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Sample records for lewis rats immunized

  1. Characterization of clinical and immune response in a rotavirus diarrhea model in suckling Lewis rats.

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    Pérez-Cano, Francisco J; Castell, Margarida; Castellote, Cristina; Franch, Angels

    2007-12-01

    Group A rotaviruses (RVs) are the leading pathogens causing diarrhea in children and animals. The present study was designed to establish an experimental model of RV infection and immune response in suckling rats. Wistar (W) and Lewis (L) suckling rats were inoculated orally with two different doses of a simian RV SA-11 strain. RV infection was evaluated by growth rate and clinical indexes. Virus-shedding and serum anti-RV antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Mucosal interferon-gamma (IFN gamma), specific splenocyte proliferation, and spleen and intestinal intraepithelial lymphocyte (IEL) phenotype were analyzed. No diarrhea was observed in any inoculated Ws. All Ls developed acute moderate diarrhea, and a high score and incidence of diarrhea were found in rats infected with higher titers of RV. Specific humoral and cell systemic immune response was confirmed by splenocyte proliferation and by the presence of serum anti-RV antibodies. Moreover, RV infection induced changes in IEL composition, which showed an increase in the proportion of innate immune cells with respect to cells involved in acquired immunity. This acute moderate diarrhea process constitutes a good experimental model that also provides some immune biomarkers that may allow establishing modulation by drugs or diet components.

  2. Effects of long-term active immunization with the second extracellular loop of human β1- or β3-adrenoceptors in thoracic aorta and mesenteric arteries in Lewis rats.

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    Montaudon, E; Dubreil, L; Lalanne, V; Jagu, B; Toumaniantz, G; Thorin, C; Henrion, D; Desfontis, J-C; Martignat, L; Mallem, M Y

    2016-12-01

    To evaluate whether active immunization producing β1- or β3-antibodies (β1-ABs and β3-ABs) detected in sera of patients with dilated cardiomyopathies has deleterious effects on vascular reactivity in Lewis rat thoracic aorta (TA) and small mesenteric arteries (SMA). Lewis rats were immunized for 6months with peptidic sequences corresponding to the second extracellular loop of β1- and β3-adrenoceptors (ARs). During the immunization, systolic blood pressure (SBP) was monitored using the tail cuff method. The vascular reactivity of immunized rats was assessed by ex vivo studies on SMA and TA using various β-AR agonists, phenylephrine and KCl. The immunizations producing functional β1-ABs and β3-ABs did not affect the SBP. However, in TA from β1-AR-immunized rats, the relaxations mediated by dobutamine and salbutamol were significantly impaired in comparison with adjuvant rats whereas nebivolol-induced relaxation was not modified. Moreover, phenylephrine and KCl-mediated contractions were enhanced in these rats. In contrast, immunization with β3-AR peptide led to the increase of relaxations induced by dobutamine in TA but did not change those induced by salbutamol and nebivolol. Surprisingly, in SMA from both rats immunized with β1- or β3-peptides, relaxations induced by the various β-agonists were not changed whereas phenylephrine and KCl-mediated contractions were impaired. Our study shows that β1- and β3-ABs can affect vascular reactivity. β1-ABs would have a pathogenic action whereas β3-ABs would have a beneficial effect on aorta reactivity. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Amelioration of experimental autoimmune uveitis by leflunomide in Lewis rats.

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    Cheng-bo Fang

    Full Text Available PURPOSE: To investigate the efficacy of leflunomide in experimental autoimmune uveitis (EAU in rats. METHODS: Lewis rats were immunized with interphotoreceptor retinoid-binding peptide (IRBP in order to generate EAU. Rats received three dose of leflunomide through intragastric administration (prevention or treatment protocols after immunization at three separate doses (3 mg/kg/d; 6 mg/kg/d; 12 mg/kg/d. Cyclosporin A was administered as a positive control. Rats were euthanized during peak disease activity (day 14 or 15. Treatment effectiveness was evaluated in vivo using clinical EAU scoring (d14 and histopathological evaluation of enucleated eyes after experimental termination. The expression levels of inflammatory cytokines in the serum were quantified by ELISA. Eyeball of rats were harvested and mRNA expression of interleukin 17 (IL17 and IFN-γ were quantified through RT-PCR. Intracellular expression of interleukin (IL-17 in the activated CD4(+ T cells was assessed by flow cytometry. The effects of leflunomide inhibition on immune responses in rats were investigated in isolated lymphocytes. RESULTS: Histopathological and clinical data revealed severe intraocular inflammation in the immunized rat. Inflammation reached its peak on day 14 in this EAU model. Treatment with leflunomide significantly prevented and treated EAU-induced ocular inflammation and decreased clinical and pathological scores compared to vehicle-treated eyes. Gene expression of IL17 and IFN-γ was markedly reduced in leflunomide-treated eyes. Leflunomide significantly decreased the serum levels of IL17 and IFN-γ. The study of IL17+ T cells in peripheral blood and spleen by flow cytometry showed a decreased number of Th17 cell in rats of leflunomide prevented group. Lymphocytes from animals treated with leflunomide had decreased antigen-specific proliferation in vitro compared with lymphocytes from untreated animals. CONCLUSIONS: Oral administration of leflunomide

  4. Activation of the adenosine A2A receptor exacerbates experimental autoimmune neuritis in Lewis rats in association with enhanced humoral immunity.

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    Zhang, Min; Li, Xiao-Li; Li, Heng; Wang, Shan; Wang, Cong-Cong; Yue, Long-Tao; Xu, Hua; Zhang, Peng; Chen, Hui; Yang, Bing; Duan, Rui-Sheng

    2016-04-15

    Accumulated evidence demonstrated that Adenosine A2A receptor (A2AR) is involved in the inflammatory diseases. In the present study, we showed that a selective A2AR agonist, CGS21680, exacerbated experimental autoimmune neuritis in Lewis rats induced with bovine peripheral myelin. The exacerbation was accompanied with reduced CD4(+)Foxp3(+) T cells, increased CD4(+)CXCR5(+) T cells, B cells, dendritic cells and antigen-specific autoantibodies, which is possibly due to the inhibition of IL-2 induced by CGS21680. Combined with previous studies, our data indicate that the effects of A2AR stimulation in vivo are variable in different diseases. Caution should be taken in the use of A2AR agonists.

  5. Impact of predatory threat on fear extinction in Lewis rats

    OpenAIRE

    Goswami, Sonal; Cascardi, Michele; Rodríguez-Sierra, Olga E.; Duvarci, Sevil; Paré, Denis

    2010-01-01

    Humans with post-traumatic stress disorder (PTSD) are deficient at extinguishing conditioned fear responses. A study of identical twins concluded that this extinction deficit does not predate trauma but develops as a result of trauma. The present study tested whether the Lewis rat model of PTSD reproduces these features of the human syndrome. Lewis rats were subjected to classical auditory fear conditioning before or after exposure to a predatory threat that mimics a type of traumatic stress ...

  6. Sodium fusidate (fusidin) ameliorates the course of monophasic experimental allergic encephalomyelitis in the Lewis rat

    DEFF Research Database (Denmark)

    Di Marco, R; Puglisi, G; Papaccio, G;

    2001-01-01

    We have evaluated the effect of the immunosuppressant sodium fusidate (fusidin) on the course of acute monophasic experimental encephalomyelitis (EAE) in male Lewis rats. Prophylactic treatment with fusidin, 80 or 120 mg/kg bd wt., markedly ameliorated the course of the disease in rats immunized ....... These data provide further evidence for the anti-inflammatory effect of fusidin and suggest that this drug may be valuable for the treatment of human multiple sclerosis....

  7. Cyclosporin a. Inhibition of experimental autoimmune uveitis in Lewis rats.

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    Nussenblatt, R B; Rodrigues, M M; Wacker, W B; Cevario, S J; Salinas-Carmona, M C; Gery, I

    1981-01-01

    Cyclosporin A (CS-A), a selective inhibitor of T lymphocytes, is reported here to prevent S antigen (S-Ag) induced uveitis in Lewis rats. The S-Ag, found in all mammalian retinas, is uveitogenic under experimental conditions and patients with certain uveitic entities demonstrate cell mediated responses to this antigen. Daily treatment with CS-A (10 mg/kg) begun on the same day as S-Ag immunization totally inhibited the development of the uveitis in this experimental autoimmune model. Moreover a greater CS-A dose (40 mg/kg) efficiently prevented the disease process when therapy was started 7 d after S-Ag immunization. Anti-S-Ag antibody titers were observed to be similar in rats either protected or not protected with CS-A. Our data support strongly the need for T cell participation in this disease model. Since ocular inflammatory disease is an important cause of visual impairment, the data further suggest that CS-A may be useful in the treatment of patients with intractable uveitis. Images PMID:7204576

  8. Impact of Predatory Threat on Fear Extinction in Lewis Rats

    Science.gov (United States)

    Goswami, Sonal; Cascardi, Michele; Rodriguez-Sierra, Olga E.; Duvarci, Sevil; Pare, Denis

    2010-01-01

    Humans with post-traumatic stress disorder (PTSD) are deficient at extinguishing conditioned fear responses. A study of identical twins concluded that this extinction deficit does not predate trauma but develops as a result of trauma. The present study tested whether the Lewis rat model of PTSD reproduces these features of the human syndrome.…

  9. The myelin basic protein-specific T cell repertoire in (transgenic) Lewis rat/SCID mouse chimeras: preferential V beta 8.2 T cell receptor usage depends on an intact Lewis thymic microenvironment.

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    Kääb, G; Brandl, G; Marx, A; Wekerle, H; Bradl, M

    1996-05-01

    In the Lewis rat, myelin basic protein (MBP)-specific, encephalitogenic T cells preferentially recognize sequence 68-88, and use the V beta 8.2 gene to encode their T cell receptors. To analyze the structural prerequisites for the development of the MBP-specific T cell repertoire, we reconstituted severe-combined immunodeficient (SCID) mice with fetal (embryonic day 15-16) Lewis rat lymphoid tissue, and then isolated MBP-specific T cell lines from the adult chimeras after immunization. Two types of chimera were constructed: SCID mice reconstituted with rat fetal liver cells only, allowing T cell maturation within a chimeric SCID thymus consisting of mouse thymic epithelium and rat interdigitating dendritic cells, and SCID mice reconstituted with rat fetal liver cells and rat fetal thymus grafts, allowing T cell maturation within the chimeric SCID and the intact Lewis rat thymic microenvironment. Without exception, the T cell lines isolated from MBP-immunized SCID chimeras were restricted by MHC class II of the Lewis rat (RT1.B1), and none by I-Ad of the SCID mouse. Most of the T cell lines recognized the immunodominant MBP epitope 68-88. In striking contrast to intact Lewis rats, in SCID mice reconstituted by rat fetal liver only, MBP-specific T cell clones used a seemingly random repertoire of V beta genes without a bias for V beta 8.2. In chimeras containing fetal Lewis liver plus fetal thymus grafted under the kidney capsule, however, dominant utilization of V beta 8.2 was restored. The migration of liver-derived stem cells through rat thymus grafts was documented by combining fetal tissues from wild-type and transgenic Lewis rats. The results confirm that the recognition of the immunodominant epitope 68-88 by MBP-specific encephalitogenic T cells is a genetically determined feature of the Lewis rat T cell repertoire. They further suggest that the formation of the repertoire requires T cell differentiation in a syngeneic thymic microenvironment.

  10. Different Characters of Spleen OX-62 Positive Dendritic Cells between Fischer and Lewis Rats

    Institute of Scientific and Technical Information of China (English)

    Linsong Yang; Yayi Hou

    2006-01-01

    The phenotype, DNA-binding activities of NF-κB, cytokine production, endocytosis and stimulatory capacity of spleen OX-62-positive dendritc cells (SDCs) from Fischer rats were compared with those from Lewis rats. Results showed that the expressions of CD11b, MHC-Ⅱ, CD8, CD45RA, CD54 and CD86 on SDCs were significantly higher in Fischer than those in Lewis rats. The levels of IL-2, IL-4, IL-10 and IFN-γ in SDCs from Fischer rats were distinctly higher than those from Lewis. Both stimulatory capacity and DNA-binding activities of NF-κB in SDCs were all lower in Fischer than those in Lewis rats. These differences may partly contribute to rat strainspecificity in susceptibility to chronic inflammatory stimuli.

  11. Gene expression in the spinal cord in female lewis rats with experimental autoimmune encephalomyelitis induced with myelin basic protein.

    Directory of Open Access Journals (Sweden)

    Hayley R Inglis

    Full Text Available BACKGROUND: Experimental autoimmune encephalomyelitis (EAE, the best available model of multiple sclerosis, can be induced in different animal strains using immunization with central nervous system antigens. EAE is associated with inflammation and demyelination of the nervous system. Micro-array can be used to investigate gene expression and biological pathways that are altered during disease. There are few studies of the changes in gene expression in EAE, and these have mostly been done in a chronic mouse EAE model. EAE induced in the Lewis with myelin basic protein (MBP-EAE is well characterised, making it an ideal candidate for the analysis of gene expression in this disease model. METHODOLOGY/PRINCIPAL FINDINGS: MBP-EAE was induced in female Lewis rats by inoculation with MBP and adjuvants. Total RNA was extracted from the spinal cords and used for micro-array analysis using AffimetrixGeneChip Rat Exon 1.0 ST Arrays. Gene expression in the spinal cords was compared between healthy female rats and female rats with MBP-EAE. Gene expression in the spinal cord of rats with MBP-EAE differed from that in the spinal cord of normal rats, and there was regulation of pathways involved with immune function and nervous system function. For selected genes the change in expression was confirmed with real-time PCR. CONCLUSIONS/SIGNIFICANCE: EAE leads to modulation of gene expression in the spinal cord. We have identified the genes that are most significantly regulated in MBP-EAE in the Lewis rat and produced a profile of gene expression in the spinal cord at the peak of disease.

  12. Normotension in Lewis and Dahl salt-resistant rats is governed by different genes.

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    Crespo, Kimberley; Chauvet, Cristina; Blain, Marilyne; Ménard, Annie; Roy, Julie; Deng, Alan Y

    2011-03-01

    Inbred rodent models simulating essential hypertension and normotension are useful tools in discovering genes controlling blood pressure (BP) homeostasis. An analysis of a F2 population made from crosses of hypertensive Dahl salt-sensitive (DSS) and normotensive Lewis rats did not detect a BP quantitative trait locus (QTL) on chromosome 7 (Chr 7). However, false negativity could not be excluded. If a BP QTL could be proven to exist, what gene(s) may be responsible for this QTL. We first constructed reciprocal congenic strains for a Chr 7 segment and determined functional domains of prominent candidate genes. A congenic strain made in the DSS rat background exhibited a BP effect, indicating that a BP QTL, C7QTL, inhabits Chr 7. Contrarily, a congenic strain constructed in the Lewis rat background did not change BP, demonstrating a dependence of C7QTL on the DSS rats environment. Among the candidate genes, tachykinin 2 (Tac2), neurexophilin 4 (Nxph4) and retinol dehydrogenase 2 (Rdh2) bear nonsynonymous changes comparing DSS and Lewis rats, but are the same comparing DSS and Dahl salt-resistant (DSR) rats. In contrast, the Lewis alleles of 11-beta-hydroxylase (Cyp11b1), aldosterone synthase (Cyp11b2) and Cytochrome P-450 11B3 (Cyp11b3) are identical to those of DSS rats, but different from those of DSR rats. Thus, the failure to detect a linkage between a Chr 7 segment and BP in F2(DSS × Lewis) can be attributed to false negativity. Tac2, Nxph4 and Rdh2 are priority candidate genes for C7QTL. Lewis and DSR rats are both normotensive, but their underlying genetic determinants are different.

  13. [Effects of green tea on growth inhibition and immune regulation of Lewis lung cancer in mice].

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    Zhu, M; Gong, Y; Ge, G

    1997-11-01

    C57/BL6J mice were inoculated with Lewis lung cancer cells as an experimental model to study the effects of green tea on cancer prevention, inhibition of tumor growth and immune regulation in mice with tumor. Results showed that weight of thymus in C57/BL6J mice and its index declined, proportion of positive CD4 subgroup of T lymphocyte and ratio of CD4+, to CD8+ reduced, baseline chemilumi-nescence decreased in peripheral white blood cells, yeast zymosan stimulated chemiluminescence increased, and number of immunoglobulin M formation cells decreased. It indicated that green tea had obvious inhibition in Lewis lung cancer and protective effects, to various extent, on adverse changes of above indices.

  14. Dimethyl Fumarate Ameliorates Lewis Rat Experimental Autoimmune Neuritis and Mediates Axonal Protection.

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    Kalliopi Pitarokoili

    Full Text Available Dimethyl fumarate is an immunomodulatory and neuroprotective drug, approved recently for the treatment of relapsing-remitting multiple sclerosis. In view of the limited therapeutic options for human acute and chronic polyneuritis, we used the animal model of experimental autoimmune neuritis in the Lewis rat to study the effects of dimethyl fumarate on autoimmune inflammation and neuroprotection in the peripheral nervous system.Experimental autoimmune neuritis was induced by immunization with the neuritogenic peptide (amino acids 53-78 of P2 myelin protein. Preventive treatment with dimethyl fumarate given at 45 mg/kg twice daily by oral gavage significantly ameliorated clinical neuritis by reducing demyelination and axonal degeneration in the nerve conduction studies. Histology revealed a significantly lower degree of inflammatory infiltrates in the sciatic nerves. In addition, we detected a reduction of early signs of axonal degeneration through a reduction of amyloid precursor protein expressed in axons of the peripheral nerves. This reduction correlated with an increase of nuclear factor (erythroid derived 2-related factor 2 positive axons, supporting the neuroprotective potential of dimethyl fumarate. Furthermore, nuclear factor (erythroid derived 2-related factor 2 expression in Schwann cells was only rarely detected and there was no increase of Schwann cells death during EAN.We conclude that immunomodulatory and neuroprotective dimethyl fumarate may represent an innovative therapeutic option in human autoimmune neuropathies.

  15. Treatment of chronic immune-mediated neuropathies: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and the Lewis-Sumner syndrome.

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    Sederholm, Benson H

    2010-09-01

    Current treatment approaches for the management of chronic immune-mediated peripheral neuropathies are reviewed, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and the Lewis-Sumner syndrome (LSS). A summary of existing evidence for commonly used treatment modalities, such as corticosteroids, intravenous immune globulin (IVIG), and plasma exchange is provided. Evidence for the use of additional immunosuppressant and immunomodulatory agents is also reviewed.

  16. Differential Gene Expression in the Nucleus Accumbens and Frontal Cortex of Lewis and Fischer 344 Rats Relevant to Drug Addiction

    OpenAIRE

    Higuera-Matas, A; Montoya, G. L.; Coria, S.M; Miguéns, M; García-Lecumberri, C.; Ambrosio, E.

    2011-01-01

    Drug addiction results from the interplay between social and biological factors. Among these, genetic variables play a major role. The use of genetically related inbred rat strains that differ in their preference for drugs of abuse is one approach of great importance to explore genetic determinants. Lewis and Fischer 344 rats have been extensively studied and it has been shown that the Lewis strain is especially vulnerable to the addictive properties of several drugs when compared with the Fi...

  17. Glucagon-Like Peptide-1 Analog, Liraglutide, Delays Onset of Experimental Autoimmune Encephalitis in Lewis Rats

    DEFF Research Database (Denmark)

    DellaValle, Brian; Brix, Gitte S; Brock, Birgitte

    2016-01-01

    the experimental model, experimental autoimmune encephalitis (EAE). Methods: EAE was induced in 30 female Lewis rats that subsequently received twice-daily liraglutide (200 μg/kg s.c.) or saline. Healthy controls were included (saline, n = 6, liraglutide, n = 7). Clinical score and weight were assessed daily...... by blinded observers. Animals were killed at peak disease severity (day 11) or if exceeding humane endpoint (clinical score ≥4). Protein levels of manganese superoxide dismutase (MnSOD), amyloid precursor protein (APP), and glial fibrillary acidic protein (GFAP) were determined. Results: Liraglutide......, that liraglutide treatment delays onset of EAE in Lewis rats and is associated with improved protective capacity against oxidative stress. These data suggest GLP-1 receptor agonists should be investigated further as a potential therapy for MS....

  18. Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis rats

    DEFF Research Database (Denmark)

    Mangano, K; Sardesai, N Y; Quattrocchi, C

    2008-01-01

    VGX-1027 is a novel, low molecular weight, immunomodulatory compound that has shown efficacy against a variety of immuno-inflammatory disease models in animals including autoimmune diabetes in NOD mice, collagen-induced arthritis and chemically induced inflammatory colitis. Here, we have studied ...... the effects of VGX-1027 on the development of endotoxin-induced uveitis (EIU) in male Lewis rats, as a model of inflammatory ocular diseases in humans....

  19. Differential Gene Expression in the Nucleus Accumbens and Frontal Cortex of Lewis and Fischer 344 Rats Relevant to Drug Addiction

    Science.gov (United States)

    Higuera-Matas, A; Montoya, G. L; Coria, S.M; Miguéns, M; García-Lecumberri, C; Ambrosio, E

    2011-01-01

    Drug addiction results from the interplay between social and biological factors. Among these, genetic variables play a major role. The use of genetically related inbred rat strains that differ in their preference for drugs of abuse is one approach of great importance to explore genetic determinants. Lewis and Fischer 344 rats have been extensively studied and it has been shown that the Lewis strain is especially vulnerable to the addictive properties of several drugs when compared with the Fischer 344 strain. Here, we have used microarrays to analyze gene expression profiles in the frontal cortex and nucleus accumbens of Lewis and Fischer 344 rats. Our results show that only a very limited group of genes were differentially expressed in Lewis rats when compared with the Fischer 344 strain. The genes that were induced in the Lewis strain were related to oxygen transport, neurotransmitter processing and fatty acid metabolism. On the contrary genes that were repressed in Lewis rats were involved in physiological functions such as drug and proton transport, oligodendrocyte survival and lipid catabolism. These data might be useful for the identification of genes which could be potential markers of the vulnerability to the addictive properties of drugs of abuse. PMID:21886580

  20. Differential gene expression in the nucleus accumbens and frontal cortex of lewis and Fischer 344 rats relevant to drug addiction.

    Science.gov (United States)

    Higuera-Matas, A; Montoya, G L; Coria, S M; Miguéns, M; García-Lecumberri, C; Ambrosio, E

    2011-03-01

    Drug addiction results from the interplay between social and biological factors. Among these, genetic variables play a major role. The use of genetically related inbred rat strains that differ in their preference for drugs of abuse is one approach of great importance to explore genetic determinants. Lewis and Fischer 344 rats have been extensively studied and it has been shown that the Lewis strain is especially vulnerable to the addictive properties of several drugs when compared with the Fischer 344 strain. Here, we have used microarrays to analyze gene expression profiles in the frontal cortex and nucleus accumbens of Lewis and Fischer 344 rats. Our results show that only a very limited group of genes were differentially expressed in Lewis rats when compared with the Fischer 344 strain. The genes that were induced in the Lewis strain were related to oxygen transport, neurotransmitter processing and fatty acid metabolism. On the contrary genes that were repressed in Lewis rats were involved in physiological functions such as drug and proton transport, oligodendrocyte survival and lipid catabolism.These data might be useful for the identification of genes which could be potential markers of the vulnerability to the addictive properties of drugs of abuse.

  1. Direct binding of autoimmune disease related T cell epitopes to purified Lewis rat MHC class II molecules

    DEFF Research Database (Denmark)

    Joosten, I; Wauben, M H; Holewijn, M C

    1994-01-01

    must be able to assess peptide-MHC interactions. Several well described autoimmune disease models exist in the Lewis rat and thus this particular rat strain provides a good model system to study the effect of competitor peptides. So far no information has been available on the peptide binding...... characteristics of the Lewis rat MHC class II RT1.B1 molecule. We have now developed a biochemical binding assay which enables competition studies in which the relative MHC binding affinity of a set of non-labelled peptides can be assessed while employing detection of biotinylated marker peptides...... by chemiluminescence. The assay is sensitive and specific. We have used this assay to determine the binding characteristics of several disease associated T cell determinants and their sequence analogues in the Lewis rat. Notably, most of the autoimmune disease associated peptide sequences tested were found...

  2. Sodium fusidate (fusidin) ameliorates the course of monophasic experimental allergic encephalomyelitis in the Lewis rat

    DEFF Research Database (Denmark)

    Di Marco, R; Puglisi, G; Papaccio, G;

    2001-01-01

    with myelin basic proteins in complete Freund's adjuvant, entailing delayed onset of symptoms, lower clinical scores and more rapid recovery than PBS-treated control rats. The fusidin-treated, immunized rats exhibited milder mononuclear cell infiltration of brains and spinal cords than control animals...

  3. Stress Alters the Discriminative Stimulus and Response Rate Effects of Cocaine Differentially in Lewis and Fischer Inbred Rats

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    Therese A. Kosten

    2012-03-01

    Full Text Available Stress enhances the behavioral effects of cocaine, perhaps via hypothalamic-pituitary-adrenal (HPA axis activity. Yet, compared to Fischer 344 (F344 rats, Lewis rats have hyporesponsive HPA axis function and more readily acquire cocaine self-administration. We hypothesized that stress would differentially affect cocaine behaviors in these strains. The effects of three stressors on the discriminative stimulus and response rate effects of cocaine were investigated. Rats of both strains were trained to discriminate cocaine (10 mg/kg from saline using a two-lever, food-reinforced (FR10 procedure. Immediately prior to cumulative dose (1, 3, 10 mg/kg cocaine test sessions, rats were restrained for 15-min, had 15-min of footshock in a distinct context, or were placed in the shock-paired context. Another set of F344 and Lewis rats were tested similarly except they received vehicle injections to test if stress substituted for cocaine. Most vehicle-tested rats failed to respond after stressor exposures. Among cocaine-tested rats, restraint stress enhanced cocaine’s discriminative stimulus effects in F344 rats. Shock and shock-context increased response rates in Lewis rats. Stress-induced increases in corticosterone levels showed strain differences but did not correlate with behavior. These data suggest that the behavioral effects of cocaine can be differentially affected by stress in a strain-selective manner.

  4. Glucagon-Like Peptide-1 Analog, Liraglutide, Delays Onset of Experimental Autoimmune Encephalitis in Lewis Rats.

    Science.gov (United States)

    DellaValle, Brian; Brix, Gitte S; Brock, Birgitte; Gejl, Michael; Landau, Anne M; Møller, Arne; Rungby, Jørgen; Larsen, Agnete

    2016-01-01

    Introduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS) pathology and influence the susceptibility to treatment, directing attention toward anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE). Methods: EAE was induced in 30 female Lewis rats that subsequently received twice-daily liraglutide (200 μg/kg s.c.) or saline. Healthy controls were included (saline, n = 6, liraglutide, n = 7). Clinical score and weight were assessed daily by blinded observers. Animals were killed at peak disease severity (day 11) or if exceeding humane endpoint (clinical score ≥4). Protein levels of manganese superoxide dismutase (MnSOD), amyloid precursor protein (APP), and glial fibrillary acidic protein (GFAP) were determined. Results: Liraglutide treatment delayed disease onset (group clinical score significantly >0) by 2 days and markedly reduced disease severity (median clinical score 2 vs. 5; p = 0.0003). Fourteen of 15 (93%) of vehicle-treated rats reached the humane endpoint (clinical score ≥4) by day 11 compared to 5 of 15 (33%) of liraglutide-treated rats (p = 0.0004). Liraglutide substantially increased the mitochondrial antioxidant MnSOD (p drug treatment (p = 0.09). Conclusion: We demonstrate, for the first time, that liraglutide treatment delays onset of EAE in Lewis rats and is associated with improved protective capacity against oxidative stress. These data suggest GLP-1 receptor agonists should be investigated further as a potential therapy for MS.

  5. Effects of Handling and Vehicle Injections on Adrenocorticotropic and Corticosterone Concentrations in Sprague–Dawley Compared with Lewis Rats

    Science.gov (United States)

    Deutsch-Feldman, Molly; Picetti, Roberto; Seip-Cammack, Katharine; Zhou, Yan; Kreek, Mary Jeanne

    2015-01-01

    The hypothalamic–pituitary–adrenal (HPA) axis is a key factor in the trajectory of the addiction-like cycle (a pattern of behavior characterized by escalating drug use, withdrawal, and relapse) in preclinical and clinical studies. Concentrations of HPA hormones change in laboratory animals in response to standard experimental procedures, including handling and vehicle injections. We compared HPA activity in adult male Lewis (inbred) and Sprague–Dawley (outbred) rats, 2 common strains in rodent models of addiction, after different schedules of handling and saline injections, to explore the extent to which HPA responses differ by strain and whether interindividual differences underlie addiction vulnerability. The 4 treatment conditions were no, short, or long handling and saline injections. In handled groups, rats were handled for 1 to 2 min for 3 times daily and were euthanized after 7 d (short handling) or 14 d (long handling). The injection schedule in the saline injection group mimicked that in a model of binge-like cocaine exposure. Across all treatment groups, concentrations of adrenocorticotropic hormone were higher in Sprague–Dawley than in Lewis rats. In Sprague–Dawley rats, corticosterone concentrations decreased after continued handling but remained constant in Lewis rats. Interindividual variability in hormone levels was greater in Sprague–Dawley than Lewis rats, although corticosterone variability decreased after continued handling. Prolactin did not differ between groups of either Sprague–Dawley and Lewis rats before or after handling. This study underscores the importance of prolonged handling before experimenter-provided drug-administration paradigms and of strain-associated differences that may affect study outcomes. PMID:25651089

  6. Effects of handling and vehicle injections on adrenocorticotropic and corticosterone concentrations in Sprague-Dawley compared with Lewis rats.

    Science.gov (United States)

    Deutsch-Feldman, Molly; Picetti, Roberto; Seip-Cammack, Katharine; Zhou, Yan; Kreek, Mary Jeanne

    2015-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a key factor in the trajectory of the addiction-like cycle (a pattern of behavior characterized by escalating drug use, withdrawal, and relapse) in preclinical and clinical studies. Concentrations of HPA hormones change in laboratory animals in response to standard experimental procedures, including handling and vehicle injections. We compared HPA activity in adult male Lewis (inbred) and Sprague-Dawley (outbred) rats, 2 common strains in rodent models of addiction, after different schedules of handling and saline injections, to explore the extent to which HPA responses differ by strain and whether interindividual differences underlie addiction vulnerability. The 4 treatment conditions were no, short, or long handling and saline injections. In handled groups, rats were handled for 1 to 2 min for 3 times daily and were euthanized after 7 d (short handling) or 14 d (long handling). The injection schedule in the saline injection group mimicked that in a model of binge-like cocaine exposure. Across all treatment groups, concentrations of adrenocorticotropic hormone were higher in Sprague-Dawley than in Lewis rats. In Sprague-Dawley rats, corticosterone concentrations decreased after continued handling but remained constant in Lewis rats. Interindividual variability in hormone levels was greater in Sprague-Dawley than Lewis rats, although corticosterone variability decreased after continued handling. Prolactin did not differ between groups of either Sprague-Dawley and Lewis rats before or after handling. This study underscores the importance of prolonged handling before experimenter-provided drug-administration paradigms and of strain-associated differences that may affect study outcomes.

  7. Antitumor effect of recombinant human endostatin combined with cisplatin on rats with transplanted Lewis lung cancer

    Institute of Scientific and Technical Information of China (English)

    Zhan-Wu Yu; Ying-Hua Ju; Cheng-Liang Yang; Han-Bing Yu; Quan Luo; Ye-Gang Ma; Yong-Yu Liu

    2015-01-01

    Objective:To observe the antitumor effect and mechanism of recombinant human endostatin (Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer in rats.Methods:A total of 30 C57 rats were selected, and the monoplast suspension of Lewis lung cancer was injected into the left axilla to prepare the subcutaneous transplanted tumor models in the axilla of right upper limb. The models were randomly divided into Groups A, B, and C. Medication was conducted when the tumor grew to 400 mm3. Group A was the control group without any interventional treatment. Group B was injected with Endostar 5 mg.kg-1.d for 10 d. Group C was given the injection of Endostar 5 mg.kg-1.d combined with intraperitoneal injection of cisplatin 5 mg.kg-1.d for 10 d. All the rats in three groups were executed the day after the 10-d medication and the tumor was taken off for measurement of volume and mass changes and calculation of antitumor rate, after which the vascular endothelial growth factor (VEGF) concentration in rats’plasma was determined by ELISA. The tumor tissues were cut for the preparation of conventional biopsies. After hematoxylin-eosin staining, the pathologic histology was examined to observe the structures of tumor tissues, VEGF score and microvessel density (MVD) in each group. Results:The volume and mass of tumor in Groups B and C were significantly lower than Group A (P< 0.05) while the tumor volume and mass in Group C were significantly lower than Group B (P < 0.05). The antitumor rate in Group C was significantly higher than Group B (P < 0.05), but the tumor VEGF score, MVD and plasma VEGF level in Group C were significantly lower than Groups A and B (P < 0.05). In Group B, the tumor VEGF score, MVD and plasma VEGF level were significantly lower than Group A (P < 0.05). The microscopic image of Group C showed that its number of active tumor cells and the blood capillary around tumor was significantly

  8. Fischer 344 and Lewis Rat Strains as a Model of Genetic Vulnerability to Drug Addiction.

    Science.gov (United States)

    Cadoni, Cristina

    2016-01-01

    Today it is well acknowledged that both nature and nurture play important roles in the genesis of psychopathologies, including drug addiction. Increasing evidence suggests that genetic factors contribute for at least 40-60% of the variation in liability to drug dependence. Human genetic studies suggest that multiple genes of small effect, rather than single genes, contribute to the genesis of behavioral psychopathologies. Therefore, the use of inbred rat strains might provide a valuable tool to identify differences, linked to genotype, important in liability to addiction and related disorders. In this regard, Lewis and Fischer 344 inbred rats have been proposed as a model of genetic vulnerability to drug addiction, given their innate differences in sensitivity to the reinforcing and rewarding effects of drugs of abuse, as well their different responsiveness to stressful stimuli. This review will provide evidence in support of this model for the study of the genetic influence on addiction vulnerability, with particular emphasis on differences in mesolimbic dopamine (DA) transmission, rewarding and emotional function. It will be highlighted that Lewis and Fischer 344 rats differ not only in several indices of DA transmission and adaptive changes following repeated drug exposure, but also in hypothalamic-pituitary-adrenal (HPA) axis responsiveness, influencing not only the ability of the individual to cope with stressful events, but also interfering with rewarding and motivational processes, given the influence of corticosteroids on dopamine neuron functionality. Further differences between the two strains, as impulsivity or anxiousness, might contribute to their different proneness to addiction, and likely these features might be linked to their different DA neurotransmission plasticity. Although differences in other neurotransmitter systems might deserve further investigation, results from the reviewed studies might open new vistas in understanding aberrant

  9. Fischer 344 and Lewis rat strains as a model of genetic vulnerability to drug addiction

    Directory of Open Access Journals (Sweden)

    Cristina eCadoni

    2016-02-01

    Full Text Available Today it is well acknowledged that both nature and nurture play important roles in the genesis of psychopathologies, including drug addiction. Increasing evidence suggests that genetic factors contribute for at least 40-60 % of the variation in liability to drug dependence. Human genetic studies suggest that multiple genes of small effect, rather than single genes, contribute to the genesis of behavioral psychopathologies. Therefore the use of inbred rat strains might provide a valuable tool to identify differences, linked to genotype, important in liability to addiction and related disorders. In this regard, Lewis and Fischer 344 inbred rats have been proposed as a model of genetic vulnerability to drug addiction, given their innate differences in sensitivity to the reinforcing and rewarding effects of drugs of abuse, as well their different responsiveness to stressful stimuli. This review will provide evidence in support of this model for the study of the genetic influence on addiction vulnerability, with particular emphasis to differences in mesolimbic dopamine (DA transmission, rewarding and emotional function. It will be highlighted that Lewis and Fischer 344 rats differ not only in several indices of DA transmission and adaptive changes following repeated drug exposure, but also in hypothalamic-pituitary-adrenal (HPA axis responsiveness, influencing not only the ability of the individual to cope with stressful events, but also interfering with rewarding and motivational processes, given the influence of corticosteroids on dopamine neurons functionality.Further differences between the two strains, as impulsivity or anxiousness, might contribute to their different proneness to addiction, and likely these features might be linked to their different DA neurotransmission plasticity. Although differences in other neurotransmitter systems might deserve further investigations, results from the reviewed studies might open new vistas in

  10. Thermal and motor behavior in experimental autoimmune encephalitis in Lewis rats.

    Science.gov (United States)

    Wrotek, Sylwia; Rosochowicz, Tomasz; Nowakowska, Anna; Kozak, Wiesław

    2014-08-01

    Thermoregulation in patients, who suffer from multiple sclerosis (MS) is impaired and may result in either increases or decreases in body temperature. Disturbances in body temperature correlate with acute relapses, and for this reason, it is an important issue in everyday life of those who suffer from MS. Although rat experimental autoimmune encephalitis (EAE) appeared useful for the examination of current therapies against MS, it has not been thoroughly investigated in terms of body temperature. The purpose of this study was to examine the effect of EAE induction on thermal and motor behavior in the rats. Subcutaneous injection of encephalitogenic emulsion into both pads of hind feet of the Lewis rats provoked symptoms of EAE. Body temperature (T(b)) and motor activity of rats were measured using biotelemetry system. We report a significant increase in body temperature within 24 h prior to the EAE manifestation (12 h average of T(b) for EAE induced animals was higher by 1.07 ± 0.06 °C during day-time and by 0.5 ± 0.05 °C during night time in comparison to the control rats). On the other hand, the onset of EAE symptoms was associated with gradual decrease of body temperature, and during the first night-time T(b) was lower by 1.03 ± 0.08 °C in comparison to the control rats. The inhibition of the motor activity started from the night time, 2 days before EAE onset. On the basis of our data, we concluded that the pattern of body temperature changes after EAE induction may be considered as useful symptom (prodrom) to predict precisely the time of EAE onset. Furthermore, we suggest that EAE in rats may be a suitable model to study mechanism of body temperature alternations observed in MS patients.

  11. Glucagon-Like Peptide-1 Analog, Liraglutide, Delays Onset of Experimental Autoimmune Encephalitis in Lewis Rats

    Science.gov (United States)

    DellaValle, Brian; Brix, Gitte S.; Brock, Birgitte; Gejl, Michael; Landau, Anne M.; Møller, Arne; Rungby, Jørgen; Larsen, Agnete

    2016-01-01

    Introduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS) pathology and influence the susceptibility to treatment, directing attention toward anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE). Methods: EAE was induced in 30 female Lewis rats that subsequently received twice-daily liraglutide (200 μg/kg s.c.) or saline. Healthy controls were included (saline, n = 6, liraglutide, n = 7). Clinical score and weight were assessed daily by blinded observers. Animals were killed at peak disease severity (day 11) or if exceeding humane endpoint (clinical score ≥4). Protein levels of manganese superoxide dismutase (MnSOD), amyloid precursor protein (APP), and glial fibrillary acidic protein (GFAP) were determined. Results: Liraglutide treatment delayed disease onset (group clinical score significantly >0) by 2 days and markedly reduced disease severity (median clinical score 2 vs. 5; p = 0.0003). Fourteen of 15 (93%) of vehicle-treated rats reached the humane endpoint (clinical score ≥4) by day 11 compared to 5 of 15 (33%) of liraglutide-treated rats (p = 0.0004). Liraglutide substantially increased the mitochondrial antioxidant MnSOD (p < 0.01) and reduced the neurodegenerative marker APP (p = 0.036) in the brain. GFAP levels were not significantly changed with drug treatment (p = 0.09). Conclusion: We demonstrate, for the first time, that liraglutide treatment delays onset of EAE in Lewis rats and is associated with improved protective capacity against oxidative stress. These data suggest GLP-1

  12. Dr. Lewis Kitchener Dahl, the Dahl Rats and the ‘Inconvenient truth’ abou the Genetics of Hypertension

    Science.gov (United States)

    Joe, Bina

    2014-01-01

    Synopsis Lewis K. Dahl is regarded as an iconic figure in the field of hypertension research. During the 1960s and 1970s he published several seminal articles in the field that shed light on the relationship between salt and hypertension. Further, the Dahl rat models of hypertension that he developed by a selective breeding strategy are among the most widely used models for hypertension research. To this day, genetic studies using this model are ongoing in our laboratory. While Dr. Dahl is known for his contributions to the field of hypertension, very little, if any, of his personal history is documented. This article details a short biography of Dr. Lewis Dahl, the history behind the development of the Dahl rats and presents an overview of the results obtained through the genetic analysis of the Dahl rat as an experimental model to study the inheritance of hypertension. PMID:25646295

  13. Relationship between vulnerability to reinforcing effects of morphine and activity of the endogenous cholecystokinin system in Lewis and Fischer rats.

    Science.gov (United States)

    Noble, Florence; Benturquia, Nadia; Crete, Dominique; Canestrelli, Corinne; Mas Nieto, Magdalena; Wilson, Jodie; Roques, Bernard P

    2012-05-01

    A great number of studies have shown the presence of physiological interactions between brain neurotransmitter systems in behavioural responses. This is the case for opioid, cholecystokinin (CCK) and dopamine systems. However, so far the role that the CCK system may play in vulnerability to consumption of drugs of abuse is not clear. This was investigated in this study using Lewis rats that are more sensitive to the reinforcing properties of drugs of abuse than Fischer rats. The extraneuronal CCK(8) levels and brain CCK(2) receptors were found higher in Fischer than in Lewis rats in the nucleus accumbens, one of the most important structures involved in drug consumption. Moreover, pharmacological modulation of the CCK system by administration of a selective CCK(2) agonist blocked, in the conditioned place preference, the reinforcing effects of morphine in Lewis rats, whereas a selective CCK(2) antagonist revealed reinforcing effects of the alkaloid in Fischer rats. These results obtained following systemic administrations of the CCK ligands were confirmed following microinjection into the nucleus accumbens. Thus, a low level of CCK efflux in the nucleus accumbens could be one of the many factors involved in drug reinforcing effects, whereas a high level of CCK efflux could attenuate it.

  14. Antitumor effect of malaria parasite infection in a murine Lewis lung cancer model through induction of innate and adaptive immunity.

    Science.gov (United States)

    Chen, Lili; He, Zhengxiang; Qin, Li; Li, Qinyan; Shi, Xibao; Zhao, Siting; Chen, Ling; Zhong, Nanshan; Chen, Xiaoping

    2011-01-01

    Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL) staining and decreased Ki-67 expression in tumors. Through natural killer (NK) cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+) T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria parasite may provide a novel strategy or therapeutic vaccine vector for anti-lung cancer

  15. Antitumor effect of malaria parasite infection in a murine Lewis lung cancer model through induction of innate and adaptive immunity.

    Directory of Open Access Journals (Sweden)

    Lili Chen

    Full Text Available BACKGROUND: Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL staining and decreased Ki-67 expression in tumors. Through natural killer (NK cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+ T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. CONCLUSIONS/SIGNIFICANCE: Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria

  16. Differential Fos expression in the paraventricular nucleus of the hypothalamus, sacral parasympathetic nucleus and colonic motor response to water avoidance stress in Fischer and Lewis rats.

    Science.gov (United States)

    Million, M; Wang, L; Martinez, V; Taché, Y

    2000-09-22

    The responsiveness of hypothalamic CRF to various stressors is reduced in the young female Lewis relative to the histocompatible Fischer rat. Whether such a difference impacts the brain-gut response to water avoidance stress was investigated by monitoring Fos immunoreactivity in the brain and sacral spinal cord and fecal pellet output. Exposure for 60 min to water avoidance stress increased the number of Fos positive cells in the paraventricular nucleus of the hypothalamus (PVN), nucleus tractus solitarius (NTS), and the parasympathetic nucleus of the lumbo-sacral spinal cord (L6-S1) in both Lewis and Fischer rats compared with non stress groups. The Fos response was lower by 32.0% in the PVN, and 63% in sacral parasympathetic nucleus in Lewis compared with Fischer rats while similar Fos expression was observed in the NTS. Stress-induced defecation was reduced by 52% in Lewis compared with Fischer rats while colonic motor response to CRF injected intracisternally resulted in a similar pattern and magnitude of defecation in both strains. The CRF receptor antagonist [D-Phe12,Nle(21,38)C(a)MeLeu(37)]-CRF(12-41) injected intracisternally antagonized partly the defecation response in Lewis and Fischer rats. These data indicate that a lower activation of PVN and sacral parasympathetic nuclei in Lewis compared with Fisher rats may contribute to the differential colonic motor response and that the blunted CRF hypothalamic response to stress, unlike responsiveness to central CRF plays a role.

  17. Comparison of estrogenic responses in bone and uterus depending on the parity status in Lewis rats.

    Science.gov (United States)

    Keiler, Annekathrin Martina; Bernhardt, Ricardo; Scharnweber, Dieter; Jarry, Hubertus; Vollmer, Günter; Zierau, Oliver

    2013-01-01

    The reproductive transition of women through peri- to postmenopause is characterized by changes in steroid hormone levels due to the cessation of the ovarian function. Beside several complaints associated with these hormonal changes, the deterioration of the trabecular bone micro-architecture and the loss of skeletal mass can cause osteoporosis. At this life stage, women often have a reproductive history of one to several pregnancies. The ovariectomized skeletally mature rat (>10 months old) is one of the most commonly used animal models for postmenopausal osteoporosis research. Despite the fact that mammals can undergo up to several reproductive cycles (primi-/pluriparous), nulliparous animals are often used and the question whether changes in the hormonal milieu subsequently affect the skeleton and influence the outcome of intervention studies is often neglected in study designs. Therefore, the aim of the present study was to compare the estrogen responsiveness of nulliparous and pluriparous rats. For this purpose, one year old virgin or retired breeder Lewis rats were either sham operated or ovariectomized, whereas half of the ovariectomized animals received subcutaneous 17β-estradiol pellets eight weeks after surgery. After another four weeks, the effects on the uterus were determined by expression analysis of estrogen-dependently regulated steroid receptor genes and well-established marker genes. Moreover, trabecular bone parameters in the tibia were analyzed by micro-computed tomography (μCT). Parity-dependency in estrogen responsiveness was observed with respect to the achieved serum E2 levels in response to similar E2 treatment. This led to differences both on the uterus wet weight and on the expression level of uterine target genes. In addition, a reversal of the ovariectomy-induced changes of the bone architecture after 17β-estradiol substitution was only observed among the nulliparous. In conclusion, the observations of this study support parity

  18. Influence of Hesperidin on the Systemic and Intestinal Rat Immune Response

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    Mariona Camps-Bossacoma

    2017-06-01

    Full Text Available Polyphenols, widely found in edible plants, influence the immune system. Nevertheless, the immunomodulatory properties of hesperidin, the predominant flavanone in oranges, have not been deeply studied. To establish the effect of hesperidin on in vivo immune response, two different conditions of immune system stimulations in Lewis rats were applied. In the first experimental design, rats were intraperitoneally immunized with ovalbumin (OVA plus Bordetella pertussis toxin and alum as the adjuvants, and orally given 100 or 200 mg/kg hesperidin. In the second experimental design, rats were orally sensitized with OVA together with cholera toxin and fed a diet containing 0.5% hesperidin. In the first approach, hesperidin administration changed mesenteric lymph node lymphocyte (MLNL composition, increasing the TCRαβ+ cell percentage and decreasing that of B lymphocytes. Furthermore, hesperidin enhanced the interferon (IFN-γ production in stimulated MLNL. In the second approach, hesperidin intake modified the lymphocyte composition in the intestinal epithelium (TCRγδ+ cells and the lamina propria (TCRγδ+, CD45RA+, natural killer, natural killer T, TCRαβ+CD4+, and TCRαβ+CD8+ cells. Nevertheless, hesperidin did not modify the level of serum anti-OVA antibodies in either study. In conclusion, hesperidin does possess immunoregulatory properties in the intestinal immune response, but this effect is not able to influence the synthesis of specific antibodies.

  19. Cocoa Flavonoid-Enriched Diet Modulates Systemic and Intestinal Immunoglobulin Synthesis in Adult Lewis Rats

    Directory of Open Access Journals (Sweden)

    Francisco J. Pérez-Cano

    2013-08-01

    Full Text Available Previous studies have reported that a diet containing 10% cocoa, a rich source of flavonoids, has immunomodulatory effects on rats and, among others effects, is able to attenuate the immunoglobulin (Ig synthesis in both systemic and intestinal compartments. The purpose of the present study was focused on investigating whether these effects were attributed exclusively to the flavonoid content or to other compounds present in cocoa. To this end, eight-week-old Lewis rats were fed, for two weeks, either a standard diet or three isoenergetic diets containing increasing proportions of cocoa flavonoids from different sources: one with 0.2% polyphenols from conventional defatted cocoa, and two others with 0.4% and 0.8% polyphenols, respectively, from non-fermented cocoa. Diet intake and body weight were monitored and fecal samples were obtained throughout the study to determine fecal pH, IgA, bacteria proportions, and IgA-coated bacteria. Moreover, IgG and IgM concentrations in serum samples collected during the study were quantified. At the end of the dietary intervention no clear changes of serum IgG or IgM concentrations were quantified, showing few effects of cocoa polyphenol diets at the systemic level. However, in the intestine, all cocoa polyphenol-enriched diets attenuated the age-related increase of both fecal IgA and IgA-coated bacteria, as well as the proportion of bacteria in feces. As these effects were not dependent on the dose of polyphenol present in the diets, other compounds and/or the precise polyphenol composition present in cocoa raw material used for the diets could be key factors in this effect.

  20. Immunity to experimental Salmonella typhimurium infections in rats. Transfer of immunity with primed CD4+CD25high and CD4+CD25low T lymphocytes

    DEFF Research Database (Denmark)

    Thygesen, P; Brandt, L; Jørgensen, T

    1994-01-01

    The protective effect of primed CD4+ T lymphocytes against a lethal dose of 10(8) viable Salmonella typhimurium was studied in Lewis rats. Primed CD4+ T lymphocytes were obtained by inoculating Lewis rats with a non-lethal dose of 10(6) viable S. typhimurium. Four weeks after the infection, spleen...... by a fluorescence-activated cell sorter. Untreated Lewis rats were injected with 10(4) different primed CD4+ T-cell populations 24 h prior to the lethal dose of 10(8) viable S. typhimurium. Blood samples were drawn from the orbital plexus 1, 2, 3, and 4 weeks after the infection, and analysed for specific Ig......M and IgG antibodies. Cell sorting revealed that 2/3 of the primed CD4+ T lymphocytes expressed high levels of CD25. Cell transfer revealed that both CD25high and CD25low expression populations could induce immunity against a lethal dose of S. typhimurium, whilst antibody analysis revealed that antibody...

  1. Dopamine treatment of brain-dead Fisher rats improves renal histology but not early renal function in Lewis recipients after prolonged static cold storage.

    Science.gov (United States)

    Fontana, J; Yard, B; Stamellou, E; Wenz, H; Benck, U; Schnuelle, P; Hoeger, S

    2014-12-01

    Brain death (BD) and cold preservation are major risk factors for an unfavorable transplantation outcome. Although donor dopamine treatment in brain-dead rats improves renal function and histology in allogeneic recipients, it remains to be assessed if this also holds true for the combinations of BD and prolonged static cold preservation. BD was induced in F344 donor rats, which were subsequently treated with NaCl 1 mL/h (BD, n = 11), NaCl/hydroxy ethyl starch (BD-norm, n = 10), or 10 μg/min/kg dopamine (BD-dopa, n = 10). Renal grafts were harvested 4 h after BD and transplanted into bilateral nephrectomized Lewis recipients 6 h after cold preservation in University of Wisconsin solution. Renal function was evaluated by use of serum creatinine and urea concentrations at days 0, 1, 3, 5, and 10. Ten days after transplantation, recipients were killed and the renal allografts were processed for light microscopy and immune histology. Serum urea concentrations at days 5 and 10 were significantly lower in recipients that received a renal graft from dopamine-treated rats; for serum creatinine, only a trend was observed at day 10. Immune histology revealed a lower degree of ED1-positive cells in the donor dopamine-treated group. Under light microscopy, Banff classification revealed significantly less intimal arteritis in these grafts (P dopamine treatment clearly improves renal histology in this model, the beneficial effect on early renal function was marginal. It remains to be assessed if donor dopamine treatment has a beneficial effect on renal function in long-term follow-up. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Immunity to experimental Salmonella typhimurium infections in rats. Transfer of immunity with primed CD45RC+ and CD45RC- CD4 T-cell subpopulations

    DEFF Research Database (Denmark)

    Thygesen, P; Christensen, H B; Hougen, H P

    1996-01-01

    The protective effect of primed CD4 T cells against a lethal dose of Salmonella typhimurium was studied in Lewis rats. Primed CD4 T cells were obtained by inoculating Lewis rats with a non-lethal dose of S. typhimurium. Four weeks after the infection, spleen CD4 T cells were separated by antibody...

  3. Histologic, cytologic, and bacteriologic examinations of experimentally induced Salmonella typhimurium infection in Lewis rats

    DEFF Research Database (Denmark)

    Thygesen, P; Martinsen, C; Hougen, H P;

    2000-01-01

    Histopathologic changes, cellular composition, and bacterial spreading were studied in rat spleen after experimentally induced infection with Salmonella typhimurium.......Histopathologic changes, cellular composition, and bacterial spreading were studied in rat spleen after experimentally induced infection with Salmonella typhimurium....

  4. Glucagon-like peptide-1 analogue, liraglutide, delays onset and reduces severity of experimental autoimmune encephalitis in Lewis rats

    Directory of Open Access Journals (Sweden)

    Brian DellaValle

    2016-11-01

    Full Text Available AbstractIntroduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS pathology and influence the susceptibility to treatment, directing attention towards anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1 family, is also anti-diabetic and weight-reducing and is moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE.Methods: EAE was induced in 30 female Lewis rats that subsequently received twice-daily liraglutide (200 µg/kg s.c. or saline. Healthy controls were included (saline, n=6, liraglutide, n=7. Clinical score and weight were assessed daily by blinded observers. Animals were killed at peak disease severity (day 11 or if exceeding humane endpoint (clinical score ≥4. Protein levels of manganese superoxide dismutase (MnSOD, amyloid precursor protein (APP, and glial fibrillary acidic protein (GFAP were determined.Results: Liraglutide treatment delayed disease onset (group clinical score significantly >0 by two days and markedly reduced disease severity (median clinical score 2 vs. 5; p=0.0003. Fourteen of 15 (93% of vehicle-treated rats reached the humane endpoint (clinical score ≥4 by day 11 compared to 5 of 15 (33% of liraglutide-treated rats (p=0.0004. Liraglutide substantially increased the mitochondrial antioxidant MnSOD (p<0.01 and reduced the neurodegenerative marker APP (p=0.036 in the brain. GFAP levels were not significantly changed with drug treatment (p=0.09Conclusion: We demonstrate, for the first time, that liraglutide treatment delays onset of EAE in Lewis rats and is associated with improved protective capacity against oxidative stress. These data suggest GLP-1 receptor

  5. Influence of decontamination on induction of arthritis in Lewis rats by cell wall fragments of Eubacterium aerofaciens. Arthropathic properties of indigenous anaerobic bacteria.

    Science.gov (United States)

    Kool, J; Severijnen, A J; Klasen, I S; Gerrits-Boeye, M Y; Hazenberg, M P

    1992-01-01

    Although the cause (or causes) of rheumatoid arthritis is unknown, many workers have suggested that microorganisms play a part. The intestinal flora in particular has been related to the development of joint inflammation. It has been shown previously that cell wall fragments of several anaerobic Gram positive intestinal bacteria of human origin are arthritogenic after a single intraperitoneal injection in Lewis rats. The part played by indigenous microflora in this model has now been studied by decontaminating Lewis rats before the injection of Eubacterium aerofaciens cell wall fragments. The pattern and severity of arthritis appeared to be comparable in decontaminated and control rats. The second goal of this work was to isolate arthritogenic bacteria from the autochthonous intestinal flora of rats. Only a limited number of bacteria showing a resemblance to arthritogenic strains from human intestinal flora (i.e. E aerofaciens and Bifidobacterium adolescentis) could be isolated. These strains did not induce chronic arthritis after intraperitoneal injection. This may explain why spontaneous arthritis did not develop in Lewis rats. Images PMID:1586251

  6. Acute morphine treatment alters cellular immune function in the lungs of healthy rats.

    Science.gov (United States)

    Coussons-Read, M E; Giese, S

    2001-08-01

    Previous work has shown that morphine suppresses the pulmonary immune response to infection and reduces pulmonary inflammation. No published studies have addressed the impact of morphine on lymphocyte function in the lungs without infection. This study addressed this question by assessing the impact of acute morphine treatment on proliferation, cytokine production, and natural killer (NK) cell activity in resident pulmonary lymphocytes from healthy rats. Male Lewis rats received either a single 15 mg/kg morphine sulfate or vehicle injection 1 h prior to sacrifice. Lungs were minced and passed through wire mesh following collagenase digestion. The resulting cell preparations were pooled (2 rats/pool) to yield sufficient cell numbers for the functional assays, and a portion of these suspensions were separated using a density gradient. Crude and purified cell suspensions were used in assays of NK cell activity and mitogen-induced proliferation and cytokine production. Morphine significantly suppressed lymphocyte proliferation and cytokine production in whole cell suspensions, but not in purified cultures. NK activity was enhanced by morphine treatment in purified treated cultures. Studies of nitrate/nitrite levels in crude and purified cultures suggest that macrophage-derived nitric oxide may be a mechanism of the suppression observed in whole cell suspensions following morphine treatment. These data are consistent with previous work showing that morphine suppresses mitogenic responsiveness and NK activity in the spleen and peripheral blood, and may do so through a macrophage-derived nitric oxide mechanism.

  7. Consecutive en-bloc liver (30%)-pancreas-duodenum-spleen-stomach transplant in Lewis rats.

    Science.gov (United States)

    Yoo, C H; Hong, I C; Lee, S; Nam, S; Bai, S; Kim, K; Pivetti, C D; Niewiadomski, S T; Wolf, P; Gittes, R F

    2003-01-01

    It is well-known that 30% of the remaining liver mass, following partial hepatectomy, regenerates to full original mass within 2 weeks in rats. In order to carry the transplanted rat liver to repeated transplantation, a technique of combining 30% of the liver with the pancreaticoduodenum and spleen transplantation is performed in this consecutive organ transplantation study. Our laboratory observed several 37-month-old transplanted rats by carrying through 2-3 generations, and histological disclosure were made. Because the partial liver transplants did not regenerate after the transplantation with other splanchnic organs, this technique is not so difficult though subsequent surgical maneuvers are needed and the liver histology proved entirely normal in every aspect when followed beyond the rat's life span of 24 months.

  8. Attenuation of salt-induced cardiac remodeling and diastolic dysfunction by the GPER agonist G-1 in female mRen2.Lewis rats.

    Directory of Open Access Journals (Sweden)

    Jewell A Jessup

    Full Text Available INTRODUCTION: The G protein-coupled estrogen receptor (GPER is expressed in various tissues including the heart. Since the mRen2.Lewis strain exhibits salt-dependent hypertension and early diastolic dysfunction, we assessed the effects of the GPER agonist (G-1, 40 nmol/kg/hr for 14 days or vehicle (VEH, DMSO/EtOH on cardiac function and structure. METHODS: Intact female mRen2.Lewis rats were fed a normal salt (0.5% sodium; NS diet or a high salt (4% sodium; HS diet for 10 weeks beginning at 5 weeks of age. RESULTS: Prolonged intake of HS in mRen2.Lewis females resulted in significantly increased blood pressure, mildly reduced systolic function, and left ventricular (LV diastolic compliance (as signified by a reduced E deceleration time and E deceleration slope, increased relative wall thickness, myocyte size, and mid-myocardial interstitial and perivascular fibrosis. G-1 administration attenuated wall thickness and myocyte hypertrophy, with nominal effects on blood pressure, LV systolic function, LV compliance and cardiac fibrosis in the HS group. G-1 treatment significantly increased LV lusitropy [early mitral annular descent (e'] independent of prevailing salt, and improved the e'/a' ratio in HS versus NS rats (P<0.05 as determined by tissue Doppler. CONCLUSION: Activation of GPER improved myocardial relaxation in the hypertensive female mRen2.Lewis rat and reduced cardiac myocyte hypertrophy and wall thickness in those rats fed a high salt diet. Moreover, these advantageous effects of the GPER agonist on ventricular lusitropy and remodeling do not appear to be associated with overt changes in blood pressure.

  9. Effects of an acetone extract of Boswellia carterii Birdw. (Burseraceae) gum resin on adjuvant-induced arthritis in lewis rats.

    Science.gov (United States)

    Fan, A Y; Lao, L; Zhang, R X; Zhou, A N; Wang, L B; Moudgil, K D; Lee, D Y W; Ma, Z Z; Zhang, W Y; Berman, B M

    2005-10-03

    Ruxiang (Gummi olibanum), the dried gum resin of Boswellia carterii (BC), has been used in traditional Chinese medicine to alleviate pain and inflammation for thousands of years. In this random, blinded study, the anti-arthritic effects of a BC extract were observed and compared to vehicle control in a Lewis rat adjuvant arthritis model (n=8/group). Arthritis was induced by injecting CFA subcutaneously into the base of the tail, and the extract was administered orally (i.g.) for 10 consecutive days beginning on day 16 after the injection. Arthritic scores, paw edema, and the local tissue pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) were assessed. Toxicity and adverse effects of the extract were evaluated. At 0.90 g/kg per day, BC significantly decreased arthritic scores between days 20 and 25 (p<0.05) and reduced paw edema on days 18, 20 and 22 compared to control (p<0.05). It also significantly suppressed local tissue TNF-alpha and IL-1beta (p<0.05). No major adverse effects were observed in animals during the repeated-dose treatment profile although mild fur discoloration was noted. The data show that BC extract has significant anti-arthritic and anti-inflammation effects and suggest that these effects may be mediated via the suppression of pro-inflammatory cytokines.

  10. Green tea and its major components ameliorate immune dysfunction in mice bearing Lewis lung carcinoma and treated with the carcinogen NNK.

    Science.gov (United States)

    Zhu, M; Gong, Y; Yang, Z; Ge, G; Han, C; Chen, J

    1999-01-01

    The protective effects of tea and/or its components on dysfunction of immune functions during tumor growth and carcinogenesis in mice were studied using two experimental models: C57/BL6J mice transplanted with Lewis lung carcinoma (LLC) and Kunming mice treated with a single dose of 4-(methylnitrosamino-)-1-(3-pyridyl)-1-butanone (NNK). In C57/BL6J mice bearing LLC, the weight of the thymus decreased, the proportion of CD4(+)-positive T lymphocytes and the ratio of CD4+ to CD8+ decreased, luminol-enhanced chemiluminescence of white blood cells in peripheral blood stimulated by zymosan increased, and plaque-forming cells (PFC) decreased. However, in LLC-bearing mice given green tea as drinking water, all immune functions were improved, along with inhibition of tumor growth. In Kunming mice treated with NNK, during the four weeks of observation, their immunologic indicators, such as phagocytosis of macrophages in the abdominal cavity, luminol-enhanced chemiluminescence of white blood cells, plaque-forming cells, and delayed-type hypersensitivity, increased or decreased to various extents compared with normal controls. However, these changes were significantly prevented in the mice given green tea, mixed tea, or tea polyphenol as drinking water. In conclusion, tea and its components ameliorated immune dysfunction in mice bearing LLC or treated with the carcinogen NNK.

  11. THE PARKINSONIAN NEUROTOXIN ROTENONE ACTIVATES CALPAIN AND CASPASE-3 LEADING TO MOTONEURON DEGENERATION IN SPINAL CORD OF LEWIS RATS

    Science.gov (United States)

    SAMANTARAY, S.; KNARYAN, V. H.; GUYTON, M. K.; MATZELLE, D. D.; RAY, S. K.; BANIK, N. L.

    2007-01-01

    Exposure to environmental toxins increases the risk of neurodegenerative diseases including Parkinson’s disease (PD). Rotenone is a neurotoxin that has been used to induce experimental parkinsonism in rats. We used the rotenone model of experimental parkinsonism to explore a novel aspect of extra-nigral degeneration, the neurodegeneration of spinal cord (SC), in PD. Rotenone administration to male Lewis rats caused significant neuronal cell death in cervical and lumbar SC as compared to control animals. Dying neurons were motoneurons as identified by double immunofluorescent labeling for TUNEL+ cells and ChAT-immunoreactivity. Neuronal death was accompanied by abundant astrogliosis and microgliosis as evidenced from GFAP-immunoreactivity and OX-42-immunoreactivity, respectively, implicating an inflammatory component during neurodegeneration in SC. However, the integrity of the white matter in SC was not affected by rotenone administration as evidenced from the non co-localization of any TUNEL+ cells with GFAP-immunoreactivity and MBP-immunoreactivity, the selective markers for astrocytes and oligodendrocytes, respectively. Increased activities of 76 kD active m-calpain and 17/19 kD active caspase-3 further demonstrated involvement of these enzymes in cell death in SC. The finding of ChAT+ cell death also suggested degeneration of SC motoneurons in rotenone-induced experimental parkinsonism. Thus, this is the first report of its kind in which the selective vulnerability of a putative parkinsonian target outside of nigrostriatal system has been tested using an environmental toxin to understand the pathophysiology of PD. Moreover, rotenone-induced degeneration of SC motoneuron in this model of experimental parkinsonism progressed with upregulation of calpain and caspase-3. PMID:17367952

  12. Effect of Feeding Status on Adjuvant Arthritis Severity, Cachexia, and Insulin Sensitivity in Male Lewis Rats

    Directory of Open Access Journals (Sweden)

    Andrea Stofkova

    2010-01-01

    Full Text Available We studied the effect of food restriction, overfeeding, and normofeeding on cachexia, inflammatory and metabolic parameters, and insulin sensitivity in chronic adjuvant arthritis (AA in rats. Food restriction during AA increased circulating ghrelin, corticosterone, decreased leptin, and ameliorated arthrogram score and systemic inflammation compared to normofeeding. Overfeeding worsened arthrogram score and systemic inflammation, and led to lipid accumulation in the liver, but not to alterations of adipokine and ghrelin plasma levels relative to normofeeding. Independently of feeding status, AA induced cachexia, in which modulation of mRNA expressions for appetite-regulating neuropeptides (NPY, AgRP, POMC, CART in the arcuate nucleus (ARC does not play a primary role. The overexpression of IL-1β mRNA in the ARC suggests its role in the mechanisms of impaired energy balance during AA under all feeding conditions. Normal HOMA index in all arthritic groups does not indicate the development of insulin resistance by feeding interventions in these rats.

  13. Experimental autoimmune cystitis in the Lewis rat: a potential animal model for interstitial cystitis.

    Science.gov (United States)

    Luber-Narod, J; Austin-Ritchie, T; Banner, B; Hollins, C; Maramag, C; Price, H; Menon, M

    1996-01-01

    To develop an autoimmune animal model for interstitial cystitis (IC), we injected rats with Freund's adjuvant (CFA) containing bladder homogenate (experimentals) or CFA alone (shams). We observed a doubling of urinary frequency in the experimental animals over the shams (P = 0.004) and histopathologic changes (venular congestion) consistent with IC. Statistically significant bladder capacity changes were not found. Mast cell (MC) number was not statistically different between experimentals and controls but the number of MCs from section to adjacent section within the same animal's bladder did vary markedly, indicating the MC counts are not a reliable measure of disease in the rat bladder. Splenocytes cultured from the experimental animals and transferred to naive syngeneic recipients were capable of transferring the urinary frequency changes and vascular congestion while splenocytes from animals which did not develop the condition were without effect. In summary, we have developed and autoimmune model for IC consistent with the clinical features of IC. The features of this model can be transferred to naive syngeneic recipients via adoptive splenocyte transfer. The model will permit us to ask and answer important questions about the pathogenesis and treatment of the human disease.

  14. Possible role of ependymal proliferation in improving experimental allergic encephalomyelitis in Lewis rats.

    Science.gov (United States)

    Mohamed, Adel; Yunus, Mohammed; Hamadain, Elgenaid; Benghuzzi, H

    2006-01-01

    Experimental autoimmune encephalomyelitis (EAE) animal models is an autoimmune demyelinating disease of the central nervous system, which is widely accepted as an animal for human multiple sclerosis (MS). Ependymal cells line the spinal canal and cerebral ventricles and proliferate in response to damage. These cells have the potential to differentiate into neural support cells. However, there is controversy as whether the response of the ependymal cells is a result of injury or repair. This study demonstrates using the rat EAE model a proliferative response of the ependymal cells occurred as a result of the disease. Interestingly, a more pronounced ependymal proliferative effect was seen in animals being fed a phase 2 enzyme inducer. The data suggests ependymal cells play a role in the post-inflammatory response of the brain and also may be involved in the remyelination process.

  15. Ocular and systemic bio-distribution of rhodamine-conjugated liposomes loaded with VIP injected into the vitreous of Lewis rats.

    Science.gov (United States)

    Camelo, S; Lajavardi, L; Bochot, A; Goldenberg, B; Naud, M C; Fattal, E; Behar-Cohen, F; de Kozak, Y

    2007-12-07

    Local delivery of therapeutic molecules encapsulated within liposomes is a promising method to treat ocular inflammation. The purpose of the present study was to define the biodistribution of rhodamine-conjugated liposomes loaded with vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide, following their intravitreal (IVT) injection in normal rats. Healthy seven- to eight-week-old Lewis male rats were injected into the vitreous with empty rhodamine-conjugated liposomes (Rh-Lip) or with VIP-loaded Rh-Lip (VIP-Rh-Lip; 50 mM of lipids with an encapsulation efficiency of 3.0+/-0.4 mmol VIP/mol lipids). Twenty-four h after IVT injection, the eyes, the cervical, mesenteric, and inguinal lymph nodes (LN), and spleen were collected. The phenotype and distribution of cells internalizing Rh-Lip and VIP-Rh-Lip were studied. Determination of VIP expression in ocular tissues and lymphoid organs and interactions with T cells in cervical LN was performed on whole mounted tissues and frozen tissue sections by immunofluorescence and confocal microscopy. In the eye, 24 h following IVT injection, fluorescent liposomes (Rh-Lip and VIP-Rh-Lip) were detected mainly in the posterior segment of the eye (vitreous, inner layer of the retina) and to a lesser extent at the level of the iris root and ciliary body. Liposomes were internalized by activated retinal Müller glial cells, ocular tissue resident macrophages, and rare infiltrating activated macrophages. In addition, fluorescent liposomes were found in the episclera and conjunctiva where free VIP expression was also detected. In lymphoid organs, Rh-Lip and VIP-Rh-Lip were distributed almost exclusively in the cervical lymph nodes (LN) with only a few Rh-Lip-positive cells detected in the spleen and mesenteric LN and none in the inguinal LN. In the cervical LN, Rh-Lip were internalized by resident ED3-positive macrophages adjacent to CD4 and CD8-positive T lymphocytes. Some of these T lymphocytes in close contact with

  16. Modeling corticosteroid effects in a rat model of rheumatoid arthritis I: mechanistic disease progression model for the time course of collagen-induced arthritis in Lewis rats.

    Science.gov (United States)

    Earp, Justin C; Dubois, Debra C; Molano, Diana S; Pyszczynski, Nancy A; Keller, Craig E; Almon, Richard R; Jusko, William J

    2008-08-01

    A mechanism-based model was developed to describe the time course of arthritis progression in the rat. Arthritis was induced in male Lewis rats with type II porcine collagen into the base of the tail. Disease progression was monitored by paw swelling, bone mineral density (BMD), body weights, plasma corticosterone (CST) concentrations, and tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and glucocorticoid receptor (GR) mRNA expression in paw tissue. Bone mineral density was determined by PIXImus II dual energy X-ray densitometry. Plasma CST was assayed by high-performance liquid chromatography. Cytokine and GR mRNA were determined by quantitative real-time polymerase chain reaction. Disease progression models were constructed from transduction and indirect response models and applied using S-ADAPT software. A delay in the onset of increased paw TNF-alpha and IL-6 mRNA concentrations was successfully characterized by simple transduction. This rise was closely followed by an up-regulation of GR mRNA and CST concentrations. Paw swelling and body weight responses peaked approximately 21 days after induction, whereas bone mineral density changes were greatest at 23 days after induction. After peak response, the time course in IL-1beta, IL-6 mRNA, and paw edema slowly declined toward a disease steady state. Model parameters indicate TNF-alpha and IL-1beta mRNA most significantly induce paw edema, whereas IL-6 mRNA exerted the most influence on BMD. The model for bone mineral density captures rates of turnover of cancellous and cortical bone and the fraction of each in the different regions analyzed. This small systems model integrates and quantitates multiple factors contributing to arthritis in rats.

  17. Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze

    Directory of Open Access Journals (Sweden)

    Takahashi R.N.

    2001-01-01

    Full Text Available The 5-HT2B/2C receptor antagonist SB 206553 exerts anxiolytic effects in rat models of anxiety. However, these effects have been reported for standard rat strains, thus raising the issue of SB 206553 effects in rat strains displaying different levels of anxiety. Herein, the effects of SB 206553 in a 5-min elevated plus-maze test of anxiety were compared to those of the reference anxiolytic, diazepam, in two rat strains respectively displaying high (Lewis rats and low (spontaneously hypertensive rats, SHR anxiety. Diazepam (0.37, 0.75, or 1.5 mg/kg; 30 min before testing increased in a dose-dependent manner the behavioral measures in SHR, but not in Lewis rats. On the other hand, SB 206553 (1.25, 2.5, or 5 mg/kg; 30 min before testing failed to alter the anxiety parameters in both strains, whereas it increased closed arm entries in Lewis rats, suggesting that it elicited hyperactivity in the latter strain. Accordingly, the hypolocomotor effect of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine (1.5 mg/kg ip 20 min before a 15-min exposure to an activity cage was prevented by the 1.25 and 2.5 mg/kg doses of SB 206553 in Lewis rats and SHR, respectively. Compared with SHR, Lewis rats may display a lower response to benzodiazepine-mediated effects and a more efficient control of locomotor activity by 5-HT2B/2C receptors.

  18. Integrated analysis of genetic, behavioral, and biochemical data implicates neural stem cell-induced changes in immunity, neurotransmission and mitochondrial function in Dementia with Lewy Body mice.

    Science.gov (United States)

    Lakatos, Anita; Goldberg, Natalie R S; Blurton-Jones, Mathew

    2017-03-10

    We previously demonstrated that transplantation of murine neural stem cells (NSCs) can improve motor and cognitive function in a transgenic model of Dementia with Lewy Bodies (DLB). These benefits occurred without changes in human α-synuclein pathology and were mediated in part by stem cell-induced elevation of brain-derived neurotrophic factor (BDNF). However, instrastriatal NSC transplantation likely alters the brain microenvironment via multiple mechanisms that may synergize to promote cognitive and motor recovery. The underlying neurobiology that mediates such restoration no doubt involves numerous genes acting in concert to modulate signaling within and between host brain cells and transplanted NSCs. In order to identify functionally connected gene networks and additional mechanisms that may contribute to stem cell-induced benefits, we performed weighted gene co-expression network analysis (WGCNA) on striatal tissue isolated from NSC- and vehicle-injected wild-type and DLB mice. Combining continuous behavioral and biochemical data with genome wide expression via network analysis proved to be a powerful approach; revealing significant alterations in immune response, neurotransmission, and mitochondria function. Taken together, these data shed further light on the gene network and biological processes that underlie the therapeutic effects of NSC transplantation on α-synuclein induced cognitive and motor impairments, thereby highlighting additional therapeutic targets for synucleinopathies.

  19. Intraspecies variability in the dose-response relationship for Salmonella Enteritidis associated with genetic differences in cellular immune response.

    NARCIS (Netherlands)

    Havelaar, A.H.; Garssen, J.; Takumi, K.; Koedam, M.I.; Ritmeester, W.; Fonteyne, L. de la; Bousema, T.; Vos, J.

    2004-01-01

    To evaluate the effects of differences in host cellular immunity, we studied the dose-response relationship for infection with Salmonella enterica serovar Enteritidis (SE) in two different rat strains, skewed towards T helper 1 (Th1, Lewis rats) or T helper 2 (Th2, Brown Norway rats) immunoregulatio

  20. The functional role of PI3K in maintenance of blood pressure and baroreflex suppression in (mRen2)27 and mRen2.Lewis rat.

    Science.gov (United States)

    Logan, Exazevia M; Aileru, Azeez A; Shaltout, Hossam A; Averill, David B; Diz, Debra I

    2011-10-01

    The phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway in brain of spontaneously hypertensive rats, but not Wistar-Kyoto (WKY) rats, contributes to elevated mean arterial pressure (MAP). The role of PI3K in the regulation of blood pressure or autonomic function in the nucleus tractus solitarii (NTS) is yet to be established in other Ang II-dependent models of hypertension. Thus, we microinjected PI3K inhibitors, wortmannin or LY294002, into the NTS, and measured MAP, baroreflex sensitivity (BRS) for heart rate (HR) control, and HR variability (HRV) in mRen2.Lewis congenic and (mRen2)27 transgenic rats. Bilateral NTS microinjections of wortmannin (100 nmol/L; 50 nL) reduced MAP in (mRen2)27 and mRen2.Lewis rats (33 ± 5 mm Hg, n = 7, and 32 ± 6 mm Hg, n = 9, respectively) for approximately 90 minutes. Spectral and sequence analysis showed improvements in spontaneous BRS and HRV (50%-100%) after treatment in both hypertensive strains. Injections of wortmannin into NTS of Hannover Sprague-Dawley or Lewis control rats failed to alter MAP, BRS, or HRV. In mRen2.Lewis, but not in control Lewis rats, LY294002 (50 μmole/L) reduced MAP and increased BRS and HRV similar to wortmannin. Thus, the pharmacologic blockade of the PI3K signaling pathway in NTS reveals an important contribution to resting MAP and BRS in rats with overexpression of the Ren2 gene.

  1. Lewy Body Disease

    Science.gov (United States)

    Lewy body disease is one of the most common causes of dementia in the elderly. Dementia is the loss ... enough to affect normal activities and relationships. Lewy body disease happens when abnormal structures, called Lewy bodies, ...

  2. Influence of age and immunization on development of gingivitis in rats

    DEFF Research Database (Denmark)

    Lekic, P; Klausen, B; Friis-Hasché, E

    1989-01-01

    To study the effect of age and antigenic priming on the development of gingivitis, 33 healthy rats were placed in contact with Streptococcus mutans, Actinomyces viscosus, Fusobacterium nucleatum, and Bacteroides gingivalis. On days 0, 3, 7, and 14 after inoculation, the gingival condition...... was judged clinically and histologically, and serum antibody titers against the bacteria were measured. The rats were divided into three groups: 1 month old, 3 months old, and 3 months old immunized. None of the young rats developed gingivitis during the experiment, whereas half of the adult and all...... of the adult immunized rats bled on probing on days 7 and 14. In general, antibody titers against the bacteria were low in young rats, moderate in adult rats, and high in adult immunized rats. These results indicate that adult rats react stronger to plaque antigens than young rats and that previous contact...

  3. Lewis, Fischer 344, and Sprague-Dawley rats display differences in lipid peroxidation, motor recovery, and rubrospinal tract preservation after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Humberto eMestre

    2015-05-01

    Full Text Available The rat is the most common animal model for the preclinical validation of neuroprotective therapies in spinal cord injury (SCI. Lipid peroxidation (LP is a hallmark of the damage triggered after SCI. Free radicals react with fatty acids causing cellular and membrane disruption. LP accounts for a considerable amount of neuronal cell death after SCI. To better understand the implications of inbred and outbred rat strain selection on preclinical SCI research we evaluated LP after laminectomy sham surgery and a severe contusion of the T9 spinal cord in female Sprague-Dawley (SPD, Lewis (LEW and Fischer 344 (F344 rats. Further analysis included locomotor recovery using the Basso, Beattie, and Bresnahan (BBB scale and retrograde rubrospinal tract tracing. LEW had the highest levels of LP products 72 hours after sham surgery and SCI, significantly different from both F344 and SPD. SPD rats had the fastest functional recovery and highest BBB scores; these were not significantly different to F344. However, LEW rats achieved the lowest BBB scores throughout the two-month follow-up, yielding significant differences when compared to SPD and F344. To see if the improvement in locomotion was secondary to an increase in axon survival we evaluated rubrospinal neurons (RSN via retrograde labeling of the rubrospinal tract and quantified cells at the red nuclei. The highest numbers of RSNs were observed in SPD rats then F344; the lowest counts were seen in LEW rats. The BBB scores significantly correlated with the amount of positively stained RSN in the red nuclei. It is critical to identify inter-strain variations as a potential confound in preclinical research. Multi-strain validation of neuroprotective therapies may increase chances of successful translation.

  4. Potential of the aminosterol, squalamine in combination therapy in the rat 13,762 mammary carcinoma and the murine Lewis lung carcinoma.

    Science.gov (United States)

    Teicher, B A; Williams, J I; Takeuchi, H; Ara, G; Herbst, R S; Buxton, D

    1998-01-01

    Squalamine, a naturally-occurring aminosterol, has demonstrated antiangiogenic activity in several experimental models. Extended treatment with other antiangiogenic agents has been shown to increase tumor oxygenation. Tumor oxygenation was measured using an Eppendorf pO2 histograph polarographic pO2 electrode system in the rat 13,762 mammary carcinoma after treatment of the tumor-bearing animals with squalamine (40 mglkg) on days 4 through 18 post tumor implantation. Under air breathing conditions, the hypoxic fraction (percent of pO2 readings squalamine treated animals. While squalamine administration alone produced only a modest effect on the growth of the 13,762 tumor, there were increases in tumor growth delay of 1.9- to 2.5-fold when squalamine was administered along with cyclophosphamide, cisplatin and paclitaxel compared with the tumor growth delays observed with the chemotherapeutic agents alone. To determine the efficacy of squalamine alone and along with cytotoxic therapies against a model of primary and systemic disease, squalamine was administered to animals bearing the Lewis lung carcinoma by daily subcutaneous injection or by continuous infusion on days 4 through 18 post tumor implantation. Squalamine as a single agent had only a modest effect on the growth of the primary Lewis lung tumor but increased the tumor growth delays produced by cyclophosphamide, cisplatin, paclitaxel and 5-fluorouracil by 2.4- to 3.8-fold compared with the anticancer drugs alone. Squalamine administration alone substantially decreased the number of lung metastases found in animals bearing the Lewis lung carcinoma and further decreased the number of lung metastases when administered along with the chemotherapeutic agents.

  5. Strain differences in the expression of endocannabinoid genes and in cannabinoid receptor binding in the brain of Lewis and Fischer 344 rats.

    Science.gov (United States)

    Coria, Santiago M; Roura-Martínez, David; Ucha, Marcos; Assis, María Amparo; Miguéns, Miguel; García-Lecumberri, Carmen; Higuera-Matas, Alejandro; Ambrosio, Emilio

    2014-08-04

    The Lewis (LEW) and Fischer 344 (F344) rat strains have been proposed as a model to study certain genetic influences on drug use. These strains differ in terms of the self-administration of several drugs, and in their expression of various components of the dopaminergic, glutamatergic, GABAergic and endogenous opioid neurotransmitter systems. As the endocannabinoid system is linked to these systems, we investigated whether these two strains exhibit differences in cannabinoid receptor binding and in the expression of cannabinoid-related genes. Quantitative autoradiography of [(3)H]-CP 55,940 binding levels and real-time PCR assays were used. F344 rats displayed higher levels of cannabinoid receptor binding in the lateral globus pallidus and weaker CNR1 gene expression in the prefrontal cortex (PFc) than LEW rats. Moreover, the N-acyl phosphatidylethanolamine-specific phospholipase D/fatty acid amide hydrolase ratio was greater in the PFc and NAcc of F344 rats. Our results suggest that the endocannabinoid system may be a mediator of the individual differences that exist in the susceptibility to the rewarding effects of drugs of abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. The Application of Cytidyl Guanosyl Oligodeoxynucleotide Can Affect the Antitumor Immune Response Induced by a Combined Protocol of Cryoablation and Dendritic Cells in Lewis Lung Cancer Model.

    Science.gov (United States)

    Zhang, Mi; Yin, Tianquan; Lu, Yuan; Feng, Huasong

    2016-04-19

    BACKGROUND Recently, several combined therapeutic strategies and targeted agents have been under investigation for their potential role in lung cancer. The combined administration of dendritic cells (DCs) and immune-adjuvant cytidyl guanosyl oligodeoxynucleotide (CpG-ODN) after cryosurgery has proven to be an effective strategy for treating lung cancer. However, whether the application of CpG-ODN could affect the therapeutic results remained to be further explored. MATERIAL AND METHODS The Lewis lung cancer (LLC)-bearing mice received cryoablation and injection of ex vivo-cultured DCs into the peritumoral zone. Subsequently, CpG-ODN was administered to experimental animals 6 hours, 12 hours, and 24 hours after DC injection. The mice in the control group received coadministration of DCs and CpG-ODN simultaneously. Therapeutic effects were evaluated by survival rates. The resistance to rechallenge of LLC cell was assessed by lung metastasis and in vitro cytotoxicity of splenocytes. Furthermore, T-cell subsets and multiple cytokines (interleukin [IL]-4, -10, and-12; interferon [IFN]-γ; tumor necrosis factor [TNF]-α) in the blood were assessed to elucidate the underlying mechanisms. RESULTS Higher ratios of CD4+ and CD8+ T cells and higher levels of IL-12, IFN-γ, and TNF-α were found in the blood of the mice that received CpG-ODN therapy 12 h after DC injection. The cytotoxicity potency of the splenocytes of these mice was significantly higher compared with the mice in other groups. Moreover, the mice receiving CpG-ODN therapy 12 h after DC injection showed significantly better resistance to rechallenge. Compared with the mice in other groups, the mice receiving CpG-ODN therapy 12 h after DC injection were superior in survival rates and antimetastatic effects. CONCLUSIONS Our study suggested that the therapeutic efficacy was closely associated with CpG-ODN administration in the combined therapeutic protocol of cryoablation, DCs, and immune adjuvant. In situ

  7. Polycystic kidney disease gene in the Lewis polycystic kidney rat is mapped to chromosome 10q21–q26

    Directory of Open Access Journals (Sweden)

    Yengkopiong JP

    2012-08-01

    Full Text Available Jada Pasquale YengkopiongDr John Garang Memorial University of Science and Technology, Faculty of Science and Technology, Bor, Republic of South SudanBackground: Polycystic kidney disease (PKD is a life-threatening disorder that affects the kidneys of millions of people across the world. The disease is normally inherited, but it can also be acquired, and leads to development of many cysts in the renal nephrons. In this study, the aim was to characterize PKD in the Lewis polycystic kidney (LPK rat, the newest model for human PKD.Methods: Mating experiments were performed between male LPK rats with PKD and female Brown Norway and Wistar Kyoto rats without PKD to raise second filial (F2 and backcross 1 (BC1 progeny, respectively. Rats that developed PKD were identified. Histological examination of the kidneys and liver was performed. Liver tissue samples were collected from each rat and used to extract DNA. The extracted DNA was amplified, and mapping and linkage analyses were performed to identify the quantitative trait locus that controlled the disease phenotypes.Results: It was established that the disease was controlled by a recessive mutation in a single gene (F2: PKD = 42, non-PKD = 110, χ2 = 0.53; BC1: PKD = 67, non-PKD = 72, χ2 = 0.18, P > 0.05 and that the disease was inherited as autosomal recessive polycystic kidney disease (ARPKD. The rats with PKD developed larger fluid-filled cystic kidneys, higher systolic blood pressure, and anemia. However, there were no extrarenal cysts and no pup deaths. Mapping studies and linkage analyses associated the disease phenotypes in both the F2 and BC1 rats to chromosome 10q21–q26, giving a maximum LOD score of 7.9 (P = 0.00001 between peak markers D10Rat180 and D10Rat26.Conclusion: The quantitative trait locus on chromosome 10q21–q26 does not contain the Pkhd-1 gene, and it is different from quantitative trait loci that control ARPKD in other murine models. The candidate genes located in the

  8. Amphetamine self-administration and dopamine function: assessment of gene × environment interactions in Lewis and Fischer 344 rats.

    Science.gov (United States)

    Meyer, Andrew C; Bardo, Michael T

    2015-07-01

    Previous research suggests both genetic and environmental influences on substance abuse vulnerability. The current work sought to investigate the interaction of genes and environment on the acquisition of amphetamine self-administration as well as amphetamine-stimulated dopamine (DA) release in nucleus accumbens shell using in vivo microdialysis. Inbred Lewis (LEW) and Fischer (F344) rat strains were raised in either an enriched condition (EC), social condition (SC), or isolated condition (IC). Acquisition of amphetamine self-administration (0.1 mg/kg/infusion) was determined across an incrementing daily fixed ratio (FR) schedule. In a separate cohort of rats, extracellular DA and the metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in the nucleus accumbens shell following an acute amphetamine injection (1 mg/kg). "Addiction-prone" LEW rats had greater acquisition of amphetamine self-administration on a FR1 schedule compared to "addiction-resistant" F344 rats when raised in the SC environment. These genetic differences were negated in both the EC and IC environments, with enrichment buffering against self-administration and isolation enhancing self-administration in both strains. On a FR5 schedule, the isolation-induced increase in amphetamine self-administration was greater in F344 than LEW rats. While no group differences were obtained in extracellular DA, gene × environment differences were obtained in extracellular levels of the metabolite DOPAC. In IC rats only, LEW rats showed attenuation in the amphetamine-induced decrease in DOPAC compared to F344 rats. IC LEW rats also had an attenuated DOPAC response to amphetamine compared to EC LEW rats. The current results demonstrate gene × environment interactions in amphetamine self-administration and amphetamine-induced changes in extracellular DOPAC in nucleus accumbens (NAc) shell. However, the behavioral and neurochemical differences were not related directly, indicating that

  9. Active and Passive Immunization Against Staphylococcus aureus Periprosthetic Osteomyelitis in Rats

    DEFF Research Database (Denmark)

    Søe, Niels H; Jensen, Nina Vendel; Jensen, Asger Lundorff

    2017-01-01

    BACKGROUND/AIM: Staphylococcus aureus infection associated with orthopedic implants cannot always be controlled. We used a knee prosthesis model with implant-related osteomyelitis in rats to explore induction of an effective immune response with active and passive immunization. MATERIALS...... AND METHODS: Fifty-two Sprague-Dawley rats were divided into active (N=28) and passive immunization groups (N=24). A bacterial inoculum of 10(3) S. aureus MN8 was injected into the tibia and the femur marrow before insertion of a non-constrained knee prosthesis in each rat. The active-immunization group...... received a synthetic oligosaccharide of polysaccharide poly-N-acetylglucosamine (PNAG), 9G1cNH2 and the passive-immunization group received immunization with immunoglobulin from rabbits infected with S. aureus. RESULTS/CONCLUSION: Active immunization against PNAG significantly reduced the consequences...

  10. Effect of Scoparia dulcis on noise stress induced adaptive immunity and cytokine response in immunized Wistar rats.

    Science.gov (United States)

    Sundareswaran, Loganathan; Srinivasan, Sakthivel; Wankhar, Wankupar; Sheeladevi, Rathinasamy

    Noise acts as a stressor and is reported to have impact on individual health depending on nature, type, intensity and perception. Modern medicine has no effective drugs or cure to prevent its consequences. Being an environmental stressor noise cannot be avoided; instead minimizing its exposure or consuming anti-stressor and adaptogens from plants can be considered. The present study was carried out to evaluate the anti-stressor, adaptogen and immunostimulatory activity of Scoparia dulcis against noise-induced stress in Wistar rat models. Noise stress in rats was created by broadband white noise generator, 100 dB A/4 h daily/15 days and S. dulcis (200 mg/kg b.w.) was administered orally. 8 groups of rats were used consisting of 6 animals each; 4 groups for unimmunized and 4 groups for immunized. For immunization, sheep red blood cells (5 × 10(9) cells/ml) were injected intraperitoneally. Sub-acute noise exposed rats showed a significant increase in corticosterone and IL-4 levels in both immunized and unimmunized rats whereas lymphocytes, antibody titration, soluble immune complex, IL-4 showed a marked increase with a significant decrease in IL-2, TNF-α, IFN-γ cytokines only in unimmunized rats. Immunized noise exposed rats presented increased leukocyte migration index and decreased foot pad thickness, IL-2, TNF-α, IFN-γ with no changes in the lymphocytes. S. dulcis (SD) has normalized and prevented the noise induced changes in cell-mediated and humoral immunity and it could be the presence of anti-stressor and immuno stimulant activity of the plant. Copyright © 2016 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

  11. Experimental Study on AT1-receptor-peptide-induced Myocardial Immune Damage in Rat

    Institute of Scientific and Technical Information of China (English)

    LUO; Yusheng; LIAO; Yuhua; WANG; Min; WEI; Yumiao; DONG; Jihua; WANG; Jinping; LU; Yingping

    2001-01-01

    In order to investigate the immunological damage in rat immunized with AT1-receptor peptide, 18 male Wistar rats were divided into two groups: immunized-group (n= 12), each rat was immunized with 150 μg AT1-receptor petide coupled to bovine serum albumin, together with Freund's adjuvant. Control group (n= 6), sham-immunized, "immunized liquid" was same as immunized-group except AT1-receptor peptide. Systolic blood pressure (SBP) was measured by using the tail-cuff technique, antibody against AT1-receptor peptide detected by using ELISA method, and left ventricular myocardium and renal cortex sections were observed under light and electron microscopy.There was no significant difference in SBP and light microscopic observation of the tissue sections between the immunized-group and control group. The O.D. value of anti-AT1-receptor peptide antiserum was significantly higher in the immunized-group than in the rats before immunization and control group (P<0.01). Positive rate in the immunized-group was 100 %, while 0 % in the control group. Ultramicroscopic morphology showed potential myocardial injury, including: increase in number of mitochondria, swelling of many mitochondria with reduction in number or absence of their cristae and cristolysis, disorder of the cardiac myofibrils, and myofibrillar disruption and myocytolysis. And lysosomes were increased in renal tubular epithelia. The AT1-receptor peptide could induce to generate the antibody against AT1-receptor peptide and lead to myocardial and renal damage in rats.

  12. Immune Responses Following Mouse Peripheral Nerve Xenotransplantation in Rats

    Directory of Open Access Journals (Sweden)

    Lai-Jin Lu

    2009-01-01

    Full Text Available Xenotransplantation offers a potentially unlimited source for tissues and organs for transplantation, but the strong xenoimmune responses pose a major obstacle to its application in the clinic. In this study, we investigate the rejection of mouse peripheral nerve xenografts in rats. Severe intragraft mononuclear cell infiltration, graft distension, and necrosis were detected in the recipients as early as 2 weeks after mouse nerve xenotransplantation. The number of axons in xenografts reduced progressively and became almost undetectable at week 8. However, mouse nerve xenotransplantation only led to a transient and moderate increase in the production of Th1 cytokines, including IL-2, IFN-γ, and TNF-α. The data implicate that cellular immune responses play a critical role in nerve xenograft rejection but that further identification of the major effector cells mediating the rejection is required for developing effective means to prevent peripheral nerve xenograft rejection.

  13. Causes of immune dysfunction in hyperbilirubinemia model rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-Min Sun; Ping Kang; Ke Tao

    2015-01-01

    Objective:To explore the causes of immune dysfunction in neonatal rats with hyperbilirubinemia.Methods: A total of 60 newborn SD rats were equally randomized into normal saline (NS) group, LPS control group, bilirubin control group, low-dose group and high-dose group. After anesthesia, 0.1 mL NS was given to the NS and LPS control group and different doses of bilirubin for the other groups; 1 h later, the NS and bilirubin control group received the intraperitoneal injection of 0.05 mL NS and 1mg/kg LPS for the other groups. After 5 or 24 hours of model establishment, spleens were collected for detecting the expression levels of MyD88 and p-TAK1 protein and the spleen cells apoptosis by immunohistochemmistry and TUNEL method. After 24 hours of model establishment, serum inflammatory factors levels and T cell subsets distribution were determined by ELISA and flow cytometry.Results: In contrast to low-dose bilirubin, high-dose bilirubin could induce spleen cells apoptosis in coordination with LPS. After 5 hours of model establishment, compared with NS group, MyD88 expression level in low-dose group elevated while p-TAK1 level in high-dose group reduced (P<0.05). In high-dose group, inflammotory factors levels and CD8+ T cells percentage were all higher than LPS control and NS group (P<0.05), while CD4+ T cells percentage was lower than NS group (P<0.05).Conclusions:High-concentration plasma bilirubin in coordination with LPS could inhibit NF-κB signal pathways activation and aggravate inflammatory reaction, thus caused immunosuppression with inflammation cascade, which resulted in the immune dysfunction.

  14. A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8

    Directory of Open Access Journals (Sweden)

    McCooke John K

    2012-08-01

    Full Text Available Abstract Background Nephronophthisis (NPHP as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK rat. Results In this study, quantitative trait locus analysis was used to define a ~1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a- related kinase 8 ( Nek8 gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation. Conclusions When assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins.

  15. Age-related changes in functional NANC innervation with VIP and substance P in the jejunum of Lewis rats.

    Science.gov (United States)

    Kasparek, Michael S; Fatima, Javairiah; Iqbal, Corey W; Duenes, Judith A; Sarr, Michael G

    2009-12-03

    Age-related changes in non-adrenergic, non-cholinergic (NANC) neurotransmission might contribute to differences in gastrointestinal motility. Our aim was to determine age-related changes in functional innervation with vasoactive intestinal polypeptide (VIP) and substance P (Sub P) in rat jejunum. We hypothesized that maturation causes changes in neurotransmission with these two neuropeptides. Longitudinal and circular jejunal muscle strips from young (3 months) and middle-aged (15 months) rats (total: 24 rats) were studied; the response to exogenous VIP and Sub P and the effect of their endogenous release from the enteric nervous system during electrical field stimulation (EFS) were evaluated. In longitudinal muscle, response to exogenous VIP and endogenously released VIP during EFS were increased in middle-aged rats, while the effect of endogenously released Sub P was decreased. In the circular muscle, the response to endogenously released VIP was increased in middle-aged rats, while the effects of exogenous VIP and endogenously released Sub P were unchanged. Response to exogenous Sub P was unaffected by maturation in both muscle layers. Spontaneous contractile activity was increased in the longitudinal and circular muscle of the older rats. In the jejunum of middle-aged rats, participation of VIP in functional NANC innervation was increased, while functional innervation with Sub P was decreased. These changes in the balance of inhibitory and excitatory neurotransmission occur during the year of maturation in rats and demonstrate an age-dependant plasticity of neuromuscular bowel function.

  16. 皮下注射子宫内膜法建立Lewis大鼠腹壁子宫内膜异位症模型%Establishment of endometriosis model by abdominal wall subcutaneous injection of endometrium in Lewis rats

    Institute of Scientific and Technical Information of China (English)

    周玲; 钱志红; 任琼珍

    2012-01-01

    Objective To establish a endometriosis model by abdominal subcutaneous injection of endometrium in Lewis rats. Methods Endometrium of Lewis rats was subcutaneously injected into abdominal wall in 28 Lewis rats. On the 7th day and 21st day after surgery, the heterotopic nodules were taken out for HE staining and pathological observation. Results All 28 rats were survived with the ectopic endometrium growing in abdominal wall The ectopic endometrium nodules grew like a small cystic mass and with the basic organizational structures of normal endometrium under microscope. Conclusion The endometriosis model of Lewis rats has been successfully established, which is beneficial to the study of endometriosis.%目的 建立Lewis大鼠皮下子宫内膜异位症(EM)模型.方法 以同系大鼠作为供体,取子宫内膜,采用皮下注射法对28只大鼠行皮下造模手术,术后第7天及第21天取异位子宫内膜结节行HE染色和病理组织学观察.结果 实验大鼠均成活,腹壁子宫内膜异位种植成功率100%.子宫内膜在腹壁内生长,呈隆起囊状小包块,具有正常子宫内膜基本组织结构.结论 以同系大鼠子宫内膜皮下注射法成功地建立了Lewis大鼠腹壁EM模型,可用于EM研究.

  17. Immune reactivity of cells from long-term rat renal allograft survivors

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, A.; Stuart, F.P.; Fitch, F.W.

    1978-11-01

    Lewis rats receiving an LBN kidney allograft demonstrate no signs of rejection if they are pretreated with donor spleen cells and antiserum reactive with the donor alloantigen. We examined the cellular reactivity of long-term kidney allograft survivors. Normal proliferative and cytolytic responses were obtained with spleen cells from long-term survivors, in marked contrast to the diminished responses of cells from neonatally tolerant rats or the heightened cytolytic response of cells from rats that had rejected a renal allograft. Serum from long-term renal allograft survivors as well as serum obtained from rats at the time of transplantation did not suppress proliferative or cytolytic responses of normal cells. The results of this study suggest that long-term renal allograft survivors possess the precursors of those cells which are responsible for proliferative and cytolytic responses in mixed leukocyte cultures, but that they have not been sensitized to their renal allograft.

  18. Nitrogen Lewis Acids.

    Science.gov (United States)

    Pogoreltsev, Alla; Tulchinsky, Yuri; Fridman, Natalia; Gandelman, Mark

    2017-03-22

    Being a major conception of chemistry, Lewis acids have found countless applications throughout chemical enterprise. Although many chemical elements can serve as the central atom of Lewis acids, nitrogen is usually associated with Lewis bases. Here, we report on the first example of robust and modifiable Lewis acids centered on the nitrogen atom, which provide stable and well-characterized adducts with various Lewis bases. On the basis of the reactivity of nitrogen Lewis acids, we prepared, for the first time, cyclic triazanes, a class of cyclic organic compounds sequentially bearing three all-saturated nitrogen atoms (N-N-N motif). Reactivity abilities of these N-Lewis acids were explained by theoretical calculations. Properties and future applications of nitrogen Lewis acids are intriguing.

  19. Lewy Body Dementia Association

    Science.gov (United States)

    ... promoting scientific advances. Featured LBD Stories & Tributes Dad's Dementia Journey It's been years since my father passed ... I received an email from the Lewy Body Dementia Association about a benefit... Read Story The Lewy ...

  20. Population pharmacokinetic-pharmacodynamic-disease progression model for effects of anakinra in Lewis rats with collagen-induced arthritis.

    Science.gov (United States)

    Liu, Dongyang; Lon, Hoi-Kei; Dubois, Debra C; Almon, Richard R; Jusko, William J

    2011-12-01

    A population pharmacokinetic-pharmacodynamic-disease progression (PK/PD/DIS) model was developed to characterize the effects of anakinra in collagen-induced arthritic (CIA) rats and explore the role of interleukin-1β (IL-1β) in rheumatoid arthritis. The CIA rats received either vehicle, or anakinra at 100 mg/kg for about 33 h, 100 mg/kg for about 188 h, or 10 mg/kg for about 188 h by subcutaneous infusion. Plasma concentrations of anakinra were assayed by enzyme-linked immunosorbent assay. Swelling of rat hind paws was measured. Population PK/PD/DIS parameters were computed for the various groups using non-linear mixed-effects modeling software (NONMEM® Version VI). The final model was assessed using visual predictive checks and nonparameter stratified bootstrapping. A two-compartment PK model with two sequential absorption processes and linear elimination was used to capture PK profiles of anakinra. A transduction-based feedback model incorporating logistic growth rate captured disease progression and indirect response model I captured drug effects. The PK and paw swelling versus time profiles in CIA rats were fitted well. Anakinra has modest effects (I ( max ) = 0.28) on paw edema in CIA rats. The profiles are well-described by our PK/PD/DIS model which provides a basis for future mechanism-based assessment of anakinra dynamics in rheumatoid arthritis.

  1. Aberrant Pregnancy Adaptations in the Peripheral Immune Response in Type 1 Diabetes: A Rat Model.

    Directory of Open Access Journals (Sweden)

    Bart Groen

    Full Text Available Despite tight glycemic control, pregnancy complication rate in type 1 diabetes patients is higher than in normal pregnancy. Other etiological factors may be responsible for the development of adverse pregnancy outcome. Acceptance of the semi-allogeneic fetus is accompanied by adaptations in the maternal immune-response. Maladaptations of the immune-response has been shown to contribute to pregnancy complications. We hypothesized that type 1 diabetes, as an autoimmune disease, may be associated with maladaptations of the immune-response to pregnancy, possibly resulting in pregnancy complications.We studied pregnancy outcome and pregnancy-induced immunological adaptations in a normoglycemic rat-model of type 1 diabetes, i.e. biobreeding diabetes-prone rats (BBDP; 5 non-pregnant rats, 7 pregnant day 10 rats and 6 pregnant day 18 rats , versus non-diabetic control rats (i.e. congenic non-diabetic biobreeding diabetes-resistant (BBDR; 6 non-pregnant rats, 6 pregnant day 10 rats and 6 pregnant day 18 rats and Wistar-rats (6 non-pregnant, 6 pregnant day 10 rats and 5 pregnant day 18 rats.We observed reduced litter size, lower fetal weight of viable fetuses and increased numbers of resorptions versus control rats. These complications are accompanied by various differences in the immune-response between BBDP and control rats in both pregnant and non-pregnant animals. The immune-response in non-pregnant BBDP-rats was characterized by decreased percentages of lymphocytes, increased percentages of effector T-cells, regulatory T-cells and natural killer cells, an increased Th1/Th2-ratio and activated monocytes versus Wistar and BBDR-rats. Furthermore, pregnancy-induced adaptations in BBDP-rats coincided with an increased Th1/Th2-ratio, a decreased mean fluorescence intensity CD161a/NKR-P1b ratio and no further activation of monocytes versus non-diabetic control rats.This study suggests that even in the face of strict normoglycemia, pregnancy complications

  2. Active and Passive Immunization Against Staphylococcus aureus Periprosthetic Osteomyelitis in Rats

    DEFF Research Database (Denmark)

    Soe, Niels H.; Jensen, Nina Vendel; Jensen, Asger Lundorff

    2017-01-01

    and Methods: Fifty-two Sprague-Dawley rats were divided into active (N=28) and passive immunization groups (N=24). A bacterial inoculum of 10(3) S. aureus MN8 was injected into the tibia and the femur marrow before insertion of a non-constrained knee prosthesis in each rat. The active-immunization group...... received a synthetic oligosaccharide of polysaccharide poly-N-acetylglucosamine (PNAG), 9G1cNH(2) and the passive-immunization group received immunization with immunoglobulin from rabbits infected with S. aureus. Results/Conclusion: Active immunization against PNAG significantly reduced the consequences...... of osteomyelitis infection from PNAG-producing intercellular adhesion (ica(+)) but not ica(-) S. aureus. Passive immunization resulted in better clinical assessments in animals challenged with either ica(+) or icaS. aureus, suggesting a lack of specificity in this antiserum....

  3. Ameliorative effects of human adipose tissue-derived mesenchymal stem cells on myelin basic protein-induced experimental autoimmune encephalomyelitis in Lewis rats

    Institute of Scientific and Technical Information of China (English)

    Myung-Soon Ko; Hyeong-geun Park; Young-Min Yun; Jeong Chan Ra; Taekyun Shin; Kyoung-Kap Lee

    2011-01-01

    Mesenchymal stem cells have been previously shown to exert an immunomodulatory function. The present study sought to investigate the effects of multipotential human adipose tissue-derived mesenchymal stem cells (hAdMSCs) on disease progression and cytokine expression in Lewis rats with experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein. The duration of EAE paralysis in the group treated on day 7 postimmunization with 5 × 106 hAdMSCs was significantly reduced compared with the vehicle-treated controls and the 1 × 106 hAdMSC- treated group. The duration of EAE paralysis in the groups treated with 5 × 106 hAdMSCs on both day 1 and day 7 postimmunization was significantly reduced compared with the vehicle-treated controls and the groups treated with 5 × 106 hAdMSCs on both day 7 and day 10 postimmunization. The mRNA expression of interleukin-10 and indoleamine 2, 3-dioxygenase was significantly decreased in the hAdMSC-treated group compared with the vehicle-treated group. These findings suggest that the ameliorative effects of hAdMSCs on EAE symptoms operate in a dose- and time-dependent manner and can be mediated in part by the ample production of anti-inflammatory cytokines.

  4. Tissue distribution of 2-methoxyestradiol nanosuspension in rats and its antitumor activity in C57BL/6 mice bearing lewis lung carcinoma.

    Science.gov (United States)

    Shen, Guopeng; Wang, Qingyu; Zhang, Qingqing; Sun, Huibin; Zhao, Ya; Zhang, Zhenzhong; Du, Bin

    2012-01-01

    The purpose of the present study was to evaluate the tissue distribution and antitumor activity of 2-methoxyestradiol (2-ME) nanosuspension compared with 2-ME solution both in vitro and in vivo. 2-ME nanosuspension was made by nanoprecipitation-high-frequency ultrasonication method with the particle size of 168.4 ± 3.2 nm and the zeta potential of -29.79 ± 1.89 mV. The overall targeting efficiency (TE(Q)) of 2-ME nanosuspension was improved from 28.71 to 51.95% in the lung of rats. MTT assay showed that 2-ME nanosuspension could significantly enhance the in vitro cytotoxicity against lewis lung carcinoma (LLC) cells compared with the 2-ME solution, the IC(50) at 72 h was reduced from 6.35 µM for 2-ME solution to 3.56 µM for 2-ME nanosuspension. The antitumor activity in vivo was investigated in C57BL/6 mice bearing LLC, and the results indicated that 2-ME nanosuspension not only exhibited significant suppression of the tumor growth when compared with that of positive group or cyclophosphamide group at the same dose, but also enhanced the spleen indices. Overall, 2-ME nanosuspension could mainly deliver the drug to lungs and made the drug accumulate in the lungs, so 2-ME nanosuspension has a possible lung cancer therapeutic potential.

  5. Time-Dependent Increases in Protease Activities for Neuronal Apoptosis in Spinal Cords of Lewis Rats During Development of Acute Experimental Autoimmune Encephalomyelitis

    Science.gov (United States)

    Das, Arabinda; Guyton, M. Kelly; Matzelle, Denise D.; Ray, Swapan K.; Banik, Naren L.

    2008-01-01

    Multiple sclerosis (MS) is characterized by axonal demyelination and neurodegeneration, the latter having been inadequately explored in the MS animal model experimental autoimmune encephalomyelitis (EAE). The purpose of this study was to examine the time-dependent correlation between increased calpain and caspase activities and neurodegeneration in spinal cord tissues from Lewis rats with acute EAE. An increase in TUNEL-positive neurons and internucleosomal DNA fragmentation in EAE spinal cords suggested that neuronal death was a result of apoptosis on days 8–10 following induction of EAE. Increases in calpain expression in EAE correlated with activation of pro-apoptotic proteases, leading to apoptotic cell death beginning on day 8 of EAE, which occurred before the appearance of visible clinical symptoms. Increases in calcineurin expression and decreases in phospho-Bad (p-Bad) suggested Bad activation in apoptosis during acute EAE. Increases in the Bax:Bcl-2 ratio and activation of caspase-9 showed the involvement of mitochondria in apoptosis. Further, caspase-8 activation suggested induction of the death receptor–mediated pathway for apoptosis. Endoplasmic reticulum stress leading to caspase-3 activation was also observed, indicating that multiple apoptotic pathways were activated following EAE induction. In contrast, cell death was mostly a result of necrosis on the later day (day 11), when EAE entered a severe stage. From these findings, we conclude that increases in calpain and caspase activities play crucial roles in neuronal apoptosis during the development of acute EAE. PMID:18521931

  6. Development of immune memory to glial brain tumours after tumour regression induced by immunotherapeutic Toll-like receptor 7/8 activation

    NARCIS (Netherlands)

    Stathopoulos, A.; Pretto, C.; Devilliers, L.; Hofman, F.M.; Kruse, C.A.; Jadus, M.; Chen, T.C.; Schijns, V.E.J.C.

    2012-01-01

    The efficacy of immunotherapeutic TLR7/8 activation by resiquimod (R848) was evaluated in vivo, in the CNS-1 rat glioma model syngeneic to Lewis rats. The immune treatment was compared with cytotoxic cyclophosphamide chemotherapy, and as well, was compared with the combination cytotoxic and

  7. Development of immune memory to glial brain tumours after tumour regression induced by immunotherapeutic Toll-like receptor 7/8 activation

    NARCIS (Netherlands)

    Stathopoulos, A.; Pretto, C.; Devilliers, L.; Hofman, F.M.; Kruse, C.A.; Jadus, M.; Chen, T.C.; Schijns, V.E.J.C.

    2012-01-01

    The efficacy of immunotherapeutic TLR7/8 activation by resiquimod (R848) was evaluated in vivo, in the CNS-1 rat glioma model syngeneic to Lewis rats. The immune treatment was compared with cytotoxic cyclophosphamide chemotherapy, and as well, was compared with the combination cytotoxic and immunoth

  8. Changes in intestinal mucosal immune barrier in rats with endotoxemia

    Institute of Scientific and Technical Information of China (English)

    Chong Liu; Ang Li; Yi-Bing Weng; Mei-Li Duan; Bao-En Wang; Shu-Wen Zhang

    2009-01-01

    AIM: To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS: Male Wistar rats were randomly distributed into two groups: control group and lipopolysaccharide (LPS) group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold (M)-cells, dendritic cells (DCs), CD4~+ T cells, CD8~+ T cells, regulatory T (Tr) cells and IgA~+ B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin (IL)-4, interferon (IFN)-γ and forkhead box P3 (Foxp3) in mucosal homogenates were measured by ELISA. The secretory IgA (sIgA) content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay. RESULTS: This research demonstrated that LPS LPSinduced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8~+ T cells, and IgA~+ B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4~+ T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-γ increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased. CONCLUSION: Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunode- ficiency.

  9. Immune Responses to Trichloroethylene and Skin Gene Expression Profiles in Sprague Dawley Rats

    Institute of Scientific and Technical Information of China (English)

    XIAO-YAN CHEN; ZHI-XIONG ZHUANG; XIAO-HUI WANG; JIN-ZHOU ZHANG

    2006-01-01

    Objective To characterize the immune reaction in SD rats exposed to trichloroethylene (TCE) and to identify the gene expression profiles involved in skin after TCE exposure. Methods Fifteen percent of TCE was injected intradermally into the rat back (100 μL/120 g) at intervals of 7 days. Whole blood was collected 24 h after the fifth or seventh intradermic administration of TCE. The percentages of CD4+ and CD8+ of T lymphocytes were measured by a flow cytometer. The concentrations of IFN-gamma and IL-4 in the serum were semi-quantified by ELISA. Total RNAs of skin samples at 3 h or 24 h after the seventh dose of TCE in SD rats were extracted, and gene expression profiles of these tissues were analyszed by rat toxicology U34 array of Affymetrix. Results Obvious decline of CD4+ in T lymphocytes was observed in theTCE-administer group. No significant concentration differences in IFN-gamma and IL-4 were found between TCE-treated and control rats. Gadd45a and Mel were significantly up regulated in skin tissue 24 h after TCE exposure. The expression regulation of immune response factors was as active as proteins associated with lipid metabolism and synthesis process in these skin samples of SD rats exposed to TCE. Conclusion T-helper type 1 cells mediate immune response can not be elicited in TCE-treated SD rats, but certain immune disorder can be induced.

  10. Time course of cyclosporine and ist motabolites in blood, liver and spleen of naive Lewis rats: comparison with preliminary data obtained in transplanted animals.

    Science.gov (United States)

    Wacher, V J; Liu, T; Roberts, J P; Ascher, N L; Benet, L Z

    1995-05-01

    the time course of intravenously administered cyclosporine (1 mg kg-1) and its metabolite AM1, AM9, and AM1c were examined in the blood, liver, and spleen of naive Lewis rats. Cyclosporine concentration versus time data for all three tissues were qualitatively similar, following a biexponential model C = Ae-gamma 1t + Be-gamma 2t with maximum cyclosporine concentrations reached at 1 h. Whole-blood cyclosporine clearance, terminal half-life, mean residence time, steady state volume of distribution, and hepatic extraction ratio (calculated from blood data) were similar to previously reported results. Cyclosporine in the liver showed the largest area under the concentration-time curve, mean residence time, and disposition and terminal half-lives. Spleen cyclosporine mean residence time and and terminal half-life were not significantly different from blood parameters. Metabolites AM1, AM9, and AM1c showed almost parallel time courses in all three tissues. The hydroxylated derivative AM9 was the major metabolite found in all tissues, with twofold greater levels in the liver compared to the blood and spleen. Slightly less AM1 was found in the liver relative to blood and spleen, where it was present in equal amounts. AM1c levels in the liver were not different from those in the spleen and were greater than observed for blood. The results obtained above were reflected in preliminary studies using liver transplanted rats treated with multiple doses of cyclosporine. Both blood and liver biopsy levels of CyA, AM1, and AM9 post-transplant showed twofold to fourfold decreases from day 3 ( samples taken 4 h post-CyA-dose) and concentrations were not significantly different from similarly sampled naive controls. More importantly, the metabolite/CyA ratios did not vary significantly between liver and blood in the two groups. For naive rats, and liver transplanted animals not undergoing rejection, changes in blood cyclosporine levels seem to predict variations in tissue

  11. Alloimmune activation promotes anti-cancer cytotoxicity after rat liver transplantation.

    Science.gov (United States)

    Lacotte, Stéphanie; Oldani, Graziano; Slits, Florence; Orci, Lorenzo A; Rubbia-Brandt, Laura; Morel, Philippe; Mentha, Gilles; Toso, Christian

    2014-01-01

    Liver transplantation for hepatocellular carcinoma (HCC) results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (ptests (pcytotoxicity (pcytotoxicity (pcytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (pcytotoxicity. Although waiting for in vivo validation, alloimmune-associated cytotoxicity after rat liver transplantation appears to be linked to increased frequencies and levels of activation of NK cells and monocyte/macrophages, and is at least in part mediated through the NKG2D receptor.

  12. Vaccenic acid favourably alters immune function in obese JCR:LA-cp rats.

    Science.gov (United States)

    Blewett, Heather J; Gerdung, Christopher A; Ruth, Megan R; Proctor, Spencer D; Field, Catherine J

    2009-08-01

    Vaccenic acid (VA) is a ruminant-derived trans-fat and precursor of conjugated linoleic acid (CLA). The objective of the present study was to explore the effects of VA on immune function in a model of the metabolic syndrome, JCR:LA-cp rats. Lean (2:1 mix of +/cp and +/+) and obese (cp/cp) rats, aged 8 weeks, were fed a control (0% VA) or a VA diet (1.5% (w/w) VA) for 3 weeks (twenty rats per group). Splenocytes and mesenteric lymph node (MLN) immune cell phenotypes (flow cytometry), ex vivo cytokine production (ELISA) and phospholipid fatty acid concentrations were measured. Obese rats had higher proportions of splenic macrophages, total T-cells, helper T-cells (total and percentage CD25+), cytotoxic T-cells (total and percentage CD25+) and produced higher concentrations of IL-6 to concanavalin A (ConA) compared with lean rats. Obese rats had lower proportions of MLN T-cells, new T-cells (CD3+CD90+) and cytotoxic T-cells, but higher proportions of helper cells that were CD45RC+, CD25+ and CD4lo, and produced higher concentrations of IL-2, IL-10, interferon gamma and TNFalpha in response to ConA compared with lean rats. VA was higher in plasma phospholipids and both VA and CLA (cis-9, trans-11) were higher in MLN phospholipids compared with control-fed rats. Lean VA-fed rats had lower proportions of MLN and splenocyte CD45RC+ helper cells, and helper T-cells. Splenocytes from VA-fed rats produced 16-23% less IL-2, IL-10 and TNFalpha compared with controls. VA normalised production of MLN IL-2 and TNFalpha in obese rats to levels similar to those seen in lean rats. These results indicate that dietary VA favourably alters the pro-inflammatory tendency of mesenteric lymphocytes from JCR:LA-cp rats.

  13. Lewy Body Dementia Research

    Science.gov (United States)

    ... a new treatment for hallucinations in Parkinson’s disease. Symptoms Differ in Alzheimer's when Lewy Bodies are Present June, 2015 - Lewy ... distinguish the underlying cause or causes of dementia symptoms. The diagnostic ... Alzheimer’s disease pathology alone versus those who have both ...

  14. Fibrogenic and redox-related but not proinflammatory genes are upregulated in Lewis rat model of chronic silicosis.

    Science.gov (United States)

    Langley, Raymond J; Mishra, Neerad C; Peña-Philippides, Juan Carlos; Rice, Brandon J; Seagrave, Jean-Clare; Singh, Shashi P; Sopori, Mohan L

    2011-01-01

    Silicosis, a fibrotic granulomatous lung disease, may occur through accidental high-dose or occupational inhalation of silica, leading to acute/accelerated and chronic silicosis, respectively. While chronic silicosis has a long asymptomatic latency, lung inflammation and apoptosis are hallmarks of acute silicosis. In animal models, histiocytic granulomas develop within days after high-dose intratracheal (IT) silica instillation. However, following chronic inhalation of occupationally relevant doses of silica, discrete granulomas resembling human silicosis arise months after the final exposure without significant lung inflammation/apoptosis. To identify molecular events associated with chronic silicosis, lung RNA samples from controls or subchronic silica-exposed rats were analyzed by Affymetrix at 28 wk after silica exposures. Results suggested a significant upregulation of 144 genes and downregulation of 7 genes. The upregulated genes included complement cascade, chemokines/chemokine receptors, G-protein signaling components, metalloproteases, and genes associated with oxidative stress. To examine the kinetics of gene expression relevant to silicosis, quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), Luminex-bead assays, Western blotting, and/or zymography were performed on lung tissues from 4 d, 28 wk, and intermediate times after subchronic silica exposure and compared with 14-d acute silicosis samples. Results indicated that genes regulating fibrosis (secreted phosphoprotein-1, Ccl2, and Ccl7), redox enzymes (superoxide dismutase-2 and arginase-1), and the enzymatic activities of matrix metalloproteinases 2 and 9 were upregulated in acute and chronic silicosis models. However, proinflammatory cytokines were strongly upregulated only in acute silicosis. Thus, inflammatory cytokines are associated with acute but not chronic silicosis. Data suggest that genes regulating fibrosis, oxidative stress, and metalloproteases may

  15. [Effect of deltaran and melatonin on immune system in rats with experimental contact dermatitis].

    Science.gov (United States)

    Shandra, O O

    2014-01-01

    The aim of the work was investigation of both humoral and cell-mediated immunity together with leukocytes functional stability indexes in rats with the experimental contact dermatitis (ECD) in conditions of complex pharmacological correction using deltaran and melatonin. Experimental trials were performed under conditions of chronic experiment on model chrome-induced ECD. Both deltaran and melatonin either alone or in combination were used for complex pharmacological correction of humoral and cell-mediated immunity and also for stability of leukocytes. The data obtained showed the expressed disturbances of humoral and cell-mediated immunity and neutrophils' functional stability damage under conditions of chrome-induced ECD in rats. The revealed alterations in functional activity of the immune system were successfully corrected using the combined administration of deltaran and melatonin. The activity of medical complex had exponential character.

  16. Reduced Incidence of Slowly Progressive Heymann Nephritis in Rats Immunized With a Modified Vaccination Technique

    Directory of Open Access Journals (Sweden)

    Arpad Z. Barabas

    2006-01-01

    Full Text Available A slowly progressive Heymann nephritis (SPHN was induced in three groups of rats by weekly injections of a chemically modified renal tubular antigen in an aqueous medium. A control group of rats received the chemically unmodified version of the antigen in an aqueous solution. One group of SPHN rats were pre- and post-treated with weekly injections of IC made up of rKF3 and rarKF3 IgM antibody at antigen excess (MIC (immune complexes [ICs] containing sonicated ultracentrifuged [u/c] rat kidney fraction 3 [rKF3] antigen and IgM antibodies specific against the antigen, at slight antigen excess. One group of SPHN rats were post-treated with MIC 3 weeks after the induction of the disease and one group of SPHN animals received no treatment. The control group of rats received pre- and post-treatment with sonicated u/c rKF3.

  17. Effect of Heavy Ion Brain Radiation on Nerve-immune System Regulation Mechanism in Rat

    Institute of Scientific and Technical Information of China (English)

    YU; Ying-qi; WANG; Xiao; KONG; Fu-quan; SUI; Li; LEI; Run-hong; MA; Hong; DENG; Yu-lin; LI; Qiang

    2013-01-01

    High-dose ionizing irradiation can cause extensive injuries in susceptible tissues.Blood,nervous and immune systems are highly radiation-sensitive.While the nerve-immune system regulation of radiationdamage in the relevant research is rare.So the brain injury model that rats were subjected to 15 Gy of head irradiation was built.By detecting hypothalamic-pituitary-adrenal axis(HPA axis)changes,the

  18. Effects of Meridian Scraping on Immune Function and Athletic Ability in Endurance Training Rats

    Directory of Open Access Journals (Sweden)

    Ronghua Liu

    2013-12-01

    Full Text Available Aim of the study-To investigate the effects of meridian scraping on immune function and athletic ability in endurance training rats. Materials and methods-Twenty four adult male Sprague-Dawley rats were randomly assigned to non-training group (A, training control group (B or meridian scraping and training group (C. Rats in groups B and C were loaded with incremental endurance training for 7 weeks and body weight, indices of immune organs, levels of serum immunoglobulin G (IgG, IgM, IL-6, &beta-endorphin and time to strength exhaustion of rats in running plate on the first day of the 8th week, were measured. Results-Meridian scraping effectively modulated the changes in body weight and immune function induced by endurance training. Meridian scraping treatment also inhibited the training-induced decrease of serum IgG, but increased serum IL-6 and &beta -endorphin levels and prolonged the time to strength exhaustion. Conclusions-Meridian scraping increased the athletic ability of rats in endurance training, delayed the occurrence of sports fatigue and improved immune function.

  19. Immunity to Schistosoma mansoni in congenitally athymic, irradiated and mast cell-depleted rats

    Energy Technology Data Exchange (ETDEWEB)

    Ford, M.J.; Bickle, Q.D.; Taylor, M.G.

    1987-04-01

    Immunity to Schistosoma mansoni was investigated in congenitally athymic (Nu/Nu) rats, irradiated rats and in mast cell-depleted rats. Nu/Nu rats failed to develop significant resistance following vaccination with irradiated cercariae, although Nu/Nu recipients of serum from vaccinated Fischer rats (VRS) manifested resistance comparable to heterozygous controls, suggesting that T-cells were required in the induction of resistance but were not involved in the efferent arm of antibody-dependent elimination. Radiosensitive cells (including eosinophils, basophils, neutrophils, lymphocytes and mast cells) were apparently not essential for the antibody-dependent elimination of lung or post-lung stages since irradiated (700-750 rad.) recipients of VRS manifested comparable degrees of resistance to unirradiated controls in spite of a greater than 85% reduction in total blood leucocyte counts after irradiation. Depletion of 99% of tissue mast cells by treatment of rats with Compound 48/80 had no significant effect on the attrition of a challenge infection in rats rendered immune by vaccination with irradiated cercariae or by transfer of VRS. However, there was a significant increase in worm recovery in unimmunized and mast cell-depleted or irradiated rats, indicating that mast cells and perhaps other radio-isotope sensitive cells may be involved in innate resistance.

  20. Probiotic Cheese Attenuates Exercise-induced Immune Suppression In Wistar Rats

    OpenAIRE

    Lollo P.C.B.; Cruz A.G.; Morato P.N.; Moura C.S.; Carvalho-Silva L.B.; Oliveira C.A.F.; Faria J.A.F.; Amaya-Farfan J.

    2012-01-01

    Intense physical activity results in a substantial volume of stress and hence a significant probability of immunosuppression in athletes, with milk proteins being, perhaps, the most recommended protein supplements. Consumption of a probiotic cheese can attenuate immune suppression induced by exhausting exercise in rats. A popular Brazilian fresh cheese (Minas Frescal cheese) containing Lactobacillus acidophilus LA14 and Bifidobacterium longum BL05 was fed for 2 wk to adult Wistar rats, which ...

  1. Induction of immune tolerance with heart-thymus composite allotransplantation in rats

    Institute of Scientific and Technical Information of China (English)

    XIONG Hai-bo; XIA Sui-sheng; WEN Hao; HUANG Zu-fa; YE Qi-fa

    2005-01-01

    Objective To study on the role of thymus transplantation for heart allograft in rats. Methods Vascularized heart-thymus combined transplantation was performed with microsurgical technique. Graft survival, histopathology, level of IL-2, IL-4 and its mRNA expression in serum and cardiac grafts were investigated. Results Heart-thymus combined transplantation achieved effect in the prolongation of cardiac graft survival with short-term administration of cyclosporine. Conclusions Vascularized thymus transplantation induced immune tolerance in thymectomized rats.

  2. Pulmonary Immune Responses to Aspergillus Fumigatus in Rats

    Institute of Scientific and Technical Information of China (English)

    MIRKOV Ivana; EL-MUZGHI Amal Atia Mhfuod; DJOKIC Jelena; NINKOV Marina; POPOV ALEKSANDROV Aleksandra; GLAMOCLIJA Jasmina; KATARANOVSKI Milena

    2014-01-01

    Objective To evaluate immunologic mechanisms underlying Aspergillus fumigatus pulmonary infections in immunocompetent Dark Agouti (DA) and Albino Oxford (AO) rats recognized as being susceptible to some inflammatory diseases in different manners. Methods Lung fungal burden (quantitative colony forming units, CFU, assay), leukocyte infiltration (histology, cell composition) and their function (phagocytosis, oxidative activity, CD11b adhesion molecule expression) and cytokine interferon-γ(IFN-γ) and interleukin-17 and-4 (IL-17 and IL-4) lung content were evaluated following infection (intratracheally, 1x107 conidia). Results Slower reduction of fungal burden was observed in AO rats in comparison with that in DA rats, which was coincided with less intense histologically evident lung cell infiltration and leukocyte recovery as well as lower level of most of the their activities including intracellular myeloperoxidase activity, the capacity of nitroblue tetrazolium salt reduction and CD11b adhesion molecule expression (except for phagocytosis of conidia) in these rats. Differential patterns of changes in proinflammatory cytokine levels (unchanged levels of IFN-γand transient increase of IL-17 in AO rats vs continuous increase of both cytokines in DA rats) and unchanged levels of IL-4 were observed. Conclusion Genetically-based differences in the pattern of antifungal lung leukocyte activities and cytokine milieu, associated with differential efficiency of fungal elimination might be useful in the future use of rat models in studies of pulmonary aspergillosis.

  3. Sleep Deprivation Induces Changes in Immunity in Trichinella spiralis-Infected Rats

    Science.gov (United States)

    Ibarra-Coronado, Elizabeth G.; Velazquéz-Moctezuma, Javier; Diaz, Daniel; Becerril-Villanueva, Luis Enrique; Pavón, Lenin; Morales-Montor, Jorge

    2015-01-01

    Sleep is considered an important predictor of immunity. A lack of sleep may reduce immunity, which increases susceptibility to any type of infection. Moreover, sleep deprivation in humans produces changes in both, the percent of circulating immune cells (T cells and NK cells) and cytokine levels (IL-1, IFNγ, TNΦ-αα, IL-6 and IL-17). The aim of our study was to investigate whether sleep deprivation produces deregulation on immune variables during the immune response generated against the helminth parasite Trichinella spiralis. Because sleep deprivation is stressful per se, we designed another experiments to compared stress alone (consisting in movement restriction and single housing) with sleep deprivation, in both control (uninfected) and experimental (infected) rats. Our results demonstrate that the sleep deprivation and stress have a differential effect in mesenteric lymph nodes (MLN) and spleen. In uninfected rats sleep deprivation alone produces an increase in natural killer cells (NK+) and B cells (CD45+), accompanied by a decrease in cytotoxic T cells (CD3+CD8+) in spleen; while, in MLN, produces only an increase in natural killer cells (NK+). Both, SD and stress, produce an increased percentage of total T cells (CD3+) in spleen. In the MLN both are also associated to an increase in cytotoxic T cells (CD3+CD8+) and B cells (CD45+). In the spleens of parasitized rats, cell populations did not change. In spleens of both, sleep-deprived and stressed infected rats, we observed an increase in B cells (CD45+). In infected rats, sleep deprivation alone produced an increase in NK cells (NK+). In mesenteric node cell populations of parasitized rats, we observed a decrease in NK cells and an increase in T helper (CD4+) cells in both SD and stressed rats. Rats that were only subjected to stress showed a decrease in B cells (CD45+). These findings suggest that the immune response generated against infection caused by T. spiralis is affected when the sleep pattern is

  4. Sleep deprivation induces changes in immunity in Trichinella spiralis-infected rats.

    Science.gov (United States)

    Ibarra-Coronado, Elizabeth G; Velazquéz-Moctezuma, Javier; Diaz, Daniel; Becerril-Villanueva, Luis Enrique; Pavón, Lenin; Morales-Montor, Jorge

    2015-01-01

    Sleep is considered an important predictor of immunity. A lack of sleep may reduce immunity, which increases susceptibility to any type of infection. Moreover, sleep deprivation in humans produces changes in both, the percent of circulating immune cells (T cells and NK cells) and cytokine levels (IL-1, IFNγ, TNΦ-αα, IL-6 and IL-17). The aim of our study was to investigate whether sleep deprivation produces deregulation on immune variables during the immune response generated against the helminth parasite Trichinella spiralis. Because sleep deprivation is stressful per se, we designed another experiments to compared stress alone (consisting in movement restriction and single housing) with sleep deprivation, in both control (uninfected) and experimental (infected) rats. Our results demonstrate that the sleep deprivation and stress have a differential effect in mesenteric lymph nodes (MLN) and spleen. In uninfected rats sleep deprivation alone produces an increase in natural killer cells (NK+) and B cells (CD45+), accompanied by a decrease in cytotoxic T cells (CD3+CD8+) in spleen; while, in MLN, produces only an increase in natural killer cells (NK+). Both, SD and stress, produce an increased percentage of total T cells (CD3+) in spleen. In the MLN both are also associated to an increase in cytotoxic T cells (CD3+CD8+) and B cells (CD45+). In the spleens of parasitized rats, cell populations did not change. In spleens of both, sleep-deprived and stressed infected rats, we observed an increase in B cells (CD45+). In infected rats, sleep deprivation alone produced an increase in NK cells (NK+). In mesenteric node cell populations of parasitized rats, we observed a decrease in NK cells and an increase in T helper (CD4+) cells in both SD and stressed rats. Rats that were only subjected to stress showed a decrease in B cells (CD45+). These findings suggest that the immune response generated against infection caused by T. spiralis is affected when the sleep pattern is

  5. Cortical Lewy Body Dementia

    Directory of Open Access Journals (Sweden)

    W. R. G. Gibb

    1990-01-01

    Full Text Available In cortical Lewy body dementia the distribution of Lewy bodies in the nervous system follows that of Parkinson's disease, except for their greater profusion in the cerebral cortex. The cortical tangles and plaques of Alzheimer pathology are often present, the likely explanation being that Alzheimer pathology provokes dementia in many patients. Pure cortical Lewy body dementia without Alzheimer pathology is uncommon. The age of onset reflects that of Parkinson's disease, and clinical features, though not diagnostic, include aphasias, apraxias, agnosias, paranoid delusions and visual hallucinations. Parkinsonism may present before or after the dementia, and survival duration is approximately half that seen in Parkinson's disease without dementia.

  6. Lewy body dementias

    DEFF Research Database (Denmark)

    Løkkegaard, Annemette; Korbo, Lise

    2017-01-01

    Dementia with Lewy bodies and Parkinson disease dementia share the same pathophysiology. Together they are called Lewy body dementias and are the second most common type of dementia. Lewy body dementias receive little attention, and patients are often misdiagnosed, leading to less than ideal...... management. In this article, diagnostic criteria combined with imaging and other biomarkers as well as current treatment recommendations are summarized, and some of the challenges for the future are outlined. Refinement of diagnosis and clarification of the pathogenesis are required in search for disease...

  7. EFFECT OF ELECTROACUPUNCTURE ON RED BLOOD CELL IMMUNE AND T-CELL SUBGROUP IN THE RAT

    Institute of Scientific and Technical Information of China (English)

    高巍; 黄裕新; 陈洪; 孙大勇; 张洪新

    2000-01-01

    In the present study, the effect of electroacupuncture (EA) on immune system was observed in the rat by using micro- whole blood direct immunofluorescence Staining assay to detect changes of the peripheral blood T lymphocyte subgroup and employing red blood cell (RBC) C3b receptor- yeast rosette test and red blood cell-IC rosette test to analyze erythrocytic immune function. Resuits showed that after EA of “Zusanli” (ST 36), CD4+, RBC-C3bRR and RBC-ICR in the peripheral blood of the normal rats increased significantly while CDs+ had no any considerable changes and a positive correlation between CD~ and RBC-C3bRR was found. In immtttaosuppression model rats, the values of CD4+ and RBC-C3bRR were obviously lower than those of the normal control group while CD8+ had no any striking changes; but after EA treatment, there were no evident differences between EAgroup and normal control group in the above-mentioned indexes. There were also no any significant differences between non-acupoint group and normal control group in those indexes. Results suggest that EA of “Zusanli” (ST 36) can raise T cell immune function and RBC adhesion function in both normal rats and immunosuppression model rats, both of which present a positive correlation.

  8. EFFECT OF ELECTROACUPUNCTURE ON RED BLOOD CELL IMMUNE AND T-CELL SUBGROUP IN THE RAT

    Institute of Scientific and Technical Information of China (English)

    GaoWei; HuangYuxin; ChenHong; SunDayong; ZhangHongxin

    2000-01-01

    In the present study, the effect of electroacupuncture (EA) on immune system was observed in the rat by using micro- whole blood direct immunofluoreseence Staining assay to detect changes of the peripheral blood T lymphocyte subgroup and employing red blood cell (RBC) C3b receptor- yeast rosette test and red blood cell-IC rosette test to analyze erythroeytic immune function. Results showed that after EA of “Zusanli” (ST 36), CD4+, RBC-C3bRR and RBC-ICR in the peripheral blood of the normal rats increased significantly while CD8+ had no any considerable changes and a positive correlation between CD4+ and RBC-C3bRR was found. In immuoosuppression model rats, the values of CD4+ and RBC-C3bRR were obviously lower than those of the normal control group while CD8+ had no any striking changes; but after EA treatment, there were no evident differences between EA group and normal control group in the above-mentioned indexes. There were also no any significant differences between non-acupoint group and normal control group in those indexes. Results suggest that EA of “Zusanli” (ST 36) can raise T cell immune function and RBC adhesion function in both normal rats and immunosuppression model rats, both of which present a positive correlation.

  9. [Dementia and Lewy bodies].

    Science.gov (United States)

    Kaufer, D

    Consensus diagnostic criteria for dementia with Lewy bodies (DLB) proposed in 1996 have provided a useful foundation for research in the field. As a clinicopathologically defined entity, DLB has overlapping features of both Alzheimer s disease (AD) and Parkinson's disease (PD). Consensus criteria for DLB distinguish it from PD dementia by the earlier appearance of motor signs in the latter. Studies evaluating the standardized clinical diagnostic criteria for DLB have generally found them to be highly predictive of Lewy body pathology. However, many cases with Lewy body pathology and concomitant pathological features of AD elude clinical detection. Emerging data suggests that AD pathological features mask the clinical expression of concomitant Lewy body pathology, and that DLB and PD dementia may be more similar than distinct.

  10. Sodium restriction modulates innate immunity and prevents cardiac remodeling in a rat model of metabolic syndrome.

    Science.gov (United States)

    Jover, Bernard; Reynes, Christelle; Rugale, Caroline; Reboul, Cyril; Jeanson, Laura; Tournier, Michel; Lajoix, Anne Dominique; Desmetz, Caroline

    2017-02-27

    In the view of the relationships between excessive sodium intake, immunity and target organ damage, we hypothesized that reduction in dietary sodium would be beneficial in the prevention of cardiac alterations through a restrained local immunity response in a rat model of metabolic syndrome. Sprague-Dawley rats were fed a 60% fructose diet with either a normal sodium (0.64% NaCl) or a low sodium content (<0.01% NaCl) for 8weeks. After 4weeks, rats were infused or not with angiotensin II (200ng.kg(-1).min(-1), sc) for 4weeks. Tail-cuff blood pressure was determined in conscious rats. Heart and left ventricle weight, cardiomyocyte size, and cardiac fibrosis were evaluated. We performed a transcriptomic analysis in order to identify differentially regulated cardiac mRNAs between normal and low sodium diets. We validated those results using qPCR and immunohistochemistry. Angiotensin II-induced blood pressure rise was blunted (~ 50%) in the low-sodium fed rats while cardiac hypertrophy and fibrosis were prevented. Transcriptomic analysis revealed 66 differentially regulated genes including 13 downregulated genes under the low sodium diet and implicated in the innate immune response. This was confirmed by reduced cardiac macrophages infiltration under the low sodium diet. Dietary sodium restriction prevents structural alterations of the heart of rats with fructose-induced insulin resistance and angiotensin II-hypertension. The reduction of cardiac inflammation and macrophage infiltration suggests that innate immunity has an important role in the beneficial effect of sodium restriction on cardiac remodeling.

  11. REDUCED ANTIBODY-RESPONSES AFTER IMMUNIZATION IN RAT LUNG TRANSPLANTS

    NARCIS (Netherlands)

    WINTER, JB; GROEN, M; PETERSEN, AH; WILDEVUUR, CRH; PROP, J

    1993-01-01

    Pulmonary infections occur so frequently in recipients of lung transplants as well as of combined heart and lung transplants that it has been suggested that the function of the defense system in lung transplants is impaired. Therefore, we investigated in rats whether antibody responses against intra

  12. Active immunization to luteinizing hormone releasing hormone to inhibit the induction of mammary tumors in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Ravdin, P.M.; Jordan, V.C.

    1988-01-01

    Immunization of female rats with a bovine serum albumin-luteinizing hormone releasing hormone conjugate results in suppression of dimethylbenzanthracene mammary tumor incidence. Tumor incidence was 1.3, and 1.29 tumors per rat in bovine serum albumin alone (n = 10) and unimmunized (n = 18) control groups, but no tumors were found in the bovine serum albumin-luteinizing hormone releasing hormone conjugate immunized animals (n = 10). In a second experiment immunization with bovine serum albumin-luteinizing hormone releasing hormone conjugates reduced tumor incidence to 0.3 tumors per rat (n = 10) from the 1.2 tumors per animal seen in the control animals (n = 10) immunized with bovine serum albumin alone. Bovine serum albumin-luteinizing hormone immunization caused the production of anti-LHRH antibodies, an interruption of estrous cycles, lowered serum estradiol and progesterone levels, and atrophy of the ovaries and uteri. Immunization BSA-hormone conjugates is a novel anti-tumor strategy.

  13. EFFECTS OF SULPIRIDE-INDUCED D2 DOPAMINE RECEPTOR BLOCKADE ON IMMUNE RESPONSIVENESS OF RATS

    Directory of Open Access Journals (Sweden)

    Lucian Hritcu

    2006-08-01

    Full Text Available The involvement of catecholamine receptors (D2 dopamine was investigated in restraint stress, influence immune system, with concomitant changes in immune response. Adults rats pretreated once with LPS (a bacterial product (25μg/250μl, i.p., produce an immune response, were subjected to i.p. injection with sulpiride (4 mg/kg b.w., i.p., a selective antagonist for D2 dopamine receptors, after 3 days postimmunization. After 18 days later, we assessed the total protein number, antibody titer, lymphocyte number and albumin/globulin ratio. In summary, we provide that D2 dopamine receptor blockade impaired immune responsiveness in restraint stress.

  14. INDICATORS OF HUMORAL IMMUNITY UNDER CHEMICAL BURNS OF ESOPHAGUS IN RATS.

    Science.gov (United States)

    Ishchuk, T V; Kravchenko, N K; Raetska, Ya B; Ostapchenko, L I

    2015-01-01

    It is well known that the immune system has been actively involved in the regeneration and healing processes of post burn wounds. However, unanswered questions remain concerning the role of humoral immunity in the healing mechanisms and development of burn wound complications. We have developed an experimental model of chemical esophageal burn (CEB) which corresponds to esophageal burn in 1-8 years old children. We studied the features of humoral immunity upon CEB in rats. A decrease in IgG levels and an increase in levels of medium- and low- molecular circulating immune complexes (CIC) on the first day of esophageal burns were observed. On the 21st day of burn, we observed an increase in the IgG concentration and a tendency to accumulation of medium- and low-molecular CIC. The studied indicators can be used to differentiate CEB development and create a timeline of burn wounds.

  15. Maternal immune activation during pregnancy in rats impairs working memory capacity of the offspring.

    Science.gov (United States)

    Murray, Brendan G; Davies, Don A; Molder, Joel J; Howland, John G

    2017-05-01

    Maternal immune activation during pregnancy is an environmental risk factor for psychiatric illnesses such as schizophrenia in the offspring. Patients with schizophrenia display an array of cognitive symptoms, including impaired working memory capacity. Rodent models have been developed to understand the relationship between maternal immune activation and the cognitive symptoms of schizophrenia. The present experiment was designed to test whether maternal immune activation with the viral mimetic polyinosinic:polycytidylic acid (polyI:C) during pregnancy affects working memory capacity of the offspring. Pregnant Long Evans rats were treated with either saline or polyI:C (4mg/kg; i.v.) on gestational day 15. Male offspring of the litters (2-3months of age) were subsequently trained on a nonmatching-to-sample task with odors. After a criterion was met, the rats were tested on the odor span task, which requires rats to remember an increasing span of different odors to receive food reward. Rats were tested using delays of approximately 40s during the acquisition of the task. Importantly, polyI:C- and saline-treated offspring did not differ in performance of the nonmatching-to-sample task suggesting that both groups could perform a relatively simple working memory task. In contrast, polyI:C-treated offspring had reduced span capacity in the middle and late phases of odor span task acquisition. After task acquisition, the rats were tested using the 40s delay and a 10min delay. Both groups showed a delay-dependent decrease in span, although the polyI:C-treated offspring had significantly lower spans regardless of delay. Our results support the validity of the maternal immune activation model for studying the cognitive symptoms of neurodevelopmental disorders such as schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Suppressive action of melatonin on the TH-2 immune response in rats infected with Trypanosoma cruzi.

    Science.gov (United States)

    Santello, Fabricia Helena; Frare, Eduardo Osório; dos Santos, Carla Domingues; Caetano, Leony Cristina; Alonso Toldo, Míriam Paula; do Prado, José Clóvis

    2008-10-01

    Control of the acute phase of Trypanosoma cruzi infection is critically dependent on cytokine-mediated macrophage activation to intracellular killing, natural killer (NK) cells, CD4(+) T cells, CD8(+) T cells and B cells. Cell-mediated immunity in T. cruzi infection is also modulated by cytokines, but in addition to parasite-specific responses, autoimmunity can be also triggered. Importantly, cytokines may also play a role in the cell-mediated immunity of infected subjects. Here we studied the role of cytokines in the regulation of innate and adaptive immunity during the acute phase of T. cruzi infection in Wistar rats. Melatonin is an effective regulator of the immune system. Macrophages and T lymphocytes, which have melatonin receptors, are target cells for the immunomodulatory function of melatonin. In this paper melatonin was orally given via two protocols: prior to and concomitant with infection. Both treatments were highly effective against T. cruzi with enhanced action for the concomitant treatment. The data suggest an up-regulation of the TH-1 immune response as all analyzed parameters, interleukin (IL)-4, IL-10, transforming growth factor-beta1 and splenocyte proliferation, displayed reduced levels as compared with the untreated counterparts. However, the direct effects of melatonin on immune cells have not been fully investigated during T. cruzi infection. We conclude that in light of the current results, melatonin exerted important therapeutic benefits through its immune regulatory effects.

  17. Bovine whey protein concentrate supplementation modulates maturation of immune system in suckling rats.

    Science.gov (United States)

    Pérez-Cano, Francisco J; Marín-Gallén, Silvia; Castell, Margarida; Rodríguez-Palmero, María; Rivero, Montserrat; Franch, Angels; Castellote, Cristina

    2007-10-01

    During neonatal life, challenges from breast milk and microbial flora promote immune system maturation. Immunonutrition in these stages may become an important way to increase natural defence systems. The aim of this study was to determine the effect of a daily bovine milk whey protein concentrate (WPC) supplement on the intestinal and systemic immune systems in suckling rats. The composition of intraepithelial and lamina propria lymphocytes (IEL and LPL) was analysed by flow cytometry. Systemic and intestinal humoral immune responses were determined by sera Ig levels and Ig-secreting cell quantification by ELISA and ELISPOT, respectively. From birth, suckling Wistar rats were supplemented with WPC or standard infant formula (SIF). The WPC group showed the same proportion of most of the main mucosal cell subsets as the reference animals. However, in the first days of life WPC enhanced the innate immunity by increasing the NK cell proportion in both epithelial and lamina propria (LP) compartments. A rise in intestinal CD8alphaalpha+ IEL was also induced by WPC supplementation. A time-course of sera Ig levels and spontaneous IgA, IgM and IgG production by LPL and mononuclear cells from blood and spleen, in the WPC group, exhibited a similar pattern to those pups fed only by dam's milk. In summary, the present results show the effects of WPC on enhancing mucosal innate immunity during early life.

  18. Fasting ameliorates metabolism, immunity, and oxidative stress in carbon tetrachloride-intoxicated rats.

    Science.gov (United States)

    Sadek, Km; Saleh, Ea

    2014-12-01

    Fasting has been recently discovered to improve overall health, but its beneficial effects in the presence of hepatic insufficiency have not been proven. The influence of fasting on the metabolism, immunological aspects, and oxidative stress of 40 male carbon tetrachloride (CCl4)-intoxicated Wistar rats was investigated in the present study. The rats were divided into four groups, including a placebo group, CCl4-intoxicated rats, which were injected subcutaneously with 1.0 ml/kg of CCl4 solution, a fasting group, which was fasted 12 h/day for 30 days, and a fourth group, which was injected with CCl4 and fasted. The metabolism, immunity, and oxidative stress improved in CCl4-intoxicated rats fasted for 12 h/day for 30 days, as evidenced in significant increase (p fasting improved metabolism, immunity, and oxidative stress in CCl4-intoxicated rats. Thus, fasting during Ramadan is safe for patients with hepatic disorders, as the prophet Mohammed (S) said "Keep the fast, keep your health". © The Author(s) 2014.

  19. Immune responsiveness associated with experimental Encephalitozoon intestinalis infection in immunocompetent rats

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    Omalu ICJ

    2007-01-01

    Full Text Available Purpose: Microsporidial infections have been recognized as an increasingly important infection in immuncompromised patients, particularly those infected with HIV/AIDS. This study was designed to study immune responses associated with experimental Encephalitozoon intestinalis infection in immunocompetent rats. Materials and Methods: Thirty-four Rats in 3 groups, A (Control, B (Intraperitoneal and C (Oral were given injections of 0.5 ml of 2 x 10 6 of purified spores of Encephalitotozoon intestinalis spores and were observed for serum specific IgG for 21 days using both direct and indirect ELISA. Results: In indirect ELISA, specific lgG were detected on days 7, 14 and 21 for the group B rats and on day 21 for group C and in direct ELISA method, specific lgG were detected in-group B rats on days 7 and 21, for group C rats on day 21 only, while in the control rats, specific lgG were not detected. There was no significant difference between the direct and indirect methods (df=1, X 2 , P>0.05. E. intestinalis was observed in stool samples of rats in 1/12 (08.33% on days 14 and 21 in group B, and in 4/10 (33.33%, 3/10 (25.00% and 2/10 (16.67% on days 7, 14 and 21 respectively in group C. In group A, which is the control rats, no microsporidia were observed on days 0, 7, 14 and 21. Conclusions: There were no changes in the T-lymphocyte counts of rats prior to and after inoculation with spores. Extensive lesions were observed along the intestinal walls especially on the middle and lower sections of group C rats only.

  20. Effect of Heavy Ion Head Irradiation on Immune System Function in Rat

    Institute of Scientific and Technical Information of China (English)

    YU; Ying-qi; WANG; Xiao; SUI; Li; KONG; Fu-quan; LEI; Run-hong; MA; Hong; DENG; Yu-lin; LI; Qiang

    2013-01-01

    Heavy ion radiation is a great threat to astronaut’s health.While as the most promising cancer radiotherapy,the effect of heavy ion brain radiation on immune system function in the relevant research is rare.So the brain injury model that rats were subjected to 15 Gy of head irradiation was built.By detecting lymphocyte percentage,thymus,spleen,body weight and different developmental stages of

  1. Glatiramer acetate immune system augmentation for peripheral nerve regeneration in rat crushed sciatic nerve model.

    Science.gov (United States)

    Luria, Shai; Waitayawinyu, Thanapong; Conniff, James; Morton, H Josette; Nemechek, Nicholas M; Sonnen, Joshua A; Katolik, Leonid I; Trumble, Thomas E

    2010-02-01

    Protective antiself response to nervous system injury has been reported to be mediated by a T-cell subpopulation that can recognize self-antigens. Immune cells have been shown to play a role in the regulation of motor neuron survival after a peripheral nerve injury. The objective of the present study was to evaluate the effects of immune system augmentation with use of the antigen glatiramer acetate, which is known to affect T-cell immunity, on peripheral nerve regeneration. Wild-type and nude-type (T-cell-deficient) rats underwent crush injury of the sciatic nerve. Three and six weeks after the injury, the sciatic nerve was examined, both functionally (on the basis of footprint analysis and the tibialis anterior muscle response and weight) and histologically (on the basis of axon count). Significantly greater muscle responses were measured after three weeks in the group of wild-type rats that were treated with glatiramer acetate (control limb:injured limb ratio, 0.05 for the glatiramer acetate group [n = 9], compared with 0.51 for the saline solution group [n = 8]; p < 0.05). Higher axon counts were also found in this group (control limb:injured limb ratio, -0.07 for the glatiramer acetate group [n = 10], compared with 0.29 for the saline solution group [n = 8]; p < 0.05). The nude-type rats showed no response to the intervention after three weeks but showed a delayed response after six weeks. A second dose of glatiramer acetate, delivered forty-eight hours after the injury, did not result in an improved response as compared with the control groups. We found that a single treatment with glatiramer acetate resulted in accelerated functional and histological recovery after sciatic nerve crush injury. The role of T-cell immunity in the mechanism of glatiramer acetate was suggested by the partial and late response found in the T-cell-deficient rats.

  2. Behavioural deficits associated with maternal immune activation in the rat model of schizophrenia.

    Science.gov (United States)

    Wolff, Amy R; Cheyne, Kirsten R; Bilkey, David K

    2011-11-20

    Schizophrenia is associated with changes in memory and contextual processing. As maternal infection is a risk factor in schizophrenia we tested for these impairments in a maternal immune activation (MIA) animal model. MIA rats displayed impaired object recognition memory, despite intact object discrimination, and a reduced reinstatement of rearing in response to a contextual manipulation. These results link MIA to contextual impairments in schizophrenia, possibly through changes in hippocampal function.

  3. [Features of immune proteasome expression in the development of rat central nervous system].

    Science.gov (United States)

    Orlova, A Sh; Liupina, Iu V; Abaturova, S B; Sharova, N P

    2014-01-01

    Formation of the central nervous system in ontogeny and function in adult mammals are controlled by universal ubiquitin-proteasome proteolytic system. The aim of this work was to study the dynamics of expression of immune proteasomes in comparison with the dynamics of ChLA and CLA proteasome and expression of the transcription factor Zif268 in the structures of the brain (cortex, hippocampus, and brainstem) in embryonic (E19, E21 days of embryonic development) and early postnatal (P1, P3, P4, P5, P7, P15 days of post-natal development) development in rats. ChLA and CLA in clarified homogenates of rat brain structures were determined by hydrolysis of fluorogenic commercial oligopeptides Suc-LLVY-AMC and Z-LLG-AMC, respectively. In the cortex and hippocampus of the brain was observed upregulation of immune subunits LMP7 during the active formation of biochemical mediatory structure and efferent neuronal projections at the period P7-P15. In the cerebral cortex during this period ChLA and CLA also are increased. In all structures of the brain the LMP2 immune subunits content was significantly increased at the period P7-P15. Contents of proteolytic constitutive subunit β1 in all structures decreased by P4 compare to P1 levels and was increased on P15 relative to the P1 levels. However, the level of expression of proteolytic constitutive subunit β5 increased in cortex, hippocampus and brainstem from E21 and reached maximum values on P3, P5 and P1, respectively with a sharp decrease to P7 in all studied structures. In all structures expression of LM P2 immune subunits and β1 constitutive subunits increased simultaneously with LMP7 immune subunits and sharply on P15. Also shown a positive correlation of increased expression regulator PA28 and constitutive β5 subunits in the hippocampus during the period P3-P5 and in the brainstem at the period P1-P5. The peculiarity of the studied brain regions during P7-P15 of rat early development is a correlation of expression of

  4. Synergetic effects of oral administration of levamisole and Echinacea purpurea on immune response in Wistar rat.

    Science.gov (United States)

    Sadigh-Eteghad, Saeed; khayat-Nuri, Hadi; Abadi, Narges; Ghavami, Siavash; Golabi, Mostafa; Shanebandi, Dariush

    2011-08-01

    This research investigated the effects of levamisole and Echinacea purpurea (EP), separately and together on the immune response of the rat as a laboratory model. In this experiment, 40 male Wistar rats were obtained and divided into four groups (n=10). These groups received normal saline (10 mg/kg), EP (500 mg/kg), levamisole (2 mg/kg) and EP (500 mg/kg) with levamisole (2 mg/kg) as oral gavages every day for a period of 4 weeks, respectively. After obtaining blood samples (at the end of each week), haematocrit (HCT), differential and total white blood cell (WBC) counts, phagocyte activity (number), total protein, albumin and globulins levels of samples were obtained. The results of the study showed that the gamma globulin level, WBC, neutrophil and monocyte counts and phagocyte activity increased significantly in comparison with normal saline group during the study. According to the results, each of the mentioned agents had a stimulant effect on the immune system separately and together on rats. In the group that received EP and levamisole simultaneously, these effects were synergistically increased. These compounds, by increasing the mentioned factors, will probably affect the immune system. Crown Copyright © 2010. Published by Elsevier India Pvt Ltd. All rights reserved.

  5. Immune response to gut Escherichia coli and susceptibility to adjuvant arthritis in the rats.

    Science.gov (United States)

    Kovačević-Jovanović, Vesna; Miletić, Tatjana; Stanojević, Stanislava; Mitić, Katarina; Dimitrijević, Mirjana

    2015-03-01

    We have investigated the humoral immune response to antigens of predominant gut aerobic bacterial strains (i.e. Escherichia coli) over the course of adjuvant arthritis and oil-induced arthritis in two inbred rat strains: Dark Agouti (DA) and Albino Oxford (AO). We report the presence of antibodies specific to proteins of E. coli in molecular weight range between 20-30 kDa in sera of diseased DA rats, and the absence of these antibodies in the sera of AO rats. In DA rats, CFA and IFA provoked a stronger antibody response to E. coli, especially of the IgG2b antibody class. Intramuscular administration of E. coli preceding the adjuvant arthritis induction had no effect on the development and course of disease, as well as on the activation of T cells in the draining inguinal lymph nodes. Higher serum levels of natural and induced IgA antibodies, combined with a higher CD3+CD26+ cell percentage were found in AO rats. The observed correlation between the serologic response to commensal flora and rats' genetic background as a defining factor for arthritis susceptibility may contribute to the process of creating a favorable (or less favorable) milieu for arthritis development.

  6. Immune Modulating Capability of Two Exopolysaccharide-Producing Bifidobacterium Strains in a Wistar Rat Model

    Directory of Open Access Journals (Sweden)

    Nuria Salazar

    2014-01-01

    Full Text Available Fermented dairy products are the usual carriers for the delivery of probiotics to humans, Bifidobacterium and Lactobacillus being the most frequently used bacteria. In this work, the strains Bifidobacterium animalis subsp. lactis IPLA R1 and Bifidobacterium longum IPLA E44 were tested for their capability to modulate immune response and the insulin-dependent glucose homeostasis using male Wistar rats fed with a standard diet. Three intervention groups were fed daily for 24 days with 10% skimmed milk, or with 109 cfu of the corresponding strain suspended in the same vehicle. A significant increase of the suppressor-regulatory TGF-β cytokine occurred with both strains in comparison with a control (no intervention group of rats; the highest levels were reached in rats fed IPLA R1. This strain presented an immune protective profile, as it was able to reduce the production of the proinflammatory IL-6. Moreover, phosphorylated Akt kinase decreased in gastroctemius muscle of rats fed the strain IPLA R1, without affecting the glucose, insulin, and HOMA index in blood, or levels of Glut-4 located in the membrane of muscle and adipose tissue cells. Therefore, the strain B. animalis subsp. lactis IPLA R1 is a probiotic candidate to be tested in mild grade inflammation animal models.

  7. A polysaccharide from Salvia miltiorrhiza Bunge improves immune function in gastric cancer rats.

    Science.gov (United States)

    Wang, Nan; Yang, Jingyue; Lu, Jianguo; Qiao, Qing; Wu, Tao; Du, Xilin; Bao, Guoqiang; He, Xianli

    2014-10-13

    A neutral polysaccharide fraction (SMPA) prepared from the roots of Salvia miltiorrhiza by DEAE-cellulose and Sephadex G-100 chromatography was tested for its immune enhancing function in N-methyl-N'-nitro-nitrosoguanidine (MNNG)-induced gastric cancer rats by intragastric administration. SMPA (200mg/kg) treatment not only increased the body weight, but also improved the immune organ indices. Furthermore, studies of various immunological activities in gastric cancer rats revealed that SMPA significantly stimulated splenocyte proliferation, promoted anti-inflammatory cytokines (IL-2, IL-4 and IL-10) production, inhibited pro-inflammatory cytokine (IL-6 and TNF-α) secretion, augmented the killing activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL), and increased phagocytotic function of macrophages in gastric cancer rats. In addition, SMPA administration evidently elevated total intracellular granzyme-B and IFN-γ levels produced by splenocytes in gastric cancer rats. Taken together, these results suggested that SMPA could act as an effective immunomodulator and might be explored as a potential supplemental source for gastric cancer therapy.

  8. Effects of glutamine supplementation on innate immune response in rats with gut-derived sepsis.

    Science.gov (United States)

    Yeh, Sung-Ling; Lai, Yu-Ni; Shang, Huey-Fang; Lin, Ming-Tsan; Chen, Wei-Jao

    2004-03-01

    The present study examined the effect of glutamine (Gln)-enriched diets before sepsis or Gln-containing total parenteral nutrition (TPN) after sepsis, or both, on the phagocytic activity and blood lymphocyte subpopulation in rats with gut-derived sepsis. Rats were assigned to a control group or one of four experimental groups. The control group and groups 1 and 2 were fed a semipurified diet; groups 3 and 4 had part of casein replaced by Gln. After feeding the diets for 10 d, sepsis was induced by caecal ligation and puncture (CLP); TPN was maintained for 3 d after CLP. The control group and groups 1 and 3 were infused with conventional TPN and groups 2 and 4 were supplemented with Gln in the TPN solution. All rats were killed 3 d after CLP or sham operation to examine their immune responses. The results showed that compared with the control group, the phagocytic activities of peritoneal macrophages were enhanced in groups 3 and 4, but not in groups 1 and 2. The proportion of CD3+ cells in group 1 was significantly lower (Psepsis. However, parenteral Gln administration after caecal ligation and puncture had no favourable effects on modulating immune response in septic rats.

  9. Experimental Salmonella typhimurium infections in rats. II. Active and passive immunization as protection against a lethal bacterial dose

    DEFF Research Database (Denmark)

    Hougen, H P; Jensen, E T; Klausen, B

    1990-01-01

    Immunization against a lethal dose of Salmonella typhimurium was studied in athymic and thymus-bearing LEW rats. Active immunization was performed with formalin-killed whole cell vaccine or sublethal infection prior to the lethal infection. After vaccination with killed bacteria the euthymic anim...

  10. The role of OX22- helper T cells in protective immunity to reinfection with Taenia taeniaeformis in rats.

    Science.gov (United States)

    Asano, K; Ito, A; Okamoto, K

    1993-12-01

    Spleen cells (SpC) and mesenteric lymph node cells (MLNC) from F344 donor rats actively immunized by oral inoculation with Taenia taeniaeformis eggs were syngeneically transferred into previously uninfected recipient rats by intravenous injection. Recipient rats were challenged with eggs after cell transfer. The degree of immunity was assessed by counting the number of growing metacestodes (MC) in the liver and compared with that in controls. Transfer of 2 x 10(8) SpC, obtained from donors immunized for ten or more (but not for three or five) days before cell transfer inhibited the establishment of most of MC. There were approximately 86-88% reductions in MC recoveries. SpC (2 x 10(8)) obtained from donors immunized for ten days inhibited the establishment of most of MC in recipient rats when transferred nought, two, or 24 h (but not 48 h) before egg challenge. Functional cells in the immune SpC were helper T cells W3/25+, OX8- and OX22-. However, immune MLNC obtained from donors immunized for three to ten days before cell transfer had no effect on transferring immunity.

  11. A novel ex vivo rat infection model to study protective immunity against Fasciola hepatica at the gut level

    NARCIS (Netherlands)

    Milligen, van F.J.; Cornelissen, J.B.W.J.; Gaasenbeek, C.P.H.; Bokhout, B.A.

    1998-01-01

    We describe an ex vivo rat infection model to study protective immunity against Fasciola hepatica at the gut level. An exact number of newly excysted juveniles (NEJs) was injected into a gut segment with an intact blood supply and which was still attached to a live anaesthetized rat. NEJs that penet

  12. Design and reactions of a carbon Lewis base/boron Lewis acid frustrated Lewis pair.

    Science.gov (United States)

    Möricke, Jennifer; Wibbeling, Birgit; Daniliuc, Constantin G; Kehr, Gerald; Erker, Gerhard

    2017-08-28

    The conjugated dienamine 4 selectively adds Piers' borane [HB(C6F5)2] to give the enamine/borane system 5, which features a boratirane structure by internal enamine carbon Lewis base to boron Lewis acid interaction. Compound 5 behaves as a C/B frustrated Lewis pair and undergoes typical addition reactions to benzaldehyde, several nitriles and to sulfur dioxide.This article is part of the themed issue 'Frustrated Lewis pair chemistry'. © 2017 The Author(s).

  13. Passive Immunization of Anti bZP3 (Zone Pellucida3 in Wistar Rat (Rattus novergicus and Mouse (Mus musculus

    Directory of Open Access Journals (Sweden)

    Y. Pantiwati

    2012-12-01

    Full Text Available This study was aimed at comparing the influence of anti bZP3’s passive immunization on anti-anti bZP3’s titer and pregnancy level on Wistar rats and mice. This study employed factorial design experiment with completely randomized design. The first factor was immunogenic type. The treated rats were immunized with 100 L anti bZP3 in 100 L Complete Freund’s Adjuvant (CFA, while the treated mice were injected with 50 L anti bZP3 in 50 L CFA. Control Wistar rats and mice were immunized with CFA and Incomplete Freund’s Adjuvant (IFA without anti bZP3. The second factor was animal type. The third factor was the length of serum incubation, i.e. 38, 49, 63, 86, 100, and 126 d. Dot blot on the treated Wistar rats and mice showed positive response proven by blue gradation; pre-immune mice as well as control Wistar rats and mice showed negative response proven by white gradation. The highest antibody titer in treated mouse serum was shown in 63 d incubation. The pregnancy on treated mice, control mice and Wistar rat occurred 100% until day 126; while the failure percentage on the treated mice was 4.5%. The pregnancy on treated mice occurred in 86 d incubation (1 rat, 100 d incubation (1 rat, and 126 d incubation (3 rats. Effective passive immunization on similar hospes occurred until day 63; while different hospes was ineffective. Antibodi anti-bZP3 was potential as a contraception through passive immunization on similar hospes.

  14. No priming of the immune response in newborn Brown Norway rats dosed with ovalbumin in the mouth

    DEFF Research Database (Denmark)

    Madsen, Charlotte Bernhard; Pilegaard, Kirsten

    2003-01-01

    Background: Other researchers have reported that the specific immune response to subsequent antigen challenge is primed in newborn mice or rats dosed orally by gavage. We wanted to investigate if priming of a subsequent specific IgE response could be achieved by dosing newborn rats orally...... with ovalbumin in the mouth as neonates do not prime the specific immune response. The decrease in immune response found in our experiments when dosing newborn animals in the mouth in opposition to the priming seen by others when dosing by intra-gastric intubation may be explained by a dissimilar antigen...

  15. The induction of species-specific immunity against Schistosoma japonicum by exposure of rats to ultra-violet attenuated cercariae.

    Science.gov (United States)

    Moloney, N A; Webbe, G; Hinchcliffe, P

    1987-02-01

    Single percutaneous immunizations of Fischer rats with 1000 ultra-violet attenuated Schistosoma japonicum cercariae induced 52-88% resistance to challenge 4 weeks later. Increasing this to 3 immunizations induced 90% resistance to challenge, and this level of protection remained undiminished for up to 40 weeks after vaccination. Rats vaccinated with gamma-irradiated S. mansoni cercariae were resistant to challenge with S. mansoni but not S. japonicum. Similarly rats vaccinated with u.v.-attenuated S. japonicum cercariae were not resistant to heterologous challenge. Thus irradiated vaccines are species-specific in both permissive and non-permissive hosts.

  16. Induction of species-specific immunity against Schistosoma japonicum by exposure of rats to ultra-violet attenuated cercariae

    Energy Technology Data Exchange (ETDEWEB)

    Moloney, N.A.; Webbe, G.; Hinchcliffe, P.

    1987-02-01

    Single percutaneous immunizations of Fischer rats with 1000 ultra-violet attenuated Schistosoma japonicum cercariae induced 52-88% resistance to challenge 4 weeks later. Increasing this to 3 immunizations induced 90% resistance to challenge, and this level of protection remained undiminished for up to 40 weeks after vaccination. Rats vaccinated with gamma-irradiated S. mansoni cercariae were resistant to challenge with S. mansoni but not S. japonicum. Similarly rats vaccinated with u.v.-attenuated S. japonicum cercariae were not resistant to heterologous challenge. Thus irradiated vaccines are species-specific in both permissive and non-permissive hosts.

  17. Daily exercise improves memory, stimulates hippocampal neurogenesis and modulates immune and neuroimmune cytokines in aging rats.

    Science.gov (United States)

    Speisman, Rachel B; Kumar, Ashok; Rani, Asha; Foster, Thomas C; Ormerod, Brandi K

    2013-02-01

    We tested whether daily exercise modulates immune and neuroimmune cytokines, hippocampus-dependent behavior and hippocampal neurogenesis in aging male F344 rats (18mo upon arrival). Twelve weeks after conditioned running or control group assignment, the rats were trained and tested in a rapid water maze followed by an inhibitory avoidance task. The rats were BrdU-injected beginning 12days after behavioral testing and killed 3weeks later to quantify cytokines and neurogenesis. Daily exercise increased neurogenesis and improved immediate and 24h water maze discrimination index (DI) scores and 24h inhibitory avoidance retention latencies. Daily exercise decreased cortical VEGF, hippocampal IL-1β and serum MCP-1, GRO-KC and leptin levels but increased hippocampal GRO-KC and IL-18 concentrations. Serum leptin concentration correlated negatively with new neuron number and both DI scores while hippocampal IL-1β concentration correlated negatively with memory scores in both tasks. Cortical VEGF, serum GRO-KC and serum MCP-1 levels correlated negatively with immediate DI score and we found novel positive correlations between hippocampal IL-18 and GRO-KC levels and new neuron number. Pathway analyses revealed distinct serum, hippocampal and cortical compartment cytokine relationships. Our results suggest that daily exercise potentially improves cognition in aging rats by modulating hippocampal neurogenesis and immune and neuroimmune cytokine signaling. Our correlational data begin to provide a framework for systematically manipulating these immune and neuroimmune signaling molecules to test their effects on cognition and neurogenesis across lifespan in future experiments. Published by Elsevier Inc.

  18. Biochemical, histopathological and morphological profiling of a rat model of early immune stimulation: relation to psychopathology.

    Directory of Open Access Journals (Sweden)

    Anna Kubesova

    Full Text Available Perinatal immune challenge leads to neurodevelopmental dysfunction, permanent immune dysregulation and abnormal behaviour, which have been shown to have translational validity to findings in human neuropsychiatric disorders (e.g. schizophrenia, mood and anxiety disorders, autism, Parkinson's disease and Alzheimer's disease. The aim of this animal study was to elucidate the influence of early immune stimulation triggered by systemic postnatal lipopolysaccharide administration on biochemical, histopathological and morphological measures, which may be relevant to the neurobiology of human psychopathology. In the present study of adult male Wistar rats we examined the brain and plasma levels of monoamines (dopamine, serotonin, their metabolites, the levels of the main excitatory and inhibitory neurotransmitters glutamate and γ-aminobutyric acid and the levels of tryptophan and its metabolites from the kynurenine catabolic pathway. Further, we focused on histopathological and morphological markers related to pathogenesis of brain diseases--glial cell activation, neurodegeneration, hippocampal volume reduction and dopaminergic synthesis in the substantia nigra. Our results show that early immune stimulation in adult animals alters the levels of neurotransmitters and their metabolites, activates the kynurenine pathway of tryptophan metabolism and leads to astrogliosis, hippocampal volume reduction and a decrease of tyrosine hydroxylase immunoreactivity in the substantia nigra. These findings support the crucial pathophysiological role of early immune stimulation in the above mentioned neuropsychiatric disorders.

  19. Biochemical, histopathological and morphological profiling of a rat model of early immune stimulation: relation to psychopathology.

    Science.gov (United States)

    Kubesova, Anna; Tejkalova, Hana; Syslova, Kamila; Kacer, Petr; Vondrousova, Jana; Tyls, Filip; Fujakova, Michaela; Palenicek, Tomas; Horacek, Jiri

    2015-01-01

    Perinatal immune challenge leads to neurodevelopmental dysfunction, permanent immune dysregulation and abnormal behaviour, which have been shown to have translational validity to findings in human neuropsychiatric disorders (e.g. schizophrenia, mood and anxiety disorders, autism, Parkinson's disease and Alzheimer's disease). The aim of this animal study was to elucidate the influence of early immune stimulation triggered by systemic postnatal lipopolysaccharide administration on biochemical, histopathological and morphological measures, which may be relevant to the neurobiology of human psychopathology. In the present study of adult male Wistar rats we examined the brain and plasma levels of monoamines (dopamine, serotonin), their metabolites, the levels of the main excitatory and inhibitory neurotransmitters glutamate and γ-aminobutyric acid and the levels of tryptophan and its metabolites from the kynurenine catabolic pathway. Further, we focused on histopathological and morphological markers related to pathogenesis of brain diseases--glial cell activation, neurodegeneration, hippocampal volume reduction and dopaminergic synthesis in the substantia nigra. Our results show that early immune stimulation in adult animals alters the levels of neurotransmitters and their metabolites, activates the kynurenine pathway of tryptophan metabolism and leads to astrogliosis, hippocampal volume reduction and a decrease of tyrosine hydroxylase immunoreactivity in the substantia nigra. These findings support the crucial pathophysiological role of early immune stimulation in the above mentioned neuropsychiatric disorders.

  20. Protective effect of rutin on humoral and cell mediated immunity in rat model.

    Science.gov (United States)

    Ganeshpurkar, Aditya; Saluja, Ajay K

    2017-08-01

    Diet and dietary intake can persuade the development, safeguard and proper functioning of immune system. Ruin, an important bioflavonoid, is abundantly found in various foodstuffs. Rutin has been acknowledged for its protective and beneficial effects on various aspects of the biological system. The present study was aimed to examine the effect of rutin on the regulation of the immune response in experimental animal models. Effect of rutin of cellular immunity was determined by delayed-type hypersensitivity (DTH) response, carbon clearance assay, leucocyte mobilization test, and cyclophosphamide-induced myelosuppression, whereas humoral immunity was analyzed by the haemagglutinating antibody (HA) titre assay. Rutin (25, 50 and 100 mg/kg, p.o.) evoked a significant increase in antibody titre in the haemagglutination test, increased immunoglobulin levels, and enhanced the delayed type hypersensitivity reaction induced by sheep red blood cells. It also significantly restored the functioning of leucocytes in cyclophosphamide treated rats and augmented phagocytic index in the carbon clearance assay. The outcomes from the present study indicate that rutin possesses sufficient potential for increasing immune activity by cellular and humoral mediated mechanisms. Copyright © 2017. Published by Elsevier B.V.

  1. Changes of cellular immune function with Chaihulongmu decoction in Lewis mice with iumg cancer%柴胡龙牡汤对Lewis肺癌小鼠细胞免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    潘玉真; 殷东风; 周立江; 朱颖

    2011-01-01

    Objective To study effects of Chaihulongmu decoction on cellular immune function such as T lymphocyte subgroup,NK cell activeness,IL-lO and γ-intefferon of Lewis mice with lung cancer. Methods The cells of Lewis lung cancer were planted in the right axilla of C57BL/6J inbred strain mice subcutaneously. The mice with cancer were randomly divided into model group ( MG), herbal group ( HG), DDP group (DG) and combination group (CG). The tumors were weighed when the mice were sacrificed in each group. Then the inhibition rate of tumor was calculated. The experiment of the lactic dehydrogenase (LDH) releasing was used to detect the activity of NK cell in the mouse spleens. The method of enzyme-linked immuno sorbent assay (ELISA) was used to detect the IL-10, γ-intefferon in the supernatant fluid of spleen. The rates of CD4, CD8 and the ratio of CD4/CD8 were detected by the flow cytometry (FCM) in the way of PE/FITC fluorescent staining in the spleens of mice. Results The inhibited effectiveness of CG was optimal, and the inhibition rate of tumor was 62.4%. There was significant difference comparing to DG and HG( P <0. 01 ). The activity of NK cell in HG was highest,and the difference was obvious comparing to MG, DG and CG( P < 0. 01 ). The content of IFN-γ was 65.78 ± 17. 68 in HG, which was higher than that in DG ( P < 0. 05 ). The content of IL-10 in MG was highest( 153. 30 ± 33. 14).In HG it was lower than MG, DG and CG( P < 0. 05 ). The figure of CD4 ± and the ratio of CD4 ± / CD8 ± in HG were the highest.Comparing to the MG and the DG, the difference was extremely obvious. (P <0.01 ). While the percentage of CD8 ± cell in each post-treatment group had no obvious changes. Conclusion The prescription of Chaihulongmu decoction can inhibit tumor and improve the cellular immune function through raising the level of IFN-γ, reducing the superior expression of IL-10, strengthening the activity of the NK cell, obviously elevating the percentage of the

  2. Experimental tuberculosis in the Wistar rat: a model for protective immunity and control of infection.

    Directory of Open Access Journals (Sweden)

    Amit Singhal

    Full Text Available BACKGROUND: Despite the availability of many animal models for tuberculosis (TB research, there still exists a need for better understanding of the quiescent stage of disease observed in many humans. Here, we explored the use of the Wistar rat model for the study of protective immunity and control of Mycobacterium tuberculosis (Mtb infection. METHODOLOGY/PRINCIPAL FINDINGS: The kinetics of bacillary growth, evaluated by the colony stimulating assay (CFU and the extent of lung pathology in Mtb infected Wistar rats were dependent on the virulence of the strains and the size of the infecting inoculums. Bacillary growth control was associated with induction of T helper type 1 (Th1 activation, the magnitude of which was also Mtb strain and dose dependent. Histopathology analysis of the infected lungs demonstrated the formation of well organized granulomas comprising epithelioid cells, multinucleated giant cells and foamy macrophages surrounded by large numbers of lymphocytes. The late stage subclinical form of disease was reactivated by immunosuppression leading to increased lung CFU. CONCLUSION: The Wistar rat is a valuable model for better understanding host-pathogen interactions that result in control of Mtb infection and potentially establishment of latent TB. These properties together with the ease of manipulation, relatively low cost and well established use of rats in toxicology and pharmacokinetic analyses make the rat a good animal model for TB drug discovery.

  3. Relationship between immune state and tumor growth rate in rats bearing progressive and non-progressive mammary tumors.

    Science.gov (United States)

    Remedi, M M; Hliba, E; Demarchi, M; Depiante-Depaoli, M

    1998-08-01

    Impaired immune responses occur frequently in cancer patients or in tumor-bearing animals, but the mechanisms of the tumor-induced immune defects remain poorly understood. The aim of the present study was to determine the relevance of the immune system in the control of tumor growth. We have developed a model of progressive and non-progressive mammary tumor, chemically induced in female Wistar rats. In this model we evaluated the development of an immune response after immunization of rats bearing progressive and non-progressive tumors with a non-related antigen, such as sheep red blood cells. We also studied the activation state of peritoneal macrophages from animals bearing tumors by evaluating the production of free radicals. Our findings indicated that the cell-mediated immunity in rats bearing progressive tumors fails to respond to heterologous antigen in vivo, as demonstrated by a negative delayed-type hypersensitivity reaction, and is accompanied by minor nitric oxide production by peritoneal exudate cells as well as a lower capacity for macrophage activation. The study of non-progressive tumor-bearing rats indicated that the cell-mediated immune response was intact and an activated state of macrophages was found in vivo. The results described in this paper should be taken into account when therapies based on cancer vaccines are chosen for the treatment of cancer.

  4. Passive adoptive transfer of antitumor immunity induced by laser-dye-immunoadjuvant treatment in a rat metastatic breast cancer model

    Science.gov (United States)

    Chen, Wei R.; Liu, Hong; Singhal, Anil K.; Nordquist, Robert E.

    2000-06-01

    The ideal cancer treatment modalities should not only cause tumor regression and eradication but also induce a systemic anti-tumor immunity. This is essential for control of metastatic tumors and for long-term tumor resistance. Laser immunotherapy using a laser, a laser-absorbing dye and an immunoadjuvant has induced such a long-term immunity in treatment of a mammary metastatic tumor. The successfully treated rats established total resistance to multiple subsequent tumor challenges. For further mechanistic studies of the antitumor immunity induced by this novel treatment modality, passive adoptive transfer was performed using splenocytes as immune cells. The spleen cells harvested from successfully treated tumor-bearing rats provided 100% immunity in the naive recipients. The passively protected first cohort rats were immune to tumor challenge with an increased tumor dose; their splenocytes also prevented the establishment of tumor in the second cohort of naive recipient rats. This immunity transfer was accomplished without the usually required T-cell suppression in recipients.

  5. Significance of Lewis Phenotyping Using Saliva and Gastric Tissue: Comparison with the Lewis Phenotype Inferred from Lewis and Secretor Genotypes

    OpenAIRE

    Yun Ji Hong; Sang Mee Hwang; Taek Soo Kim; Eun Young Song; Kyoung Un Park; Junghan Song; Kyou-Sup Han

    2014-01-01

    Lewis phenotypes using various types of specimen were compared with the Lewis phenotype predicted from Lewis and Secretor genotypes. This is the first logical step in explaining the association between the Lewis expression and Helicobacter pylori. We performed a study of the followings on 209 patients who underwent routine gastroscopy: erythrocyte and saliva Lewis phenotyping, gastric Lewis phenotyping by the tissue array, and the Lewis and Secretor genes genotyping. The results of phenotypin...

  6. Intestinal immune barrier integrity in rats with nonalcoholic hepatic steatosis and steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    SU Lin; LIU Yu-lan; WANG Jian-hua; CONG Xu; WANG Li-hong; LIU Feng; XIE Xing-wang; ZHANG Heng-hui; WANG Jiang-hua; FEI Ran

    2012-01-01

    Background Nonalcoholic fatty liver disease (NAFLD) has emerged as the major cause of chronic liver injury.Intestinal barrier plays an important role in the pathogenis of NAFLD.The aim of this article was to assess intestinal immune barrier function during the development of NAFLD.Methods Totally 60 male Sprague-Dawley (SD) rats were divided into 2 groups:normal diet (ND) group and high-fat diet (HFD) group.NAFLD rat model was established in the HFD rat group.Portal blood endotoxin level was assessed by limulus test.The percentage of CD4+ cells and CD8+ cells in peripheral blood mononuclear cells (PBMC) and lymphocytes in Peyer's patches (PP) were analysed by flow cytometry.Intestinal secretory immunoglobulin A (SIgA) level was evaluated by enzyme-linked immunosorbent assay.Paired Student's t test was used for the statistic analysis.Results HFD rats presented with simple steatosis at the 4th and 8th week and progressed to nonalcoholic steatohepatitis at the 12th week.Elevated lipopolysaccharides (LPS) level in HFD rats was observed at the 8th week ((1.54±0.30) times of ND group,P <0.01).CD4/CD8 ratios in PBMC and PP of HFD rats were increased at the 4th week ((1.50±0.47) and (1.63±0.34) times of ND group,P <0.05) and decreased at the 8th week ((0.50±0.16) and (0.61±0.26)times of ND group,P <0.05).At the 12th week,CD4/CD8 ratio ((1.47±0.46) times,P <0.05) in PP increased to levels observed in the 4th week.Intestinal SIgA expression of HFD rats was remarkably up-regulated at 12th week ((2.70±1.65)times,P <0.05).Conclusion Liver-gut axis in rats with NAFLD may mediate and improve intestinal immune function by increased CD4/CD8 ratio in PP and increased production of SIgA.

  7. Fundamental study of expression-library immunization against Taenia taeniaeformis in rats.

    Science.gov (United States)

    Okamoto, Munehiro; Matsumoto, Kanako; Shibui, Akiko; Shibahara, Toshiyuki; Ito, Akira

    2005-01-01

    Expression-library immunization has been proposed as an effective means to screen a large number of genes of the pathogen as candidate protective molecules. In this study, we examined the efficacy of expression-library immunization using a T. taeniaeformis rat model system. Total RNAs were isolated from the last 15 segments of adult T. taeniaeformis and poly A RNA was purified. cDNA library was produced using SuperScript Plasmid System, which contains a mammalian expression vector, pCMV*SPORT6. From about 3,500 clones examined, more than 800 clones were found to contain DNA fragments. About 200 clones were sequenced and the homology search was carried out. The blast search revealed that 29% of the expression genes were mitochondrial genes (rRNA; 17%, protein; 12%). Nuclear rRNA genes (10%), nuclear protein (9%) and genes from Escherichia coli were also detected. Forty-two percent of sequences did not show a significant similarity to any genes deposited in the public database. Rats were immunized with expression-library and injected orally with 1,000 T. taeniaeformis eggs. However the protective effect of expression-library vaccine was not confirmed.

  8. Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis ratsTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

    DEFF Research Database (Denmark)

    Mangano, K.; Sardesai, N.Y.; Quattrocchi, C.

    2008-01-01

    . Here, we have studied the effects of VGX-1027 on the development of endotoxin-induced uveitis (EIU) in male Lewis rats, as a model of inflammatory ocular diseases in humans. EXPERIMENTAL APPROACH: EIU was induced by a single footpad injection of 200 microg lipopolysaccharide (LPS). Groups of rats were...... treated with either VGX-1027 (25 mg kg(-1)) or its vehicle at different time points (30 min, 6 h or 12 h) after the challenge with LPS or, as positive control, with dexamethasone. The rats were killed within 16 h after LPS challenge, and the eyes and aqueous humor were collected to study serological...

  9. Effect of Inhibin α(1-32)Gene Immunization on the Follicular Development and Reproductive Hormones in Rats

    Institute of Scientific and Technical Information of China (English)

    MAO Da-gan; YANG Li-guo; YE Rong; JIANG Xun-ping

    2003-01-01

    A total of 40 rats, aged in 30 days, were divided into 4 groups and immunized (intramuscularlyinjection) with 0 μg(control), 15 μg (group 1), 25 μg (group 2) or 40 μg(group 3) of inhibin α(1-32) re-combinant expression plasmid pcINH in combination with liposome. Booster was given without liposome onday 20 after primary immunization. The results showed that 50%(13/26) rats were detected in positive anti-body against inhibin. However, the increase of immunization dosage and booster did not promote the ratio ofantibody positive rats. The number of matured follicles above 0.8 mm in diameter in the antibody positive ratswas 2.3 more than that in the negative rats (P>0.05). The concentration of blood plasma FSH increased dis-tinctively on day 10 after primary immunization (P<0.05), but no increase was observed after booster immu-nization. The 17-β-estradiol levels in blood plasma of rats between the positive and the negative groups had noremarkable differences (P>0.05). These results suggested that recombinant inhibin expression plasmid couldstimulate animal body to produce antibody against inhibin.

  10. Characterization of immune cells and cytokine localization in the rat utero-placental unit mid- to late gestation.

    Science.gov (United States)

    Tessier, Daniel R; Raha, Sandeep; Holloway, Alison C; Yockell-Lelièvre, Julien; Tayade, Chandrakant; Gruslin, Andrée

    2015-08-01

    The success of pregnancy is dependent on the precise regulation of the immune response within the utero-placental environment. Rats are beginning to be widely used as a model for human immune-related pregnancy complications. However, our knowledge of immune cells and cytokine localization in the rat utero-placental tissue is limited. The current study aimed to localize the immune cell populations, including uterine natural killer (uNK) cells, neutrophils, and macrophages within the rat utero-placental unit at two crucial gestational ages, gestational days 15.5 and 18.5. In addition, we characterized the distribution of the cytokines TNFα, IFNγ, and IL-10 in the utero-placental regions at both the above-mentioned gestational ages. Our study has demonstrated co-localization TNFα and IFNγ with uNK cells in perivascular regions of the rat mesometrial triangle at both gestational ages. Neutrophils and IL-10-positive cells were localized at the maternal-fetal interface and in the spiral artery lumen of the rat mesometrial triangle at both gestational ages. TNFα and IL-10 demonstrated a temporal change in the localization from GD15.5 to GD18.5, which coincides with the leading edge of trophoblast invasion into the mesometrial triangle. The current study furthers our knowledge of the localization of uterine immune cells and relevant cytokines, and provides a base from which to research the function of these immune cells and cytokines during rat pregnancy as a model to study human immune-related pregnancy complications.

  11. Active and passive immunization with Pseudomonas aeruginosa ribosomal vaccines and antisera in the burned rat model.

    Science.gov (United States)

    Lieberman, M M; Walker, H L; Ayala, E; Chapa, I

    1986-02-01

    Pseudomonas aeruginosa ribosomal vaccines were tested for their ability to protect rats subjected to a 20% total body surface burn against the lethal effects of infection with homologous organisms. When administered prior to burning, the vaccines provided 100% protection. When administered postburning, the vaccine from one strain also provided 100% protection when the time interval between vaccination and infection was 3 days. When this time interval was reduced to 1 or 2 days, approximately 50% protection was obtained with the same vaccine. The vaccine from a second strain tested provided about 50% protection with a 3-day time interval. In addition, passive immunization using antiserum to a ribosomal vaccine was also demonstrated to be effective in protecting burned and infected rats, especially when multiple doses of antiserum were used. In this case, 80% protection was obtained (with no protection observed using multiple doses of normal serum). Finally, a comparison of ribosomal and lipopolysaccharide vaccines and antisera was also performed.

  12. Vitamin A supplementation in early life enhances the intestinal immune response of rats with gestational vitamin A deficiency by increasing the number of immune cells.

    Directory of Open Access Journals (Sweden)

    Xia Liu

    Full Text Available Vitamin A is a critical micronutrient for regulating immunity in many organisms. Our previous study demonstrated that gestational or early-life vitamin A deficiency decreases the number of immune cells in offspring. The present study aims to test whether vitamin A supplementation can restore lymphocyte pools in vitamin A-deficient rats and thereby improve the function of their intestinal mucosa; furthermore, the study aimed to identify the best time frame for vitamin A supplementation. Vitamin A-deficient pregnant rats or their offspring were administered a low-dose of vitamin A daily for 7 days starting on gestational day 14 or postnatal day 1, day 14 or day 28. Serum retinol concentrations increased significantly in all four groups that received vitamin A supplementation, as determined by high-performance liquid chromatography. The intestinal levels of secretory immunoglobulin A and polymeric immunoglobulin receptor increased significantly with lipopolysaccharide challenge in the rats that received vitamin A supplementation starting on postnatal day 1. The rats in this group had higher numbers of CD8+ intestinal intraepithelial lymphocytes, CD11C+ dendritic cells in the Peyer's patches and CD4+CD25+ T cells in the spleen compared with the vitamin A-deficient rats; flow cytometric analysis also demonstrated that vitamin A supplementation decreased the number of B cells in the mesenteric lymph nodes. Additionally, vitamin A supplementation during late gestation increased the numbers of CD8+ intestinal intraepithelial lymphocytes and decreased the numbers of B lymphocytes in the mesenteric lymph nodes. However, no significant differences in lymphocyte levels were found between the rats in the other two vitamin A supplement groups and the vitamin A-deficient group. In conclusion, the best recovery of a subset of lymphocytes in the offspring of gestational vitamin A-deficient rats and the greatest improvement in the intestinal mucosal immune

  13. Killer dendritic cells link innate and adaptive immunity against established osteosarcoma in rats.

    Science.gov (United States)

    Chauvin, Camille; Philippeau, Jean-Marie; Hémont, Caroline; Hubert, Francois-Xavier; Wittrant, Yohann; Lamoureux, Francois; Trinité, Benjamin; Heymann, Dominique; Rédini, Françoise; Josien, Régis

    2008-11-15

    We have previously reported that a distinct subset of splenic CD4(-) rat dendritic cells (DC) induces a rapid and caspase-independent apoptosis-like cell death in a large number of tumor cells in vitro. The killing activity of these killer DC (KDC) was restricted to their immature state and was immediately followed by their engulfment of the apoptotic target cells, suggesting that these KDC could directly link innate and adaptive immunity to tumors. Here, we addressed this question using a transplantable model of rat osteosarcoma. First, we showed that rat KDC have an MHC II(+)CD103(+)CD11b(+)NKp46(-) phenotype and are therefore distinct from natural killer cells, which are MHC II(-)CD103(-)CD11b(-)NKp46(+). KDC numbers could be specifically and strongly (up to 10-fold) enhanced by Flt3L in vivo. The OSRGa cell line derived from the osteosarcoma tumor was killed and phagocytosed in vitro by both normal and Flt3L-induced splenic KDC. Such tumor antigen-loaded KDC were used to s.c. vaccinate progressive tumor-bearing rats. Vaccination with OSRGa-loaded KDC but not KDC loaded with irrelevant tumor cells (Jurkat) delayed tumor progression or even induced tumor regression. This vaccine effect was not observed in CD8 T cell-depleted animals and protective against tumor rechallenge. These results suggest that KDC possess the intrinsic capability not only to kill and then engulf tumor cells but also to efficiently cross-present tumor cell-derived antigen in vivo and subsequently induce an adaptive antitumor immune response.

  14. Lewis Acid Catalyzed Benzylic Bromination

    OpenAIRE

    Shibatomi, Kazutaka; Zhang, Yanhua; Yamamoto, Hisashi

    2008-01-01

    Lewis acid catalyzed bromination on aromatic side chain was achieved efficiently by using 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) as a bromination reagent under mild conditions. Zirconium(IV) chloride showed the highest catalytic activity for the benzylic bromination. It was revealed that the present Lewis acid catalysis proceeds via the radical generation pathway. In contrast to Lewis acid catalysis, Brønsted acid promoted aromatic ring bromination without any benzylic bromination. Monobro...

  15. Radioprotective effect of green tea and grape seed extracts mixture on gamma irradiation induced immune suppression in male albino rats.

    Science.gov (United States)

    El-Desouky, Wael; Hanafi, Amal; Abbas, Manal M

    2017-04-01

    Green tea extract (GTE) and grape seed extract (GSE) have antioxidant and radioprotective effects. The current study aimed to investigate the radioprotective effect of GTE and GSE mixture on radiation-induced immune suppression in rats. A total of 35 male albino rats were divided into five groups: group 1 (control rats). The 2nd and 3rd groups rats were exposed to a single dose of gamma radiation (5 and 10 Gy), respectively. The 4th and 5th groups of rats were gamma-irradiated with 5 and 10 Gy, respectively, then administrated by gavage with GTE and GSE mixture (100 mg: 200 mg/kg BW), respectively, for 14 consecutive days. Gamma irradiation induced hematological, immunological and biochemical effects in rats. Treated rats with GTE and GSE mixture (1:2) showed an increase in concentrations of immune cells including CD4 and CD8. The level of pro-inflammatory cytokines Tumor necrosis factor-α and C-reactive protein elevated after γ-irradiation and significantly decreased by mixture administration. Moreover, groups treated with antioxidant mixture showed a significant increase in all hematological parameters and a significant decrease in cholesterol and triglyceride levels. GTE and GSE mixture is a good radioprotector and immune modulator compound, indicating its possible use as an adjuvant during radiotherapy.

  16. Dementia with Lewy bodies.

    Science.gov (United States)

    McKeith, Ian G; Burn, David J; Ballard, Clive G; Collerton, Daniel; Jaros, Evelyn; Morris, Chris M; McLaren, Andrew; Perry, Elaine K; Perry, Robert; Piggott, Margaret A; O'Brien, John T

    2003-01-01

    The objective was to summarize recent findings about the clinical features, diagnosis and investigation of dementia with Lewy (DLB) bodies, together with its neuropathology, neurochemistry and genetics. Dementia with Lewy bodies (DLB) is a primary, neurodegenerative dementia sharing clinical and pathological characteristics with both Parkinson's disease (PD) and Alzheimer's disease (AD). Antiubiquitin immunocytochemical staining, developed in the early 1990s, allowed the frequency and distribution of cortical LBs to be defined. More recently, alpha-synuclein antibodies have revealed extensive neuritic pathology in DLB demonstrating a neurobiological link with other "synucleinopathies" including PD and multiple system atrophy (MSA). The most significant correlates of cognitive failure in DLB appear to be with cortical LB and Lewy neurites (LNs) rather than Alzheimer type pathology. Clinical diagnostic criteria for DLB, published in 1996, have been subjected to several validation studies against autopsy findings. These conclude that although diagnostic specificity is high (range 79- 100%, mean 92%), sensitivity is lower (range 0- 83 %, mean, 49%). Improved methods of case detection are therefore required. Fluctuating impairments in attention, visual recognition and construction are more indicative of DLB than AD. Relative preservation of medial temporal lobe volume on structural MRI and the use of SPECT tracers for regional blood flow and the dopamine transporter are the most reliable current biomarkers for DLB. There are no genetic or CSF tests recommended for the diagnosis of DLB at present. Between 15 and 20% of all elderly demented cases reaching autopsy have DLB, making it the most common cause of degenerative dementia after AD. Exquisite, not infrequently fatal, sensitivity to neuroleptic drugs and encouraging reports of the effects of cholinesterase inhibitors on cognitive, psychiatric and neurological features, mean that an accurate diagnosis of DLB is more

  17. Immunity

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920630 Effects of the spleen on immunestate of patients with gastric cancer.QIUDengbo (仇登波), et al. Dept General Surg,Union Hosp, Tongji Med Univ, Wuhan, 430022.Natl Med J China 1992; 72(6): 334-337. For analysing the effects of the spleen on im-mune state of gastric cancer patients.T-lym-

  18. Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate

    Energy Technology Data Exchange (ETDEWEB)

    Tonk, Elisa C.M., E-mail: ilse.tonk@rivm.nl [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Verhoef, Aart; Gremmer, Eric R. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Loveren, Henk van [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Piersma, Aldert H. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Institute for Risk Assessment Sciences, Veterinary Faculty, Utrecht University, Utrecht (Netherlands)

    2012-04-01

    The developing immune system displays a relatively high sensitivity as compared to both general toxicity parameters and to the adult immune system. In this study we have performed such comparisons using di(2-ethylhexyl) phthalate (DEHP) as a model compound. DEHP is the most abundant phthalate in the environment and perinatal exposure to DEHP has been shown to disrupt male sexual differentiation. In addition, phthalate exposure has been associated with immune dysfunction as evidenced by effects on the expression of allergy. Male wistar rats were dosed with corn oil or DEHP by gavage from postnatal day (PND) 10–50 or PND 50–90 at doses between 1 and 1000 mg/kg/day. Androgen-dependent organ weights showed effects at lower dose levels in juvenile versus adult animals. Immune parameters affected included TDAR parameters in both age groups, NK activity in juvenile animals and TNF-α production by adherent splenocytes in adult animals. Immune parameters were affected at lower dose levels compared to developmental parameters. Overall, more immune parameters were affected in juvenile animals compared to adult animals and effects were observed at lower dose levels. The results of this study show a relatively higher sensitivity of juvenile versus adult rats. Furthermore, they illustrate the relative sensitivity of the developing immune system in juvenile animals as compared to general toxicity and developmental parameters. This study therefore provides further argumentation for performing dedicated developmental immune toxicity testing as a default in regulatory toxicology. -- Highlights: ► In this study we evaluate the relative sensitivities for DEHP induced effects. ► Results of this study demonstrate the age-dependency of DEHP toxicity. ► Functional immune parameters were more sensitive than structural immune parameters. ► Immune parameters were affected at lower dose levels than developmental parameters. ► Findings demonstrate the susceptibility of the

  19. Lewis base activation of Lewis acids: development of a Lewis base catalyzed selenolactonization.

    Science.gov (United States)

    Denmark, Scott E; Collins, William R

    2007-09-13

    The concept of Lewis base activation of Lewis acids has been applied to the selenolactonization reaction. Through the use of substoichiometric amounts of Lewis bases with "soft" donor atoms (S, Se, P) significant rate enhancements over the background reaction are seen. Preliminary mechanistic investigations have revealed the resting state of the catalyst as well as the significance of a weak Brønsted acid promoter.

  20. Lewis大鼠实验性自身免疫性心肌炎模型的建立及超声评价%Experimental autoimmune myocarditis induced by porcine cardiac myosin in Lewis rats and echocardiographic assessment of left ventricular dimension and function

    Institute of Scientific and Technical Information of China (English)

    梁皓; 苑海涛; 朱梅; 冯娟; 张楠; 郭文彬

    2008-01-01

    Objective To investigate the feasibility to establish experimental model of autoimmune myocarditis and to study the value of echocardiographic assessment of left ventricular structure and function.Methods Seventy-two male 6 weeks old Lewis rats were randomly divided into 3 groups:normal control group,negative control group and positive group.Positive group were immunized with porcine cardiac myosin at days 0,7,30.Results ①The positive group showed weight loss,increased heart weight and myocardial necrosis with inflammatory infiltration.②The development of experimental autoimmune myocarditis included acute,subacute and chronic stages.The left ventricular diameter,ventricular wall thickness,left ventricular fractional shortening and ejection fraction of positive group differed significantly from those of other two groups.Conclusions Lewis rats immunized with porcine cardiac myosin may be a desirable experimental model of experimental autoimmune myocarditis,echocardiography can evaluate changes of cardiac structure and function accurately.%目的 评价Lewis大鼠自身免疫性心肌炎模型建立及超声监测心脏结构和功能的可行性.方法 72只Lewis大鼠随机等分为正常对照组、阴性对照组和免疫组.分别于第0、7、30 d给予免疫组大鼠脚垫注射猪心肌肌凝蛋白诱导自身免疫性心肌炎的产生,同期给予阴性对照组不含猪心肌肌凝蛋白的等量溶液注射.结果 ①免疫组大鼠体质量下降,心脏质量增加,心肌病理示炎细胞浸润和心肌细胞坏死.②免疫组大鼠心脏呈现心肌炎急性期、亚急性期及扩张型心肌病的周期性演变过程;免疫组大鼠的左室腔径、左室壁厚度、左室短轴缩短率及射血分数与正常对照组及阴性对照组比较差异均有统计学意义(P<0.05).结论 采用猪心肌肌凝蛋白诱导Lewis大鼠实验性自身免疫性心肌炎造模成功,超声心动图可以准确评价病程中心脏结构和功能的变化.

  1. Significance of Lewis Phenotyping Using Saliva and Gastric Tissue: Comparison with the Lewis Phenotype Inferred from Lewis and Secretor Genotypes

    Directory of Open Access Journals (Sweden)

    Yun Ji Hong

    2014-01-01

    , and le59 alleles was 74.6%, 21.3%, 3.1%, and 1.0%, respectively, among 418 alleles. The saliva Lewis phenotype was completely consistent with the Lewis phenotype inferred from Lewis and Secretor genotypes, but that of gastric mucosa could not be predicted from genotypes. Lewis phenotyping using erythrocytes is only adequate for transfusion needs. Saliva testing for the Lewis phenotype is a more reliable method for determining the peripheral Lewis phenotype of an individual and the gastric Lewis phenotype must be used for the study on the association between Helicobacter pylori and the Lewis phenotype.

  2. Changes in enteroendocrine and immune cells following colitis induction by TNBS in rats.

    Science.gov (United States)

    El-Salhy, Magdy; Hatlebakk, Jan Gunnar

    2016-12-01

    Approximately 3.6 million individuals suffer from inflammatory bowel disease (IBD) in the western world, with an annual global incidence rate of 3‑20 cases/100,000 individuals. The etiology of IBD is unknown, and the currently available treatment options are not satifactory for long‑term treatment. Patients with inflammatory bowel disease present with abnormalities in multiple intestinal endocrine cell types, and a number of studies have suggested that interactions between gut hormones and immune cells may serve a pivotal role in the pathophysiology of IBD. The aim of the present study was to investigate alterations in colonic endocrine cells in a rat model of IBD. A total of 30 male Wistar rats were divided into control and trinitrobenzene sulfonic acid (TNBS)‑induced colitis groups. Colonoscopies were performed in the control and TNBS groups at day 3 following the induction of colitis, and colonic tissues were collected from all animals. Colonic endocrine and immune cells in the obtained tissue samples were immunostained and their densities were quantified. The densities of chromogranin A, peptide YY, and pancreatic polypeptide‑producing cells were significantly lower in the TNBS group compared with the control group, whereas the densities of serotonin, oxyntomodulin, and somatostatin‑producing cells were significantly higher in the TNBS group. The densities of mucosal leukocytes, B/T‑lymphocytes, T‑lymphocytes, B‑lymphocytes, macrophages/monocytes and mast cells were significantly higher in the TNBS group compared with the controls, and these differences were strongly correlated with alterations in all endocrine cell types. In conclusion, the results suggest the presence of interactions between intestinal hormones and immune cells.

  3. The Effect of Pistacia khynjuk on Humoral Immune System of Wistar Rats

    Directory of Open Access Journals (Sweden)

    A Hadinia

    2011-01-01

    Full Text Available Introduction & Objective: Plants from the genus Pistacia family such as Pistacia atlantica, Pistacia vera and Pistacia khynjuk are considered as herbal medicines. Antibacterial and anti-inflammatory effects of these plants have been confirmed. The aim of the current study was to find the effect of Pistacia khynjuk on humoral immune system of Wistar rats. Materials & Methods: This is an experimental study which was conducted at Yasuj University of Medical Sciences in 2009. Forty male Wistar rats were randomly allocated into four groups of ten animals and orally received 10 mg/kg of the extract of nucleus, cutin and fruit of Pistacia khynjuk respectively, every day for two weeks. The control group received only placebo. Immuno-reactivity was induced using BCG vaccine (IP with Freund‘s complete adjuvant (CFA. The titer of IgG and IgM were measured after the treatment using ELISA method. Moreover, the cervical lymph nodes and spleen of animals were excised and the volume and density of the primary and secondary follicle was evaluated by steriology. The collected data were analyzed by the SPSS using one-way ANOVA. Results: The differences in the mean level of IgG and IgM between the treated and the control animals were not significant (p>.05. Also, the mean volume of the spleen and cervical lymph nodes of the first three groups in comparison with the control animals were not significant (p>.05. Conclusion: Findings of this study showed that the Pistacia khynjuk did not have any direct effect on the activity of humoral immune system and the increasing of antibody level among Wistar rats.

  4. Melatonin treatment prevents modulation of cell-mediated immune response induced by propoxur in rats.

    Science.gov (United States)

    Suke, Sanvidhan G; Pathak, Rahul; Ahmed, Rafat S; Tripathi, A K; Banerjee, B D

    2008-08-01

    The effect of melatonin, a major secretory product of the pineal gland, in attenuation of propoxur (2-isopropoxy phenyl N-methyl carbamate)-induced modulation of cell-mediated immune (CMI) response was studied in rats. Male Wistar albino rats were exposed to propoxur (a widely used pesticide) orally (10 mg/kg) and/or melatonin (10 mg/kg) orally for 4 weeks. CMI was measured by delayed-type hypersensitivity (DTH), leucocyte and macrophage migration inhibition (LMI and MMI) responses and estimation of cytokines TNF-alpha and IFN-gamma levels. Rats exposed to propoxur for 4 weeks showed significant decrease in DTH, LMI and MMI responses. Propoxur also suppressed TNF-alpha and IFN-gamma production significantly. Administration of melatonin alone caused a significant increase in DTH response. Although there were no changes in the LMI and MMI response, the cytokine levels were significantly increased, as compared to control. Co-administration of melatonin along with propoxur significantly nullified the effect of the pesticide on the CMI response, except DTH and reversed levels of cytokines to near control/normal values. Thus, melatonin treatment considerably attenuated immunomodulation caused by sub-chronic treatment of propoxur in experimental animals.

  5. Phage displaying peptides mimic schistosoma antigenic epitopes selected by rat natural antibodies and protective immunity induced by their immunization in mice

    Institute of Scientific and Technical Information of China (English)

    Min Wang; Xin-Yuan Yi; Xian-Ping Li; Dong-Ming Zhou; McReynolds Larry; Xian-Fang Zeng

    2005-01-01

    AIM: To obtain the short peptides mimic antigenic epitopes selected by rat natural antibodies to schistosomes, and to explore their immunoprotection against schistosomiasis in mice.METHODS: Adults worm antigens (AWA) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and enzyme-linked transferred immunoblotting methods with normal SD rat sera (NRS). The killing effects on schistosomula with fresh and heat-inactivated sera from SD rats were observed. Then the purified IgG from sera of SD rats was used to biopan a phage random peptide library and 20 randomly selected positive clones were detected by ELISA and 2 of them were sequenced.Sixty female mice were immunized thrice with positive phage clones (0, 2nd, 4th wk). Each mouse was challenged with 40 cercariae, and all mice were killed 42 d after challenge. The worms and the liver eggs were counted. RESULTS: NRS could specifically react to the molecules of 75 000, 47 000, 34 500 and 23 000 of AWA. Sera from SD rats showed that the mortality rate of schistosomula was 76.2%, and when the sera were heat-inactivated in vitro, the mortality rate was decreased to 41.0% after being cultured for 48 h. The specific phages bound to IgG were enriched about 300-folds after three rounds of biopanning. Twenty clones were detected by ELISA, 19 of them bound to the specific IgG of rat sera. Immunization with these epitopes was carried out in mice. Compared with the control groups, the mixture of two mimic peptides could induce 34.9% (P = 0.000) worm reduction and 67.6% (P = 0.000) total liver egg reduction in mice. Two different mimic peptides could respectively induce 31.0% (P = 0.001), 14.5% (P = 0.074) worm reduction and 61.2% (P = 0.000), 35.7% (P = 0.000) total liver egg reduction. The specific antibody could be induced by immunization of the mimic peptides, and the antibody titer in immunized mice reached more than 1:6 400 as detected by ELISA.CONCLUSION: Specific peptides mimic antigenic

  6. Organometallic frustrated Lewis pair chemistry.

    Science.gov (United States)

    Erker, Gerhard

    2011-08-07

    Frustrated Lewis pairs are playing an increasingly important role in organometallic chemistry. Examples are presented and discussed where organometallic systems themselves serve as the Lewis base or Lewis acid components in frustrated Lewis pair chemistry, mostly through their attached functional groups. Activation of dihydrogen takes place easily in many of these systems. This may lead to the generation of novel catalyst systems but also in many cases to the occurrence of specific reactions at the periphery of the organometallic frameworks. Increasingly, FLP reactions are used to carry out functional group conversions in organometallic systems under mild reaction conditions. The limits of typical FLP reactivity are explored with selected organometallic examples, a discussion that points toward new developments, such as the discovery of facile new 1,1-carboboration reactions. Learning more and more about the broad spectrum of frustrated Lewis pair chemistry helps us to find novel reactions and applications.

  7. Development of a lipopolysaccharide (LPS)-supplemented adjuvant and its effects on cell-mediated and humoral immune responses in male rats immunized against sperm

    Science.gov (United States)

    NOGUCHI, Junko; WATANABE, Shinya; NGUYEN, Thanh Q. Dang; KIKUCHI, Kazuhiro; KANEKO, Hiroyuki

    2016-01-01

    Supplementation with lipopolysaccharide (LPS) from non-pathogenic Escherichia coli was found to enhance the adjuvant effects of a veterinary vaccine adjuvant (ISA 71VG®). Sperm immunization using 71VG as an adjuvant in the immature period induced infertility in 25% of male rats, whereas this increased to 62.5% after immunization with 71VG + LPS or Freund′s complete adjuvant (FCA). Mean testicular weight of non-sterile males in the 71VG + LPS group was significantly lower than that in the 71VG or FCA group. Histological examination of testicular tissue from sterile males demonstrated severe impairment of spermatogenesis due to experimental autoimmune orchitis, a cell-mediated autoimmune condition. The serum anti-sperm titer was elevated in the three sperm-immunized groups relative to male rats treated with adjuvant alone, but the titer was higher in the 71VG + LPS and FCA groups than in the 71VG group. We consider that this LPS-supplemented adjuvant stimulates both humoral and cell-mediated immune responses to an extent comparable to FCA. PMID:27890874

  8. Role of host immune response in the occurrence of gastropathy in rats infected with larval Taenia taeniaeformis.

    Science.gov (United States)

    Abella, J A; Oku, Y; Nonaka, N; Ito, M; Kamiya, M

    1997-11-01

    Decrease of spleen weight from peak to control levels together with a corresponding decline of serum IgG level at the onset of gastric hyperplasia in Taenia taeniaeformis-infected euthymic rats, may indicate that a form of down regulation of host immune response during the course of larval T. taeniaeformis infection could facilitate the occurrence of gastropathy in rats. Gastric hyperplasia developed in T. taeniaeformis-infected athymic nude rats, indicating that occurrence of gastropathy associated with larval T. taeniaeformis infection in the rat is T cell independent. Apparently, gastric hyperplasia appeared early in nude rats which suggests that absence of T cell-mediated response could have facilitated its early occurrence.

  9. Colony-Specific Differences in Endocrine and Immune Responses to an Inflammatory Challenge in Female Sprague Dawley Rats

    Science.gov (United States)

    Hill, Lesley A.; Taves, Matthew D.; Yu, Wayne; Soma, Kiran K.; Hammond, Geoffrey L.; Weinberg, Joanne

    2015-01-01

    Sprague Dawley rats from different vendor colonies display divergent responses in a variety of experimental paradigms. An adjuvant-induced arthritis (AA) model of human rheumatoid arthritis was used to examine immune and endocrine responses to inflammatory challenge in Sprague Dawley rats from Charles River and Harlan colonies. Rats were injected with either complete Freund's adjuvant or physiological saline (control), weights, and paw volumes measured over 15 days, and blood and tissue were collected 16 days post-injection. Overall, Harlan rats developed more severe AA than Charles River rats. In addition, despite comparable corticosterone levels, corticosteroid binding globulin levels were lower in Harlan compared with Charles River rats in the absence of inflammation, suggesting that a lower corticosterone reservoir in Harlan rats may underlie their greater susceptibility to inflammation. With increasing AA severity, there was an increase in plasma corticosterone (total and free) and a decrease in corticosteroid binding globulin in both Charles River and Harlan rats. However, contrasting patterns of cytokine activation were observed in the hind paw, suggesting a reliance on different cytokine networks at different stages of inflammation, with Charles River rats exhibiting increased TNF-α, monocyte chemotactic protein-1 (MCP-1), keratinocyte chemoattractant/growth-regulated oncogene (KC/GRO), and IL-1β in the absence of clinical signs of arthritis, whereas Harlan had increased TNF-α, monocyte chemotactic protein-1, and IL-6 with mild to moderate arthritis. These colony-specific differences in endocrine and immune responses to AA in Sprague Dawley rats must be considered when comparing data from different laboratories and could be exploited to provide insight into physiological changes and therapeutic outcomes in arthritis and other inflammatory disorders. PMID:26402842

  10. Evaluation of antioxidant and immunity-enhancing activities of Sargassum pallidum aqueous extract in gastric cancer rats.

    Science.gov (United States)

    Zhang, Rui-Li; Luo, Wen-Da; Bi, Tie-Nan; Zhou, Shen-Kang

    2012-07-11

    The effect of Sargassum pallidum (brown seaweed) aqueous extract on the immunity function and antioxidant activities in was studied gastric cancer rats. Treatment with Sargassum pallidum aqueous extract at oral doses 400, 600 or 800 mg/kg body weight was found to provide a dose-dependent protection against N-methyl-N′-nitro-Nnitrosoguanidine (MNNG)-induced immunity damage and oxidative injury by enhancing serum interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10) levels, decreasing interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) levels, preserving normal antioxidant enzymes activities, and by inhibiting lipid peroxidation in gastric mucosa. It can be concluded that Sargassum pallidum aqueous extract may enhance the immunity and antioxidant activities in gastric cancer rats.

  11. Modulation of innate immune response by the vagus nerve in experimental hepatic amebiasis in rats.

    Science.gov (United States)

    Martínez-Jaimes, Mercedes D; García-Lorenzana, Mario; Muñoz-Ortega, Martin H; Quintanar-Stephano, Andrés; Ávila-Blanco, Manuel E; García-Agueda, Carlos E; Ventura-Juárez, Javier

    2016-10-01

    The parasympathetic nervous system has a crucial role in immunomodulation of the vagus nerve, its structure provides a pathogen detection system, and a negative feedback to the immune system after the pathogenic agent has been eliminated. Amebiasis is a disease caused by the protozoan parasite Entamoeba histolytica, considered the third leading cause of death in the world. The rats are used as a natural resistance model to amoebic liver infection. The aim of this study is to analyze the interaction of Entamoeba histolytica with neutrophils, macrophages, and NK cells in livers of intact and vagotomized rats. Six groups were studied (n = 4): Intact (I), Intact + amoeba (IA), Sham (S), Sham + amoeba (SA), Vagotomized (V) and Vagotomized + amoeba (VA). Animals were sacrificed at 8 h post-inoculation of E. histolytica. Then, livers were obtained and fixed in 4% paraformaldehyde. Tissue liver slides were stained with H-E, PAS and Masson. The best development time for E. histolytica infection was at 8 h. Amoeba was identified with a monoclonal anti-220 kDa E. histolytica lectin. Neutrophils (N) were identified with rabbit anti-human neutrophil myeloperoxidase, macrophages (Mɸ) with anti-CD68 antibody and NK cells (NK) with anti-NK. Stomachs weight and liver glycogen were higher in V. Collagen increased in VA, whereas vascular and neutrophilic areas were decreased. There were fewer N, Mɸ, NK around the amoeba in the following order IA > SA > VA (p < 0.05 between IA and VA). In conclusion, these results suggest that the absence of parasympathetic innervation affects the participation of neutrophils, macrophages and NK cells in the innate immune response, apparently by parasympathetic inhibition on the cellular functions and probably for participation in sympathetic activity.

  12. Immunity phenomena following olfactory ensheathing cell transplantation into experimental allergic encephalomyelitis rat brain

    Institute of Scientific and Technical Information of China (English)

    Ainong Mei; Jue Wang; Qiong Cheng; Xinqing Yang; Jin Yang; Pengli Zhu; Shougang Guo

    2010-01-01

    Olfactory ensheathing cells(OECs)can promote axonal regeneration and remyelination for the treatment of spinal cord injury.OECs can also treat experimental allergic encephalomyelitis(EAE),but it remains unclear whether OECs might be rejected by the immune system in the brain,including the destruction of the blood-brain barrier under inflammation,the release of inflammatory factors,the activation of local antigen-presenting cells(e.g.,microglia cells)and antigen drainage.We found that OECs expressed major histocompatibility complex(MHC)-Ⅰmolecules on the cell surface,barely expressed MHC-Ⅱ,but MHC-Ⅱ could be induced by interferon-y,suggesting that OECs have certain immunogenicity.When OECs were transplanted into normal animal brains,no OECs were phagocytosed by dendritic cells in the cervical lymph node,and OECs did not induce lymphocyte proliferation,which indicates that OECs share some immune privilege under normal conditions.However,OECs in the rat EAE brain were phagocytosed by dendritic cells in the cervical lymph node and enhanced lymphocyte proliferation.These findings suggest that OECs are rejected because of increased immunogenicity in EAE brain,and that brain inflammation,in particular activated dendritic cells,may be a prerequisite for rejecting OECs.

  13. Impact of Anesthetics on Immune Functions in a Rat Model of Vagus Nerve Stimulation.

    Directory of Open Access Journals (Sweden)

    Chloé A Picq

    Full Text Available Vagus nerve stimulation (VNS has been successfully performed in animals for the treatment of different experimental models of inflammation. The anti-inflammatory effect of VNS involves the release of acetylcholine by vagus nerve efferent fibers inhibiting pro-inflammatory cytokines (e.g. TNF-α produced by macrophages. Moreover, it has recently been demonstrated that splenic lymphocytic populations may also be involved. As anesthetics can modulate the inflammatory response, the current study evaluated the effect of two different anesthetics, isoflurane and pentobarbital, on splenic cellular and molecular parameters in a VNS rat model. Spleens were collected for the characterization of lymphocytes sub-populations by flow cytometry and quantification of cytokines secretion after in vitro activation. Different results were observed depending on the anesthetic used. The use of isoflurane displayed a non-specific effect of VNS characterized by a decrease of most splenic lymphocytes sub-populations studied, and also led to a significantly lower TNF-α secretion by splenocytes. However, the use of pentobarbital brought to light immune modifications in non-stimulated animals that were not observed with isoflurane, and also revealed a specific effect of VNS, notably at the level of T lymphocytes' activation. These differences between the two anesthetics could be related to the anti-inflammatory properties of isoflurane. In conclusion, pentobarbital is more adapted than isoflurane in the study of the anti-inflammatory effect of VNS on an anesthetized rat model in that it allows more accurate monitoring of subtle immunomodulatory processes.

  14. Melatonin Modulates the Immune System Response and Inflammation in Diabetic Rats Experimentally-Induced by Alloxan.

    Science.gov (United States)

    Ozkanlar, S; Kara, A; Sengul, E; Simsek, N; Karadeniz, A; Kurt, N

    2016-02-01

    Diabetes mellitus (DM) is a metabolic disease, which causes an increase in the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β), and also proliferation of monocyte chemotactic protein. In the present study, the potential effects of melatonin on proinflammatory cytokines, hematological values, and lymphoid tissues were investigated in diabetic rats. In the study, 36 male rats were randomly divided into 4 groups as follows: Control, Mel (melatonin), DM, and DM-Mel. For 15 days, an isotonic saline solution was given to the Control and DM groups; melatonin was administered to the Mel and DM-Mel groups intraperitoneally. At the end of the study, all animals were sacrificed by drawing the blood from their hearts under deep anesthesia. Samples of the spleen, thymus, and lymph nodes were fixed in 10% formaldehyde for histologic analysis. Increases in proinflammatory serum cytokine concentrations, mast cells, and total white blood cell counts as well as tissue destruction in the lymphoid organs were determined in the DM group via biochemical, hematological, and histologic analyses. However, the findings for the DM-Mel group revealed decreases in serum IL-1β concentration and mast cell densities, and destructions in lymphoid tissues by the melatonin administration. The present study suggests that melatonin treatment may control immune system regulation and inhibit the production of proinflammatory cytokines and tissue mast cell accumulation by preventing the destruction of lymphoid organs in the diabetic process.

  15. Stress-sensitive organs and blood corticosterone after immobilization of active and passive rats immunized with glutamate-bovine serum albumin conjugate.

    Science.gov (United States)

    Umryukhin, A E; Sotnikov, S V; Chekmareva, N Yu; Vetrile, L A; Zakharova, I A

    2014-12-01

    We studied stress-induced organ and hormonal responses in behaviorally active and passive rats against the background of immunization with glutamate-BSA conjugate. The relative weight of the adrenal glands after immobilization was lower in rats immunized with the conjugate in comparison with non-immunized animals. The weight of the adrenal glands in behaviorally active rats decreased in parallel with the decrease in blood corticosterone. In behaviorally active and passive rats immunized with the conjugate, ulcer formation in the stomach was slightly intensified after immobilization. It was hypothesized that immunization with glutamate-BSA conjugate suppresses activity of the hypothalamic-pituitary-adrenal feedback mechanism underlying the production of glucocorticoid hormones, which is manifested in slightly increased ulceration due to attenuation of the gastroprotective action of corticosterone under stress.

  16. Protection of gnotobiotic rats against dental caries by passive immunization with bovine milk antibodies to Streptococcus mutans.

    Science.gov (United States)

    Michalek, S M; Gregory, R L; Harmon, C C; Katz, J; Richardson, G J; Hilton, T; Filler, S J; McGhee, J R

    1987-10-01

    A multivalent vaccine consisting of whole cell antigens of seven strains, representing four serotypes (b, c, d and g), of mutans streptococci was used to hyperimmunize a group of cows. Serum samples from these animals contained immunoglobulin G1 (IgG1) antibody activity to seven serotypes (a to g) of mutans streptococci. Whey obtained from the animal with the highest serum antibody activity, which also contained high levels of IgG1 antibody, was used in passive caries immunity studies. Gnotobiotic rats monoinfected with Streptococcus mutans MT8148 serotype c or Streptococcus sobrinus OMZ176 (d) or 6715 (g) and provided a caries-promoting diet containing immune whey had lower plaque scores, numbers of streptococci in plaque, and degree of caries activity than similarly infected animals given a diet containing control whey obtained from nonimmunized cows. To establish the nature of the protective component(s) present in the immune whey, an ultrafiltrate fraction of the whey was prepared. This preparation contained higher levels of IgG1 anti-S. mutans antibody activity than the immune whey. Rats monoinfected with S. mutans MT8148 and provided with a diet supplemented with 0.1% of this fraction exhibited a degree of caries protection similar to that seen in animals provided a diet containing 100% immune whey. In fact, a diet containing as little as 0.01% of the ultrafiltrate fraction gave some degree of protection against oral S. mutans infection. The active component in the immune whey was the IgG1 anti-S. mutans antibody, since rats monoinfected with S. mutans MT8148 and provided a diet supplemented with purified immune whey IgG1 had significantly reduced plaque scores, numbers of S. mutans in plaque, and caries activity compared with control animals. Prior adsorption of the IgG fraction with killed S. mutans MT8148 whole cells removed antibody activity and abrogated caries protection.

  17. Effect of tea tree oil (Melaleuca alternifolia) on the longevity and immune response of rats infected by Trypanosoma evansi.

    Science.gov (United States)

    Baldissera, Matheus D; Da Silva, Aleksandro S; Oliveira, Camila B; Vaucher, Rodrigo A; Santos, Roberto C V; Duarte, Thiago; Duarte, Marta M M F; França, Raqueli T; Lopes, Sonia T A; Raffin, Renata P; Boligon, Aline A; Athayde, Margareth L; Stefani, Lenita M; Monteiro, Silvia G

    2014-06-01

    This study aimed to evaluate the effect of tea tree oil (TTO - Melaleuca alternifolia) on hepatic and renal functions, and the immune response of rats infected by Trypanosoma evansi. A pilot study has shown that rats treated with TTO orally (1 ml kg(-1)) had increased survival rate without curative effect. In order to verify if increased longevity was related to a better immune response against T. evansi when using tea tree oil, a second experiment was conducted. Thus, twenty-four rats were divided into four groups. The groups A and B were composed of uninfected animals, and the groups C and D had rats experimentally infected by T. evansi. Animals from the groups B and D were treated orally with TTO (1 ml kg(-1)) for three days. Blood samples were collected to verify humoral response analysis for immunoglobulins (IgA, IgM, IgE, and IgG) and cytokines (TNF-α, INF-γ, IL-1, IL-6, IL-4, and IL-10) at days 0, 3, 5 and 15 post-infection (PI). TTO treatment caused changes in the immunoglobulins and cytokines profile, as well as the course of T. evansi infection in rats. It was found that the TTO was not toxic, i.e., hepatic and renal functions were not affected. Therefore, it is possible to conclude that TTO influences the levels of inflammatory mediators and has trypanocidal effect, increasing life expectancy of rats infected by T. evansi.

  18. Impairment of blood brain barrier is related with the neuroinflammation induced peripheral immune status in intracerebroventricular colchicine injected rats: An experimental study with mannitol.

    Science.gov (United States)

    Sil, Susmita; Ghosh, Arijit; Ghosh, Tusharkanti

    2016-09-01

    The neurodegeneration in AD patients may be associated with changes of peripheral immune responses. Some peripheral immune responses are altered due to neuroinflammation in colchicine induced AD (cAD) rats. The leaky blood brain barrier (BBB) in cAD-rats may be involved in inducing peripheral inflammation, though there is no report in this regard. Therefore, the present study was designed to investigate the role of BBB in cADrats by altering the BBB in a time dependent manner with injection (i.v.) of mannitol (BBB opener). The inflammatory markers in the brain and serum along with the peripheral immune responses were measured after 30 and 60min of mannitol injection in cAD rats. The results showed higher inflammatory markers in the hippocampus and serum along with alterations in peripheral immune parameters in cAD rats. Although the hippocampal inflammatory markers did not further change after mannitol injection in cAD rats, the serum inflammatory markers and peripheral immune responses were altered and these changes were greater after 60min than that of 30min of mannitol injection. The present study shows that the peripheral immune responses in cAD rats after 30 and 60min of mannitol injection are related to magnitude of impairment of BBB in these conditions. It can be concluded from this study that impairment of BBB in cAD rats is related to the changes of peripheral immune responses observed in that condition.

  19. HSP70 immune reactivity and TUNEL positivity in the liver of toluene-inhaled and melatonin-treated rats.

    Science.gov (United States)

    Tas, Ufuk; Ogeturk, Murat; Kuloglu, Tuncay; Sapmaz, Hilal Irmak; Kocaman, Nevin; Zararsiz, Ismail; Sarsilmaz, Mustafa

    2013-07-01

    Toluene is a clear, colorless and volatile hydrocarbon that is metabolized in liver, produced free oxygen radicals and can mediate cellular damage. Melatonin which is a pineal gland hormone is a very potent antioxidant. It can make the cellular membrane more durable against oxidative attacks and protect nuclear DNA from oxidative damage. This study aimed to investigate heat shock protein (HSP)70 immune reactivity and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positivity (apoptotic activity) in the liver of toluene-inhaled and melatonin-treated rats. A total of 21 adult male Wistar albino rats were divided at random into 3 equal groups. Animals in group I were designated as control. The rats in group II were exposed to toluene (3000 ppm/1 h/day) for 30 days, while the rats in group III were treated with melatonin (10 mg/kg/day, intraperitoneally) plus toluene inhalation. At the end of the 30-day experimental period, all rats were killed by decapitation. Then the liver tissues of rats were removed and tissue specimens were embedded in paraffin blocks. The specimens were stained with periodic acid-schiff (PAS) following routine histological procedures. Sections obtained from paraffin blocks were used for immune detection of TUNEL and HSP70. In light microscopic observations of tissues from toluene-inhaled rats, massive hepatocyte degeneration, ballooning degeneration and decreased PAS positivity were observed. Increased TUNEL positivity and HSP70 immune reactivity were determined in toluene-inhaled group and melatonin treatment decreased all these adverse effects.

  20. Significance of Lewis phenotyping using saliva and gastric tissue: comparison with the Lewis phenotype inferred from Lewis and secretor genotypes.

    Science.gov (United States)

    Hong, Yun Ji; Hwang, Sang Mee; Kim, Taek Soo; Song, Eun Young; Park, Kyoung Un; Song, Junghan; Han, Kyou-Sup

    2014-01-01

    Lewis phenotypes using various types of specimen were compared with the Lewis phenotype predicted from Lewis and Secretor genotypes. This is the first logical step in explaining the association between the Lewis expression and Helicobacter pylori. We performed a study of the followings on 209 patients who underwent routine gastroscopy: erythrocyte and saliva Lewis phenotyping, gastric Lewis phenotyping by the tissue array, and the Lewis and Secretor genes genotyping. The results of phenotyping were as follows [Le(a-b-), Le(a+b-), Le(a-b+), and Le(a+b+), respectively, in order]: erythrocyte (12.4%, 25.8%, 61.2%, and 0.5%); saliva (2.4%, 27.3%, 70.3%, and 0.0%); gastric mucosa (8.1%, 6.7%, 45.5%, and 39.7%). The frequency of Le, le (59/508) , le (59/1067) , and le (59) alleles was 74.6%, 21.3%, 3.1%, and 1.0%, respectively, among 418 alleles. The saliva Lewis phenotype was completely consistent with the Lewis phenotype inferred from Lewis and Secretor genotypes, but that of gastric mucosa could not be predicted from genotypes. Lewis phenotyping using erythrocytes is only adequate for transfusion needs. Saliva testing for the Lewis phenotype is a more reliable method for determining the peripheral Lewis phenotype of an individual and the gastric Lewis phenotype must be used for the study on the association between Helicobacter pylori and the Lewis phenotype.

  1. Symptoms of Lewy Body Dementia

    Science.gov (United States)

    ... Treatment Options Join the fight against LBD! Donate Symptoms Lewy body dementia symptoms and diagnostic criteria Every person with LBD is ... or Dementia plus one or more suggestive features. Symptoms Explained In this section we'll discuss each ...

  2. INFLUENCE OF ELECTROACUPUNCTURE ON HYPERTENSION VASCULAR DEMENTIA AND ITS RED CELL IMMUNE-FUNCTION IN THE RAT

    Institute of Scientific and Technical Information of China (English)

    莫飞智; 李坚强; 雷立屏; 赖新生; 刘颂豪

    2000-01-01

    Objective: To probe into the effect of electroacupuncture (EA)on vascular dementia and red cell immune function in the rat. Methods: 30 SD rats were made into renal hypertension rats (RHR) by clamping the kidney arteries with silver clip. 42 days later, their bilateral common carotid arteries were blocked repeatedly to cause cerebral ischemia. The Hypertension vascular dementia model was then set up. Then they were randomly divided into VD model group, EA groupand medication group (Dihydroergotoxine, DHET), with 10 cases in each group. The therapeutic course was 28 days. The ability of learning and memory was using an obs erved by water maze, and the function of red blood cell immune was detected after treatment. Results: the latecy Of the EA group and medication group was shorter than that of model group (P<0.05, P<0. 005), and that of EA group was shorter than medication group (P<0.05, P<0.005). EA and medication could increase the RBC C3b receptor flower circle rate and reduce the RBC-IC flower circle rate significantly(P<0.05,P<0.01). Conclusion: The results indicated that EA therapy could raise the ability of learning and memory and improve the function of red cell immune in VD rats, while the therapeutic effect of EAis better than DHET.

  3. Effect of Scoparia dulcis on noise stress induced adaptive immunity and cytokine response in immunized Wistar rats

    Directory of Open Access Journals (Sweden)

    Loganathan Sundareswaran

    2017-01-01

    Conclusion: S. dulcis (SD has normalized and prevented the noise induced changes in cell-mediated and humoral immunity and it could be the presence of anti-stressor and immuno stimulant activity of the plant.

  4. Human and Autologous Adipose-derived Stromal Cells Increase Flap Survival in Rats Independently of Host Immune Response.

    Science.gov (United States)

    Toyserkani, Navid Mohamadpour; Jensen, Charlotte Harken; Andersen, Ditte Caroline; Sheikh, Søren Paludan; Sørensen, Jens Ahm

    2017-07-22

    There is a rising interest in adipose-derived stromal cells for clinical use; however, it is unknown whether freshly isolated stromal cells (SVF) or culture-expanded cells (ASCs) are more efficacious. We therefore aimed to compare the 2 cellular therapies in an in vivo model of angiogenesis, the ischemic flap in rats, which induces acute ischemia. We also aimed to determine the importance of cell presence and the host immune response. A total of 96 rats (n = 12 in each group) were used, and in each rat, a caudally based random flap measuring 2 × 7 cm was made. The study was conducted in 3 phases. First, each rat was treated with human SVF cells, human ASCs, or vehicle. Second, each rat was treated with human SVF, human SVF lysate, or vehicle. Finally, each rat was treated with rat (autologous) SVF cells or vehicle. Flap survival, vessel density, and stromal cell retention were evaluated after 7 days. The mean survival rates for SVF treatment regardless of human or autologous origin were significantly increased as compared with the control group. Adipose stem/stromal cell and SVF lysate injection did not increase flap survival. Vessel density was increased for human and rat SVF and human ASC but not for SVF lysate. Human cells were not detected in the flaps after 7 days. Flap survival increased with SVF treatment regardless of human or autologous origin, suggesting that increased flap survival is independent of the host immune response. All cell injections lead to increased vessel density, but it did not necessarily lead to increased flap survival. Further research should elaborate which molecular events make SVF treatment more efficacious than ASC.

  5. Impaired immune function in seals and laboratory rats exposed to dioxin-like compounds from Baltic herring

    Energy Technology Data Exchange (ETDEWEB)

    Ross, P.S. [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands); Swart, R.L. de [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[Erasmus Univ., Rotterdam (Netherlands); Timmerman, H.H.; Loveren, H. van [National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands); Osterhaus, A.D.M.E. [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands)]|[Erasmus Univ., Rotterdam (Netherlands)

    1995-12-31

    Complex mixtures of lipophilic contaminants have been shown to affect certain top predators in the aquatic food chain, including seals. A recent demonstration that harbor seals (Phoca vitulina) fed Baltic Sea herring displayed impaired natural killer cell activity and T-lymphocyte function represented the first demonstration of immunotoxicity induced by ambient levels of contaminants in the environment. While these animals had a lower ability to respond to immunizations with inactivated vaccines, specific antibody responses, and in vitro antigen-specific lymphoproliferative responses, obvious constraints limited the ability to extend these results with host resistance tests or an evaluation of thymus and other lymphoid organs. The authors therefore set up a parallel study by exposing pregnant laboratory rats to the same Baltic herring contaminant mixture as received the seals. They then examined immune function parameters and host resistance to virus infection. As in the seals, rat pups of the Baltic group had impaired T-lymphocyte function. In addition, thymus cells and/or their precursors appeared to be targeted, as their numbers and function were reduced in the rats. Following challenge with rat cytomegalovirus in a host resistance study, rat pups in the Baltic group had impaired natural killer cell responses to the virus infection, and lower specific CD8 + (cytotoxic T-lymphocyte) responses following in vitro stimulation. By extrapolation, these results suggest that the impaired immune responses observed in the Baltic group of seals may lead to a less effective defense against virus infections in marine mammals inhabiting polluted coastal waters. Toxicological profiles and results of both the captive seal and laboratory rat experiments tend to implicate the 2,3,7,8-TCDD-like PCB, dioxin and furan congeners in the immunosuppression, and point to a major role for the PCBs.

  6. Lycopene Enhances Antioxidant Enzyme Activities and Immunity Function in N-Methyl-N′-nitro-N-nitrosoguanidine–Induced Gastric Cancer Rats

    OpenAIRE

    Xian-Guo Wu; Cong Luo

    2011-01-01

    To investigate anticancer effect of lycopene, we examined the effects of lycopene on the oxidative injury and immunity activities of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer rats. The animals were divided into five groups. Group I served as the normal control and was given corn oil orally for 20 weeks. Group II were induced with MNNG 200 mg/kg body weight by oral gavage at days 0 and 14, and saturated NaCl (1 mL per rats) was given once every three days for four week...

  7. Syngeneic immune response to rat tracheal epithelial cells transformed in vitro by N-methyl-N-nitro-N-nitrosoguanidine.

    OpenAIRE

    Braslawsky, G. R.; Steele, V.; Kennel, S. J.; Nettesheim, P.

    1981-01-01

    Two cell lines (2-10-1 and 8-10-2) derived by exposure to primary tracheal explants to MNNG in vitro were not tumorigenic in syngeneic F-344 rats or athymic BALB/c (nu/nu) mice at early passage, but became tumorigenic at late passage. These cell lines are therefore suited to study the expression of neoantigens during neoplastic development. Transplantation resistance to late-passage, tumorigenic cells was indicated in syngeneic rats using an immunization protocol of repeated cell inoculation ...

  8. Immune and inflammatory gene signature in rat cerebrum in subarachnoid hemorrhage with microarray analysis.

    Science.gov (United States)

    Lee, Chu-I; Chou, An-Kuo; Lin, Ching-Chih; Chou, Chia-Hua; Loh, Joon-Khim; Lieu, Ann-Shung; Wang, Chih-Jen; Huang, Chi-Ying F; Howng, Shen-Long; Hong, Yi-Ren

    2012-01-01

    Cerebral vasospasm following subarachnoid hemorrhage (SAH) has been studied in terms of a contraction of the major cerebral arteries, but the effect of cerebrum tissue in SAH is not yet well understood. To gain insight into the biology of SAH-expressing cerebrum, we employed oligonucleotide microarrays to characterize the gene expression profiles of cerebrum tissue at the early stage of SAH. Functional gene expression in the cerebrum was analyzed 2 h following stage 1-hemorrhage in Sprague-Dawley rats. mRNA was investigated by performing microarray and quantitative real-time PCR analyses, and protein expression was determined by Western blot analysis. In this study, 18 upregulated and 18 downregulated genes displayed at least a 1.5-fold change. Five genes were verified by real-time PCR, including three upregulated genes [prostaglandin E synthase (PGES), CD14 antigen, and tissue inhibitor of metalloproteinase 1 (TIMP1)] as well as two downregulated genes [KRAB-zinc finger protein-2 (KZF-2) and γ-aminobutyric acid B receptor 1 (GABA B receptor)]. Notably, there were functional implications for the three upregulated genes involved in the inflammatory SAH process. However, the mechanisms leading to decreased KZF-2 and GABA B receptor expression in SAH have never been characterized. We conclude that oligonucleotide microarrays have the potential for use as a method to identify candidate genes associated with SAH and to provide novel investigational targets, including genes involved in the immune and inflammatory response. Furthermore, understanding the regulation of MMP9/TIMP1 during the early stages of SAH may elucidate the pathophysiological mechanisms in SAH rats.

  9. Developmental Changes in Pain and Spinal Immune Gene Expression after Radicular Trauma in the Rat

    Science.gov (United States)

    Barr, Gordon A.; Wang, Shaoning; Weisshaar, Christine L.; Winkelstein, Beth A.

    2016-01-01

    Neuropathic pain is chronic pain that develops after nerve injury and is less frequent in infants and children than in adults. Likewise, in animal models of neuropathic pain, allodynia and hyperalgesia are non-existent or attenuated in the infant, with a “switch” during development by which acute nerve injury transitions to chronic pain. Concomitant with the delay in neuropathic pain, there is a parallel delay in the ability of nerve injury to activate the immune system. Models of neuropathic pain in the infant have used various ligation methods and find that neuropathic pain does not occur under after postnatal days 21–28 (PN21–PN28), linked to activation of immune processes and developmental regulation of anti-inflammatory cytokines. We applied a model of neuropathic pain in the adult using a transient compression of the cervical nerve or nerve root in infant rats (injured at 10, 14, 21, or 28 days of age) to define transition periods during which injury results in no change in thermal and mechanical pain sensitivity or in short-term changes in pain. There was little to no hyperalgesia when the injury was imposed at PN10, but significant thermal hyperalgesia and mechanical allodynia 1 day after compression injury when performed at PN14, 21, or 28. Thermal withdrawal latencies returned to near baseline by 7 days postsurgery when the injuries were at PN14, and lasted up to 14 days when the injury was imposed at PN28. There was mechanical allodynia following injury at 1 day postinjury and at 14 days after injury at PN14. Measurements of mRNA from spinal cord at 1, 7, and 14 days postinjury at PN14, 21, and 28 showed that both the magnitude and duration of elevated immune markers and chemokines/cytokines were greater in the older animals, corresponding to the development of hyperalgesia. Thus, we confirm the late onset of neuropathic pain but found no evidence of emergent hyperalgesia if the injury was before PN21. This may be due to the use of

  10. Developmental Changes In Pain And Spinal Immune Gene Expression After Radicular Trauma In The Rat

    Directory of Open Access Journals (Sweden)

    Gordon Alfred Barr

    2016-12-01

    Full Text Available Neuropathic pain is an example of chronic pain that develops after nerve injury and is less frequent in infants and children than in adults. Likewise, in animal models of neuropathic pain, allodynia and hyperalgesia are non-existent or attenuated in the infant, with a switch during development by which acute nerve injury transitions to chronic pain. Concomitant with the delay in neuropathic pain, there is a parallel delay in the ability of nerve injury to activate the immune system. Models of neuropathic pain in the infant have used various ligation methods and find that neuropathic pain does not occur under after postnatal day 21-28 (PN21-PN28, linked to activation of immune processes and developmental regulation of anti-inflammatory cytokines. We applied a model of neuropathic pain in the adult using a transient compression of the cervical nerve or nerve root in infant rats (injured at 10, 14, 21 or 28 days of age to define transition periods during which injury results in no change in thermal and mechanical pain sensitivity or in short term changes in pain. There was little to no hyperalgesia when the injury was imposed at PN10, but significant thermal hyperalgesia and mechanical allodynia one day after compression injury when performed at PN14, 21 or 28. Thermal withdrawal latencies return to near baseline by 7 days post-surgery (PS7 when the injuries were at PN14, and lasted up to 14 days when imposed at PN28. There was mechanical allodynia following nerve injury at 7 or 14 days after injury at PN14. Measurements of mRNA from spinal cord at 1, 7 and 14 days post-injury at PN14, 21, and 28 showed that both the magnitude and duration of elevated immune markers and chemokines/cytokines were greater in the older animals, corresponding to the development of hyperalgesia. Thus we confirm the late onset of neuropathic pain but found no evidence of emergent hyperalgesia if the injury was before PN21/28. This may be due to the use of a transient

  11. Developmental Changes in Pain and Spinal Immune Gene Expression after Radicular Trauma in the Rat.

    Science.gov (United States)

    Barr, Gordon A; Wang, Shaoning; Weisshaar, Christine L; Winkelstein, Beth A

    2016-01-01

    Neuropathic pain is chronic pain that develops after nerve injury and is less frequent in infants and children than in adults. Likewise, in animal models of neuropathic pain, allodynia and hyperalgesia are non-existent or attenuated in the infant, with a "switch" during development by which acute nerve injury transitions to chronic pain. Concomitant with the delay in neuropathic pain, there is a parallel delay in the ability of nerve injury to activate the immune system. Models of neuropathic pain in the infant have used various ligation methods and find that neuropathic pain does not occur under after postnatal days 21-28 (PN21-PN28), linked to activation of immune processes and developmental regulation of anti-inflammatory cytokines. We applied a model of neuropathic pain in the adult using a transient compression of the cervical nerve or nerve root in infant rats (injured at 10, 14, 21, or 28 days of age) to define transition periods during which injury results in no change in thermal and mechanical pain sensitivity or in short-term changes in pain. There was little to no hyperalgesia when the injury was imposed at PN10, but significant thermal hyperalgesia and mechanical allodynia 1 day after compression injury when performed at PN14, 21, or 28. Thermal withdrawal latencies returned to near baseline by 7 days postsurgery when the injuries were at PN14, and lasted up to 14 days when the injury was imposed at PN28. There was mechanical allodynia following injury at 1 day postinjury and at 14 days after injury at PN14. Measurements of mRNA from spinal cord at 1, 7, and 14 days postinjury at PN14, 21, and 28 showed that both the magnitude and duration of elevated immune markers and chemokines/cytokines were greater in the older animals, corresponding to the development of hyperalgesia. Thus, we confirm the late onset of neuropathic pain but found no evidence of emergent hyperalgesia if the injury was before PN21. This may be due to the use of a

  12. Protection to Fasciola hepatica in the gut mucosa of immune rats is associated with infiltrates of eosinophils, IgG1 and IgG2a antibodies around the parasites

    NARCIS (Netherlands)

    Milligen, van F.J.; Cornelissen, J.B.W.J.; Hendriks, I.M.; Gaasenbeek, C.P.H.

    1998-01-01

    We investigated the immune effector mechanisms that underlie protection against F. hepatica in the gut wall of immune rats, using (immuno)histochemistry. In the lamina propria of immune Wistar rats, four weeks after oral infection, frequencies of IgE-positive cells, eosinophils and mucosal mast cell

  13. Effect of electromagnetic waves from mobile phone on immune status of male rats: possible protective role of vitamin D.

    Science.gov (United States)

    El-Gohary, Ola Ahmed; Said, Mona Abdel-Azeem

    2017-02-01

    There are considerable public concerns about the relationship between mobile phone radiation and human health. The present study assesses the effect of electromagnetic field (EMF) emitted from a mobile phone on the immune system in rats and the possible protective role of vitamin D. Rats were randomly divided into six groups: Group I: control group; Group II: received vitamin D (1000 IU/kg/day) orally; Group III: exposed to EMF 1 h/day; Group IV: exposed to EMF 2 h/day; Group V: exposed to EMF 1 h/day and received vitamin D (1000 IU/kg/day); Group VI: exposed to EMF 2 h/day and received vitamin D (1000 IU/kg/day). After 30 days of exposure time, 1 h/day EMF exposure resulted in significant decrease in immunoglobulin levels (IgA, IgE, IgM, and IgG); total leukocyte, lymphocyte, eosinophil and basophil counts; and a significant increase in neutrophil and monocyte counts. These changes were more increased in the group exposed to 2 h/day EMF. Vitamin D supplementation in EMF-exposed rats reversed these results when compared with EMF-exposed groups. In contrast, 7, 14, and 21 days of EMF exposure produced nonsignificant differences in these parameters among all experimental groups. We concluded that exposure to mobile phone radiation compromises the immune system of rats, and vitamin D appears to have a protective effect.

  14. The synthesis of bacteriophage ΦX174-neutralizing protein in a subcellular system obtained from the spleen of ΦX174 immunized rats

    NARCIS (Netherlands)

    Meer, J.H.H. van der; Koningsberger, V.V.

    1965-01-01

    The microsomal fraction of rat spleen was isolated at varying lengths of time after the application of a “booster”-injection of bacteriophage ΦX174 to the animal. Together with the “pH 5-enzyme” fraction, which is obtained routinely from the 100 000 × g spleen-supernatant of non-immunized rats, it f

  15. Maternal milk, but not formula, regulates the immune response to beta-lactoglobulin in allergy-prone rat pups.

    Science.gov (United States)

    Tooley, Katie L; El-Merhibi, Adaweyah; Cummins, Adrian G; Grose, Randall H; Lymn, Kerry A; DeNichilo, Mark; Penttila, Irmeli A

    2009-11-01

    Controversy exists regarding the timing of the introduction of allergic foods into the diet. We investigated the immune response of rat pups exposed to beta-lactoglobulin (BLG), one of the main allergenic proteins in cow milk. Brown Norway allergy-prone rats were allocated into groups: dam-reared and unchallenged (DR), DR challenged with BLG via gavage (11 mg/d), or rats fed via gastric cannula a formula containing BLG (11 mg/d). BLG was given from d 4 of life. Rats were killed at d 10, 14, or 21. Sera were assayed for total IgE, BLG-specific IgG1, and rat mucosal mast cell protease II (RMCPII; indicator of mucosal mast cell degranulation). Ileum was assessed for cytokine mRNA. Mesenteric lymph nodes (MLN) were assessed for forkhead boxP3 (Foxp3) and chemokine (C-C motif) receptor 7 (CCR7) expression by real-time PCR and immunostained for Foxp3(+) CD4(+) regulatory cells. Formula feeding compared with dam-rearing with or without oral BLG challenge resulted in significantly greater serum IgE, BLG-specific IgG1, RMCPII, and intestinal mast cells but reduced MLN Foxp3(+) cells, Foxp3, and CCR7 expression and ileal cytokines, interleukin (IL)-4, IL-10, and interferon-gamma (P < 0.05). Importantly, giving BLG in the presence of maternal milk resulted in an immune response profile similar to that of unchallenged DR rats but with greater Foxp3 and CCR7 mRNA expression and CD4(+) Foxp3(+) cells (P < 0.05). We conclude that introducing an allergenic food with breast milk reduces immunological indicators of an allergic response, whereas introduction during formula feeding generates an allergic response.

  16. The influence of intrauterine exposure to immunosuppressive treatment on changes in the immune system in juvenile Wistar rats

    Directory of Open Access Journals (Sweden)

    Kabat-Koperska J

    2016-07-01

    Full Text Available Joanna Kabat-Koperska,1 Agnieszka Kolasa-Wołosiuk,2 Bartosz Wojciuk,3 Iwona Wojciechowska-Koszko,3 Paulina Roszkowska,3 Barbara Krasnodębska-Szponder,3 Edyta Paczkowska,4 Krzysztof Safranow,5 Edyta Gołembiewska,1 Bogusław Machaliński,4 Kazimierz Ciechanowski1 1Department of Nephrology, Transplantology and Internal Medicine, 2Department of Histology and Embryology, 3Department of Microbiology and Immunological Diagnostics, 4Department of General Pathology, 5Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland Background: In our study, we assessed the impact of immunosuppressive drug combinations on changes in the immune system of juvenile Wistar rats exposed to these drugs during pregnancy. We primarily concentrated on changes in two organs of the immune system – the thymus and the spleen. Methods: The study was conducted on 40 (32+8 female Wistar rats administered full and half dose of drugs, respectively, subjected to regimens commonly used in therapy of human kidney transplant recipients ([1] cyclosporine A, mycophenolate mofetil, and prednisone; [2] tacrolimus, mycophenolate mofetil, and prednisone; [3] cyclosporine A, everolimus, and prednisone. The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy. Results: There were no statistically significant differences in the weight of the thymus and spleen, but changes were found in the results of blood hematology, cytometry from the spleen, and a histologic examination of the examined immune organs of juvenile Wistar rats. In the cytokine assay, changes in the level of interleukine 17 (IL-17 after increasing amounts of concanavaline A were dose-dependent; the increase of IL-17 was blocked after administration of higher doses of immunosuppressive drugs. However, after a reduction of doses, its increase resumed. Conclusion: Qualitative, quantitative, and morphological changes in the immune system of infant

  17. Rapid induction of orthotopic hepatocellular carcinoma in immune-competent rats by non-invasive ultrasound-guided cells implantation

    Directory of Open Access Journals (Sweden)

    Pan Huay-Ben

    2010-07-01

    Full Text Available Abstract Background The fact that prognoses remain poor in patients with advanced hepatocellular carcinoma highlights the demand for suitable animal models to facilitate the development of anti-cancer medications. This study employed a relatively non-invasive approach to establish an orthotopic hepatocellular carcinoma model in immune-competent rats. This was done by ultrasound-guided implantation of cancer cells and the model was used to evaluate the therapeutic efficacy of short-term and low-dose epirubicin chemotherapy. Methods Rat Novikoff hepatoma cells were injected percutaneously into the liver lobes of Sprague-Dawley rats under the guidance of high resolution ultrasound. The implantation rate and the correlation between dissected and ultrasound-measured tumor sizes were evaluated. A similar induction procedure was performed by means of laparotomy in a different group of rats. Pairs of tumor measurement were compared by ultrasound and computerized tomography scan. Rats with a successful establishment of the tumor were divided into the treatment (7-day low-dose epirubicin group and the control group. The tumor sizes were non-invasively monitored by the same ultrasound machine. Blood and tumor tissues from tumor-bearing rats were examined by biochemical and histological analysis respectively. Results Ultrasound-guided implantation of Novikoff hepatoma cells led to the formation of orthotopic hepatocellular carcinoma in 60.4% (55/91 of the Sprague-Dawley rats. Moreover, tumor sizes measured by ultrasound significantly correlated with those measured by calipers after sacrificing the animals (P Conclusions Ultrasound-guided implantation of Novikoff hepatoma cells is an effective means of establishing orthotopic hepatocellular carcinoma in Sprague-Dawley rats. Short-term and low-dose epirubicin chemotherapy had perturbed tumor progression by inducing apoptosis and neovascularization blockade.

  18. Poststroke DNA immunization against neurite growth inhibitors is beneficial to the recovery from local cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    Xingbao Zhu; Jasmine Lee; Jill Wong; Wan Loo Tan; Zhongtang Feng; Tinghua Wang; Zhicheng Xiao; Ivan Ng

    2007-01-01

    BACKGROUND: Inhibitory signals, i.e. neurite growth inhibitors (NGIs), presenting on central nervous system (CNS) myelin have been shown to play a crucial role in inhibiting lesioned axonal sprouting and leading to less functional recovery. Vaccines targeting NGIs may provide multifactorial protection against brain insults by overcoming the inhibitory effects of these NGIs and boosting the body's immune repair mechanisms.OBJECTIVE: To evaluate the effect of poststroke DNA immunization against NGIs on the rehabilitation for sensorimotor function of rat models of local cerebral ischemia.DESIGN: Completely randomized grouping design, and controlled experiment.SETTING: Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute,Singapore.MATERIALS: Sixty adult male Sprague-Dawley rats ranging in age from 45 to 120 days and in weight from 180 to 250 grams were provided by Animal Center of Department of Anatomy, Faculty of Medicine,National University of Singapore. pcDNA3.1(+)-neurite growth inhibitors (pcDNA-NGls) a gift was provided by Dr. Xiao from Department of Clinical Research, Singapore General Hospital, Singapore.METHODS: The experiment was carried out at Brain Injury Research Laboratory, Department of rats were randomized into 3 groups: pcDNA-NGIs group (group A), pcDNA3.1 (+) group (group B) and model group (group C), with 20 rats in each group. Left focal cerebral ischemia (FCI) was permanently induced through middle cerebral artery occlusion (MCAO) with the assistance of an operating microscope.Successful MCAO was determined by a 20% decrease to baseline in the ipsilateral cerebral blood flow. 100 μg of pcDNA-NGIs eluted in phosphate-buffered saline (PBS) was intramuscularly injected into the tibial muscle once a week after MCAO for 6 weeks in group A. As control, pcDNA3.1 (+) was also administrated severity score (mNSS), a composite of motor, sensory, reflex and balance tests, was used to test the sensorimotor deficit. The

  19. How Do Lipids Localize in Lewy Bodies?

    NARCIS (Netherlands)

    Chaudhary, Himanshu; Subramaniam, Vinod; Claessens, Mireille

    2014-01-01

    Lewy bodies are the pathological hallmark of Parkinson's disease (PD). While fibrillar α-synuclein (αS) is the main protein component of Lewy bodies, these structures also contain lipids. To elucidate the presence of lipids in Lewy bodies, we investigated the interaction of lipids with monomeric and

  20. Effect of active immunization against angiotensin II type 1 (AT1) receptor on hypertension & arterial remodelling in spontaneously hypertensive rats (SHR)

    OpenAIRE

    Liu-Dong Li; Miao Tian; Yu-Hua Liao; Zi-Hua Zhou; Fen Wei; Feng Zhu; Min Wang; Bin Wang; Yu-Miao Wei

    2014-01-01

    Background & objectives: a0 ngiotensin II receptor type 1 (AT1) is known to be involved in the pathogenesis of hypertension. t0 his study was undertaken to explore the effect of active immunization against AT1 receptor on blood pressure and small artery remodelling in spontaneously hypertensive rat (SHR). Methods: Male SHR and Wistar rats aged two months were actively immunized with different peptides (ATR12185ͱͲATR10014 and ATR12181) corresponding to particular sequences of rat AT1 recep...

  1. Alterations of intestinal immune function and regulatory effects of L-arginine in experimental severe acute pancreatitis rats

    Institute of Scientific and Technical Information of China (English)

    Shi-Feng Qiao; Tian-Jing Lü; Jia-Bang Sun; Fei Li

    2005-01-01

    AIM: To discuss the changes of intestinal mucosal immune function in rats with experimental severe acute pancreatitis(SAP) and the regulatory effect of L-arginine.METHODS: Male adult Wistar rats were randomly divided into pancreatitis group, sham-operation group, and L-arginine treatment group. Animals were killed at 24, 48, and 72 h after SAP models were developed and specimens were harvested. Endotoxin concentration in portal vein was determined by limulus endotoxin analysis kit. CD3+, CD4+,CD8+ T lymphocytes in intestinal mucosal lamina propria were examined by immunohistochemistry. Secretory immunoglobulin A (SIgA) in cecum feces was examined by radioimmunoassay.RESULTS: Compared to the control group, plasma endotoxin concentration in the portal vein increased, percentage of CD3+ and CD4+ T lymphocyte subsets in the end of intestinal mucosal lamina propria reduced significantly,CD4+/CD8+ ratio decreased, and SIgA concentrations in cecum feces reduced at 24, 48, and 72 h after SAP developed. Compared to SAP group, the L-arginine treatment group had a lower level of plasma endotoxin concentration in the portal vein, a higher CD3+ and CD4+ T lymphocyte percentage in the end of intestinal mucosal lamina propria,an increased ratio of CD4+/CD8+ and a higher SIgA concentration in cecum feces.CONCLUSION: Intestinal immune suppression occurs in the early stage of SAP rats, which may be the main reason for bacterial and endotoxin translocation. L-arginine can improve the intestinal immunity and reduce bacterial and endotoxin translocation in SAP rats.

  2. Lewis and Clark as Naturalists.

    Science.gov (United States)

    Smithsonian Institution, Washington, DC. National Museum of Natural History.

    Intended for use in elementary and high school education, this Web site includes a teacher's guide and three lesson plans. The site contains images of museum specimens, scientific drawings, and field photos of the plant and animal species observed by Meriwether Lewis and William Clark, along with journal excerpts, historical notes, and references…

  3. Chronic orthostatic and antiorthostatic restraint induce neuroendocrine, immune and neurophysiological disorders in rats

    Science.gov (United States)

    Assenmacher, I.; Mekaouche, M.; Maurel, D.; Barbanel, G.; Givalois, L.; Boissin, J.; Malaval, F.; Ixart, G.

    The tail-cast suspension rat model has been developed in ground laboratories interested in space physiology for extensive study of mechanisms causing the pathophysiological syndrome associated with space flights. We used individually-caged male rats to explore the effects of acute and chronic (7d) orthostatic restraint (OR) and head-down anti-orthostatic restraint (AOR) on a series of physiological variables. The acute restraint study showed that (1) the installation of the OR device induced an acute reaction for 2 days, with a substantial rise in ACTH (x2) and CORT (x6), and that (2) the head-down tilt from OR to AOR induced (i) within 10 min and lasting 60 min a 2-fold rise in the intra-cerebro-ventricular pressure (Picv) monitored with an icv telemetric recording system, which receded to normal between 60 and 120 min; and (ii) within 30 min a short-lived 4-fold rise in plasma ACTH and CORT levels. Chronic OR induced (1) the suppression of the diurnal ACTH/CORT rhythm, with increased mean levels, especially for ACTH, (2) a degraded circadian locomotor activity rhythm manifested by a significant reduction in the spectral power of the 24h periodicity and a concomitant emergence of shorter (ultradian) periodicities, (3) an associated, but less pronounced alteration of the diurnal rhythm in body temperature; and (4) a marked increase in baseline plasma levels of IL-1β and an increased reactivity in cytokine release following an E. coli endotoxin (LPS) challenge. AOR induced (1) a similar obliteration of the circadian ACTH/CORT rhythm, (2) the loss of close correlation between ACTH and CORT, (3) a generalized increase in baseline plasma IL-1β levels and (4) more extensive degradation of the arcadian periodicity for both locomotor activity and, to a lesser extent, body temperature, replaced by dominant spectral powers for ultradian periodicities (3 to 10h). In conclusion, both experimental paradigms — but AOR more than OR — caused a blockade of the arcadian

  4. Mortality and Morbidity in Different Immunization Protocols for Experimental Autoimmune Myocarditis in Rats

    DEFF Research Database (Denmark)

    Schmerler, Patrick; Jeuthe, Sarah; O H-Ici, Darach

    2014-01-01

    We aimed to investigate the histological and clinical presentations of EAM induced by different immunization schemes.......We aimed to investigate the histological and clinical presentations of EAM induced by different immunization schemes....

  5. Innate immune reactivity of the liver in rats fed a choline-deficient L-amino-acid-defined diet

    Institute of Scientific and Technical Information of China (English)

    Hideto Kawaratani; Tatsuhiro Tsujimoto; Toshiyuld Kitazawa; Mitsuteru Kitade; Hitoshi Yoshiji; Masahito Uemura; Hiroshi Fukui

    2008-01-01

    AIM:To investigate the innate immune reactivity of tumor necrosis factor-alpha (TNF-α),Toll-like receptor 4 (TLR4),and CD14 in the liver of non-alcoholic steatohepatitis (NASH) model rats.METHODS:Male F344 rats were fed a cholinedeficient L-amino-acid-defined (CDAA) diet.The rats were killed after 4 or 8 wk of the diet,and their livers were removed for immunohistochemical investigation and RNA extraction.The liver specimens were immunostained for TNF-α,TLR4,and CD14.The gene expressions of TNF-a,TLR4,and CD14 were determined by reverse-transcriptase polymerase chain reaction (RT-PCR).Kupffer cells were isolated from the liver by Percoll gradient centrifugation,and were then cultured to measure TNF-α production.RESULTS:The serum and liver levels of TNF-α in the CDAA-fed rats increased significantly as compared with the control group,as did the immunohistochemical values and gene expressions of TNF-α,TLR4,and CD14 with the progression of steatohepatitis.TNF-α production from the isolated Kupffer cells of the CDAAfed rats was elevated by lipopolysaccharide stimulation.CONCLUSION:The expressions of TNF-α,TLR4,and CD14 increased in the NASH model,suggesting that TLR4 and CD14-mediated endotoxin liver damage may also occur in NASH.

  6. Immune functions in the Fisher rat fed beluga whale (Delphinapterus leucas) blubber from the contaminated St. Lawrence estuary

    Energy Technology Data Exchange (ETDEWEB)

    Lapierre, P.; Guise, S. De [Univ. du Quebec, Montreal, Quebec (Canada). Dept. des Sciences Biologiques; Muir, D.C.G. [Freshwater Inst., Winnipeg, Manitoba (Canada); Norstrom, R. [Environment Canada, Hull, Quebec (Canada); Beland, P. [St. Lawrence National Inst. of Ecotoxicology, Montreal, Quebec (Canada); Fournier, M. [Univ. du Quebec, Montreal, Quebec (Canada). Dept. des Sciences Biologiques]|[INRS-Sante, Pointe-Claire, Quebec (Canada)]|[IML, Mont Joli, Quebec (Canada). Dept. of Fisheries and Oceans

    1999-02-01

    In order to assess the immunotoxic potential of food naturally contaminated with PCBs and other organohalogens, Fisher rats were fed a diet in which the lipids originated from the blubber of either a highly polluted St. Lawrence beluga or a relatively uncontaminated Arctic beluga. After a period of 2 months, different immune functions were evaluated, including lymphoblastic transformation, natural killer cell activity, plaque-forming cells, phagocytosis, oxidative burst, and immunophenotyping. For all assays, rats fed at St. Lawrence beluga blubber diet or a mixture of Arctic and St. Lawrence beluga blubber diet were not different from control rats fed a diet containing Arctic beluga blubber. These results are inconsistent with the well-known immunosuppressive effects of organochlorines in numerous species and with the lesions suggestive of organochlorine-related immunosuppression that are observed in St. Lawrence belugas. The lack of observable immunotoxic effects in rats fed contaminated beluga blubber might be explained by antagonistic effects in the organohalogen mixture, by a response specific to the rat, by a strain-related lack of sensitivity to organochlorines, or by insufficient dose due to the shortness of the exposure period or the route of exposure.

  7. Expression patterns and action analysis of genes associated with physiological responses during rat liver regeneration: Innate immune response

    Institute of Scientific and Technical Information of China (English)

    Guang-Wen Chen; Ming-Zhen Zhang; Li-Feng Zhao; Cun-Shuan Xu

    2006-01-01

    AIM: To study the relationship between innate immune response and liver regeneration (LR) at transcriptional level.METHODS: Genes associated with innate immunity response were obtained by collecting the data from databases and retrieving articles. Gene expression changes in rat regenerating liver were detected by rat genome 230 2.0 array.RESULTS: A total of 85 genes were found to be associated with LR. The initially and totally expressed number of genes at the phases of initiation [0.5-4 h after partial hepatectomy (PH)], transition from Go to G1 (4-6 h after PH), cell proliferation (6-66 h after PH),cell differentiation and structure-function reconstruction (66-168 h after PH) was 36, 9, 47, 4 and 36, 26, 78,50, respectively, illustrating that the associated genes were mainly triggered at the initial phase of LR and worked at different phases. According to their expression similarity, these genes were classified into 5 types: 41 up-regulated, 4 predominantly up-regulated, 26 downregulated, 6 predominantly down-regulated, and 8 approximately up/down-regulated genes, respectively.The expression of these genes was up-regulated 350 times and down-regulated 129 times respectively,demonstrating that the expression of most genes was enhanced while the expression of a small number of genes was decreased during LR. Their time relevance was classified into 14 groups, showing that the cellular physiological and biochemical activities during LR were staggered. According to the gene expression patterns,they were classified into 28 types, indicating that the cellular physiological and biochemical activities were diverse and complicated during LR.CONCLUSION: Congenital cellular immunity is enhanced mainly in the forepart, prophase and anaphase of LR while congenital molecular immunity is increased dominantly in the forepart and anaphase of LR. A total of 85 genes associated with LR play an important role in innate immunity.

  8. Nitric oxide synthase inhibitor, aminoguanidine reduces intracerebroventricular colchicine induced neurodegeneration, memory impairments and changes of systemic immune responses in rats.

    Science.gov (United States)

    Sil, Susmita; Ghosh, Tusharkanti; Ghosh, Rupsa; Gupta, Pritha

    2017-02-15

    Intracerebroventricular (i.c.v.) injection of colchicine induces neurodegeneration, memory impairments and changes of some systemic immune responses in rats. Though the role of cox 2 in these colchicine induced changes have been evaluated, the influence of nitric oxide synthase (NOS) remains to be studied. The present study was designed to assess the role of NOS on the i.c.v. colchicine induced neurodegeneration, memory impairments and changes of some systemic immune responses by inhibiting its activity with aminoguanidine. In the present study the impairments of working and reference memories, neurodegeneration (chromatolysis and plaque formation) and changes of neuroinflammatory markers in the hippocampus (increased TNF α, IL 1β, ROS and nitrite) along with changes of serum inflammatory markers (TNF α, IL 1β, ROS and nitrite) and alteration of systemic immune responses (higher phagocytic activity of blood WBC and splenic PMN, higher cytotoxicity and lower leukocyte adhesion inhibition index of splenic MNC) were measured in the intracerebroventricular colchicine injected rats (ICIR). Administration of aminoguanidine (p.o. 30/50mg/kg body weight) to ICIR resulted in recovery of neuroinflammation and partial prevention of neurodegeneration which could be corroborated with the partial recovery of memory impairments in this model. The recovery of serum inflammatory markers and the systemic immune responses in ICIR was also observed after administration of aminoguanidine. Therefore, the present study shows that aminoguanidine can protect the colchicine induced neurodegeneration, memory impairments, and changes of systemic immune systemic responses in ICIR by inhibiting the iNOS. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia.

    Science.gov (United States)

    Duchatel, Ryan J; Jobling, Phillip; Graham, Brett A; Harms, Lauren R; Michie, Patricia T; Hodgson, Deborah M; Tooney, Paul A

    2016-02-01

    Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN(+)) and somatostatin (SST(+)) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12week old offspring of GD10 (n=10) or GD19 polyI:C dams (n=18) compared to controls (n=20). NeuN(+) IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN(+) IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST(+) IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN(+) and SST(+) IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia.

  10. Cadmium-induced immune abnormality is a key pathogenic event in human and rat models of preeclampsia.

    Science.gov (United States)

    Zhang, Qiong; Huang, Yinping; Zhang, Keke; Huang, Yanjun; Yan, Yan; Wang, Fan; Wu, Jie; Wang, Xiao; Xu, Zhangye; Chen, Yongtao; Cheng, Xue; Li, Yong; Jiao, Jinyu; Ye, Duyun

    2016-11-01

    With increased industrial development, cadmium is an increasingly important environmental pollutant. Studies have identified various adverse effects of cadmium on human beings. However, the relationships between cadmium pollution and the pathogenesis of preeclampsia remain elusive. The objective of this study is to explore the effects of cadmium on immune system among preeclamptic patients and rats. The results showed that the cadmium levels in the peripheral blood of preeclamptic patients were significantly higher than those observed in normal pregnancy. Based on it, a novel rat model of preeclampsia was established by the intraperitoneal administration of cadmium chloride (CdCl2) (0.125 mg of Cd/kg body weight) on gestational days 9-14. Key features of preeclampsia, including hypertension, proteinuria, placental abnormalities and small foetal size, appeared in pregnant rats after the administration of low-dose of CdCl2. Cadmium increased immunoglobulin production, mainly angiotensin II type 1-receptor-agonistic autoantibodies (AT1-AA), by increasing the expression of activation-induced cytosine deaminase (AID) in B cells. AID is critical for the maturation of antibody and autoantibody responses. In addition, angiotensin II type 1-receptor-agonistic autoantibody, which emerged recently as a potential pathogenic contributor to PE, was responsible for the deposition of complement component 5 (C5) in kidneys of pregnant rats via angiotensin II type 1 receptor (AT1R) activation. C5a is a fragment of C5 that is released during C5 activation. Selectively interfering with C5a signalling by a complement C5a receptor-specific antagonist significantly attenuated hypertension and proteinuria in Cd-injected pregnant rats. Our results suggest that cadmium induces immune abnormalities that may be a key pathogenic contributor to preeclampsia and provide new insights into treatment strategies of preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Treatment with mPEG-SPA improves the survival of corneal grafts in rats by immune camouflage.

    Science.gov (United States)

    Wang, Shuangyong; Li, Liangliang; Liu, Ying; Li, Chaoyang; Zhang, Min; Wang, Bowen; Huang, Zheqian; Gao, Xinbo; Wang, Zhichong

    2015-03-01

    We investigated the immune camouflage effects of methoxy polyethylene glycol succinimidyl propionate (mPEG-SPA) on corneal antigens and explored a novel approach for reducing corneal antigenicity, thereby decreasing corneal graft rejection. Importantly, this approach did not alter normal local immunity. Corneal grafts were treated with mPEG-SPA 5KD or 20KD (3% W/V), which could shield major histocompatibility antigen class I molecules (RT1-A) of corneal grafts. Skin grafts of Wistar rats were transplanted to SD rats. Then the splenic lymphocytes were isolated from SD rats. Subsequently, the lymphocytes were co-cultured with autologous corneal grafts or untreated corneal grafts and PEGylated grafts treated with mPEG-SPA 5KD or 20KD obtained from the counterpart skin donors, which were used as autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group, respectively. Lymphocyte proliferation was lower in mPEG-SPA 5KD group and mPEG-SPA 20KD group than in the allogeneic control. SD rats with corneal neovascularisation were used as recipients for high-risk corneal transplantation and were randomly divided into four groups: autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group. The recipients received corneal grafts from Wistar rats. Corneal graft survival was prolonged and graft rejection was reduced in the mPEG-SPA 5KD group and the mPEG-SPA 20KD group compared to the allogeneic control. Thus, we think that mPEG-SPA could immunologically camouflage corneal antigens to prolong corneal grafts survival in high-risk transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Protective effect of Radix Astragali injection on immune organs of rats with obstructive jaundice and its mechanism

    Institute of Scientific and Technical Information of China (English)

    Rui-Ping Zhang; Xi-Ping Zhang; Yue-Fang Ruan; Shu-Yun Ye; Hong-Chan Zhao; Qi-Hui Cheng; Di-Jiong Wu

    2009-01-01

    AIM: To observe the protective effect of Radix Astragali injection on immune organs (lymph nodes, spleen and thymus) of rats with obstructive jaundice (OJ) and its mechanism. METHODS: SD rats were randomly divided into sham-operation group, model control group and Radix Astragali treatment group. On days 7, 14, 21 and 28 after operation, mortality rate of rats, pathological changes in immune organs, expression levels of Bax and nuclear factor (NF)-κB p65 proteins, apoptosis indexes and serum tumor necrosis factor (TNF)-α level in spleen and thymus were observed, respectively. spleen and thymus were observed, respectively. RESULTS: Compared to model control group, the number of dead OJ rats in Radix Astragali treatment group decreased ( P > 0.05). The TNF-α level (27.62 ± 12.61 vs 29.55 ± 18.02, 24.61 ± 9.09 vs 31.52 ± 10.95) on days 7 and 21, the pathological severity score for spleen [0.0 (0.0) vs 0.0 (2.0) on days 7 and 14 and for lymph nodes [0.0 (1.0) vs 1.0 (2.0), 1.0 (0.0) vs 2.0 (1.0)] on days 21 and 28, the product staining intensity and positive rate of Bax protein in spleen [0.0 (0.0) vs 1.0 (2.0), 0.0 (1.0) vs 2.0 (1.5) and thymus [0.0 (0.0) vs 1.0 (2.0), 0.0 (1.0) vs 2.0 (1.5)] on days 14 and 28, the apoptotic indexes [0.0 (0.0) vs 0.0 (0.01)] in spleen and thymus [0.0 (0.0) vs 0.0 (0.01) on days 14 and 21 were significantly lower in Radix Astragali treatment group than in model control group ( P < 0.05).CONCLUSION: Radix Astragali has protective effects on immune organs of OJ rats by relieving the pathological changes in immune organs, reducing TNF-α level and inhibiting Bax expression and apoptosis in spleen and thymus.

  13. Effect of Moringa oleifera Lam. seed extract on toluene diisocyanate-induced immune-mediated inflammatory responses in rats.

    Science.gov (United States)

    Mahajan, Shailaja G; Mali, Ravindra G; Mehta, Anita A

    2007-04-01

    Moringa oleifera Lam. is a small tree cultivated throughout India. We have investigated the effect of ethanolic extract of seeds of Moringa oleifera (MOEE, an herbal remedy) on the potential prevention of immune-mediated inflammatory responses in toluene diisocyanate (TDI as antigen)-induced asthma in Wistar rats. Rats were divided into five different groups (n = 8/group): Group-I = unsensitized control; Group-II = TDI control/vehicle; Group-III = dexamethasone (DXM) 2.5 mg/kg; and, Groups IV and V = 100 mg/kg and 200 mg/kg body weight [BW] of MOEE, respectively. All rats (except unsensitized controls) were sensitized by intranasal application of 10% TDI to induce airway hypersensitivity. Animals in Groups II-V were given their respective drug treatment per os from 1 wk prior to initiation of sensitization until the day of final provocation with 5% TDI. After this last challenge, all rats were examined for hyperreactivity symptoms and then sacrificed to determine their total and differential leucocytes in blood and bronchoalveolar (BAL) fluid and levels of TNF proportional, variant, IL-4, and IL-6 in their BAL and serum. Homogenates of one lung lobe from each animal were utilized to assess oxidative stress; a separate lobe underwent histologic examination to assess airway inflammatory status. The results suggest that asthmatic symptoms were found in TDI control rats only, while both MOEE- and DXM-treated rats did not manifest any airway abnormality. In MOEE- and DXM-treated rats, neutrophil and eosinophil levels in the blood were decreased significantly; levels of total cells and each different cell in their BAL fluid were markedly decreased as compared to those in TDI controls. TNF alpha, IL-4, and IL-6 were predominant in serum as well as in BAL fluids in TDI controls, but these levels were reduced significantly by MOEE treatment. The antioxidant activity in relation to antiinflammatory activity of the extract and histopathological observations also reflected a

  14. Development of immune memory to glial brain tumors after tumor regression induced by immunotherapeutic Toll-like receptor 7/8 activation.

    Science.gov (United States)

    Stathopoulos, Apostolis; Pretto, Chrystel; Devillers, Laurent; Pierre, Denis; Hofman, Florence M; Kruse, Carol; Jadus, Martin; Chen, Thomas C; Schijns, Virgil E J C

    2012-05-01

    The efficacy of immunotherapeutic TLR7/8 activation by resiquimod (R848) was evaluated in vivo, in the CNS-1 rat glioma model syngeneic to Lewis rats. The immune treatment was compared with cytotoxic cyclophosphamide chemotherapy, and as well, was compared with the combination cytotoxic and immunotherapeutic treatments. We found that parenteral treatment with the TLR7/8 agonist, resiquimod, eventually induced complete tumor regression of CNS-1 glioblastoma tumors in Lewis rats. Cyclophosphamide (CY) treatment also resulted in dramatic CNS-1 remission, while the combined treatment showed similar antitumor effects. The resiquimod efficacy appeared not to be associated with direct injury to CNS-1 growth, while CY proved to exert tumoricidal cytotoxicity to the tumor cells. Rats that were cured by treatment with the innate immune response modifier resiquimod proved to be fully immune to secondary CNS-1 tumor rechallenge. They all remained tumor-free and survived. In contrast, rats that controlled CNS-1 tumor growth as a result of CY treatment did not develop immune memory, as demonstrated by their failure to reject a secondary CNS-1 tumor challenge; they showed a concomittant outgrowth of the primary tumor upon secondary tumor exposure. Rechallenge of rats that initially contained tumor growth by combination chemo-immunotherapy also failed to reject secondary tumor challenge, indicating that the cytotoxic effect of the CY likely extended to the endogenous memory immune cells as well as to the tumor. These data demonstrate strong therapeutic antitumor efficacy for the immune response modifier resiquimod leading to immunological memory, and suggest that CY treatment, although effective as chemotherapeutic agent, may be deleterious to maintenance of long-term antitumor immune memory. These data also highlight the importance of the sequence in which a multi-modal therapy is administered.

  15. Syngeneic immune response to rat tracheal epithelial cells transformed in vitro by N-methyl-N-nitro-N-nitrosoguanidine

    Energy Technology Data Exchange (ETDEWEB)

    Braslawsky, G.R. (Oak Ridge National Lab., TN); Steele, V.; Kennel, S.J.; Nettesheim, P.

    1981-01-01

    Two cell lines (2-10-1 and 8-10-2) derived by exposure of primary tracheal explants to MNNG in vitro were not tumorigenic in syngeneic F-334 rats or athymic BALb/c (nu/nu) mice at early passage, but became tumorigenic at late passage. These cell lines are therefore suited to study the expression of neoantigens during neoplastic development. Transplantation resistance to late-passage, tumorigenic cells was induced in syngeneic rats using an immunization protocol of repeated cell inoculation and tumour ablation. Spleen cells from such animals were reactive in 20h microcytotoxicity assays against neoplastic cell lines, but unreactive to normal tracheal epithelial cells. Similarly, immune spleen cells co-cultivated in vitro for 6 days with irradiated neoplastic cell lines before assay for microcytotoxicity were strongly reactive, whereas co-cultivation with normal epithelial cells did not stimulate reactivity. Antibody to these neoplastic cell lines was demonstrated in sera of tumor-resistant rats by an indirect radiolabelled-antibody binding test and by indirect immunofluorescence. There was no significant binding to normal tracheal epithelial cell outgrowths.

  16. Effects of aspartame on hsp70, bcl-2 and bax expression in immune organs of Wistar albino rats

    Science.gov (United States)

    Choudhary, Arbind Kumar; Devi, Rathinasamy Sheela

    2016-01-01

    Abstract Aspartame, a “first generation sweetener”, is widely used in a variety of foods, beverages, and medicine. The FDA has determined the acceptable daily intake (ADI) value of aspartame to be 50 mg/kg·day, while the JECFA (Joint FAO/WHO Expert Committee on Food Additives) has set this value at 40 mg/kg of body weight/day. Safety issues have been raised about aspartame due to its metabolites, specifically toxicity from methanol and/or its systemic metabolites formaldehyde and formic acid. The immune system is now recognized as a target organ for many xenobiotics, such as drugs and chemicals, which are able to trigger unwanted apoptosis or to alter the regulation of apoptosis. Our previous studies has shown that oral administration of aspartame [40 mg/(kg·day)] or its metabolites for 90 days increased oxidative stress in immune organs of Wistar albino rats. In this present study, we aimed to clarify whether aspartame consumption over a longer period (90-days) has any effect on the expression of hsp70, bcl-2 and bax at both mRNA transcript and protein expression levels in immune organs. We observed that oral administration of aspartame for 90 days did not cause any apparent DNA fragmentation in immune organs of aspartame treated animals; however, there was a significant increase in hsp70 expression, apart from significant alteration in bcl-2 and bax at both mRNA transcript and protein expression level in the immune organs of aspartame treated animals compared to controls. Hence, the results indicated that hsp70 levels increased in response to oxidative injury induced by aspartame metabolites; however, these metabolites did not induce apoptosis in the immune organs. Furthermore, detailed analyses are needed to elucidate the precise molecular mechanisms involved in these changes.

  17. Effects of aspartame on hsp70, bcl-2 and bax expression in immune organs of Wistar albino rats.

    Science.gov (United States)

    Choudhary, Arbind Kumar; Devi, Rathinasamy Sheela

    2016-09-01

    Aspartame, a "first generation sweetener", is widely used in a variety of foods, beverages, and medicine. The FDA has determined the acceptable daily intake (ADI) value of aspartame to be 50 mg/kg·day, while the JECFA (Joint FAO/WHO Expert Committee on Food Additives) has set this value at 40 mg/kg of body weight/day. Safety issues have been raised about aspartame due to its metabolites, specifically toxicity from methanol and/or its systemic metabolites formaldehyde and formic acid. The immune system is now recognized as a target organ for many xenobiotics, such as drugs and chemicals, which are able to trigger unwanted apoptosis or to alter the regulation of apoptosis. Our previous studies has shown that oral administration of aspartame [40 mg/(kg·day)] or its metabolites for 90 days increased oxidative stress in immune organs of Wistar albino rats. In this present study, we aimed to clarify whether aspartame consumption over a longer period (90-days) has any effect on the expression of hsp70, bcl-2 and bax at both mRNA transcript and protein expression levels in immune organs. We observed that oral administration of aspartame for 90 days did not cause any apparent DNA fragmentation in immune organs of aspartame treated animals; however, there was a significant increase in hsp70 expression, apart from significant alteration in bcl-2 and bax at both mRNA transcript and protein expression level in the immune organs of aspartame treated animals compared to controls. Hence, the results indicated that hsp70 levels increased in response to oxidative injury induced by aspartame metabolites; however, these metabolites did not induce apoptosis in the immune organs. Furthermore, detailed analyses are needed to elucidate the precise molecular mechanisms involved in these changes.

  18. Protective effect of melatonin against propoxur-induced oxidative stress and suppression of humoral immune response in rats.

    Science.gov (United States)

    Suke, Sanvidhan G; Kumar, Achint; Ahmed, Rafat S; Chakraborti, Ayanabha; Tripathi, A K; Mediratta, P K; Banerjee, B D

    2006-04-01

    Effect of melatonin in attenuation of propoxur induced oxidative stress and suppression of humoral immune response was studied in rats. Oral administration of propoxur (10 mg/kg) increased lipid peroxidation in serum after 28 days treatment. Superoxide dismutase, catalase and glutathione were also altered following propoxur exposure. In addition propoxur exposure markedly suppressed humoral immune response as assessed by antibody titre and plaque forming cell assay. Simultaneous treatment with melatonin (5 mg/kg, ip) markedly attenuated the effect of propoxur on (a) lipid peroxidation, (b) oxidative stress parameters and (c) immunotoxicity. Results have been discussed in the light of possible immunopotentiating and antioxidant effects of melatonin to understand the influence of oxidative stress on propoxur induced immunomodulation.

  19. Immunostimulatory effects of the standardized extract of Tinospora crispa on innate immune responses in Wistar Kyoto rats

    Directory of Open Access Journals (Sweden)

    Ahmad W

    2015-06-01

    Full Text Available Waqas Ahmad, Ibrahim Jantan, Endang Kumolosasi, Syed Nasir Abbas Bukhari Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia Abstract: Tinospora crispa (TC has been used in folkloric medicine for the treatment of various diseases and has been reported for several pharmacological activities. However, the effects of TC extract on the immune system are largely unknown. Therefore, the present study was aimed to investigate the immunomodulatory effects of a standardized 80% ethanol extract of the stem of TC on innate immune responses. Male Wistar Kyoto rats were treated daily at 100 mg/kg, 200 mg/kg, and 400 mg/kg doses of the extract for 21 days by oral gavage. The immunomodulatory potential of TC was evaluated by determining its effect on chemotaxis and phagocytic activity of neutrophils isolated from the blood of rats. To further elucidate the mechanism of action, its effects on the proliferation of T- and B-lymphocytes and T-lymphocytes subsets (CD4+ and CD8+ and on the secretion of Th1 and Th2 cytokines were also monitored. The main components of the extracts, syringin and magnoflorine, were identified and quantitatively analyzed in the extracts by using a validated reversed-phase high-performance liquid chromatography method. It was observed that the chemotactic activity of neutrophils obtained from extract-treated rats increased as compared to controls. A dose-dependent increase in the number of migrated cells and phagocytosis activity of neutrophils was observed. Dose-dependent increase was also observed in the T- and B-lymphocytes proliferation stimulated with concanavalin A (5 µg/mL and lipopolysaccharide (10 μg/mL, and was statistically significant at 400 mg/kg (P>0.01. Apart from cell-mediated immune response, the concentrations of Th1 (TNF-α, IL-2, and IFN-γ and Th2 (IL-4 cytokines were significantly increased in sera of rats treated with

  20. Protein deprivation causes reversible impariment of mucosal immune response to cholera toxoid/toxin in rat gut.

    Science.gov (United States)

    Barry, W S; Pierce, N F

    1979-09-06

    Scretory antibodies may be the major defence against mucosal infections, especially those due to viruses and non-invasive pathogens such as Vibrio cholerae and toxinogenic Escherichia coli. The high incidence of mucosal infections in malnourished protein-deficient children may result from defective antibody production, but evidence for this is conflicting. We report here that protein deficiency markedly impairs the mucosal immune reponse to cholera toxiod/toxin (CT), a protein antigen, in rats and that this impairment is rapidly reversed by refeeding.

  1. Immunization with FSHβ fusion protein antigen prevents bone loss in a rat ovariectomy-induced osteoporosis model

    Energy Technology Data Exchange (ETDEWEB)

    Geng, Wenxin; Yan, Xingrong; Du, Huicong; Cui, Jihong; Li, Liwen, E-mail: liven@nwu.edu.cn; Chen, Fulin, E-mail: chenfl@nwu.edu.cn

    2013-05-03

    Highlights: •A GST-FSH fusion protein was successfully expressed in E. coli. •Immunization with GST-FSH antigen can raise high-titer anti-FSH polyclonal sera. •Anti-FSH polyclonal sera can neutralize osteoclastogenic effect of FSH in vitro. •FSH immunization can prevent bone loss in a rat osteoporosis model. -- Abstract: Osteoporosis, a metabolic bone disease, threatens postmenopausal women globally. Hormone replacement therapy (HTR), especially estrogen replacement therapy (ERT), is used widely in the clinic because it has been generally accepted that postmenopausal osteoporosis is caused by estrogen deficiency. However, hypogonadal α and β estrogen receptor null mice were only mildly osteopenic, and mice with either receptor deleted had normal bone mass, indicating that estrogen may not be the only mediator that induces osteoporosis. Recently, follicle-stimulating hormone (FSH), the serum concentration of which increases from the very beginning of menopause, has been found to play a key role in postmenopausal osteoporosis by promoting osteoclastogenesis. In this article, we confirmed that exogenous FSH can enhance osteoclast differentiation in vitro and that this effect can be neutralized by either an anti-FSH monoclonal antibody or anti-FSH polyclonal sera raised by immunizing animals with a recombinant GST-FSHβ fusion protein antigen. Moreover, immunizing ovariectomized rats with the GST-FSHβ antigen does significantly prevent trabecular bone loss and thereby enhance the bone strength, indicating that a FSH-based vaccine may be a promising therapeutic strategy to slow down bone loss in postmenopausal women.

  2. PROTECTIVE EFFECT OF N-ACETYLCYSTIENE AGAINST TITANIUM DIOXIDE NANOPARTICLES MODULATED IMMUNE RESPONSES IN MALE ALBINO RATS

    Directory of Open Access Journals (Sweden)

    Mohamed Mohamed Soliman

    2013-01-01

    Full Text Available The protective effects of N-Acetylcysteine (NAC against orally administered titanium dioxide nanoparticles (TiO2 for 3 months on male albino rats were examined. Adult male albino rats were given saline as a control group, TiO2 (1200 mg kg-1 BW, NAC (100 mg kg-1 BW and co-treatment of NAC and TiO2 as a protective group for 3 months. Blood was assayed for serum changes in GPT, GOT, lipid profiles, cytokines and immunoglobulins profiles. Moreover, spleen was examined for alterations in cytokines expression and histopathology. Administration of TiO2 significantly increased serum levels of GPT, GOT and increased lipid profiles. Administration of NAC to TiO2 rats improved significant changes induced by TiO2 alone. There were an increase in IL-1β and IL-6 secretion in TiO2 administered rats which is normalized by NAC administration. TiO2 administration down regulated IL-8 and IL-10 secretion, while co-administration of rats by NAC together with TiO2 normalized that down regulation. Moreover, TiO2 induced toxicity in spleen that accompanied by a decrease in IgA, IgG and IgM that are normalized by NAC administration. Finally, TiO2 up-regulated IL-1β, IL-6 and TNF-β expression in spleen and NAC administration together with TiO2 normalized cytokines expression. In conclusion, present findings confirmed the protective effect of NAC on TiO2 induced alteration in immune responses in male albino rats.

  3. PROTECTIVE EFFECTS OF PROPOLIS ON GAMMA- IRRADIATED NIGELLA SATIVA EXTRACT INDUCED BLOOD AND IMMUNE CHANGES IN WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Osama Moseilhy Saleh

    2013-01-01

    Full Text Available The present study conducted to test the effect of Nigella Sativa (NS, 5 mg kg-1 of body weight, or γ-irradiated Nigella Sativa (GRNS on the changes of blood component profiles, liver, kidney functions and immune cytokines secretion in male Wistar rats. Moreover, the possible protection by propolis (200 mg kg-1 B. W. on the changes induced by NS and GRNS was examined. Results revealed that both NS and GRNS administration for two weeks induced changes in blood, GPT, GOT and urea levels and co-administration with propolis significantly ameliorated such changes. Also, liver histology showed numerous vacuolar degeneration and fatty changes in γ-irradiated groups which disappeared in presence of propolis. Kidney histology of NS administered rats showed less lymphocytic infiltration, while GRNS groups showed desquamation in the cytoplasm of the renal tubules, hemorrhage in the renal corpuscle and lymphocytic infiltration which disappeared when propolis given together with GRNS. Finally propolis induced protective effect on the changes induced in TNF-α and IL-10 secretion by either NS or GRNS in Wistar rats. In conclusion, the findings of present study clarified the protective effect of propolis on changes induced by γ-irradiated NS on blood, liver, kidney and cytokines changes in Wistar rats.

  4. Inlfuence of Different-Frequency Glucocorticoid Induction on Morphological Structures of Humeri, Soft Tissues and Immune System in Rats

    Institute of Scientific and Technical Information of China (English)

    LI Jian-min; LI Heng

    2016-01-01

    Objective: To explore the influence of different-frequency glucocorticoid (GC) induction on morphological structures of humeri and soft tissues as well as immune system in rats. Methods: A total of 32 speciifc pathogen-free (SPF) SD rats at the age of 3 months were selected and randomly divided into 4 groups, 8 cases in each group. The rats in control group were not given any treatment, while those in low-, moderate- and high-frequency groups were treated with intramuscular injection of dexamethasone 1 mg/kg per time for twice, 4 times and 6 times per week, respectively. All the rats were sacriifced on d30 to measure their body mass and qualities of soft tissues and immune organs, and bone histomorphometry was applied to analyze humeral bone mass and bone structural changes. Results: Compared with control group, there was no change in cancellous bone mass and bone structures of upper humeri in low-frequency group, but serious loss of bone mass, signiifcantly degenerated bone structure, markedly reduced trabecular thickness and number as well as notably increased trabecular separation was all observed in moderate- and high-frequency groups. The size of cortical bones, total size of bone structure, thickness of cortical bones and size percentage of cortical bones in middle humeri reduced apparently, while the size percentage of medullary cavity increased dramatically in high-frequency group. Growth plate thickness of upper humeri decreased in low-, moderate- and high-frequency groups, and the diameters of mastocytes diminished in moderate- and high-frequency groups. Compared with control group, body mass decreased obviously, qualities and indexes of spleen and thymus showed decreasing tendency along with the increase of drug administration frequency in low-, moderate- and high-frequency groups. Conclusion: Low-frequency GC cannot change humeral morphology. The higher the frequency of drug administration is, the more the loss of cancellous bone mass is. When the

  5. Extracellular Adenosine Triphosphate Affects Systemic and Kidney Immune Cell Populations in Pregnant Rats

    NARCIS (Netherlands)

    Spaans, Floor; Melgert, Barbro N.; Borghuis, Theo; Klok, Pieter A.; de Vos, Paul; Bakker, Winston W.; van Goor, Harry; Faas, Marijke

    PROBLEM: Changes in the systemic immune response are found in preeclampsia. This may be related to high extracellular adenosine triphosphate (ATP) levels. The question arose whether ATP could affect immune responses in pregnancy. Previously, we investigated whether ATP affected monocyte activation

  6. Prolactin: does it exert an up-modulation of the immune response in Trypanosoma cruzi-infected rats?

    Science.gov (United States)

    Filipin, Marina Del Vecchio; Brazão, Vânia; Santello, Fabricia Helena; Caetano, Leony Cristina; Toldo, Míriam Paula Alonso; do Prado, José Clóvis

    2011-09-27

    During the course of infection by Trypanosoma cruzi, the host immune system is involved in distinct, complex interactions with the endocrine system, and prolactin (PRL) is one of several hormones involved in immunoregulation. Although intensive studies attempting to understand the mechanisms that underlie Chagas' disease have been undertaken, there are still some pieces missing from this complex puzzle. Because data are scarce concerning the role of PRL involvement in Chagas' disease and taking into account the existence of crosstalk between neuroendocrine hormones and the immune system, the current study evaluates a possible up-regulation of the cellular immune response triggered by PRL in T. cruzi-infected rats and the role of PRL in reversing immunosuppression caused by the parasitic infection. The data shown herein demonstrate that PRL induces the proliferation of T lymphocytes, coupled with an activation of macrophages and the production of nitric oxide (NO), leading to a reduction in the number of blood trypomastigotes during the peak of parasitemia. During the acute phase of T. cruzi infection, an enhancement of both CD3+CD4+ and CD3+CD8+ T cell populations were observed in infected groups, with the highest numbers of these T cell subsets found in the infected group treated with PRL. Because NO is a signaling molecule involved in a number of cellular interactions with components of the immune system and the neuroendocrine system, PRL can be considered an alternative hormone able to up-regulate the host's immune system, consequently lowering the pathological effects of a T. cruzi infection.

  7. Effects of recombinant sCR1 on the immune inflammatory reaction in acute spinal cord injury tissue of rats

    Institute of Scientific and Technical Information of China (English)

    李良满; 朱悦; 范广宇

    2005-01-01

    Objective: To determine the effects of recombinant soluble complement receptor type I (sCR1) on the immune inflammatory reaction in acute spinal cord injury tissue of rats and its protective effects. Results: The motor function of rat in sCR1 group at 3 d, 7 d, and 14 d was obviously better than that in NS group (P<0.01, P<0.01, P<0.01). C3c positive expression in sCR1 group at each time point after injury was obviously less than that in NS group (P<0.01). The myeloperoxidase activity in sCR1 group at each time point after injury was obviously less than that in NS group (P<0.01). Conclusions: Recombinant soluble complement receptor type I (sCR1) can lessen the immune inflammatory reaction in acute spinal cord injury tissue and relieve secondary spinal cord injury by inhibiting the activation of the complement system.

  8. Frustrated Lewis pairs: Design and reactivity

    Indian Academy of Sciences (India)

    Sanjoy Mukherjee; Pakkirisamy Thilagar

    2015-02-01

    The interaction of a Lewis acid with a Lewis base results in the formation of a Lewis acid–base adduct. Understanding Lewis acids and bases is central to conceptualizing chemical interactions and constitutes a major portion of metal–ligand chemistry. Sterically encumbered/constrained Lewis pairs cannot form acid–base adducts, but such ‘Frustrated Lewis Pairs’ (FLPs), with their unquenched electronic demands can be elegantly used to simultaneously react with a third species, resulting in unusual reactivity of small molecules. Such unusual reactions, explored only in the last few years, have found several applications, e.g., heterolytic splitting of H2, activation of small molecules (CO2, N2O, etc.). FLPs have opened new opportunities in synthetic chemistry, covering organic, main group as well as transition metal chemistry. The design strategies adopted for FLP systems and their unique reactivity are discussed here.

  9. Immunosuppressive effects of the standardized extract of Phyllanthus amarus on cellular immune responses in Wistar-Kyoto rats

    Directory of Open Access Journals (Sweden)

    Ilangkovan M

    2015-08-01

    Full Text Available Menaga Ilangkovan, Ibrahim Jantan, Mohamed Ahmed Mesaik, Syed Nasir Abbas BukhariDrug and Herbal Research Center, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, MalaysiaAbstract: Phyllanthus amarus (family: Euphorbiaceae is of immense interest due to its wide spectrum of biological activities. In the present study, the standardized 80% ethanol extract of P. amarus was investigated for its modulatory activity on various cellular immune parameters, including chemotaxis of neutrophils, engulfment of Escherichia coli by neutrophils, and Mac-1 expression, in leukocytes isolated from treated/nontreated Wistar-Kyoto rats. The detailed cell-mediated activity of P. amarus was also investigated, including analysis of the effects on T- and B-cell proliferation and CD4+ and CD8+ T-cell subsets in splenic mononuclear cells, and estimation of serum cytokine production by activated T-cells. The main components of the extract, phyllanthin, hypophyllanthin, corilagin, geraniin, ellagic acid, and gallic acid were identified and quantitatively analyzed in the extracts, using validated reversed-phase high-performance liquid chromatography (HPLC methods. N-formyl-methionyl-leucyl-phenylalanine (fMLP-induced neutrophils isolated from rats administered with the extract of P. amarus, at doses ranging from 100 to 400 mg/kg for 14 days, revealed a significant dose-dependent reduction in neutrophil migration (P<0.05. Similar patterns of inhibition were also observed in phagocytic activity and in fMLP-induced changes in expression of β2 integrin polymorphonuclear neutrophils. The results in P. amarus-treated rats also demonstrated a dose-dependent inhibition of both lipopolysaccharide-stimulated B-cell proliferation and concanavalin A–stimulated T-cell proliferation as compared with sensitized control. At a dose of 400 mg/kg (P<0.01, there was a significant decrease in the (% expression of CD4+ and CD8+ in splenocytes and in serum cytokines of T

  10. Supplementing suckling rats with whey protein concentrate modulates the immune response and ameliorates rat rotavirus-induced diarrhea.

    Science.gov (United States)

    Pérez-Cano, Francisco J; Marín-Gallén, Silvia; Castell, Margarida; Rodríguez-Palmero, María; Rivero, Montserrat; Castellote, Cristina; Franch, Angels

    2008-12-01

    Group A rotaviruses (RV) are the most common causative agents of acute gastroenteritis in children diarrhea incidence from approximately 90% in RV group to approximately 60% in WPC-RV and WPC+LF-RV groups (P immune response against the pathogen.

  11. Effects of combined immune therapy on survival and Th1/rh2 cytokine balance in rat orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    CAO Hui; LIU Hua; WU Zhi-yong

    2007-01-01

    Background The induction of immune tolerance and suppression of allograft rejection has become the focus in the study of liver transplantation. The effect of immune therapy with anti-CD40L mAb alone or in combination with cyclosporine A (CsA) on the recipient survival and Th1/Th2 cytokine profile was studied to elucidate its immunological mechanism and role in rat orthotopic liver transplantation.Methods The model of rat orthotopic liver transplantation was established by modified Kamada's technique.Recipients were divided into group A (control group): SD→SD; group B (group of rejection): SD→Wistar without any treatment; group C: SD→Wistar with CsA monotherapy from day 1 to day 5; and group D: SD→Wistar with CsA from day 1 to day 5 and anti-CD40L mAb on day 0 and day 2. The survival of the recipients in all groups was observed and ELISA technique was used to detect the level of cytokines in peripheral blood on post-transplant day 7.Results The survival period of recipients in groups A (>60 days) and D (>60 days) was significantly longer than that in group B (13.8±2.4 days). The serum levels of interleukin 2 (IL-2) and interferon y in group B were significantly higher than those in other groups; the level of tumor necrosis factor α was higher but not statistically significant. In contrast, the serum levels of IL-4 and IL-10 in group D were elevated more significantly than those in group B (P<0.05).Conclusions Combined immune therapy can prolong the survival of allografts. Increased expression of Th2 cytokines, which is closely related to the induction of tolerance and suppression of rejection, is beneficial to the long-term survival of recipients and allografts.

  12. Expression patterns and action analysis of genes associated with physiological responses during rat liver regeneration: Cellular immune response

    Institute of Scientific and Technical Information of China (English)

    Lian-Xing Zhang; Li-Feng Zhao; An-Shi Zhang; Xiao-Guang Chen; Cun-Shuan Xu

    2006-01-01

    AIM: To study the cellular immune response during rat liver regeneration (LR) at a transcriptional level.METHODS: Genes associated with the cellular immune response were obtained by collecting the data from databases and retrieving articles. Gene expression changes during LR were detected by rat genome 230 2.0 array.RESULTS: A total of 127 genes were found to be associated with LR. The number of initially and totally expressing genes in the initial phase of LR [0.5-4 h after partial hepatectomy (PH)], transition from G0-G1(4-6 h after PH), cell proliferation (6-66 h after PH),cell differentiation and structure-function reconstruction (66-168 h after PH) was 54, 11, 34, 3 and 54, 49, 70, 49 respectively, illustrating that the associated genes were mainly triggered at the initiation of LR, and worked at different phases. According to their expression similarity,these genes were classified into 41 up-regulated, 21 predominantly up-regulated, 41 down-regulated, 14 predominantly down-regulated, 10 similarly up-regulated and down-regulated genes, respectively. The total upand down-regulated expression times were 419 and 274,respectively, demonstrating that the expression of most genes was increased while the expression of a small number of genes was decreased. Their time relevance was classified into 14 groups, showing that the cellular physiological and biochemical activities were staggered during LR. According to the gene expression patterns,they were classified into 21 types, showing the activities were diverse and complicated during LR.CONCLUSION: Antigen processing and presentation are enhanced mainly in the forepart, prophase and anaphase of LR. T-cell activation and antigen elimination are enhanced mainly in the forepart and prophase of LR. A total of 127 genes associated with LR play an important role in cellular immunity.

  13. Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in rats treated with N-acetylcysteine

    Directory of Open Access Journals (Sweden)

    S.G. Suke

    2008-09-01

    Full Text Available The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of phosphamidon-induced oxidative stress and immune dysfunction was evaluated in adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8 animals/group, and treated with phosphamidon, N-acetylcysteine or the combination of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg, an organophosphate insecticide, increased serum malondialdehyde (3.83 ± 0.18 vs 2.91 ± 0.24 nmol/mL; P < 0.05 and decreased erythrocyte superoxide dismutase (567.8 ± 24.36 vs 749.16 ± 102.61 U/gHb; P < 0.05, catalase activity (1.86 ± 0.18 vs 2.43 ± 0.08 U/gHb; P < 0.05 and whole blood glutathione levels (1.25 ± 0.21 vs 2.28 ± 0.08 mg/gHb; P < 0.05 showing phosphamidon-induced oxidative stress. Phosphamidon exposure markedly suppressed humoral immune response as assessed by antibody titer to ovalbumin (4.71 ± 0.51 vs 8.00 ± 0.12 -log2; P < 0.05, and cell-mediated immune response as assessed by leukocyte migration inhibition (25.24 ± 1.04 vs 70.8 ± 1.09%; P < 0.05 and macrophage migration inhibition (20.38 ± 0.99 vs 67.16 ± 5.30%; P < 0.05 response. Phosphamidon exposure decreased IFN-у levels (40.7 ± 3.21 vs 55.84 ± 3.02 pg/mL; P < 0.05 suggesting a profound effect of phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in TNF-α level (64.19 ± 6.0 vs 23.16 ± 4.0 pg/mL; P < 0.05 suggests a contributory role of immunocytes in oxidative stress. Co-administration of N-acetylcysteine (3.5 mmol/kg, orally with phosphamidon attenuated the adverse effects of phosphamidon. These findings suggest that oral N-acetylcysteine treatment exerts protective effect and attenuates free radical injury and immune dysfunction caused by subchronic phosphamidon exposure.

  14. Gene expression changes in immune response pathways following oral administration of tetrabromobisphenol A (TBBPA) in female Wistar Han rats.

    Science.gov (United States)

    Hall, Samantha M; Coulter, Sherry J; Knudsen, Gabriel A; Sanders, J Michael; Birnbaum, Linda S

    2017-04-15

    Tetrabromobisphenol A (TBBPA) is a brominated flame retardant used globally at high volumes, primarily in the epoxy resin of circuit boards. It has been detected in the environment and in humans. The National Toxicology Program found that chronic oral TBBPA treatment of 250mg/kg and higher caused an increased incidence of uterine lesions in female Wistar Han rats. The present laboratory has previously reported changes in gene expression associated with estrogen homeostasis in liver and uterine tissue of adult female Wistar Han rats after five days of gavage with 250mg/kg of TBBPA. Microarray analysis of tissue from these same TBBPA-treated rats was performed to detect additional pathways perturbed by TBBPA. Microarray analysis of uterine tissue detected downregulation of genes in pathways of the immune response following TBBPA treatment. These results, along with validation of associated gene expression changes using droplet digital PCR, are reported here. Our findings suggest mechanisms that may be related to estrogen-mediated immunosuppression. Published by Elsevier B.V.

  15. Immune function and hematology of male cotton rats (Sigmodon hispidus) in response to food supplementation and methionine

    Science.gov (United States)

    Webb, R.E.; Leslie, David M.; Lochmiller, R.L.; Masters, R.E.

    2003-01-01

    We examined effects of supplementation of food quantity and quality (=enhanced methionine) on hematologic and immunologic parameters of wild, but enclosed, adult male cotton rats (Sigmodon hispidus) in north-central Oklahoma. Sheet metal enclosures were stocked with a high density of wild-caught cotton rats (160 animals/ha) and randomly assigned a treatment of no supplementation, mixed-ration supplementation or methionine-enhanced supplementation. Aside from small increases in counts of red blood cells and hematocrit levels, most indices of erythrocytic characteristics were not affected by supplementation with the mixed-ration or enhanced methionine. In contrast, platelet counts were highest in mixed-ration and methionine treatments and counts of total white blood cells were highest with methionine supplementation, albeit relative proportions of different leukocytes did not differ among treatments. Immunologically, neither delayed-type hypersensitivity response nor hemolytic-complement activity differed among treatments. Supplementation of food quantity and quality did not broadly affect hematologic parameters and immune function of male cotton rats, but enhanced platelet and leukocyte counts may confer advantages to overall health. Clarification of the role of such effects on population limitation or regulation requires additional research. ?? 2003 Elsevier Inc. All rights reserved.

  16. Modifications to Ivor Lewis esophagectomy.

    Science.gov (United States)

    David, Elizabeth A; Marshall, M Blair

    2010-11-01

    The surgical approach to esophagectomy is variable. A number of factors are considered when determining the optimal approach to esophagectomy: location and extent of disease, fibrosis, additional patient factors and surgeon preference. One of the disadvantages to some approaches is the need for a change in position, which increases operative time. Also, because typically the abdomen is initially explored, patients may later be deemed unresectable at thoracotomy. We describe time saving modifications to the standard Ivor Lewis esophagectomy that eliminate the need for repositioning and facilitate a stapled end-to-end anastomosis.

  17. Refinement of the Collagen Induced Arthritis Model in Rats by Infrared Thermography

    DEFF Research Database (Denmark)

    Jasemian, Yousef; Deleuran, Bent Winding; Svendsen, Pia

    2011-01-01

    . Methodology: Arthritis was induced with collagen immunization in sixteen Lewis rats. Four of the animals were treated with dexamethasone to function as negative controls. Clinical scores were based on the magnitude of paw edema. The mean temperature of the hind feet (region covering the metatarsus and tarsus......Aims: Collagen induced arthritis in rats is an important model for human rheumatoid arthritis. This study was designed to improve and refine this model by use of infrared thermography by measuring surface temperature of hind feet. Our hypothesis is that the local temperature on the feet correlates...

  18. Pre-stroke DNA immunization against neurite growth inhibitors is beneficial to the recovery from focal cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Inhibitory signals, I.e. Neurite growth inhibitors (NGIs), presenting on central nervous system (CNS) myelin have been shown to play a crucial role in inhibiting lesioned axonal sprouting and leading to less functional recovery. Vaccines targeting NGIs may provide multifactorial protection against brain insults by overcoming the inhibitory effects of these NGIs and boosting the immune repair mechanisms of body.OBJECTIVE: To evaluate the effect of pre-stroke DNA immunization against NGIs on the rehabilitation for sensorimotor function of rat models of focal cerebral ischemia.DESIGN: A completely randomized design, and controlled experiment.SETTING: Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute,Singapore.MATERIALS: Sixty adult male Sprague-Dawley rats ranging in age from 45 to 120 days and in body mass from 180 to 250 g were provided by the Animal Center of Department of Anatomy, Faculty of Medicine,National University of Singapore. pcDNA3.1(+)-neurite growth inhibitors (pcDNA-NGIs) a gift was provided by Dr. Xiao from the Department of Clinical Research, Singapore General Hospital, Singapore.METHODS: The experiment was carried out at Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore from August 2003 to April 2005. ① The involved rats were randomized into 3 groups: model group (group A), pcDNA3.1 (+) group (group B) and pcDNA-NGIs group (group C), with 20 rats in each group. Left focal cerebral ischemia was permanently induced through middle cerebral artery occlusion with the assistance of an operating microscope.Successful middle cerebral artery occlusion was determined by a 20% decrease to baseline in the ipsilateral cerebral blood flow. 100 μ g of pcDNA-NGIs eluted in phosphate-buffered saline (PBS) was intramuscularly injected into the tibial muscle once a week before middle cerebral artery occlusion for 6 weeks in group C. As control, pcDNA3

  19. Drawing Lewis Structures without Anticipating Octets.

    Science.gov (United States)

    Carroll, James Allen

    1986-01-01

    After noting the grounds for labelling structures as incorrect, the guidelines for selecting which Lewis structures are most important for a molecule are introduced. Several examples of appropriate Lewis structures and the fine structural predictions that are possible are included. (JN)

  20. Experimental autoimmune myasthenia gravis may occur in the context of a polarized Th1- or Th2-type immune response in rats

    DEFF Research Database (Denmark)

    Saoudi, A; Bernard, I; Hoedemaekers, A

    1999-01-01

    Experimental autoimmune myasthenia gravis (EAMG) is a T cell-dependent, Ab-mediated autoimmune disease induced in rats by a single immunization with acetylcholine receptor (AChR). Although polarized Th1 responses have been shown to be crucial for the development of mouse EAMG, the role of Th cell...

  1. Prophylactic antibody treatment and intramuscular immunization reduce infectious human rhinovirus 16 load in the lower respiratory tract of challenged cotton rats

    Directory of Open Access Journals (Sweden)

    Jorge C.G. Blanco

    2014-01-01

    Full Text Available Human rhinoviruses (HRV represent the single most important etiological agents of the common cold and are the most frequent cause of acute respiratory infections in humans. Currently the performance of available animal models for immunization studies using HRV challenge is very limited. The cotton rat (Sigmodon hispidus is a well-recognized model for the study of human respiratory viral infections. In this work we show that, without requiring any genetic modification of either the host or the virus, intranasal infection of cotton rats with HRV16 resulted in measurable isolation of infective virus, lower respiratory tract pathology, mucus production, and expression of interferon-activated genes. Intramuscular immunization with live HRV16 generated robust protective immunity that correlated with high serum levels of neutralizing antibodies. In addition, cotton rats treated prophylactically with hyperimmune anti-HRV16 serum were protected against HRV16 intranasal challenge. Finally, protection by immunization was efficiently transferred from mothers to newborn animals resulting in a substantial reduction of infectious virus loads in the lung following intranasal challenge. Overall, our results demonstrate that the cotton rat provides valuable additional model development options for testing vaccines and prophylactic therapies against rhinovirus infection.

  2. On the concept of frustrated Lewis pairs.

    Science.gov (United States)

    Fontaine, Frédéric-Georges; Stephan, Douglas W

    2017-08-28

    In this concept article, we consider the notion of 'frustrated Lewis pairs' (FLPs). While the original use of the term referred to steric inhibition of dative bond formation in a Lewis pair, work in the intervening decade demonstrates the limitation of this simplistic view. Analogies to known transition metal chemistry and the applications in other areas of chemistry are considered. In the light of these findings, we present reflections on the criteria for a definition of the term 'frustrated Lewis pair'. Segregation of the Lewis acid and base and the kinetic nature of FLP reactivity are discussed. We are led to the conclusion that, while an all-inclusive definition of FLP is challenging, the notion of 'FLP chemistry' is more readily recognized.This article is part of the themed issue 'Frustrated Lewis pair chemistry'. © 2017 The Author(s).

  3. Alpha1A-adrenergic receptor-directed autoimmunity induces left ventricular damage and diastolic dysfunction in rats.

    Directory of Open Access Journals (Sweden)

    Katrin Wenzel

    Full Text Available BACKGROUND: Agonistic autoantibodies to the alpha(1-adrenergic receptor occur in nearly half of patients with refractory hypertension; however, their relevance is uncertain. METHODS/PRINCIPAL FINDINGS: We immunized Lewis rats with the second extracellular-loop peptides of the human alpha(1A-adrenergic receptor and maintained them for one year. Alpha(1A-adrenergic antibodies (alpha(1A-AR-AB were monitored with a neonatal cardiomyocyte contraction assay by ELISA, and by ERK1/2 phosphorylation in human alpha(1A-adrenergic receptor transfected Chinese hamster ovary cells. The rats were followed with radiotelemetric blood pressure measurements and echocardiography. At 12 months, the left ventricles of immunized rats had greater wall thickness than control rats. The fractional shortening and dp/dt(max demonstrated preserved systolic function. A decreased E/A ratio in immunized rats indicated a diastolic dysfunction. Invasive hemodynamics revealed increased left ventricular end-diastolic pressures and decreased dp/dt(min. Mean diameter of cardiomyocytes showed hypertrophy in immunized rats. Long-term blood pressure values and heart rates were not different. Genes encoding sarcomeric proteins, collagens, extracellular matrix proteins, calcium regulating proteins, and proteins of energy metabolism in immunized rat hearts were upregulated, compared to controls. Furthermore, fibrosis was present in immunized hearts, but not in control hearts. A subset of immunized and control rats was infused with angiotensin (Ang II. The stressor raised blood pressure to a greater degree and led to more cardiac fibrosis in immunized, than in control rats. CONCLUSIONS/SIGNIFICANCE: We show that alpha(1A-AR-AB cause diastolic dysfunction independent of hypertension, and can increase the sensitivity to Ang II. We suggest that alpha(1A-AR-AB could contribute to cardiovascular endorgan damage.

  4. Quantification of Lewis acid induced Brønsted acidity of protogenic Lewis bases.

    Science.gov (United States)

    Lathem, A Paige; Heiden, Zachariah M

    2017-05-09

    Proton transfer promoted by the coordination of protogenic Lewis bases to a Lewis acid is a critical step in catalytic transformations. Although the acidification of water upon coordination to a Lewis acid has been known for decades, no attempts have been made to correlate the Brønsted acidity of the coordinated water molecule with Lewis acid strength. To probe this effect, the pKa's (estimated error of 1.3 pKa units) in acetonitrile of ten protogenic Lewis bases coordinated to seven Lewis acids containing Lewis acidities varying 70 kcal mol(-1), were computed. To quantify Lewis acid strength, the ability to transfer a hydride (hydride donor ability) from the respective main group hydride was used. Coordination of a Lewis acid to water increased the acidity of the bound water molecule between 20 and 50 pKa units. A linear correlation exhibiting a 2.6 pKa unit change of the Lewis acid-water adduct per ten kcal mol(-1) change in hydride donor ability of the respective main group hydride was obtained. For the ten protogenic Lewis bases studied, the coordinated protogenic Lewis bases were acidified between 10 and 50 pKa units. On average, a ten kcal mol(-1) change in hydride donor ability of the respective main group hydride resulted in about a 2.8 pKa unit change in the Brønsted acidity of the Lewis acid-Lewis base adducts. Since attempts to computationally investigate the pKa of main group dihydrogen complexes were unsuccessful, experimental determination of the first reported pKa of a main group dihydrogen complex is described. The pKa of H2-B(C6F5)3 was determined to be 5.8 ± 0.2 in acetonitrile.

  5. Human and Autologous Adipose-derived Stromal Cells Increase Flap Survival in Rats Independently of Host Immune Response

    DEFF Research Database (Denmark)

    Toyserkani, Navid Mohamadpour; Jensen, Charlotte Harken; Andersen, Ditte Caroline

    2017-01-01

    evaluated after 7 days. RESULTS: The mean survival rates for SVF treatment regardless of human or autologous origin were significantly increased as compared with the control group. Adipose stem/stromal cell and SVF lysate injection did not increase flap survival. Vessel density was increased for human...... and rat SVF and human ASC but not for SVF lysate. Human cells were not detected in the flaps after 7 days. CONCLUSIONS: Flap survival increased with SVF treatment regardless of human or autologous origin, suggesting that increased flap survival is independent of the host immune response. All cell...... injections lead to increased vessel density, but it did not necessarily lead to increased flap survival. Further research should elaborate which molecular events make SVF treatment more efficacious than ASC....

  6. Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis.

    Science.gov (United States)

    Barichello, Tatiana; Ceretta, Renan A; Generoso, Jaqueline S; Moreira, Ana Paula; Simões, Lutiana R; Comim, Clarissa M; Quevedo, João; Vilela, Márcia Carvalho; Zuardi, Antonio Waldo; Crippa, José A; Teixeira, Antônio Lucio

    2012-12-15

    Pneumococcal meningitis is a life-threatening disease characterized by an acute infection affecting the pia matter, arachnoid and subarachnoid space. The intense inflammatory response is associated with a significant mortality rate and neurologic sequelae, such as, seizures, sensory-motor deficits and impairment of learning and memory. The aim of this study was to evaluate the effects of acute and extended administration of cannabidiol on pro-inflammatory cytokines and behavioral parameters in adult Wistar rats submitted to pneumococcal meningitis. Male Wistar rats underwent a cisterna magna tap and received either 10μl of sterile saline as a placebo or an equivalent volume of S. pneumoniae suspension. Rats subjected to meningitis were treated by intraperitoneal injection with cannabidiol (2.5, 5, or 10mg/kg once or daily for 9 days after meningitis induction) or a placebo. Six hours after meningitis induction, the rats that received one dose were killed and the hippocampus and frontal cortex were obtained to assess cytokines/chemokine and brain-derived neurotrophic factor levels. On the 10th day, the rats were submitted to the inhibitory avoidance task. After the task, the animals were killed and samples from the hippocampus and frontal cortex were obtained. The extended administration of cannabidiol at different doses reduced the TNF-α level in frontal cortex. Prolonged treatment with canabidiol, 10mg/kg, prevented memory impairment in rats with pneumococcal meningitis. Although descriptive, our results demonstrate that cannabidiol has anti-inflammatory effects in pneumococcal meningitis and prevents cognitive sequel.

  7. Evaluation of Antioxidant and Immunity-Enhancing Activities of Sargassum pallidum Aqueous Extract in Gastric Cancer Rats

    Directory of Open Access Journals (Sweden)

    Shen-Kang Zhou

    2012-07-01

    Full Text Available The effect of Sargassum pallidum (brown seaweed aqueous extract on the immunity function and antioxidant activities in was studied gastric cancer rats. Treatment with Sargassum pallidum aqueous extract at oral doses 400, 600 or 800 mg/kg body weight was found to provide a dose-dependent protection against N-methyl-N′-nitro-N-nitrosoguanidine (MNNG-induced immunity damage and oxidative injury by enhancing serum interleukin-2 (IL-2, interleukin-4 (IL-4, interleukin-10 (IL-10 levels, decreasing interleukin-6 (IL-6, interleukin-1β (IL-1β, tumor necrosis factor-alpha (TNF-α levels, preserving normal antioxidant enzymes activities, and by inhibiting lipid peroxidation in gastric mucosa. It can be concluded that Sargassum pallidum aqueous extract may enhance the immunity and antioxidant activities in gastric cancer rats.

  8. Widespread alterations in the synaptic proteome of the adolescent cerebral cortex following prenatal immune activation in rats.

    Science.gov (United States)

    Györffy, Balázs A; Gulyássy, Péter; Gellén, Barbara; Völgyi, Katalin; Madarasi, Dóra; Kis, Viktor; Ozohanics, Olivér; Papp, Ildikó; Kovács, Péter; Lubec, Gert; Dobolyi, Árpád; Kardos, József; Drahos, László; Juhász, Gábor; Kékesi, Katalin A

    2016-08-01

    An increasing number of studies have revealed associations between pre- and perinatal immune activation and the development of schizophrenia and autism spectrum disorders (ASDs). Accordingly, neuroimmune crosstalk has a considerably large impact on brain development during early ontogenesis. While a plethora of heterogeneous abnormalities have already been described in established maternal immune activation (MIA) rodent and primate animal models, which highly correlate to those found in human diseases, the underlying molecular background remains obscure. In the current study, we describe the long-term effects of MIA on the neocortical pre- and postsynaptic proteome of adolescent rat offspring in detail. Molecular differences were revealed in sub-synaptic fractions, which were first thoroughly characterized using independent methods. The widespread proteomic examination of cortical samples from offspring exposed to maternal lipopolysaccharide administration at embryonic day 13.5 was conducted via combinations of different gel-based proteomic techniques and tandem mass spectrometry. Our experimentally validated proteomic data revealed more pre- than postsynaptic protein level changes in the offspring. The results propose the relevance of altered synaptic vesicle recycling, cytoskeletal structure and energy metabolism in the presynaptic region in addition to alterations in vesicle trafficking, the cytoskeleton and signal transduction in the postsynaptic compartment in MIA offspring. Differing levels of the prominent signaling regulator molecule calcium/calmodulin-dependent protein kinase II in the postsynapse was validated and identified specifically in the prefrontal cortex. Finally, several potential common molecular regulators of these altered proteins, which are already known to be implicated in schizophrenia and ASD, were identified and assessed. In summary, unexpectedly widespread changes in the synaptic molecular machinery in MIA rats were demonstrated which

  9. Immune system augmentation by glatiramer acetate of peripheral nerve regeneration-crush versus transection models of rat sciatic nerve.

    Science.gov (United States)

    Luria, Shai; Cohen, Avraham; Safran, Ori; Firman, Shimon; Liebergall, Meir

    2013-10-01

    Immune system augmentation, using the antigen glatiramer acetate (GA), which is known to affect cellular immunity, has been shown to have a positive effect on peripheral nerve regeneration. We aimed to compare the effect of GA on the regeneration of crushed versus transected nerves. Wild-type rats underwent crush or transection and repair of the sciatic nerve. They were examined 3 weeks postinjury histologically (axon count) and functionally (tibialis anterior muscle weight and footprint analysis). GA was found to augment regeneration both histologically and functionally. In the transected nerve, a significant increase in axon count distal to the injury site was seen in the GA group versus control. A similar yet statistically insignificant trend was found in the crushed nerve. Improvement was found in the footprint analysis between the GA and control groups in both crush and transected nerve groups. We found improvement in the footprint analysis in the crush versus transection group. GA was found to improve the regeneration of the peripheral nerve. Histologically, this was more pronounced in the transection injury. The discrepancy between the different functional measures examined may be explained by the distance of the reinnervated muscles evaluated from the injury site. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  10. Wound healing treatment by high frequency ultrasound, microcurrent, and combined therapy modifies the immune response in rats

    Directory of Open Access Journals (Sweden)

    Raciele I. G. Korelo

    2016-01-01

    Full Text Available BACKGROUND: Therapeutic high-frequency ultrasound, microcurrent, and a combination of the two have been used as potential interventions in the soft tissue healing process, but little is known about their effect on the immune system. OBJECTIVE: To evaluate the effects of therapeutic high frequency ultrasound, microcurrent, and the combined therapy of the two on the size of the wound area, peritoneal macrophage function, CD4+ and CD8+, T lymphocyte populations, and plasma concentration of interleukins (ILs. METHOD: Sixty-five Wistar rats were randomized into five groups, as follows: uninjured control (C, group 1, lesion and no treatment (L, group 2, lesion treated with ultrasound (LU, group 3, lesion treated with microcurrent (LM, group 4, and lesion treated with combined therapy (LUM, group 5. For groups 3, 4 and 5, treatment was initiated 24 hours after surgery under anesthesia and each group was allocated into three different subgroups (n=5 to allow for the use of the different therapy resources at on days 3, 7 and 14 Photoplanimetry was performed daily. After euthanasia, blood was collected for immune analysis. RESULTS: Ultrasound increased the phagocytic capacity and the production of nitric oxide by macrophages and induced the reduction of CD4+ cells, the CD4+/CD8+ ratio, and the plasma concentration of IL-1β. Microcurrent and combined therapy decreased the production of superoxide anion, nitric oxide, CD4+-positive cells, the CD4+/CD8+ ratio, and IL-1β concentration. CONCLUSIONS: Therapeutic high-frequency ultrasound, microcurrent, and combined therapy changed the activity of the innate and adaptive immune system during healing process but did not accelerate the closure of the wound.

  11. Wound healing treatment by high frequency ultrasound, microcurrent, and combined therapy modifies the immune response in rats

    Science.gov (United States)

    Korelo, Raciele I. G.; Kryczyk, Marcelo; Garcia, Carolina; Naliwaiko, Katya; Fernandes, Luiz C.

    2016-01-01

    BACKGROUND: Therapeutic high-frequency ultrasound, microcurrent, and a combination of the two have been used as potential interventions in the soft tissue healing process, but little is known about their effect on the immune system. OBJECTIVE: To evaluate the effects of therapeutic high frequency ultrasound, microcurrent, and the combined therapy of the two on the size of the wound area, peritoneal macrophage function, CD4+ and CD8+, T lymphocyte populations, and plasma concentration of interleukins (ILs). METHOD: Sixty-five Wistar rats were randomized into five groups, as follows: uninjured control (C, group 1), lesion and no treatment (L, group 2), lesion treated with ultrasound (LU, group 3), lesion treated with microcurrent (LM, group 4), and lesion treated with combined therapy (LUM, group 5). For groups 3, 4 and 5, treatment was initiated 24 hours after surgery under anesthesia and each group was allocated into three different subgroups (n=5) to allow for the use of the different therapy resources at on days 3, 7 and 14 Photoplanimetry was performed daily. After euthanasia, blood was collected for immune analysis. RESULTS: Ultrasound increased the phagocytic capacity and the production of nitric oxide by macrophages and induced the reduction of CD4+ cells, the CD4+/CD8+ ratio, and the plasma concentration of IL-1β. Microcurrent and combined therapy decreased the production of superoxide anion, nitric oxide, CD4+-positive cells, the CD4+/CD8+ ratio, and IL-1β concentration. CONCLUSIONS: Therapeutic high-frequency ultrasound, microcurrent, and combined therapy changed the activity of the innate and adaptive immune system during healing process but did not accelerate the closure of the wound. PMID:26786082

  12. Fish oil-supplemented parenteral nutrition could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis.

    Science.gov (United States)

    Li, Xiaolong; Zhang, Xianxiang; Yang, Enqin; Zhang, Nanyang; Cao, Shougen; Zhou, Yanbing

    2015-09-01

    The objectives were to confirm that intravenous fish oil (FO) emulsions could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis and to explore the mechanisms of these effects. Thirty-six adult male Sprague-Dawley rats were divided into 4 groups randomly. Two days after central venous catheterization, rats were subjected to cecal ligation and puncture to produce abdominal sepsis. Rats were assigned to receive normal saline or total parenteral nutrition (TPN) containing standard soybean oil emulsions or FO-supplemented TPN at the onset of sepsis for 5 days. A sham operation and control treatment were performed in control group rats. Acute lung injury scores, peripheral blood lymphocyte subsets, plasma cytokines, and Foxp3 expression in the spleen were determined. Compared with the normal saline and TPN without FO, FO-supplemented TPN beneficially altered the distributions of the T-lymphocyte subsets and downregulated the acute lung injury scores, plasma cytokines, and expression of Foxp3 due to sepsis. Fish oil-supplemented TPN can decrease acute lung injury scores, alleviate histopathology, reduce the bacterial load in the peritoneal lavage fluid, modulate the lymphocyte subpopulation in the peripheral blood, downregulate Foxp3 expression in the spleen, and reduce plasma cytokines, which means that FO-supplemented TPN can alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis.

  13. Variable immune cell frequencies in peripheral blood of LEW.1AR1-iddm rats over time compared to other congenic LEW strains

    Science.gov (United States)

    Arndt, T; Jörns, A; Hedrich, H-J; Lenzen, S; Wedekind, D

    2014-01-01

    The LEW.1AR1-iddm rat is an animal model of human type 1 diabetes (T1D), which arose through a spontaneous mutation within the major histocompatibility complex (MHC)-congenic background strain LEW.1AR1. The LEW.1AR1-iddm rat is characterized by two phenotypes: diabetes development with a diabetes incidence of 60% and a variable T cell frequency in peripheral blood. In this study the immune cell repertoire of LEW.1AR1-iddm rats was analysed over time from days 30 to 90 of life and compared to the background strain LEW.1AR1 and the LEW rat strain as well as the LEW.1WR1 rat strain. The LEW.1AR1-iddm rats are characterized by a high variability of CD3+, CD4+ and CD8+ T cell frequencies in peripheral blood over time, and the frequency is unique for each animal. The variability within the frequencies resulted in changes of the CD4+ : CD8+ T cell ratio. The other three rat strains studied were characterized by a stable but nevertheless strain-specific T cell frequency resulting in a specific CD4+ : CD8+ T cell ratio. The frequency of natural killer (NK) cells and B cells in LEW.1AR1-iddm rats was increased, with a higher variability compared to the other strains. Only monocytes showed no differences in frequency and variability between all strains studied. These variabilities of immune cell frequencies in the LEW.1AR1-iddm rats might lead to imbalances between autoreactive and regulatory T cells in peripheral blood as a prerequisite for diabetes development. PMID:24628466

  14. Recruitment of hypothalamic orexin neurons after formalin injections in adult male rats exposed to a neonatal immune challenge

    Directory of Open Access Journals (Sweden)

    Erin Jane Campbell

    2015-03-01

    Full Text Available Exposure to early life physiological stressors, such as infection, is thought to contribute to the onset of psychopathology in adulthood. In animal models, injections of the bacterial immune challenge, lipopolysaccharide (LPS, during the neonatal period has been shown to alter both neuroendocrine function and behavioural pain responses in adulthood. Interestingly, recent evidence suggests a role for the lateral hypothalamic peptide orexin in stress and nociceptive processing. However, whether neonatal LPS exposure affects the reactivity of the orexin system to formalin-induced inflammatory pain in later life remains to be determined. Male Wistar rats (n=13 were exposed to either LPS or saline (0.05mg/kg, i.p on postnatal days (PND 3 and 5. On PND 80-97, all rats were exposed to a subcutaneous hindpaw injection of 2.25% formalin. Following behavioural testing, animals were perfused and brains processed for Fos-protein and orexin immunohistochemistry. Rats treated with LPS during the neonatal period exhibited decreased licking behaviours during the interphase of the formalin test, the period typically associated with the active inhibition of pain, and increased grooming responses to formalin in adulthood. Interestingly, these behavioural changes were accompanied by an increase in the percentage of Fos-positive orexin cells in the dorsomedial and perifornical hypothalamus in LPS-exposed animals. Similar increases in Fos-protein were also observed in stress and pain sensitive brain regions that receive orexinergic inputs. These findings highlight a potential role for orexin in the behavioural responses to pain and provide further evidence that early life stress can prime the circuitry responsible for these responses in adulthood.

  15. Evidences for vagus nerve in maintenance of immune balance and transmission of immune information from gut to brain in STM-infected rats

    Institute of Scientific and Technical Information of China (English)

    Xi Wang; Bai-Ren Wang; Xi-Jing Zhang; Zhen Xu; Yu-Qiang Ding; Gong Ju

    2002-01-01

    AIM: To determine whether Salmonella Typhimurium (STM)in gastrointestinal tract can induce the functional activationof brain, whether the vagus nerve involves in signalingimmune information from gastrointestinal tract to brain andhow it influences the immune function under naturalinfection condition.VETHODS: Animal model of gastrointestinal tract infectionin the rat was established by an intubation of SalmonellaTyphimurium (STM) into stomach to mimic the condition ofnatural bacteria infectionSubdiagphragmatic vagotomy wasperformed in some of the animals 28 days before infection.The changes of Fos expression visualized withimmunohistochemistry technique in hypothalamicparaventricular nucleus (PVN) and superaoptic nucleus(SON) were counted. Meanwhile, the percentage and theMean Intensities of Fluorescent (MIFs) of CD4 + and CD8 +T cells in peripheral blood were measured by using flowcytometry (FCM), and the pathological changes in ileumand mesenteric lymph node were observed in HE stainedsections.RESUTLTS: In bacteria-stimulated groups, inflammatorypathological changes were seen in ileum and mesentericlymph node. The percentages of CD4 + T cells in peripheralblood wera decreased from 42 % +4.5 % to34% +4.9 % (P< 0.05) and MIFs of CD8 + T cells were also decreased from2.9 + 0.39 to 2.1 + 0.36 ( P< 0.05) with STM stimulation. Allof them proved that our STM-infection model was reliable.Fos immunoreactive (Fos-ir) cells in PVN and SONincreased significantly with STM stimulation, from 189 + 41 to467+62 (P< 0.05) and from 64+21 to 282± 47 (P< 0.05)individually, which suggested that STM in gastrointestinaltract induced the functional activation of brain.Subdiagphragmatic vagotomy attenuated Fos expression inPVN and SON induced by STM, from 467 ± 62 to 226 ± 45 ( P< 0.05) and from 282 ± 47 to 71 ± 19 ( P < 0.05) individually,and restored the decreased percentages of CD4 ± T cellsinduced by STM from 34 % ± 4.9 % to original level 44 % ± 6.0 % ( P < 0

  16. Experimental Salmonella typhimurium infections in rats. III. Transfer of immunity with primed lymphocyte subpopulations

    DEFF Research Database (Denmark)

    Hougen, H P; Jensen, E T

    1990-01-01

    The protective effect of primed lymphocytes against a lethal dose of Salmonella typhimurium was studied in athymic and euthymic LEW rats. Primed lymphocytes were obtained by inoculating euthymic and thymus-grafted animals with a non-lethal dose of Salmonella typhimurium. Four weeks after...... and athymic rats were injected with different doses of primed pan B, pan T, CD4+ and CD8+ T lymphocytes before inoculation with a lethal bacterial dose. Most of the animals treated with pan B, pan T or CD8+ cells died within two weeks. After treatment with primed CD4+ cells, only six of 39 animals died. Doses...... as low as 10(4) cells from both euthymic or thymus-grafted animals were effective, and athymic and euthymic recipients survived equally well. Four weeks after the infection both athymic and euthymic animals housed very few bacteria and had high antibacterial antibody titres. The percentages of splenic...

  17. Immune responses in rats and sheep induced by a DNA vaccine containing the phosphoglycerate kinase gene of Fasciola hepatica and liver fluke infection.

    Science.gov (United States)

    Wesołowska, Agnieszka; Zawistowska-Deniziak, Anna; Norbury, Luke J; Wilkowski, Przemysław; Januszkiewicz, Kamil; Pyziel, Anna M; Zygner, Wojciech; Wędrychowicz, Halina

    2016-03-01

    Immune responses of rats and sheep following vaccination with cDNA encoding phosphoglycerate kinase of Fasciola hepatica (cDNA-FhPGK/pCMV) and F. hepatica infection were investigated in the present study. cDNA-FhPGK/pCMV vaccinated female Sprague-Dawley rats were better protected by vaccination than their male counterparts - 48% reduction in fluke burden for females and no protection for males when compared with appropriate infection control groups. Moreover, male rats developed marked leukocytosis during the study with higher neutrophil, eosinophil and monocyte responses than females. Additionally, dynamics of eosinophil and monocyte responses varied between sexes. Increased titres of anti-FhPGK IgG1 and IgG2a correlated with the protective effect of vaccination that was observed among female rats. In the case of male sheep, no differences in worm burdens and in the course of the immune response were observed following vaccination. Titres of specific antibodies detected were low, and cellular responses were not significant. Apparently, sheep immune responses induced by cDNA-FhPGK/pCMV vaccination are not effective at controlling F. hepatica infection. Poor immunogenicity of DNA vaccines in large animals is still a major obstacle of this technology that has to be overcome.

  18. The development and use of a drug-induced immunosuppressed rat-model to screen Phela for mechanism of immune stimulation.

    Science.gov (United States)

    Lekhooa, Makhotso Rose; Walubo, Andrew; du Plessis, Jan B; Matsabisa, Motlalepula Gilbert

    2017-07-12

    Phela, is code name for a medicinal product made from four South African traditional medicinal plants (Clerodendrum glabrum E. Mey, Polianthes tuberosa (Linn.), Rotheca myricoides (Hochst.) Steane & Mabb. and Senna occidentalis (L.) Link). All these plants have established traditional use in a wide spectrum of diseases. Phela is under development for use as an immune booster in immunocompromised patients, which includes patients with the human immunodeficiency virus (HIV). Already several studies, both pre-clinical and clinical, have shown that Phela is a safe and effective immune booster. Despite some studies on the action of Phela, the mechanism of action by Phela is still not known. Understanding the mechanism of action will enable safer and effective use of the drug for the right indications. Unfortunately, there is no well characterized test-system for screening products for immune stimulant activity. Therefore, the objective of this study was to use Phela as the test article, to develop and validate a rat-model (test system) by which to screen medicines for immune stimulant activity. First, the batch of Phela used was authenticated by high performance liquid chromatography (HPLC) techniques; analytical methods for the immunosuppressant drugs, cyclosporine A (CsA), cyclophosphamide (CP) and dexamethasone (Dex) were developed and validated; and a slide-A-Lyzer dialysis was used to test for potential interactions in rat plasma of Phela with CsA, CP and Dex. Thereafter, using Sprague Dawley (SD) rats and in separate experiments, the effective dose of Phela in the study animals was determined in a dose ranging study with levamisole, a known immune stimulant as the positive control; the appropriate doses for immunosuppression by CsA, CP and Dex were determined; the time to reach 'established immunosuppression' with each drug was determined (it was also the time for intervention with Phela); and eventually, the effect of Phela on the immune system was tested

  19. [The influence of immunization of rats with BSA-conjugated peptide 269-280 of type 3 melanocortin receptor on the metabolic parameters and thyroid functions].

    Science.gov (United States)

    Derkach, K V; Shpakova, E A; Zharova, O A; Bondareva, V M; Shpakov, A O

    2014-01-01

    One of the approaches to study the role of the brain hormonal signaling systems in the regulation of biochemical and physiological processes is their shutdown using the antibodies generated to peptides corresponding to extracellular regions of receptors. The brain type 3 melanocortin receptors (M3R) play an important role in the central regulation of the metabolism and the endocrine system. However, the influence of prolonged inhibition of M3R on energy metabolism, insulin resistance, and thyroid gland (TG) function is practically not studied. The aim of the study was to investigate the influence of prolonged repeated immunization of male rats with the BSA-conjugated peptide Ala-[Pro-Thr-Asn-Pro-Tyr-Cys-Ile-Cys-Thr-Thr-Ala-His269-280]-Ala (A[269- 280]A) corresponding to the third extracellular loop of M3R on their metabolic parameters and functional activity of TG. 9 months after the first immunization, the weight of rats was reduced and after 12-13 months was significantly lower than in controls. The weight of abdominal and brown adipose tissues, on the contrary, increased. At the same timeline there was an increase in the fasting glucose and insulin levels, and increase of the HOMA-IR index (by 75%) indicating that immunized animals develop insulin resistance. The rats have increased glucose utilization due to an increase of insulin production by pancreatic β-cells. 12 months after the first immunization, the increase of the triglycerides level (by 74%) and the ratio of LDL- and HDL-cholesterol (by 36%) were revealed. 13 months after the start of immunization, the levels of free and total thyroxine and total triiodothyronine significantly decreased. In the TG plasma membranes of immunized rats the weakening adenylyl cyclase stimulating effect of thyroid-stimulating hormone was detected. Thus, long-term decrease in the bra- in M3R activity due to repeated immunization of rats with BSA-conjugated peptide A[269-280]A induces the disturbances of the peripheral

  20. Peripheral Lewy body pathology in Parkinson's disease and incidental Lewy body disease: four cases.

    Science.gov (United States)

    Del Tredici, Kelly; Duda, John E

    2011-11-15

    The accumulation of Lewy pathology (LP) within autonomic nervous system tissues has received increased attention recently as a possible induction site for Lewy neurodegeneration and a possible source of biopsy material for biomarkers of early Parkinson's disease (PD). Here, we describe LP accumulation within various tissues involving peripheral autonomic nervous system neurons in three PD cases and one case of incidental Lewy body disease. Findings highlight the value of examining pathology within functional neuroanatomical systems and particularly the importance of Lewy neurites (LNs) in the pathophysiology of PD.

  1. Abegg, Lewis, Langmuir, and the Octet Rule.

    Science.gov (United States)

    Jensen, William B.

    1984-01-01

    Discusses major events leading to the development of the octet rule. Three conclusions based on the work of Mendeleev, Abegg, Thompson, Kossel, Lewis, and Langmuir are considered as is the debate over the rule's validity. (JN)

  2. Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain

    Institute of Scientific and Technical Information of China (English)

    Yong-min LIU; Sheng-mei ZHU; Kui-rong WANG; Zhi-ying FENG; Qing-lian CHEN

    2008-01-01

    Objective: To evaluate the effects oftramadol on the proinflammatory responses in a rat model of incisional pain by investigating its effects on nociceptive thresholds and serum interleukin-6 (IL-6) and IL-2 levels. Methods: Forty-two male Sprague-Dawley (SD) rats scheduled for plantar incision were randomly divided into 7 groups (n=6 in each group). Rats in Group 1 receiving general anesthesia with no incision were served as control; At 30 min before skin incision, Groups 2~5 were given 5 ml normal saline or 1, 10, and 20 mg/kg tramadol, respectively, intraperitoneally (i.p.); Group 6 received 10 mg/kg tramadol after operation; Group 7 received 10 mg/kg tramadol before incision, followed by 200 μg/kg naloxone after operation. Mechanical allodynia was measured by electronic von Frey filament to evaluate the nociceptive thresholds 1 h before incision, and 1 h and 2 h after operation. Serum IL-6 and IL-2 levels were measured by enzyme-linked immunosorbent assay (ELISA) 2 h after operation. Results: Mechanical thresholds decreased significantly and serum IL-6 level increased significantly after operation in Group 2 compared with control (P<0.01), and these changes were reversed respectively by tramadol in a dose-dependent manner (P<0.05 and P<0.01, respectively). IL-2 level remained unchanged after operation in Group 2, but decreased in Group 3 (P<0.05), then gradually returned to the normal level in Groups 4 and 5. The intraperitoneally injected tramadol (10 and 20 mg/kg) produced a potent and dose-dependent antinocicptive effect on the lesioned paw. The antinocicptive effects of tramadol were partially an-tagonized by naloxone (200 μg/kg), suggesting an additional non-opioid mechanism. Conclusion: The results suggest that tramadol could be a good choice for the treatment of pain under the conditions that immunosuppression may be particularly contraindicated.

  3. Experimental chronic Pseudomonas aeruginosa lung infection in rats. Non-specific stimulation with LPS reduces lethality as efficiently as specific immunization

    DEFF Research Database (Denmark)

    Lange, K H; Hougen, H P; Høiby, N

    1995-01-01

    stimulation of the non-specific defence mechanisms by Escherichia coli lipopolysaccharide (LPS) or P. aeruginosa sonicate, or the acquired specific immune response by vaccination with the same bacterial antigens. One day prior to challenge with P. aeruginosa embedded in alginate beads, rats were stimulated...... to earlier recruitment of PMNs most likely mediated by either cytokines and other chemotactic factors (stimulated group) or the immune response in concert with the complement cascade (vaccinated group). The results of the present and previous vaccination studies show that it is possible to improve survival...

  4. Neurophysiological biomarkers for Lewy body dementias

    OpenAIRE

    Cromarty, Ruth A.; Elder, Greg J.; Graziadio, Sara; Baker, Mark; Bonanni, Laura; Onofrj, Marco; O’Brien, John T.; Taylor, John-Paul

    2016-01-01

    Objective Lewy body dementias (LBD) include both dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD), and the differentiation of LBD from other neurodegenerative dementias can be difficult. Currently, there are few biomarkers which might assist early diagnosis, map onto LBD symptom severity, and provide metrics of treatment response. Traditionally, biomarkers in LBD have focussed on neuroimaging modalities; however, as biomarkers need to be simple, inexpensive and non-...

  5. Long-term function of islets encapsulated in a re-designed alginate microcapsule construct in omentum pouches of immune-competent diabetic rats

    Science.gov (United States)

    Pareta, Rajesh; McQuilling, John P; Sittadjody, Sivanandane; Jenkins, Randy; Bowden, Stephen; Orlando, Giuseppe; Farney, Alan C; Brey, Eric M; Opara, Emmanuel C

    2014-01-01

    Objectives Our study aim was to determine encapsulated islet graft viability in an omentum pouch and the effect of FGF-1 released from our redesigned alginate microcapsules on the function of the graft. Methods Isolated rat islets were encapsulated in an inner core made with 1.5% low-viscosity high-mannuronic acid (LVM) alginate followed by an external layer made with 1.25% low-viscosity high-guluronic acid (LVG) alginate with or without FGF-1, in microcapsules measuring 300 – 400 μm in diameter. The two alginate layers were separated by a perm-selective membrane made with 0.1 % Poly-L-Ornithine (PLO), and the inner LVM core was partially chelated using 55 mM sodium citrate for 2 min. Results A marginal mass of encapsulated islet allografts (~2000 islets/kg) in Streptozotocin-diabetic Lewis rats caused significant reduction in blood glucose levels similar to the effect observed with encapsulated islet isografts. Transplantation of allo-islets co-encapsulated with FGF-1 did not result in better glycemic control, but induced greater body weight maintenance in transplant recipients compared to those that received only allo-islets. Histological examination of the retrieved tissue demonstrated morphologically and functionally intact islets in the microcapsules, with no signs of fibrosis. Conclusion We conclude that the omentum is a viable site for encapsulated islet transplantation. PMID:24681880

  6. Immune protection conferred by recombinant MRLC (myosin regulatory light chain) antigen in TiterMax Gold® adjuvant against experimental fasciolosis in rats.

    Science.gov (United States)

    Henker, Luan C; Schwertz, Claiton I; Lucca, Neuber J; Piva, Manoela M; Prior, Keila C; Baska, Piotr; Norbury, Luke; Januszkiewicz, Kamil; Dezen, Diogenes; Duarte, Marta M M F; Moresco, Rafael N; Bertagnolli da Rosa, Liana; Mendes, Ricardo E

    2017-01-23

    Protection against experimental fasciolosis in rats immunized with recombinant myosin regulatory light chain (MRLC) in TiterMax Gold® adjuvant was assessed. The experimental trial consisted of four groups of 15 animals; group 1 was unimmunized and infected, group 2 was immunized with MRLC in adjuvant and infected, group 3 was infected and immunized with adjuvant only and group 4 was unimmunized and uninfected. Immunization with MRLC in TiterMax Gold® adjuvant (group 2) induced a reduction in fluke burdens of 51.0% (p<0.001) when compared with the adjuvant control group, and 61.5% (p<0.001) when compared with the unimmunized infected controls. There was a reduction in fecal egg output in group 2 of 44.8% and 37.3% compared with group 1 and group 3, respectively; although this difference was not statistically significant. Measurement of cytokine levels revealed higher levels of TNF-alpha and IL-2 as well as lower levels of IL-4 in group 2 during the chronic stage of infection (p<0.05), along with higher levels of IFN-gamma during early stages of infection (p<0.05). These results suggest a mixed Th1/Th2 phenotype immune response; however predominance of Th1 cytokines was observed. Levels of anti-MRLC serum IgG in group 2 were significantly higher than controls at the time of euthanasia (p<0.05). This is the first report of immunization with recombinant MRLC in rats, demonstrating that this antigen significantly reduces fluke burdens, increases the Th1 immune response and encourages further studies to improve the vaccine's efficacy.

  7. Slovene critics on Sinclair Lewis's novels

    Directory of Open Access Journals (Sweden)

    Vanja Avsenak

    2010-12-01

    Full Text Available The purpose of this article is to present the reception of Sinclair Lewis's novels by Slovene critics. Initially, the article focuses on the life and workof Sinclair Lewis, giving special emphasis to social influences that made the author a representative figure in the literary and social world. Thus his works are nowadays to be understood primarily as fiction, but on the other hand also as sociological documents of a social and political situation of the period between the two world wars. Generally, the effect they produce is one of a critical discussion of the nation of the United States. When speaking of the social relevance that Lewis's novels have, it is obvious that his works are the portrayals of Americans and their deficiencies. At the time of their publication Lewis's novels received unfavourable criticism on accountof his overly open pro-European attitude and Slovene critics of the period before World War II emphasise this in much detail. It was precisely this anti-American propaganda in the novels themselves and sincerity on the part of the novelist that won the European critics as well as the readers whenit came to appreciating his works. However, Lewis's view of the Americans, as presented throughout his works, only enhanced his literary credibility as a modern writer. That is why the articles by Slovene critics that appeared after the Second World War, and even more significantly after Lewis's death, almost minutely reflect a more favourable attitude to Sinclair Lewis, which was also the case with foreign literary criticism of the post-war period. Critics still discuss the qualities and flaws of Lewis's novels, but being more lenient they no longer profess that the novels lack in artistic value. They remain, however, primarily relevant as social documents of the pre- and post-war era, which fully presented the American middle-class mentality in America and elsewhere. For this reason, the Nobel Prize for Literature awarded to

  8. Effects of dietary protein type on oxidized cholesterol-induced alteration in age-related modulation of lipid metabolism and indices of immune function in rats.

    Science.gov (United States)

    Minehira, K; Inoue, S; Nonaka, M; Osada, K; Yamada, K; Sugano, M

    2000-01-03

    Exogenous oxidized cholesterol disturbs both lipid metabolism and immune functions. Therefore, it may perturb these modulations with ageing. Effects of the dietary protein type on oxidized cholesterol-induced modulations of age-related changes in lipid metabolism and immune function was examined using differently aged (4 weeks versus 8 months) male Sprague-Dawley rats when casein, soybean protein or milk whey protein isolate (WPI) was the dietary protein source, respectively. The rats were given one of the three proteins in diet containing 0.2% oxidized cholesterols mixture. Soybean protein, as compared with the other two proteins, significantly lowered both the serum thiobarbituric acid reactive substances value and cholesterol, whereas it elevated the ratio of high density lipoprotein-cholesterol/cholesterol in young rats, but not in adult. Moreover, soybean protein, but not casein and WPI, suppressed the elevation of Delta6 desaturation indices of phospholipids in both liver and spleen, particularly in young. On the other hand, WPI, compared to the other two proteins, inhibited the leukotriene B4 production of spleen, irrespective of age. Soybean protein reduced the ratio of CD4(+)/CD8(+) T-cells in splenic lymphocytes. Therefore, the levels of immunoglobulin (Ig)A, IgE and IgG in serum were lowered in rats given soybean protein in both age groups except for IgA in adult, although these observations were not shown in rats given other proteins. Thus, various perturbations of lipid metabolism and immune function caused by oxidized cholesterol were modified depending on the type of dietary protein. The moderation by soybean protein on the change of lipid metabolism seems to be susceptible in young rats whose homeostatic ability is immature. These observations may be exerted through both the promotion of oxidized cholesterol excretion to feces and the change of hormonal release, while WPI may suppress the disturbance of immune function by oxidized cholesterol in

  9. Ferrocene-based Lewis acids and Lewis pairs: Synthesis and structural characterization

    Indian Academy of Sciences (India)

    Pagidi Sudhakar; Pakkirisamy Thilagar

    2013-01-01

    Optically active Lewis acids and Lewis pairs were synthesized and characterized by multinuclear NMR, UV/Vis spectroscopy and elemental analysis. Optical rotation measurements were carried out and the absolute configuration of the new chiral molecules confirmed by single crystal X-ray diffraction.

  10. Respiratory syncytial virus fusion glycoprotein expressed in insect cells form protein nanoparticles that induce protective immunity in cotton rats.

    Directory of Open Access Journals (Sweden)

    Gale Smith

    Full Text Available Respiratory Syncytial Virus (RSV is an important viral agent causing severe respiratory tract disease in infants and children as well as in the elderly and immunocompromised individuals. The lack of a safe and effective RSV vaccine represents a major unmet medical need. RSV fusion (F surface glycoprotein was modified and cloned into a baculovirus vector for efficient expression in Sf9 insect cells. Recombinant RSV F was glycosylated and cleaved into covalently linked F2 and F1 polypeptides that formed homotrimers. RSV F extracted and purified from insect cell membranes assembled into 40 nm protein nanoparticles composed of multiple RSV F oligomers arranged in the form of rosettes. The immunogenicity and protective efficacy of purified RSV F nanoparticles was compared to live and formalin inactivated RSV in cotton rats. Immunized animals induced neutralizing serum antibodies, inhibited virus replication in the lungs, and had no signs of disease enhancement in the respiratory track of challenged animals. RSV F nanoparticles also induced IgG competitive for binding of palivizumab neutralizing monoclonal antibody to RSV F antigenic site II. Antibodies to this epitope are known to protect against RSV when passively administered in high risk infants. Together these data provide a rational for continued development a recombinant RSV F nanoparticle vaccine candidate.

  11. Adolescent olanzapine sensitization is correlated with hippocampal stem cell proliferation in a maternal immune activation rat model of schizophrenia.

    Science.gov (United States)

    Chou, Shinnyi; Jones, Sean; Li, Ming

    2015-08-27

    Previous work established that repeated olanzapine (OLZ) administration in normal adolescent rats induces a sensitization effect (i.e. increased behavioral responsiveness to drug re-exposure) in the conditioned avoidance response (CAR) model. However, it is unclear whether the same phenomenon can be detected in animal models of schizophrenia. The present study explored the generalizability of OLZ sensitization from healthy animals to a preclinical neuroinflammatory model of schizophrenia in the CAR. Maternal immune activation (MIA) was induced via polyinosinic:polycytidylic acid (PolyI:C) administration into pregnant dams. Behavioral assessments of offspring first identified decreased maternal separation-induced pup ultrasonic vocalizations and increased amphetamine-induced hyperlocomotion in animals prenatally exposed to PolyI:C. In addition, repeated adolescent OLZ administration confirmed the generalizability of the sensitization phenomenon. Using the CAR test, adolescent MIA animals displayed a similar increase in behavioral responsiveness after repeated OLZ exposure during both the repeated drug test days as well as a subsequent challenge test. Neurobiologically, few studies examining the relationship between hippocampal cell proliferation and survival and either antipsychotic exposure or MIA have incorporated concurrent behavioral changes. Thus, the current study also sought to reveal the correlation between OLZ behavioral sensitization in the CAR and hippocampal cell proliferation and survival. 5'-bromodeoxyuridine immunohistochemistry identified a positive correlation between the magnitude of OLZ sensitization (i.e. change in avoidance suppression induced by OLZ across days) and hippocampal cell proliferation. The implications of the relationship between behavioral and neurobiological results are discussed.

  12. Passive immunization with LINGO-1 polyclonal antiserum afforded neuroprotection and promoted functional recovery in a rat model of spinal cord injury.

    Science.gov (United States)

    Lv, Jun; Xu, Ru-xiang; Jiang, Xiao-dan; Lu, Xin; Ke, Yi-quan; Cai, Ying-qian; Du, Mou-xuan; Hu, Changchen; Zou, Yu-xi; Qin, Ling-sha; Zeng, Yan-jun

    2010-01-01

    LINGO-1 (leucine-rich repeat and Ig domain-containing, Nogo receptor-interacting protein) is an important component of the NgR receptor complex involved in RhoA activation and axon regeneration. The authors report on passive immunization with LINGO-1 polyclonal antiserum, a therapeutic approach to overcome NgR-mediated growth inhibition after spinal cord injury (SCI). The intrathecally administered high-titer rabbit-derived antiserum can be detected around the injury site within a wide time window; it blocks LINGO-1 in vivo with high molecular specificity. In this animal model, passive immunization with LINGO-1 antiserum significantly decreased RhoA activation and increased neuronal survival. Adult rats immunized in this manner show recovery of certain hindlimb motor functions after dorsal hemisection of the spinal cord. Thus, passive immunotherapy with LINGO-1 polyclonal antiserum may represent a promising repair strategy following acute SCI.

  13. Scales of Lewis basicities toward C-centered Lewis acids (carbocations).

    Science.gov (United States)

    Mayr, Herbert; Ammer, Johannes; Baidya, Mahiuddin; Maji, Biplab; Nigst, Tobias A; Ofial, Armin R; Singer, Thomas

    2015-02-25

    Equilibria for the reactions of benzhydryl cations (Ar2CH(+)) with phosphines, tert-amines, pyridines, and related Lewis bases were determined photometrically in CH2Cl2 and CH3CN solution at 20 °C. The measured equilibrium constants can be expressed by the sum of two parameters, defined as the Lewis Acidity (LA) of the benzhydrylium ions and the Lewis basicity (LB) of the phosphines, pyridines, etc. Least-squares minimization of log K = LA + LB with the definition LA = 0 for (4-MeOC6H4)2CH(+) gave a Lewis acidity scale for 18 benzhydrylium ions covering 18 orders of magnitude in CH2Cl2 as well as Lewis basicities (with respect to C-centered Lewis acids) for 56 bases. The Lewis acidities correlated linearly with the quantum chemically calculated (B3LYP/6-311++G(3df,2pd)//B3LYP/6-31G(d,p) level) methyl anion affinities of the corresponding benzhydrylium ions, which can be used as reference compounds for characterizing a wide variety of Lewis bases. The equilibrium measurements were complemented by isothermal titration calorimetry studies. Rates of SN1 solvolyses of benzhydryl chlorides, bromides, and tosylates derived from E(13-33)(+), i.e., from highly reactive carbocations, correlate excellently with the corresponding Lewis acidities and the quantum chemically calculated methyl anion affinities. This correlation does not hold for solvolyses of derivatives of the better stabilized amino-substituted benzhydrylium ions E(1-12)(+). In contrast, the correlation between electrophilic reactivities and Lewis acidities (or methyl anion affinities) is linear for all donor-substituted benzhydrylium ions E(1-21)(+), while the acceptor-substituted benzhydrylium ions E(26-33)(+) react more slowly than expected from their thermodynamic stabilities. The boundaries of linear rate-equilibrium relationships were thus defined.

  14. Augmentation of anti-tumor activity by immunization with Mycobacterium tuberculosis (Tbc and tuberculin-coupled tumor cells.

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    Yada,Yoshihiko

    1985-04-01

    Full Text Available The anti-tumor effect of immunization with heat-killed Mycobacterium tuberculosis (Tbc and Tuberculin (PPD-coupled syngeneic tumor cells was examined in vivo. Three tumor cell lines were employed. Immunization of Tbc-primed BALB/c mice with PPD-coupled syngeneic Meth-A tumor cells displayed a potent anti-tumor effect on viable Meth-A cells inoculated subcutaneously. Neither PPD-coupled LLC (Lewis Lung Carcinoma cells nor sonicated PPD-coupled Meth-A cells were capable of immunizing these mice. PPD-coupled syngeneic whole tumor cells were indispensable for induction of this tumor-specific resistance. Immunization of Tbc-primed C3H/He mice with PPD-coupled syngeneic MH134 tumor cells did not elicit anti-tumor activity against MH134, but additional pretreatment of mice with cyclophosphamide brought on an anti-tumor effect. Antimetastatic reactivity was investigated in C57BL/6 mice bearing LLC, with a reduction in metastases noted. This antimetastatic effect was observed even when the mice were immunized with PPD-coupled LLC cells three days after removal of the initial tumor. Immunization with Tbc and PPD-coupled Meth-A cells together with intraperitoneal administration of murine or rat interleukin 2 (IL 2 further augmented anti-Meth-A resistance. Murine IL 2 further inhibited tumor growth during the early stage, while rat IL 2 showed an anti-tumor effect throughout the course of tumor growth.

  15. Protective effects of Ligustrazine, Kakonein and Panax Notoginsenoside on the small intestine and immune organs of rats with severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Xi-Ping Zhang; Jun Jiang; Qi-Hui Cheng; QianYe; Wei-Juan Li; Hua Zhu; Jun-Ya Shen

    2011-01-01

    BACKGROUND: Severeacutepancreatitis(SAP)ischaracterized by fatal pathogenic conditions and a high mortality. It is important to study SAP complicated with multiple organ injury. In this study we compared the protective effects of three traditional Chinese medicines (Ligustrazine, Kakonein and Panax Notoginsenoside) on the small intestine and immune organs (thymus, spleen and lymph nodes) of rats with SAP and explored their mechanism of action. METHODS: One hundred forty-four rats with SAP were randomly divided into model control, Ligustrazine-treated, Kakonein-treated, and Panax Notoginsenoside-treated groups (n=36 per group). Another 36 normal rats comprised the sham-operated group. According to the different time points after operation, the experimental rats in each group were subdivided into 3-, 6- and 12-hour subgroups (n=12). At various time points after operation, the mortality rate of rats and pathological changes in the small intestine and immune organs were recorded and the serum amylase levels were measured. RESULTS: Compared to the model control groups, the mortality rates in all treated groups declined and the pathological changes in the small intestine and immune tissues were relieved to different degrees. The serum amylase levels in the three treated groups were significantly lower than those in the model control group at 12 hours. The pathological severity scores for the small intestinal mucosa, thymus and spleen (at 3 and 12 hours) in the Ligustrazine-treated group, for the thymus (at 3 and 12 hours) and spleen (at 3 and 6 hours) in the Kakonein-treated group, and for the thymus (at 3 hours) and spleen (at 3 hours) in the Panax Notoginsenoside-treated group were significantly lower than those in the model control group. The pathological severity scores of the small intestinal mucosa (at 6 and 12 hours) and thymus (at 6 hours) in the Ligustrazine-treated group were significantly lower than those in the Kakonein- and Panax Notoginsenoside

  16. Host stress and immune responses during aerosol challenge of Brown Norway rats with Yersinia pestis

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    Susan T Gater

    2012-11-01

    Full Text Available Inhalation exposure models are becoming the preferred method for the comparative study of respiratory infectious diseases due to their resemblance to the natural route of infection. To enable precise delivery of pathogen to the lower respiratory tract in a manner that imposes minimal biosafety risk, nose-only exposure systems have been developed. Early inhalation exposure technology for infectious disease research grew out of technology used in asthma research where predominantly the Collison nebulizer is used to generate an aerosol by beating a liquid sample against glass. Although infectious aerosol droplets of 1-5µm in size can be generated, the Collison often causes loss of viability. In this work, we evaluate a gentler method for aerosolization of living cells and describe the use of the Sparging Liquid Aerosol Generator (SLAG in a rat pneumonic plague model. The SLAG creates aerosols by continuous dripping of liquid sample on a porous metal disc. We show the generation of 0.5 to 1µm Y. pestis aerosol particles using the SLAG with spray factors typically ranging from 10-7 to 10-8 with no detectable loss of bacterial viability. Delivery of these infectious particles via nose-only exposure led to the rapid development of lethal pneumonic plague. Further, we evaluated the effect of restraint-stress imposed by the nose-only exposure chamber on early inflammatory responses and bacterial deposition. Elevated serum corticosterone which peaked at 2 hrs post-procedure indicated the animals experienced stress as a result of restraint in the nose-only chamber. However, we observed no correlation between elevated corticosterone and the amount of bacterial deposition or inflammation in the lungs. Together these data demonstrate the utility of the SLAG and the nose-only chamber for aerosol challenge of rodents by Y. pestis.

  17. The influence of refractory ceramic fibres on pulmonary morphology, redox and immune system in rats.

    Science.gov (United States)

    Tátrai, Erzsébet; Kováciková, Z; Brózik, M; Six, E; Csík, M; Tulinska, J; Drahos, Agnes; Dám, Annamária

    2006-01-01

    Refractory ceramic fibres (RCF) were studied in male SPRD rats by both in vivo long term sequential and in vitro methods. RCF was administered by single intratracheal instillation and the lungs were examined at the end of months 1, 3 and 6 after exposure. In addition, the direct toxicity of the fibres was examined in a primary culture of alveolar macrophages (AM) and in pneumocytes type II (T2). Pulmonary morphological changes, a number of parameters of the redox system, such as activity of extracellular Cu,Zn/superoxide dismutase (EC-SOD), total glutathione content of the lungs (GSH) and immunoglobulins in bronchoalveolar lavage (IgA, IgG, IgM) and in the blood were measured. The composition of the original RCF and the elemental content of the lung tissue were compared by energy dispersive x-ray analysis (EDXA) before and after exposure. Macrophage alveolitis became confluent and moderate fibrosis developed by the end of month 3, and after 6 months of exposure the intensity decreased to the level of the first month. The RCF did not significantly influence the activity of EC-SOD or the total glutathione content of the lungs. Although aluminium and silicon could be demonstrated by EDXA in the lung tissue at the end of month 3, these elements were no longer detectable by the end of month 6. The RCF decreased IgA significantly in bronchoalveolar lavage (BAL). The main components of RCF induced pulmonary alterations, whereas no significant change could be detected in EC-SOD and GSH. Injuries caused by direct toxicity could be observed in the cell membranes only at the highest concentration. On the basis of these results RCF can be determined as moderately toxic fibres.

  18. Effect of maternal probiotic intervention on HPA axis, immunity and gut microbiota in a rat model of irritable bowel syndrome.

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    Javad Barouei

    Full Text Available OBJECTIVE: To examine whether maternal probiotic intervention influences the alterations in the brain-immune-gut axis induced by neonatal maternal separation (MS and/or restraint stress in adulthood (AS in Wistar rats. DESIGN: Dams had free access to drinking water supplemented with Bifidobacterium animalis subsp lactis BB-12® (3 × 10(9 CFU/mL and Propionibacterium jensenii 702 (8.0 × 10(8 CFU/mL from 10 days before conception until postnatal day (PND 22 (weaning day, or to control ad lib water. Offspring were subjected to MS from PND 2 to 14 or left undisturbed. From PND 83 to 85, animals underwent 30 min/day AS, or were left undisturbed as controls. On PND 24 and 86, blood samples were collected for corticosterone, ACTH and IgA measurement. Colonic contents were analysed for the composition of microflora and luminal IgA levels. RESULTS: Exposure to MS significantly increased ACTH levels and neonatal fecal counts of aerobic and anaerobic bacteria, E. coli, enterococci and clostridia, but reduced plasma IgA levels compared with non-MS animals. Animals exposed to AS exhibited significantly increased ACTH and corticosterone levels, decreased aerobic bacteria and bifidobacteria, and increased Bacteroides and E. coli counts compared to non-AS animals. MS coupled with AS induced significantly decreased anaerobes and clostridia compared with the non-stress adult controls. Maternal probiotic intervention significantly increased neonatal corticosterone levels which persisted until at least week 12 in females only, and also resulted in elevated adult ACTH levels and altered neonatal microflora comparable to that of MS. However, it improved plasma IgA responses, increased enterococci and clostridia in MS adults, increased luminal IgA levels, and restored anaerobes, bifidobacteria and E. coli to normal in adults. CONCLUSION: Maternal probiotic intervention induced activation of neonatal stress pathways and an imbalance in gut microflora. Importantly

  19. Interleukin-1 mediates Alzheimer and Lewy body pathologies

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    Liu Ling

    2006-03-01

    Full Text Available Abstract Background Clinical and neuropathological overlap between Alzheimer's (AD and Parkinson's disease (PD is now well recognized. Such cases of concurrent AD and Lewy body disease (AD/LBD show neuropathological changes that include Lewy bodies (α-synuclein aggregates, neuritic amyloid plaques, and neurofibrillary tangles (hyperphosphorylated tau aggregates. The co-occurrence of these clinical and neuropathological changes suggests shared pathogenic mechanisms in these diseases, previously assumed to be distinct. Glial activation, with overexpression of interleukin-1 (IL-1 and other proinflammatory cytokines, has been increasingly implicated in the pathogenesis of both AD and PD. Methods Rat primary cultures of microglia and cortical neurons were cultured either separately or as mixed cultures. Microglia or cocultures were treated with a secreted fragment (sAPPα of the β-amyloid precursor protein (βAPP. Neurons were treated with IL-1β or conditioned medium from sAPPα-activated microglia, with or without IL-1 receptor antagonist. Slow-release pellets containing either IL-1β or bovine serum albumin (control were implanted in cortex of rats, and mRNA for various neuropathological markers was analyzed by RT-PCR. Many of the same markers were assessed in tissue sections from human cases of AD/LBD. Results Activation of microglia with sAPPα resulted in a dose-dependent increase in secreted IL-1β. Cortical neurons treated with IL-1β showed a dose-dependent increase in sAPPα release, an effect that was enhanced in the presence of microglia. IL-1β also elevated the levels of α-synuclein, activated MAPK-p38, and phosphorylated tau; a concomitant decrease in levels of synaptophysin occurred. Delivery of IL-1β by slow-release pellets elevated mRNAs encoding α-synuclein, βAPP, tau, and MAPK-p38 compared to controls. Finally, human cases of AD/LBD showed colocalization of IL-1-expressing microglia with neurons that simultaneously

  20. Complexation of Nitrous Oxide by Frustrated Lewis Pairs

    NARCIS (Netherlands)

    Otten, Edwin; Neu, Rebecca C.; Stephan, Douglas W.

    2009-01-01

    Frustrated Lewis pairs comprised of a basic yet sterically encumbered phosphine with boron Lewis acids bind nitrous oxide to give intact PNNOB linkages. The synthesis, structure, and bonding of these species are described.

  1. Pavlovian conditioning of morphine-induced alterations of immune status: evidence for opioid receptor involvement.

    Science.gov (United States)

    Coussons-Read, M E; Dykstra, L A; Lysle, D T

    1994-12-01

    Prior work in our laboratory has shown that morphine's immunomodulatory effects can become conditioned to environmental stimuli that predict drug administration. These immune alterations include conditioned changes in natural killer cell activity, interleukin-2 production, and mitogen-induced lymphocyte proliferation. The present study examined the involvement of opioid receptor activity in the establishment and expression of conditioned morphine-induced alterations of immune status. During the training phase of the experiment, Lewis rats received two conditioning sessions during which a subcutaneous injection of 15 mg/kg morphine sulfate was paired with exposure to a distinctive environment. On the test day, animals were re-exposed to the distinctive environment alone prior to sacrifice. Saline or naltrexone (0.3, 1.0, 3.0 or 10.0 mg/kg) was administered during either the training or the test session. Administration of naltrexone prior to training antagonized the development of all of the conditioned alterations of immune status including changes in the mitogenic responsiveness of splenocytes, suppression of natural killer cell activity, and interleukin-2 production by splenocytes. Naltrexone administration prior to testing also was effective in antagonizing the expression of a subset of morphine-induced conditioned alterations in immune status. Taken together, these studies indicate that opioid receptor activity is involved in the establishment of conditioned morphine-induced immune alterations, as well as in the expression of a subset of these conditioned alterations of immune status.

  2. Effects of Melatonin on Morphological and Functional Parameters of the Pineal Gland and Organs of Immune System in Rats During Natural Light Cycle and Constant Illumination.

    Science.gov (United States)

    Litvinenko, G I; Shurlygina, A V; Gritsyk, O B; Mel'nikova, E V; Tenditnik, M V; Avrorov, P A; Trufakin, V A

    2015-10-01

    We studied the response of the pineal gland and organs of the immune system to melatonin treatment in Wistar rats kept under conditions of abnormal illumination regimen. The animals were kept under natural light regimen or continuous illumination for 14 days and then received daily injections of melatonin (once a day in the evening) for 7 days. Administration of melatonin to rats kept at natural light cycle was followed by a decrease in percent ratio of CD4+8+ splenocytes and CD4-8+ thymocytes. In 24-h light with the following melatonin injections were accompanied by an increase in percent rate and absolute amount of CD4+8+ cells in the spleen, and a decrease in percent rate of CD11b/c and CD4-8+ splenocytes. In the thymus amount of CD4-8+ cells increased, and absolute number of CD4+25+ cells reduced. Melatonin significantly decreased lipofuscin concentration in the pineal gland during continuous light. Direction and intensity of effects of melatonin on parameters of cell immunity and state of the pineal gland were different under normal and continuous light conditions. It should be taken into account during using of this hormone for correction of immune and endocrine impairments developing during change in light/dark rhythm.

  3. A DNC function that computes no effectively bi-immune set

    OpenAIRE

    Beros, Achilles A.

    2013-01-01

    In Diagonally Non-Computable Functions and Bi-Immunity, Carl Jockusch and Andrew Lewis proved that every DNC function computes a bi-immune set. They asked whether every DNC function computes an effectively bi-immune set. We construct a DNC function that computes no effectively bi-immune set, thereby answering their question in the negative.

  4. Teaching Beginning Chemistry Students Simple Lewis Dot Structures

    Science.gov (United States)

    Nassiff, Peter; Czerwinski, Wendy A.

    2015-01-01

    Students beginning their initial study of chemistry often have a difficult time mastering simple Lewis dot structures. Textbooks show students how to manipulate Lewis structures by moving valence electron dots around the chemical structure so each atom has an octet or duet. However, an easier method of teaching Lewis structures for simple…

  5. Metal-free electrocatalytic hydrogen oxidation using frustrated Lewis pairs and carbon-based Lewis acids.

    Science.gov (United States)

    Lawrence, Elliot J; Clark, Ewan R; Curless, Liam D; Courtney, James M; Blagg, Robin J; Ingleson, Michael J; Wildgoose, Gregory G

    2016-04-21

    Whilst hydrogen is a potentially clean fuel for energy storage and utilisation technologies, its conversion to electricity comes at a high energetic cost. This demands the use of rare and expensive precious metal electrocatalysts. Electrochemical-frustrated Lewis pairs offer a metal-free, CO tolerant pathway to the electrocatalysis of hydrogen oxidation. They function by combining the hydrogen-activating ability of frustrated Lewis pairs (FLPs) with electrochemical oxidation of the resultant hydride. Here we present an electrochemical-FLP approach that utilises two different Lewis acids - a carbon-based N-methylacridinium cation that possesses excellent electrochemical attributes, and a borane that exhibits fast hydrogen cleavage kinetics and functions as a "hydride shuttle". This synergistic interaction provides a system that is electrocatalytic with respect to the carbon-based Lewis acid, decreases the required potential for hydrogen oxidation by 1 V, and can be recycled multiple times.

  6. Lewis Mumford and the Ecology of Technics.

    Science.gov (United States)

    Strate, Lance; Lum, Casey Man Kong

    2000-01-01

    Examines Lewis Mumford's scholarship and his contribution to the emergence of media ecology as both an intellectual tradition and a theoretical perspective on the study of technology, media, and culture. Focuses on Mumford's epochal historiography of technology, the techno-organicism in his thinking about technology and human development, and his…

  7. Pavlovian conditioning of morphine-induced alterations of immune status: evidence for peripheral beta-adrenergic receptor involvement.

    Science.gov (United States)

    Coussons-Read, M E; Dykstra, L A; Lysle, D T

    1994-09-01

    The present studies examined the involvement of peripheral beta-adrenergic receptor activity in the establishment and expression of conditioned morphine-induced alterations of immune status. Previous work in our laboratory has shown that morphine's immunomodulatory effects can become conditioned to environmental stimuli which predict drug administration. These immune alterations include conditioned changes in natural killer cell activity, interleukin-2 production, and mitogen-induced lymphocyte proliferation. During the training phase of these experiments, Lewis rats received two conditioning sessions during which a subcutaneous injection of 15 mg/kg morphine sulfate was paired with exposure to a distinctive environment. On the test day, rats were reexposed to the conditioned stimulus prior to sacrifice. Saline or nadolol (0.002, 0.02, 0.2, or 2.0 mg/kg) was administered either prior to the training sessions or prior to the test session. Administration of nadolol prior to training did not affect the development of conditioned alterations of immune status. Conversely, nadolol administration prior to testing completely attenuated the expression of a subset of the conditioned morphine-induced changes in immune status. Taken together, these studies suggest that whereas peripheral beta-adrenergic receptor activity is not required for the establishment of conditioned morphine-induced alterations of immune status, it is involved in the expression of a subset of these conditioned immunomodulatory effects.

  8. [EFFECT OF 4-METHYLPYRAZOLE ON IMMUNE RESPONSE, FUNCTION OF Th1 AND Th2 LYMPHOCYTES, AND CYTOKINE CONCENTRATION IN RAT BLOOD AFTER ACUTE METHANOL POISONING].

    Science.gov (United States)

    Zabrodskii, P F; Maslyakov, V V; Gromov, M S

    2016-01-01

    It was established in experiments on noninbred albino rats that the acute intoxication with methanol (1.0 LD50) decreased cellular and humoral immune responses, Th2-lymphocyte activity (to a greater extent as compared to the function of Th1 cells), reduced the blood concentration of immunoregulatory (IFN-g, IL-2, IL-4) and proinflammatory (TNF, IL-1b, IL-6) cytokines on the average by 36.5% (p Methanol antidote 4-methylpyrazole (non-competitive inhibitor of alcohol dehydrogenase) administered upon acute intoxication with methanol at a dose of 1.0 DL50 partially reduces the intoxication-induced suppression of humoral and cellular immune response, activity of T-helper cells, and production of IL-4 and restores blood levels of TNF, IL-1b, IFN-γ, IL-4, IL-2, IL-6 to the control values.

  9. Small interfering RNA therapy against carbohydrate sulfotransferase 15 inhibits cardiac remodeling in rats with dilated cardiomyopathy.

    Science.gov (United States)

    Watanabe, Kenichi; Arumugam, Somasundaram; Sreedhar, Remya; Thandavarayan, Rajarajan A; Nakamura, Takashi; Nakamura, Masahiko; Harima, Meilei; Yoneyama, Hiroyuki; Suzuki, Kenji

    2015-07-01

    Carbohydrate sulfotransferase 15 (CHST15) is a sulfotransferase responsible for biosynthesis of chondroitin sulfate E (CS-E), which plays important roles in numerous biological events such as biosynthesis of proinflammatory cytokines. However, the effects of CHST15 siRNA in rats with chronic heart failure (CHF) after experimental autoimmune myocarditis (EAM) have not yet been investigated. CHF was elicited in Lewis rats by immunization with cardiac myosin, and after immunization, the rats were divided into two groups and treated with either CHST15 siRNA (2μg/week) or vehicle. Age matched normal rats without immunizations were also included in this study. After 7weeks of treatment, we investigated the effects of CHST15 siRNA on cardiac function, proinflammatory cytokines, and cardiac remodeling in EAM rats. Myocardial functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by CHST15 siRNA treatment in rats with CHF compared with that of vehicle-treated CHF rats. CHST15 siRNA significantly reduced cardiac fibrosis, and hypertrophy and its marker molecules (left ventricular (LV) mRNA expressions of transforming growth factor beta1, collagens I and III, and atrial natriuretic peptide) compared with vehicle-treated CHF rats. CHF-induced increased myocardial mRNA expressions of proinflammatory cytokines [interleukin (IL)-6, IL-1β], monocyte chemoattractant protein-1, and matrix metalloproteinases (MMP-2 and -9), and CHST15 were also suppressed by the treatment with CHST15 siRNA. Western blotting study has confirmed the results obtained from mRNA analysis as CHST15 siRNA treated rats expressed reduced levels of inflammatory and cardiac remodeling marker proteins. Our results demonstrate for the first time, that CHST15 siRNA treatment significantly improved LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM.

  10. Early gene expression analysis in 9L orthotopic tumor-bearing rats identifies immune modulation in molecular response to synchrotron microbeam radiation therapy.

    Science.gov (United States)

    Bouchet, Audrey; Sakakini, Nathalie; El Atifi, Michèle; Le Clec'h, Céline; Brauer, Elke; Moisan, Anaïck; Deman, Pierre; Rihet, Pascal; Le Duc, Géraldine; Pelletier, Laurent

    2013-01-01

    Synchrotron Microbeam Radiation Therapy (MRT) relies on the spatial fractionation of the synchrotron photon beam into parallel micro-beams applying several hundred of grays in their paths. Several works have reported the therapeutic interest of the radiotherapy modality at preclinical level, but biological mechanisms responsible for the described efficacy are not fully understood to date. The aim of this study was to identify the early transcriptomic responses of normal brain and glioma tissue in rats after MRT irradiation (400Gy). The transcriptomic analysis of similarly irradiated normal brain and tumor tissues was performed 6 hours after irradiation of 9 L orthotopically tumor-bearing rats. Pangenomic analysis revealed 1012 overexpressed and 497 repressed genes in the irradiated contralateral normal tissue and 344 induced and 210 repressed genes in tumor tissue. These genes were grouped in a total of 135 canonical pathways. More than half were common to both tissues with a predominance for immunity or inflammation (64 and 67% of genes for normal and tumor tissues, respectively). Several pathways involving HMGB1, toll-like receptors, C-type lectins and CD36 may serve as a link between biochemical changes triggered by irradiation and inflammation and immunological challenge. Most immune cell populations were involved: macrophages, dendritic cells, natural killer, T and B lymphocytes. Among them, our results highlighted the involvement of Th17 cell population, recently described in tumor. The immune response was regulated by a large network of mediators comprising growth factors, cytokines, lymphokines. In conclusion, early response to MRT is mainly based on inflammation and immunity which appear therefore as major contributors to MRT efficacy.

  11. Cyprinus carpio Decoction Improves Nutrition and Immunity and Reduces Proteinuria through Nephrin and CD2AP Expressions in Rats with Adriamycin-Induced Nephropathy

    Directory of Open Access Journals (Sweden)

    Yumei Qi

    2012-01-01

    Full Text Available Cyprinus carpio decoction (CCD is a well-known Chinese food medicine formula, accepted widely as a useful therapy in preventing edema and proteinuria caused by renal disease. However, the mechanism underlying this effect remains unclear. The current study investigated the potential mechanism of CCD in alleviating nephropathy induced by adriamycin (ADR in rats. 70  eight-week-old Wistar rats were randomly divided into normal, model, fosinopril, YD, YG groups. All rats except for the normal group received 6.5 mg/kg⋅bw of ADR injection into the vena caudalis once. Different doses of CCD (11.3 and 22.5 g kg-1 were lavaged to rats in YD and YG groups, respectively. Then the serum biochemical values of the total protein (TP, albumin (ALB, blood urea nitrogen (BUN, creatinine (Cr, electrolyte levels, and the urinary protein (UP content in 12 hr urine were measured. Interleukin-4 (IL-4 and interferon (INF-γ were measured by enzyme-like immunosorbent assay (ELISA. The pathomorphological analysis was observed using light and electron microscopy, and the expressions of nephrin and CD2-associated protein (CD2AP in renal tissues were determined by immunohistochemical assay. The results indicated that CCD can relieve ADR-induced nephropathy (ADN by improving the nutrition status, regulating the immunity, and inhibiting proteinuria by increasing nephrin and CD2AP expressions.

  12. Effect of supplementation of different levels of selenium as nanoparticles/sodium selenite on blood biochemical profile and humoral immunity in male Wistar rats

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    S. J. Bunglavan

    2014-12-01

    Full Text Available Aim: To study the effect of supplementation of different levels of selenium as nanoparticles/sodium selenite on blood biochemical profile and humoral immunity in male Wistar rats. Materials and Methods: The experimental research was conducted at Division of Animal Nutrition, Indian Veterinary Research Institute, Izatnagar. 63 male Wistar rats were divided into 9 equal groups on the basis of their mean body weight (BW (124.3±3.1 g BW following completely randomized design. Experimental feeding was similar in all the groups except for the source and level of selenium (Se in the diet. While Group 1 (control was fed a basal diet with no Se supplementation, in Groups 2 and 3, 150 ppb Se was supplemented either as sodium selenite or Se nanoparticles, respectively. In Groups 4, 5, 6 and 7, Se was supplemented as its nanoparticles at 50%, 25%, 12.5% and 6.25% levels respectively i.e. at 75 ppb, 37.5 ppb, 18.75 ppb and 9.375 ppb levels respectively. In Groups 8 and 9, 300 ppb Se was supplemented either as Se nanoparticles or sodium selenite, respectively. Experimental feeding was conducted for a period of 91 days. At the end of the experimental trial, blood samples were collected to analyze the blood serum biochemical profile (serum glucose, serum total protein (TP, serum albumin, serum globulin, serum albumin: globulin ratio [A:G ratio], serum total cholesterol and humoral immunity. Results: The levels of serum glucose, serum TP and serum albumin were comparable (p>0.05 among the nine groups of male Wistar rats. The mean serum total cholesterol was significantly (p<0.001 lowered in all the Se supplemented Wistar rats compared to the control group. The mean serum globulin level was significantly (p<0.05 higher and A:G ratio was significantly (p<0.05 lowered in Group 3 (supplemented with 150 ppb selenium nanoparticles followed by Groups 2, 4, 5, 6, 8, and 9 as compared to the control group. The mean serum antibody titer was significantly (p<0.001 higher

  13. Modulatory effects of levamisole and garlic oil on the immune response of Wistar rats: Biochemical, immunohistochemical, molecular and immunological study.

    Science.gov (United States)

    Mohamed, Essam Hassan; Baiomy, Ahmed Abdel-Aziz; Ibrahim, Zein Shaban; Soliman, Mohamed Mohamed

    2016-09-01

    Levamisole (LEVA) and garlic are prevalent immunomodulators in humans and animals. Therefore, the present study aimed to examine the immunomodulatory effects of LEVA and garlic oil (GO) alone or in combination on the immune response of Wistar rats. A total of 24 male Wistar rats were allocated into four equal groups: Control group, which was given ad libitum access to food and water; and groups 2‑4, which were orally administered LEVA [2.5 mg/kg body weight (BW) every 2 days], GO, (5 ml/kg BW daily), or LEVA plus GO, respectively for 4 consecutive weeks. Serum immunoglobulin (Ig)G and IgM levels were measured using a radial immunodiffusion assay. Serum cytokine levels, including interferon (IFN)-γ, interleukin (IL)-5 and tumor necrosis factor (TNF)-α, were measured using enzyme‑linked immunosorbent assay kits. Total blood counts were measured automatically using a cell counter. Serum lysozyme enzymatic activity was determined by measuring the diameters of the zones of clearance relative to lysozyme. Immunohistochemical detection of CD4 and CD8 was carried out using the streptavidin-biotin-peroxidase method. Furthermore, the mRNA expression levels of IL‑4, IL‑5 and IL‑12 were measured in the leukocytes and thymus gland by semi-quantitative polymerase chain reaction. The results revealed that LEVA increased serum levels of IFN‑γ, IL‑5 and TNF‑α cytokines, whereas co‑administration of LEVA and GO decreased the stimulatory action of LEVA alone. LEVA and GO alone increased the serum levels of IgG, IgM and total blood cell counts, and co‑administration of GO and LEVA inhibited the effects of LEVA. At the cellular level, in the spleen, LEVA increased immunoreactivity of CD4 and CD8, whereas co‑administration of GO with LEVA decreased this strong expression. At the molecular level, in leukocytes, LEVA upregulated the mRNA expression levels of IL‑2, IL‑4 and IL‑5, whereas GO alone downregulated mRNA expression. Co‑administration of

  14. A Biography of Distinguished Scientist Gilbert Newton Lewis (by Edward S. Lewis)

    Science.gov (United States)

    Harris, Reviewed By Harold H.

    1999-11-01

    The Edward Mellen Press: Lewiston, NY, 1998. 114 pp + index. ISBN 0-7734-8284-9. $69.95. There may not be a surname better known to students of chemistry than Lewis, from the Lewis electron-dot diagrams and the Lewis theory of acids and bases. More advanced students may know of the groundbreaking textbook Thermodynamics, by Lewis and Randall. Yet few Americans know much about this remarkable U.S.-born scholar, whose contributions equal those of the greatest scientists. He is a chemist-educator of whom we should be as proud and as well informed as we are of Linus Pauling, who was part of the westward movement of science in this country that G. N. Lewis began, or of the recently deceased Glenn Seaborg, who was one of the many students of Lewis who achieved renown. Gilbert N. Lewis was born in Weymouth, Massachusetts, in 1875, but his family moved to near Lincoln, Nebraska, in 1884. He spent two years at the University of Nebraska, but then moved to Harvard when his father became an executive at Merchants Trust Company in Boston. Young Lewis (then only 17) was also said to have been disappointed with the quality of education in Nebraska, and this may have been part of the impetus for the family's move east. After earning his baccalaureate at Harvard, he taught for a year at Phillips Andover Academy before returning to Harvard to study for his doctorate, which he completed 100 years ago, in 1899, under T. W. Richards. Lewis's doctoral work was on the thermodynamics of zinc and cadmium amalgams. At that time, physical chemistry was only beginning to achieve recognition as a branch of science, and its boundaries were ill defined. Edward Lewis quotes his father as often saying, "Physical chemistry is anything interesting." Like many chemists of his time, Lewis went to Europe to complete his preparation for a career; he was in the laboratories of Ostwald in Leipzig and Nernst in Göttingen in 1900-1901. On his return to the United States, he was an instructor at Harvard

  15. Ermakov–Lewis invariants and Reid systems

    Energy Technology Data Exchange (ETDEWEB)

    Mancas, Stefan C., E-mail: stefan.mancas@erau.edu [Department of Mathematics, Embry-Riddle Aeronautical University, Daytona Beach, FL 32114-3900 (United States); Rosu, Haret C., E-mail: hcr@ipicyt.edu.mx [IPICyT, Instituto Potosino de Investigacion Cientifica y Tecnologica, Camino a la presa San José 2055, Col. Lomas 4a Sección, 78216 San Luis Potosí, S.L.P. (Mexico)

    2014-06-13

    Reid's mth-order generalized Ermakov systems of nonlinear coupling constant α are equivalent to an integrable Emden–Fowler equation. The standard Ermakov–Lewis invariant is discussed from this perspective, and a closed formula for the invariant is obtained for the higher-order Reid systems (m≥3). We also discuss the parametric solutions of these systems of equations through the integration of the Emden–Fowler equation and present an example of a dynamical system for which the invariant is equivalent to the total energy. - Highlights: • Reid systems of order m are connected to Emden–Fowler equations. • General expressions for the Ermakov–Lewis invariants both for m=2 and m≥3 are obtained. • Parametric solutions of the Emden–Fowler equations related to Reid systems are obtained.

  16. Rendezvous, un juego de Lewis Carroll

    Directory of Open Access Journals (Sweden)

    José Manuel Sánchez Muñoz

    2011-10-01

    Full Text Available Todos en mayor o menor medida asociamos el nombre de Lewis Carrolla la literatura, sobre todo a la de temática infantil, con títulos a sus espaldas como Alicia en el País de las Maravillas, Alicia a través del espejo, o La Caza del Snark. Pero además de literato, Lewis Carrol fue un hombre con bastantes inquietudes en torno a la matemática, la lógica y el pensamiento filosófico. Pero no todo el mundo es conocedor de su faceta como creativo en el campo de los juegos. Rendezvous es una de sus más sorprendentes invenciones,un juego de inteligencia para todos los públicos, cuyas directrices hacen de él un entretenimiento bastante original.

  17. Rendezvous, un juego de Lewis Carroll

    OpenAIRE

    José Manuel Sánchez Muñoz

    2011-01-01

    Todos en mayor o menor medida asociamos el nombre de Lewis Carrolla la literatura, sobre todo a la de temática infantil, con títulos a sus espaldas como Alicia en el País de las Maravillas, Alicia a través del espejo, o La Caza del Snark. Pero además de literato, Lewis Carrol fue un hombre con bastantes inquietudes en torno a la matemática, la lógica y el pensamiento filosófico. Pero no todo el mundo es conocedor de su faceta como creativo en el campo de los juegos. Rendezvous es una de sus más...

  18. The Critical Reception of Lewis Nordan

    DEFF Research Database (Denmark)

    Bjerre, Thomas Ærvold

    2010-01-01

    The essay covers the critical reception of Mississippi-writer Lewis Nordan from his debut in 1983 to the boost in scholarly attention in the new millennium. The essay covers newspaper reviews but pays particular attention to the many academic essays that have placed Nordan as a writer in the sout...... in the southern literary tradition and have highlighted themes such as magical realism, the grotesque, race relations, music, and gender....

  19. Effect of concanavalin A (Con-A) on the hormone production of the unicellular Tetrahymena and the immune cells of the rat. A comparative study.

    Science.gov (United States)

    Csaba, György; Pállinger, Eva

    2008-01-01

    Tetrahymena populations were treated with 10(-15) g ml(-1) or 10(-6) g ml(-1) concanavalin-A (Con-A) in tryptone-yeast medium for 1 h. Rat peritoneal immune cells (mast cells, lymphocytes, monocyte-granulocyte group) were also treated with 10(-6) g ml(-1) Con-A, for 1 h. The cells' hormone (ACTH, histamine, serotonin, endorphin, triiodothyronine (T(3))) content was measured by using immunocytochemistry and flow cytometry. The extremely low dose of Con-A universally and significantly elevated the hormone contents, while the result of higher dose was uncertain. In the immune cells, Con-A significantly decreased the ACTH level in each cell type and histamine level in mast cells. The results demonstrate the very high sensitivity of Tetrahymena receptors for a non-hormone (lectin) molecule, which can bind to the insulin receptors and mimics the effect of insulin. The results also show that Tetrahymena receptors are more sensitive to lower concentrations of molecules than to higher ones. The universal hormone-production stimulating effect of Con-A-which is observed in Tetrahymena-is specified in rat.

  20. [Interrelations of pineal gland morpho-functional indices and immune system organs in rats exposed to natural illumination regime and continuous illumination].

    Science.gov (United States)

    Litvinenko, G I; Shurlygina, A V; Gritsyk, O B; Mel'nikova, E V; Avrorov, P A; Tendinitnik, M V; Trufakin, V A

    2014-01-01

    The objective of this investigation was to determine the complex response of the pineal gland (PG) and of the organs of the immune system in Wistar rats in response to a violation of the illumination regime in the experiment. Animals were kept under natural light regime and continuous illumination for 14 days. After that rats were sacrificed and the mass of the body, PG, gonads, thymus and spleen was measured. Thymus and spleen cell subpopulations were determined by flow cytometry. The lipofuscin content in PG was determined by measuring an autofluorescence intensity in frozen tissue sections in the wavelength range of 505-545 nm using a confocal laser scanning microscope LSM 510 META (Carl Zeiss). The correlation analysis showed an increase in the amount and the change of sign and direction of relations between the indices of the state of PG and the immune system. This indicates the up-regulation of the intensity of inter-system relationships and the change of migration and differentiation vector of immunocompetent cells.

  1. Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon

    Science.gov (United States)

    Bettini, Sarah; Boutet-Robinet, Elisa; Cartier, Christel; Coméra, Christine; Gaultier, Eric; Dupuy, Jacques; Naud, Nathalie; Taché, Sylviane; Grysan, Patrick; Reguer, Solenn; Thieriet, Nathalie; Réfrégiers, Matthieu; Thiaudière, Dominique; Cravedi, Jean-Pierre; Carrière, Marie; Audinot, Jean-Nicolas; Pierre, Fabrice H.; Guzylack-Piriou, Laurence; Houdeau, Eric

    2017-01-01

    Food-grade titanium dioxide (TiO2) containing a nanoscale particle fraction (TiO2-NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing concerns that daily oral TiO2-NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer’s patches (PP) as observed with the TiO2-NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO2 treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment. In all TiO2-treated rats, stimulation of immune cells isolated from PP showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased. E171 or NM-105 for one week did not initiate intestinal inflammation, while a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model. These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO2 from dietary sources. PMID:28106049

  2. Dual Lewis Acid/Lewis Base Catalyzed Acylcyanation of Aldehydes: A Mechanistic Study.

    Science.gov (United States)

    Laurell Nash, Anna; Hertzberg, Robin; Wen, Ye-Qian; Dahlgren, Björn; Brinck, Tore; Moberg, Christina

    2016-03-07

    A mechanistic investigation, which included a Hammett correlation analysis, evaluation of the effect of variation of catalyst composition, and low-temperature NMR spectroscopy studies, of the Lewis acid-Lewis base catalyzed addition of acetyl cyanide to prochiral aldehydes provides support for a reaction route that involves Lewis base activation of the acyl cyanide with formation of a potent acylating agent and cyanide ion. The cyanide ion adds to the carbonyl group of the Lewis acid activated aldehyde. O-Acylation by the acylated Lewis base to form the final cyanohydrin ester occurs prior to decomplexation from titanium. For less reactive aldehydes, the addition of cyanide is the rate-determining step, whereas, for more reactive, electron-deficient aldehydes, cyanide addition is rapid and reversible and is followed by rate-limiting acylation. The resting state of the catalyst lies outside the catalytic cycle and is believed to be a monomeric titanium complex with two alcoholate ligands, which only slowly converts into the product. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Lewis' Educational and Research Collaborative Internship Program

    Science.gov (United States)

    Heyward, Ann; Gott, Susan (Technical Monitor)

    2004-01-01

    The Lewis Educational and Research Collaborative Internship Program (LERCIP) is a collaborative undertaking by the Office of Educational Programs at NASA Glenn Research Center at Lewis Field (formerly NASA Lewis Research Center) and the Ohio Aerospace Institute. This program provides 10-week internships in addition to summer and winter extensions if funding is available and/or is requested by mentor (no less than 1 week no more than 4 weeks) for undergraduate/graduate students and secondary school teachers. Students who meet the travel reimbursement criteria receive up to $500 for travel expenses. Approximately 178 interns are selected to participate in this program each year and begin arriving the fourth week in May. The internships provide students with introductory professional experiences to complement their academic programs. The interns are given assignments on research and development projects under the personal guidance of NASA professional staff members. Each intern is assigned a NASA mentor who facilitates a research assignment. In addition to the research assignment, the summer program includes a strong educational component that enhances the professional stature of the participants. The educational activities include a research symposium and a variety of workshops, and lectures. An important aspect of the program is that it includes students with diverse social, cultural and economic backgrounds. The purpose of this report is to document the program accomplishments for 2004.

  4. Ovariectomy and subsequent treatment with estrogen receptor agonists tune the innate immune system of the hippocampus in middle-aged female rats.

    Science.gov (United States)

    Sárvári, Miklós; Kalló, Imre; Hrabovszky, Erik; Solymosi, Norbert; Liposits, Zsolt

    2014-01-01

    The innate immune system including microglia has a major contribution to maintenance of the physiological functions of the hippocampus by permanent monitoring of the neural milieu and elimination of tissue-damaging threats. The hippocampus is vulnerable to age-related changes ranging from gene expression to network connectivity. The risk of hippocampal deterioration increases with the decline of gonadal hormone supply. To explore the impact of hormone milieu on the function of the innate immune system in middle-aged female rats, we compared mRNA expression in the hippocampus after gonadal hormone withdrawal, with or without subsequent estrogen replacement using estradiol and isotype-selective estrogen receptor (ER) agonists. Targeted profiling assessed the status of the innate immune system (macrophage-associated receptors, complement, inhibitory neuronal ligands), local estradiol synthesis (P450 aromatase) and estrogen reception (ER). Results established upregulation of macrophage-associated (Cd45, Iba1, Cd68, Cd11b, Cd18, Fcgr1a, Fcgr2b) and complement (C3, factor B, properdin) genes in response to ovariectomy. Ovariectomy upregulated Cd22 and downregulated semaphorin3A (Sema3a) expression, indicating altered neuronal regulation of microglia. Ovariectomy also led to downregulation of aromatase and upregulation of ERα gene. Of note, analogous changes were observed in the hippocampus of postmenopausal women. In ovariectomized rats, estradiol replacement attenuated Iba1, Cd11b, Fcgr1a, C3, increased mannose receptor Mrc1, Cd163 and reversed Sema3a expression. In contrast, reduced expression of aromatase was not reversed by estradiol. While the effects of ERα agonist closely resembled those of estradiol, ERβ agonist was also capable of attenuating the expression of several macrophage-associated and complement genes. These data together indicate that the innate immune system of the aging hippocampus is highly responsive to the gonadal hormone milieu. In

  5. Ovariectomy and subsequent treatment with estrogen receptor agonists tune the innate immune system of the hippocampus in middle-aged female rats.

    Directory of Open Access Journals (Sweden)

    Miklós Sárvári

    Full Text Available The innate immune system including microglia has a major contribution to maintenance of the physiological functions of the hippocampus by permanent monitoring of the neural milieu and elimination of tissue-damaging threats. The hippocampus is vulnerable to age-related changes ranging from gene expression to network connectivity. The risk of hippocampal deterioration increases with the decline of gonadal hormone supply. To explore the impact of hormone milieu on the function of the innate immune system in middle-aged female rats, we compared mRNA expression in the hippocampus after gonadal hormone withdrawal, with or without subsequent estrogen replacement using estradiol and isotype-selective estrogen receptor (ER agonists. Targeted profiling assessed the status of the innate immune system (macrophage-associated receptors, complement, inhibitory neuronal ligands, local estradiol synthesis (P450 aromatase and estrogen reception (ER. Results established upregulation of macrophage-associated (Cd45, Iba1, Cd68, Cd11b, Cd18, Fcgr1a, Fcgr2b and complement (C3, factor B, properdin genes in response to ovariectomy. Ovariectomy upregulated Cd22 and downregulated semaphorin3A (Sema3a expression, indicating altered neuronal regulation of microglia. Ovariectomy also led to downregulation of aromatase and upregulation of ERα gene. Of note, analogous changes were observed in the hippocampus of postmenopausal women. In ovariectomized rats, estradiol replacement attenuated Iba1, Cd11b, Fcgr1a, C3, increased mannose receptor Mrc1, Cd163 and reversed Sema3a expression. In contrast, reduced expression of aromatase was not reversed by estradiol. While the effects of ERα agonist closely resembled those of estradiol, ERβ agonist was also capable of attenuating the expression of several macrophage-associated and complement genes. These data together indicate that the innate immune system of the aging hippocampus is highly responsive to the gonadal hormone milieu

  6. Zebularine induces long-term survival of pancreatic islet allotransplants in streptozotocin treated diabetic rats.

    Directory of Open Access Journals (Sweden)

    Henrietta Nittby

    Full Text Available BACKGROUND: Coping with the immune rejection of allotransplants or autologous cells in patients with an active sensitization towards their autoantigens and autoimmunity presently necessitates life-long immune suppressive therapy acting on the immune system as a whole, which makes the patients vulnerable to infections and increases their risk of developing cancer. New technologies to induce antigen selective long-lasting immunosuppression or immune tolerance are therefore much needed. METHODOLOGY/PRINCIPAL FINDINGS: The DNA demethylating agent Zebularine, previously demonstrated to induce expression of the genes for the immunosuppressive enzymes indolamine-2,3-deoxygenase-1 (IDO1 and kynureninase of the kynurenine pathway, is tested for capacity to suppress rejection of allotransplants. Allogeneic pancreatic islets from Lewis rats were transplanted under the kidney capsule of Fischer rats previously made diabetic by a streptozotocin injection (40 mg/kg. One group was treated with Zebularine (225 mg/kg daily for 14 days from day 6 or 8 after transplantation, and a control group received no further treatment. Survival of the transplants was monitored by blood sugar measurements. Rats, normoglycemic for 90 days after allografting, were subjected to transplant removal by nephrectomy to confirm whether normoglycemia was indeed due to a surviving insulin producing transplant, or alternatively was a result of recovery of pancreatic insulin production in some toxin-treated rats. Of 9 Zebularine treated rats, 4 were still normoglycemic after 90 days and became hyperglycemic after nephrectomy. The mean length of normoglycemia in the Zebularine group was 67±8 days as compared to 14±3 days in 9 controls. Seven rats (2 controls and 5 Zebularine treated were normoglycemic at 90 days due to pancreatic recovery as demonstrated by failure of nephrectomy to induce hyperglycemia. CONCLUSIONS/SIGNIFICANCE: Zebularine treatment in vivo induces a long

  7. Cortical grey matter demyelination can be induced by elevated pro-inflammatory cytokines in the subarachnoid space of MOG-immunized rats.

    Science.gov (United States)

    Gardner, Christopher; Magliozzi, Roberta; Durrenberger, Pascal F; Howell, Owain W; Rundle, Jon; Reynolds, Richard

    2013-12-01

    A substantial proportion of cases with secondary progressive multiple sclerosis have extensive inflammation in the leptomeninges that is associated with increased subpial demyelination, neuronal loss and an exacerbated disease course. However, the mechanisms underlying this extensive subpial pathology are poorly understood. We hypothesize that pro-inflammatory cytokine production within the meninges may be a key to this process. Post-mortem cerebrospinal fluid and dissected cerebral leptomeningeal tissue from patients with multiple sclerosis were used to study the presence of tumour necrosis factor and interferon gamma protein and messenger RNA levels. A novel model of subpial cortical grey matter demyelination was set up in Dark Agouti rats and analysed using quantitative immunohistochemistry. Increased expression of the pro-inflammatory cytokines tumour necrosis factor and interferon gamma was found in the meninges of cases with secondary progressive multiple sclerosis exhibiting tertiary lymphoid-like structures. Injection of tumour necrosis factor and interferon gamma into the subarachnoid space of female Dark Agouti rats pre-immunized with a subclinical dose of myelin oligodendrocyte glycoprotein mimicked the pathology seen in multiple sclerosis, including infiltration of lymphocytes (CD4+ and CD8+ T cells and CD79+ B cells) into the meninges and extensive subpial demyelination. Extensive microglial/macrophage activation was present in a gradient from the pial surface to deeper cortical layers. Demyelination did not occur in control animals immunized with incomplete Freund's adjuvant and injected with cytokines. These results support the hypothesis that pro-inflammatory molecules produced in the meninges play a major role in cortical demyelination in multiple sclerosis, but also emphasize the involvement of an anti-myelin immune response.

  8. Prebiotic potential of Jerusalem artichoke (Helianthus tuberosus L.) in Wistar rats: effects of levels of supplementation on hindgut fermentation, intestinal morphology, blood metabolites and immune response.

    Science.gov (United States)

    Samal, Lipismita; Chaturvedi, Vishwa Bandhu; Saikumar, Guttula; Somvanshi, Ramesh; Pattanaik, Ashok Kumar

    2015-06-01

    Many studies have been conducted using purified prebiotics such as inulin or fructooligosaccharides (FOS) as nutraceuticals, but there is very little information available on the prebiotic potential of raw products rich in inulin and FOS, such as Jerusalem artichoke (JA; Helianthus tuberosus L.). The present experiment aimed to evaluate the prebiotic effects of JA tubers in rats. Seventy-two Wistar weanling rats divided into four groups were fed for 12 weeks on a basal diet fortified with pulverized JA tubers at 0 (control), 20, 40 and 60 g kg(-1) levels. Enhanced cell-mediated immunity in terms of skin indurations (P = 0.082) and CD4+ T-lymphocyte population (P = 0.002) was observed in the JA-supplemented groups compared with the control group. Blood haemoglobin (P = 0.017), glucose (P = 0.001), urea (P = 0.004) and calcium (P = 0.048) varied favourably upon inclusion of JA. An increasing trend (P = 0.059) in the length of large intestine was apparent in the JA-fed groups. The tissue mass of caecum (P = 0.069) and colon (P = 0.003) was increased in the JA-supplemented groups, accompanied by higher (P = 0.007) caecal crypt depth. The pH and ammonia concentrations of intestinal digesta decreased and those of lactate and total volatile fatty acids increased in the JA-fed groups. The results suggest that JA had beneficial effects on immunity, blood metabolites, intestinal morphometry and hindgut fermentation of rats. © 2014 Society of Chemical Industry.

  9. Effect of Polygoni Cuspidati Rhizoma et Radix and Its Ingredient Resveratrol on Experimental Autoimmune Myasthenia Gravis by Suppressing Immune Response

    Institute of Scientific and Technical Information of China (English)

    Shen Liu; Xin-xin Zhang; Shan Zhuang; Chun-hong Li; Yan-bin Li

    2016-01-01

    Objective To investigate the effects of Polygoni Cuspidati Rhizoma et Radix(PCRR) and its ingredient resveratrol(Res) on experimental autoimmune myasthenia gravis(EAMG). Methods EAMG was induced in Lewis rats by the immunization of a synthetic peptide corresponding to region 97–116 of the rat acetylcholine receptor(ACh R) α subunit(R97-116). EAMG rats were randomly divided into PCRR group, Res group, and control(C) group, and were ig administered respectively with PCRR(2 g/kg), Res(20 mg/kg), and DMSO(0.4 m L/kg) every day from day 5 after immunization to day 42. Clinical evaluation, lymphocyte proliferation, cytokines, and anti-97-116 antibodies were performed for examination of their therapeutic effects. Results Treatments with PCRR and Res significantly ameliorated clinical symptoms, down-regulated TNF-α and up-regulated IL-10 in serum and culture supernatants of lymphocytes stimulated with R97-116, and decreased levels of anti-R97-116 Ig G1 and Ig G2 a in serum compared with C group. Unexpectedly, PCRR but not Res inhibited lymphocyte proliferation compared with C group. Conclusion PCRR and Res ameliorating EAMG is associated with suppressing immune response, and indicates a therapeutic potential for EAMG and even human myasthenia gravis(MG). Res may be the main effective ingredient from PCRR ameliorating EAMG, but further experiments are necessary.

  10. Contrasting Frustrated Lewis Pair Reactivity with Selenium- and Boron-Based Lewis Acids.

    Science.gov (United States)

    Wilkins, Lewis C; Günther, Benjamin A R; Walther, Melanie; Lawson, James R; Wirth, Thomas; Melen, Rebecca L

    2016-09-05

    The activation of π-bonds in diynyl esters has been investigated by using soft and hard Lewis acids. In the case of the soft selenium Lewis acid PhSeCl, sequential activation of the alkyne bonds leads initially to an isocoumarin (1 equiv PhSeCl) and then to a tetracyclic conjugated structure with the isocoumarin subunit fused to a benzoselenopyran (3 equiv PhSeCl). Conversely, the reaction with the hard Lewis acidic borane B(C6 F5 )3 initiates a cascade reaction to yield a complex π-conjugated system containing phthalide and indene subunits. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Immunomodulatory effects of zinc and DHEA on the Th-1 immune response in rats infected with Trypanosoma cruzi.

    Science.gov (United States)

    Brazão, Vânia; Santello, Fabricia Helena; Caetano, Leony Cristina; Del Vecchio Filipin, Marina; Toldo, Míriam Paula Alonso; do Prado, José Clóvis

    2010-05-01

    Chagas' disease is considered the sixth most important neglected tropical disease worldwide. Considerable knowledge has been accumulated concerning the role of zinc on cellular immunity. The steroid hormone dehydroepiandrosterone (DHEA) is also known to modulate the immune system. The aims of this paper were to investigate a possible synchronization of their effects on cytokines and NO production and the resistance to Trypanosoma cruzi during the acute phase of infection. It was found that zinc, DHEA or zinc and DHEA supplementation enhanced the immune response, as evidenced by a significant reduction in parasitemia levels. Zinc and DHEA supplementation exerted additive effects on the immune response by elevation of macrophage counts, and by increasing concentrations of IFN-gamma and NO.

  12. Differential effect of severe and moderate social stress on blood immune and endocrine measures and susceptibility to collagen type II arthritis in male rats.

    Science.gov (United States)

    Stefanski, Volker; Hemschemeier, Susanne K; Schunke, Kerstin; Hahnel, Anja; Wolff, Christine; Straub, Rainer H

    2013-03-01

    The effects of social stress on several blood immune measures and collagen-induced arthritis (CIA) were investigated in Wistar rats using the resident-intruder confrontation paradigm to induce stress of different intensity. Male intruders were exposed for one week to a dominant opponent either repeatedly for 4h daily (moderate stress) or continuously (severe stress). Arthritis was induced by intradermal injection of collagen type II (CII) into the tail skin at the end of day 3 of confrontation. Only severe stress was associated with decreased CD4 and CD8 T cells, and the increase in granulocyte numbers and body mass loss was more pronounced under these conditions. Only severe stress reduced the susceptibility to arthritis by about 50%. Severity scores did not differ in the first five days after disease onset between all groups. Subsequent experiments focused on severely stressed rats indicated that disease progressed until day 10 only in control animals, but not in severely stressed males. Stressor exposure resulted in increased blood monocyte numbers, but these males failed to accumulate macrophages into the skin at the site of CII injection. High numbers of attacks experienced by intruders correlated with delayed disease onset in severely stressed rats. We hypothesize that severe stress persisting after disease induction exhibits beneficial effects on the susceptibility of CIA and propose that the specific endocrine and immunological profile associated with severe stress is an important factor for disease outcome--a factor which probably explains many of the conflicting data of previous stress studies on CIA.

  13. Transcutaneous vaccination using a hydrogel patch induces effective immune responses to tetanus and diphtheria toxoid in hairless rat.

    Science.gov (United States)

    Matsuo, Kazuhiko; Ishii, Yumiko; Quan, Ying-Shu; Kamiyama, Fumio; Mukai, Yohei; Yoshioka, Yasuo; Okada, Naoki; Nakagawa, Shinsaku

    2011-01-01

    Transcutaneous immunization (TCI) targeting the Langerhans cells (LCs) of the epidermal layer is a promising needle-free, easy-to-use, and non-invasive vaccination method. We developed a hydrogel patch formulation to promote the penetration of antigenic proteins into the stratum corneum. Here, we investigated the characteristics of the immune responses induced by this vaccination method and the vaccine efficacy of TCI using a hydrogel patch containing tetanus and diphtheria toxoids. Our TCI system induced toxoid-specific IgG production in an antigen dose-, patch area-, and application period-dependent manner. Moreover, IgG subclass analysis indicated that our TCI predominantly elicited a Th2-type immune response rather than a Th1-type immune response. Importantly, our TCI system induced antigen-specific immune memory based on the booster effect and showed potent efficacy, comparable to that of subcutaneous immunization in toxin-challenge experiments. On the basis of these results, we are now performing translational research to apply TCI for tetanus and diphtheria.

  14. Phosphorus Lewis acids: emerging reactivity and applications in catalysis.

    Science.gov (United States)

    Bayne, J M; Stephan, D W

    2016-02-21

    Part of the renaissance in main group chemistry has been a result of the focus on reactivity. This has led to the development of applications in stoichiometric reactivity and catalysis. In this tutorial review, we focus attention on the role of phosphorus-based Lewis acids in such advances. While early literature recognizes the role of P(iii) and P(v) electrophiles in coordination chemistry, it has generally been more recent studies that have focused on applications of this Lewis acidity. Applications of these novel P-based Lewis acids in stoichiometric reactivity, Lewis acid catalysis and frustrated Lewis pair (FLP) reactivity are reviewed. These advances demonstrate that P-based Lewis acids are a powerful tool for further developments in metal-free catalysis.

  15. Visual signs and symptoms of dementia with Lewy bodies

    OpenAIRE

    Armstrong, Richard A.

    2012-01-01

    Dementia with Lewy bodies ('Lewy body dementia' or 'diffuse Lewy body disease') (DLB) is the second most common form of dementia to affect elderly people, after Alzheimer's disease. A combination of the clinical symptoms of Alzheimer's disease and Parkinson's disease is present in DLB and the disorder is classified as a 'parkinsonian syndrome', a group of diseases which also includes Parkinson's disease, progressive supranuclear palsy, corticobasal degeneration and multiple system atrophy. Ch...

  16. Digital Joint Reconstruction with Osteotendinous Joint Allograft: Experimental Study in Rats.

    Science.gov (United States)

    Iglesias, Martin; Cruz-Reyes, Ángel Uriel; Butrón, Patricia; Hernández-Agallo, Ricardo; de la Barrera, Víctor Antonio Torres; Reyes-Montero, Claudio; Durand-Carbajal, Marta; Torres-Villalobos, Gonzalo

    2017-04-01

    Fresh or frozen nonvascularized osteotendinous joint allografts (OTJA) have not been used previously, clinically or experimentally, for metacarpophalangeal joint reconstruction. Therefore, we evaluated the viability of OTJA for metatarsophalangeal joint (MTJ) reconstruction in rats. In the experimental group of 12 Lewis rats, we reconstructed the MTJ of the third digit of the hindlimb with a fresh, nonvascularized OTJA obtained from the same digit from 12 donor rats. In the control group of 6 Lewis rats, an autologous composite osteotendinous graft of the MTJ of the same digit was obtained and repositioned in situ as an auto-transplant. Weight, pain, edema, dehiscence, and wound infection were evaluated every 24 hours for 30 days postoperatively. At the end of 30 days, we evaluated digit position, flexion and extension, passive mobility, radiological bone healing, and histological grades of rejection. We found no statistically different changes in weight, edema, pain, digit position, or radiological bone healing in either group. No wound dehiscence or infection was seen in any of the rats. Ten degrees of flexion and extension mobility were lost in the control group; the experimental group lost up to 30 degrees (P = 0.009). Histologically, 9 of the experimental group rats (9/12, 75%) showed rejection reactions compared with none of the controls (0%) (P = 0.009). Fresh nonvascularized OTJA caused an immune reaction without exposure of the graft, but with bone resorption. However, the rats maintained digital form and alignment with decreased passive flexion and extension of 10-30 degrees.

  17. Evaluation of humoral and cellular immune responses to a DNA vaccine encoding chicken type II collagen for rheumatoid arthritis in normal rats.

    Science.gov (United States)

    Xiao, Zhao; Juan, Long; Song, Yun; Zhijian, Zhang; Jing, Jin; Kun, Yu; Yuna, Hao; Dongfa, Dai; Lili, Ding; Liuxin, Tan; Fei, Liang; Nan, Liu; Fang, Yuan; Yuying, Sun; Yongzhi, Xi

    2015-01-01

    A major challenge in the development of effective therapies for rheumatoid arthritis (RA) is finding a method for the specific inhibition of the inflammatory disease processes without the induction of generalized immunosuppression. Of note, the development of therapeutic DNA vaccines and boosters that may restore immunological tolerance remains a high priority. pcDNA-CCOL2A1 is a therapeutic DNA vaccine encoding chicken type II collagen(CCII). This vaccine was developed by our laboratory and has been shown to exhibit efficacy comparable to that of the current "gold standard" treatment, methotrexate (MTX). Here, we used enzyme-linked immunosorbent assays with anti-CII IgG antibodies, quantified the expression levels of Th1, Th2, and Th3 cytokines, and performed flow cytometric analyses of different T-cell subsets, including Th1, Th2, Th17, Tc, Ts, Treg, and CD4(+)CD29(+)T cells to systemically evaluate humoral and cellular immune responses to pcDNA-CCOL2A1 vaccine in normal rats. Similar to our observations at maximum dosage of 3 mg/kg, vaccination of normal rats with 300 μg/kg pcDNA-CCOL2A1 vaccine did not induce the production of anti-CII IgG. Furthermore, no significant changes were observed in the expression levels of pro-inflammatory cytokines interleukin (IL)-1α, IL-5, IL-6, IL-12(IL-23p40), monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, regulated on activation in normal T-cell expressed and secreted (RANTES), receptor activator for nuclear factor-κB ligand (RANKL), and granulocyte colony-stimulating factor (G-CSF) or anti-inflammatory cytokines IL-4 and IL-10 in vaccinated normal rats relative to that in controls(P > 0.05). However, transforming growth factor (TGF)-β levels were significantly increased on days 10 and 14, while interferon (IFN)-γ and tumor necrosis factor (TNF)-α levels were significantly decreased on days 28 and 35 after vaccination(P 0.05), with the exception of Treg cells, which were significantly

  18. Effects of Long-Term Oral Administration of Arachidonic Acid and Docosahexaenoic Acid on the Immune Functions of Young Rats

    Directory of Open Access Journals (Sweden)

    Osamu Shido

    2013-05-01

    Full Text Available Natural killer (NK cells have many functional activities, including cytotoxicity and the capacity to produce cytokines and chemokines. NK cell activity is regulated partly by eicosanoids, which are produced from arachidonic acid (ARA and eicosapentaenoic (EPA acid. In this study, we investigated the effects of long-term therapy with ARA or docosahexaenoic acid (DHA on the cytotoxic effects of the NK cells of young rats, which were fed on a nonfish oil diet for two generations. Control oil, ARA (240 mg/kg BW/day or DHA (240 mg/kg BW/day were orally administrated to the rats for 13 weeks before determining the cytotoxic activity of NK cells from the spleen against YAC-1 mouse lymphoma cell line, as well as the plasma levels of docosanoids or eicosanoids and inflammatory cytokines. Long-term ARA administration significantly suppressed the cytotoxic activity of NK cells. Moreover, ARA administration significantly increased the plasma levels of ARA, prostaglandin (PG E2, and PGD2. However, DHA administration did not produce any different effects compared with those in the control rats. Furthermore, the inflammatory cytokine levels were not affected by the administration of ARA or DHA. These results suggest that long-term ARA administration has an inhibitory effect on the tumor cytotoxicity of NK cells in rat spleen lymphocytes owing to the enhanced synthesis of PGE2 and PGD2 from ARA because of the elevated plasma ARA levels in young rats.

  19. Lewis-Sumner syndrome in hepatitis C virus infection: a possible pathogenetic association with therapeutic problems.

    Science.gov (United States)

    Caporale, Christina M; Capasso, Margherita; Ragno, Michele; Di Muzio, Antonio; Uncini, Antonino

    2006-07-01

    A patient with chronic hepatitis from hepatitis C virus (HCV) infection developed Lewis-Sumner syndrome (LSS). The neuropathy worsened after intravenous immunoglobulins, remitted after intravenous methylprednisolone, relapsed during interferon-alpha, but responded again to steroids continued for 68 weeks with clinical remission and without worsening of hepatitis. We are not aware of other reports of HCV infection and LSS. This association may be coincidental or related to a virus-triggered immune-mediated process. Although the coexistence of a dysimmune neuropathy with hepatitis makes problematic the choice of treatment, we emphasize that the patient's condition during treatment with steroids and the 46 following weeks without therapy has been excellent.

  20. Lewis-Sumner syndrome associated with infliximab therapy in rheumatoid arthritis.

    Science.gov (United States)

    Hooper, Davyd R; Tarnopolsky, Mark A; Baker, Steven K

    2008-10-01

    We report 2 cases of Lewis-Sumner syndrome (LSS) diagnosed in patients suffering from rheumatoid arthritis undergoing treatment with the antitumor necrosis factor alpha (TNF-alpha) monoclonal antibody infliximab. While experiencing clinical improvement in their arthritic symptoms, both patients experienced sensory deficits and weakness in multiple nerve distributions. They had electrodiagnostic evidence of motor conduction block and subsequent improvement with intravenous immunoglobulin (IVIg). We describe the details of the cases and review the literature on immune-mediated neuropathies associated with anti-TNF-alpha therapy.

  1. Evaluation of the immune response of male and female rats vaccinated with cDNA encoding a cysteine proteinase of Fasciola hepatica (FhPcW1).

    Science.gov (United States)

    Wesołowska, Agnieszka; Norbury, Luke J; Januszkiewicz, Kamil; Jedlina, Luiza; Jaros, Sławomir; Zawistowska-Deniziak, Anna; Zygner, Wojciech; Wędrychowicz, Halina

    2013-06-01

    Not only do males and females of many species vary in their responses to certain parasitic infections, but also to treatments such as vaccines. However, there are very few studies investigating differences among sexes following vaccination and infection. Here we demonstrate that female Sprague-Dawley rats vaccinated with cDNA encoding a recently discovered cysteine proteinase of Fasciola hepatica (FhPcW1) develop considerably lower liver fluke burdens after F. hepatica infection than their male counterparts. This is accompanied by differences in the course of their immune responses which involve different eosinophil and monocyte responses throughout the study as well as humoral responses. It is evident that host gender influences the outcome of parasitic infections after vaccination and research on both sexes should be considered when developing new treatments against parasites.

  2. Immune therapy with cultured microglia grafting into the injured spinal cord promoting the recovery of rat's hind limb motor function

    Institute of Scientific and Technical Information of China (English)

    YU Teng-bo; CHENG Yong-shuai; ZHAO Peng; KOU De-wei; SUN Kang; CHEN Bo-hua; WANG Ai-min

    2009-01-01

    Objective: To study the effect of activated microglia grafting on rats' hind limb motor function recovery after spinal cord injury.Methods: Microglia were separated from primary culture and subcultured for 3 generations. Lipopolysaccharide was added to the culture medium with the terminal concentrition of 10 μl/L for microglia activation 3 days before transplantation. Totally 80 adult Wistar rats were divided into transplantation group and control group, with 40 rats in each group. Spinal cord injury model of rats was set by hitting onto the spinal cord using a modified Allen impactor. With a 5 μl micro-syringe, the activated microglia suspension was injected into the injured area 7 days after the first operation. Basso, Beattie and Bresnahan (BBB) scoring for hind limb motor function was taken on the 1st, 7th, 14th, 21st, and 28th day after microglia transplantation, and 8 rats were sacrificed at each time point mentioned above, respectively. Frozen sections of the spinal cord were made for haematoxylin-eosin (HE) and Naoumenko-Feigin stainings. SPSS 11.0 software was used for statistical analysis.Results: BBB scores for hind limb motor function on the 14th, 21 st, and 28th day were significantly higher compared with the control group. Most liquefaction necrosis areas disappeared and only a few multicystic cavities surrounded by aggregated microglia remained in the transplantation group. Naoumenko-Feigin staining for microglia showed that the transplantation group had significantly more positive cells (P<0.05).Conclusions: Grafting of activated microglia into the injured spinal cord can significantly promote the hind limb motor function recovery in rats with spinal cord injury and reduce the size of liquefaction necrosis area. The extent of lower limb motor function improvement has a positive correlation with the number of aggregated microglia.

  3. High IFN-α expression is associated with the induction of experimental autoimmune uveitis (EAU) in Fischer 344 rat

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Thl-response plays a crucial role in determining pathogenesis of organ-specific autoimmune diseases. It is believed that both IL-12 and INF-α are initiators to regulate Th1- response. In our experimental autoimmune uveitis (EAU) model, both Lewis and Fischer 344 rats share the same MHC class ⅡI molecules,while Lewis rat is EAU susceptible and Fischer 344 rat is EAU resistant. However, under the same condition of immunization, if pertussis toxin (PTX) was injected intraperitoneally as an additional adjuvant, Fischer 344 rat can develop EAU. In this study we investigate which mechanisms are involved in the induction of EAU in CFA+R16+PTX-treated (CRP-treated) Fischer 344 rats. In vivo and in vitro data demonstrated that Thl-cytokine, IFN-γ mRNA expression was significantly increased in disease target tissue-eyes and in draining lymph node cells of CRP-treated Fischer 344 rat. When IL-12 and IFN-α mRNA expression were compared in the experimental groups, only IFN-α mRNA expression was associated with EAU development.To distinguish the sources of IFN-α producing cells, it was observed that IFN-α expression was mainly produced by macrophages. It was further confirmed that normal macrophage from Fischer 344 rat was able to produce significant IFN-α in the presence of PTX. The data strongly suggested that IFN-α might be involved in initiating Thl-cell differentiation and in turn contribute to the induction of EAU. High IFN-αexpression induced by PTX may represent a novel pathway to initiate Thl response in Fischer 344 rat.

  4. Mucosal immunization with live attenuated Francisella novicida U112ΔiglB protects against pulmonary F. tularensis SCHU S4 in the Fischer 344 rat model.

    Directory of Open Access Journals (Sweden)

    Aimee L Signarovitz

    Full Text Available The need for an efficacious vaccine against Francisella tularensis is a consequence of its low infectious dose and high mortality rate if left untreated. This study sought to characterize a live attenuated subspecies novicida-based vaccine strain (U112ΔiglB in an established second rodent model of pulmonary tularemia, namely the Fischer 344 rat using two distinct routes of vaccination (intratracheal [i.t.] and oral. Attenuation was verified by comparing replication of U112ΔiglB with wild type parental strain U112 in F344 primary alveolar macrophages. U112ΔiglB exhibited an LD(50>10(7 CFU compared to the wild type (LD(50 = 5 × 10(6 CFU i.t.. Immunization with 10(7 CFU U112ΔiglB by i.t. and oral routes induced antigen-specific IFN-γ and potent humoral responses both systemically (IgG2a>IgG1 in serum and at the site of mucosal vaccination (respiratory/intestinal compartment. Importantly, vaccination with U112ΔiglB by either i.t. or oral routes provided equivalent levels of protection (50% survival in F344 rats against a subsequent pulmonary challenge with ~25 LD(50 (1.25 × 10(4 CFU of the highly human virulent strain SCHU S4. Collectively, these results provide further evidence on the utility of a mucosal vaccination platform with a defined subsp. novicida U112ΔiglB vaccine strain in conferring protective immunity against pulmonary tularemia.

  5. Protracted, relapsing and demyelinating experimental autoimmune encephalomyelitis in DA rats immunized with syngeneic spinal cord and incomplete Freund's adjuvant

    DEFF Research Database (Denmark)

    Lorentzen, J C; Issazadeh-Navikas, Shohreh; Storch, M;

    1995-01-01

    , protracted and relapsing EAE (SPR-EAE) after a subcutaneous immunization at the tail base with syngeneic spinal cord and incomplete Freund's adjuvant (IFA). The neurological deficits were accompanied by demyelinating inflammatory lesions in the spinal cord, with infiltrating T lymphocytes and perivascular...

  6. Carnap and Lewis on the External World

    Directory of Open Access Journals (Sweden)

    Ivan Ferreira da Cunha

    2014-08-01

    Full Text Available This paper compares the claims about our knowledge of the external world presented by Rudolf Carnap, in the book known as the Aufbau, to those of Clarence Irving Lewis, in Mind and the World-Order. This comparison is made in terms of the opposition to Kantian epistemology that both books establish; the Aufbau is regarded as the peak of the logicist tradition and Mind and the World-Order is taken in continuity with pragmatism. It is found that both books present knowledge of the external world as a consequence of a structural organization of human experience. However, there is an important point of divergence: the concept of verification each author adopts is different, such a concept was even a matter of discussion between Lewis and the Vienna Circle. This paper shows this disagreement but also shows how Carnap changed his point of view in the decade after the Aufbau was published, towards a standpoint which is much closer to Lewis’s ideas. In that process, nevertheless, Carnap changed his focus and did not deal with the problem of the external world anymore. This paper also seeks to draw attention to some features of the relation between Carnap and the pragmatist tradition which have only recently started to attract interest.

  7. Immunohistochemical characterisation of the local immune response in azoxymethane-induced colon tumours in the BDIX inbred rat strain

    DEFF Research Database (Denmark)

    Kobæk Larsen, Morten; Diederichsen, Axel Cosmus Pyndt; Agger, Ralf

    2004-01-01

    by four weekly subcutaneous azoxymethane injections in inbred rats of the BDIX/OrlIco strain in two separate studies. Azoxymethane-induced tumours show many similarities to spontaneously occurring human colon carcinomas with respect to histopathological appearance. In our studies, the overall inflammatory...

  8. Transfer of primed CD4+OX40- T lymphocytes induces increased immunity to experimental Salmonella typhimurium infections in rats

    DEFF Research Database (Denmark)

    Thygesen, P; Christensen, H B; Hougen, H P

    1997-01-01

    isolated. The cells were separated according to their expression of CD4 and the OX40 antigen by FACS. OX40+ and OX40- CD4+ T-cell subpopulations were together with unsorted CD4+ T cells transferred to untreated rats 24 h prior to infection with S. typhimurium. Transfer of either unsorted CD4+ T cells or CD...

  9. Interview with Smithsonian NASM Spacesuit Curator Dr. Cathleen Lewis

    Science.gov (United States)

    Lewis, Cathleen; Wright, Rebecca

    2012-01-01

    Dr. Cathleen Lewis was interviewed by Rebecca Wright during the presentation of an "Interview with Smithsonian NASM Spacesuit Curator Dr. Cathleen Lewis" on May 14, 2012. Topics included the care, size, and history of the spacesuit collection at the Smithsonian and the recent move to the state-of-the-art permanent storage facility at the Udvar-Hazy facility in Virginia.

  10. Impairments of Speech Fluency in Lewy Body Spectrum Disorder

    Science.gov (United States)

    Ash, Sharon; McMillan, Corey; Gross, Rachel G.; Cook, Philip; Gunawardena, Delani; Morgan, Brianna; Boller, Ashley; Siderowf, Andrew; Grossman, Murray

    2012-01-01

    Few studies have examined connected speech in demented and non-demented patients with Parkinson's disease (PD). We assessed the speech production of 35 patients with Lewy body spectrum disorder (LBSD), including non-demented PD patients, patients with PD dementia (PDD), and patients with dementia with Lewy bodies (DLB), in a semi-structured…

  11. Dalgarno-Lewis perturbation theory for scattering states

    Energy Technology Data Exchange (ETDEWEB)

    Amore, Paolo [Facultad de Ciencias, Universidad de Colima, Bernal Diaz del Castillo 340, Colima, Colima Mexico (Mexico)]. E-mail: paolo@ucol.mx; Fernandez, Francisco M. [INIFTA (Conicet, UNLP), Division Quimica Teorica, Diag. 113 y 64 S/N, Sucursal 4, Casilla de Correo 16, 1900 La Plata (Argentina)]. E-mail: fernande@quimica.unlp.edu.ar

    2007-07-23

    We apply the method of Dalgarno and Lewis to scattering states and discuss the choice of the unperturbed model in order to have a convergent perturbation series for the phase shift. We show that a recently proposed approach is a particular case of the method of Dalgarno and Lewis.

  12. [THE CHANGES OF THE INTERRELATIONS OF THE PINEAL GLAND AND THE ORGANS OF THE IMMUNE SYSTEM IN RATS IN RESPONSE TO MELATONIN ADMINISTRATION IN LIGHT REGIME DISTURBANCES].

    Science.gov (United States)

    Litvinenko, G I; Gritzyk, O B; Mel'nikova, Ye V; Avrorov, P A; Tenditnik, M V; Shurlygina, A V; Trufakin, V A

    2015-01-01

    In this work the correlation analysis was applied to detect the integrated response of the pineal gland (PG) and immunocompetent organs of male Wistar rats in response to administration of melatonin (MT) in light regime disturbances. Animals were kept for 14 days under natural or continuous light (CL). Then for 7 days they received the injections of either 0.9% solution of sodium chloride or MT, after which the rats were decapitated and the mass of their body, PG, thymus and spleen was determined. The lymphocyte subpopulations of the thymus and spleen were studied by flow cytometry. The amount of lipofuscin in PG was assessed by the intensity of autofluorescence in organ frozen sections in 560-600 nm wavelength range. It was found that under the influence of MT, the number of intraorgan correlations in the immune system increased, regardless of the light regime. In animals on CL treated with MT, the number of interorgan connections was reduced, while negative correlations appeared between PG lipofuscin content and cellular composition of the spleen. The synchronizing and adaptogenic effects of MT were most pronounced under conditions of CL.

  13. Development of a cyclosporin-A-induced immune tolerant rat model to test marrow allograft cell type effects on bone repair.

    Science.gov (United States)

    Espitalier, Florent; Durand, Nicolas; Rémy, Séverine; Corre, Pierre; Sourice, Sophie; Pilet, Paul; Weiss, Pierre; Guicheux, Jérôme; Malard, Olivier

    2015-05-01

    Bone repair is an important concept in tissue engineering, and the ability to repair bone in hypotrophic conditions such as that of irradiated bone, represents a challenge for this field. Previous studies have shown that a combination of bone marrow and (BCP) was effective to repair irradiated bone. However, the origin and role played by each cell type in bone healing still remains unclear. In order to track the grafted cells, the development of an animal model that is immunotolerant to an allograft of bone marrow would be useful. Furthermore, because the immune system interacts with bone turnover, it is of critical importance to demonstrate that immunosuppressive drugs do not interfere with bone repair. After a preliminary study of immunotolerance, cyclosporin-A was chosen to be used in immunosuppressive therapy. Ten rats were included to observe qualitative and quantitative bone repair 8 days and 6 weeks after the creation of bone defects. The defects were filled with an allograft of bone marrow alone or in association with BCP under immunosuppressive treatment (cyclosporin-A). The results showed that there was no significant interaction of cyclosporin-A with osseous regeneration. The use of this new immunotolerant rat model of bone marrow allograft in future studies will provide insight on how the cells within the bone marrow graft contribute to bone healing, especially in irradiated conditions.

  14. HTLV-1 Tax-Specific CTL Epitope-Pulsed Dendritic Cell Therapy Reduces Proviral Load in Infected Rats with Immune Tolerance against Tax.

    Science.gov (United States)

    Ando, Satomi; Hasegawa, Atsuhiko; Murakami, Yuji; Zeng, Na; Takatsuka, Natsuko; Maeda, Yasuhiro; Masuda, Takao; Suehiro, Youko; Kannagi, Mari

    2017-02-01

    Adult T cell leukemia/lymphoma (ATL), a CD4(+) T cell malignancy with a poor prognosis, is caused by human T cell leukemia virus type 1 (HTLV-1) infection. High proviral load (PVL) is a risk factor for the progression to ATL. We previously reported that some asymptomatic carriers had severely reduced functions of CTLs against HTLV-1 Tax, the major target Ag. Furthermore, the CTL responses tended to be inversely correlated with PVL, suggesting that weak HTLV-1-specific CTL responses may be involved in the elevation of PVL. Our previous animal studies indicated that oral HTLV-1 infection, the major route of infection, caused persistent infection with higher PVL in rats compared with other routes. In this study, we found that Tax-specific CD8(+) T cells were present, but not functional, in orally infected rats as observed in some human asymptomatic carriers. Even in the infected rats with immune unresponsiveness against Tax, Tax-specific CTL epitope-pulsed dendritic cell (DC) therapy reduced the PVL and induced Tax-specific CD8(+) T cells capable of proliferating and producing IFN-γ. Furthermore, we found that monocyte-derived DCs from most infected individuals still had the capacity to stimulate CMV-specific autologous CTLs in vitro, indicating that DC therapy may be applicable to most infected individuals. These data suggest that peptide-pulsed DC immunotherapy will be useful to induce functional HTLV-1-specific CTLs and decrease PVL in infected individuals with high PVL and impaired HTLV-1-specific CTL responses, thereby reducing the risk of the development of ATL. Copyright © 2017 by The American Association of Immunologists, Inc.

  15. Toxicology and humoral immunity assessment of octamethylcyclotetrasiloxane (D4) following a 28-day whole body vapor inhalation exposure in Fischer 344 rats.

    Science.gov (United States)

    Klykken, P C; Galbraith, T W; Kolesar, G B; Jean, P A; Woolhiser, M R; Elwell, M R; Burns-Naas, L A; Mast, R W; McCay, J A; White, K L; Munson, A E

    1999-11-01

    Octamethylcyclotetrasiloxane, D4, is a low viscosity, silicone fluid consisting of four dimethyl-siloxy units ((CH3)2SiO)4 in a cyclic structure. It is primarily used as a building block in the industrial synthesis of long chain silicone polymers. The combination of D4 with decamethylcyclopentasiloxane (D5) is commonly referred to as cyclomethicone which has a wide range of applications as a formulation aid in personal care products. To extend the existing database regarding the biological activities of D4, a 28 day whole body vapor inhalation study was conducted using Fischer 344 rats at 0 (room air), 7, 20, 60, 180 and 540 ppm for 6 hours/day, 5 days/week. Parameters measured included body weights, organ weights, gross pathology, histopathology, serum chemistries, and urinalysis. In addition to these standard toxicological endpoints, the ability of D4 exposed animals to mount an IgM antibody response was evaluated by a splenic antibody forming cell (AFC) assay and a serum enzyme-linked immunosorbant assay (ELISA). The results of this 28-day inhalation study indicate that D4 exposure caused no adverse effects on body weight, food consumption, or urinalysis parameters. In addition, there were no exposure related histopathological alterations at any site for any exposure group. A statistically significant increase in liver weight and the liver to body weight ratio was observed in both male (180-540 ppm) and female (20-540 ppm) rats, which was not observed in the 14-day recovery group animals. There were no other significant organ weight changes. Although statistically significant changes were observed in several hematological and serum chemistry parameters in both the terminal and 14-day recovery animals, the changes were marginal and within the normal range of values for the rat. Under these experimental conditions, there were no alterations noted in immune system function at any of the D4 exposure levels.

  16. Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

    Energy Technology Data Exchange (ETDEWEB)

    Marín-Prida, Javier [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Pavón-Fuentes, Nancy [International Centre for Neurological Restoration (CIREN), Ave. 25 e/ 158 y 160, Playa, PO Box: 11300, Havana (Cuba); Llópiz-Arzuaga, Alexey; Fernández-Massó, Julio R. [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Delgado-Roche, Liván [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Mendoza-Marí, Yssel; Santana, Seydi Pedroso; Cruz-Ramírez, Alieski; Valenzuela-Silva, Carmen; Nazábal-Gálvez, Marcelo; Cintado-Benítez, Alberto [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Pardo-Andreu, Gilberto L. [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Polentarutti, Nadia [Istituto Clinico Humanitas (IRCCS), Rozzano (Italy); Riva, Federica [Department of Veterinary Science and Public Health (DIVET), University of Milano (Italy); Pentón-Arias, Eduardo [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Pentón-Rol, Giselle [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba)

    2013-10-01

    Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24 h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H{sub 2}O{sub 2} and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. - Highlights: • Phycocyanobilin (PCB) prevents H{sub 2}O{sub 2} and glutamate induced PC12 cell viability loss. • Anterior cortex and striatum are highly vulnerable to cerebral hypoperfusion (CH). • PCB modulates 190 genes associated to inflammation in acute CH. • PCB regulates 19 genes mostly related to a detrimental pro-inflammatory environment. • PCB restores redox and immune balances showing promise as potential stroke therapy.

  17. LEWIS BINFORD AND HIS MORAL MAJORITY (Lewis Binford y su mayoría moral

    Directory of Open Access Journals (Sweden)

    Alice Beck Kehoe

    2011-06-01

    Full Text Available This essay looks at the late Lewis Binford’s career from the standpoint of sociology of science. His thinking and manner reflect his socialization in Virginia Baptist subculture. As convinced of his authority on science as Jerry Falwell was of his authority on Biblical morality, Lewis Binford and his third wife Sally Rosen Binford excited a group of 1960s students to follow Lewis in an outmoded version of science (hypothetico-deductive and in trusting statistics. The “frames of reference” he laboriously constructed are naïve on environmental interpretation and, because he expressed contempt for “political” aspects of archaeology, fail to take into account effects of colonialism. His work is often scientistic, in the “modern” mode that historian Dorothy Ross describes as characteristic of twentieth-century American social sciences. ESPAÑOL: En este ensayo se analiza la etapa final de la carrera de Lewis Binford desde el punto de vista de la sociología de la ciencia. Su pensamiento refleja su socialización en el seno de la subcultura de la Virginia baptista. Tan convencido de su autoridad en la ciencia como Jerry Falwell lo fuera sobre la moralidad bíblica, Lewis Binford y su tercera esposa Sally Rosen Binford animaron a un grupo estudiantes de los sesenta a seguir a Lewis a través de una versión anticuada de la ciencia (hipotético-deductiva y a confiar en la estadística. Los “marcos de referencia” que laboriosamente construyó son ingenuos en la interpretación del medio ambiente y, como expresó el desprecio por los aspectos “políticos” de la arqueología, no tienen en cuenta los efectos del colonialismo. Su trabajo es a menudo cientificista, en el sentido “moderno” que la historiadora Dorothy Ross describe como una característica de las ciencias sociales norteamericanas del siglo XX.

  18. The development of Lewis Henry Morgan's evolutionism.

    Science.gov (United States)

    Kuper, A

    1985-01-01

    Lewis Henry Morgan never used the term evolution in any of his major sociological works. If he may be labeled an evolutionist, the specificity of his views must be taken into account. The main "evolutionist" issue that concerned him was that of the unity or diversity of the human species. This was an urgent political and theological issue in the America of his day, and it impinged also on research on the American Indians. Morgan's first major study was designed to demonstrate the unity of origin of the American aborigines and their "Asian" origins. His methods were derived from the tradition of Indo-European philology. It was virtually as an afterthought that he added a social evolutionary component to what he conceived of as an exercise in philology. Later he came under the direct influence of the English evolutionists, and this was crucial for the conception of Ancient Society.

  19. Dementia with Lewy bodies: current concepts.

    Science.gov (United States)

    Buracchio, Teresa; Arvanitakis, Zoe; Gorbien, Martin

    2005-01-01

    As life expectancy continues to increase over time, dementia is becoming an increasingly more common problem and a major cause of disability in older persons. It is now more important than ever to identify and manage common causes of dementia given variations in disease course, treatments and the possibility for modification of risk factors. Dementia with Lewy bodies (DLB) is a dementia syndrome characterized by progressive cognitive decline, with fluctuating cognition, recurrent detailed and well-formed hallucinations, and parkinsonism. This article aims to provide an overview of current concepts of DLB, including a description of the key clinical features and neuropathology, neurochemistry, and genetics of DLB, then a discussion of the relationship of DLB with Alzheimer's disease and Parkinson's disease, and, finally, a summary of current management strategies available for this disorder.

  20. Aluminium Diphosphamethanides: Hidden Frustrated Lewis Pairs.

    Science.gov (United States)

    Styra, Steffen; Radius, Michael; Moos, Eric; Bihlmeier, Angela; Breher, Frank

    2016-07-04

    The synthesis and characterisation of two aluminium diphosphamethanide complexes, [Al(tBu)2 {κ(2) P,P'-Mes*PCHPMes*}] (3) and [Al(C6 F5 )2 {κ(2) P,P'-Mes*PCHPMes*}] (4), and the silylated analogue, Mes*PCHP(SiMe3 )Mes* (5), are reported. The aluminium complexes feature four-membered PCPAl core structures consisting of diphosphaallyl ligands. The silylated phosphine 5 was found to be a valuable precursor for the synthesis of 4 as it cleanly reacts with the diaryl aluminium chloride [(C6 F5 )2 AlCl]2 . The aluminium complex 3 reacts with molecular dihydrogen at room temperature under formation of the acyclic σ(2) λ(3) ,σ(3) λ(3) -diphosphine Mes*PCHP(H)Mes* and the corresponding dialkyl aluminium hydride [tBu2 AlH]3 . Thus, 3 belongs to the family of so-called hidden frustrated Lewis pairs.

  1. NASA Lewis Meshed VSAT Workshop meeting summary

    Science.gov (United States)

    Ivancic, William

    1993-11-01

    NASA Lewis Research Center's Space Electronics Division (SED) hosted a workshop to address specific topics related to future meshed very small-aperture terminal (VSAT) satellite communications networks. The ideas generated by this workshop will help to identify potential markets and focus technology development within the commercial satellite communications industry and NASA. The workshop resulted in recommendations concerning these principal points of interest: the window of opportunity for a meshed VSAT system; system availability; ground terminal antenna sizes; recommended multifrequency for time division multiple access (TDMA) uplink; a packet switch design concept for narrowband; and fault tolerance design concepts. This report presents a summary of group presentations and discussion associated with the technological, economic, and operational issues of meshed VSAT architectures that utilize processing satellites.

  2. Superconducting Microwave Electronics at Lewis Research Center

    Science.gov (United States)

    Warner, Joseph D.; Bhasin, Kul B.; Leonard, Regis F.

    1991-01-01

    Over the last three years, NASA Lewis Research Center has investigated the application of newly discovered high temperature superconductors to microwave electronics. Using thin films of YBa2Cu3O7-delta and Tl2Ca2Ba2Cu3Ox deposited on a variety of substrates, including strontium titanate, lanthanum gallate, lanthanum aluminate and magnesium oxide, a number of microwave circuits have been fabricated and evaluated. These include a cavity resonator at 60 GHz, microstrip resonators at 35 GHz, a superconducting antenna array at 35 GHz, a dielectric resonator at 9 GHz, and a microstrip filter at 5 GHz. Performance of some of these circuits as well as suggestions for other applications are reported.

  3. Determinants of renal tissue hypoxia in a rat model of polycystic kidney disease.

    Science.gov (United States)

    Ow, Connie P C; Abdelkader, Amany; Hilliard, Lucinda M; Phillips, Jacqueline K; Evans, Roger G

    2014-11-15

    Renal tissue oxygen tension (PO2) and its determinants have not been quantified in polycystic kidney disease (PKD). Therefore, we measured kidney tissue PO2 in the Lewis rat model of PKD (LPK) and in Lewis control rats. We also determined the relative contributions of altered renal oxygen delivery and consumption to renal tissue hypoxia in LPK rats. PO2 of the superficial cortex of 11- to 13-wk-old LPK rats, measured by Clark electrode with the rat under anesthesia, was higher within the cysts (32.8 ± 4.0 mmHg) than the superficial cortical parenchyma (18.3 ± 3.5 mmHg). PO2 in the superficial cortical parenchyma of Lewis rats was 2.5-fold greater (46.0 ± 3.1 mmHg) than in LPK rats. At each depth below the cortical surface, tissue PO2 in LPK rats was approximately half that in Lewis rats. Renal blood flow was 60% less in LPK than in Lewis rats, and arterial hemoglobin concentration was 57% less, so renal oxygen delivery was 78% less. Renal venous PO2 was 38% less in LPK than Lewis rats. Sodium reabsorption was 98% less in LPK than Lewis rats, but renal oxygen consumption did not significantly differ between the two groups. Thus, in this model of PKD, kidney tissue is severely hypoxic, at least partly because of deficient renal oxygen delivery. Nevertheless, the observation of similar renal oxygen consumption, despite markedly less sodium reabsorption, in the kidneys of LPK compared with Lewis rats, indicates the presence of inappropriately high oxygen consumption in the polycystic kidney.

  4. Protection of gnotobiotic rats against dental caries by passive immunization with bovine milk antibodies to Streptococcus mutans.

    OpenAIRE

    Michalek, S. M.; Gregory, R L; Harmon, C C; Katz, J; Richardson, G J; Hilton, T.; Filler, S J; McGhee, J R

    1987-01-01

    A multivalent vaccine consisting of whole cell antigens of seven strains, representing four serotypes (b, c, d and g), of mutans streptococci was used to hyperimmunize a group of cows. Serum samples from these animals contained immunoglobulin G1 (IgG1) antibody activity to seven serotypes (a to g) of mutans streptococci. Whey obtained from the animal with the highest serum antibody activity, which also contained high levels of IgG1 antibody, was used in passive caries immunity studies. Gnotob...

  5. [THE THYROID STATUS OF RATS IMMUNIZED WITH PEPTIDES DERIVED FROM THE EXTRACELLULAR REGIONS OF THE TYPES 3 AND 4 MELANOCORTIN RECEPTORS AND THE 1B-SUBTYPE 5-HYDROXYTRYPTAMINE RECEPTOR].

    Science.gov (United States)

    Derkach, K V; Moyseuk, I V; Shpakova, E A; Sphakov, A O

    2015-01-01

    The activity of the hypothalamic-pituitary-thyroid (HPT) axis is controlled by the brain neurotransmitter systems, including the melanocortin signaling system. Pharmacological inhibition of type 4 melanocortin receptor (M4R) leads to disruption of the functioning of HPT axis and to reduction of the level of thyroid hormones. At the same time, the data on how prolonged inhibition of M4R affects this axis and on its role in regulation of M3R are absent. The relationship between the thyroid status and the activity of 1B-subtype 5-hydroxytryptamine receptor (5-HT1BR) is scarcely explored. The aim of this work to study the effects of chronic inhibition of M3R, M4R and 5-HT1BR induced by immunization of rats with BSA-conjugated peptide derived from the extracellular regions of these receptors on the thyroid status and the activity of thyroid stimulating hormone (TSH)-sensitive adenylyl cyclase signaling system (ACSS) in the thyroid glarid (TG) of the immunized animals. In rats immunized with the peptides K-[TSLHL WNRSSHGLHG11-25]-A of M4R, A[PTNPYCICTTAH269-280]-A of M3R and. [QAKAEE-EVSEC(Acm)-VVNTDH189-205]-A of 5-HT1BR levels of thyroid hormones such as fT4, tT4 and tT3 were significantly reduced. In rats immunized with M4R and M3R peptides, an increase of TSH was detected whereas in the animals immunized with 5-HT1BR peptide the level of TSH, on the contrary, was reduced. In the TG of rats immunized with M4R and M3R peptides, the stimulatory effects of hormones (TSH, PA-CAP-3 8) and GppNHp on adenylyl cyclase activity were attenuated, and the changes were most pronounced in the case M4R peptide immunization. After immunization with 5-HT1BR peptide the stimulatory effects of TSH, PACAP-38 and GppNHp were retained. Thus, the main cause of thyroid hormones deficit in rats immunized with M4R and M3R peptides was the decreased sensitivity of ACSS thyrocytes to TSH, whereas in rats iimunized with 5-HT1BR peptide the deficit of thyroid hormones was associated with decreased

  6. Feeding long-chain n-3 polyunsaturated fatty acids to obese leptin receptor-deficient JCR:LA- cp rats modifies immune function and lipid-raft fatty acid composition.

    Science.gov (United States)

    Ruth, Megan R; Proctor, Spencer D; Field, Catherine J

    2009-05-01

    Dietary EPA and DHA modulate immunity and thereby may improve the aberrant immune function in obese states. To determine the effects of feeding fish oil (FO) containing EPA and DHA on splenocyte phospholipid (PL) and lipid-raft fatty acid composition, phenotypes and cytokine production, 14-week-old obese, leptin receptor-deficient JCR:LA-cp rats (cp/cp; n 10) were randomised to one of three nutritionally adequate diets for 3 weeks: control (Ctl, 0 % EPA+DHA); low FO (LFO, 0.8 % (w/w) EPA+DHA); high FO (HFO, 1.4 % (w/w) EPA+DHA). Lean JCR:LA-cp (+/ - or +/+) rats (n 5) were fed the Ctl diet. Obese Ctl rats had a higher proportion of n-3 PUFA in splenocyte PL than lean rats fed the same diet (P JCR:LA-cp rats. Feeding FO lowered the ex vivo inflammatory response, without altering IL-2 production from ConA-stimulated splenocytes which may occur independent of leptin signalling.

  7. Expression of immune molecules in epileptogenic rats%实验性癫痫大鼠免疫分子的表达

    Institute of Scientific and Technical Information of China (English)

    曾常茜; 王金岩

    2006-01-01

    BACKGROUND: The relation of epilepsy to immunity has been investigated at cellular and molecular levels in recent years, and the results show many immunological changes in epileptic patients such as immunocytes,immune molecules and immune functions.OBJECTIVE: To investigate the immunologic pathogenesis of epilepsy and expression of MHC- Ⅰ, MHC- Ⅱ and C3b receptor of microglia. DESIGN: Randomized and controlled trial. SETTING: Medical College of Dalian University; University of Sanchong,Japan.MATERIALS: The experiment was conducted in the Immunology Laboratory of Jilin Beihua University from 2001 to 2002. Forty adult Wistar rats were randomized into model group and control group with 20 in each group.METHODS: 12 mg/kg kainic acid was administered subcutaneously into rats in model group, while no intervention was given to rats in control group. Seizure was observed within 6 hours following kainic acid administration. Rats were killed 3 days after medication. Neuronal degeneration was observed with crystal violet staining and the expression of MHC molecules and C3b receptor in the hippocampus of epileptogenic rats was observed immunnhistochemically.administration, spasm occurred within 3 hours after kainic acid administration and continued from the first stage to the fifth stage. More severe served in cone-like cell layer of hippocampus of rats in model group, but molecule, MHC- Ⅱ molecule and C3b receptor was (201.6±6.43), (493.8±7.92) and (362.5±3.18) cells per visual field respectively in the hippocampus of epileptogenic rats inmodel group, but no obvious expression was observed in control group. The differences were significant between the two groups (P < 0.01).pocampal sclerosis, immunological inflammation is observed combined with the complement system, which indicates immunologic inflammatory mechanism of epilepsy.%背景:近年来,许多学者对癫痫与免疫的关系从细胞和分子水平进行了研究,发现癫痫患者存在细胞、分子

  8. Protective effect of topical Cordia verbenacea in a rat periodontitis model: immune-inflammatory, antibacterial and morphometric assays

    Directory of Open Access Journals (Sweden)

    Pimentel Suzana

    2012-11-01

    Full Text Available Abstract Background This study evaluated the effects of C. verbenacea essential oil topically administered in a rat periodontitis model. Methods Periodontitis was induced on rats in one of the mandibular first molars assigned to receive a ligature. Animals were randomly divided into two groups: a non-treatment group (NT (n = 18: animals received 1mL of vehicle; b C. verbenacea group (C.v. (n = 18: animals received 5mg/Kg of essential oils isolated from C. verbenacea. The therapies were administered topically 3 times daily for 11 days. Then, the specimens were processed for morphometric analysis of bone loss. The ligatures were used for microbiological assessment of the presence of Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Porphyromonas gingivalis using PCR. The gingival tissue was collected to Elisa assay of interleukin (IL-1α and IL-10 levels. Results Bone loss was inhibited by C. verbenacea when compared to the NT group (p p P. gingivalis was found in C.v. group (p  Conclusion C. verbenacea essential oil topically administered diminished alveolar bone resorption, promoting a positive local imbalance in the pro/anti-inflammatory system and reducing the frequency of detection of P. gingivalis.

  9. Dose-effect relationship of CpG oligodeoxyribonucleotide 1826 in murine Lewis lung cancer treated with irradiation

    Directory of Open Access Journals (Sweden)

    Zhuang XB

    2013-05-01

    Full Text Available Xibing Zhuang,1 Tiankui Qiao,1 Sujuan Yuan,1 Wei Chen,1 Lin Zha,2 Li Yan11Department of Oncology, Jinshan Hospital, Medical Center of Fudan University, Shanghai, People's Republic of China; 2Department of Oncology, Tongling People's Hospital, Tongling, Anhui, People's Republic of ChinaBackground: Cytosine-phosphate-guanine (CpG oligodeoxyribonucleotides (ODNs, which induce signaling via Toll-like receptor 9, have recently been suggested to enhance sensitivity to traditional therapies, including chemotherapy, in certain cancer cell lines. This study aimed to define the dose-effect relationship for CpG ODN 1826 in increasing radiosensitivity and its impact on immune function in a mouse model of Lewis lung cancer.Methods: The tumor-bearing mouse model was induced by injecting Lewis lung cancer cells into the right anterior leg subcutaneously. Sixty-four C57BL/6 J mice were evenly randomized into eight groups, comprising: a control group; an irradiation group; a CpG ODN 0.15 group; a CpG ODN 0.3 group; a CpG ODN 0.45 group; a CpG 0.15 + irradiation group; a CpG 0.3 + irradiation group; and a CpG 0.45 + irradiation group. Tumor growth, serum tumor necrosis factor-alpha and interleukin-12 concentrations, spleen and thymus exponents, and effect of CpG on the secondary immune response were measured, and apoptosis of tumor cells was investigated using TdT-mediated dUTP nick end labeling (TUNEL after treatment.Results: Tumor volumes in the treated groups were smaller than in the control group, with those of the CpG 0.45 + irradiation group being the smallest. TUNEL showed that the apoptosis rate in all the active treatment groups was higher than in the control group. CpG ODN apoptosis rate, serum tumor necrosis factor-alpha and interleukin-12 levels, and the spleen and thymus exponent showed greater improvement in the groups receiving combination therapy of CpG ODN and irradiation than the control group or the group receiving irradiation alone. With the

  10. Detection of the effects of repeated dose combined propoxur and heavy metal exposure by measurement of certain toxicological, haematological and immune function parameters in rats.

    Science.gov (United States)

    Institóris, L; Siroki, O; Undeger, U; Basaran, N; Banerjee, B D; Dési, I

    2001-06-21

    In the present study, an immunotoxicity test system, containing general toxicological (body weight gain, organ weights), haematological (WBC,RBC, Ht, mean cell volume of the RBCs, cell content of the femoral bone marrow), and immune function (PFC assay, DTH reaction) investigations, was used for detection the effects of a 4 weeks repeated low dose combined oral exposure of male Wistar rats with propoxur and the heavy metals arsenic or mercury. Two doses of the compounds were used: a higher one (the lowest dose which resulted in significant change of at least one parameter examined in previous dose-effect experiments), and a lower one (the highest dose which proved to be non-effective). The applied doses were: 8.51 and 0.851 mg kg(-1) of propoxur, 13.3 and 3.33 mg kg(-1) of NaAsO(2), and 3.20 and 0.40 mg kg(-1) of HgCl(2). In the combination treatment, the high dose of propoxur was combined with the low dose of arsenic or mercury, and the high doses of each heavy metals were combined with the low dose of propoxur. The main finding of this study was that some of the combinations significantly altered the relative weight of liver, adrenals and kidneys, related to both the untreated and the high dose internal control. Among the immune functions examined, only the PFC content of the spleen showed a trend of changes in certain combinations versus the corresponding high dose control. According to the present results, combined exposure with propoxur and the heavy metals examined can modify the detection limit of the single compounds and/or may alter their toxic effects.

  11. Omega 3 (peripheral type benzodiazepine binding) site distribution in the rat immune system: an autoradiographic study with the photoaffinity ligand (/sup 3/H)PK 14105

    Energy Technology Data Exchange (ETDEWEB)

    Benavides, J.; Dubois, A.; Dennis, T.; Hamel, E.; Scatton, B.

    1989-04-01

    The anatomical distribution of omega 3 (peripheral type benzodiazepine binding) sites in the immune system organs of the rat has been studied autoradiographically at both macroscopic and microscopic levels of resolution using either reversible or irreversible (UV irradiation) labeling with (/sup 3/H)PK 14105. In thymus sections, (/sup 3/H)PK 14105 labeled with high affinity (Kd, derived from saturation experiments = 10.8 nM) a single population of sites which possessed the pharmacological characteristics of omega 3 sites. In the thymus gland, higher omega 3 site densities were detected in the cortex than in the medulla; in these subregions, silver grains were associated to small (10-18 microns diameter) cells. In the spleen, omega 3 sites were more abundant in the white than in the red pulp. In the white pulp, silver grains were denser in the marginal zone than in the vicinity of the central artery and labeling was, as in the thymus, associated to small cytoplasm-poor cells. In the red pulp, omega 3 site associated silver grains were observed mainly in the Bilroth cords. In the lymph nodes, the medullary region showed a higher labeling than the surrounding follicles and paracortex. A significant accumulation of silver grains was observed in the lymph node medullary cords. In the intestine, Peyer patches were particularly enriched in omega 3 sites (especially in the periphery of the follicles). The distribution of omega 3 sites in the immune system organs suggests a preferential labeling of cells of T and monocytic lineages. This is consistent with the proposed immunoregulatory properties of some omega 3 site ligands.

  12. The rat ErbB2 tyrosine kinase receptor produced in plants is immunogenic in mice and confers protective immunity against ErbB2(+) mammary cancer.

    Science.gov (United States)

    Matić, Slavica; Quaglino, Elena; Arata, Lucia; Riccardo, Federica; Pegoraro, Mattia; Vallino, Marta; Cavallo, Federica; Noris, Emanuela

    2016-01-01

    The rat ErbB2 (rErbB2) protein is a 185-kDa glycoprotein belonging to the epidermal growth factor-related proteins (ErbB) of receptor tyrosine kinases. Overexpression and mutations of ErbB proteins lead to several malignancies including breast, lung, pancreatic, bladder and ovary carcinomas. ErbB2 is immunogenic and is an ideal candidate for cancer immunotherapy. We investigated the possibility of expressing the extracellular (EC) domain of rErbB2 (653 amino acids, aa) in Nicotiana benthamiana plants, testing the influence of the 23 aa transmembrane (TM) sequence on protein accumulation. Synthetic variants of the rErbB2 gene portion encoding the EC domain, optimized with a human codon usage and either linked to the full TM domain (rErbB2_TM, 676 aa), to a portion of it (rErbB2-pTM, 662 aa), or deprived of it (rErbB2_noTM, 653 aa) were cloned in the pEAQ-HT expression vector as 6X His tag fusions. All rErbB2 variants (72-74.5 kDa) were transiently expressed, but the TM was detrimental for rErbB2 EC accumulation. rERbB2_noTM was the most expressed protein; it was solubilized and purified with Nickel affinity resin. When crude soluble extracts expressing rErbB2_noTM were administered to BALB/c mice, specific rErbB2 immune responses were triggered. A potent antitumour activity was induced when vaccinated mice were challenged with syngeneic transplantable ErbB2(+) mammary carcinoma cells. To our knowledge, this is the first report of expression of rErbB2 in plants and of its efficacy in inducing a protective antitumour immune response, opening interesting perspectives for further immunological testing.

  13. Effects of acute inhalation of aerosols generated during resistance spot welding with mild-steel on pulmonary, vascular and immune responses in rats

    Science.gov (United States)

    Zeidler-Erdely, Patti C.; Meighan, Terence G.; Erdely, Aaron; Fedan, Jeffrey S.; Thompson, Janet A.; Bilgesu, Suzan; Waugh, Stacey; Anderson, Stacey; Marshall, Nikki B.; Afshari, Aliakbar; McKinney, Walter; Frazer, David G.; Antonini, James M.

    2015-01-01

    Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m3 to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (RL) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline RL was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased RL and result in endothelial dysfunction, but otherwise had minor effects on the lung. PMID:25140454

  14. Dietary ethyl-eicosapentaenoic acid but not soybean oil reverses central interleukin-1-induced changes in behavior, corticosterone and immune response in rats.

    Science.gov (United States)

    Song, Cai; Leonard, Brian E; Horrobin, David F

    2004-03-01

    Omega (n)-3 and n-6 fatty acids are important membrane components of neurons and immune cells, and related to psychiatric and inflammatory diseases. Increased ratio of n-6/n-3 in the blood has been reported in depressed patients and in students following stress exposure. The n-3 fatty acid, eicosapentaenoic acid (ethyl-EPA) suppresses inflammation and has antidepressant properties. Interleukin (IL)-1beta can stimulate corticosterone secretion, induce anxiety and stress-like behavior and inflammatory responses. This study was to evaluate the effect of diets enriched with coconut oil, ethyl-EPA and soybean oil on central IL-1beta induced stress and anxiety-like behavior, induced changes in the concentration of prostaglandin (PG) E2 and corticosterone and the release of IL-10. Groups of rats were fed with either 5% coconut oil (as control diet), 0.2% EPA with 4.8% coconut oil or 1% EPA with 4% coconut oil and 5% soybean oil for 7 weeks. The central administration of IL-1beta induced sickness, stress and anxiety-like behavior as indicated by a reduction in body weight, decreased time spent, and the number of entries, into the open arms of the elevated plus maze and decreased exploration and entry into the central zone of the "open field" apparatus. IL-1beta also increased PGE2 and corticosterone concentrations and decreased the release of IL-10 from leucocytes. Food enriched with ethyl-EPA but not soybean oil, significantly attenuated most of these changes. These results demonstrate that ethyl-EPA has anti-inflammatory, anti-stress and anti-anxiety effects in rats.

  15. Lewis Acid-Base, Molecular Modeling, and Isotopic Labeling in a Sophomore Inorganic Chemistry Laboratory

    Science.gov (United States)

    Nataro, Chip; Ferguson, Michelle A.; Bocage, Katherine M.; Hess, Brian J.; Ross, Vincent J.; Swarr, Daniel T.

    2004-01-01

    An experiment to prepare a deuterium labeled adduct of a Lewis acid and Lewis base, to use computational methods allowing students to visualize the LUMO of Lewis acids, the HOMO of Lewis bases and the molecular orbitals of the adduct that is formed is developed. This allows students to see the interplay between calculated and experimental results.

  16. Regulation of Daicong solution on immune function for aged rat dementia model%呆聪液对老龄大鼠痴呆模型免疫功能的调节作用

    Institute of Scientific and Technical Information of China (English)

    赵淑梅; 张太国; 岳启安; 左凤英; 李光宗; 高敬宗; 尤敏; 管福来

    2002-01-01

    Objective Explore the effect of Daicong solution on immune function for aged rat dementia model.Method Basal nuclei of 22 months old rat being destroyed by bilateral electrolytic method have been established animal dementia model of learning and memory function.Lymphocyte proliferation was tested by 3H TdR incorporation methods.Spleen cell producing antibody function was determined by spleen cell mediated red cell hemolysis method.Result Daicong solution has remarkably increased lymphocyte proliferation function,compared with model groups(P< 0.01).It has strengthened the producing antibody function of the spleen cell too,compared with model group (P< 0.01). Conclusion Daicong solution has marked increased functions of cellular and humoral immunity for dementia animal model. Which is heavier than that of Naofukang.

  17. Transduction of interleukin-10 through renal artery attenuates vascular neointimal proliferation and infiltration of immune cells in rat renal allograft.

    Science.gov (United States)

    Xie, Jingxin; Li, Xueyi; Meng, Dan; Liang, Qiujuan; Wang, Xinhong; Wang, Li; Wang, Rui; Xiang, Meng; Chen, Sifeng

    2016-08-01

    Renal transplantation is the treatment of choice for end-stage renal failure. Although acute rejection is not a major issue anymore, chronic rejection, especially vascular rejection, is still a major factor that might lead to allograft dysfunction on the long term. The role of the local immune-regulating cytokine interleukin-10 (IL-10) in chronic renal allograft is unclear. Many clinical observations showed that local IL-10 level was negatively related to kidney allograft function. It is unknown this negative relationship was the result of immunostimulatory property or insufficient immunosuppression property of local IL-10. We performed ex vivo transduction before transplantation through artery of the renal allograft using adeno-associated viral vectors carrying IL-10 gene. Twelve weeks after transplantation, we found intrarenal IL-10 gene transduction significantly inhibited arterial neointimal proliferation, the number of occluded intrarenal artery, interstitial fibrosis, peritubular capillary congestion and glomerular inflammation in renal allografts compared to control allografts receiving PBS or vectors carrying YFP. IL-10 transduction increased serum IL-10 level at 4 weeks but not at 8 and 12 weeks. Renal IL-10 level increased while serum creatinine decreased significantly in IL-10 group at 12 weeks compared to PBS or YFP controls. Immunohistochemical staining showed unchanged total T cells (CD3) and B cells (CD45R/B220), decreased cytotoxic T cells (CD8), macrophages (CD68) and increased CD4+ and FoxP3+ cells in IL-10 group. In summary, intrarenal IL-10 inhibited the allograft rejection while modulated immune response.

  18. I-Metaiodobenzylguanidine Myocardial Scintigraphy in Lewy Body-Related Disorders: A Literature Review

    Directory of Open Access Journals (Sweden)

    Eun Joo Chung

    2015-05-01

    Full Text Available Lewy body-related disorders are characterized by the presence of Lewy bodies and Lewy neurites, which have abnormal aggregations of α-synuclein in the nigral and extranigral areas, including in the heart. 123I-metaiodobenzylguanidine (MIBG scintigraphy is a well-known tool to evaluate cardiac sympathetic denervation in the Lewy body-related disorders. MIBG scintigraphy showed low uptake of MIBG in the Lewy body-related disorders, including Parkinson’s disease, dementia with Lewy bodies, pure autonomic failure and rapid eye movement sleep behavior disorder. This review summarizes previous results on the diagnostic applications of MIBG scintigraphy in Lewy body-related disorders.

  19. Hydrogen activation using a novel tribenzyltin Lewis acid.

    Science.gov (United States)

    Cooper, Robert T; Sapsford, Joshua S; Turnell-Ritson, Roland C; Hyon, Dong-Hun; White, Andrew J P; Ashley, Andrew E

    2017-08-28

    Over the last decade there has been an explosion in the reactivity and applications of frustrated Lewis pair (FLP) chemistry. Despite this, the Lewis acids (LAs) in these transformations are often boranes, with heavier p-block elements receiving surprisingly little attention. The novel LA Bn3SnOTf (1) has been synthesized from simple, inexpensive starting materials and has been spectroscopically and structurally characterized. Subtle modulation of the electronics at the tin centre has led to an increase in its Lewis acidity in comparison with previously reported R3SnOTf LAs, and has facilitated low temperature hydrogen activation and imine hydrogenation. Deactivation pathways of the R3Sn(+) LA core have also been investigated.This article is part of the themed issue 'Frustrated Lewis pair chemistry'. © 2017 The Authors.

  20. Is It Lewy Body Dementia or Something Else?

    Science.gov (United States)

    ... Options Join the fight against LBD! Donate Is It LBD or Something Else? Early and accurate diagnosis ... dementia with Lewy bodies’ (DLB). Symptoms that differentiate it from Alzheimer’s include unpredictable levels of cognitive ability, ...

  1. Modulation effect of n-3 polyunsaturated fatty acids (PUFA) on target organ function as well as immune and inflammatory response of cecal ligation and puncture-induced septic rats

    Institute of Scientific and Technical Information of China (English)

    Dian-Xun Liu

    2016-01-01

    Objective:To study the modulation effect of n-3 polyunsaturated fatty acids (PUFA) on target organ function as well as immune and inflammatory reaction of cecal ligation and puncture-induced septic rats.Methods:Adult SD rats were selected as research subjects and randomly divided into control group, model group and PUFA group. Septic rat models were made by cecal ligation and puncture method and given n-3 polyunsaturated fatty acid for parenteral nutrition. Then number of apoptosis cells in intestinal mucosa, contents of intestinal flora, intestinal mucosal barrier function and immune function were detected.Results: (1) Intestinal mucosa function: the number of apoptosis cells in intestinal mucosa, intestinal E. coli contents, serum D-lactose and DAO contents as well as L/M ratio in urine of model group were higher than those of control group, and contents of bifidobacteria and lactobacilli were lower than those of control group; the number of apoptosis cells in intestinal mucosa, intestinal E. coli contents, serum D-lactose and DAO contents as well as L/M ratio in urine of PUFA group were lower than those of model group, and contents of bifidobacteria and lactobacilli were higher than those of model group; (2) Immune and inflammatory response: the number of PP nodes and PP node cells as well as contents of B cells and T cells in intestinal mucosa of model group were lower than those of control group; the number of PP nodes and PP node cells as well as contents of B cells and T cells in intestinal mucosa of PUFA group were higher than those of model group.Conclusion: n-3 polyunsaturated fatty acids (n-3PUFAs) are helpful to protect intestinal mucosal barrier function of cecal ligation and puncture-induced septic rats, regulate intestinal flora balance and improve immune and inflammatory response.

  2. The nuclear factor-κB inhibitor pyrrolidine dithiocarbamate reduces polyinosinic-polycytidilic acid-induced immune response in pregnant rats and the behavioral defects of their adult offspring

    Directory of Open Access Journals (Sweden)

    Song Xueqin

    2011-12-01

    Full Text Available Abstract Background Epidemiological studies have indicated that maternal infection during pregnancy may lead to a higher incidence of schizophrenia in the offspring. It is assumed that the maternal infection increases the immune response, leading to neurodevelopmental disorders in the offspring. Maternal polyinosinic-polycytidilic acid (PolyI:C treatment induces a wide range of characteristics in the offspring mimicking some schizophrenia symptoms in humans. These observations are consistent with the neurodevelopmental hypothesis of schizophrenia. Methods We examined whether suppression of the maternal immune response could prevent neurodevelopmental disorders in adult offspring. PolyI:C or saline was administered to early pregnant rats to mimic maternal infection, and the maternal immune response represented by tumor necrosis factor alpha (TNF-α and interleukin-10 (IL-10 levels was determined by enzyme-linked immunosorbent assays (ELISA. The NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC was used to suppress the maternal immune response. Neurodevelopmental disorders in adult offspring were examined by prepulse inhibition (PPI, passive avoidance, and active avoidance tests. Results PolyI:C administration to early pregnant rats led to elevated serum cytokine levels as shown by massive increases in serum TNF-α and IL-10 levels. The adult offspring showed defects in prepulse inhibition, and passive avoidance and active avoidance tests. PDTC intervention in early pregnant rats suppressed cytokine increases and reduced the severity of neurodevelopmental defects in adult offspring. Conclusions Our findings suggest that PDTC can suppress the maternal immune response induced by PolyI:C and partially prevent neurodevelopmental disorders of adult offspring.

  3. DatSCAN In Differential Diagnostics of Lewy Body Disease.

    Science.gov (United States)

    Luzny, Jan; Ivanova, Katerina

    2016-06-01

    Differential diagnosis between Lewy body disease and Alzheimer´s disease might be difficult because of similarities of clinical symptoms in both neurodegenerative diseases. DatSCAN is a modern functional neuroimmaging method which differentiates between this similar diseases and helps in correct treatment strategy. We report our positive experience with DatSCAN in differentiating Lewy body disease from Alzheimer´s disease. This is a case report of a woman with Lewy body disease, initially diagnosed as Alzheimer´s disease. DatSCAN neuroimmaging method was used in differential diagnosis of dementia. Memory impairment, impaired activities of daily living, sleep and behavioral disturbances were present in our case. Donepezil was well tolerated, but haloperidol administration was followed by development of severe dystonia. DatSCAN showed deficient dopaminergic presynaptic transport in substantia nigra and striatum. This finding is typical for Lewy body disease not for Alzheimer´s disease. DatSCAN neuroimmaging is a suitable method for differentiating Lewy body disease from Alzheimer´s disease. Deficient dopaminergic presynaptic transport in substantia nigra and striatum is typical for Lewy body disease.

  4. Oxidative stress-dependent changes in immune responses and cell death in the substantia nigra after ozone exposure in rat

    Science.gov (United States)

    Rivas-Arancibia, Selva; Zimbrón, Luis Fernando Hernández; Rodríguez-Martínez, Erika; Maldonado, Perla D.; Borgonio Pérez, Gabino; Sepúlveda-Parada, María

    2015-01-01

    Parkinson's disease has been associated with the selective loss of neurons in the substantia nigra pars compacta. Increasing evidence suggests that oxidative stress plays a major role. The resulting increase in reactive oxygen species triggers a sequence of events that leads to cell damage, activation of microglia cells and neuroinflammatory responses. Our objective was to study whether chronic exposure to low doses of ozone, which produces oxidative stress itself, induces progressive cell death in conjunction with glial alterations in the substantia nigra. Animals were exposed to an ozone-free air stream (control) or to low doses of ozone for 7, 15, 30, 60, or 90 days. Each group underwent (1) spectrophotometric analysis for protein oxidation; (2) western blot testing for microglia reactivity and nuclear factor kappa B expression levels; and (3) immunohistochemistry for cytochrome c, GFAP, Iba-1, NFkB, and COX-2. Our results indicate that ozone induces an increase in protein oxidation levels, changes in activated astrocytes and microglia, and cell death. NFkB and cytochrome c showed an increase until 30 days of exposure, while cyclooxygenase 2 in the substantia nigra increased from 7 days up to 90 days of repetitive ozone exposure. These results suggest that oxidative stress caused by ozone exposure induces changes in inflammatory responses and progressive cell death in the substantia nigra in rats, which could also be occurring in Parkinson's disease. PMID:25999851

  5. Lewis base activation of Lewis acids: catalytic, enantioselective vinylogous aldol addition reactions.

    Science.gov (United States)

    Denmark, Scott E; Heemstra, John R

    2007-07-20

    The generality of Lewis base catalyzed, Lewis acid mediated, enantioselective vinylogous aldol addition reactions has been investigated. The combination of silicon tetrachloride and chiral phosphoramides is a competent catalyst for highly selective additions of a variety of alpha,beta-unsaturated ketone-, 1,3-diketone-, and alpha,beta-unsaturated amide-derived dienolates to aldehydes. These reactions provided high levels of gamma-site selectivity for a variety of substitution patterns on the dienyl unit. Both ketone- and morpholine amide-derived dienol ethers afforded high enantio- and diastereoselectivity in the addition to conjugated aldehydes. Although alpha,beta-unsaturated ketone-derived dienolate did not react with aliphatic aldehydes, alpha,beta-unsaturated amide-derived dienolates underwent addition at reasonable rates affording high yields of vinylogous aldol product. The enantioselectivities achieved with the morpholine derived-dienolate in the addition to aliphatic aldehydes was the highest afforded to date with the silicon tetrachloride-chiral phosphoramide system. Furthermore, the ability to cleanly convert the morpholine amide to a methyl ketone was demonstrated.

  6. Neuroimaging characteristics of dementia with Lewy bodies.

    Science.gov (United States)

    Mak, Elijah; Su, Li; Williams, Guy B; O'Brien, John T

    2014-01-01

    This review summarises the findings and applications from neuroimaging studies in dementia with Lewy bodies (DLB), highlighting key differences between DLB and other subtypes of dementia. We also discuss the increasingly important role of imaging biomarkers in differential diagnosis and outline promising areas for future research in DLB. DLB shares common clinical, neuropsychological and pathological features with Parkinson's disease dementia and other dementia subtypes, such as Alzheimer's disease. Despite the development of consensus diagnostic criteria, the sensitivity for differential diagnosis of DLB in clinical practice remains low and many DLB patients will be misdiagnosed. The importance of developing accurate imaging markers in dementia is highlighted by the potential for treatments targeting specific molecular abnormalities as well as the responsiveness to cholinesterase inhibitors and marked neuroleptic sensitivity of DLB. We review various brain imaging techniques that have been applied to investigate DLB, including the characteristic nigrostriatal degeneration in DLB using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers. Dopamine transporter loss has proven to reliably differentiate DLB from other dementias and has been incorporated into the revised clinical diagnostic criteria for DLB. To date, this remains the 'gold standard' for diagnostic imaging of DLB. Regional cerebral blood flow, 18 F-fluorodeoxygluclose-PET and SPECT have also identified marked deficits in the occipital regions with relative sparing of the medial temporal lobe when compared to Alzheimer's disease. In addition, structural, diffusion, and functional magnetic resonance imaging techniques have shown alterations in structure, white matter integrity, and functional activity in DLB. We argue that the multimodal identification of DLB-specific biomarkers has the potential to improve ante-mortem diagnosis and contribute to our

  7. Immune Imbalance of Rats with Severe Abdominal Infection%腹腔感染大鼠机体免疫状态变化

    Institute of Scientific and Technical Information of China (English)

    喻文立; 崔乃强; 傅强; 李东华

    2011-01-01

    Objective To investigate the cellular immune function changes during sever abdominal infection, the mechanism of cellular immune imbalance and the effect of Qingrejiedu (清热解毒) decoction on the immune balance.Methods The rat model of severe abdominal infection was established by intra-abdominal E.coli administration.One hundred and 20 rats were divided into 3 groups randomly, including the control group,the model group and the treatment group.At the time of 12 h, 24, 48 h after the operation, blood sample in the abdominal aorta were collected.Th1/Th2 ratio and Regulatory T cells (Treg) percentage of CD4+ T cell was determined by means of flow cytometry respectively.Results The level of Th1/Th2 ratio increased in the early period of sepsis (12 h) but decreased in the late period of sepsis (from 24 to 72 h) in the model group; while the percentages of Treg in CD4+ T cells were significantly decreased at 12 h and 24 h and increased at 48 h and 72 h in the model group compared with those in the control group.The trends of these parameters were similar in the treatment group, but the magnitudes were smaller.There were negative correlations between the ration of Th1/Th2 and the percentage of Treg both in the model group and in the treatment group.Conclusion There is a dissonance in immunological function in rats with abdominal infection, including a depression in T cell immunological function, whereas Treg may participate in sepsis-induced immunoparalysis.Qingrejiedu( 清热解毒) herbal decoction can obviously ameliorate the immunological disturbance in rats with severe abdominal infection.%目的:观察腹腔感染大鼠的机体免疫状态变化,研究清热解毒方剂对机体细胞免疫失衡的影响.方法:采用人工胃液联合大肠杆菌腹腔内注射的方法建立大鼠腹腔感染模型,取Wistar大鼠120只随机分为对照组、模型组、清热解毒方剂组,造模后12 h、24 h、48 h、72 h经腹主动脉取血,采用流式细胞仪

  8. Identification of a nutrient-sensing transcriptional network in monocytes by using inbred rat models on a cafeteria diet.

    Science.gov (United States)

    Martínez-Micaelo, Neus; González-Abuín, Noemi; Terra, Ximena; Ardévol, Ana; Pinent, Montserrat; Petretto, Enrico; Behmoaras, Jacques; Blay, Mayte

    2016-10-01

    Obesity has reached pandemic levels worldwide. The current models of diet-induced obesity in rodents use predominantly high-fat based diets that do not take into account the consumption of variety of highly palatable, energy-dense foods that are prevalent in Western society. We and others have shown that the cafeteria (CAF) diet is a robust and reproducible model of human metabolic syndrome with tissue inflammation in the rat. We have previously shown that inbred rat strains such as Wistar Kyoto (WKY) and Lewis (LEW) show different susceptibilities to CAF diets with distinct metabolic and morphometric profiles. Here, we show a difference in plasma MCP-1 levels and investigate the effect of the CAF diet on peripheral blood monocyte transcriptome, as powerful stress-sensing immune cells, in WKY and LEW rats. We found that 75.5% of the differentially expressed transcripts under the CAF diet were upregulated in WKY rats and were functionally related to the activation of the immune response. Using a gene co-expression network constructed from the genes differentially expressed between CAF diet-fed LEW and WKY rats, we identified acyl-CoA synthetase short-chain family member 2 (Acss2) as a hub gene for a nutrient-sensing cluster of transcripts in monocytes. The Acss2 genomic region is significantly enriched for previously established metabolism quantitative trait loci in the rat. Notably, monocyte expression levels of Acss2 significantly correlated with plasma glucose, triglyceride, leptin and non-esterified fatty acid (NEFA) levels as well as morphometric measurements such as body weight and the total fat following feeding with the CAF diet in the rat. These results show the importance of the genetic background in nutritional genomics and identify inbred rat strains as potential models for CAF-diet-induced obesity. © 2016. Published by The Company of Biologists Ltd.

  9. Identification of a nutrient-sensing transcriptional network in monocytes by using inbred rat models on a cafeteria diet

    Science.gov (United States)

    Martínez-Micaelo, Neus; González-Abuín, Noemi; Terra, Ximena; Ardévol, Ana; Pinent, Montserrat; Petretto, Enrico; Blay, Mayte

    2016-01-01

    ABSTRACT Obesity has reached pandemic levels worldwide. The current models of diet-induced obesity in rodents use predominantly high-fat based diets that do not take into account the consumption of variety of highly palatable, energy-dense foods that are prevalent in Western society. We and others have shown that the cafeteria (CAF) diet is a robust and reproducible model of human metabolic syndrome with tissue inflammation in the rat. We have previously shown that inbred rat strains such as Wistar Kyoto (WKY) and Lewis (LEW) show different susceptibilities to CAF diets with distinct metabolic and morphometric profiles. Here, we show a difference in plasma MCP-1 levels and investigate the effect of the CAF diet on peripheral blood monocyte transcriptome, as powerful stress-sensing immune cells, in WKY and LEW rats. We found that 75.5% of the differentially expressed transcripts under the CAF diet were upregulated in WKY rats and were functionally related to the activation of the immune response. Using a gene co-expression network constructed from the genes differentially expressed between CAF diet-fed LEW and WKY rats, we identified acyl-CoA synthetase short-chain family member 2 (Acss2) as a hub gene for a nutrient-sensing cluster of transcripts in monocytes. The Acss2 genomic region is significantly enriched for previously established metabolism quantitative trait loci in the rat. Notably, monocyte expression levels of Acss2 significantly correlated with plasma glucose, triglyceride, leptin and non-esterified fatty acid (NEFA) levels as well as morphometric measurements such as body weight and the total fat following feeding with the CAF diet in the rat. These results show the importance of the genetic background in nutritional genomics and identify inbred rat strains as potential models for CAF-diet-induced obesity. PMID:27483348

  10. Interaction of a Cannabinoid-2 Agonist With Tramadol on Nociceptive Thresholds and Immune Responses in a Rat Model of Incisional Pain.

    Science.gov (United States)

    Stachtari, Chrysoula C; Thomareis, Olympia N; Tsaousi, Georgia G; Karakoulas, Konstantinos A; Chatzimanoli, Foteini I; Chatzopoulos, Stavros A; Vasilakos, Dimitrios G

    The aim of this study was to elucidate the antinociceptive interaction between cannabinoids and tramadol and their impact on proinflammatory response, in terms of serum intereleukin-6 (IL-6) and interleukin-2 (IL-2) release, in a rat model of incisional pain. Prospective randomized trial assessing the individual or combined application of intraperitoneal tramadol (10 mg/kg) and the selective cannabinoid-2 (CB-2) agonist (R,S)-AM1241 (1 mg/kg) applied postsurgical stress stimulus. Pharmacological specificity was established by antagonizing tramadol with naloxone (0.3 mg/kg) and (R,S)-AM1241 with SR144528 (1 mg/kg). Thermal allodynia was assessed by hot plate test 30 (T30), 60 (T60), and 120 (T120) minutes after incision. Blood samples for plasma IL-6 and IL-2 level determination were obtained 2 hours after incision. Data from 42 rats were included in the final analyses. Significant augmentation of thermal threshold was observed at all time points, after administration of either tramadol or (R,S)-AM1241 compared with the control group (P = 0.004 and P = 0.015, respectively). The combination of (R,S)-AM1241 plus tramadol promoted the induced antinociception in an important manner compared with control (P = 0.002) and (R,S)-AM1241 (P = 0.022) groups. Although the antiallodynic effect produced by tramadol was partially reversed by naloxone 30 and 60 minutes after incision (P = 0.028 and P = 0.016, respectively), SR144528 blocked the effects of (R,S)-AM1241 administration in a significant manner (P = 0.001) at all time points. Similarly, naloxone plus SR144528 also blocked the effects of the combination of (R,S)-AM1241 with tramadol at all time points (P = 0.000). IL-6 level in (R,S)-AM1241 plus tramadol group was significantly attenuated compared with control group (P = 0.000). Nevertheless, IL-2 levels remained unchanged in all experimental groups. It seems that the concomitant administration of a selective CB-2 agonist with tramadol in incisional pain model may

  11. Common Textbook and Teaching Misrepresentations of Lewis Structures

    Science.gov (United States)

    Suidan, Laila; Badenhoop, Jay K.; Glendening, Eric D.; Weinhold, Frank

    1995-07-01

    Current freshman chemistry textbooks commonly advise the drawing of Lewis structures with much emphasis on the reduction of formal charge and little on the preservation of the octet rule. This currently accepted method produces structures different from the original Lewis structures, which rarely had expanded valence shells on central atoms. Computational results from Gaussian 92 have shown us that the leading resonance structures cited in freshman chemistry textbooks are often not the most accurate to represent the molecules and are, at best, minor resonance structures, whose presentation is not worth the confusion that it causes for many first-year students. Instead, the Lewis structures that most accurately represent these molecules are the original Lewis structures, which generally abide by the octet rule. If the octet rule is more strongly stressed in the teaching of Lewis structures-thus avoiding the many complications and sources of confusion related to valence-shell expansion and reduction of formal charge-freshman chemistry students will be able to rest a little easier at night.

  12. Influence of chronic L-DOPA treatment on immune response following allogeneic and xenogeneic graft in a rat model of Parkinson's disease.

    Science.gov (United States)

    Breger, Ludivine S; Kienle, Korbinian; Smith, Gaynor A; Dunnett, Stephen B; Lane, Emma L

    2017-03-01

    Although intrastriatal transplantation of fetal cells for the treatment of Parkinson's disease had shown encouraging results in initial open-label clinical trials, subsequent double-blind studies reported more debatable outcomes. These studies highlighted the need for greater preclinical analysis of the parameters that may influence the success of cell therapy. While much of this has focused on the cells and location of the transplants, few have attempted to replicate potentially critical patient centered factors. Of particular relevance is that patients will be under continued L-DOPA treatment prior to and following transplantation, and that typically the grafts will not be immunologically compatible with the host. The aim of this study was therefore to determine the effect of chronic L-DOPA administered during different phases of the transplantation process on the survival and function of grafts with differing degrees of immunological compatibility. To that end, unilaterally 6-OHDA lesioned rats received sham surgery, allogeneic or xenogeneic transplants, while being treated with L-DOPA before and/or after transplantation. Irrespective of the L-DOPA treatment, dopaminergic grafts improved function and reduced the onset of L-DOPA induced dyskinesia. Importantly, although L-DOPA administered post transplantation was found to have no detrimental effect on graft survival, it did significantly promote the immune response around xenogeneic transplants, despite the administration of immunosuppressive treatment (cyclosporine). This study is the first to systematically examine the effect of L-DOPA on graft tolerance, which is dependent on the donor-host compatibility. These findings emphasize the importance of using animal models that adequately represent the patient paradigm.

  13. Thierry Paquot, Lewis Mumford, Lewis Mumford. Pour une juste plénitude

    OpenAIRE

    Denoun, Martin

    2015-01-01

    La collection « Les précurseurs de la décroissance » des éditions du Passager clandestin s’étoffe rapidement et couvre une période historique très large, d’Épicure ou Lao-Tseu à Murray Bookchin ou André Gorz. L’objectif de la collection est de rendre visible la continuité de thématiques appelées aujourd’hui « décroissantes » chez des auteurs aux traditions a priori hétérogènes. Lewis Mumford, historien autodidacte des villes et des techniques, entre aujourd’hui dans cette bibliothèque décrois...

  14. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  15. Experimental crescentic glomerulonephritis: a new bicongenic rat model

    Directory of Open Access Journals (Sweden)

    Zelpha D’Souza

    2013-11-01

    Crescentic glomerulonephritis (CRGN is a major cause of human kidney failure, but the underlying mechanisms are not fully understood. Wistar Kyoto (WKY rats are uniquely susceptible to CRGN following injection of nephrotoxic serum, whereas Lewis (LEW rats are resistant. Our previous genetic studies of nephrotoxic nephritis (NTN, a form of CRGN induced by nephrotoxic serum, identified Fcgr3 and Jund as WKY genes underlying the two strongest quantitative trait loci for NTN phenotypes: Crgn1 and Crgn2, respectively. We also showed that introgression of WKY Crgn1 or Crgn2 individually into a LEW background did not lead to the formation of glomerular crescents. We have now generated a bicongenic strain, LEW.WCrgn1,2, in which WKY Crgn1 and Crgn2 are both introgressed into the LEW genetic background. These rats show development of NTN phenotypes, including glomerular crescents. Furthermore, we characterised macrophage function and glomerular cytokine profiles in this new strain. Additionally, we show that LEW.WCrgn1,2 rats are resistant to the development of glomerular crescents that is usually induced following immunisation with recombinant rat α3(IVNC1, the specific Goodpasture autoantigen located in the glomerular basement membrane against which the immune response is directed in experimental autoimmune glomerulonephritis. Our results show that the new bicongenic strain responds differently to two distinct experimental triggers of CRGN. This is the first time that CRGN has been induced on a normally resistant rat genetic background and identifies the LEW.WCrgn1,2 strain as a new, potentially valuable model of macrophage-dependent glomerulonephritis.

  16. Structural features of N-glycans linked to glycoproteins expressed in three kinds of water plants: Predominant occurrence of the plant complex type N-glycans bearing Lewis a epitope.

    Science.gov (United States)

    Maeda, Megumi; Tani, Misato; Yoshiie, Takeo; Vavricka, Christopher J; Kimura, Yoshinobu

    2016-11-29

    The Japanese cedar pollen allergen (Cry j1) and the mountain cedar pollen allergen (Jun a1) are glycosylated with plant complex type N-glycans bearing Lewis a epitope(s) (Galβ1-3[Fucα1-4]GlcNAc-). The biological significance of Lewis a type plant N-glycans and their effects on the human immune system remain to be elucidated. Since a substantial amount of such plant specific N-glycans are required to evaluate immunological activity, we have searched for good plant-glycan sources to characterize Lewis a epitope-containing plant N-glycans. In this study, we have found that three water plants, Elodea nuttallii, Egeria densa, and Ceratophyllum demersum, produce glycoproteins bearing Lewis a units. Structural analysis of the N-glycans revealed that almost all glycoproteins expressed in these three water plants predominantly carry plant complex type N-glycans including the Lewis a type, suggesting that these water plants are good sources for preparation of Lewis a type plant N-glycans in substantial amounts.

  17. The Role of Naturalness in Lewis's Theory of Meaning

    Directory of Open Access Journals (Sweden)

    Brian Weatherson

    2013-05-01

    Full Text Available Many writers have held that in his later work, David Lewis adopted a theory of predicate meaning such that the meaning of a predicate is the most natural property that is (mostly consistent with the way the predicate is used. That orthodox interpretation is shared by both supporters and critics of Lewis's theory of meaning, but it has recently been strongly criticised by Wolfgang Schwarz. In this paper, I accept many of Schwarze's criticisms of the orthodox interpretation, and add some more. But I also argue that the orthodox interpretation has a grain of truth in it, and seeing that helps us appreciate the strength of Lewis's late theory of meaning.

  18. Development of a metastatic fluorescent Lewis Lung carcinoma mouse model

    DEFF Research Database (Denmark)

    Rask, Lene; Fregil, Marianne; Høgdall, Estrid;

    2013-01-01

    models. To examine the mechanisms involved in tumor metastasis, we first generated a stably transfected Lewis Lung carcinoma cell line expressing a far-red fluorescent protein, called Katushka. After in vivo growth in syngeneic mice, two fluorescent Lewis Lung cancer subpopulations were isolated from...... primary tumors and lung metastases. The metastasis-derived cells exhibited a significant improvement in in vitro invasive activity compared to the primary tumor-derived cells, using a quantitative invasion chamber assay. Moreover, expression levels of 84 tumor metastasis-related mRNAs, 88 cancer......-related microRNAs as well as Dicer and Drosha were determined using RT-qPCR. Compared to the primary Lewis Lung carcinoma subculture, the metastasis-derived cells exhibited statistically significantly increased mRNA levels for several matrix metalloproteinases as well as hepatocyte growth factor (HGF...

  19. Lewis Acid Coupled Electron Transfer of Metal-Oxygen Intermediates.

    Science.gov (United States)

    Fukuzumi, Shunichi; Ohkubo, Kei; Lee, Yong-Min; Nam, Wonwoo

    2015-12-01

    Redox-inactive metal ions and Brønsted acids that function as Lewis acids play pivotal roles in modulating the redox reactivity of metal-oxygen intermediates, such as metal-oxo and metal-peroxo complexes. The mechanisms of the oxidative CH bond cleavage of toluene derivatives, sulfoxidation of thioanisole derivatives, and epoxidation of styrene derivatives by mononuclear nonheme iron(IV)-oxo complexes in the presence of triflic acid (HOTf) and Sc(OTf)3 have been unified as rate-determining electron transfer coupled with binding of Lewis acids (HOTf and Sc(OTf)3 ) by iron(III)-oxo complexes. All logarithms of the observed second-order rate constants of Lewis acid-promoted oxidative CH bond cleavage, sulfoxidation, and epoxidation reactions of iron(IV)-oxo complexes exhibit remarkably unified correlations with the driving forces of proton-coupled electron transfer (PCET) and metal ion-coupled electron transfer (MCET) in light of the Marcus theory of electron transfer when the differences in the formation constants of precursor complexes were taken into account. The binding of HOTf and Sc(OTf)3 to the metal-oxo moiety has been confirmed for Mn(IV) -oxo complexes. The enhancement of the electron-transfer reactivity of metal-oxo complexes by binding of Lewis acids increases with increasing the Lewis acidity of redox-inactive metal ions. Metal ions can also bind to mononuclear nonheme iron(III)-peroxo complexes, resulting in acceleration of the electron-transfer reduction but deceleration of the electron-transfer oxidation. Such a control on the reactivity of metal-oxygen intermediates by binding of Lewis acids provides valuable insight into the role of Ca(2+) in the oxidation of water to dioxygen by the oxygen-evolving complex in photosystem II. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Fugle og andre observationer på Lewis og Harris

    DEFF Research Database (Denmark)

    Provencal, Philippe

    2017-01-01

    En beskrivelse af observationer af især fugle men også nogle få pattedyr på øen Lewis and Harris i de Ydre Hebrider. Observationerne fandt sted fra den 19. til den 23- april 2017.......En beskrivelse af observationer af især fugle men også nogle få pattedyr på øen Lewis and Harris i de Ydre Hebrider. Observationerne fandt sted fra den 19. til den 23- april 2017....

  1. Gear and Transmission Research at NASA Lewis Research Center

    Science.gov (United States)

    Townsend, Dennis P.

    1997-01-01

    This paper is a review of some of the research work of the NASA Lewis Research Center Mechanical Components Branch. It includes a brief review of the NASA Lewis Research Center and the Mechanical Components Branch. The research topics discussed are crack propagation of gear teeth, gear noise of spiral bevel and other gears, design optimization methods, methods we have investigated for transmission diagnostics, the analytical and experimental study of gear thermal conditions, the analytical and experimental study of split torque systems, the evaluation of several new advanced gear steels and transmission lubricants and the evaluation of various aircraft transmissions. The area of research needs for gearing and transmissions is also discussed.

  2. Mercury-induced renal autoimmunity: changes in RT6+ T-lymphocytes of susceptible and resistant rats.

    Science.gov (United States)

    Kosuda, L L; Greiner, D L; Bigazzi, P E

    1993-06-01

    The repeated administration of mercury to rats of the Brown Norway (BN) inbred strain results in a self-limiting production of autoantibodies to renal antigens (e.g., laminin) and autoimmune glomerulonephritis. In contrast, rats of the Lewis (LEW) strain do not develop renal autoimmunity after mercury treatment. Suppressor T-cells and/or the idiotype-anti-idiotype network have been implicated in the control of autoimmunity in susceptible (BN) rats as well as the "resistant" state of nonsusceptible (LEW) animals. In our investigations of the immune regulation of mercury-induced autoimmune glomerulonephritis, we have performed a phenotypic analysis of lymphocyte subpopulation in the spleens and lymph nodes of mercury-treated and control LEW, BN, and (BN x LEW) F1 hybrid rats. Of particular interest were RT6+ T-cells, a subpopulation of lymphocytes that may have immunoregulatory properties and show a relative decrease in mercury-treated BN rats concomitantly with the development of autoimmune responses to renal autoantigens. LEW rats did not develop renal autoimmunity after mercury treatment and had no significant change in the ratio of RT6+ to RT6- T-lymphocytes. Interestingly, the administration of mercury to (BN x LEW) F1 hybrid rats caused effects similar to those observed in the BN strain. Auto-immune responses to antigens of the kidney coincided with a change in the balance within the RT6 cell population, which was altered in favor of T-lymphocytes that do not express the RT6 phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. N-methylacridinium salts: carbon Lewis acids in frustrated Lewis pairs for σ-bond activation and catalytic reductions.

    Science.gov (United States)

    Clark, Ewan R; Ingleson, Michael J

    2014-10-13

    N-methylacridinium salts are Lewis acids with high hydride ion affinity but low oxophilicity. The cation forms a Lewis adduct with 4-(N,N-dimethylamino)pyridine but a frustrated Lewis pair (FLP) with the weaker base 2,6-lutidine which activates H2, even in the presence of H2O. Anion effects dominate reactivity, with both solubility and rate of H2 cleavage showing marked anion dependency. With the optimal anion, a N-methylacridinium salt catalyzes the reductive transfer hydrogenation and hydrosilylation of aldimines through amine-boranes and silanes, respectively. Furthermore, the same salt is active for the catalytic dehydrosilylation of alcohols (primary, secondary, tertiary, and ArOH) by silanes with no observable over-reduction to the alkanes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Lewis acid enhanced switching of the 1,1-dicyanodihydroazulene/vinylheptafulvene photo/thermoswitch

    DEFF Research Database (Denmark)

    Parker, Christian Richard; Tortzen, Christian Gregers; Broman, Søren Lindbæk

    2011-01-01

    Mild Lewis acids enhance the rate of the thermal conversion of vinylheptafulvene (VHF) to dihydroazulene (DHA). In the absence of light, stronger Lewis acids promote the otherwise photoinduced DHA to VHF conversion.......Mild Lewis acids enhance the rate of the thermal conversion of vinylheptafulvene (VHF) to dihydroazulene (DHA). In the absence of light, stronger Lewis acids promote the otherwise photoinduced DHA to VHF conversion....

  5. Prenatal immune challenge in rats: altered responses to dopaminergic and glutamatergic agents, prepulse inhibition of acoustic startle, and reduced route-based learning as a function of maternal body weight gain after prenatal exposure to poly IC.

    Science.gov (United States)

    Vorhees, Charles V; Graham, Devon L; Braun, Amanda A; Schaefer, Tori L; Skelton, Matthew R; Richtand, Neil M; Williams, Michael T

    2012-08-01

    Prenatal maternal immune activation has been used to test the neurodevelopmental hypothesis of schizophrenia. Most of the data are in mouse models; far less is available for rats. We previously showed that maternal weight change in response to the immune activator polyinosinic-polycytidylic acid (Poly IC) in rats differentially affects offspring. Therefore, we treated gravid Harlan Sprague-Dawley rats i.p. on embryonic day 14 with 8 mg/kg of Poly IC or Saline. The Poly IC group was divided into those that lost or gained the least weight, Poly IC (L), versus those that gained the most weight, Poly IC (H), following treatment. The study design controlled for litter size, litter sampling, sex distribution, and test experience. We found no effects of Poly IC on elevated zero maze, open-field activity, object burying, light-dark test, straight channel swimming, Morris water maze spatial acquisition, reversal, or shift navigation or spatial working or reference memory, or conditioned contextual or cued fear or latent inhibition. The Poly IC (H) group showed a significant decrease in the rate of route-based learning when visible cues were unavailable in the Cincinnati water maze and reduced prepulse inhibition of acoustic startle in females, but not males. The Poly IC (L) group exhibited altered responses to acute pharmacological challenges: exaggerated hyperactivity in response to (+)-amphetamine and an attenuated hyperactivity in response to MK-801. This model did not exhibit the cognitive, or latent inhibition deficits reported in Poly IC-treated rats but showed changes in response to drugs acting on neurotransmitter systems implicated in the pathophysiology of schizophrenia (dopaminergic hyperfunction and glutamatergic hypofunction).

  6. Lewis acidic metal catalysed organic transformations by designed multi-component structures and assemblies

    Indian Academy of Sciences (India)

    Afsar Ali; Amit P Singh; Rajeev Gupta

    2010-05-01

    This paper presents the recent developments in designing multi-component structures including metal-organic frameworks containing Lewis acidic metal ions. The emphasis has been given to understand the design elements adopted to synthesize such structures bearing Lewis acidic metal ion. Further, few important Lewis acidic metal catalysed organic transformation reactions have been discussed demonstrating the importance of such materials for practical purposes.

  7. File list: Unc.Lng.50.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Pol.Lng.05.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Oth.Lng.20.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: Unc.Lng.10.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: Unc.Lng.05.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: His.Lng.20.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: DNS.Lng.50.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: His.Lng.10.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: Pol.Lng.50.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: Pol.Lng.20.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: Oth.Lng.10.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: DNS.Lng.20.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: His.Lng.05.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Oth.Lng.05.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Lng.05.AllAg.Carcinoma,_Lewis_Lung mm9 TFs and others Lung Carcinoma, Lewis Lun...g http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Lng.05.AllAg.Carcinoma,_Lewis_Lung.bed ...

  1. File list: Unc.Lng.20.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Lng.20.AllAg.Carcinoma,_Lewis_Lung mm9 Unclassified Lung Carcinoma, Lewis Lung ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Lng.20.AllAg.Carcinoma,_Lewis_Lung.bed ...

  2. File list: Pol.Lng.10.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: DNS.Lng.10.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: His.Lng.50.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: Oth.Lng.50.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Lng.50.AllAg.Carcinoma,_Lewis_Lung mm9 TFs and others Lung Carcinoma, Lewis Lun...g http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Lng.50.AllAg.Carcinoma,_Lewis_Lung.bed ...

  6. Immune response

    Science.gov (United States)

    ... and tetanus antitoxin are examples of passive immunization. BLOOD COMPONENTS The immune system includes certain types of white ... lymphocytes develop, they normally learn to tell the difference between your own body tissues and substances that ...

  7. Traditional Chinese medicine Yisui Tongjing relieved neural severity in experimental autoimmune neuritis rat model

    Science.gov (United States)

    Zhang, Erli; Li, Mingquan; Zhao, Jianjun; Dong, Yuxiang; Yang, Xueqin; Huang, Jingbo

    2016-01-01

    Objective To study the effect of Yisui Tongjing (YSTJ) prescription on motor nerve conduction velocity (MNCV) and microstructure of the sciatic nerve in experimental autoimmune neuritis (EAN) rats, the Guillain–Barré syndrome classic animal models. Materials and methods In this study, we established an EAN model in Lewis rats by immunization. We evaluated the potential clinical application of a traditional Chinese medicine YSTJ by intragastric administration and compared its effect with immunoglobulin. The sciatic MNCV was measured by electrophysiology experiment. Hematoxylin–eosin staining and transmission electron microscope analysis were used to determine the pathologically morphological changes before and after YSTJ application. Results We found that application of YSTJ could significantly alleviate the clinical signs in EAN rats. The treatment also increased MNCV in the sciatic nerve compared to that in the untreated nerve. Demyelination in the sciatic nerve in EAN rats was significantly ameliorated, and newly generated myelinated nerve fibers were observed with treatment of high dose of YSTJ. Conclusion This study showed that the traditional Chinese medicine YSTJ was likely to serve as a therapeutic medicine in autoimmune neuropathies, providing an effective and economic means to the treatment of Guillain–Barré syndrome. PMID:27729792

  8. Frustrated Lewis pairs-assisted reduction of carbonyl compounds

    DEFF Research Database (Denmark)

    Marek, Ales; Pedersen, Martin Holst Friborg

    2015-01-01

    An alternative and robust method for the reduction of carbonyl groups by frustrated Lewis pairs (FLPs) is reported in this paper. With its very mild reaction conditions, good to excellent yields, absolute regioselectivity and the non-metallic character of the reagent, it provides an excellent too...

  9. Probability without certainty : foundationalism and the Lewis-Reichenbach debate

    NARCIS (Netherlands)

    Atkinson, David; Peijnenburg, Jeanne

    2006-01-01

    Like many discussions on the pros and cons of epistemic foundationalism, the debate between C. I. Lewis and H. Reichenbach dealt with three concerns: the existence of basic beliefs, their nature, and the way in which beliefs are related. In this paper we concentrate on the third matter, especially o

  10. Daniel Day-Lewis - veri peab voolama / Kristiina Davidjants

    Index Scriptorium Estoniae

    Davidjants, Kristiina, 1974-

    2008-01-01

    Iiri-juudi näitleja Daniel Day-Lewis, kes võitis oma rolliga P.T. Andersoni filmis "Veri hakkab voolama" parima meespeaosatäitja Oscari. Tema põhjalikust tööst rollidega läbi tema filmiloomingu

  11. Californian Genius: Lewis Terman's Gifted Child in Regional Perspective

    Science.gov (United States)

    Beauvais, Clémentine

    2016-01-01

    This article pays attention to the regional embeddedness of early research on giftedness, looking principally at the works of Lewis Terman and his peers, between the 1910s and 1930s. The rhetoric, ideology, and aesthetics of giftedness in those early works were, I argue, stamped by the context and imaginary of Progressive-Era California and shaped…

  12. Sialyl Lewis x expression in cervical scrapes of premalignant lesions

    Indian Academy of Sciences (India)

    Noé Velázquez-Márquez; Gerardo Santos López; Lucio Jiménez Aranda; Julio Reyes Leyva; Verónica Vallejo Ruiz

    2012-12-01

    Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumour progression and metastases. Altered expression of glycosidic antigens has been reported in cervical cancer. In cervix premalignant lesions, an increased expression of sialic acid has been reported. In the present study we determined the expression profiles of the glycosidic antigens Tn, sialyl Tn (sTn), Lewis a (Lea), sialyl Lewis a (sLea), Lewis x (Lex) and sialyl Lewis x (sLex) in cervical scrapes with cytological diagnoses of normal, low-grade squamous intraepithelial lesions (LGSIL) and high-grade squamous intraepithelial lesions (HGSIL). Cervical scrapings were collected to detect tumour antigens expressions by flow cytometry using monoclonal antibodies. Cytometry analysis of Tn, sTn, Lea and Lex did not reveal differences at the expression level among groups. The number of positive cells to sLea antigen increased in the HGSIL group with respect to the normal group (=0.0495). The number of positive cells to sLex antigen in the samples increased with respect to the grade of squamous intraepithelial lesion (SIL) ( < 0.001, Mann–Whitney U test). The intensity of expression of this antigen increased in the HGSIL samples with respect to normal samples ( < 0.0068). sLex antigen could be a candidate to be used as biomarker for the early diagnosis of cervical cancer.

  13. Telling Lewis Hine's Story: Russell Freedman's "Kids at Work."

    Science.gov (United States)

    Zarnowski, Myra

    In "Kids at Work," Russell Freedman explores the world of child labor during the years 1908-1918 when Lewis Hine, "teacher-crusader," worked as an investigative photographer for the National Child Labor Committee (NCLC). Hine's writing and the photos he gathered from across the country revealed a "shocking reality that…

  14. Californian Genius: Lewis Terman's Gifted Child in Regional Perspective

    Science.gov (United States)

    Beauvais, Clémentine

    2016-01-01

    This article pays attention to the regional embeddedness of early research on giftedness, looking principally at the works of Lewis Terman and his peers, between the 1910s and 1930s. The rhetoric, ideology, and aesthetics of giftedness in those early works were, I argue, stamped by the context and imaginary of Progressive-Era California and shaped…

  15. Modified NASA-Lewis Chemical Equilibrium Code for MHD applications

    Energy Technology Data Exchange (ETDEWEB)

    Sacks, R. A.; Geyer, H. K.; Grammel, S. J.; Doss, E. D.

    1979-12-01

    A substantially modified version of the NASA-Lewis Chemical Equilibrium Code has recently been developed. The modifications were designed to extend the power and convenience of the Code as a tool for performing combustor analysis for MHD systems studies. This report describes the effect of the programming details from a user point of view, but does not describe the Code in detail.

  16. Probability without certainty : foundationalism and the Lewis-Reichenbach debate

    NARCIS (Netherlands)

    Atkinson, David; Peijnenburg, Jeanne

    Like many discussions on the pros and cons of epistemic foundationalism, the debate between C. I. Lewis and H. Reichenbach dealt with three concerns: the existence of basic beliefs, their nature, and the way in which beliefs are related. In this paper we concentrate on the third matter, especially

  17. Daniel Day-Lewis - veri peab voolama / Kristiina Davidjants

    Index Scriptorium Estoniae

    Davidjants, Kristiina, 1974-

    2008-01-01

    Iiri-juudi näitleja Daniel Day-Lewis, kes võitis oma rolliga P.T. Andersoni filmis "Veri hakkab voolama" parima meespeaosatäitja Oscari. Tema põhjalikust tööst rollidega läbi tema filmiloomingu

  18. 金双歧肠内免疫生态营养对创伤后大鼠肠道免疫功能及损失修复的影响%Effects of golden bifid intestinal immune ecological supplements on rat intestinal immune and its damage repair

    Institute of Scientific and Technical Information of China (English)

    李诗杰; 栗芳军; 杨志家; 郭俊强; 王勇

    2015-01-01

    Objective To explore the efficacy of live combined bifidobacterium and lactobacillus tablets ( Jinshuangqi) enteral ccological immune nutrition on the intestinal immune and its damage repair in wound Wistar rats.Methods Thirty male Wistar rats of small intestine trauma model were divided into two groups:experiment and control groups with each 15 rats.Rats in the control group were given regular nutrition forage and rats in the experiment group were given live combined bifidobacterium and lactobacillus tablets with 10 CFU・ d -1 .At time of 7 days after administration the rates were put to death.And the status of small bowel of the rats was observed.The immunoglobulin A ( IgA ) , CD3+, CD4+and CD8+cell quantity of the small bowel mueosa were de-tected by immunohistochemical array.Results The villus height,intesti-nal gland crypt depth and mucosal thickness in the experiment group were better than that of control group (P<0.05).The quantity of IgA,CD3+, CD4+,CD8+cell of the rats in experiment group were significantly higher than control group(P<0.05).Conclusion Intestinal immune ecologi-cal nutrition can strengthen the rat intestinal immune function and pro-mote restoration of the damage.%目的:探讨金双歧肠内免疫生态营养制剂对大鼠肠道免疫及损伤修复功能的影响。方法雄性清洁级Wistar大鼠30只,小肠损伤造模成功后,按体重随机分为对照组15只和实验组15只。造模成功后12 h,2组开始分4次给予180 kcal・( kg・ d)-1的标准等氮热量灌胃,实验组同时给予金双歧10 CFU・ d-1,灌胃7 d后,断颈处死大鼠。取大鼠小肠组织,苏木素-伊红染色,观察小肠绒毛高度、肠腺隐窝深度;用免疫组织化学技术检测小肠组织中免疫球蛋白A( IgA)、及CD3+阳性T淋巴细胞、CD4+阳性T淋巴细胞、CD8+阳性T淋巴细胞表达水平,比较2组的差别。结果对照组,大鼠体重增长速度低于实验组,第5

  19. Effects of Immune Activation during Early or Late Gestation on N-Methyl-d-Aspartate Receptor Measures in Adult Rat Offspring

    Directory of Open Access Journals (Sweden)

    Tasnim Rahman

    2017-09-01

    Full Text Available BackgroundGlutamatergic receptor [N-methyl-d-aspartate receptor (NMDAR] alterations within cortex, hippocampus, and striatum are linked to schizophrenia pathology. Maternal immune activation (MIA is an environmental risk factor for the development of schizophrenia in offspring. In rodents, gestational timing of MIA may result in distinct behavioral outcomes in adulthood, but how timing of MIA may impact the nature and extent of NMDAR-related changes in brain is not known. We hypothesize that NMDAR-related molecular changes in rat cortex, striatum, and hippocampus are induced by MIA and are dependent on the timing of gestational inflammation and sex of the offspring.MethodsWistar dams were treated the with viral mimic, polyriboinosinic:polyribocytidylic acid (polyI:C, or vehicle on either gestational day 10 or 19. Fresh-frozen coronal brain sections were collected from offspring between postnatal day 63–91. Autoradiographic binding was used to infer levels of the NMDAR channel, and NR2A and NR2B subunits in cortex [cingulate (Cg, motor, auditory], hippocampus (dentate gyrus, cornu ammonis area 3, cornu ammonis area 1, and striatum [dorsal striatum, nucleus accumbens core, and nucleus accumbens shell (AS]. NR1 and NR2A mRNA levels were measured by in situ hybridization in cortex, hippocampus, and striatum in male offspring only.ResultsIn the total sample, NMDAR channel binding was elevated in the Cg of polyI:C offspring. NR2A binding was elevated, while NR2B binding was unchanged, in all brain regions of polyI:C offspring overall. Male, but not female, polyI:C offspring exhibited increased NMDAR channel and NR2A binding in the striatum overall, and increased NR2A binding in the cortex overall. Male polyI:C offspring exhibited increased NR1 mRNA in the AS, and increased NR2A mRNA in cortex and subregions of the hippocampus.ConclusionMIA may alter glutamatergic signaling in cortical and hippocampal regions via alterations in NMDAR indices; however

  20. Cyprinus carpio Decoction Improves Nutrition and Immunity and Reduces Proteinuria through Nephrin and CD2AP Expressions in Rats with Adriamycin-Induced Nephropathy

    OpenAIRE

    Yumei Qi; Huijuan Xiao; Changjie Xu; Xiaojian Tian; Hui Wu; Wei Shen

    2012-01-01

    Cyprinus carpio decoction (CCD) is a well-known Chinese food medicine formula, accepted widely as a useful therapy in preventing edema and proteinuria caused by renal disease. However, the mechanism underlying this effect remains unclear. The current study investigated the potential mechanism of CCD in alleviating nephropathy induced by adriamycin (ADR) in rats. 70  eight-week-old Wistar rats were randomly divided into normal, model, fosinopril, YD, YG groups. All rats except for the normal g...

  1. Guanethidine-induced sympathectomy in the nude rat

    DEFF Research Database (Denmark)

    Juul, A; Juul, P; Christensen, H B

    1989-01-01

    Guanethidine sulphate 40 mg/kg was administered intraperitoneally daily for 14 days to normal Lewis rats and athymic nude rats of a Lewis background (rnu/rnu). Histological examination of the superior cervical ganglia demonstrated a pronounced chromatolysis of the neurones and a loss of the major...... part of the nerve cells accompanied by an increased number of small mononuclear inflammatory cells. The extent of chromatolysis and nerve cell death induced by guanethidine did not differ between normal and nude rats, whereas the increase of the number of mononuclear cells was lower in the nude rats...... than in the normal rats (163 and 268 per cent respectively of the saline treated controls, P less than 0.01). Since guanethidine induced nerve cell death in the T-cell deficient nude rat to the same extent as in normal rats, it is concluded, that the effect is caused by either a thymus...

  2. Tribute to Erwin Felix Lewy-Bertaut; Hommage a Erwin Felix Lewy-Bertaut

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-07-01

    Erwin Lewy (alias Felix Bertaut) was born in 1913 in Germany, he emigrated to France where he undertook graduate studies in chemistry. Then, he joined the powder central laboratory where he learnt how to use international tables for structure determination. His thesis work was the X-ray study of the statistical distribution of the size of iron grains. The method Bertaut developed is still a reference in powder granulometry. Bertaut was also interested in the nascent neutron diffraction method and he flew to the United-States to improve his knowledge on this topic. Felix Bertaut created the neutron diffraction laboratory in the atomic research center in Grenoble and later he headed the CNRS' crystallography laboratory till 1982. Felix Bertaut and his laboratories became internationally renowned in crystallography, neutron diffraction and magnetism. He favored the scientific cooperation between France and Germany that led to the creation of the Laue-Langevin Institute (ILL). The ILL became European and was a key partner for building the European Synchrotron Facility (ESRF) in Grenoble. Bertaut was elected as a full member of the French Academy of Sciences in 1979, he died in 2003. (A.C.)

  3. LRRK2 in Parkinson's disease and dementia with Lewy bodies

    Directory of Open Access Journals (Sweden)

    Zhu Xiongwei

    2006-11-01

    Full Text Available Abstract Background Mutations in LRRK2 encoding leucine-rich repeat kinase 2 are thus far the most frequent genetic cause associated with autosomal dominant and idiopathic Parkinson's disease (PD. To examine whether LRRK2 is directly associated with neuropathology of PD and other related disorders, we analyzed LRRK2 in brains of patients affected by PD and dementia with Lewy bodies (DLB using highly specific antibodies to LRRK2. Results We demonstrated that anti-LRRK2 antibodies strongly labelled brainstem and cortical Lewy bodies, the pathological hallmarks of PD and DLB, respectively. In addition, anti-LRRK2 also labelled brain vasculature, axons, and neuronal cell bodies. Interestingly, the immunocytochemical profile of LRRK2 varied with different antibodies depending upon specific antigenic sites along the LRRK2 protein. All anti-LRRK2 antibodies tested that were raised against various regions of LRRK2, were found to be immunoreactive to recombinant LRRK2 on Western blots. However, only the antibodies raised against the N-terminal and C-terminal regions of LRRK2, but not the regions containing folded protein domains, were positive in immunolabeling of Lewy bodies, suggesting a differential exposure of specific antigenic sites of LRRK2 on tissue sections. Conclusion We conclude that LRRK2 is a component of Lewy bodies in both PD and DLB, and therefore plays an important role in the Lewy body formation and disease pathogenesis. Information on the cellular localization of LRRK2 under normal and pathological conditions will deepen our understanding of its functions and molecular pathways relevant to the progression of PD and related disorders.

  4. Comentarios sobre dos ensayos de sir Arthur Lewis

    Directory of Open Access Journals (Sweden)

    Currie Lauchlin

    1999-06-01

    Full Text Available

    Es un texto inédito del Profesor Lauchlin Currie, escrito en 1980 cuando todavía ocupaba su oficina en el Departamento Nacional de Planeación, En lo esencial, se trata de una crítica de algunos argumentos expuestos por Lewis en su breve libro
    The Evolution of the International Economic Order, publicado en inglés en 1978 y dos años más tarde en castellano por el Colegio de México. El problema central de este libro es el de por qué algunos países son ricos y otros son pobres. La respuesta de Lewis no dejó satisfecho al profesor Currie. A lo largo de este comentario, se observa un contrapunteo entre dos enfoques teóricos de la economía del desarrollo: la de Lewis -inicialmente expuesta en su celebre artículo sobre el desarrollo económico con oferta ilimitada de trabajo-que enfatiza la necesidad de generar un excedente agrícola como punto de partida del proceso; y la de Currie, que señala la posibilidad del crecimiento desequlibrado liderado por la actividad económica urbana, específicamente por el sector de la construcción. Aunque el profesor Currie destaca sus diferencias con Lewis, las conclusiones de ambos autores tienden a converger en torno de un punto que se resume en una frase del ensayo de Lewis, no citada en el comentario: "El motor del crecimiento debe ser el cambio tecnológico, y el comercio internacional debe servir como lubricante y no como combustible". Como bien señala el profesor Currie en su análisis, a la larga es irrelevante cuál sea el sector donde se presente ese cambio tecnológico.

  5. Lewis Acids as Activators in CBS-Catalysed Diels-Alder Reactions: Distortion Induced Lewis Acidity Enhancement of SnCl4.

    Science.gov (United States)

    Nödling, Alexander R; Möckel, Robert; Tonner, Ralf; Hilt, Gerhard

    2016-09-05

    The effect of several Lewis acids on the CBS catalyst (named after Corey, Bakshi and Shibata) was investigated in this study. While (2) H NMR spectroscopic measurements served as gauge for the activation capability of the Lewis acids, in situ FT-IR spectroscopy was employed to assess the catalytic activity of the Lewis acid oxazaborolidine complexes. A correlation was found between the Δδ((2) H) values and rate constants kDA , which indicates a direct translation of Lewis acidity into reactivity of the Lewis acid-CBS complexes. Unexpectedly, a significant deviation was found for SnCl4 as Lewis acid. The SnCl4 -CBS adduct was much more reactive than the Δδ((2) H) values predicted and gave similar reaction rates to those observed for the prominent AlBr3 -CBS adduct. To rationalize these results, quantum mechanical calculations were performed. The frontier molecular orbital approach was applied and a good correlation between the LUMO energies of the Lewis acid-CBS-naphthoquinone adducts and kDA could be found. For the SnCl4 -CBS-naphthoquinone adduct an unusual distortion was observed leading to an enhanced Lewis acidity. Energy decomposition analysis with natural orbitals for chemical valence (EDA-NOCV) calculations revealed the relevant interactions and activation mode of SnCl4 as Lewis acid in Diels-Alder reactions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Triazole-linked fluorescent bisboronic acid capable of selective recognition of the Lewis Y antigen.

    Science.gov (United States)

    Wang, Yan'en; Rong, Ruixue; Chen, Hua; Zhu, Mengyuan; Wang, Binghe; Li, Xiaoliu

    2017-05-01

    Cell surface carbohydrates of the Lewis blood group antigens, Lewis X (Le(x)), Lewis Y (Le(y)), Lewis A (Le(a)), and their sialylated derivatives, such as sialy Lewis X (sLe(x)) and sialy Lewis A (sLe(a)), play important roles in various recognition processes. These cell surface carbohydrates have also been associated with the development and progression of many types of cancers. Recently, we synthesized four anthracene-based fluorescent bisboronic acid sensors (compounds 2a-d) linked by 'click' chemistry with tethers of different lengths to match the epitope of various Lewis group of sugars. Among the four compounds, 2a appears to have both high sensitivity and selectivity for Le(y) among other carbohydrate antigens. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Regulatory effects of electro-acupuncture at Zusanli on ir-SP content in rat pituitary gland and peripheral blood and their immunity

    Institute of Scientific and Technical Information of China (English)

    Wei Gao; Yu Xin Huang; Qin Li Wang; Hong Chen; Da Yong Song

    2000-01-01

    It has been reported in many studies that electroacupuncture (EA) can positively regulate erythrocytic immunity and T-lymphocytic subgroups[1-8].Nevertheless, its mechanism remains to be explored. In the present study, a multi-group, multi-stepped and multiindexed observation was conducted on the effects of EA on erythyrocytic immunity and T-lymphocytic subgroups. A simultaneous assay of the changes in immunoreactivesubstance-P (ir-SP) content in the pituitary gland and peripheral blood was also carried out. The objective of the study was to investigate the regulatory effects of the immune system and their possible mechanism in the treatment of relevant diseases with EA.

  8. Effect of a high-fat--high-fructose diet, stress and cinnamon on central expression of genes related to immune system, hypothalamic-pituitary-adrenocortical axis function and cerebral plasticity in rats.

    Science.gov (United States)

    Marissal-Arvy, Nathalie; Batandier, Cécile; Dallennes, Julien; Canini, Frédéric; Poulet, Laurent; Couturier, Karine; Hininger-Favier, Isabelle; Moisan, Marie-Pierre; Roussel, Anne-Marie; Mormède, Pierre

    2014-04-14

    The intake of a high-fat/high-fructose (HF/HFr) diet is described to be deleterious to cognitive performances, possibly via the induction of inflammatory factors. An excess of glucocorticoids is also known to exert negative effects on cerebral plasticity. In the present study, we assessed the effects of an unbalanced diet on circulating and central markers of inflammation and glucocorticoid activity, as well as their reversal by dietary cinnamon (CN) supplementation. A group of male Wistar rats were subjected to an immune challenge with acute lipopolysaccharide under a HF/HFr or a standard diet. Another group of Wistar rats were fed either a HF/HFr or a control diet for 12 weeks, with or without CN supplementation, and with or without restraint stress (Str) application before being killed. We evaluated the effects of such regimens on inflammation parameters in the periphery and brain and on the expression of actors of brain plasticity. To assess hypothalamic-pituitary-adrenocortical axis activity, we measured the plasma concentrations of corticosterone and the expression of central corticotrophin-releasing hormone, mineralocorticoid receptor, glucocorticoid receptor and 11β-hydroxysteroid dehydrogenase. We found that the HF/HFr diet induced the expression of cytokines in the brain, but only after an immune challenge. Furthermore, we observed the negative effects of Str on the plasma concentrations of corticosterone and neuroplasticity markers in rats fed the control diet but not in those fed the HF/HFr diet. Additionally, we found that CN supplementation exerted beneficial effects under the control diet, but that its effects were blunted or even reversed under the HF/HFr diet. CN supplementation could be beneficial under a standard diet. [corrected].

  9. From Bidentate Gallium Lewis Acids to Supramolecular Complexes.

    Science.gov (United States)

    Horstmann, Jan; Hyseni, Mentor; Mix, Andreas; Neumann, Beate; Stammler, Hans-Georg; Mitzel, Norbert W

    2017-05-22

    Bidentate gallium Lewis acids were prepared by the reaction of diethynyldiphenylsilane with neat trimethyl- or triethylgallium. Bis[(dimethylgallyl)ethynyl]diphenylsilane (1) and diethylgallyl derivative 2 were characterized as Et2 O or pyridine adducts by NMR spectroscopy; 2⋅2Py was isolated. Lewis acids 1 and 2 form host-guest adducts with bidentate nitrogen bases, but defined cyclic 1:1 adducts are only formed between 1 and bases with matching N⋅⋅⋅N distances: 4,4'-dimethyl-3,3'-bipyridinylacetylene (3), bis[(pyridin-3-yl)ethynyl]diphenylsilane (4), and bis[(2-methylpyridin-5-yl)ethynyl]diphenylsilane (5). The structures of adducts 1⋅3, 1⋅4, and 1⋅5 were established by X-ray diffraction experiments. 2⋅2Py reacts with DABCO to afford polymeric (DABCO-2-)n . © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Chemical Inventory Management at NASA Lewis Research Center

    Science.gov (United States)

    Kraft, Shirley S.; Homan, Joseph R.; Bajorek, Michael J.; Dominguez, Manuel B.; Smith, Vanessa L.

    1997-01-01

    The Chemical Management System (CMS) is a client/server application developed with Power Builder and Sybase for the Lewis Research Center (LeRC). Power Builder is a client-server application development tool, Sybase is a Relational Database Management System. The entire LeRC community can access the CMS from any desktop environment. The multiple functions and benefits of the CMS are addressed.

  11. C.S.Lewis: The Chronicles of Narnia and imagination

    OpenAIRE

    Gojkošek, Monika

    2015-01-01

    The thesis entitled C. S. Lewis: The Chronicles of Narnia and imagination primarily focuses on the term fantastic novel, its development in Slovene literature and the definition of the term itself which changed during time. Since J. J. Kenda places The Chronicles of Narnia among fantasy literature a special emphasis is also given to the latter term. The second part of the thesis deals with the stories of The Chronicles of Narnia and the circumstances of their origin. An important part of the...

  12. Thermal degradation of polystyrene by Lewis acids in solution

    OpenAIRE

    2002-01-01

    The degradation of polystyrene in various Lewis acids [aluminum chloride, ferric chloride, borontriflouride etherate, and tin(IV) chloride] at different temperatures (75-125 degreesC) has been studied in this work. The evolution of the molecular weight distribution (MWD) has been modeled using continuous distribution kinetics with a stoichiometric kernel for random chain scission. The degradation rate was the highest in the presence of aluminum chloride. The reactions were also carried out at...

  13. Olmesartan, an AT1 Antagonist, Attenuates Oxidative Stress, Endoplasmic Reticulum Stress and Cardiac Inflammatory Mediators in Rats with Heart Failure Induced by Experimental Autoimmune Myocarditis

    Science.gov (United States)

    Sukumaran, Vijayakumar; Watanabe, Kenichi; Veeraveedu, Punniyakoti T.; Gurusamy, Narasimman; Ma, Meilei; Thandavarayan, Rajarajan A.; Lakshmanan, Arun Prasath; Yamaguchi, Ken'ichi; Suzuki, Kenji; Kodama, Makoto

    2011-01-01

    Studies have demonstrated that angiotensin II has been involved in immune and inflammatory responses which might contribute to the pathogenesis of immune-mediated diseases. Recent evidence suggests that oxidative stress may play a role in myocarditis. Here, we investigated whether olmesartan, an AT1R antagonist protects against experimental autoimmune myocarditis (EAM) by suppression of oxidative stress, endoplasmic reticulum (ER) stress and inflammatory cytokines. EAM was induced in Lewis rats by immunization with porcine cardiac myosin, were divided into two groups and treated with either olmesartan (10 mg/kg/day) or vehicle for a period of 21 days. Myocardial functional parameters measured by hemodynamic and echocardiographic analyses were significantly improved by the treatment with olmesartan compared with those of vehicle-treated rats. Treatment with olmesartan attenuated the myocardial mRNA expressions of proinflammatory cytokines, [Interleukin (IL)-1β, monocyte chemoattractant protein-1, tumor necrosis factor-α and interferon-γ)] and the protein expression of tumor necrosis factor-α compared with that of vehicle-treated rats. Myocardial protein expressions of AT1R, NADPH oxidase subunits (p47phox, p67phox, gp91phox) and the expression of markers of oxidative stress (3-nitrotyrosine and 4-hydroxy-2-nonenal), and the cardiac apoptosis were also significantly decreased by the treatment with olmesartan compared with those of vehicle-treated rats. Furthermore, olmesartan treatment down-regulated the myocardial expressions of glucose regulated protein-78, growth arrest and DNA damage-inducible gene, caspase-12, phospho-p38 mitogen-activated protein kinase (MAPK) and phospho-JNK. These findings suggest that olmesartan protects against EAM in rats, at least in part via suppression of oxidative stress, ER stress and inflammatory cytokines. PMID:21383952

  14. Development of Fluorous Lewis Acid-Catalyzed Reactions

    Directory of Open Access Journals (Sweden)

    Joji Nishikido

    2006-08-01

    Full Text Available Organic synthetic methodology in the 21st century aims to conform to the principles of green sustainable chemistry (GSC and we may expect that in the future, the realization of GSC will be an important objective for chemical industries. An important aim of synthetic organic chemistry is to implement waste-free and environmentally-benign industrial processes using Lewis acids as versatile as aluminum choride. A key technological objective of our work in this area has been to achieve a “catalyst recycling system that utilizes the high activity and structural features of fluorous Lewis acid catalysts”. Thus, we have developed a series of novel fluorous Lewis acid catalysts, namely the ytterbium(III, scandium(III, tin(IV or hafnium(IV bis(perfluoroalkanesulfonylamides or tris(perfluoro- alkanesulfonylmethides. Our catalysts are recyclable and effective for acylations of alcohols and aromatics, Baeyer-Villiger reactions, direct esterifications and transesterifications in a fluorous biphasic system (FBS, in supercritical carbon dioxide and on fluorous silica gel supports.

  15. Lewis acidity enhancement of triarylborane by appended phosphine oxide groups.

    Science.gov (United States)

    Kwak, Jaewoo; Nghia, Nguyen Van; Lee, Junseong; Kim, Hyoseok; Park, Myung Hwan; Lee, Min Hyung

    2015-03-14

    A series of mono-, di-, and tri-phosphine oxide substituted triarylboranes, Mes2BAr (1), MesBAr2 (2), and BAr3 (3) (Ar = 4-(Ph2PO)-2,6-Me2-C6H2) were prepared to investigate the effect of a phosphine oxide group (Ph2PO) on Lewis acidity enhancement of triarylboranes. The X-ray crystal structure of 3 revealed peripheral decoration of Ph2PO groups with a C3-axis perpendicular to the trigonal boron center. UV/Vis absorption and PL spectra indicated a significant contribution of π(Mes or phenylene) → pπ(B) charge transfer in the lower-energy electronic transition. The reduction potential measured by cyclic voltammetry showed apparent LUMO stabilization by introduction of phosphine oxide groups, the extent of which gradually increased with the increasing number of phosphine oxide groups. Lewis acidity enhancement was also supported by the gradual increase in fluoride ion affinity in the order 3 > 2 > 1. Theoretical calculations suggest that introduction of a Ph2PO group into a triarylborane significantly enhances the Lewis acidity of the boron center via an inductive electron-withdrawing effect and this effect is additive for multiple phosphine oxide groups.

  16. Diagnosis and management of dementia with Lewy bodies

    Science.gov (United States)

    Boeve, Bradley F.; Dickson, Dennis W.; Halliday, Glenda; Taylor, John-Paul; Weintraub, Daniel; Aarsland, Dag; Galvin, James; Attems, Johannes; Ballard, Clive G.; Bayston, Ashley; Beach, Thomas G.; Blanc, Frédéric; Bohnen, Nicolaas; Bonanni, Laura; Bras, Jose; Brundin, Patrik; Burn, David; Chen-Plotkin, Alice; Duda, John E.; El-Agnaf, Omar; Feldman, Howard; Ferman, Tanis J.; ffytche, Dominic; Fujishiro, Hiroshige; Galasko, Douglas; Goldman, Jennifer G.; Gomperts, Stephen N.; Graff-Radford, Neill R.; Honig, Lawrence S.; Iranzo, Alex; Kantarci, Kejal; Kaufer, Daniel; Kukull, Walter; Lee, Virginia M.Y.; Leverenz, James B.; Lewis, Simon; Lippa, Carol; Lunde, Angela; Masellis, Mario; Masliah, Eliezer; McLean, Pamela; Mollenhauer, Brit; Montine, Thomas J.; Moreno, Emilio; Mori, Etsuro; Murray, Melissa; O'Brien, John T.; Orimo, Sotoshi; Postuma, Ronald B.; Ramaswamy, Shankar; Ross, Owen A.; Salmon, David P.; Singleton, Andrew; Taylor, Angela; Thomas, Alan; Tiraboschi, Pietro; Toledo, Jon B.; Trojanowski, John Q.; Tsuang, Debby; Walker, Zuzana; Yamada, Masahito; Kosaka, Kenji

    2017-01-01

    The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support. PMID:28592453

  17. Lewis' Educational and Research Collaborative Intership Program Grant Closeout Report

    Science.gov (United States)

    2003-01-01

    The Lewis' Educational and Research Collaborative Internship Program (LERCIP) is a collaborative undertaking by the Office of Educational Programs at NASA Glenn Research Center at Lewis Field (formerly NASA Lewis Research Center) and the Ohio Aerospace Institute. This program provides 10-week internships and 10 or 12-week fellowships for undergraduate/graduate students and secondary school teachers. Approximately 130 interns are selected to participate in this program each year and begin arriving the second week in May. The internships provide students with introductory professional experiences to complement their academic programs. The interns are given assignments on research and development projects under the personal guidance of NASA professional staff members. Each intern is assigned a NASA mentor who facilitates a research assignment. In addition to the research assignment, the summer program includes a strong educational component that enhances the professional stature of the participants. The educational activities include a research symposium and a variety of workshops, lectures and short courses. An important aspect of the program is that it includes students with diverse social, cultural and economic backgrounds.

  18. Fullerene–Carbene Lewis Acid–Base Adducts

    KAUST Repository

    Li, Huaping

    2011-08-17

    The reaction between a bulky N-heterocylic carbene (NHC) and C60 leads to the formation of a thermally stable zwitterionic Lewis acid-base adduct that is connected via a C-C single bond. Low-energy absorption bands with weak oscillator strengths similar to those of n-doped fullerenes were observed for the product, consistent with a net transfer of electron density to the C60 core. Corroborating information was obtained using UV photoelectron spectroscopy, which revealed that the adduct has an ionization potential ∼1.5 eV lower than that of C60. Density functional theory calculations showed that the C-C bond is polarized, with a total charge of +0.84e located on the NHC framework and -0.84e delocalized on the C 60 cage. The combination of reactivity, characterization, and theoretical studies demonstrates that fullerenes can behave as Lewis acids that react with C-based Lewis bases and that the overall process describes n-doping via C-C bond formation. © 2011 American Chemical Society.

  19. Mechanisms of Hexachlorobenzene-induced Adverse Immune Effects

    NARCIS (Netherlands)

    Ezendam, Janine

    2004-01-01

    Hexachlorobenzene (HCB) is an environmental pollutant that can induce adverse immune effects in humans and rats. Brown Norway rats (BN) appeared to be very susceptible to HCB-induced immune effects. Oral exposure causes inflammatory skin and lung lesions, enlarged spleen and lymph nodes (LN) and

  20. Mechanisms of Hexachlorobenzene-induced Adverse Immune Effects

    NARCIS (Netherlands)

    Ezendam, Janine

    2004-01-01

    Hexachlorobenzene (HCB) is an environmental pollutant that can induce adverse immune effects in humans and rats. Brown Norway rats (BN) appeared to be very susceptible to HCB-induced immune effects. Oral exposure causes inflammatory skin and lung lesions, enlarged spleen and lymph nodes (LN) and ele

  1. Changes in the Expression and Distribution of Claudins, Increased Epithelial Apoptosis, and a Mannan-Binding Lectin-Associated Immune Response Lead to Barrier Dysfunction in Dextran Sodium Sulfate-Induced Rat Colitis

    Science.gov (United States)

    Yuan, Bosi; Zhou, Shuping; Lu, Youke; Liu, Jiong; Jin, Xinxin; Wan, Haijun; Wang, Fangyu

    2015-01-01

    Background/Aims This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. Methods Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. Results The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%±1.2% in controls and was significantly increased to 7.2%±1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. Conclusions There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability. PMID:25717051

  2. Immune System

    NARCIS (Netherlands)

    Kuper, C.F.; Ruehl-Fehlert, C.; Elmore, S.A.; Parker, G.A.

    2013-01-01

    Cells of the immune system are found in every organ, from the classic lymphoid organs to tissues such as liver, mucosae, and omental adipose tissue. Toxicity to the immune system may be from a direct or indirect injury to lymphoid organs. The morphological responses range from lymphocyte depletion t

  3. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  4. Lewis acid catalyzed transformations of Z-ligustilide

    Energy Technology Data Exchange (ETDEWEB)

    Rios, Maria Yolanda [Universidad Autonoma del Estado de Morelos, Cuernavaca, Morelos (Mexico); Delgado, Guillermo [Universidad Nacional Autonoma de Mexico, Mexico, D.F. (Mexico)

    1999-08-01

    Some Lewis acid mediated reactions of Z-ligustilide (1), a bioactive constituent of the medicinal species Ligusticum porteri, were investigated. These reactions provided varying mixtures of Z-butylidenephthalide (7), E-butylidenephthalide (8), n-butyphthalide (13), and novel linear dimeric phthalides (9-12) as the main products. The formation of the dimers occurred in low yields and with regio and situ-selectivity. Initial competitive O- and C- complexation of the Lewis acid with Z-ligustilide promoted the formation of the dimers occurred in low yields and with regio and situ- selectivity. Initial competitive O- and C- complexation of the Lewis acid with Z-ligustilide promoted the formation of carbocations at C(8), C(6) and C(7), which were stabilized by the addition of the C(6')-C(7') olefin of a second unit of the starting material, to provide cations at C(6') and C(7'). Subsequent isomerizations and elimination of the catalyst afforded the dimeric products 9-12. The yields and structure of the products are quite dependent on variations of the reaction conditions and the catalyst employed. [Spanish] Se investigaron algunas reacciones de Z-ligustilidas (1), un constituyente bioactivo de la planta medicinal Ligusticum porteri, catalizadas por acidos de Lewis. Estas reacciones produjeron mezclas variables de Z-butilidenftalida (7), E-butilidenftalida (8), n-butilftalida (13), y ftalidos dimetricos lineales novedosos (9-12) como productos principales. La formacion de los dimeros procedio en rendimientos bajos y con regio- y situ-selectividad. La O- y C- complejacion competitiva inicial del acido de Lewis con Z-lingustilida promueve la formacion de cationes en C(8), C(6) y C(7), los cuales son estabilizados por la adicion de la olefina C(6')-C(7') de una segunda unidad de la materia prima para generar los cationes en C(6')-C(7'). Isomerizaciones subsecuentes y la eliminacion del catalizador conducen a los productos dimericos 9

  5. Cardioprotective Effects of Telmisartan against Heart Failure in Rats Induced By Experimental Autoimmune Myocarditis through the Modulation of Angiotensin-Converting Enzyme-2/Angiotensin 1-7/Mas Receptor Axis

    Science.gov (United States)

    Sukumaran, Vijayakumar; Veeraveedu, Punniyakoti T.; Gurusamy, Narasimman; Yamaguchi, Ken'ichi; Lakshmanan, Arun Prasath; Ma, Meilei; Suzuki, Kenji; Kodama, Makoto; Watanabe, Kenichi

    2011-01-01

    Angiotensin-converting enzyme-2 (ACE-2) is a homolog of ACE that preferentially forms angiotensin-(ANG)-1-7 from angiotensin II (ANG II). We investigated the cardioprotective effects of telmisartan, a well-known angiotensin receptor blockers (ARBs) against experimental autoimmune myocarditis (EAM). EAM was induced in Lewis rats by immunization with porcine cardiac myosin. The rats were divided into two groups and treated with telmisartan (10 mg/kg/day) or vehicle for 21 days. Myocardial functional parameters were significantly improved by treatment with telmisartan compared with vehicle-treated rats. Telmisartan lowered myocardial protein expressions of NADPH oxidase subunits 3-nitrotyrosine, p47phox, p67 phox, Nox-4 and superoxide production significantly than vehicle-treated rats. In contrast myocardial protein levels of ACE-2, ANG 1-7 mas receptor were upregulated in the telmisartan treated group compared with those of vehicle-treated rats. The myocardial protein expression levels of tumor necrosis factor receptor (TNFR)-associated factor (TRAF)-2, C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP) 78 were decreased in the telmisartan treated rats compared with those of vehicle-treated rats. In addition, telmisartan treatment significantly decreased the protein expression levels of phospho-p38 mitogen-activated protein kinase (MAPK), phospho-JNK, phospho-ERK and phospho (MAPK) activated protein kinase-2 than with those of vehicle-treated rats. Moreover, telmisartan significantly decreased the production of proinflammatory cytokines, myocardial apoptotic markers and caspase-3 positive cells compared with those of vehicle-treated rats. Therefore, we suggest that telmisartan was beneficial protection against heart failure in rats, at least in part by suppressing inflammation, oxidative stress, ER stress as well as signaling pathways through the modulation of ACE2/ANG1-7/Mas receptor axis. PMID:21927577

  6. In Vivo Quantification of Inflammation in Experimental Autoimmune Encephalomyelitis Rats Using Fluorine-19 Magnetic Resonance Imaging Reveals Immune Cell Recruitment outside the Nervous System.

    Directory of Open Access Journals (Sweden)

    Jia Zhong

    Full Text Available Progress in identifying new therapies for multiple sclerosis (MS can be accelerated by using imaging biomarkers of disease progression or abatement in model systems. In this study, we evaluate the ability to noninvasively image and quantitate disease pathology using emerging "hot-spot" 19F MRI methods in an experimental autoimmune encephalomyelitis (EAE rat, a model of MS. Rats with clinical symptoms of EAE were compared to control rats without EAE, as well as to EAE rats that received daily prophylactic treatments with cyclophosphamide. Perfluorocarbon (PFC nanoemulsion was injected intravenously, which labels predominately monocytes and macrophages in situ. Analysis of the spin-density weighted 19F MRI data enabled quantification of the apparent macrophage burden in the central nervous system and other tissues. The in vivo MRI results were confirmed by extremely high-resolution 19F/1H magnetic resonance microscopy in excised tissue samples and histopathologic analyses. Additionally, 19F nuclear magnetic resonance spectroscopy of intact tissue samples was used to assay the PFC biodistribution in EAE and control rats. In vivo hot-spot 19F signals were detected predominantly in the EAE spinal cord, consistent with the presence of inflammatory infiltrates. Surprising, prominent 19F hot-spots were observed in bone-marrow cavities adjacent to spinal cord lesions; these were not observed in control animals. Quantitative evaluation of cohorts receiving cyclophosphamide treatment displayed significant reduction in 19F signal within the spinal cord and bone marrow of EAE rats. Overall, 19F MRI can be used to quantitatively monitored EAE disease burden, discover unexpected sites of inflammatory activity, and may serve as a sensitive biomarker for the discovery and preclinical assessment of novel MS therapeutic interventions.

  7. In Vivo Quantification of Inflammation in Experimental Autoimmune Encephalomyelitis Rats Using Fluorine-19 Magnetic Resonance Imaging Reveals Immune Cell Recruitment outside the Nervous System.

    Science.gov (United States)

    Zhong, Jia; Narsinh, Kazim; Morel, Penelope A; Xu, Hongyan; Ahrens, Eric T

    2015-01-01

    Progress in identifying new therapies for multiple sclerosis (MS) can be accelerated by using imaging biomarkers of disease progression or abatement in model systems. In this study, we evaluate the ability to noninvasively image and quantitate disease pathology using emerging "hot-spot" 19F MRI methods in an experimental autoimmune encephalomyelitis (EAE) rat, a model of MS. Rats with clinical symptoms of EAE were compared to control rats without EAE, as well as to EAE rats that received daily prophylactic treatments with cyclophosphamide. Perfluorocarbon (PFC) nanoemulsion was injected intravenously, which labels predominately monocytes and macrophages in situ. Analysis of the spin-density weighted 19F MRI data enabled quantification of the apparent macrophage burden in the central nervous system and other tissues. The in vivo MRI results were confirmed by extremely high-resolution 19F/1H magnetic resonance microscopy in excised tissue samples and histopathologic analyses. Additionally, 19F nuclear magnetic resonance spectroscopy of intact tissue samples was used to assay the PFC biodistribution in EAE and control rats. In vivo hot-spot 19F signals were detected predominantly in the EAE spinal cord, consistent with the presence of inflammatory infiltrates. Surprising, prominent 19F hot-spots were observed in bone-marrow cavities adjacent to spinal cord lesions; these were not observed in control animals. Quantitative evaluation of cohorts receiving cyclophosphamide treatment displayed significant reduction in 19F signal within the spinal cord and bone marrow of EAE rats. Overall, 19F MRI can be used to quantitatively monitored EAE disease burden, discover unexpected sites of inflammatory activity, and may serve as a sensitive biomarker for the discovery and preclinical assessment of novel MS therapeutic interventions.

  8. Frustrated Lewis Pair Behavior of Intermolecular Annine/B(C6F5)(3) Pairs

    NARCIS (Netherlands)

    Voss, Tanja; Mahdi, Tayseer; Otten, Edwin; Froehlich, Roland; Kehr, Gerald; Stephan, Douglas W.; Erker, Gerhard

    2012-01-01

    Reactions of N,N-dimethylaniline, N-isopropyl-aniline, 1,4-C6H4(CH(2)NHtBu)(2), and benzyldimethylamine with the Lewis acid B(C6F5)(3) have been studied. In the case of N,N-dirnethylaniline the combination of the Lewis acid and base forms an almost completely noninteracting frustrated Lewis pair, wh

  9. Influence of Lewis Antigen Expression by Helicobacter pylori on Bacterial Internalization by Gastric Epithelial Cells

    OpenAIRE

    Lozniewski, Alain; Haristoy, Xavier; Rasko, David A.; Hatier, Renée; Plénat, François; Diane E Taylor; Angioi-Duprez, Karine

    2003-01-01

    The role of Helicobacter pylori lipopolysaccharide (LPS) Lewis antigens in infection is still not well known. We investigated the influence of Lewis antigen expression by H. pylori on its internalization by AGS cells and the epithelium of human gastric xenografts in nude mice using isogenic mutants in LPS biosynthetic genes. In vivo, colonization rates were unaffected by the change in H. pylori Lewis antigen expression, whereas the number of viable intracellular bacteria was significantly hig...

  10. Difference between immune-related pain induced by antigen-specific immune complex and inflammatory pain induced by formalin and the expression of macrophage migration inhibitory factor (mif) in two rat models%免疫复合物致疼痛与甲醛致炎性痛的大鼠模型比较及巨噬细胞游走抑制因子在两组模型中的表达

    Institute of Scientific and Technical Information of China (English)

    吴锐; 李荣亨

    2012-01-01

    目的 比较免疫复合物所致疼痛模型与甲醛致炎性疼痛模型的大鼠疼痛行为、局部炎症反应及巨噬细胞游走抑制因子在不同模型不同部位的表达,探讨免疫复合物所致疼痛的病理机制.方法 成年SD清洁级大鼠15只,随机分为正常对照组,甲醛组及免疫复合物组,每组5只.分别在大鼠右后足底注入20 μL PBS、甲醛及免疫复合物.于30 min、1h、2h、4h、8h、12 h测定疼痛行为.并于12 h后采血、取大鼠局部皮肤及脊髓测定巨噬细胞游走抑制因子(MIF)表达.结果 疼痛行为变化:在甲醛致炎后大鼠立刻出现明显的自发痛,疼痛阈值明显下降,注射足高度肿胀并于1h达高峰后逐渐缓解.免疫复合物组的疼痛阈值低峰在4h后,并持续至8h后逐渐缓解,注射足肿胀不明显.皮肤及脊髓的MIF表达在甲醛组明显增加(P<0.05),在免疫复合物组中无明显改变.结论 MIF参与炎症性疼痛病理过程,但无证据参与免疫复合物所致疼痛.抗原抗体复合物所致疼痛与甲醛炎性痛病理机制有一定区别.%Objective To investigate the differences between immune-related pain induced by antigen-specific immune complex and inflammatory pain induced by formalin. Methods Fifteen adult health SD rats were randomly divided into control group, formalin group and immune-complex group with 5 rats in each group. The right hindpaws of rats were respectively injected with PBS, formalin and rat IgG immune-complex. The changes of hindpaw thickness and pain behavior were observed at 0, 30 min, 1 h, 2 h, 4 h, 8h and 12 h after injection. Serum macrophage migration-inhibitory factor ( MIF) was detected by ELISA. Expression of MIF in the hindpaw skin and spinal cord was determined by RT- PCR. Results 1. Changes of nociceptive behavior; rats in the formalin group showed significant nociceptive behavior immediately, such as licking foot, limping and highly swollen foot which could not touch the ground

  11. The limits and robustness of reinforcement learning in Lewis signalling games

    Science.gov (United States)

    Catteeuw, David; Manderick, Bernard

    2014-04-01

    Lewis signalling games are a standard model to study the emergence of language. We introduce win-stay/lose-inaction, a random process that only updates behaviour on success and never deviates from what was once successful, prove that it always ends up in a state of optimal communication in all Lewis signalling games, and predict the number of interactions it needs to do so: N3 interactions for Lewis signalling games with N equiprobable types. We show three reinforcement learning algorithms (Roth-Erev learning, Q-learning, and Learning Automata) that can imitate win-stay/lose-inaction and can even cope with errors in Lewis signalling games.

  12. Lewis Carrol: la lógica de la imaginación

    OpenAIRE

    Cadavid, Jorge Hernando; Pontificia Universidad Javeriana, Bogotá

    2014-01-01

    Lewis Carroll es el seudónimo del autor de Alice 's Adventures in Wonderland! (Las aventuras de Alicia en el País de !as Maravillas), cyo nombre real era Charles Lutwidge Dodgson. El seudommo fue construido con los nombresde pila: Lutwidge-Lewis y Charles-Carroll (los tradujo primero al latín: Carolus yLudovico; invirtió el orden y volvió a traducirlos al inglés: Lewis Carroll). En verdad,Lewis Carroll era su alter ego: un domesticador de serpientes y sapos, prestidigitador(por arte de birlib...

  13. Direct catalytic asymmetric addition of allyl cyanide to ketones via soft Lewis acid/hard Brønsted base/hard Lewis base catalysis.

    Science.gov (United States)

    Yazaki, Ryo; Kumagai, Naoya; Shibasaki, Masakatsu

    2010-04-21

    We report that a hard Lewis base substantially affects the reaction efficiency of direct catalytic asymmetric gamma-addition of allyl cyanide (1a) to ketones promoted by a soft Lewis acid/hard Brønsted base catalyst. Mechanistic studies have revealed that Cu/(R,R)-Ph-BPE and Li(OC(6)H(4)-p-OMe) serve as a soft Lewis acid and a hard Brønsted base, respectively, allowing for deprotonative activation of 1a as the rate-determining step. A ternary catalytic system comprising a soft Lewis acid/hard Brønsted base and an additional hard Lewis base, in which the basicity of the hard Brønsted base Li(OC(6)H(4)-p-OMe) was enhanced by phosphine oxide (the hard Lewis base) through a hard-hard interaction, outperformed the previously developed binary soft Lewis acid/hard Brønsted base catalytic system, leading to higher yields and enantioselectivities while using one-tenth the catalyst loading and one-fifth the amount of 1a. This second-generation catalyst allows efficient access to highly enantioenriched tertiary alcohols under nearly ideal atom-economical conditions (0.5-1 mol % catalyst loading and a substrate molar ratio of 1:2).

  14. Analysis of the immune-inducible transcriptome from microbial stress resistant, rat-tailed maggots of the drone fly Eristalis tenax

    Directory of Open Access Journals (Sweden)

    Vilcinskas Andreas

    2007-09-01

    Full Text Available Abstract Background The saprophagous and coprophagous maggots of the drone fly Eristalis tenax (Insecta, Diptera have evolved the unique ability to survive in aquatic habitats with extreme microbial stress such as drains, sewage pools, and farmyard liquid manure storage pits. Therefore, they represent suitable models for the investigation of trade-offs between the benefits resulting from colonization of habitats lacking predators, parasitoids, or competitors and the investment in immunity against microbial stress. In this study, we screened for genes in E. tenax that are induced upon septic injury. Suppression subtractive hybridization was performed to selectively amplify and identify cDNAs that are differentially expressed in response to injected crude bacterial endotoxin (LPS. Results Untreated E. tenax maggots exhibit significant antibacterial activity in the hemolymph which strongly increases upon challenge with LPS. In order to identify effector molecules contributing to this microbial defense we constructed a subtractive cDNA library using RNA samples from untreated and LPS injected maggots. Analysis of 288 cDNAs revealed induced expression of 117 cDNAs corresponding to 30 novel gene clusters in E. tenax. Among these immune-inducible transcripts we found homologues of known genes from other Diptera such as Drosophila and Anopheles that mediate pathogen recognition (e.g. peptidoglycan recognition protein or immune-related signaling (e.g. relish. As predicted, we determined a high diversity of novel putative antimicrobial peptides including one E. tenax defensin. Conclusion We identified 30 novel genes of E. tenax that were induced in response to septic injury including novel putative antimicrobial peptides. Further analysis of these immune-related effector molecules from Eristalis may help to elucidate the interdependency of ecological adaptation and molecular evolution of the innate immunity in Diptera.

  15. PD-L1Ig对大鼠肝移植免疫耐受影响的实验研究%The Study of the Immune Tolerance Induced by PD-L1Ig in Rat Liver Transplantation

    Institute of Scientific and Technical Information of China (English)

    刘晓明; 胡明道; 樊少敏; 陈鹏; CHENPeng

    2011-01-01

    目的 探讨PD-L1Ig对诱导大鼠肝移植免疫耐受的影响.方法 采用雄性大鼠构建Wistar→SD大鼠肝移植模型20例后,将大鼠随机分为两组:空白对照组和PD-L1Ig组,每组数量为10只,其中空白对照组不给予任何药物,PD-L1Ig组给予PD-L1Ig腹腔内注射,分别在手术当天、第2天、第4天及第6天重复给予腹腔内注射,术后观察动物生存情况、精神、食欲,术后1周处死部分动物取肝脏及血标本.血清酶学检测血肝功、流式细胞仪检测CD4+CD25+Treg比例分析,肝脏病理检测排斥反应情况.结果 血清肝功能测定谷丙转氨酶、谷草转氨酶及总胆红素指标,PD-L1Ig腹腔内注射组要低于对照组(P<0.05);肝脏病理检测发现空白对照组大鼠肝脏汇管区大量单核细胞积聚,并波及汇管周正常肝细胞,注射PD-L1Ig组大鼠肝脏汇管区炎症则相对较轻,只有少量炎症细胞积聚,参照Baff评分标准,肝脏排斥反应注射PD-L1Ig组为中度,空白对照组为重度;流式分析CD4+CD25+Treg比例显示,PD-L1Ig组外周血中CD4+CD25Treg细胞的比例较对照组高(P<0.05).结论 PD-L1Ig提高大鼠受损的肝功能,可减轻肝移大鼠肝损伤程度;可引起肝移植后大鼠外周血中CD4 CD25+Treg比例升高,具有诱导肝移植免疫耐受作用.%Objective To explore the effert of PD-Lllg on the immune ioieranre in rats wild liver transplantation. Methods Twenty ROLT models were established by Kamada two-tuft technique, with inbred male Wistar rats and male SI) rats served as donor and recipient respeclive.lv. The ivcipienls were randonib devided into 2 groups according to different treatments: no treatment A (Wistar->SD n -- 10) and B treated with Pl)-Lllg (Wistar→SD n = 10) after the day of operation, the following day, the lourlh day and sixth day. The clinical characters, the animal survival, mental and appelite were observed. The liver and blood samples were taken form rals after one week

  16. Immunization Coverage

    Science.gov (United States)

    ... Brazil, the Democratic Republic of the Congo, Ethiopia, India, Indonesia, Iraq, Nigeria, Pakistan and South Africa. Monitoring ... information on vaccines and immunization You are here: Media centre Fact sheets Quick Links Sitemap Home Health ...

  17. Yersinia pestis YopJ suppresses tumor necrosis factor alpha induction and contributes to apoptosis of immune cells in the lymph node but is not required for virulence in a rat model of bubonic plague.

    Science.gov (United States)

    Lemaître, Nadine; Sebbane, Florent; Long, Daniel; Hinnebusch, B Joseph

    2006-09-01

    The virulence of the pathogenic Yersinia species depends on a plasmid-encoded type III secretion system that transfers six Yop effector proteins into host cells. One of these proteins, YopJ, has been shown to disrupt host cell signaling pathways involved in proinflammatory cytokine production and to induce macrophage apoptosis in vitro. YopJ-dependent apoptosis in mesenteric lymph nodes has also been demonstrated in a mouse model of Yersinia pseudotuberculosis infection. These results suggest that YopJ attenuates the host innate and adaptive immune response during infection, but the role of YopJ during bubonic plague has not been completely established. We evaluated the role of Yersinia pestis YopJ in a rat model of bubonic plague following intradermal infection with a fully virulent Y. pestis strain and an isogenic yopJ mutant. Deletion of yopJ resulted in a twofold decrease in the number of apoptotic immune cells in the bubo and a threefold increase in serum tumor necrosis factor alpha levels but did not result in decreased virulence, systemic spread, or colonization levels in the spleen and blood. Our results indicate that YopJ is not essential for bubonic plague pathogenesis, even after peripheral inoculation of low doses of Y. pestis. Instead, the effects of YopJ appear to overlap and augment the immunomodulatory effects of other Y. pestis virulence factors.

  18. Gene array analysis of a rat model of liver transplant tolerance identifies increased complement C3 and the STAT-1/IRF-1 pathway during tolerance induction.

    Science.gov (United States)

    Cordoba, Shaun P; Wang, Chuanmin; Williams, Rohan; Li, Jian; Smit, Lynn; Sharland, Alexandra; Allen, Richard; McCaughan, Geoffrey; Bishop, Alex

    2006-04-01

    This study aimed to define the molecular mechanism during induction of spontaneous liver transplant tolerance using microarrays and to focus on molecular pathways associated with tolerance by meta-analysis with published studies. The differences in the early immune response between PVG to DA liver transplant recipients that are spontaneously tolerant (TOL) and PVG to Lewis liver transplants that reject (REJ) were examined. Spleens from TOL and REJ on days 1 and 3 were compared by 2 color microarray. Forty-six of 199 genes differentially expressed between TOL and REJ had an immunological function. More immune genes were increased in TOL vs. REJ on day 1, including STAT-1, IRF-1 and complement C3. Differential expression of selected genes was confirmed by quantitative RT-PCR. The results were compared to two published high-throughput studies of rat liver transplant tolerance and showed that C3 was increased in all three models, while STAT-1 and IRF-1 were increased in two models. The early increases in immune genes in TOL confirmed previous reports of an active early immune response in TOL. In conclusion, the increase in STAT-1, IRF-1 and complement component C3 in several models of liver transplant tolerance suggests that the STAT-1/IRF-1 apoptotic pathway and C3 may be involved in the tolerogenic mechanism.

  19. Structure of Flame Balls at Low Lewis-Number

    Science.gov (United States)

    Weiland, Karen J.; Ronney, Paul

    1998-01-01

    The Structure of Flame Balls at Low Lewis-Number (SOFBALL) experiment explored the behavior of a newly discovered flame phenomena called "flame balls." These spherical, stable, stationary flame structures, observed only in microgravity, provide a unique opportunity to study the interactions of the two most important processes necessary for combustion (chemical reaction and heat and mass transport) in the simplest possible configuration. The previously unobtainable experimental data provided a comparison with models of flame stability and flame propagation limits that are crucial both in assessing fire safety and in designing efficient, clean-burning combustion engines.

  20. Reduced CSF CART in dementia with Lewy bodies

    DEFF Research Database (Denmark)

    Schultz, Kristofer; Wiehager, Sara; Nilsson, Karin

    2009-01-01

    Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia after Alzheimer's disease (AD). The underlying neurobiological mechanism of DLB is not fully understood and no generally accepted biomarkers are yet available for the diagnosis of DLB. In a recent MRI study......, DLB patients displayed hypothalamic atrophy whereas this region was not affected in AD patients. Cocaine and amphetamine regulated transcript (CART) is a neuropeptide expressed selectively in neurons in the hypothalamus. Here, we found that CSF CART levels were significantly reduced by 30% in DLB...

  1. Telecommuting (Work-At-Home) at NASA Lewis Research Center

    Science.gov (United States)

    Srinidhi, Saragur M.

    1994-01-01

    This report presents a study in evaluating the viability of providing a work-at-home (telecommuting) program for Lewis Research Center's corporate employees using Integrated Services Digital Network (ISDN). Case studies have been presented for a range of applications from casual data access to interactive access. The network performance of telemedia applications were studied against future requirements for such level of remote connectivity. Many of the popular ISDN devices were characterized for network and service functionality. A set of recommendations to develop a telecommuting policy have been proposed.

  2. Feminine Hypostases in Epic Fantasy: Tolkien, Lewis, Rowling

    Directory of Open Access Journals (Sweden)

    Măcineanu Laura

    2015-12-01

    Full Text Available The paper identifies the types of female figures present in the works of three well-known fantasy writers, J.R.R. Tolkien, C.S. Lewis and J.K. Rowling, discussing the ways in which these characters are presented, their relationship with other characters, and their role in the economy of the novel, which is more important than may appear from a first reading. It also tries to explain the reasons that prompted the above-mentioned authors to choose these female hypostases.

  3. 转Bt基因大米暴露对亲代雌性大鼠免疫系统影响的研究%The effect of exposure to transgenic Bt rice on the immune system of parental female rats

    Institute of Scientific and Technical Information of China (English)

    冯永全; 胡静; 支媛; 于洲

    2013-01-01

    目的 研究转Bt基因大米(TT51)对亲代雌性大鼠免疫系统的影响.方法 试验分为转Bt基因大米组(TT51组)、亲本明恢63大米组(明恢63组)和市售大米组,各组大米按60%的比例掺入饲料进行全食物喂养.Wistar雌、雄大鼠喂养10周后进行交配繁殖,对亲代雌性大鼠于断乳后进行免疫毒性评价.指标包括血常规、全血淋巴细胞分型、脾细胞的NK活性检测、刀豆蛋白A诱导淋巴细胞转化试验、抗体生成细胞检测以及淋巴结的淋巴细胞分型.结果 脾淋巴细胞分型中,TT51组的Th细胞、T细胞比例与市售大米组比较差异有统计学意义(P<0.01),明恢63组的B细胞、T细胞比例与市售大米组比较差异有统计学意义(P<0.01);颈部淋巴结淋巴细胞分型中,TT51组的Th细胞比例与市售大米组比较差异有统计学意义(P<0.01);各组其他功能性试验结果之间差异无统计学意义.结论 转Bt基因大米(TT51)对亲代雌性大鼠免疫系统功能未见不良影响.%Objective To investigate the effect of transgenic Bt rice (TT51) exposure on immune system of parental female rats.Methods Wistar rats were divided into Bt rice group,parent rice group and market rice group.All groups were fed on mixture containing 60% rice.Female and male rats were fed for 10 weeks before copulation,and the parental female rats were carried on the immunotoxicity assessment after being weaned.The parental female rats were sacrificed for blood routine,blood lymphocyte typing,NK activity assay,conA induced lymphocyte transformation test,antibody-producing cell assay as well as lymph node lymphocyte typing.Results Statistical significances were observed on spleen lymphocyte typing and cervical lymph node lymphocyte typing between TT51 rice and market rice,and the proportion of B and T cell between parent rice and market rice.There was no significant difference of other functional experiment among various groups

  4. Fish oil versus arachis oil food supplementation in relation to pregnancy duration in rats

    DEFF Research Database (Denmark)

    Olsen, S.F.; Hansen, Harald S.; Jensen, B.

    1990-01-01

    Throughout pregnancy, Lewis rats were fed standard rat chow supplemented with 15% (w/w) of either MaxEPA fish oil (FO) or arachis oil (AO); a third group was fed standard rat chow only (St) (n = 15, 15, and 16 rats, respectively). Compared to AO-rats, FO-rats had substantially higher levels of n-3...... may be related to the lower maternal weight gain during pregnancy and the lower food consumption observed in FO-rats (p 0.1). The findings are compatible with the hypothesis that gestational age...

  5. Intratumor chemotherapy in combination with a systemic antimetastatic drug in the treatment of Lewis-lung carcinoma.

    Science.gov (United States)

    De-Oliveira, M M; Nakamura, I T; Joussef, A C; Giannotti Filho, O

    1985-01-01

    The effect of an antimetastatic agent plus intratumor chemotherapy was evaluated in mice bearing Lewis-lung carcinoma by measuring survival time and by histological examination. Polymeric flavan-3,4-diol (APF) from avocado seeds, Persea gratissima, administered alone directly into the tumor did not change survival time, although it partially destroyed the primary tumor. However, the drug administered in combination with an antimetastatic, 1,2-bis(3,5-dioxopiperazin-1-yl)ethane (ICRF-154), resulted in an increase in survival time. When 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was used in place of polymeric flavanadiol as an intralesional drug, a significant increase in survival was also achieved. The effect of each drug alone and of their combination was evaluated by "responder analyses". Animals "cured" by the combination and rechallenged with 2 X 10(6) tumor cells showed that immunization could occur.

  6. Targeting beta- and alpha-adrenergic receptors differentially shifts Th1, Th2, and inflammatory cytokine profiles in immune organs to attenuate adjuvant arthritis

    Directory of Open Access Journals (Sweden)

    Dianne eLorton

    2014-08-01

    Full Text Available The sympathetic nervous system (SNS regulates host defense responses and restores homeostasis. SNS-immune regulation is altered in rheumatoid arthritis (RA and rodent models of RA, characterized by nerve remodeling in immune organs and defective adrenergic receptor (AR signaling to immune cell targets that typically promotes or suppresses inflammation via α- and β2-AR activation, respectively, and indirectly drives humoral immunity by blocking Th1 cytokine secretion. Here, we investigate how β2-AR stimulation and/or α-AR blockade at disease onset affects disease pathology and cytokine profiles in relevant immune organs from male Lewis rats with adjuvant-induced arthritis (AA. Rats challenged to induce AA were treated with terbutaline (TERB, a β2-AR agonist (600 μg/kg/day and/or phentolamine (PHEN, an α-AR antagonist (5.0 mg/kg/day or vehicle from disease onset through severe disease. We report that in spleen, mesenteric (MLN and draining lymph node (DLN cells, TERB reduces proliferation, an effect independent of IL-2. TERB also fails to shift Th cytokines from a Th1 to Th2 profile in spleen and MLN (no effect on IFN-γ and DLN (greater IFN-γ cells. In splenocytes, TERB, PHEN and co-treatment (PT promotes an anti-inflammatory profile (greater IL-10 and lowers TNF-α (PT only. In DLN cells, drug treatments do not affect inflammatory profiles, except PT, which raised IL-10. In MLN cells, TERB or PHEN lowers MLN cell secretion of TNF-α or IL-10, respectively. Collectively, our findings indicate disrupted β2-AR, but not α-AR signaling in AA. Aberrant β2-AR signaling consequently derails the sympathetic regulation of lymphocyte expansion, Th cell differentiation, and inflammation in the spleen, DLNs and MLNs that is required for immune system homeostasis. Importantly, this study provides potential mechanisms through which reestablished balance between α- and β2-AR function in the immune system ameliorates inflammation and joint

  7. 急性出血坏死性胰腺炎大鼠肠道免疫功能的改变%Intestinal mucosal immune barrier injury of rats with acute hemorrhagic necrotic pancreatiti

    Institute of Scientific and Technical Information of China (English)

    金英朝; 王海宽; 张弘超; 李小东; 刘大伟

    2015-01-01

    ObjectiveTo observe intestinal mucosal immune barrier relative factors TNF-α in serum, sIgA levels of intestinal juice, and CD3+ and CD4+ cell change of intestinal tissue in rats with acute hemorrhagic necrotic pancreatitis. To investigate the change of intestinal mucosal immune barrier injury in this model.Methods36 wistar rats were randomly divided into three groups: SAP model group(A group), the sham operation control group (B group) (N = 18). Abdominal aortic and Portal vein blood were collected, and stored in refrigerator for next assays. Intestinal juice were collected and stored in refrigerator for next assays. The intestinal tissue were ifxed in 4% neutral formaldehyde buffer. TNF-α concentration of blood and sIgA levels of intestinal juice were evaluated by ELISA method. Immunohistochemistry was adopted to detect intestinal tissue CD3+ and CD4+ expression. Endotoxin levels of portal vein blood was detected following the kit instruction.ResultsTesting the indicators after model building of each group,we have the following ifndings: In group A, Blood TNF-a and sIgA levels of intestinal juice are signiifcantly lower than that in the group B, while endotoxin levels of portal vein blood signiifcantly higher. The expression of CD3+ and CD4+ T immune cell are signiifcantly lower in group A.ConclusionThis study conifrmed the participation of the intestinal mucosal immune barrier function injury are important inlfammatory disorders in acute pancreatitis in rats with acute hemorrhagic necrotic pancreatitis.%目的:探讨分析急性出血坏死性胰腺炎(AHNP)大鼠肠道黏膜免疫功能的变化情况。方法选取成年的Wistar雄性大鼠,随机分成AHNP组、假手术组。分别于造模后24 h取标本检测(主要包括内毒素的含量、CD3、CD4及CD8的阳性T淋巴细胞的比例、盲肠内容物sIgA的浓度,血清肿瘤坏死因子-α(TNF-α)的水平等。结果 AHNP组各时间段的门静脉血内毒素含量均有显著

  8. Lewis base activation of Lewis acids: catalytic, enantioselective addition of glycolate-derived silyl ketene acetals to aldehydes.

    Science.gov (United States)

    Denmark, Scott E; Chung, Won-Jin

    2008-06-20

    A catalytic system involving silicon tetrachloride and a chiral, Lewis basic bisphosphoramide catalyst is effective for the addition of glycolate-derived silyl ketene acetals to aldehydes. It was found that the sense of diastereoselectivity could be modulated by changing the size of the substituents on the silyl ketene acetals. In general, the trimethylsilyl ketene acetals derived from methyl glycolates with a large protecting group on the alpha-oxygen provide enantiomerically enriched alpha,beta-dihydroxy esters with high syn-diastereoselectivity, whereas the tert-butyldimethylsilyl ketene acetals derived from bulky esters of alpha-methoxyacetic acid provide enantiomerically enriched alpha,beta-dihydroxy esters with high anti-diastereoselecitvity.

  9. Michael Lewis: Flash Boys. Cracking the Money Code

    OpenAIRE

    Gylfi Magnússon

    2014-01-01

    Í umsögn gagnrýnanda kemur meðal annars eftirfarandi fram: Þegar á heildina er litið er þetta ágæt bók þótt hún sé ekki gallalaus. Lewis er ónákvæmur á köflum og dregur stundum upp helst til svart-hvíta mynd með því að viðra einungis hluta þeirra sjónarmiða sem máli skipta. Bókin vekur verðskuldaða athygli á ákveðnum skuggahliðum fjármálamarkaða sem full ástæða er til að gefa frekari gaum. Lewis tekst jafnframt að gæða söguna lífi með því að draga fram áhugaverðar persónur sem tengjast henni ...

  10. Michael Lewis: Flash Boys. Cracking the Money Code

    Directory of Open Access Journals (Sweden)

    Gylfi Magnússon

    2014-06-01

    Full Text Available Í umsögn gagnrýnanda kemur meðal annars eftirfarandi fram: Þegar á heildina er litið er þetta ágæt bók þótt hún sé ekki gallalaus. Lewis er ónákvæmur á köflum og dregur stundum upp helst til svart-hvíta mynd með því að viðra einungis hluta þeirra sjónarmiða sem máli skipta. Bókin vekur verðskuldaða athygli á ákveðnum skuggahliðum fjármálamarkaða sem full ástæða er til að gefa frekari gaum. Lewis tekst jafnframt að gæða söguna lífi með því að draga fram áhugaverðar persónur sem tengjast henni með ýmsum hætti.

  11. Parkinson's disease dementia: a diminished role for the Lewy body.

    Science.gov (United States)

    Libow, Leslie S; Frisina, Pasquale G; Haroutunian, Vahram; Perl, Daniel P; Purohit, Dushyant P

    2009-09-01

    The literature currently views Lewy bodies as central in the pathogenesis of Parkinson's disease dementia (PDD) when Alzheimer's disease (AD) or vascular pathology is not present. Because the neuropathology of PDD is not well understood, the pathological features of PDD were characterized in eighteen PD brain specimens using published criteria for AD, Diffuse Lewy Body Disease (DLBD), and Vascular Disease as a framework. Among the PD dementia (n=16) subjects, 3 (19%) did not have LBs outside of the brain stem, nor AD or vascular pathology. In two additional cases, one did have rare LBs in the neocortex and cingulate gyrus. However, these two cases did not meet the diagnostic criteria for DLBD. Beyond these 5 cases, the remaining PD dementia subjects fitted a classical pathological profile consistent with AD (38%), vascular disease (12.5%), DLBD (6%), or a combination of these pathologies (12.5%). The findings from this study do not support the hypothesis that LBs are the main substrate for dementia in PD. More research with a larger sample size is needed to determine whether the LB may be a secondary phenomenon and/or an "innocent-bystander". The entire role of the LB in PD dementia is again brought into question.

  12. Inhibition of rat gut reperfusion injury with an agent developed for the mouse. Evidence that amplification of injury by innate immunity is conserved between two animal species.

    Science.gov (United States)

    Afnan, Jalil; Ahmadi-Yazdi, Cyrus; Sheu, Eric G; Oakes, Sean M; Moore, Francis D

    2010-06-01

    Murine reperfusion injury follows binding of specific IgM natural antibodies to neo-antigens exposed in ischemic tissue. Peptides that mimic the site of antibody binding in the injury prevent IgM binding when administered intravenously before reperfusion. To determine whether this pathogenic sequence is restricted to mice, we have tested the ability of the peptide to prevent reperfusion injury in a dissimilar species, the rat. Sprague-Dawley rats were subjected to 40 min of mesenteric ischemia followed by 180 min of reperfusion. The peptide mimic was administered intravenously prior to reperfusion. Gut injury was quantified using a scoring system based on the hematoxylin-and-eosin section. (125)I-labeled albumin was used to assess local (gut) and remote (lung) injury. The macroscopic appearance of bowel from peptide-treated animals was less edematous and hemorrhagic. Microscopic analysis showed a significantly reduced injury score in peptide-treated animals. Permeability data indicated a significant reduction in local and remote injury in peptide-treated animals. The data demonstrate attenuation of rat gut microvillus injury, of gut edema, and of remote injury following mesenteric ischemia-reperfusion due to administration of an intravenous peptide mimic of a murine ischemia neo-antigen, indicating a second species uses a similar ischemia neo-antigen and corresponding natural antibody specificity to amplify reperfusion injury to the point of necrosis. This mechanism of inflammation is potentially applicable to higher species.

  13. Antibody is responsible for the passive transfer of immunity to mice from rabbits, rats or mice vaccinated with attenuated Schistosoma japonicum cercariae.

    Science.gov (United States)

    Moloney, N A; Webbe, G

    1990-04-01

    Sera from rabbits, rats and mice multiply-vaccinated with attenuated cercariae of Schistosoma japonicum conferred high levels of resistance against challenge to naive recipient mice (up to 97, 64 and 60% respectively). Vaccinated rabbit and rat sera were given before challenge and vaccinated mouse serum 5 days after challenge. To show that the protective factors in these sera were antibodies, vaccinated rabbit and mouse sera were fractionated by protein A-Sepharose and the fractions precipitated by 50% ammonium sulphate. The protein A-Sepharose binding or non-binding fractions in vaccinated rabbit serum transferred approximately equal levels of significant resistance to mice, suggesting that both the IgG and non-IgG components of vaccinated rabbit serum are protective. The major part of the protective activity in vaccinated mouse serum was transferred to recipients by the protein A-Sepharose binding fraction, i.e. the IgG antibodies. Heat inactivation of sera at 56 degrees C for 3 h affected the protective capacity of vaccinated rat sera, but not that of vaccinated rabbit or mouse sera.

  14. Immune regulation of ovarian development: programming by neonatal immune challenge

    Directory of Open Access Journals (Sweden)

    Luba eSominsky

    2013-06-01

    Full Text Available Neonatal immune challenge by administration of lipopolysaccharide (LPS produces enduring alterations in the development and activity of neuroendocrine, immune and other physiological systems. We have recently reported that neonatal exposure to an immune challenge by administration of LPS results in altered reproductive development in the female Wistar rat. Specifically, LPS-treated animals exhibited diminished ovarian reserve and altered reproductive lifespan. In the current study, we examined the cellular mechanisms that lead to the previously documented impaired ovulation and reduced follicular pool. Rats were administered intraperitoneally either 0.05mg/kg of LPS (Salmonella Enteritidis or an equivalent volume of non-pyrogenic saline on postnatal days (PNDs 3 and 5, and ovaries were obtained on PND 7. Microarray analysis revealed a significant upregulation in transcript expression (2-fold change; p<.05 for a substantial number of genes in the ovaries of LPS-treated animals, implicated in immune cell signalling, inflammatory responses, reproductive system development and disease. Several canonical pathways involved in immune recognition were affected by LPS treatment, such as nuclear factor-κB (NF-kB activation and LPS-stimulated mitogen-activated protein kinase (MAPK signalling. Real-time PCR analysis supported the microarray results. Protein expression analysis of several components of the MAPK signalling pathway revealed a significant upregulation in the expression of Toll-like receptor 4 (TLR4 in the neonatal ovary of LPS-treated animals. These results indicate that neonatal immune challenge by administration of LPS has a direct effect on the ovary during the sensitive period of follicular formation. Given the pivotal role of inflammatory processes in the regulation of reproductive health, our findings suggest that early life immune activation via TLR signalling may have significant implications for the programming of ovarian development

  15. Lewis acid catalysis of a Diels-Alder reaction in water

    NARCIS (Netherlands)

    Otto, S; Bertoncin, F; Engberts, JBFN

    1996-01-01

    Here we report the first detailed study of a Diels-Alder (DA) reaction that is catalyzed by Lewis acids in water. The effect of Co2+, Ni2+, Cu2+ and Zn2+ ions as Lewis acid catalysts on the rate and endo-exo selectivity of the DA reaction between the bidentate dienophiles 3-phenyl-1-(2-pyridyl)-2-pr

  16. Catalytic Conversion of Glucose into 5-Hydroxymethylfurfural by Hf(OTf4 Lewis Acid in Water

    Directory of Open Access Journals (Sweden)

    Junjie Li

    2015-12-01

    Full Text Available A series of Lewis acidic metal salts were used for glucose dehydration to 5-hydroymethylfurfural (HMF in water. Effect of valence state, ionic radii of Lewis acidic cation, and the type of anions on the catalytic performance have been studied systematically. The experimental results showed that the valence state played an important role in determining catalytic activity and selectivity. It was found that a higher glucose conversion rate and HMF selectivity could be obtained over high valent Lewis acid salts, where the ionic radii of these Lewis acidic metal salts are usually relatively small. Analysis on the effect of the anions of Lewis acid salts on the catalytic activity and the selectivity suggested that a higher glucose conversion and HMF selectivity could be readily obtained with Cl−. Furthermore, the recyclability of high valence state Lewis acid salt was also studied, however, inferior catalytic performance was observed. The deactivation mechanism was speculated to be the fact that high valence state Lewis acid salt was comparatively easier to undergo hydrolysis to yield complicated metal aqua ions with less catalytic activity. The Lewis acidic activity could be recovered by introducing a stoichiometric amount of hydrochloric acid (HCl to the catalytic before the reaction.

  17. Lewis acid-catalyzed depolymerization of soda lignin in supercritical ethanol/water mixtures

    NARCIS (Netherlands)

    Güvenatam, Burcu; Heeres, Erik H.J.; Pidko, Evgeny A.; Hensen, Emiel J M

    2016-01-01

    The depolymerization of lignin model compounds and soda lignin by super Lewis acidic metal triflates has been investigated in a mixture of ethanol and water at 400 °C. The strong Lewis acids convert representative model compounds for the structure-forming linkages in lignin, namely α-O-4, 5-O-4

  18. Lewis acid catalysis of a Diels-Alder reaction in water

    NARCIS (Netherlands)

    Otto, S; Bertoncin, F; Engberts, JBFN

    1996-01-01

    Here we report the first detailed study of a Diels-Alder (DA) reaction that is catalyzed by Lewis acids in water. The effect of Co2+, Ni2+, Cu2+ and Zn2+ ions as Lewis acid catalysts on the rate and endo-exo selectivity of the DA reaction between the bidentate dienophiles

  19. Specific acid catalysis and Lewis acid catalysis of Diels–Alder reactions in aqueous media

    NARCIS (Netherlands)

    Mubofu, Egid B.; Engberts, Jan B.F.N.

    2004-01-01

    A comparative study of specific acid catalysis and Lewis acid catalysis of Diels–Alder reactions between dienophiles (1, 4 and 6) and cyclopentadiene (2) in water and mixed aqueous media is reported. The reactions were performed in water with copper(II) nitrate as the Lewis acid catalyst whereas

  20. Specific acid catalysis and Lewis acid catalysis of Diels-Alder reactions in aqueous media

    NARCIS (Netherlands)

    Mubofu, E.B.; Engberts, J.B.F.N.

    A comparative study of specific acid catalysis and Lewis acid catalysis of Diells-Alder reactions between dienophiles (1, 4 and 6) and cyclopentadiene (2) in water and mixed aqueous media is reported. The reactions were performed in water with copper(II) nitrate as the Lewis acid catalyst whereas

  1. An Integrated Perspective of Humanism and Supernaturalism for Education: C. S. Lewis's Version of Education

    Science.gov (United States)

    Lee, Seung Chun

    2013-01-01

    This paper explores some theoretical reflections on the connection between C. S. Lewis's thoughts on the purpose and process of education and his understanding of supernatural human nature which has been relatively little explored. An introduction about Lewis's career as a college teacher blends into the background of this paper. It is followed by…

  2. An Integrated Perspective of Humanism and Supernaturalism for Education: C. S. Lewis's Version of Education

    Science.gov (United States)

    Lee, Seung Chun

    2013-01-01

    This paper explores some theoretical reflections on the connection between C. S. Lewis's thoughts on the purpose and process of education and his understanding of supernatural human nature which has been relatively little explored. An introduction about Lewis's career as a college teacher blends into the background of this paper. It is followed by…

  3. Oral Interpretation of C.S. Lewis'"Narnia Tales": A Refracting of "Pictures."

    Science.gov (United States)

    Keefe, Carolyn

    "The Chronicles of Narnia" are a series of seven fairy tales written by C.S. Lewis that have become popular with both children and adults. Lewis points to five aspects of the fairy tale form that made the form suitable for expressing the images he saw. The aspects are: (1) no love interest; (2) no close psychology; (3) severe restraints…

  4. Specific acid catalysis and Lewis acid catalysis of Diels-Alder reactions in aqueous media

    NARCIS (Netherlands)

    Mubofu, E.B.; Engberts, J.B.F.N.

    2004-01-01

    A comparative study of specific acid catalysis and Lewis acid catalysis of Diells-Alder reactions between dienophiles (1, 4 and 6) and cyclopentadiene (2) in water and mixed aqueous media is reported. The reactions were performed in water with copper(II) nitrate as the Lewis acid catalyst whereas hy

  5. Specific acid catalysis and Lewis acid catalysis of Diels–Alder reactions in aqueous media

    NARCIS (Netherlands)

    Mubofu, Egid B.; Engberts, Jan B.F.N.

    2004-01-01

    A comparative study of specific acid catalysis and Lewis acid catalysis of Diels–Alder reactions between dienophiles (1, 4 and 6) and cyclopentadiene (2) in water and mixed aqueous media is reported. The reactions were performed in water with copper(II) nitrate as the Lewis acid catalyst whereas hyd

  6. Sentence Processing in Lewy Body Spectrum Disorder: The Role of Working Memory

    Science.gov (United States)

    Gross, Rachel G.; McMillan, Corey T.; Chandrasekaran, Keerthi; Dreyfuss, Michael; Ash, Sharon; Avants, Brian; Cook, Philip; Moore, Peachie; Libon, David J.; Siderowf, Andrew; Grossman, Murray

    2012-01-01

    Prior work has related sentence processing to executive deficits in non-demented patients with Parkinson's disease (PD). We extended this investigation to patients with dementia with Lewy bodies (DLB) and PD dementia (PDD) by examining grammatical and working memory components of sentence processing in the full range of patients with Lewy body…

  7. 78 FR 36591 - David M. Lewis, D.M.D., Dismissal of Proceeding

    Science.gov (United States)

    2013-06-18

    ... Enforcement Administration David M. Lewis, D.M.D., Dismissal of Proceeding On December 5, 2012, the Deputy... to Show Cause to David M. Lewis, D.M.D. (Registrant), of Sacramento, California. The Show Cause Order..., according to the DI, is the Registrant's attorney. However, `` umerous Federal Courts have held that `...

  8. Reduced frequency of blood group Lewis a-b- in female Type 1 diabetes patients

    DEFF Research Database (Denmark)

    Kharagjitsingh, A.V.; Prinsen, K.; Lemkes, H.H.;

    2008-01-01

    AIMS: To examine a disputed association between the Lewis(a(-)b(-)) phenotype and Type 1 diabetes (T1D). METHODS: Lewis red blood cell phenotyping was performed for 97 T1D White patients and 100 control subjects using monoclonal antibodies. Two historical cohorts were also included as a control...

  9. Oral Interpretation of C.S. Lewis'"Narnia Tales": A Refracting of "Pictures."

    Science.gov (United States)

    Keefe, Carolyn

    "The Chronicles of Narnia" are a series of seven fairy tales written by C.S. Lewis that have become popular with both children and adults. Lewis points to five aspects of the fairy tale form that made the form suitable for expressing the images he saw. The aspects are: (1) no love interest; (2) no close psychology; (3) severe restraints…

  10. LewiSpace: An Exploratory Study with a Machine Learning Model in an Educational Game

    Science.gov (United States)

    Ghali, Ramla; Ouellet, Sébastien; Frasson, Claude

    2016-01-01