor involved in its development.

  8. Agmatine increases proliferation of cultured hippocampal progenitor cells and hippocampal neurogenesis in chronically stressed mice

    Institute of Scientific and Technical Information of China (English)

    Yun-feng LI; Hong-xia CHEN; Ying LIU; You-zhi ZHANG; Yan-qin LIU; Jin LI

    2006-01-01

    Aim:To explore the mechanism of agmatine's antidepressant action.Methods: Male mice were subjected to a variety of unpredictable stressors on a daily basis over a 24-d period.The open-field behaviors of the mice were displayed and recorded using a Videomex-V image analytic system automatically.For bromodeoxyuridine (BrdU;thymidine analog as a marker for dividing cells) labeling,the mice were injected with BrdU (100 mg/kg,ip,twice per d for 2 d),and the hippocampal neurogenesis in stressed mice was measured by immunohistochemistry.The proliferation of cultured hippocampal progenitor cells from neonatal rats was determined by colorimetric assay (cell counting kit-8) and 3H-thymidine incorporation assay.Results:After the onset of chronic stress,the locomotor activity of the mice in the open field significantly decreased,while coadministration of agmatine 10 mg/kg (po) blocked it.Furthermore,the number of BrdU-labeled cells in the hippocampal dentate gyrus significantly decreased in chronically stressed mice, which was also blocked by chronic coadministration with agmatine 10 mg/kg (po). Four weeks after the BrdU injection, some of the new born cells matured and became neurons, as determined by double labeling for BrdU and neuron specific enolase (NSE), a marker for mature neurons.In vitro treatment with agmatine 0.1-10 μmo1/L for 3 d significantly increased the proliferation of the cultured hippocampal progenitor cells in a dose-dependent manner.Conclusion:We have found that agmatine increases proliferation of hippocampal progenitor cells in vitro and the hippocampal neurogenesis in vivo in chronically stressed mice.This may be one of the important mechanisms involved in agmatine's antidepressant action.

  9. Natural cocoa ingestion reduced liver damage in mice infected with Plasmodium berghei (NK65

    Directory of Open Access Journals (Sweden)

    Aidoo E

    2012-09-01

    Full Text Available Eric Aidoo,1 Frederick K Addai,1 John Ahenkorah,1 Bismarck Hottor,1 Kwasi A Bugyei,2 Ben A Gyan31Department of Anatomy, 2Department of Pharmacology, University of Ghana Medical School, College of Health Sciences, Korle-Bu, Accra, Ghana; 3Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra, GhanaPurpose: This study tested whether natural cocoa powder ingestion could mitigate hepatic injury coincident with murine malaria. Plasmodium berghei infection causes liver damage including hepatic sinusoidal distension, and elevated serum alanine transaminase (ALT and aspartate transaminase (AST levels. According to literature, these pathologies largely result from activity of reactive oxygen species (ROS and may be extenuated by antioxidants.Animals and methods: Thirty Balb/c mice were randomly assigned to three equal groups. One of two groups of mice inoculated with 0.2 mL of P. berghei-parasitized red blood cells (RBCs was given unrestricted 24-hour access to a natural cocoa powder beverage (2% by weight in place of water. The third group of mice were neither infected nor given cocoa. All mice were fed the same standard chow. After 6 days, mice were sacrificed and their livers processed for histomorphometric assessment of mean hepatic sinusoidal diameter as a quantitative measure of altered morphology. Serum ALT and AST were measured as a gauge of functional impairment.Results: Compared with uninfected mice, hepatic sinusoidal diameter in P. berghei-infected mice not given cocoa increased by 150%, whereas a smaller increase of 83% occurred in infected mice that ingested cocoa. Mean serum ALT increased by 127% in infected mice not given cocoa and 80% in infected mice that consumed cocoa, compared with the value for uninfected mice. Similarly, mean serum AST was raised by 141% in infected mice not given cocoa and 93% in infected mice that drank cocoa.Conclusion: Distension of hepatic sinusoidal

  10. Effect of Escherichia coli infection on the histopathology of albino mice visceral organs

    Directory of Open Access Journals (Sweden)

    Abin Biswas

    2010-03-01

    Full Text Available Histopathology is very essential in assessing the nature and state of the tissues. It is used widely to examine the visceral organs in various diseases, infections and disorders. It provides the required insight and details about the possible malfunctioning of the disease or infection. Albino mice were taken and test group was infected withEscherichia coli. The control group was not infected with any linical pathogen. The histopathological examination was carried out to determine the effect of infection in the test group. Liver, spleen and kidney were the visceral organs which were used for the study. The size, shape and other morphological characteristics had markeddifference in case of infected mice when compared with control group mice. Histopathological analysis can be further extended in the case of other clinical pathogenic infections which could lead to nteresting results.

  11. Immune therapy including dendritic cell based therapy in chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    Sk Md Fazle Akbar; Norio Horiike; Morikazu Onji

    2006-01-01

    Hepatitis B virus (HBV) infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of chronic HBV carriers suffer from progressive liver diseases. In addition, all HBV carriers are permanent source of this virus. There is no curative therapy for chronic HBV carriers. Antiviral drugs are recommended for about 10% patients, however, these drugs are costly, have limited efficacy, and possess considerable side effects.Recent studies have shown that immune responses of the host to the HBV are critically involved at every stage of chronic HBV infection: (1) These influence acquisition of chronic HBV carrier state, (2) They are important in the context of liver damages, (3) Recovery from chronic HBV-related liver diseases is dependent on nature and extent of HBV-specific immune responses.However, induction of adequate levels of HBV-specific immune responses in chronic HBV carriers is difficult.During the last one decade, hepatitis B vaccine has been administered to chronic HBV carriers as a therapeutic approach (vaccine therapy). The present regimen of vaccine therapy is safe and cheap, but not so effective.A dendritic cell-based therapeutic vaccine has recently been developed for treating chronic HBV infection. In this review, we will discuss about the concept, scientific logics, strategies and techniques of development of HBV-specific immune therapies including vaccine therapy and dendritic cell-based vaccine therapy for treating chronic HBV infection.

  12. Chronic inhibition of dopamine β-hydroxylase facilitates behavioral responses to cocaine in mice.

    Directory of Open Access Journals (Sweden)

    Meriem Gaval-Cruz

    Full Text Available The anti-alcoholism medication, disulfiram (Antabuse, decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH, the enzyme that converts dopamine (DA to norepinephrine (NE in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh -/- mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/- and Dbh -/- mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh -/- mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/- mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/- mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh -/- mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor enhance qualitatively different cocaine-induced behaviors.

  13. EFFICACY OF NITAZOXANIDE AGAINST Toxocara canis: LARVAL RECOVERY AND HUMORAL IMMUNE RESPONSE IN EXPERIMENTALLY INFECTED MICE.

    Science.gov (United States)

    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

  14. EFFICACY OF NITAZOXANIDE AGAINST Toxocara canis: LARVAL RECOVERY AND HUMORAL IMMUNE RESPONSE IN EXPERIMENTALLY INFECTED MICE

    Directory of Open Access Journals (Sweden)

    Susana A. Zevallos LESCANO

    2015-08-01

    Full Text Available 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.

  15. Tularemia among free-ranging mice without infection of exposed humans, Switzerland, 2012.

    Science.gov (United States)

    Origgi, Francesco C; König, Barbara; Lindholm, Anna K; Mayor, Désirée; Pilo, Paola

    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.

  16. Lymphocyte proliferation in Peyer's patches of Giardia muris-infected mice.

    OpenAIRE

    Hill, D R

    1990-01-01

    Gastrointestinal immune events in giardiasis are important in controlling infection. In this study, Peyer's patch lymphocytes from mice infected with Giardia muris developed specific, proliferative responses to G. muris antigen. This proliferation correlated with clearance of infection. Further understanding of the gut immune response will be helpful in developing immunoprophylactic strategies in the control of giardiasis.

  17. Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice.

    Directory of Open Access Journals (Sweden)

    Lu Zhao

    Full Text Available Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also associated with increased tumor associated macrophages infiltration into the primary tumor and increased the expression of metastatic genes. Interestingly, β-blocker treatment reversed the effects of chronic stress on liver metastasis. Our results suggest the β-adrenergic signaling pathway is involved in regulating colorectal cancer progression and liver metastasis. Additionally, we submit that adjunctive therapy with a β-blocker may complement existing colorectal cancer therapies.

  18. Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice.

    Science.gov (United States)

    Zhao, Lu; Xu, Jianhua; Liang, Fang; Li, Ao; Zhang, Yong; Sun, Jue

    2015-01-01

    Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also associated with increased tumor associated macrophages infiltration into the primary tumor and increased the expression of metastatic genes. Interestingly, β-blocker treatment reversed the effects of chronic stress on liver metastasis. Our results suggest the β-adrenergic signaling pathway is involved in regulating colorectal cancer progression and liver metastasis. Additionally, we submit that adjunctive therapy with a β-blocker may complement existing colorectal cancer therapies. PMID:26444281

  19. Human glial chimeric mice reveal astrocytic dependence of JC virus infection

    DEFF Research Database (Denmark)

    Kondo, Yoichi; Windrem, Martha S; Zou, Lisa;

    2014-01-01

    with humanized white matter by engrafting human glial progenitor cells (GPCs) into neonatal immunodeficient and myelin-deficient mice. Intracerebral delivery of JCV resulted in infection and subsequent demyelination of these chimeric mice. Human GPCs and astrocytes were infected more readily than...... oligodendrocytes, and viral replication was noted primarily in human astrocytes and GPCs rather than oligodendrocytes, which instead expressed early viral T antigens and exhibited apoptotic death. Engraftment of human GPCs in normally myelinated and immunodeficient mice resulted in humanized white matter...... that was chimeric for human astrocytes and GPCs. JCV effectively propagated in these mice, which indicates that astroglial infection is sufficient for JCV spread. Sequencing revealed progressive mutation of the JCV capsid protein VP1 after infection, suggesting that PML may evolve with active infection...

  20. Macrophage dysfunction and susceptibility to pulmonary Pseudomonas aeruginosa infection in surfactant protein C-deficient mice.

    Science.gov (United States)

    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

  1. Protective Effects of Lentinan against T Lymphocytes Injury in Mice under Chronic Radiation Stress

    Institute of Scientific and Technical Information of China (English)

    WANG Yong; LI Ming-chun; FU Qing-jie

    2013-01-01

    Objective To study the effects of lentinan (LTN) on mice exposed to chronic radiation.Methods Animals were divided into three groups (n =10),they were animals exposed to radiation (Rad),normal control animals (Ctr),and irradiated animals treated with LTN (Rad + LTN).Animal model of chronic radiation stress injury was induced by irradiating mice with 60Co γ-ray for 6 weeks from Monday to Friday consecutively.Before radiation,the mice in Rad + LTN group were ip injected with 0.5 mL LTN (0.01 mg/mL),whereas mice in other groups were injected with 0.9% physiological saline.The effects of LTN treatment on irradiated mice were examined by histological analysis on the spleen.The cell numbers and viability of T lymphocytes,which were isolated from the spleen,were determined by Trypan blue staining.Nitric oxide (NO) production and interleukin-2 (IL-2) secretion in T lymphocytes were also measured.Results Chronic radiation significantly reduced the body weights and the spleen and thymus indexes,associated with reduced T lymphocytes viability and functions,and elevated NO production.Treatment with LTN significantly normalized the elevated NO production,and attenuated the negative outcomes resulting from radiation mentioned above.Conclusion The results suggest that radioprotective effect of LTN may be contributed by improved T lymphocytes viability and functions via regulating the NO and IL-2 production in T lymphocytes.

  2. Protective Effects of Lentinan against T Lymphocytes Injury in Mice under Chronic Radiation Stress

    Institute of Scientific and Technical Information of China (English)

    WANG; Yong; LI; Ming-chun; FU; Qing-jie

    2013-01-01

    Objective To study the effects of lentinan (LTN) on mice exposed to chronic radiation. Methods Animals were divided into three groups (n = 10), they were animals exposed to radiation (Rad), normal control animals (Ctr), and irradiated animals treated with LTN (Rad + LTN). Animal model of chronic radiation stress injury was induced by irradiating mice with 60 Co γ-ray for 6 weeks from Monday to Friday consecutively. Before radiation, the mice in Rad + LTN group were ip injected with 0.5 mL LTN (0.01 mg/mL), whereas mice in other groups were injected with 0.9% physiological saline. The effects of LTN treatment on irradiated mice were examined by histological analysis on the spleen. The cell numbers and viability of T lymphocytes, which were isolated from the spleen, were determined by Trypan blue staining. Nitric oxide (NO) production and interleukin-2 (IL-2) secretion in T lymphocytes were also measured. Results Chronic radiation significantly reduced the body weights and the spleen and thymus indexes, associated with reduced T lymphocytes viability and functions, and elevated NO production. Treatment with LTN significantly normalized the elevated NO production, and attenuated the negative outcomes resulting from radiation mentioned above. Conclusion The results suggest that radioprotective effect of LTN may be contributed by improved T lymphocytes viability and functions via regulating the NO and IL-2 production in T lymphocytes.

  3. Interleukin-18 Mediates Immune Responses to Campylobacter jejuni Infection in Gnotobiotic Mice.

    Directory of Open Access Journals (Sweden)

    Stefan Bereswill

    Full Text Available Human Campylobacter jejuni infections are progressively rising worldwide. Information about the molecular mechanisms underlying campylobacteriosis, however, are limited. In the present study we investigated whether cytokines such as IL-23, IL-22 and IL-18, which share pivotal functions in host immunity, were involved in mediating intestinal and systemic immunopathological responses upon C. jejuni infection.To assure stable infection, gnotobiotic (i.e. secondary abiotic IL-23p19-/-, IL-22-/- and IL-18-/- mice were generated by broad-spectrum antibiotic treatment. Following peroral C. jejuni strain 81-176 infection, mice of all genotypes harbored comparably high pathogenic loads in their intestines. As compared to wildtype controls, however, IL-18-/- mice displayed less distinct C. jejuni induced sequelae as indicated by less pronounced large intestinal shrinkage and lower numbers of apoptotic cells in the colonic epithelial layer at day 8 postinfection (p.i.. Furthermore, lower colonic numbers of adaptive immune cells including regulatory T cells and B lymphocytes were accompanied by less distinct secretion of pro-inflammatory cytokines such as TNF and IFN-γ and lower IL-17A mRNA expression levels in colonic ex vivo biopsies of infected IL-18-/- as compared to wildtype mice. Upon C. jejuni infection, colonic IL-23p19 expression was up-regulated in IL-18-/- mice only, whereas IL-22 mRNA levels were lower in uninfected and infected IL-23p19-/- as well as infected IL-18-/- as compared to respective wildtype control mice. Remarkably, not only intestinal, but also systemic infection-induced immune responses were less pronounced in IL-18-/- mice as indicated by lower TNF, IFN-γ and IL-6 serum levels as compared to wildtype mice.We here show for the first time that IL-18 is essentially involved in mediating C. jejuni infection in the gnotobiotic mouse model. Future studies need to further unravel the underlying regulatory mechanisms orchestrating

  4. Antileishmanial activity of licochalcone A in mice infected with Leishmania major and in hamsters infected with Leishmania donovani

    DEFF Research Database (Denmark)

    Chen, M; Christensen, S B; Theander, T G;

    1994-01-01

    This study was designed to examine the antileishmanial activity of the oxygenated chalcone licochalcone A in mice and hamsters infected with Leishmania parasites. Intraperitoneal administration of licochalcone A at doses of 2.5 and 5 mg/kg of body weight per day completely prevented lesion...... development in BALB/c mice infected with Leishmania major. Treatment of hamsters infected with L. donovani with intraperitoneal administration of licochalcone A at a dose of 20 mg/kg of body weight per day for 6 consecutive days resulted in a > 96% reduction of parasite load in the liver and the spleen...

  5. Basic fibroblast growth factor improves learning and memory functions in chronic stress mice

    Institute of Scientific and Technical Information of China (English)

    Xian Qu; Chunying Li; Hongchang Liu; Chang Su

    2011-01-01

    Four weeks of uncertain stress was used to establish an animal model of chronic stress.Basic fibroblast growth factor was injected daily for 15 days following stress induction.Cell morphology in the hippocampal CA3 region of chronic stress mice revealed cell damage.Nitric oxide content and calcium concentration were significantly increased in the hippocampus,and learning and memory functions were significantly decreased.After basic fibroblast growth factor intervention,Ca2+ overload was decreased and neuronal damage was relieved in hippocampal neurons,which improved learning and memory functions in chronic stress mice.Latency was prolonged and the number of errors was decreased in a passive avoidance test.

  6. Opposing actions of chronic stress and chronic nicotine on striatal function in mice

    OpenAIRE

    Salas, Ramiro; De Biasi, Mariella

    2008-01-01

    Stress is a major risk factor in drug addiction development and relapse. Virtually all drugs of abuse act by increasing extracellular dopamine levels in the striatum. To gain an understanding of the interaction between stress and drug exposure, we studied the effects of concomitant chronic nicotine and chronic stress exposure on mouse striatal dopamine levels.

  7. Chronic consumption of distilled sugarcane spirit induces anxiolytic-like effects in mice

    Directory of Open Access Journals (Sweden)

    Maria Clecia P. Sena

    2011-01-01

    Full Text Available OBJECTIVE: Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. METHOD: Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n = 16 had access to sugarcane spirit + distilled water, the mice in Group B (n = 15 had access to ethanol + distilled water, and the mice in Group C (control, n = 14 had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2% for the first week, 5% for the second week and 10% for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. RESULTS: In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 + 8 vs. 7 + 2 s, n = 9 or sugarcane spirit (36 + 9 vs. 7 + 2 s, n = 9 compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 + 1 for the control group, 27 + 2 for the ethanol group, and 31 + 3 for the sugarcane-spirit group; n = 9 for each group. In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 + 0.17 for the control group and 2.67 + 0.17 for the sugarcane spirit group; n = 8 for each group. CONCLUSION: The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice.

  8. Pulmonary immunostimulation with MALP-2 in influenza virus-infected mice increases survival after pneumococcal superinfection.

    Science.gov (United States)

    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

  9. Natural infection of murine norovirus in conventional and specific pathogen-free (SPF laboratory mice

    Directory of Open Access Journals (Sweden)

    Takeo eOhsugi

    2013-01-01

    Full Text Available Noroviruses cause most cases of acute viral gastroenteritis worldwide. The lack of a cell culture infection model for human norovirus necessitates the use of molecular methods and/or viral surrogate models amenable to cell culture to predict norovirus inactivation. Murine norovirus (MNV may be used to construct a small animal model for studying the biology and pathogenesis of noroviruses because MNV is the only norovirus that replicates in cell culture and a small animal model. However, recent studies have shown that natural MNV infection is widespread in laboratory mouse colonies. We investigated MNV infection in both conventional and specific pathogen-free (SPF genetically modified mice from Japan and the US, and commercial mice from several animal breeders in Japan, using serological and molecular techniques. MNV antibodies were detected in 67.3% of conventional mice and 39.1% of SPF mice from Japan and 62.5% of conventional mice from the US. MNV antibodies were also found in 20% of commercial SPF C57BL/6 mice from one of three breeders. Partial gene amplification of fecal isolates from infected animals showed that the isolates were homologous to reported MNV sequences. These results suggest that both conventional and SPF laboratory mice, including commercial mice, are widely infected with MNV, which might require considerable attention as an animal model of human disease.

  10. Perturbation of the intestinal microbiota of mice infected with Cryptosporidium parvum.

    Science.gov (United States)

    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

  11. Chandipura Virus infection in mice: the role of toll like receptor 4 in pathogenesis

    Directory of Open Access Journals (Sweden)

    Anukumar Balakrishnan

    2012-05-01

    Full Text Available Abstract Background The susceptibility of mice and humans to Chandipura virus infection is age-dependent. Upon experimental infection, mice secrete significant amounts of proinflammatory cytokines. Similarly, children who recover from natural infection with the virus show significant amounts of TNF-α production, suggesting that innate immunity plays a major role in the response to Chandipura virus. Toll-like receptors (TLR are key host molecules involved in innate immune responses in infections. Therefore, the aim of this study was to examine the role of TLR in the response to Chandipura virus infection. Methods The mouse monocyte-macrophage cell line, RAW 264.7, and C3H/HeJ mice were used as models. Micro array techniques were used to identify the type of TLR involved in the response to infection. The results were validated by examining TLR expression using flow cytometry and by measuring the levels of proinflammatory cytokines and nitric oxide (NO in the culture supernatants using bead assays and the Griess method, respectively. The pathogenic role of Toll-like receptor 4 (TLR4 was studied in a TLR4 mutant strain of mice -C3H/HeJ and the results compared with those from wild-type mice- C3H/CaJ. The pathogenic effects of NO were studied by treating experimentally infected mice with the NO inhibitor, aminoguanidine (AG. Results The micro array results showed that TLR4 was regulated after Chandipura virus infection. At high multiplicities of infection (10 MOI, RAW cells up- regulated cell surface expression of TLR4 and secreted significant amounts of TNF-α, MCP-1, IL-10 and IL-12 and NO. The survival rate of C3H/HeJ mice was higher than those of wild-type C3H/CaJ mice. The survived C3H/HeJ mice secreted significant quantity of MCP-1 and IFN-γ cytokines and cleared virus from brain. Similarly, the survival rate of AG-treated mice was higher than those of the untreated controls. Conclusions Chandipura virus regulates TLR4, which leads to the

  12. Sera from patients with chronic Lyme disease protect mice from Lyme borreliosis.

    Science.gov (United States)

    Fikrig, E; Bockenstedt, L K; Barthold, S W; Chen, M; Tao, H; Ali-Salaam, P; Telford, S R; Flavell, R A

    1994-03-01

    Sera from selected patients with Lyme disease in different stages were used to passively immunize mice against Borrelia burgdorferi challenge to determine if human antibodies could protect the animals from infection. Sera from 2 patients with late-stage Lyme disease that contained strong antibody reactivity to proteins in B. burgdorferi lysates, including antibodies to the outer surface proteins (Osps) A and B, partly protected mice from infection after challenge with a small inoculum (10(2)) of B. burgdorferi. Mice immunized with sera from either of these 2 patients developed significantly fewer infections from the borreliae (patient 1 serum, 5%; patient 2 serum, 25%) relative to control mice (patient 1 serum, 90%; patient 2 serum, 74%). In contrast, sera from 2 patients with early or late Lyme disease that lacked antibodies reactive to OspA and OspB did not confer protection. Immunity appeared to be related, at least in part, to the presence of a strong humoral response to the Osps. These results suggest that during prolonged infection, some patients develop an immune response that may be partly protective against reinfection with B. burgdorferi. Therefore, although most patients do not mount a strong humoral response to the Osps during natural infection, vaccination with an Osp may elicit protective immunity.

  13. Time course of gene expression profiling in the liver of experimental mice infected with Echinococcus multilocularis.

    Directory of Open Access Journals (Sweden)

    Renyong Lin

    Full Text Available BACKGROUND: Alveolar echinococcosis (AE is a severe chronic parasitic disease which behaves like a slow-growing liver cancer. Clinical observations suggest that the parasite, Echinococcus multilocularis (E. multilocularis influences liver homeostasis and hepatic cell metabolism. However, this has never been analyzed during the time course of infection in the common model of secondary echinococcosis in experimental mice. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiles were assessed using DNA microarray analysis, 1, 2, 3 and 6 months after injection of E. multilocularis metacestode in the liver of susceptible mice. Data were collected at different time points to monitor the dynamic behavior of gene expression. 557 differentially expressed genes were identified at one or more time points, including 351 up-regulated and 228 down-regulated genes. Time-course analysis indicated, at the initial stage of E. multilocularis infection (month 1-2, that most of up-regulated pathways were related to immune processes and cell trafficking such as chemokine-, mitogen-activated protein kinase (MAPK signaling, and down-regulated pathways were related to xenobiotic metabolism; at the middle stage (month 3, MAPK signaling pathway was maintained and peroxisome proliferator-activated receptor (PPAR signaling pathway emerged; at the late stage (month 6, most of up-regulated pathways were related to PPAR signaling pathway, complement and coagulation cascades, while down-regulated pathways were related to metabolism of xenobiotics by cytochrome P450. Quantitative RT-PCR analysis of a random selection of 19 genes confirmed the reliability of the microarray data. Immunohistochemistry analysis showed that proliferating cell nuclear antigen (PCNA was increased in the liver of E. multilocularis infected mice from 2 months to 6 months. CONCLUSIONS: E. multilocularis metacestode definitely exerts a deep influence on liver homeostasis, by modifying a number of gene

  14. Chronic toxicity of a mixture of chlorinated alkanes and alkenes in ICR mice.

    Science.gov (United States)

    Wang, Fun-In; Kuo, Min-Liang; Shun, Chia-Tung; Ma, Yee-Chung; Wang, Jung-Der; Ueng, Tzuu-Huei

    2002-02-01

    The aim of this study was to determine the chronic toxicity of a mixture of chlorinated alkanes and alkenes (CA) consisting of chloroform, 1,1-dichloroethane, 1,1-dichloroethylene, 1,1,1-trichloroethane, trichloroethylene, and tetrachloroethylene. These chlorinated organic solvents were present in the underground water near an electronic appliances manufactory in Taoyuan, Taiwan. Male and female weanling ICR mice were treated with low-, medium-, and high-dose CA mixtures in drinking water for 16 and 18 mo, respectively. A significant number of male mice treated with the high-dose CA mixture developed tail alopecia and deformation, which was not prominent in CA-treated female mice. Medium- and high-dose CA mixtures induced marginal increases of liver and lung weights, blood urea nitrogen, and serum creatinine levels in male mice. In female mice, the high-dose CA mixture increased liver, kidney, and uterus and ovary total weights, without affecting serum biochemistry parameters. CA mixtures had no effects on the total glutathione content or the level of glutathione S-transferase activity in the livers and kid- neys of male and female mice. Treatments with CA mixtures produced a trend of increasing frequency of hepatocelluar neoplasms in male mice, compared to male and female controls and CA-treated female mice. The high-dose CA mixture induced a significantly higher incidence of mammary adenocarcinoma in female mice. The calculated odds ratios of mammary adenocarcinoma in female mice induced by low-, medium-, and high-dose CA mixtures were 1.14, 1.37, and 3.53 times that of the controls, respectively. The low-dose CA mixture induced a higher incidence of cysts and inflammation in and around the ovaries. This study has demonstrated that the CA mixture is a potential carcinogen to male and female mice. These animal toxicology data may be important in assessing the health effects of individuals exposed to the CA mixture.

  15. Trypanosoma brucei gambiense Infections in Mice Lead to Tropism to the Reproductive Organs, and Horizontal and Vertical Transmission.

    Science.gov (United States)

    Biteau, Nicolas; Asencio, Corinne; Izotte, Julien; Rousseau, Benoit; Fèvre, Muriel; Pillay, Davita; Baltz, Théo

    2016-01-01

    Trypanosoma brucei gambiense, transmitted by the tsetse fly, is the main causative agent of Human African trypanosomosis in West Africa and poses a significant health risk to 70 million people. Disease progression varies depending on host immunity, but usually begins with a haemo-lymphatic phase, followed by parasite invasion of the central nervous system. In the current study, the tropism of T. b. gambiense 1135, causing a low level chronic 'silent' infection, was monitored in a murine model using bioluminescence imaging and PCR. A tropism to the reproductive organs, in addition to the central nervous system, after 12-18 months of infection was observed. Bioluminescent analysis of healthy females crossed with infected males showed that 50%, 62.5% and 37.5% of the female mice were subsequently positive for parasites in their ovaries, uteri and brain respectively. Although PCR confirmed the presence of parasites in the uterus of one of these mice, the blood of all mice was negative by PCR and LAMP. Subsequently, bioluminescent imaging of the offspring of infected female mice crossed with healthy males indicated parasites were present in the reproductive organs of both male (80%) and female (60%) offspring. These findings imply that transmission of T. b. gambiense 1135 occurs horizontally, most probably via sexual contact, and vertically in a murine model, which raises the possibility of a similar transmission in humans. This has wide reaching implications. Firstly, the observations made in this study are likely to be valid for wild animals acting as a reservoir for T. b. gambiense. Also, the reproductive organs may act as a refuge for parasites during drug treatment in a similar manner to the central nervous system. This could leave patients at risk of a relapse, ultimately allowing them to act as a reservoir for subsequent transmission by tsetse and possibly, horizontally and vertically. PMID:26735855

  16. Chronic Trypanosoma cruzi infection potentiates adipose tissue macrophage polarization toward an anti-inflammatory M2 phenotype and contributes to diabetes progression in a diet-induced obesity model.

    Science.gov (United States)

    Cabalén, María E; Cabral, María F; Sanmarco, Liliana M; Andrada, Marta C; Onofrio, Luisina I; Ponce, Nicolás E; Aoki, María P; Gea, Susana; Cano, Roxana C

    2016-03-22

    Chronic obesity and Chagas disease (caused by the protozoan Trypanosoma cruzi) represent serious public health concerns. The interrelation between parasite infection, adipose tissue, immune system and metabolism in an obesogenic context, has not been entirely explored. A novel diet-induced obesity model (DIO) was developed in C57BL/6 wild type mice to examine the effect of chronic infection (DIO+I) on metabolic parameters and on obesity-related disorders. Dyslipidemia, hyperleptinemia, and cardiac/hepatic steatosis were strongly developed in DIO mice. Strikingly, although these metabolic alterations were collectively improved by infection, plasmatic apoB100 levels remain significantly increased in DIO+I, suggesting the presence of pro-atherogenic small and dense LDL particles. Moreover, acute insulin resistance followed by chronic hyperglycemia with hypoinsulinemia was found, evidencing an infection-related-diabetes progression. These lipid and glucose metabolic changes seemed to be highly dependent on TLR4 expression since TLR4-/- mice were protected from obesity and its complications. Notably, chronic infection promoted a strong increase in MCP-1 producing macrophages with a M2 (F4/80+CD11c-CD206+) phenotype associated to oxidative stress in visceral adipose tissue of DIO+I mice. Importantly, infection reduced lipid content but intensified inflammatory infiltrates in target tissues. Thus, parasite persistence in an obesogenic environment and the resulting host immunometabolic dysregulation may contribute to diabetes/atherosclerosis progression. PMID:26921251

  17. Evaluating the potential of a new isotope-labelled glyco-ligand for estimating the remnant liver function of schistosoma-infected mice.

    Science.gov (United States)

    Cheng, P-C; Chiang, P-F; Lee, K-M; Yeh, C-H; Hsu, K-L; Liu, S-W; Shen, L-H; Peng, C-L; Fan, C-K; Luo, T-Y

    2013-01-01

    A new glyco-derivative compound (OCTAM) was developed and labelled with isotope to form (188) Re-OCTAM as a candidate nuclear medicine imaging agent for testing the liver function. We evaluated the potential of isotope-labelled OCTAM for estimating the remnant liver function in vitro and in vivo schistosoma-infected mice. The affinity of OCTAM to liver asialoglycoprotein receptors (ASGPR) was assessed by competitive inhibition assay in vitro. In vivo assessments were performed to score the remnant liver function in mice at different schistosomal infection stages. OCTAM binds specifically to ASGPR and showed competitive inhibition of anti-ASGPR antibody binding to hepatocytes, and was higher than that of other galactosyl ligands. Micro-SPECT/CT images of uninfected mice revealed strong liver uptake. Quantified serial images of mice infected for 9, 12 and 18 weeks showed delayed liver uptake, and the retention of uptake was inversely correlated with stage and grade of schistosoma infection. Pathological and biochemical analysis demonstrated that gradually accumulating liver injury caused by infection significantly influenced uptake of (188) Re-OCTAM. Hepatic ASGPR expression diminished only in the chronic infection stage. This study demonstrated that the isotope-labelled OCTAM could accumulate in the liver, might have potential as an imaging agent for in vivo hepatic function evaluation of schistosomiasis.

  18. The role of fluoxetine on macrophage function in chronic pain (Experimental study in Balb/c mice

    Directory of Open Access Journals (Sweden)

    Dwi Pudjonarko

    2015-11-01

    Full Text Available Chronic pain raises stress conditions such as depression that can lower the cellular immunity. Fluoxetine is an antidepressant  used as an adjuvant in pain management but no one has been linked it with the body immune system. The objectives of this research were to proof the benefits of fluoxetine in  preventing degradation of macrophage function in chronic pain by measuring the macrophage phagocytic index , macrophage NO levels and the liver bacterial count in BALB/c mice infected with Listeria Monocytogenes.A Post Test - Only Control Group Design was conducted using 28 male mice strain BALB /c, age 8-10 weeks. The control group (C, mice got the same standard feed as the other groups. Chronic pain group (P, mice were injected with 20μL intraplantar CFA on day-1. Pain + fluoxetine early group (PFE were treated with P + fluoxetine 5 mg / kg ip day-1, the 4th, the 7th and the 10th, while the Pain + fluoxetine late group (PFL were treated with P + fluoxetine 5 mg / kg ip on day 7th and 10th. All mice were injected with 104 live Listeria monocytogenes iv on day 8th. Termination was performed on day 13th. Differences within groups  were analyzed using  One-way ANOVA and Kruskall Wallis, whereas the correlation of variables were analyzed using  Pearson's product moment. The experimental results showed that The macrophage phagocytic index and NO macrophage level (pg/mL in PFE group(2,24±1,013; 0,24±0,239 was higher than than P group (1,68±0,920; 0,21±0,263 and there was no different in the macrophage phagocytic index of PFE group compared to C group (p=0,583; p=0,805. In PFL group (4,32±1,459; 0,54±0,294 the macrophage phagocytic index as well as NO macrophage level (pg/mL was higher than P group (1,68±0,920; 0,21±0,263 with p=0,002; p=0,017. P group Bacterial count (log cfu/gram (2,30±0,849 was significantly higher than C group(1,15±0,223 (p=0,007, while PFE group bacterial count (1,96±0,653 and PFL group bacterial count (1,84±0

  19. Management of Chronic Hepatitis B Infection in India.

    Science.gov (United States)

    Amarapurkar, Deepak N; Madan, Kaushal; Kapoor, Dharmesh

    2015-11-01

    Chronic hepatitis B (CHB) infection is a substantial global health problem with highest prevalence observed in the sub-Saharan Africa and East Asia. India lies in the intermediate endemicity zone with prevalence ranging from 0.1% to 11.7%. The predominant route of transmission is horizontal and the most commonly occurring genotypes are A and D. The high mortality and morbidity associated with CHB constitutes significant health and economic burden in developing countries like India. Antiviral agents decrease HBV DNA load and prevent disease progression. Several regional and country expert associations have developed treatment guidelines for appropriate management of CHB; however, various factors like prevalence, disease awareness, immunization status, cost implications, availability of resources, type of transmission and emerging significance of HBV genotypes have influenced the management of CHB in a country. This article focuses on expert's recommendations on CHB management including initiation, monitoring and termination of treatment with emphasis on borderline cases. The article also throws light on the challenges to optimum management and provides preferred therapeutic approaches in Indian perspective. PMID:27608783

  20. Endothelial Dysfunction Correlates with Liver Fibrosis in Chronic HCV Infection

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    Michele Barone

    2015-01-01

    Full Text Available Background. Hepatitis C virus (HCV infection can exert proatherogenic activities due to its direct action on vessel walls and/or via the chronic inflammatory process involving the liver. Aims. To clarify the role of HCV in atherosclerosis development in monoinfected HCV patients at different degrees of liver fibrosis and with no risk factors for coronary artery disease. Methods. Forty-five patients were included. Clinical, serological, and anthropometric parameters, liver fibrosis (transient liver elastometry (fibroscan and aspartate aminotransferase to platelet ratio index (APRI, carotid intima-media thickness (c-IMT, and brachial artery flow-mediated vasodilatation (FMD were assessed. Patients were divided into 3 tertiles according to fibroscan values. Results. Patients in the third tertile (fibroscan value >11.5 KPa showed FMD values were significantly lower than second and first tertiles (4.7±1.7% versus 7.1±2.8%, p=0.03. FMD values were inversely related to liver elastomeric values. c-IMT values were normal. The risk for endothelial dysfunction development in the third tertile (p=0.02 was 6.9 higher than the first tertile. A fibroscan value >11.5 KPa had a positive predictive power equal to 79% for endothelial dysfunction. Conclusions. HCV advanced liver fibrosis promotes atherosclerosis by inducing endothelial dysfunction independently of common cardiovascular risk factors.

  1. Plasminogen initiates and potentiates the healing of acute and chronic tympanic membrane perforations in mice

    OpenAIRE

    Shen, Yue; Guo, Yongzhi; Wilczynska, Malgorzata; Li, Jinan; Hellström, Sten; Ny, Tor

    2014-01-01

    Background: Most tympanic membrane (TM) perforations heal spontaneously, but approximately 10-20% remain open as chronic TM perforations. Chronic perforations can lead to an impaired hearing ability and recurrent middle ear infections. Traditionally, these perforations must be surgically closed, which is costly and time consuming. Therefore, there is a need for simpler therapeutic strategies. Previous studies by us have shown that plasminogen (plg) is a potent pro-inflammatory regulator that ...

  2. Transplanted Bone Marrow Cells Repair Heart Tissue and Reduce Myocarditis in Chronic Chagasic Mice

    OpenAIRE

    MILENA B. P. SOARES; Lima, Ricardo S.; Rocha, Leonardo L.; Takyia, Christina M; Pontes-de-Carvalho, Lain; Campos de Carvalho, Antonio C.; Ribeiro-dos-Santos, Ricardo

    2004-01-01

    A progressive destruction of the myocardium occurs in ∼30% of Trypanosoma cruzi-infected individuals, causing chronic chagasic cardiomyopathy, a disease so far without effective treatment. Syngeneic bone marrow cell transplantation has been shown to cause repair and improvement of heart function in a number of studies in patients and animal models of ischemic cardiopathy. The effects of bone marrow transplant in a mouse model of chronic chagasic cardiomyopathy, in the presence of the disease ...

  3. Requirements for Pseudomonas aeruginosa acute burn and chronic surgical wound infection.

    Directory of Open Access Journals (Sweden)

    Keith H Turner

    2014-07-01

    Full Text Available Opportunistic infections caused by Pseudomonas aeruginosa can be acute or chronic. While acute infections often spread rapidly and can cause tissue damage and sepsis with high mortality rates, chronic infections can persist for weeks, months, or years in the face of intensive clinical intervention. Remarkably, this diverse infectious capability is not accompanied by extensive variation in genomic content, suggesting that the genetic capacity to be an acute or a chronic pathogen is present in most P. aeruginosa strains. To investigate the genetic requirements for acute and chronic pathogenesis in P. aeruginosa infections, we combined high-throughput sequencing-mediated transcriptome profiling (RNA-seq and genome-wide insertion mutant fitness profiling (Tn-seq to characterize gene expression and fitness determinants in murine models of burn and non-diabetic chronic wound infection. Generally we discovered that expression of a gene in vivo is not correlated with its importance for fitness, with the exception of metabolic genes. By combining metabolic models generated from in vivo gene expression data with mutant fitness profiles, we determined the nutritional requirements for colonization and persistence in these infections. Specifically, we found that long-chain fatty acids represent a major carbon source in both chronic and acute wounds, and P. aeruginosa must biosynthesize purines, several amino acids, and most cofactors during infection. In addition, we determined that P. aeruginosa requires chemotactic flagellar motility for fitness and virulence in acute burn wound infections, but not in non-diabetic chronic wound infections. Our results provide novel insight into the genetic requirements for acute and chronic P. aeruginosa wound infections and demonstrate the power of using both gene expression and fitness profiling for probing bacterial virulence.

  4. The woodchuck as an animal model for pathogenesis and therapy of chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes,and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, and for the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and

  5. Critical Role of Airway Macrophages in Modulating Disease Severity during Influenza Virus Infection of Mice

    OpenAIRE

    Tate, M.D.; Pickett, D L; Rooijen, van, J.; Brooks, A G; Reading, P C

    2010-01-01

    Airway macrophages provide a first line of host defense against a range of airborne pathogens, including influenza virus. In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus str...

  6. Increased microRNA-155 expression in the serum and peripheral monocytes in chronic HCV infection

    OpenAIRE

    Bala Shashi; Tilahun Yaphet; Taha Odette; Alao Hawau; Kodys Karen; Catalano Donna; Szabo Gyongyi

    2012-01-01

    Abstract Background Hepatitis C Virus (HCV), a single stranded RNA virus, affects millions of people worldwide and leads to chronic infection characterized by chronic inflammation in the liver and in peripheral immune cells. Chronic liver inflammation leads to progressive liver damage. MicroRNAs (miRNA) regulate inflammation (miR-155, -146a and -125b) as well as hepatocyte function (miR-122). Methods Here we hypothesized that microRNAs are dysregulated in chronic HCV infection. We examined mi...

  7. Radiocomplexation and evaluation of the 99mTc-Gemifloxacin in artificially Escherichia coli infected mice

    International Nuclear Information System (INIS)

    Gemifloxacin as a broad spectrum quinolone antibacterial agent was radiocomplexed with high activity of 99mTc and was evaluated as an infection imaging agent in artificially Escherichia coli (E. Coli) infected mice. 99mTc-Gemifloxacin with high specific activity (0.148 GBq/μmol) and labeling yield (98.60 ± 0.70 %) was obtained. Our main achievement was high accumulation in the E. Coli infected right thigh muscle in mice (T/NT = 1.89 at 4 h post injection) which may diagnostically be beneficial to distinguish sites of E. Coli infection. (author)

  8. Effect of the histaminergic antagonist over the pulmonary oedema growth in P. berghei - infected mice

    International Nuclear Information System (INIS)

    The involvement of histaminergic mechanisms in the pathogenesis of pulmonary oedema observed in p. berghei - infected mice was investigated. Histamine concentrations in plasma and whole blood of infected and normal mice were determined by radioenzymatic assay during the seven days of the infection. Elevated plasma and whole blood histamine levels were found at the last stages of infection (sixth day and seventh day) after intraperitoneal injection of parasitized erythrocytes, showing a close temporal correlation between the development of the oedema and the elevation of the circulating histamine concentrations. The participation of H 1 and H 2 receptors in the increase in vascular permeability (IVP) induced by histamine was also verified. (author)

  9. Stressful Presentations: Mild Chronic Cold Stress in Mice Influences Baseline Properties of Dendritic Cells

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    Kathleen Marie Kokolus

    2014-02-01

    Full Text Available The ability of dendritic cells to stimulate and regulate T cells is critical to effective anti-tumor immunity. Therefore, it is important to fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily to study immune responses. Physiological stress is well recognized to impair several arms of immune protection. The goals of this report are to briefly summarize previous work revealing how DCs respond to various forms of physiologically relevant stress and to present new data highlighting the potential for chronic mild cold stress inherent in mice housed at standard ambient temperatures required for laboratory mice to influence baseline DCs properties. Since recent data from our group shows that CD8+ T cell function is altered by mild chronic cold stress and since DC function is crucial for CD8+ T cell activation, we wondered whether mild cold stress may also be influencing DC properties. We found increased numbers of splenic DCs (CD11c+ in cold stressed mice compared to mice housed at a thermoneutral temperature, which significantly reduces cold stress. However, many of the DCs which are expanded in cold stressed mice express an immature phenotype. We also found that antigen presentation and ability of splenocytes to activate T cells were impaired compared to that seen in DCs isolated from mice at thermoneutrality. The new data presented here strongly suggest that the housing temperature of mice can affect fundamental properties of DC function which in turn could be influencing the response of DCs to added experimental stressors or other treatments.

  10. Altered energy balance and cytokine gene expression in a murine model of chronic infection with Toxoplasma gondii.

    Science.gov (United States)

    Arsenijevic, D; Girardier, L; Seydoux, J; Chang, H R; Dulloo, A G

    1997-05-01

    The temporal pattern of changes in energy balance and cytokine mRNA expression in spleen and brain were examined in a mouse model of infection with Toxoplasma gondii. During days 1-7 postinfection, food intake was unaltered, but energy expenditure was significantly increased, and this was associated with elevated tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-5, and interferon (IFN)-gamma. The hypermetabolic state persisted during subsequent anorexia, whose onset coincided with elevated IL-2, and at the end of the acute phase of cachexia, the dual anorexic and hypermetabolic states were associated with the cytokines examined: TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-gamma. In the chronic phase of the infection, the mice showed either partial weight recovery (gainers) or no weight regain (nongainers). The infected gainers, though still hypophagic, were no longer hypermetabolic, and their cytokine mRNA was no longer elevated, except for TNF-alpha and IL-10. In contrast, the infected nongainers continued to show both anoroxia and hypermetabolism, which were associated with elevations in all cytokines examined and particularly those of the TH2 profile (IL-4 and IL-5) and IL-6. Taken together, these studies reveal a distinct pattern of cytokine mRNA expression underlying 1) hypermetabolism vs. anorexia, 2) acute vs. chronic cachexia, and 3) stable weight loss vs. partial weight recovery. PMID:9176193

  11. Serial histopathological examination of the lungs of mice infected with influenza A virus PR8 strain.

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    Masaya Fukushi

    Full Text Available Avian influenza H5N1 and pandemic (H1N1 2009 viruses are known to induce viral pneumonia and subsequent acute respiratory distress syndrome (ARDS with diffuse alveolar damage (DAD. The mortality rate of ARDS/DAD is extremely high, at approximately 60%, and no effective treatment for ARDS/DAD has been established. We examined serial pathological changes in the lungs of mice infected with influenza virus to determine the progress from viral pneumonia to ARDS/DAD. Mice were intranasally infected with influenza A/Puerto Rico/8/34 (PR8 virus, and their lungs were examined both macro- and micro-pathologically every 2 days. We also evaluated general condition, survival rate, body weight, viral loads in lung, and surfactant proteins in serum. As a result, all infected mice died within 9 days postinfection. At 2 days postinfection, inflammation in alveolar septa, i.e., interstitial pneumonia, was observed around bronchioles. From 4 to 6 days postinfection, interstitial pneumonia with alveolar collapse expanded throughout the lungs. From 6 to 9 days postinfection, DAD with severe alveolar collapse was observed in the lungs of all of dying and dead mice. In contrast, DAD was not observed in the live infected-mice from 2 to 6 days postinfection, despite their poor general condition. In addition, histopathological analysis was performed in mice infected with a dose of PR8 virus which was 50% of the lethal dose for mice in the 20-day observation period. DAD with alveolar collapse was observed in all dead mice. However, in the surviving mice, instead of DAD, glandular metaplasia was broadly observed in their lungs. The present study indicates that DAD with severe alveolar collapse is associated with death in this mouse infection model of influenza virus. Inhibition of the development of DAD with alveolar collapse may decrease the mortality rate in severe viral pneumonia caused by influenza virus infection.

  12. Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans

    Science.gov (United States)

    Park, Dong Ik; Dournes, Carine; Sillaber, Inge; Uhr, Manfred; Asara, John M.; Gassen, Nils C.; Rein, Theo; Ising, Marcus; Webhofer, Christian; Filiou, Michaela D.; Müller, Marianne B.; Turck, Christoph W.

    2016-01-01

    Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively. Proteomics and metabolomics profiles of PLF and PSF groups were acquired for the hippocampus and plasma to identify molecular pathways and biosignatures that stratify paroxetine-treated mouse sub-groups. The critical role of purine and pyrimidine metabolisms for chronic paroxetine treatment response in the mouse was further corroborated by pathway protein expression differences in both mice and patients that underwent chronic antidepressant treatment. The integrated -omics data indicate purine and pyrimidine metabolism pathway activity differences between PLF and PSF mice. Furthermore, the pathway protein levels in peripheral specimens strongly correlated with the antidepressant treatment response in patients. Our results suggest that chronic SSRI treatment differentially affects purine and pyrimidine metabolisms, which may explain the heterogeneous antidepressant treatment response and represents a potential biosignature. PMID:27731396

  13. Defective insulin secretion by chronic glucagon receptor activation in glucose intolerant mice.

    Science.gov (United States)

    Ahlkvist, Linda; Omar, Bilal; Valeur, Anders; Fosgerau, Keld; Ahrén, Bo

    2016-03-01

    Stimulation of insulin secretion by short-term glucagon receptor (GCGR) activation is well characterized; however, the effect of long-term GCGR activation on β-cell function is not known, but of interest, since hyperglucagonemia occurs early during development of type 2 diabetes. Therefore, we examined whether chronic GCGR activation affects insulin secretion in glucose intolerant mice. To induce chronic GCGR activation, high-fat diet fed mice were continuously (2 weeks) infused with the stable glucagon analog ZP-GA-1 and challenged with oral glucose and intravenous glucose±glucagon-like peptide 1 (GLP1). Islets were isolated to evaluate the insulin secretory response to glucose±GLP1 and their pancreas were collected for immunohistochemical analysis. Two weeks of ZP-GA-1 infusion reduced insulin secretion both after oral and intravenous glucose challenges in vivo and in isolated islets. These inhibitory effects were corrected for by GLP1. Also, we observed increased β-cell area and islet size. We conclude that induction of chronic ZP-GA-1 levels in glucose intolerant mice markedly reduces insulin secretion, and thus, we suggest that chronic activation of the GCGR may contribute to the failure of β-cell function during development of type 2 diabetes.

  14. Differential Lymphocyte and Antibody Responses in Deer Mice Infected with Sin Nombre Hantavirus or Andes Hantavirus

    OpenAIRE

    Schountz, Tony; Quackenbush, Sandra; Rovnak, Joel; Haddock, Elaine; Black, William C.; Feldmann, Heinz; Prescott, Joseph

    2014-01-01

    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...

  15. Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity

    OpenAIRE

    Chang, Y.J.; Kim, H. Y.; Albacker, L.A.; Lee, H H; Baumgarth, N; Akira, S; Savage, P. B.; Endo, S.; T. Yamamura; Maaskant, J.; Kitano, N.; A Singh; Bhatt, A; Besra, G S; Elzen, van den, SJ Stef

    2010-01-01

    Infection with influenza A virus represents a major public health threat worldwide, particularly in patients with asthma. However, immunity induced by influenza A virus may have beneficial effects, particularly in young children, that might protect against the later development of asthma, as suggested by the hygiene hypothesis. Herein, we show that infection of suckling mice with influenza A virus protected the mice as adults against allergen-induced airway hyperreactivity (AHR), a cardinal f...

  16. Cigarette smoke worsens lung inflammation and impairs resolution of influenza infection in mice

    Directory of Open Access Journals (Sweden)

    Jones Jessica E

    2008-07-01

    Full Text Available Abstract Background Cigarette smoke has both pro-inflammatory and immunosuppressive effects. Both active and passive cigarette smoke exposure are linked to an increased incidence and severity of respiratory virus infections, but underlying mechanisms are not well defined. We hypothesized, based on prior gene expression profiling studies, that upregulation of pro-inflammatory mediators by short term smoke exposure would be protective against a subsequent influenza infection. Methods BALB/c mice were subjected to whole body smoke exposure with 9 cigarettes/day for 4 days. Mice were then infected with influenza A (H3N1, Mem71 strain, and analyzed 3 and 10 days later (d3, d10. These time points are the peak and resolution (respectively of influenza infection. Results Inflammatory cell influx into the bronchoalveolar lavage (BALF, inflammatory mediators, proteases, histopathology, viral titres and T lymphocyte profiles were analyzed. Compared to smoke or influenza alone, mice exposed to smoke and then influenza had more macrophages, neutrophils and total lymphocytes in BALF at d3, more macrophages in BALF at d10, lower net gelatinase activity and increased activity of tissue inhibitor of metalloprotease-1 in BALF at d3, altered profiles of key cytokines and CD4+ and CD8+ T lymphocytes, worse lung pathology and more virus-specific, activated CD8+ T lymphocytes in BALF. Mice smoke exposed before influenza infection had close to 10-fold higher lung virus titres at d3 than influenza alone mice, although all mice had cleared virus by d10, regardless of smoke exposure. Smoke exposure caused temporary weight loss and when smoking ceased after viral infection, smoke and influenza mice regained significantly less weight than smoke alone mice. Conclusion Smoke induced inflammation does not protect against influenza infection. In most respects, smoke exposure worsened the host response to influenza. This animal model may be useful in studying how smoke worsens

  17. Bone marrow-derived microglia infiltrate into the paraventricular nucleus of chronic psychological stress-loaded mice.

    Directory of Open Access Journals (Sweden)

    Koji Ataka

    Full Text Available BACKGROUND: Microglia of the central nervous system act as sentinels and rapidly react to infection or inflammation. The pathophysiological role of bone marrow-derived microglia is of particular interest because they affect neurodegenerative disorders and neuropathic pain. The hypothesis of the current study is that chronic psychological stress (chronic PS induces the infiltration of bone marrow-derived microglia into hypothalamus by means of chemokine axes in brain and bone marrow. METHODS AND FINDINGS: Here we show that bone marrow-derived microglia specifically infiltrate the paraventricular nucleus (PVN of mice that received chronic PS. Bone marrow derived-microglia are CX3CR1(lowCCR2(+CXCR4(high, as distinct from CX3CR1(highCCR2(-CXCR4(low resident microglia, and express higher levels of interleukin-1β (IL-1β but lower levels of tumor necrosis factor-α (TNF-α. Chronic PS stimulates the expression of monocyte chemotactic protein-1 (MCP-1 in PVN neurons, reduces stromal cell-derived factor-1 (SDF-1 in the bone marrow and increases the frequency of CXCR4(+ monocytes in peripheral circulation. And then a chemokine (C-C motif receptor 2 (CCR2 or a β3-adrenoceptor blockade prevents infiltration of bone marrow-derived microglia in the PVN. CONCLUSION: Chronic PS induces the infiltration of bone marrow-derived microglia into PVN, and it is conceivable that the MCP-1/CCR2 axis in PVN and the SDF-1/CXCR4 axis in bone marrow are involved in this mechanism.

  18. Nutritional status in chronically hospitalized stroke patients complicated with pulmonary infection

    Institute of Scientific and Technical Information of China (English)

    Yue Chen; Lufang Chen; Yiqing Tao; Maomao Han; Chunlan Cui; Shichao Liu

    2011-01-01

    Complicated pulmonary infection following stroke has traditionally been considered an aspirated infection by many physicians, and little attention has been paid to concomitant protein-energy malnutrition. In the present study, we hypothesized that protein-energy malnutrition may be present in hospitalized chronic stroke patients complicated with pulmonary infection. The results revealed that body protein and fat stores were significantly depleted in stroke patients with pulmonary infection. Protein-energy malnutrition was present in 12 of 27 patients with pulmonary infection. In comparison, only eight of 42 stroke patients without pulmonary infection exhibited protein-energy malnutrition. A significantly higher prevalence of protein-energy malnutrition was found in the pulmonary infection group, suggesting that protein-energy malnutrition is more likely to be present in hospitalized chronic stroke patients with pulmonary infection.

  19. Resistance of neonatal mice to scrapie is associated with inefficient infection of the immature spleen.

    Science.gov (United States)

    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

  20. Effects of chronic stress on the onset and progression of Huntington's disease in transgenic mice.

    Science.gov (United States)

    Mo, Christina; Renoir, Thibault; Hannan, Anthony J

    2014-11-01

    Huntington's disease (HD) is a neurodegenerative disease caused by a tandem repeat mutation encoding an expanded polyglutamine tract. Our previous work showed that memory deficits in HD transgenic mice could be accelerated by increased levels of stress hormone, while memory in WT mice remained unaffected. HD patients experience higher levels of stress compared to the general population and symptoms of HD also include motor, cognitive, psychiatric, sexual and olfactory abnormalities, and an associated decline in activities of daily living. Therefore we investigated the impact of a robust stressor (i.e. restraint) on the onset and progression of a range of behavioral phenotypes in R6/1 transgenic HD mice. Restraint was administered for 1h daily from 6weeks of age and continued until R6/1 mice were clearly motor symptomatic at 14weeks of age. Serum corticosterone levels in both R6/1 and WT littermates were elevated immediately after the last restraint session and weight gain was suppressed in restrained animals throughout the treatment period. Motor coordination and locomotor activity were enhanced by chronic restraint in males, regardless of genotype. However, there was no effect of restraint on motor performances in female animals. At 8weeks of age, olfactory sensitivity was impaired by restraint in R6/1 HD female mice, but not in WT mice. In male R6/1 mice, the olfactory deficit was exacerbated by restraint and olfaction was also impaired in male WT mice. The development of deficits in saccharin preference, Y-maze memory, nest-building and sexually-motivated vocalizations was unaffected by chronic restraint in R6/1 and had little impact on such behavioral performances in WT animals. We provide evidence that chronic stress can negatively modulate specific endophenotypes in HD mice, while the same functions were affected to a lesser extent in WT mice. This vulnerability in HD animals seems to be sex-specific depending on the stress paradigm used. It is hoped that our

  1. The anti-infective activity of punicalagin against Salmonella enterica subsp. enterica serovar typhimurium in mice.

    Science.gov (United States)

    Li, Guanghui; Feng, Yuqing; Xu, Yunfeng; Wu, Qian; Han, Qi'an; Liang, Xiujun; Yang, Baowei; Wang, Xin; Xia, Xiaodong

    2015-07-01

    Punicalagin, a major bioactive component of pomegranate peel, has been proven to have antioxidant, antiviral, anti-apoptosis, and hepatoprotective properties. The aim of this study was to investigate the anti-infective activity of punicalagin in a mouse model. C57BL/6 mice were initially challenged with Salmonella enterica subsp. enterica serovar typhimurium (S. typhimurium) and then treated with punicalagin. Food and water consumption and body weight were recorded daily. On day 8 post infection, the mice were sacrificed to examine pathogen counts in tissues, hematological parameters, cytokine levels, and histological changes. Compared to mice only infected with S. typhimurium, punicalagin-treated mice had more food consumption and less weight loss. A higher survival rate and lower counts of viable S. typhimurium in feces, liver, spleen, and kidney were found in the punicalagin-treated mice. The enzyme linked immunosorbent assay showed that the levels of IL-6, IL-10, and IFN-γ in serum and the spleen and TNF-α in serum, the spleen and the liver were reduced by punicalagin. Moreover, more neutrophils and higher neutrophil-to-mononuclear cell ratios in the punicalagin-treated mice were observed. Histological examination showed that punicalagin protected cells in the liver and spleen from hemorrhagic necrosis. It is concluded that punicalagin has a beneficial effect against S. typhimurium infection in mice. The anti-infective properties, together with other nutritionally beneficial effects, make punicalagin a promising supplement in human food or animal feeds to prevent disease associated with S. typhimurium.

  2. Late effects of chronic low dose-rate γ-rays irradiation on mice

    International Nuclear Information System (INIS)

    To evaluate late biological effects of chronic low dose-rate radiation, the life-span and pathological changes were evaluated in mice which had been continuously irradiated with gamma-rays for 400 days. Two hundred (100 male and 100 female) specific-pathogen-free (SPF) B6C3F1 mice at six weeks of age were purchased every month. After a 2-week quarantine, they were divided into 4 groups (1 unirradiated control and 3 irradiated). Irradiation was performed using 137Cs gamma-rays at dose-rates of 20 mGy/day, 1 mGy/day and 0.05 mGy/day with accumulated doses equivalent to 8000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept until they died a natural death. Results of the monthly microbiological examinations confirmed that the mice were maintained under SPF-conditions throughout the experimental period. A total of 4000 mice have been admitted into the experiment since it started in February 1996, all of which have received their predetermined doses and have been transferred to the animal room. Data on the 20 mGy/day group of both sexes suggested a shortened life span. The most common lethal neoplasms in pooled data of unirradiated control and irradiated male mice in order of frequency were neoplasms of the lymphohematopoietic system, liver, and lung. In female mice, neoplasms of the lymphohematopoietic system, soft tissue, and endocrine system were common. (author)

  3. Targeting connexin 43 protects against the progression of experimental chronic kidney disease in mice.

    Science.gov (United States)

    Abed, Ahmed; Toubas, Julie; Kavvadas, Panagiotis; Authier, Florence; Cathelin, Dominique; Alfieri, Carlo; Boffa, Jean-Jacques; Dussaule, Jean-Claude; Chatziantoniou, Christos; Chadjichristos, Christos E

    2014-10-01

    Excessive recruitment of monocytes and progression of fibrosis are hallmarks of chronic kidney disease (CKD). Recently we reported that the expression of connexin 43 (Cx43) was upregulated in the kidney during experimental nephropathy. To investigate the role of Cx43 in the progression of CKD, we interbred RenTg mice, a genetic model of hypertension-induced CKD, with Cx43+/- mice. The renal cortex of 5-month-old RenTgCx43+/- mice showed a marked decrease of cell adhesion markers leading to reduced monocyte infiltration and interstitial renal fibrosis compared with their littermates. In addition, functional and histological parameters such as albuminuria and glomerulosclerosis were ameliorated in RenTgCx43+/- mice. Interestingly, treatment with Cx43 antisense produced remarkable improvement of renal function and structure in 1-year-old RenTg mice. Similar results were found in Cx43+/- or wild-type mice treated with Cx43 antisense after obstructive nephropathy. Furthermore, in these mice, Cx43 antisense attenuated E-cadherin downregulation and phosphorylation of the transcription factor Sp1 by the ERK pathway resulting in decreased transcription of type I collagen gene. Interestingly, Cx43-specific blocking peptide inhibited monocyte adhesion in activated endothelium and profibrotic pathways in tubular cells. Cx43 was highly increased in biopsies of patients with CKD. Thus, Cx43 may represent a new therapeutic target against the progression of CKD.

  4. Mycobacterium tuberculosis universal stress protein Rv2623 regulates bacillary growth by ATP-Binding: requirement for establishing chronic persistent infection.

    Directory of Open Access Journals (Sweden)

    Joshua E Drumm

    2009-05-01

    Full Text Available Tuberculous latency and reactivation play a significant role in the pathogenesis of tuberculosis, yet the mechanisms that regulate these processes remain unclear. The Mycobacterium tuberculosisuniversal stress protein (USP homolog, rv2623, is among the most highly induced genes when the tubercle bacillus is subjected to hypoxia and nitrosative stress, conditions thought to promote latency. Induction of rv2623 also occurs when M. tuberculosis encounters conditions associated with growth arrest, such as the intracellular milieu of macrophages and in the lungs of mice with chronic tuberculosis. Therefore, we tested the hypothesis that Rv2623 regulates tuberculosis latency. We observed that an Rv2623-deficient mutant fails to establish chronic tuberculous infection in guinea pigs and mice, exhibiting a hypervirulence phenotype associated with increased bacterial burden and mortality. Consistent with this in vivo growth-regulatory role, constitutive overexpression of rv2623 attenuates mycobacterial growth in vitro. Biochemical analysis of purified Rv2623 suggested that this mycobacterial USP binds ATP, and the 2.9-A-resolution crystal structure revealed that Rv2623 engages ATP in a novel nucleotide-binding pocket. Structure-guided mutagenesis yielded Rv2623 mutants with reduced ATP-binding capacity. Analysis of mycobacteria overexpressing these mutants revealed that the in vitro growth-inhibitory property of Rv2623 correlates with its ability to bind ATP. Together, the results indicate that i M. tuberculosis Rv2623 regulates mycobacterial growth in vitro and in vivo, and ii Rv2623 is required for the entry of the tubercle bacillus into the chronic phase of infection in the host; in addition, iii Rv2623 binds ATP; and iv the growth-regulatory attribute of this USP is dependent on its ATP-binding activity. We propose that Rv2623 may function as an ATP-dependent signaling intermediate in a pathway that promotes persistent infection.

  5. Structural changes in the jejunal mucosa of mice infected with Schistosoma mansoni, fed low or high protein diets

    OpenAIRE

    Couto Janira Lúcia Assumpção; Ferreira Haroldo da Silva; Rocha Dinalva Bezerra da; Duarte Maria Eugênia Leite; Assunção Monica Lopes; Coutinho Eridan de Medeiros

    2002-01-01

    The effects of high and low-protein diets on the structure of the jejunal mucosa were studied in Schistosoma mansoni infected mice (morphology and histomorphometry). Weaning male albino mice were infected with 80 cercariae, fed with high (20%) or low-protein (5%) diets and compared to uninfected controls under the same conditions. Mice were sacrificed 12 weeks after infection. Animals submitted to a low-protein diet showed lower weight curves, mainly when infected. In the jejunal mucosa, fing...

  6. Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice

    International Nuclear Information System (INIS)

    Trichloroethene (TCE) exacerbates the development of autoimmune responses in autoimmune-prone MRL +/+ mice. Although TCE-mediated autoimmune responses are associated with an increase in serum immunoglobulins and autoantibodies, the underlying mechanism of autoimmunity is not known. To determine the progression of TCE-mediated immunotoxicity, female MRL +/+ mice were chronically exposed to TCE through the drinking water (0.5 mg/ml of TCE) for various periods of time. Serum concentrations of antinuclear antibodies increased after 36 and 48 weeks of TCE exposure. Histopathological analyses showed lymphocyte infiltration in the livers of MRL +/+ mice exposed to TCE for 36 or 48 weeks. Lymphocyte infiltration was also apparent in the pancreas, lungs, and kidneys of mice exposed to TCE for 48 weeks. Immunoglobulin deposits in kidney glomeruli were found after 48 weeks of exposure to TCE. Our results suggest that chronic exposure to TCE promotes inflammation in the liver, pancreas, lungs, and kidneys, which may lead to SLE-like disease in MRL +/+ mice

  7. Effects of intraperitoneal injection of microencapsulated Sertoli cells on chronic and presymptomatic dystrophic mice

    Science.gov (United States)

    Chiappalupi, Sara; Luca, Giovanni; Mancuso, Francesca; Madaro, Luca; Fallarino, Francesca; Nicoletti, Carmine; Calvitti, Mario; Arato, Iva; Falabella, Giulia; Salvadori, Laura; Di Meo, Antonio; Bufalari, Antonello; Giovagnoli, Stefano; Calafiore, Riccardo; Donato, Rosario; Sorci, Guglielmo

    2015-01-01

    We report data about the effects of intraperitoneal (i.p.) injection of specific pathogen-free (SPF) porcine Sertoli cells (SeC) encapsulated into clinical grade alginate-based microcapsules (SeC-MC) on muscles of chronic and presymptomatic dystrophic, mdx mice. Mdx mouse is the best characterized animal model of Duchenne muscular dystrophy (DMD), an X-linked lethal myopathy due to mutation in the gene of dystrophin, which is crucial for myofiber integrity during muscle contraction. Our data show that three weeks after i.p. injection of SeC-MC significantly reduced adipose and fibrous tissue deposition, reduced macrophage infiltrate, and reduced numbers of damaged myofibers are found in muscles of 12-month-old mdx mice, which reproduce chronic DMD conditions. Compared with muscles of mock-treated mdx mice muscles of SeC-MC-treated mice show upregulation of the dystrophin paralogue, utrophin which is localized to the periphery of myofibers. Moreover, our data show that i.p. injection of SeC-MC into presymptomatic, 2-week-old mdx mice, although not fully preventing myofiber degeneration, results in protection against myofiber necrosis and muscle inflammation. Extensive discussion of these data can be found in Ref. [1]. PMID:26759818

  8. Effects of intraperitoneal injection of microencapsulated Sertoli cells on chronic and presymptomatic dystrophic mice

    Directory of Open Access Journals (Sweden)

    Sara Chiappalupi

    2015-12-01

    Full Text Available We report data about the effects of intraperitoneal (i.p. injection of specific pathogen-free (SPF porcine Sertoli cells (SeC encapsulated into clinical grade alginate-based microcapsules (SeC-MC on muscles of chronic and presymptomatic dystrophic, mdx mice. Mdx mouse is the best characterized animal model of Duchenne muscular dystrophy (DMD, an X-linked lethal myopathy due to mutation in the gene of dystrophin, which is crucial for myofiber integrity during muscle contraction. Our data show that three weeks after i.p. injection of SeC-MC significantly reduced adipose and fibrous tissue deposition, reduced macrophage infiltrate, and reduced numbers of damaged myofibers are found in muscles of 12-month-old mdx mice, which reproduce chronic DMD conditions. Compared with muscles of mock-treated mdx mice muscles of SeC-MC-treated mice show upregulation of the dystrophin paralogue, utrophin which is localized to the periphery of myofibers. Moreover, our data show that i.p. injection of SeC-MC into presymptomatic, 2-week-old mdx mice, although not fully preventing myofiber degeneration, results in protection against myofiber necrosis and muscle inflammation. Extensive discussion of these data can be found in Ref. [1].

  9. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    Science.gov (United States)

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia.

  10. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    Science.gov (United States)

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. PMID:26965573

  11. Chronic hepatitis E virus infection in a patient with leukemia and elevated transaminases: a case report

    Directory of Open Access Journals (Sweden)

    Gauss Annika

    2012-10-01

    Full Text Available Abstract Introduction Acute hepatitis E virus infection may cause mild, self-limiting hepatitis, either as epidemic outbreaks or sporadic cases, the latter of which have been reported in industrialized countries. Chronic infections are uncommon and have been reported in immunosuppressed patients, patients with human immunodeficiency virus infection, and patients with hematological malignancies. Case presentation A 46-year-old Caucasian man was admitted to the gastroenterology clinic with a history of increasing transaminases, persistent exhaustion, and occasional right-side abdominal pain over the course of a 6-month period. B-cell chronic lymphocytic leukemia had been diagnosed several years earlier, and the patient was treated with rituximab, pentostatin, and cyclophosphamide. A diagnostic workup ruled out autoimmune and metabolic liver disease, hepatitis A-C, and herpes virus infection. A physical examination revealed enlarged axillary lymph nodes. The results of an abdominal ultrasound examination were otherwise unremarkable. Hepatitis E virus infection was diagnosed by detection of hepatitis E virus-specific antibodies. Blood samples were positive for hepatitis E virus ribonucleic acid with high viral loads for at least 8 months, demonstrating a rare chronic hepatitis E virus infection. Sequencing and phylogenetic analysis revealed hepatitis E virus genotype 3c with homologies to other European isolates from humans and swine, indicating an autochthonous infection. Conclusions Usually, hepatitis E virus infection appears as an acute infection; rare chronic infections have been reported for transplant patients, patients with human immunodeficiency virus, and patients with hematological malignancies. The chronic nature of hepatitis E infection in our patient was most likely induced by the immunosuppressive B-cell chronic lymphocytic leukemia treatment. The differential diagnosis in patients with unexplained hepatitis should include hepatitis E

  12. Opioid tolerance in periaqueductal gray neurons isolated from mice chronically treated with morphine

    OpenAIRE

    Bagley, Elena E.; Chieng, Billy C H; Christie, MacDonald J.; Connor, Mark

    2005-01-01

    The midbrain periaqueductal gray (PAG) is a major site of opioid analgesic action, and a significant site of cellular adaptations to chronic morphine treatment (CMT). We examined μ-opioid receptor (MOP) regulation of voltage-gated calcium channel currents (ICa) and G-protein-activated K channel currents (GIRK) in PAG neurons from CMT mice.Mice were injected s.c. with 300 mg kg−1 of morphine base in a slow release emulsion three times over 5 days, or with emulsion alone (vehicles). This protoc...

  13. Rapamycin Prevents Experimental Sclerodermatous Chronic Graft-versus-Host Disease in mice

    OpenAIRE

    Belle, Ludovic; Binsfeld, Marilène; Dubois, Sophie; Hannon, Muriel; Caers, Jo; Briquet, Alexandra; MENTEN, Catherine; Beguin, Yves; Humblet-Baron, S; Baron, Frédéric

    2012-01-01

    Background: The most widely used mice model of chronic graft-versus-host disease (cGvHD) is an MHC-matched bone marrow transplantation model of sclerodermatous cGvHD. A limitation of that model is that mortality is relatively low, making difficult to study the impact of potentially therapeutic compounds. Aims: To develop a more severe model of cGVHD and to assess the impact of Rapamycin administration in that model. Results: Lethally irradiated Balb/C mice were injected with 10x106 bon...

  14. Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.

    Science.gov (United States)

    Ferns, R Bridget; Tarr, Alexander W; Hue, Stephane; Urbanowicz, Richard A; McClure, C Patrick; Gilson, Richard; Ball, Jonathan K; Nastouli, Eleni; Garson, Jeremy A; Pillay, Deenan

    2016-05-01

    HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization.

  15. Effects of prophylactic administration of bacteriophages to immunosuppressed mice infected with Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Borysowski Jan

    2009-08-01

    Full Text Available Abstract Background Bacteriophages can be successfully applied to treat infections caused by antibiotic-resistant bacteria. Until now no attempts have been undertaken to treat infections in immunosuppressed patients with phages. In this work we investigated the prophylactic efficacy of specific bacteriophages in CBA mice treated with cyclophosphamide (CP and infected with Staphylococcus aureus. Results High numbers of bacterial colony-forming units in the organs as well as elevated tumor necrosis factor and interleukin-6 serum concentrations in CP-treated and S. aureus-infected mice were significantly lowered upon application of phages. The phages markedly increased the percentage of circulating neutrophils and immature cells from the myelocytic and lymphocytic lineages in CP-treated, S. aureus-infected mice as well as of myelocytes and immature neutrophils in the bone marrow. In addition, phages stimulated in such mice generation of specific agglutinins against S. aureus. Conclusion Application of specific phages to immunosuppressed mice prior to infection with S. aureus proved very effective, suggesting a potential benefit of phage therapy in immunocompromised patients experiencing bacterial infections.

  16. Glucocorticoid treatment of MCMV infected newborn mice attenuates CNS inflammation and limits deficits in cerebellar development.

    Directory of Open Access Journals (Sweden)

    Kate Kosmac

    2013-03-01

    Full Text Available Infection of the developing fetus with human cytomegalovirus (HCMV is a major cause of central nervous system disease in infants and children; however, mechanism(s of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV.

  17. The role of helicobacter pylori infection in the pathogenesis of chronic urticaria

    International Nuclear Information System (INIS)

    Objective: To determine the prevalence of H. pylori infection in patients with idiopathic chronic urticaria (ICU) and to see if eradication of the bacterium affects the course of the urticaria. Patients and Methods: One hundred patients with idiopathic chronic urticaria and 43 healthy subjects (matched for age and sex) underwent serological testing for H. pylori infection. All patients with idiopathic chronic urticaria were examined for Helicobacter pylori infection with the /sup 13/C-urea test as well as the serological testing. Gastric biopsy was obtained from 36 patients. Patients with proven Helicobacter pylori infection were given treatment for 2 weeks. Six weeks afterwards they were tested again for Helicobacter pylori infection, and their urticaria was clinically assessed. Results: There was no significant difference in the seroprevalence of H. pylori infection between : idiopathic chronic urticaria patients and healthy subjects. Helicobacter pylori was detected in 76% of patients and 69.8% of controls. Out of the 76 patients treated, only 24 showed complete remission of their urticaria after successfully eradicating Helicobacter pylori infection, the others only having some improvement in their symptoms. Conclusion: Patients with idiopathic chronic urticaria have similar high rates of H. pylori infection as healthy subjects. Bacterium eradication is associated with improvement of urticaria symptoms, suggesting a possible role of Helicobacter pylori in the pathogenesis of this skin disorder. (author)

  18. Intrinsic and environmental mutagenesis drive diversification and persistence of Pseudomonas aeruginosa in chronic lung infections.

    Science.gov (United States)

    Rodríguez-Rojas, Alexandro; Oliver, Antonio; Blázquez, Jesús

    2012-01-01

    Pseudomonas aeruginosa is a versatile opportunistic pathogen causing a wide variety of hospital-acquired acute infections in immunocompromised patients as well as chronic respiratory infections in patients suffering from cystic fibrosis or other chronic respiratory diseases. Several traits contribute to its ability to colonize and persist in the lungs of chronically infected patients, including development of high resistance to antimicrobials and hypermutability, biofilm growth, and alginate hyperproduction, or a customized pathogenicity, which may include the loss of classical virulence factors and metabolic changes. Here we argue that a combination of both intrinsic and environmental mutagenesis leads to a high number of mutant variants in the population. The conducive environment then triggers a positive feedback loop leading to adaptation and persistence of P. aeruginosa, rendering these chronic infections almost impossible to eradicate. PMID:22080096

  19. EVALUATION OF EFFECTS OF OZONE EXPOSURE ON INFLUENZA INFECTION IN MICE USING SEVERAL INDICATORS OF SUSCEPTIBILITY (JOURNAL VERSION)

    Science.gov (United States)

    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...

  20. Murine Norovirus Infection Variably Alters Atherosclerosis in Mice Lacking Apolipoprotein E.

    Science.gov (United States)

    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

  1. Chronic hepatitis C virus infection and post-liver transplantation diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Yun Ma; Wen-Wei Yan

    2005-01-01

    Patients with chronic hepatitis C virus (HCV) infection have a significantly increased prevalence of type 2 diabetes mellitus compared to controls or HBV-infected patients.Moreover, the incidence rate of post-liver transplantation diabetes mellitus (PTDM) also appears to be higher among patients with HCV infection. PTDM is often associated with direct viral infection, autoimmune disorders, and immunosuppressive regimen. Activation of tumor necrosis factor-α may be the link between HCV infection and diabetes. In this article, we reviewed the epidemiologic association between HCV infection and PTDM, highlighting the most recent pathophysiologic insights into the mechanisms underlying this association.

  2. Antidepressant-like activity of gallic acid in mice subjected to unpredictable chronic mild stress.

    Science.gov (United States)

    Chhillar, Ritu; Dhingra, Dinesh

    2013-08-01

    This study was designed to evaluate antidepressant-like activity of gallic acid in Swiss young male albino mice subjected to unpredictable chronic mild stress and to explore the possible underlying mechanisms for this activity. Gallic acid (5, 10, 20 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) per se were administered daily to unstressed mice and other groups of mice subjected to unpredictable mild stress, 30 min after the injection for 21 successive days. The antidepressant-like activity was evaluated using forced swim test (FST) and sucrose preference test. Stress significantly increased immobility period of mice in FST. Gallic acid (10 and 20 mg/kg, i.p.) and fluoxetine significantly decreased immobility period of unstressed and stressed mice in FST and prevented the stress-induced decrease in sucrose preference, indicating significant antidepressant-like activity. There was no significant effect on locomotor activity of the mice by the drugs. Gallic acid (10 and 20 mg/kg, i.p.) significantly decreased Monoamine oxidase-A (MAO-A) activity, malondialdehyde levels, and catalase activity in unstressed mice; and significantly prevented the stress-induced decrease in reduced glutathione and catalase activity; and also significantly prevented stress-induced increase in MAO-A activity, malondialdehyde levels, plasma nitrite, and corticosterone levels. Thus, gallic acid showed antidepressant-like activity in unstressed and stressed mice probably due to its antioxidant activity and through inhibition of MAO-A activity and decrease in plasma nitrite levels. In addition, gallic acid also showed antidepressant-like activity in stressed mice probably through decrease in plasma corticosterone levels.

  3. Metabolic Manifestations and Complications Associated With Chronic Hepatitis C Virus Infection.

    Science.gov (United States)

    Wong, Robert J; Gish, Robert G

    2016-05-01

    Chronic hepatitis C virus (HCV) infection is associated with many extrahepatic manifestations that contribute to morbidity and mortality. It is especially important to be aware of metabolic manifestations and serious complications that affect other organs and cancer risks. Chronic HCV infection itself contributes to de novo development of insulin resistance and hepatic steatosis, both of which increase the risk of cardiovascular diseases. Through these metabolic pathways (as well as through other hypothesized mechanisms that involve lipid metabolism, systemic inflammatory signals, and endothelial dysfunction), chronic HCV infection also contributes to significant systemic cardiovascular morbidity and mortality. While chronic HCV infection contributes to incident development of metabolic complications, the presence of concurrent metabolic diseases also contributes to disease progression, such as higher risks of hepatocellular carcinoma and progression to advanced fibrosis, among patients with chronic HCV infection. The implications of these observations are particularly important given the rising prevalence of obesity and metabolic syndrome in the United States and worldwide. Furthermore, concurrent nonalcoholic fatty liver disease, either as a result of underlying metabolic syndrome or as a direct result of HCV-induced fatty liver disease, further complicates the management of chronic HCV-infected patients. Greater awareness is needed toward the systemic manifestations of chronic HCV infection, with focused attention on the associated metabolic manifestations and complications. Successful treatment and cure of chronic HCV infection with the currently available, highly effective antiviral therapies will significantly improve long-term outcomes among these patients. It is also important to recognize and address the associated metabolic manifestations and complications to reduce cardiovascular-related morbidity and mortality. PMID:27499712

  4. Schistosome syntenin partially protects vaccinated mice against Schistosoma mansoni infection.

    Directory of Open Access Journals (Sweden)

    Barbara C Figueiredo

    2014-08-01

    Full Text Available Schistosomiasis is a neglected tropical disease caused by several species of trematode of the genus Schistosoma. The disease affects more than 200 million people in the world and causes up to 280,000 deaths per year, besides having high morbidity due to chronic illness that damages internal organs. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control disease is a combination of drug treatment and immunization with an anti-schistosome vaccine. Among the most promising molecules as vaccine candidates are the proteins present in the tegument and digestive tract of the parasite.In this study, we describe for the first time Schistosoma mansoni syntenin (SmSynt and we evaluate its potential as a recombinant vaccine. We demonstrate by real-time PCR that syntenin is mainly expressed in intravascular life stages (schistosomula and adult worms of the parasite life cycle and, by confocal microscopy, we localize it in digestive epithelia in adult worms and schistosomula. Administration of siRNAs targeting SmSynt leads to the knock-down of syntenin gene and protein levels, but this has no demonstrable impact on parasite morphology or viability, suggesting that high SmSynt gene expression is not essential for the parasites in vitro. Mice immunization with rSmSynt, formulated with Freund's adjuvant, induces a Th1-type response, as suggested by the production of IFN-γ and TNF-α by rSmSynt-stimulated cultured splenocytes. The protective effect conferred by vaccination with rSmSynt was demonstrated by 30-37% reduction of worm burden, 38-43% reduction in the number, and 35-37% reduction in the area, of liver granulomas.Our report is the first characterization of syntenin in Schistosoma mansoni and our data suggest that this protein is a potential candidate for the development of a multi-antigen vaccine to control schistosomiasis.

  5. Chronic Hepatitis E Infection Resulting in Graft Failure in a Liver Transplant Tourist

    OpenAIRE

    Kiat-Hon Lim; Jason Pik-Eu Chang; Chee-Kiat Tan; Lynette Lin-Ean Oon; Boon-Huan Tan; Hoe-Nam Leong; Hui-Hui Tan

    2011-01-01

    Hepatitis E, usually an acute hepatitis in the immunocompetent, has a chronic form described in immunocompromised hosts. We report the clinical course and outcome of an adult liver transplant recipient whose posttransplant period was complicated by chronic hepatitis E, Epstein-Barr virus infection, and cellular rejection of the graft.

  6. Phyllanthus species versus antiviral drugs for chronic hepatitis B virus infection

    DEFF Research Database (Denmark)

    Yun, Xia; Luo, Hui; Liu, Jian Ping;

    2013-01-01

    Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists. When compared with placebo or no intervention, we were unable to identify convincing evidence that phyllanthus species...... are beneficial in patients with chronic hepatitis B. Some randomised clinical trials have compared phyllanthus species versus antiviral drugs....

  7. Mortality in patients with chronic and cleared hepatitis C viral infection: a nationwide cohort study

    DEFF Research Database (Denmark)

    Omland, Lars Haukali; Krarup, Henrik; Jepsen, Peter;

    2010-01-01

    It is unknown whether mortality differs between patients with chronic hepatitis C virus (HCV) replication and those who cleared the virus after infection. We examined the impact of chronic HCV replication on mortality among Danish patients testing positive for HCV antibodies....

  8. CHARACTERIZATION OF A CRYPTOSPORIDIUM MURIS INFECTION AND REINFECTION IN CF-1 MICE

    Science.gov (United States)

    To establish control values for circulating cells and immune associated organs over the course of a self-limiting Cryptosporidium muris infection and rechallenge infection, mice were evaluated at intervals starting before oral inoculation and ending after oocyst shedding had ceas...

  9. Protection of mice from Mycobacterium avium infection by recombinant interleukin-12.

    OpenAIRE

    Kobayashi, K; Kasama, T.; Yamazaki, J.; Hosaka, M; Katsura, T.; Mochizuki, T; Soejima, K; Nakamura, R M

    1995-01-01

    Treatment with interleukin-12 (IL-12) significantly reduced the number of viable bacteria in mice infected with Mycobacterium avium. IL-12 itself, however, could not inhibit directly mycobacterial growth in vitro. IL-12 exerts antimycobacterial activity in vivo with a low level of toxicity, possibly by enhancing the host defense against the infection.

  10. Health implications of chronic hepatosplenomegaly in Kenyan school-aged children chronically exposed to malarial infections and Schistosoma mansoni

    DEFF Research Database (Denmark)

    Wilson, Shona; Vennervald, Birgitte J; Kadzo, Hilda;

    2010-01-01

    Hepatosplenomegaly among school-aged children in sub-Saharan Africa is highly prevalent. Two of the more common aetiological agents of hepatosplenomegaly, namely chronic exposure to malaria and Schistosoma mansoni infection, can result in similar clinical presentation, with the liver and spleen b...

  11. Phenotypes selected during chronic lung infection in cystic fibrosis patients: implications for the treatment of Pseudomonas aeruginosa biofilm infections.

    Science.gov (United States)

    Ciofu, Oana; Mandsberg, Lotte F; Wang, Hengzhuang; Høiby, Niels

    2012-07-01

    During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated by genetic variation. Mucoidy, hypermutability and acquirement of mutational antibiotic resistance are important adaptive phenotypes that are selected during chronic P. aeruginosa infection. This review dicsusses the role played by these phenotypes for the tolerance of biofilms to antibiotics and show that mucoidy and hypermutability change the architecture of in vitro formed biofilms and lead to increase tolerance to antibiotics. Production of high levels of beta-lactamase impairs penetration of beta-lactam antibiotics due to inactivation of the antibiotic. In conclusion, these data underline the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis.

  12. Effects of intraperitoneal injection of microencapsulated Sertoli cells on chronic and presymptomatic dystrophic mice

    OpenAIRE

    Sara Chiappalupi; Giovanni De Luca; Francesca Mancuso; Luca Madaro; Francesca Fallarino; Carmine Nicoletti; Mario Calvitti; Iva Arato; Giulia Falabella; Laura Salvadori; Antonio Di Meo; Antonello Bufalari; Stefano Giovagnoli; Riccardo Calafiore; Rosario Donato

    2015-01-01

    We report data about the effects of intraperitoneal (i.p.) injection of specific pathogen-free (SPF) porcine Sertoli cells (SeC) encapsulated into clinical grade alginate-based microcapsules (SeC-MC) on muscles of chronic and presymptomatic dystrophic, mdx mice. Mdx mouse is the best characterized animal model of Duchenne muscular dystrophy (DMD), an X-linked lethal myopathy due to mutation in the gene of dystrophin, which is crucial for myofiber integrity during muscle contraction. Our data ...

  13. Modeling PD pathogenesis in mice: advantages of a chronic MPTP protocol

    OpenAIRE

    Meredith, Gloria E.; Totterdell, Susan; Potashkin, Judith A.; Surmeier, D. James

    2008-01-01

    Formidable challenges for Parkinson's disease (PD) research are to understand the processes underlying nigrostriatal degeneration and how to protect the dopamine neurons. Fundamental research relies on good animal models that demonstrate the pathological hallmarks and motor deficits of PD. Using a chronic regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTP/p) in mice, dopamine cell loss exceeds 60%, extracellular glutamate is elevated, cytoplasmic inclusions are forme...

  14. Essential role for telomerase in chronic myeloid leukemia induced by BCR-ABL in mice

    OpenAIRE

    Vicente-Dueñas, Carolina; Barajas-Diego, Marcos; Romero-Camarero, Isabel; González-Herrero, Inés; Flores, Teresa; Sánchez García, Isidro

    2012-01-01

    The telomerase protein is constitutively activated in malignant cells from many patients with cancer, including the chronic myeloid leukemia (CML), but whether telomerase is essential for the pathogenesis of this disease is not known. Here, we used telomerase deficient mice to determine the requirement for telomerase in CML induced by BCR-ABL in mouse models of CML. Loss of one telomerase allele or complete deletion of telomerase prevented the development of leukemia induced by BCR-ABL. Howev...

  15. The Acute Phase of Trypanosoma cruzi Infection Is Attenuated in 5-Lipoxygenase-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Adriana M. C. Canavaci

    2014-01-01

    Full Text Available In the present work we examine the contribution of 5-lipoxygenase- (5-LO- derived lipid mediators to immune responses during the acute phase of Trypanosoma cruzi infection in 5-LO gene knockout (5-LO−/− mice and wild-type (WT mice. Compared with WT mice, the 5-LO−/− mice developed less parasitemia/tissue parasitism, less inflammatory cell infiltrates, and a lower mortality. This resistance of 5-LO−/− mice correlated with several differences in the immune response to infection, including reduced PGE2 synthesis; sustained capacity of splenocytes to produce high levels of interleukin (IL-12 early in the infection; enhanced splenocyte production of IL-1β, IL-6, and IFN-γ; rapid T-cell polarization to secrete high quantities of IFN-γ and low quantities of IL-10; and greater numbers of CD8+CD44highCD62Llow memory effector T cells at the end of the acute phase of infection. The high mortality in WT mice was associated with increased production of LTB4/LTC4, T cell bias to produce IFN-γ, high levels of serum nitrite, and marked protein extravasation into the peritoneal cavity, although survival was improved by treatment with a cys-LT receptor 1 antagonist. These data also provide evidence that 5-LO-derived mediators negatively affect host survival during the acute phase of T. cruzi infection.

  16. Surfactant protein C-deficient mice are susceptible to respiratory syncytial virus infection.

    Science.gov (United States)

    Glasser, Stephan W; Witt, Teah L; Senft, Albert P; Baatz, John E; Folger, Dusti; Maxfield, Melissa D; Akinbi, Henry T; Newton, Danforth A; Prows, Daniel R; Korfhagen, Thomas R

    2009-07-01

    Patients with mutations in the pulmonary surfactant protein C (SP-C) gene develop interstitial lung disease and pulmonary exacerbations associated with viral infections including respiratory syncytial virus (RSV). Pulmonary infection with RSV caused more severe interstitial thickening, air space consolidation, and goblet cell hyperplasia in SP-C-deficient (Sftpc(-/-)) mice compared with SP-C replete mice. The RSV-induced pathology resolved more slowly in Sftpc(-/-) mice with lung inflammation persistent up to 30 days postinfection. Polymorphonuclear leukocyte and macrophage counts were increased in the bronchoalveolar lavage (BAL) fluid of Sftpc(-/-) mice. Viral titers and viral F and G protein mRNA were significantly increased in both Sftpc(-/-) and heterozygous Sftpc(+/-) mice compared with controls. Expression of Toll-like receptor 3 (TLR3) mRNA was increased in the lungs of Sftpc(-/-) mice relative to Sftpc(+/+) mice before and after RSV infection. Consistent with the increased TLR3 expression, BAL inflammatory cells were increased in the Sftpc(-/-) mice after exposure to a TLR3-specific ligand, poly(I:C). Preparations of purified SP-C and synthetic phospholipids blocked poly(I:C)-induced TLR3 signaling in vitro. SP-C deficiency increases the severity of RSV-induced pulmonary inflammation through regulation of TLR3 signaling. PMID:19304906

  17. Parasitological characteristics of Schistosoma mansoni infection in swiss mice with underlying malnutrition

    Directory of Open Access Journals (Sweden)

    Simões Carla

    2002-01-01

    Full Text Available The effects of a protein-restricted diet (8% protein, 81% carbohydrate and 11% lipids on Schistosoma mansoni infectivity, fecal egg excretion and intestinal egg distribution in Swiss (SW mice were studied. Pregnant mice received a deficient diet from the middle of gestation until delivery. Seven-days-old mice were exposed to 50 cercariae (BH strain, Brazil. Offspring mice had a free access to the deficient diet since lactation until adulthood. The controls were fed with a commercial mice diet. A parasitological examination was performed between six and eight weeks post-infection while both groups were necropsied one week later. Mice on the experimental diet showed a significant loss in body weight. There was no significant difference (p > 0.05 in pre-patent period, kinetics of egg excretion and worm recovery from mice on either diet. Significant differences (p < 0.05 were found concerning to the percentage of deposited eggs in the distal segment of the small intestine from hosts on the experimental diet.Our data suggest that experimental malnutrition induced for a long term has no detrimental effect on the acute schistosomiais infection in SW mice.

  18. Chronic hepcidin induction causes hyposideremia and alters the pattern of cellular iron accumulation in hemochromatotic mice.

    Science.gov (United States)

    Viatte, Lydie; Nicolas, Gaël; Lou, Dan-Qing; Bennoun, Myriam; Lesbordes-Brion, Jeanne-Claire; Canonne-Hergaux, François; Schönig, Kai; Bujard, Hermann; Kahn, Axel; Andrews, Nancy C; Vaulont, Sophie

    2006-04-01

    We report the generation of a tetracycline-regulated (Tet ON) transgenic mouse model for acute and chronic expression of the iron regulatory peptide hepcidin in the liver. We demonstrate that short-term and long-term tetracycline-dependent activation of hepcidin in adult mice leads to hypoferremia and iron-limited erythropoiesis, respectively. This clearly establishes the key role of hepcidin in regulating the extracellular iron concentration. We previously demonstrated that, when expressed early in fetal development, constitutive transgenic hepcidin expression prevented iron accumulation in an Hfe-/- mouse model of hemochromatosis. We now explore the effect of chronic hepcidin expression in adult Hfe-/- mice that have already developed liver iron overload. We demonstrate that induction of chronic hepcidin expression in 2-month-old Hfe-/- mice alters their pattern of cellular iron accumulation, leading to increased iron in tissue macrophages and duodenal cells but less iron in hepatocytes. These hepcidin-induced changes in the pattern of cellular iron accumulation are associated with decreased expression of the iron exporter ferroportin in macrophages but no detectable alteration of ferroportin expression in the hepatocytes. We speculate that this change in iron homeostasis could offer a therapeutic advantage by protecting against damage to parenchymal cells. PMID:16339398

  19. Inhibitory effects of sunitinib on ovalbumin-induced chronic experimental asthma in mice

    Institute of Scientific and Technical Information of China (English)

    HUANG Mao; LIU Xuan; DU Qiang; YAO Xin; YIN Kai-sheng

    2009-01-01

    Background Tyrosine kinase signaling cascades play a critical role in the pathogenesis of allergic airway inflammation. Sunitinib, a multitargeted receptor tyrosine kinase inhibitor, has been reported to exert potent immunoregulatory, anti-inflammatory and anti-fibrosis effects. We investigated whether sunitinib could suppress the progression of airway inflammation, airway hyperresponsiveness (AHR), and airway remodeling in a murine model of chronic asthma. Methods Ovalbumin (OVA)-sensitized mice were chronically challenged with aerosolized OVA for 8 weeks. Some mice were intragastrically administered with sunitinib (40 mg/kg) daily during the period of OVA challenge. Twelve hours after the last OVA challenge, mice were evaluated for the development of airway inflammation, AHR and airway remodeling. The levels of total serum immunoglobulin E (IgE) and Th2 cytokines (interieukin (IL)-4 and IL-13) in bronchoalveolar lavage fluid (BALF) were measured by ELISA. The expression of phosphorylated c-kit protein in the lungs was detected by immunoprecipitation/Western blotting (IP/WB) analysis.Results Sunitinib significantly inhibited eosinophilic airway inflammation, persistent AHR and airway remodeling in chronic experimental asthma. It reduced levels of total serum IgE and BALF Th2 cytokines and also lowered the expression of phosphorylated c-kit protein in remodelled airways.Conclusions Sunitinib may inhibit the development of airway inflammation, AHR and airway remodeling. It is potentially beneficial to the prevention or treatment of asthma.

  20. Hypericum perforatum treatment: effect on behaviour and neurogenesis in a chronic stress model in mice

    Directory of Open Access Journals (Sweden)

    Cuzzocrea Salvatore

    2011-01-01

    Full Text Available Abstract Background Extracts of Hypericum perforatum (St. John's wort have been traditionally recommended for a wide range of medical conditions, in particular mild-to-moderate depression. The present study was designed to investigate the effect of Hypericum perforatum treatment in a mouse model of anxiety/depressive-like behavior, induced by chronic corticosterone administration. Methods CD1 mice were submitted to 7 weeks corticosterone administration and then behavioral tests as Open Field (OF, Novelty-Suppressed Feeding (NSF, Forced Swim Test (FST were performed. Cell proliferation in hippocampal dentate gyrus (DG was investigated by both 5-bromo-2'-deoxyuridine (BrdU and doublecortin (DCX immunohistochemistry techniques and stereological procedure was used to quantify labeled cells. Golgi-impregnation method was used to evaluate changes in dendritic spines in DG. Hypericum perforatum (30 mg/Kg has been administered for 3 weeks and then neural development in the adult hippocampus and behavioral changes have been examined. Results The anxiety/depressive-like state due to chronic corticosterone treatment was reversed by exogenous administration of Hypericum perforatum; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment, whereas a long term treatment with Hypericum perforatum prevented the corticosterone-induced decrease in hippocampal cell proliferation. Corticosterone-treated mice exhibited a reduced spine density that was ameliorated by Hypericum perforatum administration. Conclusion These results provide evidence of morphological adaptations occurring in mature hippocampal neurons that might underlie resilient responses to chronic stress and contribute to the therapeutic effects of chronic Hypericum perforatum treatment.

  1. Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice

    Science.gov (United States)

    Udoh, Uduak S.; Swain, Telisha M.; Filiano, Ashley N.; Gamble, Karen L.; Young, Martin E.

    2015-01-01

    Chronic ethanol consumption has been shown to significantly decrease hepatic glycogen content; however, the mechanisms responsible for this adverse metabolic effect are unknown. In this study, we examined the impact chronic ethanol consumption has on time-of-day-dependent oscillations (rhythms) in glycogen metabolism processes in the liver. For this, male C57BL/6J mice were fed either a control or ethanol-containing liquid diet for 5 wk, and livers were collected every 4 h for 24 h and analyzed for changes in various genes and proteins involved in hepatic glycogen metabolism. Glycogen displayed a robust diurnal rhythm in the livers of mice fed the control diet, with the peak occurring during the active (dark) period of the day. The diurnal glycogen rhythm was significantly altered in livers of ethanol-fed mice, with the glycogen peak shifted into the inactive (light) period and the overall content of glycogen decreased compared with controls. Chronic ethanol consumption further disrupted diurnal rhythms in gene expression (glycogen synthase 1 and 2, glycogenin, glucokinase, protein targeting to glycogen, and pyruvate kinase), total and phosphorylated glycogen synthase protein, and enzyme activities of glycogen synthase and glycogen phosphorylase, the rate-limiting enzymes of glycogen metabolism. In summary, these results show for the first time that chronic ethanol consumption disrupts diurnal rhythms in hepatic glycogen metabolism at the gene and protein level. Chronic ethanol-induced disruption in these daily rhythms likely contributes to glycogen depletion and disruption of hepatic energy homeostasis, a recognized risk factor in the etiology of alcoholic liver disease. PMID:25857999

  2. In Vivo Antiprotozoal Activity of the Chloroform Extract from Carica papaya Seeds against Amastigote Stage of Trypanosoma cruzi during Indeterminate and Chronic Phase of Infection

    Directory of Open Access Journals (Sweden)

    Matilde Jimenez-Coello

    2014-01-01

    Full Text Available In order to evaluate the antiprotozoal activity of the chloroform extract of Carica papaya seeds during the subacute and chronic phase of infection of Trypanosoma cruzi, doses of 50 and 75 mg/kg were evaluated during the subacute phase, including a mixture of their main components (oleic, palmitic, and stearic acids. Subsequently, doses of 50 and 75 mg/kg in mice during the chronic phase of infection (100 dpi were also evaluated. It was found that chloroform extract was able to reduce the amastigote nests numbers during the subacute phase in 55.5 and 69.7% (P > 0.05 as well as in 56.45% in animals treated with the mixture of fatty acids. Moreover, the experimental groups treated with 50 and 75 mg/kg during the chronic phase of the infection showed a significant reduction of 46.8 and 53.13% respectively (P < 0.05. It is recommended to carry out more studies to determine if higher doses of chloroformic extract or its administration in combination with other antichagasic drugs allows a better response over the intracellular stage of T. cruzi in infected animal models and determine if the chloroform extract of C. papaya could be considered as an alternative for treatment during the indeterminate and chronic phase of the infection.

  3. Evolution of sarcoma 180 (ascitic tumor in mice infected with Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Fausto Edmundo Lima Pereira

    1986-03-01

    Full Text Available Mice infected with 60 cercariae of Schistosoma mansoni were more resistant to the sarcoma 180 ascites tumor. Tumor inoculation was performed 50 days after schistosoma infection and the animals were observed and weighed at 48 hours intervals for development and progression of malignancy. In infected mice the weight gain (ascites formation started later and was shorter than in uninfected Controls. Also, the number of tumor cells into the peritoneal cavity 72h after tumor implantation was shorter in infected group than incontrols. This in creased resistance against a transplantable tumor probably is related to the effect of endotoxin on tumoricidal activity of macrophages activated by the infection. The immunodepression induced by Schistosoma mansoni infection enhances the proliferation of endogenous bacteria increasing the amount of endotoxin absorbed from the gut.

  4. Outcome of urogenital infection with Chlamydia muridarum in CD-14 gene knockout mice

    Directory of Open Access Journals (Sweden)

    Ramsey Kyle H

    2006-09-01

    Full Text Available Abstract Background CD14 has been postulated to play a role in chlamydial immunity and immunopathology. There is evidence to support this role in human infections but its function in a mouse model has not been investigated. Methods Female CD14 gene knockout and C57BL/6J wild type mice were infected intravaginally with Chlamydia muridarum. The infection course was monitored by detection of viable chlamydiae from serially collected cervical-vaginal swabs. The sequela of tubal factor infertility was assessed using hydrosalpinx formation as a surrogate marker. Results A significantly abbreviated infection course was observed in the CD14 gene knockout mice but hydrosalpinx formation occurred at similar rates between the two groups. Conclusion Involvement of CD14 during chlamydial infection impedes infection resolution but this does not affect the sequela of infertility as assessed by hydrosalpinx formation.

  5. Experimental infection of mice with hamster parvovirus: evidence for interspecies transmission of mouse parvovirus 3.

    Science.gov (United States)

    Christie, Rachel D; Marcus, Emily C; Wagner, April M; Besselsen, David G

    2010-04-01

    Hamster parvovirus (HaPV) was isolated 2 decades ago from hamsters with clinical signs similar to those induced in hamsters experimentally infected with other rodent parvoviruses. Genetically, HaPV is most closely related to mouse parvovirus (MPV), which induces subclinical infection in mice. A novel MPV strain, MPV3, was detected recently in naturally infected mice, and genomic sequence analysis indicates that MPV3 is almost identical to HaPV. The goal of the present studies was to examine the infectivity of HaPV in mice. Neonatal and weanling mice of several mouse strains were inoculated with HaPV. Tissues, excretions, and sera were harvested at 1, 2, 4, and 8 wk after inoculation and evaluated by quantitative PCR and serologic assays specific for HaPV. Quantitative PCR detected viral DNA quantities that greatly exceeded the quantity of virus in inocula in multiple tissues of infected mice. Seroconversion to both nonstructural and structural viral proteins was detected in most immunocompetent mice 2 or more weeks after inoculation with HaPV. In neonatal SCID mice, viral transcripts were detected in lymphoid tissues by RT-PCR and viral DNA was detected in feces by quantitative PCR at 8 wk after inoculation. No clinical signs, gross, or histologic lesions were observed. These findings are similar to those observed in mice infected with MPV. These data support the hypothesis that HaPV and MPV3 are likely variants of the same viral species, for which the mouse is the natural rodent host with rare interspecies transmission to the hamster.

  6. Distribution of rabies virus in infected mice, vaccinated and submitted to P. acnes as immunomodulator.

    Science.gov (United States)

    Megid, J; Cremonini, D N; Leomil, H

    2002-07-01

    The lethality and distribution of rabies virus were evaluated in swiss mice experimentally infected with street rabies virus, vaccinated and submitted to immunomodulation by P .acnes (formerly Corynebacterium parvum). The animals were sacrificed at different times,when the different tissues were collected and submitted to fluorescent antibody test (FAT) and mouse inoculation test (MIT). The group submitted to vaccination and P. acnes treatment presented a percentage of survival superior to that observed in infected mice only treated with P. acnes. Control infected animals had the lowest survival rates. The distribution of rabies virus in spleen of infected mice, vaccinated and submitted to P. acnes was superior to that verified in infected mice not treated with P.acnes. The increased survival correlated with the distribution of rabies virus in lymphoid tissues, could be interpreted as the consequence of P. acnes activity on macrophages. The results suggest the role of macrophages against rabies virus infection in mice and the importance of vaccination in the post expositive treatment of rabies. PMID:12135238

  7. Risk of Infections in Patients with Chronic Diseases

    DEFF Research Database (Denmark)

    Mor, Anil; Thomsen, Reimar W.

    2013-01-01

    This review provides an update on the risk of several important community-acquired infections seen in patients with diabetes: respiratory tract infections, urinary tract infections, and bacteremia. Respiratory tract infections: Recent epidemiological evidence shows a modest (1.25 to 1.75-fold) risk...... tuberculosis. Limited data is available for diabetes and influenza, yet both influenza and pneumococcal vaccination is recommended in patients with diabetes. Urinary tract infections: The risk of asymptomatic bacteriuria and cystitis is 1.5 to 2 times increased in diabetes patients, while their risk of...... bacteremia. Conclusions: Increased infection surveillance and unmeasured confounding factors among diabetic patients may contribute to the observed increased infection risk, yet outcomes following infection are similar or worse in diabetes patients. In conclusion, there is epidemiological evidence that...

  8. Invasive Aspergillus infections in hospitalized patients with chronic lung disease

    Directory of Open Access Journals (Sweden)

    Wessolossky M

    2013-05-01

    Full Text Available Mireya Wessolossky,1 Verna L Welch,2 Ajanta Sen,1 Tara M Babu,1 David R Luke21Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, MA, USA; 2Medical Affairs, Pfizer Inc, Collegeville, PA, USABackground: Although invasive pulmonary aspergillosis (IPA is more prevalent in immunocompromised patients, critical care clinicians need to be aware of the occurrence of IPA in the nontraditional host, such as a patient with chronic lung disease. The purpose of this study was to describe the IPA patient with chronic lung disease and compare the data with that of immunocompromised patients.Methods: The records of 351 patients with Aspergillus were evaluated in this single-center, retrospective study for evidence and outcomes of IPA. The outcomes of 57 patients with chronic lung disease and 56 immunocompromised patients were compared. Patients with chronic lung disease were defined by one of the following descriptive terms: emphysema, asthma, idiopathic lung disease, bronchitis, bronchiectasis, sarcoid, or pulmonary leukostasis.Results: Baseline demographics were similar between the two groups. Patients with chronic lung disease were primarily defined by emphysema (61% and asthma (18%, and immunocompromised patients primarily had malignancies (27% and bone marrow transplants (14%. A higher proportion of patients with chronic lung disease had a diagnosis of IPA by bronchoalveolar lavage versus the immunocompromised group (P < 0.03. The major risk factors for IPA were found to be steroid use in the chronic lung disease group and neutropenia and prior surgical procedures in the immunocompromised group. Overall, 53% and 69% of chronic lung disease and immunocompromised patients were cured (P = 0.14; 55% of chronic lung patients and 47% of immunocompromised patients survived one month (P = 0.75.Conclusion: Nontraditional patients with IPA, such as those with chronic lung disease, have outcomes and mortality similar to that in the

  9. Sleep loss and the inflammatory response in mice under chronic environmental circadian disruption.

    Directory of Open Access Journals (Sweden)

    Allison J Brager

    Full Text Available Shift work and trans-time zone travel lead to insufficient sleep and numerous pathologies. Here, we examined sleep/wake dynamics during chronic exposure to environmental circadian disruption (ECD, and if chronic partial sleep loss associated with ECD influences the induction of shift-related inflammatory disorder. Sleep and wakefulness were telemetrically recorded across three months of ECD, in which the dark-phase of a light-dark cycle was advanced weekly by 6 h. A three month regimen of ECD caused a temporary reorganization of sleep (NREM and REM and wake processes across each week, resulting in an approximately 10% net loss of sleep each week relative to baseline levels. A separate group of mice were subjected to ECD or a regimen of imposed wakefulness (IW aimed to mimic sleep amounts under ECD for one month. Fos-immunoreactivity (IR was quantified in sleep-wake regulatory areas: the nucleus accumbens (NAc, basal forebrain (BF, and medial preoptic area (MnPO. To assess the inflammatory response, trunk blood was treated with lipopolysaccharide (LPS and subsequent release of IL-6 was measured. Fos-IR was greatest in the NAc, BF, and MnPO of mice subjected to IW. The inflammatory response to LPS was elevated in mice subjected to ECD, but not mice subjected to IW. Thus, the net sleep loss that occurs under ECD is not associated with a pathological immune response.

  10. Chronic fluoride exposure-induced testicular toxicity is associated with inflammatory response in mice.

    Science.gov (United States)

    Wei, Ruifen; Luo, Guangying; Sun, Zilong; Wang, Shaolin; Wang, Jundong

    2016-06-01

    Previous studies have indicated that fluoride (F) can affect testicular toxicity in humans and rodents. However, the mechanism underlying F-induced testicular toxicity is not well understood. This study was conducted to evaluate the sperm quality, testicular histomorphology and inflammatory response in mice followed F exposure. Healthy male mice were randomly divided into four groups with sodium fluoride (NaF) at 0, 25, 50, 100 mg/L in the drinking water for 180 days. At the end of the exposure, significantly increased percentage of spermatozoa abnormality was found in mice exposed to 50 and 100 mg/L NaF. Disorganized spermatogenic cells, vacuoles in seminiferous tubules and loss and shedding of sperm cells were also observed in the NaF treated group. In addition, chronic F exposure increased testicular interleukin-17(IL-17), interleukin-17 receptor C (IL-17RC), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in transcriptional levels, as well as IL-17 and TNF-α levels in translational levels. Interestingly, we observed that F treated group elevated testicular inducible nitric oxide synthase (iNOS) mRNA level and nitric oxide (NO) concentration. Taken together, these results indicated that testicular inflammatory response could contribute to chronic F exposure induced testicular toxicity in mice.

  11. Lycorine reduces mortality of human enterovirus 71-infected mice by inhibiting virus replication

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    Qin Chuan

    2011-10-01

    Full Text Available Abstract Human enterovirus 71 (EV71 infection causes hand, foot and mouth disease in children under 6 years old and this infection occasionally induces severe neurological complications. No vaccines or drugs are clinical available to control EV71 epidemics. In present study, we show that treatment with lycorine reduced the viral cytopathic effect (CPE on rhabdomyosarcoma (RD cells by inhibiting virus replication. Analysis of this inhibitory effect of lycorine on viral proteins synthesis suggests that lycorine blocks the elongation of the viral polyprotein during translation. Lycorine treatment of mice challenged with a lethal dose of EV71 resulted in reduction of mortality, clinical scores and pathological changes in the muscles of mice, which were achieved through inhibition of viral replication. When mice were infected with a moderate dose of EV71, lycorine treatment was able to protect them from paralysis. Lycorine may be a potential drug candidate for the clinical treatment of EV71-infected patients.

  12. Experimental foreign body infections in mice challenged with slime-producing Staphylococcus epidermidis.

    OpenAIRE

    Christensen, G D; Simpson, W A; Bisno, A L; Beachey, E H

    1983-01-01

    The virulence of two previously described Staphylococcus epidermidis strains was examined in an experimental model of foreign body infection in mice. Animals challenged with the slime-producing strain developed three times as many infections as animals challenged with the strain that did not produce slime (P less than 0.001). Bacterial isolates recovered from the infected sites retained the characteristics of the inoculated strain. Animals without foreign bodies but challenged in a similar ma...

  13. Heme oxygenase-1 regulates the immune response to influenza virus infection and vaccination in aged mice

    OpenAIRE

    Cummins, Nathan W.; Weaver, Eric A.; May, Shannon M.; Croatt, Anthony J.; Foreman, Oded; Kennedy, Richard B.; Poland, Gregory A.; Michael A. Barry; Nath, Karl A.; Badley, Andrew D.

    2012-01-01

    Underlying mechanisms of individual variation in severity of influenza infection and response to vaccination are poorly understood. We investigated the effect of reduced heme oxygenase-1 (HO-1) expression on vaccine response and outcome of influenza infection. HO-1-deficient and wild-type (WT) mice (kingdom, Animalia; phylum, Chordata; genus/species, Mus musculus) were infected with influenza virus A/PR/8/34 with or without prior vaccination with an adenoviral-based influenza vaccine. A genom...

  14. Late effects of chronic low dose-rate γ-rays irradiation on mice

    International Nuclear Information System (INIS)

    To evaluate late biological effects of chronic low dose-rate radiation, the life-span and pathological changes were evaluated in mice that were continuously irradiated with gamma-rays for 400 days. Two hundred (100 male and 100 female) specific-pathogen-free (SPF) B6C3F1 mice at six weeks of age were purchased every month. After a 2-week quarantine, they were divided into 4 groups (1 unirradiated control and 3 irradiated). Irradiation was performed using 137Cs gamma-rays at dose-rates of 20 mGy (22 h-day)-1, 1 mGy (22 h-day)-1 and 0.05 mGy (22 h-day)''-1 with accumulated doses equivalent to 8,000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept until they died a natural death. Results of the monthly microbiological examinations confirmed that the mice were maintained under SPF-conditions throughout the experimental period. A total of 4,000 mice have been admitted into the experiment since it started in February 1996, all of which have received their predetermined doses and have been transferred to the animal room. Data on the 20 mGy (22 h-day)-1 group of both sexes suggested a shortened life span. The most common lethal neoplasms in pooled data of unirradiated control male mice and irradiated male mice in order of frequency were neoplasms of the lymphohematopoietic system, liver, lung, and soft tissue. In female mice, neoplasms of the lymphohematopoietic system, soft tissue, endocrine system, and liver were most common. (author)

  15. Use of a safe, reproducible, and rapid aerosol delivery method to study infection by Burkholderia pseudomallei and Burkholderia mallei in mice.

    Directory of Open Access Journals (Sweden)

    Eric R Lafontaine

    Full Text Available 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

  16. Use of a safe, reproducible, and rapid aerosol delivery method to study infection by Burkholderia pseudomallei and Burkholderia mallei in mice.

    Science.gov (United States)

    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

  17. Use of a safe, reproducible, and rapid aerosol delivery method to study infection by Burkholderia pseudomallei and Burkholderia mallei in mice.

    Science.gov (United States)

    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

  18. Is chronic hepatitis C virus infection a risk factor for breast cancer?

    Institute of Scientific and Technical Information of China (English)

    Dominique; Larrey; Marie-Cécile; Bozonnat; Ihab; Kain; Georges-Philippe; Pageaux; Eric; Assenat

    2010-01-01

    AIM:To evaluate the prevalence of breast tumors in adult females with chronic hepatitis C virus(HCV) infection.METHODS:Prospective,single-center study,based on female outpatients consulting in a liver unit,for 1 year.The study group included females with present and/or past history of chronic infection by HCV.Patients with spontaneous recovery were excluded.Chronic hepatitis had been proved by liver biopsy in the majority of cases and/or biological markers of inflammation and fibrosis.The control group incl...

  19. Does bovine besnoitiosis affect the sexual function of chronically infected bulls?

    Science.gov (United States)

    Esteban-Gil, A; Jacquiet, P; Florentin, S; Decaudin, A; Berthelot, X; Ronsin, P; Grisez, C; Prevot, F; Alzieu, J P; Marois, M; Corboz, N; Peglion, M; Vilardell, C; Liénard, E; Bouhsira, E; Castillo, J A; Franc, M; Picard-Hagen, N

    2016-09-15

    Bovine besnoitiosis is a reemerging disease in Europe. The clinically Besnoitia besnoiti infection in bulls is characterized by fever, nasal discharge, and orchitis in the acute phase and by scleroderma in the chronic phase. However, in many bulls, B besnoiti infection remains at a subclinical stage. Bull infertility is an economically relevant consequence of besnoitiosis infection. It is not clear, however, if semen quality returns to normal levels when infected animals have clinically recovered. The aim of this study was to examine the relationship between chronic besnoitiosis and bull sexual function in a region of eastern France, where the disease is reemerging, by comparing semen quality and genital lesions in 11 uninfected, 17 subclinically infected, and 12 clinically infected bulls. The presence of anti-B besnoiti antibodies was detected by Western blot test. Semen was collected by electroejaculation. Bulls clinically infected with B besnoiti showed significantly more genital tract alterations than uninfected or subclinically infected bulls. No relationship was evidenced between besnoitiosis infectious status and semen quality, whereas a significant relationship was noted between genital lesions and semen score. This means that in the absence of moderate to severe genital lesions, chronic bovine besnoitiosis is unlikely to alter semen quality. However, as the presence of infected animals could lead to spread of the disease, culling or separation of clinically infected bulls from the remaining healthy animals is strongly recommended. PMID:27264738

  20. Pattern recognition receptor responses in children with chronic hepatitis B virus infection

    DEFF Research Database (Denmark)

    Heiberg, Ida Louise; Winther, Thilde Nordmann; Paludan, Søren Riis;

    2012-01-01

    Several studies have demonstrated that hepatitis B virus (HBV) affects the expression and function of Toll like receptors (TLRs), but data on TLR function in HBV infection are mainly from adult patients. The natural history of chronic hepatitis B (CHB) infection is distinctly different in children...

  1. Shared immune and repair markers during experimental toxoplasma chronic brain infection and schizophrenia

    NARCIS (Netherlands)

    J.J. Tomasik (Jakub); T.L. Schultz (Tracey L.); W. Kluge (Wolfgang); R.H. Yolken (Robert H.); S. Bahn (Sabine); V.B. Carruthers (Vern B.)

    2016-01-01

    textabstractChronic neurologic infection with Toxoplasma gondii is relatively common in humans and is one of the strongest known risk factors for schizophrenia. Nevertheless, the exact neuropathological mechanisms linking T gondii infection and schizophrenia remain unclear. Here we utilize a mouse m

  2. 77 FR 30293 - Recommendations for the Identification of Hepatitis C Virus (HCV) Chronic Infection

    Science.gov (United States)

    2012-05-22

    ... chronic infection, which places infected persons at risk for liver cirrhosis, liver cancer or... liver disease that ranges in severity from a mild illness lasting a few weeks to a serious, lifelong... health services to prevent additional harm to the liver (e.g., hepatitis A virus and hepatitis B...

  3. Recurrent Burkholderia Infection in Patients with Chronic Granulomatous Disease: 11-Year Experience at a Large Referral Center

    OpenAIRE

    Greenberg, David E.; Goldberg, Joanna B.; Stock, Frida; Murray, Patrick R.; Holland, Steven M.; LiPuma, John J.

    2009-01-01

    The epidemiology of Burkholderia infection in persons with chronic granulomatous disease is poorly understood. We used species-specific polymerase chain reaction–based assays and genotyping analyses to identify 32 strains representing 9 Burkholderia species among 50 isolates recovered from 18 patients with chronic granulomatous disease. We found that recurrent pulmonary infection with distinct Burkholderia strains is common in chronic granulomatous disease.

  4. Effect of infection by irradiated Trichinella Spirals larvae on mice and assessment the role of Al bendazole in treating them

    International Nuclear Information System (INIS)

    The present study was carried out to investigate the effect of infection with irradiated Trichinella Spiralis larvae on mice and to asses the role of albendazole in treating them. This study included parasitological and histopathological studies on mice infected with irradiated Trichinella Spiralis larvae in comparison with mice infected with non-irradiated Trichinella Spiralis only or with mice treated after infection by albendazole. The obtained data revealed that, in mice infected with irradiated Trichinella Spiralis larvae (50 Krad or 80 Krad), the number and length of worms in the small intestine, as well as, the number of encysted larvae in muscles of mice, especially diaphragm and tongue, were significantly decreased. Also, using al bendazole 24 hours after infection with irradiated larvae lead to high significant decrease in all the previously mentioned parameters

  5. TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice

    DEFF Research Database (Denmark)

    Reinert, Line; Harder, Louis Andreas; Holm, Christian;

    2012-01-01

    , it is not known what cell type mediates the role of TLR3 in the immunological control of HSV, and it is not known whether TLR3 sensing occurs prior to or after CNS entry. Here, we show that in mice TLR3 provides early control of HSV-2 infection immediately after entry into the CNS by mediating type I IFN...

  6. Current progress in the development of therapeutic vaccines for chronic hepatitis B virus infection

    Directory of Open Access Journals (Sweden)

    Faezeh Ghasemi

    2016-07-01

    Full Text Available Chronic hepatitis B is still a major public health issue despite the successful prophylactic vaccination attempts. Chronicity of hepatitis B virus(HBV is mainly due to its ability to debilitate host's immune system. Therefore, major measures have been taken to stop this process and help patients with chronic hepatitis B infection recover from their illness. While satisfactory results have been achieved using preventive HBV vaccines, a reliable and effective therapeutic treatment is still in need of extensive studies. Current treatments for chronic hepatitis B include direct antiviral agents and nucleoside/nucleotide analogs, which are not always effective and are also costly. In addition, due to the fact that chronic HBV is responsible for debilitation of the immune system, studies have focused on developing therapeutic vaccines to help host's immune system recover and limit the infection. Several approaches including but not restricted to recombinant peptide-based, DNA-based, viral vector-based, and cell-based approaches are currently in use to develop therapeutic vaccines against the chronic form of HBV infection. In the current review, the authors will first discuss the role of the immune system in chronic hepatitis B infection and will then focus on latest advancements in therapeutic vaccination of HBV especially the clinical trials that have been carried out so far.

  7. Current progress in the development of therapeutic vaccines for chronic hepatitis B virus infection.

    Science.gov (United States)

    Ghasemi, Faezeh; Rostami, Sina; Ghayour-Mobarhan, Majid; Meshkat, Zahra

    2016-07-01

    Chronic hepatitis B is still a major public health issue despite the successful prophylactic vaccination attempts. Chronicity of hepatitis B virus (HBV) is mainly due to its ability to debilitate host's immune system. Therefore, major measures have been taken to stop this process and help patients with chronic hepatitis B infection recover from their illness. While satisfactory results have been achieved using preventive HBV vaccines, a reliable and effective therapeutic treatment is still in need of extensive studies. Current treatments for chronic hepatitis B include direct antiviral agents and nucleoside/nucleotide analogs, which are not always effective and are also costly. In addition, due to the fact that chronic HBV is responsible for debilitation of the immune system, studies have focused on developing therapeutic vaccines to help host's immune system recover and limit the infection. Several approaches including but not restricted to recombinant peptide-based, DNA-based, viral vector-based, and cell-based approaches are currently in use to develop therapeutic vaccines against the chronic form of HBV infection. In the current review, the authors will first discuss the role of the immune system in chronic hepatitis B infection and will then focus on latest advancements in therapeutic vaccination of HBV especially the clinical trials that have been carried out so far. PMID:27635192

  8. Pilot-Scale Pulsed UV Light Irradiation of Experimentally Infected Raspberries Suppresses Cryptosporidium parvum Infectivity in Immunocompetent Suckling Mice.

    Science.gov (United States)

    Le Goff, L; Hubert, B; Favennec, L; Villena, I; Ballet, J J; Agoulon, A; Orange, N; Gargala, G

    2015-12-01

    Cryptosporidium spp., a significant cause of foodborne infection, have been shown to be resistant to most chemical food disinfectant agents and infective for weeks in irrigation waters and stored fresh vegetal produce. Pulsed UV light (PL) has the potential to inactivate Cryptosporidium spp. on surfaces of raw or minimally processed foods or both. The present study aimed to evaluate the efficacy of PL on viability and in vivo infectivity of Cryptosporidium parvum oocysts present on raspberries, a known source of transmission to humans of oocyst-forming apicomplexan pathogens. The skin of each of 20 raspberries was experimentally inoculated with five 10-μl spots of an oocyst suspension containing 6 × 10(7) oocysts per ml (Nouzilly isolate). Raspberries were irradiated by PL flashes (4 J/cm(2) of total fluence). This dose did not affect colorimetric or organoleptic characteristics of fruits. After immunomagnetic separation from raspberries, oocysts were bleached and administered orally to neonatal suckling mice. Seven days after infection, mice were euthanized, and the number of oocysts in the entire small intestine was individually assessed by immunofluorescence flow cytometry. Three of 12 and 12 of 12 inoculated mice that received 10 and 100 oocysts isolated from nonirradiated raspberries, respectively, were found infected. Four of 12 and 2 of 12 inoculated mice that received 10(3) and 10(4) oocysts from irradiated raspberries, respectively, were found infected. Oocyst counts were lower in animals inoculated with 10(3) and 10(4) oocysts from irradiated raspberries (92 ± 144 and 38 ± 82, respectively) than in animals infected with 100 oocysts from nonirradiated raspberries (35,785 ± 66,221, P = 0.008). PL irradiation achieved oocyst reductions of 2 and 3 log for an inoculum of 10(3) and 10(4) oocysts, respectively. The present pilot-scale evaluation suggests that PL is an effective mode of decontamination for raspberries and prompts further applicability

  9. Analysis of gene expression in ceca of Helicobacter hepaticus-infected A/JCr mice before and after development of typhlitis.

    Science.gov (United States)

    Myles, Matthew H; Livingston, Robert S; Livingston, Beth A; Criley, Jennifer M; Franklin, Craig L

    2003-07-01

    The inflammatory bowel diseases, Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract. The causes of these diseases remain unknown; however, prevailing theories suggest that chronic intestinal inflammation results from a dysregulated immune response to ubiquitous bacterial antigens. While a substantial body of data has been amassed describing the role of the adaptive immune system in perpetuating and sustaining inflammation, very little is known about the early signals, prior to the development of inflammation, that initiate and direct the abnormal immune response. To this end, we characterized the gene expression profile of A/JCr mice with Helicobacter hepaticus-induced typhlitis at month 1 of infection, prior to the onset of histologic disease, and month 3 of infection, after chronic inflammation is fully established. Analysis of the gene expression in ceca of H. hepaticus infected mice revealed 25 up-regulated and 3 down-regulated genes in the month-1 postinoculation group and 31 up-regulated and 2 down-regulated genes in the month-3 postinoculation group. Among these was a subset of immune-related genes, including interferon-inducible protein 10, monokine induced by gamma interferon, macrophage-induced protein 1 alpha, and serum amyloid A1. Semiquantitative real-time reverse transcriptase PCR confirmed the increased expression levels of these genes, as well as elevated expression of gamma interferon. To our knowledge, this is the first report profiling cecal gene expression in H. hepaticus-infected A/JCr mice. The findings of altered gene expression prior to the development of any features of pathology and the ensuing chronic disease course make this an attractive model for studying early host response to microbe-induced inflammatory bowel disease.

  10. Oral P. gingivalis infection alters the vascular reactivity in healthy and spontaneously atherosclerotic mice

    Directory of Open Access Journals (Sweden)

    Stefanon Ivanita

    2011-05-01

    Full Text Available Abstract Background Considering that recent studies have demonstrated endothelial dysfunction in subjects with periodontitis and that there is no information about vascular function in coexistence of periodontitis and atherosclerosis, we assessed the impact of oral inoculation with the periodontal pathogen Porphyromonas gingivalis on vascular reactivity in healthy and hypercholesterolemic apolipoprotein E-deficient (ApoE mice. In vitro preparations of mesenteric arteriolar bed were used to determine the vascular responses to acetylcholine, sodium nitroprusside and phenylephrine (PE. Results Alveolar bone resorption, an evidence of periodontitis, was assessed and confirmed in all infected mice. Acetylcholine- and sodium nitroprusside-induced vasorelaxations were similar among all groups. Non-infected ApoE mice were hyperreactive to PE when compared to non-infected healthy mice. P gingivalis infection significantly enhanced the vasoconstriction to PE in both healthy and spontaneous atherosclerotic mice, when compared to their respective controls. Conclusions This study demonstrates that oral P gingivalis affects the alpha-adrenoceptor-mediated vascular responsiveness in both healthy and spontaneous atherosclerotic mice, reinforcing the association between periodontitis and cardiovascular diseases.

  11. Mycobacterium ulcerans infection as a cause of chronic diarrhea in an AIDS patient: A case report

    Institute of Scientific and Technical Information of China (English)

    Jin-Gook Huh; Myoung-Don Oh; You-Sun Kim; Jong-Sung Lee; Tae-Yeob Jeong; Soo-Hyung Ryu; Jung-Hwan Lee; Jeong-Seop Moon; Yun-Kyung Kang; Myung-Shup Shim

    2008-01-01

    Chronic diarrhea is one of the most frequent gastro-intestinal manifestations in acquired immunodeficiency syndrome (AIDS).Protozoa and nontuberculous mycobacteria (NTM) are opportunistic pathogens that can easily infect these patients.Among the NTM,Mycobacterium avium complex (MAC) is the most frequently observed pathogen in HIV-infected patients.However,NTMs other than MAC have not been reported as a gastrointestinal pathogen as yet.We present a case of chronic diarrhea in an AIDS patient in whom Mycobacterium ulcerans and cryptosporidium co-infection is evidenced from colonic tissue.

  12. Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis

    DEFF Research Database (Denmark)

    Hoffmann, Nadine; Rasmussen, Thomas Bovbjerg; Jensen, Peter Østrup;

    2005-01-01

    Pseudomonas aeruginosa causes a chronic infection in the lungs of cystic fibrosis (CF) patients by establishing an alginate-containing biofilm. The infection has been studied in several animal models; however, most of the models required artificial embedding of the bacteria. We present here a new...... pulmonary mouse model without artificial embedding. The model is based on a stable mucoid CF sputum isolate (NH57388A) with hyperproduction of alginate due to a deletion in mucA and functional N-acylhomoserine lactone (AHL)-based quorum-sensing systems. Chronic lung infection could be established in both CF...

  13. Requirements for CD4+ cells and gamma interferon in resolution of established Cryptosporidium parvum infection in mice.

    OpenAIRE

    W. Chen; Harp, J A; Harmsen, A G

    1993-01-01

    The importance of CD4+ cells and gamma interferon (IFN-gamma) in the resolution of established Cryptosporidium parvum infection was investigated with a murine model of cryptosporidiosis in severe combined immunodeficient (SCID) mice. C. parvum-infected SCID mice were reconstituted with spleen cells from immunocompetent donors. The recipients were able to resolve their C. parvum infection by 17 days postreconstitution. Treatment of reconstituted SCID mice with either anti-CD4 monoclonal antibo...

  14. Influence of experimental context on the development of anhedonia in male mice imposed to chronic social stress

    OpenAIRE

    Bondar, N. P.; Kovalenko, I. L.; Avgustinovich, D. F.; Kudryavtseva, N. N.

    2007-01-01

    Anhedonia is one of the key symptoms of depression in humans. Consumption of 1% sucrose solution supplemented with 0.2% vanillin was studied in two experimental contexts in male mice living under chronic social stress induced by daily experience of defeats in agonistic interactions and leading to development of depression. In the first experiment, vanillin sucrose solution was made available as an option of water during 10 days to mice living in group home cages. Then the mice were subjected ...

  15. Chronic microsporidian infection of the nasal mucosae, sinuses and conjunctivae in HIV disease.

    OpenAIRE

    Lacey, C. J.; Clarke, A. M.; Fraser, P; Metcalfe, T; Bonsor, G; Curry, A.

    1992-01-01

    A case of chronic infection of the nasal mucosae, sinuses and conjunctivae with a microsporidian parasite in association with HIV infection and immune deficiency is reported. This microsporidian resembles both Encephalitozoon cuniculi and the newly described Encephalitozoon hellem by electron microscopy. This occurred in an adult male resident in the UK with no history of foreign travel. Although there are previous descriptions of conjunctival infections from the USA, this is the first descri...

  16. Clinical and epidemiological features of patients with chronic hepatitis C co-infected with HIV

    Directory of Open Access Journals (Sweden)

    Braga Eduardo Lorens

    2006-02-01

    Full Text Available Co-infection with hepatitis C virus (HCV and human immunodeficiency virus (HIV is increasingly common and affects the clinical course of chronic hepatitis C. Highly active antiretroviral therapy has improved the life expectancy of HIV infected patients, but, by extending survival, it permits the development of HCV cirrhosis. This study tried to evaluate clinical and epidemiological features of patients with chronic hepatitis C co-infected with HIV. We evaluated 134 HCV-infected patients: i group A - 65 co-infected HCV/HIV patients, ii group B - 69 mono-infected HCV patients. The impact of HIV infection on HCV liver disease was analyzed using Child's score, ultrasound findings and liver histology. Patients were subjected to HCV genotyping and anti-HBs dosage. Patients mean age was 42.4 years (±9.1 and 97 (72.4% were males. Injected drug use and homo/bisexual practice were more frequently encountered in the co-infected group: 68.3% and 78.0%, respectively. Antibodies against hepatitis B virus (anti-HBs were found in only 38.1% of the patients (66.7% group A x 33.3% group B. Ten out of 14 individuals (71.4% who had liver disease (Child B or C and 25 out of 34 (73.5% who showed ultrasound evidence of chronic liver disease were in the co-infection group. HCV genotype-2/3 was more frequently encountered in co-infected patients (36.9% group A vs. 21.8% group B. Conclusions: a HIV infection seems to adversely affect the clinical course of chronic hepatitis C, b injected drug use, bi/homosexual practice and genotype-2/3 were more frequently encountered in co-infected patients, c immunization against HBV should be encouraged in these patients.

  17. Transmission of chronic wasting disease identifies a prion strain causing cachexia and heart infection in hamsters.

    Directory of Open Access Journals (Sweden)

    Richard A Bessen

    Full Text Available Chronic wasting disease (CWD is an emerging prion disease of free-ranging and captive cervids in North America. In this study we established a rodent model for CWD in Syrian golden hamsters that resemble key features of the disease in cervids including cachexia and infection of cardiac muscle. Following one to three serial passages of CWD from white-tailed deer into transgenic mice expressing the hamster prion protein gene, CWD was subsequently passaged into Syrian golden hamsters. In one passage line there were preclinical changes in locomotor activity and a loss of body mass prior to onset of subtle neurological symptoms around 340 days. The clinical symptoms included a prominent wasting disease, similar to cachexia, with a prolonged duration. Other features of CWD in hamsters that were similar to cervid CWD included the brain distribution of the disease-specific isoform of the prion protein, PrP(Sc, prion infection of the central and peripheral neuroendocrine system, and PrP(Sc deposition in cardiac muscle. There was also prominent PrP(Sc deposition in the nasal mucosa on the edge of the olfactory sensory epithelium with the lumen of the nasal airway that could have implications for CWD shedding into nasal secretions and disease transmission. Since the mechanism of wasting disease in prion diseases is unknown this hamster CWD model could provide a means to investigate the physiological basis of cachexia, which we propose is due to a prion-induced endocrinopathy. This prion disease phenotype has not been described in hamsters and we designate it as the 'wasting' or WST strain of hamster CWD.

  18. Infected dendritic cells facilitate systemic dissemination and transplacental passage of the obligate intracellular parasite Neospora caninum in mice.

    Directory of Open Access Journals (Sweden)

    Esther Collantes-Fernandez

    Full Text Available The obligate intracellular parasite Neospora caninum disseminates across the placenta and the blood-brain barrier, to reach sites where it causes severe pathology or establishes chronic persistent infections. The mechanisms used by N. caninum to breach restrictive biological barriers remain elusive. To examine the cellular basis of these processes, migration of different N. caninum isolates (Nc-1, Nc-Liverpool, Nc-SweB1 and the Spanish isolates: Nc-Spain 3H, Nc-Spain 4H, Nc-Spain 6, Nc-Spain 7 and Nc-Spain 9 was studied in an in vitro model based on a placental trophoblast-derived BeWo cell line. Here, we describe that infection of dendritic cells (DC by N. caninum tachyzoites potentiated translocation of parasites across polarized cellular monolayers. In addition, powered by the parasite's own gliding motility, extracellular N. caninum tachyzoites were able to transmigrate across cellular monolayers. Altogether, the presented data provides evidence of two putative complementary pathways utilized by N. caninum, in an isolate-specific fashion, for passage of restrictive cellular barriers. Interestingly, adoptive transfer of tachyzoite-infected DC in mice resulted in increased parasitic loads in various organs, e.g. the central nervous system, compared to infections with free parasites. Inoculation of pregnant mice with infected DC resulted in an accentuated vertical transmission to the offspring with increased parasitic loads and neonatal mortality. These findings reveal that N. caninum exploits the natural cell trafficking pathways in the host to cross cellular barriers and disseminate to deep tissues. The findings are indicative of conserved dissemination strategies among coccidian apicomplexan parasites.

  19. Infected Dendritic Cells Facilitate Systemic Dissemination and Transplacental Passage of the Obligate Intracellular Parasite Neospora caninum in Mice

    Science.gov (United States)

    Collantes-Fernandez, Esther; Arrighi, Romanico B. G.; Álvarez-García, Gema; Weidner, Jessica M.; Regidor-Cerrillo, Javier; Boothroyd, John C.; Ortega-Mora, Luis M.; Barragan, Antonio

    2012-01-01

    The obligate intracellular parasite Neospora caninum disseminates across the placenta and the blood-brain barrier, to reach sites where it causes severe pathology or establishes chronic persistent infections. The mechanisms used by N. caninum to breach restrictive biological barriers remain elusive. To examine the cellular basis of these processes, migration of different N. caninum isolates (Nc-1, Nc-Liverpool, Nc-SweB1 and the Spanish isolates: Nc-Spain 3H, Nc-Spain 4H, Nc-Spain 6, Nc-Spain 7 and Nc-Spain 9) was studied in an in vitro model based on a placental trophoblast-derived BeWo cell line. Here, we describe that infection of dendritic cells (DC) by N. caninum tachyzoites potentiated translocation of parasites across polarized cellular monolayers. In addition, powered by the parasite's own gliding motility, extracellular N. caninum tachyzoites were able to transmigrate across cellular monolayers. Altogether, the presented data provides evidence of two putative complementary pathways utilized by N. caninum, in an isolate-specific fashion, for passage of restrictive cellular barriers. Interestingly, adoptive transfer of tachyzoite-infected DC in mice resulted in increased parasitic loads in various organs, e.g. the central nervous system, compared to infections with free parasites. Inoculation of pregnant mice with infected DC resulted in an accentuated vertical transmission to the offspring with increased parasitic loads and neonatal mortality. These findings reveal that N. caninum exploits the natural cell trafficking pathways in the host to cross cellular barriers and disseminate to deep tissues. The findings are indicative of conserved dissemination strategies among coccidian apicomplexan parasites. PMID:22403627

  20. Vitamin D supplementation enhances the fixation of titanium implants in chronic kidney disease mice.

    Science.gov (United States)

    Liu, Weiqing; Zhang, Shiwen; Zhao, Dan; Zou, Huawei; Sun, Ningyuan; Liang, Xing; Dard, Michel; Lanske, Beate; Yuan, Quan

    2014-01-01

    Vitamin D (Vit D) deficiency is a common condition in chronic kidney disease (CKD) patients that negatively affects bone regeneration and fracture healing. Previous study has shown that timely healing of titanium implants is impaired in CKD. This study aimed to investigate the effect of Vit D supplementation on implant osseointegration in CKD mice. Uremia was induced by 5/6 nephrectomy in C57BL mice. Eight weeks after the second renal surgery, animals were given 1,25(OH)2D3 three times a week intraperitoneally for four weeks. Experimental titanium implants were inserted into the distal end of femurs two weeks later. Serum measurements confirmed decreased 1,25(OH)2D levels in CKD mice, which could be successfully corrected by Vit D injections. Moreover, the hyperparathyroidism observed in CKD mice was also corrected. X-ray examination and histological sections showed successful osseointegration in these mice. Histomorphometrical analysis revealed that the bone-implant contact (BIC) ratio and bone volume (BV/TV) around the implant were significantly increased in the Vit D-supplementation group. In addition, resistance of the implant, as measured by a push-in method, was significantly improved compared to that in the vehicle group. These results demonstrate that Vit D supplementation is an effective approach to improve the fixation of titanium implants in CKD.

  1. Vitamin D supplementation enhances the fixation of titanium implants in chronic kidney disease mice.

    Directory of Open Access Journals (Sweden)

    Weiqing Liu

    Full Text Available Vitamin D (Vit D deficiency is a common condition in chronic kidney disease (CKD patients that negatively affects bone regeneration and fracture healing. Previous study has shown that timely healing of titanium implants is impaired in CKD. This study aimed to investigate the effect of Vit D supplementation on implant osseointegration in CKD mice. Uremia was induced by 5/6 nephrectomy in C57BL mice. Eight weeks after the second renal surgery, animals were given 1,25(OH2D3 three times a week intraperitoneally for four weeks. Experimental titanium implants were inserted into the distal end of femurs two weeks later. Serum measurements confirmed decreased 1,25(OH2D levels in CKD mice, which could be successfully corrected by Vit D injections. Moreover, the hyperparathyroidism observed in CKD mice was also corrected. X-ray examination and histological sections showed successful osseointegration in these mice. Histomorphometrical analysis revealed that the bone-implant contact (BIC ratio and bone volume (BV/TV around the implant were significantly increased in the Vit D-supplementation group. In addition, resistance of the implant, as measured by a push-in method, was significantly improved compared to that in the vehicle group. These results demonstrate that Vit D supplementation is an effective approach to improve the fixation of titanium implants in CKD.

  2. Age influence on mice lung tissue response to [i]Aspergillus fumigatus[/i] chronic exposure

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    Marta Kinga Lemieszek

    2015-02-01

    Full Text Available [b]Introduction and objective[/b]. Exposure to conidia of [i]Aspergillus fumigatus[/i] was described as a causative factor of a number of the respiratory system diseases, including asthma, chronic eosinophilic pneumonia, hypersensitivity pneumonitis and bronchopulmonary aspergillosis. The study investigates the effects of the repeated exposure to [i]A. fumigatus[/i] in mice pulmonary compartment. Our work tackles two, so far insufficiently addressed, important aspects of interaction between affected organism and[i] A. fumigatus[/i]: 1 recurrent character of exposure (characteristic for pathomechanism of the abovementioned disease states and 2 impact of aging, potentially important for the differentiation response to an antigen. [b]Materials and methods[/b]. In order to dissect alterations of the immune system involved with both aging and chronic exposure to [i]A. fumigatus[/i], we used 3- and 18-month-old C57BL/6J mice exposed to repeated[i] A. fumigatus[/i] inhalations for 7 and 28 days. Changes in lung tissue were monitored by histological and biochemical evaluation. Concentration of pro- and anti-inflammatory cytokines in lung homogenates was assessed by ELISA tests. [b]Results and conclusions. [/b]Our study demonstrated that chronic inflammation in pulmonary compartment, characterized by the significant increase of proinflammatory cytokines (IL1, IL6, IL10 levels, was the dominant feature of mice response to repeated [i]A. fumigatus[/i] inhalations. The pattern of cytokines’ profile in the course of exposure was similar in both age groups, however in old mice the growth of the cytokines’ levels was more pronounced (especially in case of IL1.

  3. Antidepressant-like effects of BCEF0083 in the chronic unpredictable stress models in mice

    Institute of Scientific and Technical Information of China (English)

    ZHOU Lan-lan; MING Liang; MA Chuan-geng; CHENG Yan; JIANG Qin

    2005-01-01

    Background Up to now there have been no satisfactory drugs to treat psychiatric disorders, and now bioactive compound from entomagenous fungi (BCEF0083) is a new type of bioactive compound from entomopathogenic fungi. Our previous investigations have shown that BCEF has an inhibition effect on monoamine oxidase. So, BCEF may be a latent antidepressant. This study aimed at observing the antidepressant effects and its mechanism of BCEF in the chronic unpredictable stress models in mice. Methods The antidepressant effects of BCEF were examined on the chronic unpredictable stress models in mice. Sixty mice were randomly divided to six groups. Animals were housed and isolated except saline group. Mice were exposed to different stressors per day randomly from day 1 to day 21. Body weight were weighed on day 1,day 10 and on day 21 during the 21-day stress procedure. Awarding response was detected by using method of calculating the 24-hour consumption of saccharum water. Step through test was used to evaluate the behavioral response. AVP contents in plasma were also detected by using radioimmunoassays. Results Chronic unpredictable stress resulted in a significant decrease of the body weight and could apparently cause escape behavior disturbance and gradual reduction of sensitivity to reward in animal models. Drug treatment (BCEF 25, 50, 100 mg/kg) could significantly ameliorate the decreased body weight and effectively reverse the escape behavior disturbance. The gradual reduction of sensitivity to reward, the anhedonic state, was also effectively reversed by BCEF. BCEF (50, 100 mg/kg) could also effectively restore the AVP content in the plasma.Conclusions This evidence suggests that BCEF can effectively inhibit the depression behavior and show strong antidepressant effect. BCEF can effectively restore the plasma AVP release and this may be an important mechanism of its antidepressant effect.

  4. Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice.

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    Silvennoinen, Reija; Quesada, Helena; Kareinen, Ilona; Julve, Josep; Kaipiainen, Leena; Gylling, Helena; Blanco-Vaca, Francisco; Escola-Gil, Joan Carles; Kovanen, Petri T; Lee-Rueckert, Miriam

    2015-05-11

    Psychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The transfer of cholesterol from macrophage foam cells to liver and feces (the macrophage-specific reverse cholesterol transport, m-RCT) is an important antiatherogenic pathway. Because exposure of mice to physical restraint, a model of psychological stress, increases serum levels of corticosterone, and as bile acid homeostasis is disrupted in glucocorticoid-treated animals, we investigated if chronic intermittent restraint stress would modify m-RCT by altering the enterohepatic circulation of bile acids. C57Bl/6J mice exposed to intermittent stress for 5 days exhibited increased transit through the large intestine and enhanced fecal bile acid excretion. Of the transcription factors and transporters that regulate bile acid homeostasis, the mRNA expression levels of the hepatic farnesoid X receptor (FXR), the bile salt export pump (BSEP), and the intestinal fibroblast growth factor 15 (FGF15) were reduced, whereas those of the ileal apical sodium-dependent bile acid transporter (ASBT), responsible for active bile acid absorption, remained unchanged. Neither did the hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), the key enzyme regulating bile acid synthesis, change in the stressed mice. Evaluation of the functionality of the m-RCT pathway revealed increased fecal excretion of bile acids that had been synthesized from macrophage-derived cholesterol. Overall, our study reveals that chronic intermittent stress in mice accelerates m-RCT specifically by increasing fecal excretion of bile acids. This novel mechanism of m-RCT induction could have antiatherogenic potential under conditions of chronic stress. PMID:25969465

  5. Simultaneous Chronic Invasive Fungal Infection and Tracheal Fungus Ball Mimicking Cancer in an Immunocompetent Patient

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    Çetinkaya, Erdoğan; Gül, Şule; Mert, Ali; Boyacı, Hilal; Çam, Ertan; Dincer, H. Erhan

    2016-01-01

    Fungal infections of the lung are uncommon and mainly affect people with immune deficiency. There are crucial problems in the diagnosis and treatment of this condition. Invasive pulmonary aspergillosis and candidiasis are the most common opportunistic fungal infections. Aspergillus species (spp.) are saprophytes molds that exist in nature as spores and rarely cause disease in immunocompetent individuals. In patients with immune deficiency or chronic lung disease, such as cavitary lung disease or bronchiectasis, Aspergillus may cause a variety of aspergillosis infections. Here we present a case of a 57-year-old patient without immunodeficiency or chronic lung disease who was diagnosed with endotracheal fungus ball and chronic fungal infection, possibly due to Aspergillus. Bronchoscopic examination showed a paralyzed right vocal cord and vegetating mass that was yellow in color, at the posterior wall of tracheal lumen. After 3 months, both the parenchymal and tracheal lesions were completely resolved. PMID:27418930

  6. Simultaneous Chronic Invasive Fungal Infection and Tracheal Fungus Ball Mimicking Cancer in an Immunocompetent Patient

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    Erdoğan Çetinkaya

    2016-01-01

    Full Text Available Fungal infections of the lung are uncommon and mainly affect people with immune deficiency. There are crucial problems in the diagnosis and treatment of this condition. Invasive pulmonary aspergillosis and candidiasis are the most common opportunistic fungal infections. Aspergillus species (spp. are saprophytes molds that exist in nature as spores and rarely cause disease in immunocompetent individuals. In patients with immune deficiency or chronic lung disease, such as cavitary lung disease or bronchiectasis, Aspergillus may cause a variety of aspergillosis infections. Here we present a case of a 57-year-old patient without immunodeficiency or chronic lung disease who was diagnosed with endotracheal fungus ball and chronic fungal infection, possibly due to Aspergillus. Bronchoscopic examination showed a paralyzed right vocal cord and vegetating mass that was yellow in color, at the posterior wall of tracheal lumen. After 3 months, both the parenchymal and tracheal lesions were completely resolved.

  7. Simultaneous Chronic Invasive Fungal Infection and Tracheal Fungus Ball Mimicking Cancer in an Immunocompetent Patient.

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    Çetinkaya, Erdoğan; Çörtük, Mustafa; Gül, Şule; Mert, Ali; Boyacı, Hilal; Çam, Ertan; Dincer, H Erhan

    2016-01-01

    Fungal infections of the lung are uncommon and mainly affect people with immune deficiency. There are crucial problems in the diagnosis and treatment of this condition. Invasive pulmonary aspergillosis and candidiasis are the most common opportunistic fungal infections. Aspergillus species (spp.) are saprophytes molds that exist in nature as spores and rarely cause disease in immunocompetent individuals. In patients with immune deficiency or chronic lung disease, such as cavitary lung disease or bronchiectasis, Aspergillus may cause a variety of aspergillosis infections. Here we present a case of a 57-year-old patient without immunodeficiency or chronic lung disease who was diagnosed with endotracheal fungus ball and chronic fungal infection, possibly due to Aspergillus. Bronchoscopic examination showed a paralyzed right vocal cord and vegetating mass that was yellow in color, at the posterior wall of tracheal lumen. After 3 months, both the parenchymal and tracheal lesions were completely resolved. PMID:27418930

  8. MicroRNA Transcriptome Profiling in Heart of Trypanosoma cruzi-Infected Mice: Parasitological and Cardiological Outcomes.

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    Isabela Cunha Navarro

    Full Text Available 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.

  9. Concurrent Helicobacter bilis Infection in C57BL/6 Mice Attenuates Proinflammatory H. pylori-Induced Gastric Pathology▿

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    Lemke, Laura B.; Ge, Zhongming; Whary, Mark T.; Feng, Yan; Rogers, Arlin B.; MUTHUPALANI, SURESHKUMAR; James G Fox

    2009-01-01

    Because coinfections can alter helicobacter gastritis, we investigated whether enterohepatic Helicobacter bilis modulates Helicobacter pylori gastritis in C57BL/6 mice. Thirty mice per group were sham dosed, H. bilis or H. pylori infected, or H. bilis infected followed in 2 weeks by H. pylori and then evaluated at 6 and 11 months postinfection (mpi) for gastritis and premalignant lesions. Compared to H. pylori-infected mice, H. bilis/H. pylori-infected mice at 6 and 11 mpi had less severe gas...

  10. Chronic Lyme Disease and Co-infections: Differential Diagnosis.

    Science.gov (United States)

    Berghoff, Walter

    2012-01-01

    In Lyme disease concurrent infections frequently occur. The clinical and pathological impact of co-infections was first recognized in the 1990th, i.e. approximately ten years after the discovery of Lyme disease. Their pathological synergism can exacerbate Lyme disease or induce similar disease manifestations. Co-infecting agents can be transmitted together with Borrelia burgdorferi by tick bite resulting in multiple infections but a fraction of co-infections occur independently of tick bite. Clinically relevant co-infections are caused by Bartonella species, Yersinia enterocolitica, Chlamydophila pneumoniae, Chlamydia trachomatis, and Mycoplasma pneumoniae. In contrast to the USA, human granulocytic anaplasmosis (HGA) and babesiosis are not of major importance in Europe. Infections caused by these pathogens in patients not infected by Borrelia burgdorferi can result in clinical symptoms similar to those occurring in Lyme disease. This applies particularly to infections caused by Bartonella henselae, Yersinia enterocolitica, and Mycoplasma pneumoniae. Chlamydia trachomatis primarily causes polyarthritis. Chlamydophila pneumoniae not only causes arthritis but also affects the nervous system and the heart, which renders the differential diagnosis difficult. The diagnosis is even more complex when co-infections occur in association with Lyme disease. Treatment recommendations are based on individual expert opinions. In antibiotic therapy, the use of third generation cephalosporins should only be considered in cases of Lyme disease. The same applies to carbapenems, which however are used occasionally in infections caused by Yersinia enterocolitica. For the remaining infections predominantly tetracyclines and macrolides are used. Quinolones are for alternative treatment, particularly gemifloxacin. For Bartonella henselae, Chlamydia trachomatis, and Chlamydophila pneumoniae the combination with rifampicin is recommended. Erythromycin is the drug of choice for

  11. Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears.

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    Miner, Jonathan J; Sene, Abdoulaye; Richner, Justin M; Smith, Amber M; Santeford, Andrea; Ban, Norimitsu; Weger-Lucarelli, James; Manzella, Francesca; Rückert, Claudia; Govero, Jennifer; Noguchi, Kevin K; Ebel, Gregory D; Diamond, Michael S; Apte, Rajendra S

    2016-09-20

    Zika virus (ZIKV) is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, given that Axl(-/-), Mertk(-/-), and Axl(-/-)Mertk(-/-) double knockout mice sustained levels of infection similar to those of control animals. We also detected abundant viral RNA in tears, suggesting that virus might be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye. PMID:27612415

  12. Subcutaneous infection model facilitates treatment assessment of secondary Alveolar echinococcosis in mice.

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    Tatiana Küster

    Full Text Available Alveolar echinococcosis (AE in humans is a parasitic disease characterized by severe damage to the liver and occasionally other organs. AE is caused by infection with the metacestode (larval stage of the fox tapeworm Echinococcus multilocularis, usually infecting small rodents as natural intermediate hosts. Conventionally, human AE is chemotherapeutically treated with mebendazole or albendazole. There is, however still the need for improved chemotherapeutical options. Primary in vivo studies on drugs of interest are commonly performed in small laboratory animals such as mice and Mongolian jirds, and in most cases, a secondary infection model is used, whereby E. multilocularis metacestodes are directly injected into the peritoneal cavity or into the liver. Disadvantages of this methodological approach include risk of injury to organs during the inoculation and, most notably, a limitation in the macroscopic (visible assessment of treatment efficacy. Thus, in order to monitor the efficacy of chemotherapeutical treatment, animals have to be euthanized and the parasite tissue dissected. In the present study, mice were infected with E. multilocularis metacestodes through the subcutaneous route and were then subjected to chemotherapy employing albendazole. Serological responses to infection were comparatively assessed in mice infected by the conventional intraperitoneal route. We demonstrate that the subcutaneous infection model for secondary AE facilitates the assessment of the progress of infection and drug treatment in the live animal.

  13. Structured approach to design of diagnostic test evaluation studies for chronic progressive infections in animals.

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    Nielsen, Søren Saxmose; Toft, Nils; Gardner, Ian Andrew

    2011-05-12

    Diagnostic test evaluations (DTEs) for chronic infections are challenging because a protracted incubation period has to be considered in the design of the DTE, and the adverse effects of infection may be widespread and progressive over an animal's entire life. Frequently, the specific purpose of the test is not formally considered when a test is evaluated. Therefore, the result is often a DTE where test sensitivity and specificity estimates are biased, either because of problems with establishing the true infection status or because the test detects another aspect of the infection (and analyte) than originally intended. The objective of this paper is to outline a structured approach to the design and conduct of a DTE for diagnostic tests used for chronic infections in animals, and intended for different purposes. We describe the process from reflections about test purpose and the underlying target condition through considerations of the pathogenesis, and specification of a practical case definition, which can subsequently be used in the DTE for the specific purpose. The process is illustrated by two examples of Mycobacterium avium subsp. paratuberculosis (MAP) infections in cattle. MAP infections are chronic and can result in different adverse effects at different time points during the incubation period. The description provides input on the process and deductive reasoning which are integral parts to develop a high-quality design of a DTE for chronic infectious diseases.

  14. RANTES gene single nucleotide polymorphisms and expression in patients with chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    DUAN Zhong-ping; ZHAO Xiu-ying; HUANG De-zhuang; HE Li-xiang; CHEN Yu; ZHAO Chun-hui; ZHENG Bo-jian

    2005-01-01

    Background Regulated on activation, normal T-cell expressed and secreted (RANTES) plays a critical role in T-lymphocyte activation and proliferation. The process is involved in both acute and chronic phases of inflammation. The present study was to ascertain the possible correlations between chronic hepatitis B virus (HBV) infection and the RANTES gene polymorphisms and their expression. Methods The study included 130 HBV negative healthy donors and 152 patients with chronic hepatitis B (CHB) virus infection. The polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLPs) were used to detect RANTES gene single nucleotide polymorphisms (SNPs). RANTES levels in the platelet depleted plasma were detected by enzyme linked immunosorbent assay (ELISA). Results RANTES alleles -403G, -28C and In1.1T were the predominant alleles in the subjects studied. No significant correlation was found between CHB infection and the RANTES alleles, while a significant correlation was found between CHB infection and increased RANTES expression in platelet depleted plasma (P<0.05). Conclusions SNPs in RANTES gene do not affect chronic HBV infection or the outcome of interferon-α treatment in patients positive for HBV "e" antigen (HBeAg+). However, patients with CHB infection express the higher levels of plasma RANTES, which is thus associated with CHB infection.

  15. Experimental Andes virus infection in deer mice: characteristics of infection and clearance in a heterologous rodent host.

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    Jessica R Spengler

    Full Text Available New World hantaviruses can cause hantavirus cardiopulmonary syndrome with high mortality in humans. Distinct virus species are hosted by specific rodent reservoirs, which also serve as the vectors. Although regional spillover has been documented, it is unknown whether rodent reservoirs are competent for infection by hantaviruses that are geographically separated, and known to have related, but distinct rodent reservoir hosts. We show that Andes virus (ANDV of South America, carried by the long tailed pygmy rice rat (Oligoryzomys longicaudatus, infects and replicates in vitro and in vivo in the deer mouse (Peromyscus maniculatus, the reservoir host of Sin Nombre virus (SNV, found in North America. In experimentally infected deer mice, viral RNA was detected in the blood, lung, heart and spleen, but virus was cleared by 56 days post inoculation (dpi. All of the inoculated deer mice mounted a humoral immune response by 14 dpi, and produced measurable amounts of neutralizing antibodies by 21 dpi. An up-regulation of Ccl3, Ccl4, Ccl5, and Tgfb, a strong CD4⁺ T-cell response, and down-regulation of Il17, Il21 and Il23 occurred during infection. Infection was transient with an absence of clinical signs or histopathological changes. This is the first evidence that ANDV asymptomatically infects, and is immunogenic in deer mice, a non-natural host species of ANDV. Comparing the immune response in this model to that of the immune response in the natural hosts upon infection with their co-adapted hantaviruses may help clarify the mechanisms governing persistent infection in the natural hosts of hantaviruses.

  16. Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice

    OpenAIRE

    Bahi, Amine; Dreyer, Jean-luc

    2014-01-01

    Objective: Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP.Methods: Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were s...

  17. Toxoplasma gondii Infection Promotes Neuroinflammation Through Cytokine Networks and Induced Hyperalgesia in BALB/c Mice.

    Science.gov (United States)

    Mahmoudvand, Hossein; Ziaali, Naser; Ghazvini, Hamed; Shojaee, Saeideh; Keshavarz, Hossein; Esmaeilpour, Khadijeh; Sheibani, Vahid

    2016-02-01

    We hypothesized that in Toxoplasma gondii infection, communication among immune cells promotes neuroinflammation through cytokine networks and induces pain sensitivity under conditions of neuropathic pain. The animal model of Toxoplasma infection was established by the intraperitoneal inoculation of 20-25 tissue cysts from Tehran strain of T. gondii to BALB/c mice. Amitriptyline (20 mg/kg, i.p., 1/day) administrated to animals for 7 days before behavioral tests. Pain behavioral tests including tail flick, hot plate, and formalin test were evaluated in all the groups. The mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were examined by real-time PCR. Results revealed that T. gondii induce hyperalgesia in the infected mice, whereas amitriptyline showed a promising effect against the hyperalgesia induced by Toxoplasma infection. The mRNA levels of the aforementioned cytokines significantly (P < 0.05) increased in the infected mice compared to the uninfected ones. Obtained findings suggested that T. gondii infection could promote neuroinflammation through cytokine networks and induced hyperalgesia in BALB/c mice, whereas amitriptyline as an analgesic drug reverses them. PMID:26490968

  18. Parasitological and immunological aspects of early Ascaris spp. infection in mice.

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    Gazzinelli-Guimarães, Pedro Henrique; Gazzinelli-Guimarães, Ana Clara; Silva, Flaviane Nunes; Mati, Vitor Luís Tenório; Dhom-Lemos, Lucas de Carvalho; Barbosa, Fernando Sérgio; Passos, Lívia Silva Araújo; Gaze, Soraya; Carneiro, Cláudia Martins; Bartholomeu, Daniella Castanheira; Bueno, Lilian Lacerda; Fujiwara, Ricardo Toshio

    2013-08-01

    Studies related to the immunobiological aspects of an Ascaris spp. infection are still scarce, especially those that aim to elucidate the early events of the immune response. In this study, we demonstrated a novel standardized method for early experimental Ascaris infection, providing additional information about the infectivity of eggs embryonated in vitro as well as the influence of host age on development of the infection. Finally, we characterised the immunopathology of early infection, focusing on the tissue and systemic cytokine profiles and the histopathology of infection in the lungs of BALB/c mice. Our results demonstrated that the highest egg infectivity occurred on the 100th and 200th days of in vitro embryonation and that 8 week-old BALB/c mice were more susceptible to infection than 16 week-old mice. Ascaris-infected mice showed an early, significant level of IL-5 production in the lungs 4 days p.i., followed by an increase in the level of neutrophils in the inflammatory infiltrate at 8 days p.i, which was correlated with the peak of larval migration in the tissue and a significant level of IL-6 production. The inflammatory infiltrate in the lungs was gradually replaced by mononuclear cells and eosinophils on the 10th and 12th days p.i., respectively, and an increase in TNF levels was observed. The downmodulation of systemic TCD4(+) cell numbers might suggest that T cell hyporesponsiveness was induced by the Ascaris spp. larvae, contributing to safeguarding parasite survival during larval migration. Taken together, the novel aspects of Ascaris infection presented here enabled a better understanding of the immunopathological events during larval migration, providing insight for further studies focused on immunisation and immunoprophylatic assays. PMID:23665127

  19. Occult hepatitis B virus infection and cryptogenic chronic hepatitis in an area with intermediate prevalence of HBV infection

    Institute of Scientific and Technical Information of China (English)

    Mohammad Javad Kaviani; Behzad Behbahani; Mohammad Jafar Mosallaii; Fatemeh Sari-Aslani; Seyed Alireza Taghavi

    2006-01-01

    AIM: To assess the possible role of occult HBV infection in the pathogenesis of chronic hepatitis in Iranian patients.METHODS: After exclusion of autoimmune, metabolic and viral etiologies, 104 consecutive adult patients with histologic and biochemical features of chronic hepatitis and negative HBsAg were enrolled in the study.Qualitative PCR with a sensitivity of 150 × 103 copies/L,using two primers for Pre-S and core regions was applied to measure presence of HBV DNA in serum of the patients.RESULTS: All 104 patients completed the study.Qualitative HBV DNA was positive in two patients (1.9%).CONCLUSION: Occult HBV infection has negligible role in the pathogenesis of cryptogenic chronic hepatitis in Iranian patients.

  20. Exacerbation of allergic inflammation in mice exposed to diesel exhaust particles prior to viral infection

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    Chason Kelly D

    2009-08-01

    Full Text Available Abstract Background Viral infections and exposure to oxidant air pollutants are two of the most important inducers of asthma exacerbation. Our previous studies have demonstrated that exposure to diesel exhaust increases the susceptibility to influenza virus infections both in epithelial cells in vitro and in mice in vivo. Therefore, we examined whether in the setting of allergic asthma, exposure to oxidant air pollutants enhances the susceptibility to respiratory virus infections, which in turn leads to increased virus-induced exacerbation of asthma. Ovalbumin-sensitized (OVA male C57BL/6 mice were instilled with diesel exhaust particles (DEP or saline and 24 hours later infected with influenza A/PR/8. Animals were sacrificed 24 hours post-infection and analyzed for markers of lung injury, allergic inflammation, and pro-inflammatory cytokine production. Results Exposure to DEP or infection with influenza alone had no significant effects on markers of injury or allergic inflammation. However, OVA-sensitized mice that were exposed to DEP and subsequently infected with influenza showed increased levels of eosinophils in lung lavage and tissue. In addition Th2-type cytokines, such as IL-4 and IL-13, and markers of eosinophil chemotaxis, such as CCL11 and CCR3, were increased in OVA-sensitized mice exposed to DEP prior to infection with influenza. These mice also showed increased levels of IL-1α, but not IL-10, RANTES, and MCP-1 in lung homogenates. Conclusion These data suggest that in the setting of allergic asthma, exposure to diesel exhaust could enhance virus-induced exacerbation of allergic inflammation.

  1. Voluntary exercise and increased food intake after mild chronic stress improve social avoidance behavior in mice.

    Science.gov (United States)

    Otsuka, Airi; Shiuchi, Tetsuya; Chikahisa, Sachiko; Shimizu, Noriyuki; Séi, Hiroyoshi

    2015-11-01

    It is well-established that exercise can influence psychological conditions, cognitive function, and energy metabolism in peripheral tissues including the skeletal muscle. However, it is not clear whether exercise can influence social interaction with others and alleviate defeat stress. This study investigated the effect of voluntary wheel running on impaired social interaction induced by chronic social defeat stress (SDS) using the resident-intruder social defeat model. Mice were divided into three groups: control, stress alone, and stress+exercise. SDS was performed by exposing C57BL/6 mice to retired ICR mice for 2.5 min. The C57BL/6 mice were continuously defeated by these resident (aggressor) mice and, following 5 days of SDS, experienced 2 days of rest with no SDS. Mice in the stress+exercise group were allowed to voluntarily run on a wheel for 2h after every SDS exposure. Two weeks later, compared to the control group, the stress group showed a higher ratio of time spent in the corner zone of a social interaction paradigm even though SDS did not elicit depressive- and anxiety-like behaviors. We also observed that voluntary exercise, which did not affect muscle weight and gene expression, decreased social avoidance behavior of stressed mice without clear changes in brain monoamine levels. Interestingly, food intake in the stress+exercise group was the greatest among the three groups. To test the effect of the exercise-induced increase in food intake on social behavior, we set up a pair-fed group where food intake was restricted. We then compared these mice to mice in the stress alone group. We found that the ratio of time spent in the corner zone of the social interaction test was not different between ad libitum- and pair-fed groups, although pair-fed mice spent more time in the corner zone when an aggressor mouse was present than when it was absent. In addition, pair-feeding did not show exercise-induced reductions of adrenal gland weight and enhanced the

  2. Chronic caffeine exposure attenuates blast-induced memory deficit in mice

    Institute of Scientific and Technical Information of China (English)

    Ya-Lei Ning; Nan Yang; Xing Chen; Zi-Ai Zhao; Xiu-Zhu Zhang; Xing-Yun Chen; Ping Li

    2015-01-01

    Objective:To investigate the effects of three different ways of chronic caffeine administration on blastinduced memory dysfunction and to explore the underlying mechanisms.Methods:Adult male C57BL/6 mice were used and randomly divided into five groups:control:without blast exposure,con-water:administrated with water continuously before and after blast-induced traumatic brain injury (bTBI),con-caffeine:administrated with caffeine continuously for 1 month before and after bTBI,pre-caffeine:chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI,post-caffeine:chronically administrated with caffeine after bTBI.After being subjected to moderate intensity of blast injury,mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1,4,and 8 weeks post-blast injury.Neurological deficit scoring,glutamate concentration,proinflammatory cytokines production,and neuropathological changes at 24 h,1,4,and 8 weeks post-bTBI were examined to evaluate the brain injury in early and prolonged stages.Adenosine A1 receptor expression was detected using qPCR.Results:All of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit,which is correlated with the neuroprotective effects against excitotoxicity,inflammation,astrogliosis and neuronal loss at different stages of injury.Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI;pre-bTBl and post-bTBl treatment of caffeine tended to exert neuroprotective effects at early and prolonged stages of bTBI respectively.Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption.Conclusion:Since caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get,the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.

  3. Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice

    International Nuclear Information System (INIS)

    Highlights: • Mfn1 and Fis1 are significantly increased in the hippocampal region of the ME7 prion-infected brain, whereas Dlp1 is significantly decreased in the infected brain. • Dlp1 is significantly decreased in the cytosolic fraction of the hippocampus in the infected brain. • Neuronal mitochondria in the prion-infected brains are enlarged and swollen compared to those of control brains. • There are significantly fewer mitochondria in the ME7-infected brain compared to the number in control brain. - Abstract: Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress in scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the

  4. Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hong-Seok [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Choi, Yeong-Gon; Shin, Hae-Young; Oh, Jae-Min [Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Park, Jeong-Ho [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Kim, Jae-Il [Department of Food Science and Nutrition, Pukyong National University, 599-1 Daeyeon-3-dong, Nam-gu, Busan 608-737 (Korea, Republic of); Carp, Richard I. [New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 (United States); Choi, Eun-Kyoung, E-mail: ekchoi@hallym.ac.kr [Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Kim, Yong-Sun, E-mail: yskim@hallym.ac.kr [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of)

    2014-05-30

    Highlights: • Mfn1 and Fis1 are significantly increased in the hippocampal region of the ME7 prion-infected brain, whereas Dlp1 is significantly decreased in the infected brain. • Dlp1 is significantly decreased in the cytosolic fraction of the hippocampus in the infected brain. • Neuronal mitochondria in the prion-infected brains are enlarged and swollen compared to those of control brains. • There are significantly fewer mitochondria in the ME7-infected brain compared to the number in control brain. - Abstract: Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress in scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the

  5. Chronic UVB-irradiation actuates perpetuated dermal matrix remodeling in female mice: Protective role of estrogen

    Science.gov (United States)

    Röck, Katharina; Joosse, Simon Andreas; Müller, Julia; Heinisch, Nina; Fuchs, Nicola; Meusch, Michael; Zipper, Petra; Reifenberger, Julia; Pantel, Klaus; Fischer, Jens Walter

    2016-01-01

    Chronic UVB-exposure and declined estradiol production after menopause represent important factors leading to extrinsic and intrinsic aging, respectively. Remodeling of the extracellular matrix (ECM) plays a crucial role in both responses. Whether the dermal ECM is able to recover after cessation of UVB-irradiation in dependence of estradiol is not known, however of relevance when regarding possible treatment options. Therefore, the endogenous sex hormone production was depleted by ovariectomy in female mice. Half of the mice received estradiol substitution. Mice were UVB-irradiated for 20 weeks and afterwards kept for 10 weeks without irradiation. The collagen-, hyaluronan- and proteoglycan- (versican, biglycan, lumican) matrix, collagen cleavage products and functional skin parameters were analyzed. The intrinsic aging process was characterized by increased collagen fragmentation and accumulation of biglycan. Chronic UVB-irradiation additionally augmented the lumican, versican and hyaluronan content of the dermis. In the absence of further UVB-irradiation the degradation of collagen and accumulation of biglycan in the extrinsically aged group was perpetuated in an excessive matter. Whereas estradiol increased the proteoglycan content, it reversed the effects of the perpetuated extrinsic response on collagen degradation. Suspension of the intrinsic pathway might therefore be sufficient to antagonize UVB-evoked long-term damage to the dermal ECM. PMID:27460287

  6. Assessing behavioural effects of chronic HPA axis activation using conditional CRH-overexpressing mice.

    Science.gov (United States)

    Dedic, Nina; Touma, Chadi; Romanowski, Cristoph P; Schieven, Marcel; Kühne, Claudia; Ableitner, Martin; Lu, Ailing; Holsboer, Florian; Wurst, Wolfgang; Kimura, Mayumi; Deussing, Jan M

    2012-07-01

    The corticotropin-releasing hormone (CRH) and its cognate receptors have been implicated in the pathophysiology of stress-related disorders. Hypersecretion of central CRH and elevated glucocorticoid levels, as a consequence of impaired feedback control, have been shown to accompany mood and anxiety disorders. However, a clear discrimination of direct effects of centrally hypersecreted CRH from those resulting from HPA axis activation has been difficult. Applying a conditional strategy, we have generated two conditional CRH-overexpressing mouse lines: CRH-COE ( Del ) mice overexpress CRH throughout the body, while CRH-COE ( APit ) mice selectively overexpress CRH in the anterior and intermediate lobe of the pituitary. Both mouse lines show increased basal plasma corticosterone levels and consequently develop signs of Cushing's syndrome. However, while mice ubiquitously overexpressing CRH exhibited increased anxiety-related behaviour, overexpression of CRH in the pituitary did not produce alterations in emotional behaviour. These results suggest that chronic hypercorticosteroidism alone is not sufficient to alter anxiety-related behaviour but rather that central CRH hyperdrive on its own or in combination with elevated glucocorticoids is responsible for the increase in anxiety-related behaviour. In conclusion, the generated mouse lines represent valuable animal models to study the consequences of chronic CRH overproduction and HPA axis activation.

  7. Toxicogenomic analysis of susceptibility to inhaled urban particulate matter in mice with chronic lung inflammation

    Directory of Open Access Journals (Sweden)

    Yauk Carole L

    2009-03-01

    Full Text Available Abstract Background Individuals with chronic lung disease are at increased risk of adverse health effects from airborne particulate matter. Characterization of underlying pollutant-phenotype interactions may require comprehensive strategies. Here, a toxicogenomic approach was used to investigate how inflammation modifies the pulmonary response to urban particulate matter. Results Transgenic mice with constitutive pulmonary overexpression of tumour necrosis factor (TNF-α under the control of the surfactant protein C promoter and wildtype littermates (C57BL/6 background were exposed by inhalation for 4 h to particulate matter (0 or 42 mg/m3 EHC-6802 and euthanized 0 or 24 h post-exposure. The low alveolar dose of particles (16 μg did not provoke an inflammatory response in the lungs of wildtype mice, nor exacerbate the chronic inflammation in TNF animals. Real-time PCR confirmed particle-dependent increases of CYP1A1 (30–100%, endothelin-1 (20–40%, and metallothionein-II (20–40% mRNA in wildtype and TNF mice (p Conclusion Our data support the hypothesis that health effects of acute exposure to urban particles are dominated by activation of specific physiological response cascades rather than widespread changes in gene expression.

  8. Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

    Science.gov (United States)

    Bahi, Amine

    2013-07-01

    Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

  9. Lipid A’s Structure Mediates Neisseria gonorrhoeae Fitness during Experimental Infection of Mice and Men

    OpenAIRE

    Hobbs, Marcia M; Anderson, James E.; Balthazar, Jacqueline T.; Justin L Kandler; Carlson, Russell W.; Ganguly, Jhuma; Begum, Afrin A.; Duncan, Joseph A.; Lin, Jessica T.; Sparling, P. Frederick; Jerse, Ann E.; Shafer, William M.

    2013-01-01

    ABSTRACT Phosphoethanolamine (PEA) on Neisseria gonorrhoeae lipid A influences gonococcal inflammatory signaling and susceptibility to innate host defenses in in vitro models. Here, we evaluated the role of PEA-decorated gonococcal lipid A in competitive infections in female mice and in male volunteers. We inoculated mice and men with mixtures of wild-type N. gonorrhoeae and an isogenic mutant that lacks the PEA transferase, LptA. LptA production conferred a marked survival advantage for wild...

  10. Listeriolysin as a virulence factor in Listeria monocytogenes infection of neonatal mice and murine decidual tissue.

    OpenAIRE

    McKay, D B; Lu, C Y

    1991-01-01

    Listeriolysin is a 60-kDa protein which allows the growth of Listeria monocytogenes in macrophages and other cells and has been shown to be a virulence factor in Listeria infections of adult mice. However, the neonate and fetoplacental unit are major populations susceptible to listeriosis. Recent data indicate that macrophage and T-cell functions are markedly inhibited in these young mice, and the virulence of listeriolysin-negative (HLY-) and listeriolysin-positive (HLY+) Listeria cells in t...

  11. The art of persistence-the secrets to Burkholderia chronic infections.

    Science.gov (United States)

    Lewis, Eric R G; Torres, Alfredo G

    2016-08-01

    The Gram-negative proteobacteria genus Burkholderia encompasses multiple bacterial species that are pathogenic to humans and other vertebrates. Two pathogenic species of interest within this genus are Burkholderia pseudomallei (Bpm) and the B. cepacia complex (Bcc); the former is the causative agent of melioidosis in humans and other mammals, and the latter is associated with pneumonia in immunocompromised patients. One understudied and shared characteristic of these two pathogenic groups is their ability to persist and establish chronic infection within the host. In this review, we will explore the depth of knowledge about chronic infections caused by persistent Bpm and Bcc. We examine the host risk factors and immune responses associated with more severe chronic infections. We also discuss host adaptation and phenotypes associated with persistent Burkholderia species. Lastly, we survey how other intracellular bacteria associated with chronic infections are combatted and explore possible future applications to target Burkholderia Our goal is to highlight understudied areas that should be addressed for a more thorough understanding of chronic Burkholderia infections and how to combat them. PMID:27440810

  12. Inhibition of lung serine proteases in mice: a potentially new approach to control influenza infection

    Directory of Open Access Journals (Sweden)

    Błazejewska Paulina

    2011-01-01

    Full Text Available Abstract Background Host serine proteases are essential for the influenza virus life cycle because the viral haemagglutinin is synthesized as a precursor which requires proteolytic maturation. Therefore, we studied the activity and expression of serine proteases in lungs from mice infected with influenza and evaluated the effect of serine protease inhibitors on virus replication both in cell culture and in infected mice. Results Two different inbred mouse strains were investigated: DBA/2J as a highly susceptible and C57Bl/6J as a more resistant strain to influenza virus infection. The serine proteases from lung homogenates of mice exhibited pH optima of 10.00. Using the substrate Bz-Val-Gly-Arg-p-nitroanilide or in zymograms, the intensities of proteolysis increased in homogenates from both mouse strains with time post infection (p.i. with the mouse-adapted influenza virus A/Puerto Rico/8/34 (H1N1; PR8. In zymograms at day 7 p.i., proteolytic bands were stronger and numerous in lung homogenates from DBA/2J than C57Bl/6J mice. Real-time PCR results confirmed differential expression of several lung proteases before and after infecting mice with the H1N1 virus. The most strongly up-regulated proteases were Gzma, Tmprss4, Elane, Ctrl, Gzmc and Gzmb. Pretreatment of mouse and human lung cell lines with the serine protease inhibitors AEBSF or pAB or a cocktail of both prior to infection with the H1N1 or the A/Seal/Massachusetts/1/80 (H7N7; SC35M virus resulted in a decrease in virus replication. Pretreatment of C57Bl/6J mice with either AEBSF or a cocktail of AEBSF and pAB prior to infection with the H1N1 virus significantly reduced weight loss and led to a faster recovery of treated versus untreated mice while pAB alone exerted a very poor effect. After infection with the H7N7 virus, the most significant reduction of weight loss was obtained upon pretreatment with either the protease inhibitor cocktail or pAB. Furthermore, pretreatment of C57BL/6J

  13. Structured approach to design of diagnostic test evaluation studies for chronic progressive infections in animals

    DEFF Research Database (Denmark)

    Nielsen, Søren Saxmose; Toft, Nils; Gardner, Ian Andrew

    2011-01-01

    Diagnostic test evaluations (DTEs) for chronic infections are challenging because a protracted incubation period has to be considered in the design of the DTE, and the adverse effects of infection may be widespread and progressive over an animal's entire life. Frequently, the specific purpose......) than originally intended. The objective of this paper is to outline a structured approach to the design and conduct of a DTE for diagnostic tests used for chronic infections in animals, and intended for different purposes. We describe the process from reflections about test purpose and the underlying...... of the test is not formally considered when a test is evaluated. Therefore, the result is often a DTE where test sensitivity and specificity estimates are biased, either because of problems with establishing the true infection status or because the test detects another aspect of the infection (and analyte...

  14. Investigation on the possibility of spontaneous cure of mice infected with different strains of Trypanosoma cruzi Investigação da possibilidade de cura espontânea de camundongos infectados com cepas diferentes de Trypanosoma cruzi

    OpenAIRE

    Juracy B. Magalhães; Sonia G Andrade

    1994-01-01

    Seventy Swiss mice chronically infected with different strains of Trypanosoma cruzi, with persistently negative parasitemia on routine blood examination were parasitologically investigated to find out whether spontaneous cure occurred. Duration of infection varied from 90 to 250 days in the initial phase of this investigation. Parasitological tests consisted of daily direct blood examination performed during at least 25 days, followed by xenodiagnosis and subinoculation of blood into newborn ...

  15. Characterising novel anti-biofilm targets for the treatment of chronic Pseudomonas aeruginosa infection in the cystic fibrosis lung

    OpenAIRE

    McCarthy, Ronan

    2014-01-01

    The global rise in antibiotic resistance is a significant problem facing healthcare professionals. In particular within the cystic fibrosis (CF) lung, bacteria can establish chronic infection and resistance to a wide array of antibiotic therapies. One of the principle pathogens associated with chronic infection in the CF lung is Pseudomonas aeruginosa. P. aeruginosa can establish chronic infection in the CF lung partly through the use of the biofilm mode of growth. This biofilm mode of growth...

  16. Experimental infection of Balb/c nude mice with Hepatitis E virus

    Directory of Open Access Journals (Sweden)

    Zhu Jianguo

    2009-06-01

    Full Text Available Abstract Background Several animal species can reportedly act as reservoirs for Hepatitis E virus (HEV, a zoonotic pathogen. HEV and antibody to the virus have been detected in a variety of animals including rodents. Pig and rat models for HEV have been established for HEV, but a nude mouse has not yet been developed. Methods Balb/c nude mice were inoculated with swine HEV, both orally and via intravenous injection to insure infection. Negative control and experimental contact-exposed groups of mice were also included in the study. The liver, spleen, kidney, jejunum, ileum, cecum and colon of each mouse from all three groups were collected for reverse transcription nested polymerase chain reaction (RT-nPCR detection, indirect immunofluorescence observation and histopathologic examination. The sera from nude mice were tested for anti-HEV IgG by enzyme linked immunosorbent assay (ELISA. Activities of liver enzymes, including alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP, as well as total bilirubin (TBIL were also measured in the sera of the nude mice. Results HEV antigens and HEV RNA were detected in liver, spleen, kidney, jejunum, ileum and colon both by indirect immunofluorescence and by RT-nPCR in all of the inoculated and in one of the contact-exposed nude mice. Histopathological changes were observed in the liver and spleen of these mice. Infected mice showed increased levels of AST, ALP, and anti-HEV IgG in sera. The livers of contact-exposed mice showed obvious histopathological damage. Conclusion Nude mice could be readily infected by HEV isolated from pigs. The nude mouse may therefore be a useful animal model for studying the pathogenesis of HEV.

  17. Dietary L-glutamine supplementation improves pregnancy outcome in mice infected with type-2 porcine circovirus.

    Science.gov (United States)

    Ren, Wenkai; Luo, Wei; Wu, Miaomiao; Liu, Gang; Yu, Xinglong; Fang, Jun; Li, Teijun; Yin, Yulong; Wu, Guoyao

    2013-09-01

    Porcine circovirus type 2 (PCV2) causes reproductive failure in swine. As glutamine can enhance immune function in animals, this study was conducted with mice to test the hypothesis that dietary glutamine supplementation will improve pregnancy outcome in PCV2-infected dams. Beginning on day 0 of gestation, mice were fed a standard diet supplemented with 1.0% L-glutamine or 1.22% L-alanine (isonitrogenous control). All mice were infected with PCV2 (2000 TCID50) on day 10 of gestation. On day 17 of gestation, six mice from each group were euthanized to obtain maternal tissues and fetuses for hematology and histopathology tests. The remaining mice continued to receive their respective diets supplemented with 1.0% L-glutamine or 1.22% L-alanine through lactation. The PCV2 virus was present in maternal samples (serum and lung) of most mice in the control group but was not detected in the glutamine-supplemented mice. Dietary glutamine supplementation reduced abortion, decreased fetal deaths, and enhanced neonatal survival. The glutamine treatment also reduced concentrations of interleukin-6, while increasing concentrations of tumor necrosis factor-α and C-reactive protein, in the maternal serum of mice. Furthermore, glutamine supplementation attenuated microscopic lesions in maternal tissues (lung, spleen, and liver). Collectively, these results indicate that dietary glutamine supplementation is beneficial for ameliorating reproductive failure in virus-infected mice. The findings support the notion that gestating dams require adequate amounts of dietary glutamine for the optimal survival and growth of embryos, fetuses, and neonates, and have important implications for nutritional support of mammals (including swine and humans) during gestation and lactation.

  18. Helicobacter hepaticus infection promotes hepatitis and preneoplastic foci in farnesoid X receptor (FXR deficient mice.

    Directory of Open Access Journals (Sweden)

    Alton G Swennes

    Full Text Available Farnesoid X receptor (FXR is a nuclear receptor that regulates bile acid metabolism and transport. Mice lacking expression of FXR (FXR KO have a high incidence of foci of cellular alterations (FCA and liver tumors. Here, we report that Helicobacter hepaticus infection is necessary for the development of increased hepatitis scores and FCA in previously Helicobacter-free FXR KO mice. FXR KO and wild-type (WT mice were sham-treated or orally inoculated with H. hepaticus. At 12 months post-infection, mice were euthanized and liver pathology, gene expression, and the cecal microbiome were analyzed. H. hepaticus induced significant increases hepatitis scores and FCA numbers in FXR KO mice (P<0.01 and P<0.05, respectively. H. hepaticus altered the beta diversity of cecal microbiome in both WT and FXR KO mice compared to uninfected mice (P<0.05. Significant upregulation of β-catenin, Rela, Slc10a1, Tlr2, Nos2, Vdr, and Cyp3a11 was observed in all FXR KO mice compared to controls (P<0.05. Importantly, H. hepaticus and FXR deficiency were necessary to significantly upregulate Cyp2b10 (P<0.01. FXR deficiency was also a potent modulator of the cecal microbiota, as observed by a strong decrease in alpha diversity. A significant decrease in Firmicutes, particularly members of the order Clostridiales, was observed in FXR KO mice (P<0.05 and FDR<5%, ANOVA. While FXR deficiency strongly affects expression of genes related to immunity and bile acid metabolism, as well as the composition of the microbiome; however, its deficiency was not able to produce significant histopathological changes in the absence of H. hepaticus infection.

  19. Exogenous interleukin-6, interleukin-13, and interferon-gamma provoke pulmonary abnormality with mild edema in enterovirus 71-infected mice

    OpenAIRE

    Huang Szu-Wei; Lee Yi-Ping; Hung Yu-Ting; Lin Chun-Hung; Chuang Jih-Ing; Lei Huan-Yao; Su Ih-Jen; Yu Chun-Keung

    2011-01-01

    Abstract Background Neonatal mice developed neurological disease and pulmonary dysfunction after an infection with a mouse-adapted human Enterovirus 71 (EV71) strain MP4. However, the hallmark of severe human EV71 infection, pulmonary edema (PE), was not evident. Methods To test whether EV71-induced PE required a proinflammatory cytokine response, exogenous pro-inflammatory cytokines were administered to EV71-infected mice during the late stage of infection. Results After intracranial infecti...

  20. Pregnancy reduces the genetic resistance of C57BL/6 mice to Listeria monocytogenes infection by intragastric inoculation

    OpenAIRE

    Poulsen, Keith P; Faith, Nancy G.; Steinberg, Howard; Czuprynski, Charles J.

    2011-01-01

    In this study, we compared genetically resistant C57BL/6 and susceptible A/J mice for their resistance to L. monocytogenes infection model during pregnancy. Intragastric infection with modest numbers of bacterial cells (105 CFU) caused reproducible fetal infection and abortion in both mouse strains. Bioluminescence imaging demonstrated dissemination of L. monocytogenes cells from maternal to fetal organs within 3 days of intragastric infection. Although non-pregnant C57BL/6 mice were signific...

  1. The Emerging Extrahepatic Manifestations of Hepatitis C Virus Infection in Chronic Hepatitis and Mixed Cryoglobulinemia

    Directory of Open Access Journals (Sweden)

    Poupak Fallahi

    2008-08-01

    Full Text Available Hepatitis C virus (HCV is known to be responsible for both hepatic and extrahepatic diseases. Mixed cryoglobulinemia, Sjögren syndrome, and chronic polyarthritis are the most documented rheumatologic extrahepatic manifestations of HCV infection. The most frequent and clinically important extrahepatic endocrine manifestations of chronic HCV infection are thyroid disorders and type 2 diabetes mellitus. From a meta-analysis of the literature, a significant association between HCV infection and thyroid autoimmunity and/or hypothyroidism as well as a high prevalence of thyroid cancer have been reported. The pattern of thyroid disorders observed in HCV infected patients is characterized by the presence of elevated circulating anti-thyroid peroxidase antibodies with increased risk of hypothyroidism. Several clinical epidemiologic studies have reported that HCV infection is a risk factor for type 2 diabetes. The type of diabetes manifested by subjects with chronic HCV infection is not of the classical type 2 diabetes; in fact, HCV-related diabetic patients are leaner than the classical diabetic patients, and have a significantly lower LDL-cholesterol, and both systolic and diastolic blood pressure. Furthermore, patients with mixed cryoglobulinemia (mixed cryoglobulinemia and chronic HCV infection with type 2 diabetes have more frequently non-organ-specific-autoantibodies than non-diabetic patients with mixed cryoglobulinemia and those with chronic HCV infection. Based on the above-mentioned findings, it has been hypothesized that diabetes in HCV infection may have an immune-mediated pathogenesis. In patients with chronic HCV infection, we found an increased risk of carotid artery plaque and carotid intima-media thickening. These findings suggested a possible role for chronic hepatitis C in the pathogenesis of carotid artery remodelling. Recently, high prevalence rates of anti-HCV antibodies were shown in patients with hypertrophic cardiomyopathy or

  2. Effect of bee venom or proplis on molecular and parasitological aspects of Schistosoma mansoni infected mice.

    Science.gov (United States)

    Mohamed, Azza H; Hassab El-Nabi, Sobhy E; Bayomi, Asmaa E; Abdelaal, Ahmed A

    2016-06-01

    The present study was performed to elucidate the efficacy of Apis mellifera L bee venom (BV) or proplis (200 mg/kg orally for three consecutive days) on Schistosoma mansoni infected mice. The results recorded reduction in the total worm burden, numbers of immature eggs and the ova count in hepatic tissue in BV (sting or injection) or proplis treated groups as compared to the infected group. Histological examination illustrated a significant increase (P ≤ 0.05) in the diameter of hepatic granuloma in BV treated groups (272.78 and 266.9, respectively) and a significant decrease in proplis treated mice (229.35) compared with the infected group (260.67). Electrophoretic pattern of RNA showed a decrease in mean of maximal optical density in liver and intestine of S. mansoni infected mice treated with bee venom (sting or injection) as compared with infected group. Flow cytometry analyses of RNA or apoptotic percentage of worms recovered from BV sting (19 and 49 % respectively); BV injected (20.5 and 51.17 %, respectively) and proplis (35 and 23.93 %, respectively) groups were compared with S. mansoni infected group (37.87 and 39.21 %, respectively). It can be concluded that administration of bee venom or proplis are effective in case of S. mansoni infection. Although bee venom cause increase of granuloma diameter and this might be due to venom concentration and further studies are required to avoid such harmful effect. PMID:27413311

  3. Association between Helicobacter pylori Infection and Chronic Urticaria: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Huiyuan Gu

    2015-01-01

    Full Text Available Background. Some studies have shown the possible involvement of Helicobacter pylori (H. pylori infection in chronic urticaria, but the relationship remains controversial. The aim of this meta-analysis was to quantitatively assess the association between H. pylori infection and chronic urticaria. Methods. Observational studies comparing the prevalence of H. pylori infection in patients with chronic urticaria and control subjects were identified through a systematic search in MEDLINE and EMBASE up to July 2014. H. pylori infection was confirmed by serological or nonserological tests. For subgroup analyses, studies were separated by region, publication year, and H. pylori detection method to screen the potential factors resulting in heterogeneity. Results. 16 studies involving 965 CU cases and 1235 controls were included. Overall, the prevalence of H. pylori infection was higher in urticarial patients than in controls (OR = 1.66; 95% CI: 1.12–2.45; P=0.01. This result persisted in subanalysis of nine high-quality studies (OR = 1.36; 95% CI: 1.03–1.80; P=0.03. Subgroup analysis showed that detection method of H. pylori is also a potential influential factor for the overall results. Conclusions. Our present meta-analysis suggests that H. pylori infection is significantly, though weakly, associated with an increased risk of chronic urticaria.

  4. Non-lethal infection parameters in mice separate sheep Type II Toxoplasma gondii isolates by virulence

    DEFF Research Database (Denmark)

    Jungersen, Gregers; Jensen, L; Rask, M.R.;

    2002-01-01

    The zoonotic protozoan parasite Toxoplasma gondii can infect all warm-blooded animals, but virulence of isolates has previously been characterised mainly by the ability to kill mice after experimental infections. In the present study, 15 Type II strains of T. gondii, isolated from five adult sheep....... Although Type II T gondii strains are non-virulent to mice by lethality studies, significant differences in mouse virulence were observed between the strains of T gondii isolated either from adult sheep or from sheep abortions. It was not possible to characterise strains isolated front sheep abortions...

  5. Competitive inhibitor of cellular alpha-glucosidases protects mice from lethal dengue virus infection

    OpenAIRE

    Chang, Jinhong; Schul, Wouter; Yip, Andy; Xu, Xiaodong; Guo, Ju-Tao; Block, Timothy M.

    2011-01-01

    Dengue virus infection causes diseases in people, ranging from the acute febrile illness Dengue fever, to life-threatening Dengue Hemorrhagic Fever/Dengue Shock Syndrome. We previously reported that a host cellular α-glucosidases I and II inhibitor, imino sugar CM-10-18, potently inhibited dengue virus replication in cultured cells, and significantly reduced viremia in dengue virus infected AG129 mice. In this report we show that CM-10-18 also significantly protects mice from death and/or dis...

  6. Antiviral activity of bacteria-derived human alpha interferons against encephalomyocarditis virus infection of mice.

    OpenAIRE

    Weck, P K; Rinderknecht, E; Estell, D A; Stebbing, N

    1982-01-01

    Bacteria-derived human leukocyte interferon (IFN) subtypes, IFN-alpha A, -alpha B, and -alpha D, and two hybrid IFNs, IFN-alpha AD and -alpha DA, were examined for both in vitro and in vivo antiviral activity. Two of these materials in highly purified form (IFN-alpha D and -alpha D) protect mice against lethal doses of encephalomyocarditis virus infection. A single dose of 1 microgram of protein of IFN-alpha D 3 h before infection conferred protection in both BDF1 and CD-1 mice against enceph...

  7. Detection of Corynebacterium bovis infection in athymic nude mice from a research animal facility in Korea

    OpenAIRE

    Kim, Tae-Hyoun; Kim, Dong-Su; Han, Ju-Hee; Chang, Seo-Na; Kim, Kyung-Sul; Seok, Seung-Hyeok; Kim, Dong-Jae; Park, Jong-Hwan; Park, Jae-Hak

    2014-01-01

    Corynebacterium (C.) bovis infection in nude mice causes hyperkeratosis and weight loss and has been reported worldwide but not in Korea. In 2011, nude mice from an animal facility in Korea were found to have white flakes on their dorsal skin. Histopathological testing revealed that the mice had hyperkeratosis and Gram-positive bacteria were found in the skin. We identified isolated bacteria from the skin lesions as C. bovis using PCR and 16S rRNA sequencing. To the best of our knowledge, thi...

  8. La Crosse virus infectivity, pathogenesis, and immunogenicity in mice and monkeys

    Directory of Open Access Journals (Sweden)

    Murphy Brian R

    2008-02-01

    Full Text Available Abstract Background La Crosse virus (LACV, family Bunyaviridae, was first identified as a human pathogen in 1960 after its isolation from a 4 year-old girl with fatal encephalitis in La Crosse, Wisconsin. LACV is a major cause of pediatric encephalitis in North America and infects up to 300,000 persons each year of which 70–130 result in severe disease of the central nervous system (CNS. As an initial step in the establishment of useful animal models to support vaccine development, we examined LACV infectivity, pathogenesis, and immunogenicity in both weanling mice and rhesus monkeys. Results Following intraperitoneal inoculation of mice, LACV replicated in various organs before reaching the CNS where it replicates to high titer causing death from neurological disease. The peripheral site where LACV replicates to highest titer is the nasal turbinates, and, presumably, LACV can enter the CNS via the olfactory neurons from nasal olfactory epithelium. The mouse infectious dose50 and lethal dose50 was similar for LACV administered either intranasally or intraperitoneally. LACV was highly infectious for rhesus monkeys and infected 100% of the animals at 10 PFU. However, the infection was asymptomatic, and the monkeys developed a strong neutralizing antibody response. Conclusion In mice, LACV likely gains access to the CNS via the blood stream or via olfactory neurons. The ability to efficiently infect mice intranasally raises the possibility that LACV might use this route to infect its natural hosts. Rhesus monkeys are susceptible to LACV infection and develop strong neutralizing antibody responses after inoculation with as little as 10 PFU. Mice and rhesus monkeys are useful animal models for LACV vaccine immunologic testing although the rhesus monkey model is not optimal.

  9. Protective effect of Plantago major L. Pectin polysaccharide against systemic Streptococcus pneumoniae infection in mice.

    Science.gov (United States)

    Hetland, G; Samuelsen, A B; Løvik, M; Paulsen, B S; Aaberge, I S; Groeng, E C; Michaelsen, T E

    2000-10-01

    The antibacterial effect of a soluble pectin polysaccharide, PMII, isolated from the leaves of Plantago major, was examined in inbred NIH/OlaHsd and Fox Chase SCID mice experimentally infected with Streptococcus pneumoniae serotype 6B. Serotype 6B is known to give a more protracted infection when injected intraperitoneally into susceptible mice than more virulent serotypes like type 4. PMII was administered i.p. either once 3 days before challenge or once to thrice from 3 to 48 h after challenge. The number of bacteria in blood and the mouse survival rate were recorded. Pre-challenge administration of PMII and also lipopolysaccharide (LPS), included as a control, gave a dose-dependent protective effect against S. pneumoniae type 6B infection. However, injection of PMII after establishment of the infection in NIH/OlaHsd mice had no effect. The data demonstrate that, firstly, the polysaccharide fraction PMII from P. major protects against pneumococcal infection in mice when administered systemically prechallenge, and secondly that the protective effect is owing to stimulation of the innate and not the adaptive immune system.

  10. Virus-like particle-based vaccine against coxsackievirus A6 protects mice against lethal infections.

    Science.gov (United States)

    Shen, Chaoyun; Ku, Zhiqiang; Zhou, Yu; Li, Dapeng; Wang, Lili; Lan, Ke; Liu, Qingwei; Huang, Zhong

    2016-07-25

    Coxsackievirus A6 (CA6) is emerging as one of the major causative agents of hand, foot, and mouth disease (HFMD) worldwide. However, no vaccine is currently available for preventing CA6 infection. Here, we report the development of a virus-like particle (VLP)-based recombinant vaccine for CA6. We produced CA6 VLPs in insect cells by infecting the cells with a baculovirus coexpressing the genes encoding CA6 P1 and 3CD. Biochemical analyses showed that the produced VLPs consisted of VP0, VP1, and VP3 capsid subunit proteins generated by the cleavage of P1 by 3CD. Mice immunized with these VLPs produced CA6-specific serum antibodies. Passive transfer of antisera from CA6 VLP-immunized mice protected recipient mice from lethal infections caused by homologous and heterologous CA6 strains. Moreover, active immunization of mice with CA6 VLPs efficiently conferred protection against both homologous and heterologous CA6 infections. These results suggested that CA6 VLP-based recombinant vaccine is a promising candidate vaccine for preventing CA6 infection and can be incorporated into a multivalent HFMD vaccine formulation to achieve broad-spectrum and effective prevention of this disease. PMID:27340093

  11. Effect of Chronic Use of Recreational Drugs on the Sperm Count in Albino Mice

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    Sravonee Purkayastha

    2014-05-01

    Full Text Available Chronic use of various recreational drugs is leading to drug abuse which is increasingly developed in the modern society among the various populations throughout the world. The present study was conducted to investigate the impact of a few recreational drugs viz., anabolic androgenic steroids (AAS, alcohol and nicotine on male fertility status which was assessed by measuring sperm count in male albino mice. Semen samples were collected from normal, AAS-treated, alcohol-treated and nicotine-treated mice and the sperm count (in millions/ml semen was assessed at regular intervals i.e. on 10th, 20th, 30th, 45th,60th,75th and 90th day of treatment during the experimental period of 90 days. The results showed a significant decrease in the sperm count in AAS-treated, nicotine-treated (p<0.01 and alcohol-treated mice (p<0.05 compared to that of the normal mice. The present study clearly indicates suppression of sperm count on AAS, alcohol and nicotine treatment which may be one of the contributing factors in male infertility.

  12. Ultrastructural Changes of Caudate Nucleus in Mice Chronically Treated with Manganese.

    Science.gov (United States)

    Villalobos, Virginia; Hernández-Fonseca, Juan Pablo; Bonilla, Ernesto; Medina-Leendertz, Shirley; Mora, Marylu; Mosquera, Jesús

    2015-01-01

    Manganese (Mn) is able to cross the blood-brain barrier and induces functional and structural alterations during the intoxication by this metal. Therefore, the effects of chronic administration of Mn in the caudate nucleus of mice were evaluated by electron microscopy. Male albino mice were injected intraperitoneally with MnCl2 (5 mg/kg/d) 5 d per week during 9 weeks. The control group received only 0.9% of NaCl solution. The caudate nuclei were extracted and subsequently processed to be observed on a conventional transmission electron microscope at 2, 4, 6, and 9 weeks after treatment. A high percentage of vacuolated and swollen mitochondria were found throughout all the analyzed periods. Myelin disarrangement and ultrastructural alterations related to edema were observed increased in Mn-treated mice at week 9. Granular degeneration of myelin at week 9 accompanied with deposition of electron dense granules in the neuropil was also observed. Edema in neuropil and glial cells was detected from week 2 to week 9 accompanied by swollen mitochondria. Neuronal bodies, synaptic terminals, and perivascular cells were found swollen. Decreased electron density in postsynaptic areas and decreased and dispersed synaptic vesicles in presynaptic areas were noted in Mn-treated animals. Some neurons from Mn-treated mice showed cisternae dilation of the Golgi apparatus. These results suggest that Mn-treatment produces structural alterations in the caudate nucleus that could be responsible for some of the neurotoxic effects of this metal. PMID:25569534

  13. Characterization of Lethal Zika Virus Infection in AG129 Mice

    OpenAIRE

    Aliota, Matthew T; Elizabeth A Caine; Emma C Walker; Katrina E Larkin; Erwin Camacho; Jorge E Osorio

    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 ...

  14. Bioluminescence Imaging of Chlamydia muridarum Ascending Infection in Mice

    OpenAIRE

    Jessica Campbell; Yumeng Huang; Yuanjun Liu; Robert Schenken; Bernard Arulanandam; Guangming Zhong

    2014-01-01

    Chlamydial pathogenicity in the upper genital tract relies on chlamydial ascending from the lower genital tract. To monitor chlamydial ascension, we engineered a luciferase-expressing C. muridarum. In cells infected with the luciferase-expressing C. muridarum, luciferase gene expression and enzymatic activity (measured as bioluminescence intensity) correlated well along the infection course, suggesting that bioluminescence can be used for monitoring chlamydial replication. Following an intrav...

  15. Bile signalling promotes chronic respiratory infections and antibiotic tolerance.

    Science.gov (United States)

    Reen, F Jerry; Flynn, Stephanie; Woods, David F; Dunphy, Niall; Chróinín, Muireann Ní; Mullane, David; Stick, Stephen; Adams, Claire; O'Gara, Fergal

    2016-01-01

    Despite aggressive antimicrobial therapy, many respiratory pathogens persist in the lung, underpinning the chronic inflammation and eventual lung decline that are characteristic of respiratory disease. Recently, bile acid aspiration has emerged as a major comorbidity associated with a range of lung diseases, shaping the lung microbiome and promoting colonisation by Pseudomonas aeruginosa in Cystic Fibrosis (CF) patients. In order to uncover the molecular mechanism through which bile modulates the respiratory microbiome, a combination of global transcriptomic and phenotypic analyses of the P. aeruginosa response to bile was undertaken. Bile responsive pathways responsible for virulence, adaptive metabolism, and redox control were identified, with macrolide and polymyxin antibiotic tolerance increased significantly in the presence of bile. Bile acids, and chenodeoxycholic acid (CDCA) in particular, elicited chronic biofilm behaviour in P. aeruginosa, while induction of the pro-inflammatory cytokine Interleukin-6 (IL-6) in lung epithelial cells by CDCA was Farnesoid X Receptor (FXR) dependent. Microbiome analysis of paediatric CF sputum samples demonstrated increased colonisation by P. aeruginosa and other Proteobacterial pathogens in bile aspirating compared to non-aspirating patients. Together, these data suggest that bile acid signalling is a leading trigger for the development of chronic phenotypes underlying the pathophysiology of chronic respiratory disease. PMID:27432520

  16. Chronic renal failure among HIV-1-infected patients

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Kirk, Ole; Gatell, Jose;

    2007-01-01

    BACKGROUND: The role of exposure to antiretrovirals in chronic renal failure (CRF) is not well understood. Glomerular filtration rates (GFR) are estimated using the Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) equations. METHODS: Baseline was arbitrarily defined as the first...

  17. Therapy chronic trichomoniasis at patients with associated urogenital chlamydial infection

    Directory of Open Access Journals (Sweden)

    A. L. Poznyak

    2009-01-01

    Full Text Available Present material of problem question therapy chronic trichomoniasis. Study clinical and bacteriological effectiveness basic etiotropic preparation and their combination, used in treatment patients trichomoniasis. Found that the combined application antiprotozoal drugs have a more pronounced effect on kills T. vaginalis and shortens the rehabilitation of the patient.

  18. Anti-inflammatory and Anti-tumorigenic Effects of Açai Berry in Helicobacter felis-infected mice

    OpenAIRE

    Lee, Ju Yup; Kim, Nayoung; Choi, Yoon Jeong; Nam, Ryoung Hee; Lee, Seonmin; Ham, Min Hee; Suh, Ji Hyung; Choi, Yoon Jin; Lee, Hye Seung; Lee, Dong Ho

    2016-01-01

    Background: The aim of this study was to evaluate the anti-inflammatory and anti-tumorigenic effect of açai berry after chronic Helicobacter felis colonization in the stomachs of C57BL/6 mice. Methods: A total of 57 four-week-old female C57BL/6 mice (18 control mice and 39 experimental mice) were used. The mice were administered orogastrically with vehicle only or vehicle containing H. felis, 5 times every other day. After inoculation of H. felis, mice were fed either a standard or an açai-co...

  19. Blastocystis hominis and Endolimax nana Co-Infection Resulting in Chronic Diarrhea in an Immunocompetent Male

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    Mitanshu Shah

    2012-06-01

    Full Text Available Blastocystis hominis and Endolimax nana exist as two separate parasitic organisms; however co-infection with the two individual parasites has been well documented. Although often symptomatic in immunocompromised individuals, the pathogenicity of the organisms in immunocompetent subjects causing gastrointestinal symptoms has been debated, with studies revealing mixed results. Clinically, both B. hominis and E. nana infection may result in acute or chronic diarrhea, generalized abdominal pain, nausea, vomiting, flatulence and anorexia. We report the case of a 24-year-old immunocompetent male presenting with chronic diarrhea and abdominal pain secondary to B. hominis and E. nana treated with metronidazole, resulting in symptom resolution and eradication of the organisms. Our case illustrates that clinicians should be cognizant of both B. hominis and E. nana infection as a cause of chronic diarrhea in an immunocompetent host. Such awareness will aid in a timely diagnosis and possible parasitic eradication with resolution of gastrointestinal symptoms.

  20. Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise.

    Science.gov (United States)

    Miner, Jonathan J; Cao, Bin; Govero, Jennifer; Smith, Amber M; Fernandez, Estefania; Cabrera, Omar H; Garber, Charise; Noll, Michelle; Klein, Robyn S; Noguchi, Kevin K; Mysorekar, Indira U; Diamond, Michael S

    2016-05-19

    Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and fetal disease associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling (Ifnar1(-/-)) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in fetal demise that was associated with ZIKV infection of the placenta and fetal brain. We identified ZIKV within trophoblasts of the maternal and fetal placenta, consistent with a trans-placental infection route. Antibody blockade of Ifnar1 signaling in WT pregnant mice enhanced ZIKV trans-placental infection although it did not result in fetal death. These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations.

  1. The RenTg mice: a powerful tool to study renin-dependent chronic kidney disease.

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    Anne-Cecile Huby

    Full Text Available BACKGROUND: Several studies have shown that activation of the renin-angiotensin system may lead to hypertension, a major risk factor for the development of chronic kidney disease (CKD. The existing hypertension-induced CDK mouse models are quite fast and consequently away from the human pathology. Thus, there is an urgent need for a mouse model that can be used to delineate the pathogenic process leading to progressive renal disease. The objective of this study was dual: to investigate whether mice overexpressing renin could mimic the kinetics and the physiopathological characteristics of hypertension-induced renal disease and to identify cellular and/or molecular events characterizing the different steps of the progression of CKD. METHODOLOGY/PRINCIPAL FINDINGS: We used a novel transgenic strain, the RenTg mice harboring a genetically clamped renin transgene. At 3 months, heterozygous mice are hypertensive and slightly albuminuric. The expression of adhesion markers such as vascular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 are increased in the renal vasculature indicating initiation of endothelial dysfunction. At 5 months, perivascular and periglomerular infiltrations of macrophages are observed. These early renal vascular events are followed at 8 months by leukocyte invasion, decreased expression of nephrin, increased expression of KIM-1, a typical protein of tubular cell stress, and of several pro-fibrotic agents of the TGFβ family. At 12 months, mice display characteristic structural alterations of hypertensive renal disease such as glomerular ischemia, glomerulo- and nephroangio-sclerosis, mesangial expansion and tubular dilation. CONCLUSIONS/SIGNIFICANCE: The RenTg strain develops CKD progressively. In this model, endothelial dysfunction is an early event preceding the structural and fibrotic alterations which ultimately lead to the development of CKD. This model can provide new insights into the

  2. Multimodal assessment of painful peripheral neuropathy induced by chronic oxaliplatin-based chemotherapy in mice

    Directory of Open Access Journals (Sweden)

    Dorsey Susan G

    2011-04-01

    Full Text Available Abstract Background A major clinical issue affecting 10-40% of cancer patients treated with oxaliplatin is severe peripheral neuropathy with symptoms including cold sensitivity and neuropathic pain. Rat models have been used to describe the pathological features of oxaliplatin-induced peripheral neuropathy; however, they are inadequate for parallel studies of oxaliplatin's antineoplastic activity and neurotoxicity because most cancer models are developed in mice. Thus, we characterized the effects of chronic, bi-weekly administration of oxaliplatin in BALB/c mice. We first studied oxaliplatin's effects on the peripheral nervous system by measuring caudal and digital nerve conduction velocities (NCV followed by ultrastructural and morphometric analyses of dorsal root ganglia (DRG and sciatic nerves. To further characterize the model, we examined nocifensive behavior and central nervous system excitability by in vivo electrophysiological recording of spinal dorsal horn (SDH wide dynamic range neurons in oxaliplatin-treated mice Results We found significantly decreased NCV and action potential amplitude after oxaliplatin treatment along with neuronal atrophy and multinucleolated DRG neurons that have eccentric nucleoli. Oxaliplatin also induced significant mechanical allodynia and cold hyperalgesia, starting from the first week of treatment, and a significant increase in the activity of wide dynamic range neurons in the SDH. Conclusions Our findings demonstrate that chronic treatment with oxaliplatin produces neurotoxic changes in BALB/c mice, confirming that this model is a suitable tool to conduct further mechanistic studies of oxaliplatin-related antineoplastic activity, peripheral neurotoxicity and pain. Further, this model can be used for the preclinical discovery of new neuroprotective and analgesic compounds.

  3. Puerarin protects against damage to spatial learning and memory ability in mice with chronic alcohol poisoning

    Directory of Open Access Journals (Sweden)

    S.Q. Cui

    2015-06-01

    Full Text Available We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each. The model group received 60% (v/v ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N and microglia (by Ib1 were conducted. Glutamic acid (Glu and gamma amino butyric acid (GABA in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC, and tumor necrosis factor (TNF-α and interleukin (IL-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05 by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01, and neurons were reduced only in the hippocampal dentate gyrus (P<0.01 in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05, and Glu/GABA, TNF-α, and IL-1β increased (P<0.01 with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.

  4. Sex differences in shotgun proteome analyses for chronic oral intake of cadmium in mice.

    Directory of Open Access Journals (Sweden)

    Yoshiharu Yamanobe

    Full Text Available Environmental diseases related to cadmium exposure primarily develop owing to industrial wastewater pollution and/or contaminated food. In regions with high cadmium exposure in Japan, cadmium accumulation occurs primarily in the kidneys of individuals who are exposed to the metal. In contrast, in the itai-itai disease outbreak that occurred in the Jinzu River basin in Toyama Prefecture in Japan, cadmium primarily accumulated in the liver. On the other hand, high concentration of cadmium caused renal tubular disorder and osteomalacia (multiple bone fracture, probably resulting from the renal tubular dysfunction and additional pathology. In this study, we aimed to establish a mouse model of chronic cadmium intake. We administered cadmium-containing drinking water (32 mg/l to female and male mice ad libitum for 11 weeks. Metal analysis using inductively coupled plasma mass spectrometry revealed that cadmium accumulated in the kidneys (927 x 10 + 185 ng/g in females and 661 x 10 + 101 ng/g in males, liver (397 x 10 + 199 ng/g in females and 238 x 10 + 652 ng/g in males, and thyroid gland (293 + 93.7 ng/g in females and 129 + 72.7 ng/g in males of mice. Female mice showed higher cadmium accumulation in the kidney, liver, and thyroid gland than males did (p = 0.00345, p = 0.00213, and p = 0.0331, respectively. Shotgun proteome analyses after chronic oral administration of cadmium revealed that protein levels of glutathione S-transferase Mu2, Mu4, and Mu7 decreased in the liver, and those of A1 and A2 decreased in the kidneys in both female and male mice.

  5. Changes in Autophagic Response in Patients with Chronic Hepatitis C Virus Infection

    OpenAIRE

    Rautou, Pierre-Emmanuel; Cazals-Hatem, Dominique; Feldmann, Gérard; Mansouri, Abdellah; Grodet, Alain; Barge, Sandrine; Martinot-Peignoux, Michèle; Duces, Aurélie; Bièche, Ivan; Lebrec, Didier; Bedossa, Pierre; Paradis, Valérie; Marcellin, Patrick; Valla, Dominique; Asselah, Tarik

    2011-01-01

    Autophagy is a regulated process that can be involved in the elimination of intracellular microorganisms and in antigen presentation. Some in vitro studies have shown an altered autophagic response in hepatitis C virus infected hepatocytes. The present study aimed at evaluating the autophagic process in the liver of chronic hepatitis C (CHC) patients. Fifty-six CHC patients and 47 control patients (8 with nonalcoholic steatohepatitis or alcoholic liver disease, 18 with chronic heptatitis B vi...

  6. Virus-Like Vesicle-Based Therapeutic Vaccine Vectors for Chronic Hepatitis B Virus Infection

    OpenAIRE

    Tracy D Reynolds; Buonocore, Linda; Rose, Nina F.; Rose, John K.; Robek, Michael D.

    2015-01-01

    More than 500,000 people die each year from the liver diseases that result from chronic hepatitis B virus (HBV) infection. Therapeutic vaccines, which aim to elicit an immune response capable of controlling the virus, offer a potential new treatment strategy for chronic hepatitis B. Recently, an evolved, high-titer vaccine platform consisting of Semliki Forest virus RNA replicons that express the vesicular stomatitis virus glycoprotein (VSV G) has been described. This platform generates virus...

  7. Histology of chronic gastritis with and without duodenitis in patients with Helicobacter pylori infection.

    OpenAIRE

    Phull, P S; Price, A. B.; Stephens, J; Rathbone, B J; Jacyna, M R

    1996-01-01

    AIM: To compare the histological characteristics of Helicobacter pylori positive chronic gastritis in patients with and without associated duodenitis. METHODS: Gastric mucosal biopsy specimens were obtained from patients undergoing endoscopy for dyspepsia. Severity of gastritis and density of H pylori infection were graded according to the Sydney system. RESULTS: Of the 69 patients studied, 15 had normal histology, 22 had chronic gastritis only (77.3% H pylori positive), 21 had duodenitis (90...

  8. Gastric metaplasia and Campylobacter pylori infection of duodenum in patients with chronic renal failure.

    OpenAIRE

    Shousha, S; Keen, C; Parkins, R A

    1989-01-01

    Duodenal biopsy specimens from 80 patients with chronic renal failure, who were undergoing haemodialysis, were examined by light microscopy for evidence of inflammation, gastric metaplasia, and Campylobacter pylori infection. Chronic duodenitis was present in 47 (59%) of patients, of whom only seven (9%) showed evidence of active inflammation. Gastric metaplasia was present in 50 (62.5%) of patients, yet Campylobacter pylori was identified in only two patients (2.5%). It is suggested that the...

  9. Variable impact of chronic stress on spatial learning and memory in BXD mice.

    Science.gov (United States)

    Shea, Chloe J A; Carhuatanta, Kimberly A K; Wagner, Jessica; Bechmann, Naomi; Moore, Raquel; Herman, James P; Jankord, Ryan

    2015-10-15

    The effects of chronic stress on learning are highly variable across individuals. This variability stems from gene-environment interactions. However, the mechanisms by which stress affects genetic predictors of learning are unclear. Thus, we aim to determine whether the genetic pathways that predict spatial memory performance are altered by previous exposure to chronic stress. Sixty-two BXD recombinant inbred strains of mice, as well as parent strains C57BL/6J and DBA/2J, were randomly assigned as behavioral control or to a chronic variable stress paradigm and then underwent behavioral testing to assess spatial memory and learning performance using the Morris water maze. Quantitative trait loci (QTL) mapping was completed for average escape latency times for both control and stress animals. Loci on chromosomes 5 and 10 were found in both control and stress environmental populations; eight additional loci were found to be unique to either the control or stress environment. In sum, results indicate that certain genetic loci predict spatial memory performance regardless of prior stress exposure, while exposure to stress also reveals unique genetic predictors of training during the memory task. Thus, we find that genetic predictors contributing to spatial learning and memory are susceptible to the presence of chronic stress.

  10. Congenital and nursing effects on the evolution of Schistosoma mansoni infection in mice

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    J. A. Lenzi

    1987-01-01

    Full Text Available Modification of the immune response to schistosomal infection in children or offspring born to mother R infected with Schistosoma mansoni has been demonstrated in human and in experimental schistosomiasis. One of the hypothesis to explain this fact could be the transfer of circulating antigens and antibodies from mother to foetus through the placenta or from mother to child by milk. The results of this spontaneous transference are controversial in the literature. In an attempt to investigate these questions, we studied one hundred and twenty offspring (Swiss mice, sixty born to infected-mothers (group A and sixty born to non-infected mothers (group B. These were percutaneously infected with 50 cercariae/mouse, and divided in six sub-groups (20 mice/sub-group, according to the following schedule: after birth (sub-groups A.I and B.I, 10 days old (sub-groups A.II and B.II and 21 days old (sub-groups A.III and B.III. After the exposure period, the young mice returned to their own mothers for nursing. Six weeks later, the mice were killed. We obtained the following results: 1 There is transference of antibody to cercariae (CAP, adult worms (SWAP and egg antigens (SEA from the infected mothers to the offspring, probably through placenta and milk; 2 Offspring born to infected mothers exhibit much less coagulative hepatic necrosis and show a lower number of eggs in the small intestine and a less intense and predominant exsudative stage of the hepatic granulomas when compared with the exsudative-productive stage of the control groups. The findings suggest that congenital and nursing factors can interfere on the development of the schistosomiasis infection, causing an hyporesponse to the eggs.

  11. High Dietary Folate in Mice Alters Immune Response and Reduces Survival after Malarial Infection.

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    Danielle N Meadows

    Full Text Available Malaria is a significant global health issue, with nearly 200 million cases in 2013 alone. Parasites obtain folate from the host or synthesize it de novo. Folate consumption has increased in many populations, prompting concerns regarding potential deleterious consequences of higher intake. The impact of high dietary folate on the host's immune function and response to malaria has not been examined. Our goal was to determine whether high dietary folate would affect response to malarial infection in a murine model of cerebral malaria. Mice were fed control diets (CD, recommended folate level for rodents or folic acid-supplemented diets (FASD, 10x recommended level for 5 weeks before infection with Plasmodium berghei ANKA. Survival, parasitemia, numbers of immune cells and other infection parameters were assessed. FASD mice had reduced survival (p<0.01, Cox proportional hazards and higher parasitemia (p< 0.01, joint model of parasitemia and survival compared with CD mice. FASD mice had lower numbers of splenocytes, total T cells, and lower numbers of specific T and NK cell sub-populations, compared with CD mice (p<0.05, linear mixed effects. Increased brain TNFα immunoreactive protein (p<0.01, t-test and increased liver Abca1 mRNA (p<0.01, t-test, a modulator of TNFα, were observed in FASD mice; these variables correlated positively (rs = 0.63, p = 0.01. Bcl-xl/Bak mRNA was increased in liver of FASD mice (p<0.01, t-test, suggesting reduced apoptotic potential. We conclude that high dietary folate increases parasite replication, disturbs the immune response and reduces resistance to malaria in mice. These findings have relevance for malaria-endemic regions, when considering anti-folate anti-malarials, food fortification or vitamin supplementation programs.

  12. Bone SPECT/CT detection of a sequestrum in chronic-infected nonunion of the tibia

    DEFF Research Database (Denmark)

    Madsen, Jan L

    2008-01-01

    Abstract: Sequestra are dead pieces of bone most often seen in long bones affected with prior or current infection. In addition to antibiotic therapy, chronic osteomyelitis with sequestration requires surgical debridement for cure. The author presents a case of tibial fracture associated with chr......Abstract: Sequestra are dead pieces of bone most often seen in long bones affected with prior or current infection. In addition to antibiotic therapy, chronic osteomyelitis with sequestration requires surgical debridement for cure. The author presents a case of tibial fracture associated...

  13. Protective Effect of Moderate Exercise for BALB/c Mice with Salmonella Typhimurium Infection.

    Science.gov (United States)

    Campos-Rodríguez, R; Godínez-Victoria, M; Arciniega-Martínez, I M; Reséndiz-Albor, A A; Reyna-Garfias, H; Cruz-Hernández, T R; Drago-Serrano, M E

    2016-01-01

    Moderate exercise enhances resistance to pathogen-associated infections. However, its influence on intestinal IgA levels and resistance to Salmonella typhimurium in mice has not been reported. The aim of this study was to assess the impact of moderate exercise on bacterial resistance and the intestinal-IgA response in a murine typhoid model. Sedentary and exercised (under a protocol of moderate swimming) BALB/c mice were orally infected with Salmonella typhimurium and sacrificed on days 7 or 14 post-infection (n=5 per group). Compared with infected sedentary mice, infected exercised animals had i) lower intestinal and systemic bacterial loads; ii) higher total and specific intestinal-IgA levels, iii) a higher percentage of IgA plasma cells in lamina propria; iv) a higher level on day 7 and lower level on day 14 of intestinal α- and J-chain mRNA and plasma corticosterone, v) unchanged mRNA expression of intestinal pIgR, and vi) a higher mRNA expression of liver pIgR, α-chain and J-chain on day 7. Hence, it is likely that an increase in corticosterone levels (stress response) induced by moderate exercise increased intestinal IgA levels by enabling greater liver expression of pIgR mRNA, leading to a rise in IgA transcytosis from the liver to intestine. The overall effect of these changes is an enhanced resistance to infection.

  14. Antihemolytic Activities of Green Tea, Safflower, and Mulberry Extracts during Plasmodium berghei Infection in Mice

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    Suthin Audomkasok

    2014-01-01

    Full Text Available Malaria-associated hemolysis is associated with mortality in adult patients. It has been speculated that oxidative stress and inflammation induced by malaria parasite are involved in its pathophysiology. Hence, we aimed to investigate the antihemolytic effect of green tea, safflower, and mulberry extracts against Plasmodium berghei infection. Aqueous crude extracts of these plants were prepared using hot water method and used for oral treatment in mice. Groups of ICR mice were infected with 6 × 106 infected red blood cells of P. berghei ANKA by intraperitoneal injection and given the extracts (500, 1500, and 3000 mg/kg twice a day for 4 consecutive days. To assess hemolysis, hematocrit levels were then evaluated. Malaria infection resulted in hemolysis. However, antihemolytic effects were observed in infected mice treated with these extracts at dose-dependent manners. In conclusion, aqueous crude extracts of green tea, safflower, and mulberry exerted antihemolysis induced by malaria infection. These plants may work as potential source in the development of variety of herbal formulations for malarial treatment.

  15. Mild Staphylococcus aureus Skin Infection Improves the Course of Subsequent Endogenous S. aureus Bacteremia in Mice.

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    Sanne van den Berg

    Full Text Available Staphylococcus aureus carriers with S. aureus bacteremia may have a reduced mortality risk compared to non-carriers. A role for the immune system is suggested. Here, we study in mice the effect of mild S. aureus skin infection prior to endogenous or exogenous S. aureus bacteremia, and evaluate protection in relation to anti-staphylococcal antibody levels. Skin infections once or twice by a clinical S. aureus isolate (isolate P or S. aureus strain 8325-4 were induced in mice free of S. aureus and anti-staphylococcal antibodies. Five weeks later, immunoglobulin G (IgG levels in blood against 25 S. aureus antigens were determined, and LD50 or LD100 bacteremia caused by S. aureus isolate P was induced. S. aureus skin infections led to elevated levels of anti-staphylococcal IgG in blood. One skin infection improved the course of subsequent severe endogenous bacteremia only. A second skin infection further improved animal survival rate, which was associated with increased pre-bacteremia IgG levels against Efb, IsaA, LukD, LukE, Nuc, PrsA and WTA. In conclusion, S. aureus isolate P skin infection in mice reduces the severity of subsequent endogenous S. aureus bacteremia only. Although cellular immune effects cannot be rules out, anti-staphylococcal IgG against specified antigens may contribute to this effect.

  16. Chronic kidney disease of uncertain etiology in Sri Lanka: Are leptospirosis and Hantaviral infection likely causes?

    Science.gov (United States)

    Gamage, Chandika Damesh; Sarathkumara, Yomani Dilukshi

    2016-06-01

    Chronic kidney disease of uncertain etiology (CKDu) has been a severe burden and a public health crisis in Sri Lanka over the past two decades. Many studies have established hypotheses to identify potential risk factors although causative agents, risk factors and etiology of this disease are still uncertain. Several studies have postulated that fungal and bacterial nephrotoxins are a possible etiological factor; however, the precise link between hypothesized risk factors and the pathogenesis of chronic kidney disease has yet to